50% reduction of basal (T(0)) total irritable bowel syndrome symptoms score compared with 38% in the placebo group (P<0.009). With peppermint oil at T(4) and at T(8) compared with T(0) a statistically significant reduction of the total irritable bowel syndrome symptoms score was found (T(0): 2.19+/-0.13, T(4): 1.07+/-0.10*, T(8): 1.60+/-0.10*, *P<0.01 compared with T(0), mean+/-S.E.M.), while no change was found with the placebo. CONCLUSION: A 4 weeks treatment with peppermint oil improves abdominal symptoms in patients with irritable bowel syndrome.\",\n \"title\": \"Peppermint oil (Mintoil) in the treatment of irritable bowel syndrome: a prospective double blind placebo-controlled randomized trial.\"\n },\n {\n \"docid\": \"MED-4850\",\n \"text\": \"Plants are rich natural sources of antioxidants in addition to other nutrients. Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food (LF) have been carried out. We have clarified the efficacy of LF in rheumatoid diseases as an example of a health problem where inflammation is one of the main concerns. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts, i.e. rich sources of carotenoids, vitamins C and E. The subjects eating LF showed highly increased levels of beta and alfa carotenes, lycopen and lutein in their sera. Also the increases of vitamin C and vitamin E (adjusted to cholesterol) were statistically significant. As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin, myricetin and kaempherol was much higher than in the omnivorous controls. The LF diet is rich in fibre, substrate of lignan production, and the urinary excretion of polyphenols like enterodiol and enterolactone as well as secoisolaricirecinol were much increased in subjects eating LF. The shift of fibromyalgic subjects to LF resulted in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health. The rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding. The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms. In conclusion the rheumatoid patients subjectively benefited from the vegan diet rich in antioxidants, lactobacilli and fibre, and this was also seen in objective measures.\",\n \"title\": \"Antioxidants in vegan diet and rheumatic disorders.\"\n },\n {\n \"docid\": \"MED-2571\",\n \"text\": \"Background Prospective, randomized, pilot clinical study was conducted to evaluate the beneficial effects of inositol hexaphosphate (IP6) + Inositol in breast cancer patients treated with adjuvant therapy. Patients and methods Patients with invasive ductal breast cancer where polychemotherapy was indicated were monitored in the period from 2005-2007. Fourteen patients in the same stage of ductal invasive breast cancer were involved in the study, divided in two randomized groups. One group was subjected to take IP6 + Inositol while the other group was taking placebo. In both groups of patients the same laboratory parameters were monitored. When the treatment was finished, all patients have filled questionnaires QLQ C30 and QLQ-BR23 to determine the quality of life. Results Patients receiving chemotherapy, along with IP6 + Inositol did not have cytopenia, drop in leukocyte and platelet counts. Red blood cell counts and tumor markers were unaltered in both groups. However, patients who took IP6 + Inositol had significantly better quality of life (p = 0.05) and functional status (p = 0.0003) and were able to perform their daily activities. Conclusion IP6 + Inositol as an adjunctive therapy is valuable help in ameliorating the side effects and preserving quality of life among the patients treated with chemotherapy.\",\n \"title\": \"Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study\"\n },\n {\n \"docid\": \"MED-5066\",\n \"text\": \"Context Evidence is lacking that a dietary pattern high in vegetables, fruit, and fiber and low in total fat can influence breast cancer recurrence or survival. Objective To assess whether a major increase in vegetable, fruit, and fiber intake and a decrease in dietary fat intake reduces the risk of recurrent and new primary breast cancer and all-cause mortality among women with previously treated early stage breast cancer. Design, Setting, and Participants Multi-institutional randomized controlled trial of dietary change in 3088 women previously treated for early stage breast cancer who were 18 to 70 years old at diagnosis. Women were enrolled between 1995 and 2000 and followed up through June 1, 2006. Intervention The intervention group (n=1537) was randomly assigned to receive a telephone counseling program supplemented with cooking classes and newsletters that promoted daily targets of 5 vegetable servings plus 16 oz of vegetable juice; 3 fruit servings; 30 g of fiber; and 15% to 20% of energy intake from fat. The comparison group (n=1551) was provided with print materials describing the \\\"5-A-Day\\\" dietary guidelines. Main Outcome Measures Invasive breast cancer event (recurrence or new primary) or death from any cause. Results From comparable dietary patterns at baseline, a conservative imputation analysis showed that the intervention group achieved and maintained the following statistically significant differences vs the comparison group through 4 years: servings of vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake from fat, −13%. Plasma carotenoid concentrations validated changes in fruit and vegetable intake. Throughout the study, women in both groups received similar clinical care. Over the mean 7.3-year follow-up, 256 women in the intervention group (16.7%) vs 262 in the comparison group (16.9%) experienced an invasive breast cancer event (adjusted hazard ratio, 0.96; 95% confidence interval, 0.80–1.14; P=.63), and 155 intervention group women (10.1%) vs 160 comparison group women (10.3%) died (adjusted hazard ratio, 0.91; 95% confidence interval, 0.72–1.15; P=.43). No significant interactions were observed between diet group and baseline demographics, characteristics of the original tumor, baseline dietary pattern, or breast cancer treatment. Conclusion Among survivors of early stage breast cancer, adoption of a diet that was very high in vegetables, fruit, and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period. Trial Registration clinicaltrials.gov Identifier: NCT00003787\",\n \"title\": \"Influence of a Diet Very High in Vegetables, Fruit, and Fiber and Low in Fat on Prognosis Following Treatment for Breast Cancer\"\n },\n {\n \"docid\": \"MED-3503\",\n \"text\": \"BACKGROUND: Dysmenorrhoea is a common gynaecological complaint consisting of painful cramps accompanying menstruation, which in the absence of any underlying abnormality is known as primary dysmenorrhoea. Research has shown that women with dysmenorrhoea have high levels of prostaglandins, hormones known to cause cramping abdominal pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs which act by blocking prostaglandin production. OBJECTIVES: The purpose of this review is to compare all nonsteroidal anti-inflammatory drugs used in the treatment of primary dysmenorrhoea with placebo, with paracetamol and with each other to evaluate their effectiveness and safety. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (11 April 2003), Cochrane Central Register of Controlled Trials (1st quarter 2003), MEDLINE (1966-April 2003), and EMBASE (1980 - Week 15 2003). Attempts were also made to identify trials from the National Research Register and the Clinical Trials Register. Citation lists of relevant publications, review articles, abstracts of major scientific meetings and included studies were also searched. SELECTION CRITERIA: All randomised controlled comparisons of NSAID therapies versus placebo, versus other NSAIDs or versus paracetamol when used to treat primary dysmenorrhoea. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for quality and extracted data, calculating odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Crossover trial data were presented in additional tables and other data were summarised descriptively. MAIN RESULTS: In women with dysmenorrhoea, NSAIDs were found significantly more effective for pain relief than placebo (OR 7.91, 95% CI 5.65 to 11.09), though overall adverse effects were also significantly more common (OR 1.52 95% CI 1.09 to 2.12). When NSAIDs were compared with each other or with paracetamol, there was little evidence of the superiority of any individual NSAID with regard to either efficacy or safety. However the available evidence had little power to detect such differences, as most individual comparisons were based on very few small trials, most of which were unsuitable for meta-analysis. REVIEWER'S CONCLUSIONS: NSAIDs are an effective treatment for dysmenorrhoea, though women using them need to be aware of the significant risk of adverse effects. There is insufficient evidence to determine which (if any) individual NSAID is the most safe and effective for the treatment of dysmenorrhoea.\",\n \"title\": \"Nonsteroidal anti-inflammatory drugs for primary dysmenorrhoea.\"\n },\n {\n \"docid\": \"MED-3517\",\n \"text\": \"Preliminary studies have shown that repeated nasal applications of capsaicin prevented the occurrence of cluster headache attacks. The present study was designed to verify the difference in efficacy of treatment with nasal capsaicin, depending on the side of application. Fifty-two patients affected by episodic form were divided into 2 groups, one receiving the treatment on the same side where the attacks occurred (ipsilateral side), the other on the controlateral side. Eighteen patients with a chronic form alternately received both ipsilateral and controlateral treatments. Seventy percent of the episodic patients, treated on the ipsilateral side, showed a marked amelioration whereas no improvement was noted in the patients treated on the contralateral side. The efficacy of ipsilateral treatment was emphasized by the results obtained in chronic patients. However, in these patients, the maximum period of amelioration lasted no more than 40 days. The difference between the effects of the 2 treatments (contralateral and ipsilateral) was statistically significant in both episodic and chronic sufferers. The efficacy of repeated nasal applications of capsaicin in cluster headache is congruent with previous reports on the therapeutic effect of capsaicin in other pain syndromes (post-herpetic neuralgia, diabetic neuropathy, trigeminal neuralgia) and supports the use of the drug to produce a selective analgesia.\",\n \"title\": \"Preventative effect of repeated nasal applications of capsaicin in cluster headache.\"\n },\n {\n \"docid\": \"MED-1049\",\n \"text\": \"Bowel movements provide vital information on how the body is functioning, and constipation among older adults is especially problematic. Although we do not like hearing the details of someone else's bowel movement, it is a function that nurses need to assess, support, and treat with the same attitude as when caring for patients with pain.\",\n \"title\": \"Bowel movement: the sixth vital sign.\"\n },\n {\n \"docid\": \"MED-946\",\n \"text\": \"BACKGROUND: Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder. The role of pharmacotherapy for IBS is limited and focused mainly on symptom control. OBJECTIVES: The objective of this systematic review was to evaluate the efficacy of bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. SEARCH STRATEGY: Computer assisted structured searches of MEDLINE, EMBASE, The Cochrane library, CINAHL and PsychInfo were conducted for the years 1966-2009. An updated search in April 2011 identified 10 studies which will be considered for inclusion in a future update of this review. SELECTION CRITERIA: Randomized controlled trials comparing bulking agents, antispasmodics or antidepressants with a placebo treatment in patients with irritable bowel syndrome aged over 12 years were considered for inclusion. Only studies published as full papers were included. Studies were not excluded on the basis of language. The primary outcome had to include improvement of abdominal pain, global assessment or symptom score. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from the selected studies. Risk Ratios (RR) and Standardized Mean Differences (SMD) with 95% confidence intervals (CI) were calculated. A proof of practice analysis was conducted including sub-group analyses for different types of bulking agents, spasmolytic agents or antidepressant medication. This was followed by a proof of principle analysis where only the studies with adequate allocation concealment were included. MAIN RESULTS: A total of 56 studies (3725 patients) were included in this review. These included 12 studies of bulking agents (621 patients), 29 of antispasmodics (2333 patients), and 15 of antidepressants (922 patients). The risk of bias was low for most items. However, selection bias is unclear for many of the included studies because the methods used for randomization and allocation concealment were not described. No beneficial effect for bulking agents over placebo was found for improvement of abdominal pain (4 studies; 186 patients; SMD 0.03; 95% CI -0.34 to 0.40; P = 0.87), global assessment (11 studies; 565 patients; RR 1.10; 95% CI 0.91 to 1.33; P = 0.32) or symptom score (3 studies; 126 patients SMD -0.00; 95% CI -0.43 to 0.43; P = 1.00). Subgroup analyses for insoluble and soluble fibres also showed no statistically significant benefit. Separate analysis of the studies with adequate concealment of allocation did not change these results. There was a beneficial effect for antispasmodics over placebo for improvement of abdominal pain (58% of antispasmodic patients improved compared to 46% of placebo; 13 studies; 1392 patients; RR 1.32; 95% CI 1.12 to 1.55; P < 0.001; NNT = 7), global assessment (57% of antispasmodic patients improved compared to 39% of placebo; 22 studies; 1983 patients; RR 1.49; 95% CI 1.25 to 1.77; P < 0.0001; NNT = 5) and symptom score (37% of antispasmodic patients improved compared to 22% of placebo; 4 studies; 586 patients; RR 1.86; 95% CI 1.26 to 2.76; P < 0.01; NNT = 3). Subgroup analyses for different types of antispasmodics found statistically significant benefits for cimteropium/ dicyclomine, peppermint oil, pinaverium and trimebutine. Separate analysis of the studies with adequate allocation concealment found a significant benefit for improvement of abdominal pain. There was a beneficial effect for antidepressants over placebo for improvement of abdominal pain (54% of antidepressants patients improved compared to 37% of placebo; 8 studies; 517 patients; RR 1.49; 95% CI 1.05 to 2.12; P = 0.03; NNT = 5), global assessment (59% of antidepressants patients improved compared to 39% of placebo; 11 studies; 750 patients; RR 1.57; 95% CI 1.23 to 2.00; P < 0.001; NNT = 4) and symptom score (53% of antidepressants patients improved compared to 26% of placebo; 3 studies; 159 patients; RR 1.99; 95% CI 1.32 to 2.99; P = 0.001; NNT = 4). Subgroup analyses showed a statistically significant benefit for selective serotonin releasing inhibitors (SSRIs) for improvement of global assessment and for tricyclic antidepressants (TCAs) for improvement of abdominal pain and symptom score. Separate analysis of studies with adequate allocation concealment found a significant benefit for improvement of symptom score and global assessment. Adverse events were not assessed as an outcome in this review. AUTHORS' CONCLUSIONS: There is no evidence that bulking agents are effective for treating IBS. There is evidence that antispasmodics are effective for the treatment of IBS. The individual subgroups which are effective include: cimetropium/dicyclomine, peppermint oil, pinaverium and trimebutine. There is good evidence that antidepressants are effective for the treatment of IBS. The subgroup analyses for SSRIs and TCAs are unequivocal and their effectiveness may depend on the individual patient. Future research should use rigorous methodology and valid outcome measures.\",\n \"title\": \"Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome.\"\n },\n {\n \"docid\": \"MED-1012\",\n \"text\": \"GOALS: The aim of this study was to assess the efficacy and safety of enteric-coated peppermint oil capsules compared with placebo for the treatment of active irritable bowel syndrome (IBS). BACKGROUND: IBS is a common disorder that is often encountered in clinical practice. Medical interventions are limited and the focus is on symptom control. STUDY: Randomized placebo-controlled trials with a minimum treatment duration of 2 weeks were considered for inclusion. Cross-over studies that provided outcome data before the first cross-over were included. A literature search upto February 2013 identified all applicable randomized-controlled trials. Study quality was evaluated using the Cochrane risk of bias tool. Outcomes included global improvement of IBS symptoms, improvement in abdominal pain, and adverse events. Outcomes were analyzed using an intention-to-treat approach. RESULTS: Nine studies that evaluated 726 patients were identified. The risk of bias was low for most of the factors assessed. Peppermint oil was found to be significantly superior to placebo for global improvement of IBS symptoms (5 studies, 392 patients, relative risk 2.23; 95% confidence interval, 1.78-2.81) and improvement in abdominal pain (5 studies, 357 patients, relative risk 2.14; 95% confidence interval, 1.64-2.79). Although peppermint oil patients were significantly more likely to experience an adverse event, such events were mild and transient in nature. The most commonly reported adverse event was heartburn. CONCLUSIONS: Peppermint oil is a safe and effective short-term treatment for IBS. Future studies should assess the long-term efficacy and safety of peppermint oil and its efficacy relative to other IBS treatments including antidepressants and antispasmodic drugs.\",\n \"title\": \"Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis.\"\n },\n {\n \"docid\": \"MED-5009\",\n \"text\": \"OBJECTIVE: To evaluate the efficacy of preparations with avocado-soybean unsaponifiables (ASUs) in osteoarthritis (OA) patients using meta-analysis on randomized controlled trials (RCTs). METHOD: RCTs from systematic searches were included if they explicitly stated that hip and/or knee OA patients were randomized to either ASU or placebo. The co-primary outcome was reduction in pain and Lequesne index, leading to effect size (ES), calculated as the standardized mean difference. As secondary analysis, the number of responders to therapy was analyzed as odds ratios (ORs). Restricted maximum likelihood methods were applied for the meta-analyses, using mixed effects models. RESULTS: Four trials--all supported by the manufacturer--were included, with 664 OA patients with either hip (41.4%) or knee (58.6%) OA allocated to either 300 mg ASU (336) or placebo (328). Average trial duration was 6 months (range: 3-12 months). Though based on heterogeneous results, the combined pain reduction favored ASU (I(2) = 83.5%, ES = 0.39 [95% confidence intervals: 0.01-0.76], P=0.04). Applying the Lequesne index also favored ASU (I(2) = 61.0%, ES = 0.45 [0.21-0.70], P = 0.0003). Secondarily, the number of responders following ASU compared to placebo (OR = 2.19, P = 0.007) corresponded to a number needed to treat of six (4-21) patients. CONCLUSIONS: Based on the available evidence, patients may be recommended to give ASU a chance for e.g., 3 months. Meta-analysis data support better chances of success in patients with knee OA than in those with hip OA.\",\n \"title\": \"Symptomatic efficacy of avocado-soybean unsaponifiables (ASU) in osteoarthritis (OA) patients: a meta-analysis of randomized controlled trials.\"\n },\n {\n \"docid\": \"MED-4055\",\n \"text\": \"Heterocyclic amines (HCAs) are formed when meat products such as beef, chicken, pork and fish are cooked at high temperatures. The most abundant HCA found in the human diet is 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP). PhIP causes mammary carcinomas in female rats and mice, and is associated with an increased risk of developing colon, breast, and prostate cancer in humans. PhIP is metabolized by cytochrome P-450s producing N-OH-PhIP. The N-OH-PhIP can be esterified by phase II enzymes forming an arylnitrenium ion that binds to DNA causing adducts. Furthermore, N-OH-PhIP may be reduced by cytochrome b5 reductase producing superoxide anions and hydroxyl radicals causing DNA strand breaks. Diallyl sulfide (DAS) has been shown to prevent cancer in several animal models, presumably by metabolic modulation. We hypothesize that PhIP produces reactive oxygen species causing DNA strand breaks and that DAS will inhibit the formation of PhIP induced DNA strand breaks. To test this hypothesis we treated normal breast epithelial (MCF-10A) cells with PhIP, DAS and a combination of PhIP and DAS. The detection of lipid peroxides was used as a surrogate for ROS. Lipid peroxides were detected using a PeroxiDetect kit (Sigma). PhIP increased the production of lipid peroxides and DAS decreased the PhIP-induced peroxidation by 47%. To determine if PhIP causes DNA strand breaks in MCF-10A cells, cells were treated for 3, 6, 9, and 24 h with PhIP (100 microM), DAS (100 microM) and a combination of PhIP (100 microM) and DAS (100 microM). DNA strand breaks were evaluated using the Comet assay. PhIP produced DNA strand breaks in a dose- and time-dependent fashion. We have shown that DAS inhibits PhIP-induced DNA strand breaks by inhibiting the production of reactive oxygen species. Therefore, we propose that DAS can prevent PhIP-induced breast cancer.\",\n \"title\": \"Diallyl sulfide inhibits PhIP-induced DNA strand breaks in normal human breast epithelial cells.\"\n },\n {\n \"docid\": \"MED-3832\",\n \"text\": \"Oestrogen is an important determinant of breast cancer risk. Oestrogen-mimicking plant compounds called phytoestrogens can bind to oestrogen receptors and exert weak oestrogenic effects. Despite this activity, epidemiological studies suggest that the incidence of breast cancer is lower in countries where the intake of phytoestrogens is high, implying that these compounds may reduce breast cancer risk, and possibly have an impact on survival. Isoflavones and lignans are the most common phytoestrogens in the diet. In this article, we present findings from human observational and intervention studies related to both isoflavone and lignan exposure and breast cancer risk and survival. In addition, the clinical implications of these findings are examined in the light of a growing dietary supplement market. An increasing number of breast cancer patients seek to take supplements together with their standard treatment in the hope that these will either prevent recurrence or treat their menopausal symptoms. Observational studies suggest a protective effect of isoflavones on breast cancer risk and the case may be similar for increasing lignan consumption although evidence so far is inconsistent. In contrast, short-term intervention studies suggest a possible stimulatory effect on breast tissue raising concerns of possible adverse effects in breast cancer patients. However, owing to the dearth of human studies investigating effects on breast cancer recurrence and survival the role of phytoestrogens remains unclear. So far, not enough clear evidence exists on which to base guidelines for clinical use, although raising patient awareness of the uncertain effect of phytoestrogens is recommended.\",\n \"title\": \"Do phytoestrogens reduce the risk of breast cancer and breast cancer recurrence? What clinicians need to know.\"\n },\n {\n \"docid\": \"MED-2055\",\n \"text\": \"BACKGROUND: Chronic diarrhea is the most common gastrointestinal symptom of intolerance of cow's milk among children. On the basis of a prior open study, we hypothesized that intolerance of cow's milk can also cause severe perianal lesions with pain on defecation and consequent constipation in young children. METHODS: We performed a double-blind, crossover study comparing cow's milk with soy milk in 65 children (age range, 11 to 72 months) with chronic constipation (defined as having one bowel movement every 3 to 15 days). All had been referred to a pediatric gastroenterology clinic and had previously been treated with laxatives without success; 49 had anal fissures and perianal erythema or edema. After 15 days of observation, the patients received cow's milk or soy milk for two weeks. After a one-week washout period, the feedings were reversed. A response was defined as eight or more bowel movements during a treatment period. RESULTS: Forty-four of the 65 children (68 percent) had a response while receiving soy milk. Anal fissures and pain with defecation resolved. None of the children who received cow's milk had a response. In all 44 children with a response, the response was confirmed with a double-blind challenge with cow's milk. Children with a response had a higher frequency of coexistent rhinitis, dermatitis, or bronchospasm than those with no response (11 of 44 children vs. 1 of 21, P=0.05); they were also more likely to have anal fissures and erythema or edema at base line (40 of 44 vs. 9 of 21, P<0.001), evidence of inflammation of the rectal mucosa on biopsy (26 of 44 vs. 5 of 21, P=0.008), and signs of hypersensitivity, such as specific IgE antibodies to cow's-milk antigens (31 of 44 vs. 4 of 21, P<0.001). CONCLUSIONS: In young children, chronic constipation can be a manifestation of intolerance of cow's milk.\",\n \"title\": \"Intolerance of cow's milk and chronic constipation in children.\"\n },\n {\n \"docid\": \"MED-3447\",\n \"text\": \"To investigate the chemopreventive effects of seaweed on breast cancer, we have been studying the relationship between iodine and breast cancer. We found earlier that the seaweed, wakame, showed a suppressive effect on the proliferation of DMBA (dimethylbenz(a)anthracene)-induced rat mammary tumors, possibly via apoptosis induction. In the present study, powdered mekabu was placed in distilled water, and left to stand for 24 h at 4 degrees C. The filtered supernatant was used as mekabu solution. It showed an extremely strong suppressive effect on rat mammary carcinogenesis when used in daily drinking water, without toxicity. In vitro, mekabu solution strongly induced apoptosis in 3 kinds of human breast cancer cells. These effects were stronger than those of a chemotherapeutic agent widely used to treat human breast cancer. Furthermore, no apoptosis induction was observed in normal human mammary cells. In Japan, mekabu is widely consumed as a safe, inexpensive food. Our results suggest that mekabu has potential for chemoprevention of human breast cancer.\",\n \"title\": \"Seaweed prevents breast cancer?\"\n },\n {\n \"docid\": \"MED-4536\",\n \"text\": \"The cytotoxic effects of aqueous extract of Triphala, an ayurvedic formulation, were investigated on human breast cancer cell line (MCF-7) and a transplantable mouse thymic lymphoma (barcl-95). The viability of treated cells was found to decrease with the increasing concentrations of Triphala. On the other hand, treatment of normal breast epithelial cells, MCF-10 F, human peripheral blood mononuclear cells, mouse liver and spleen cells, with similar concentrations of Triphala did not affect their cytotoxicity significantly. The drug treatment was found to induce apoptosis in MCF-7 and barcl-95 cells in vitro as determined by annexin-V fluorescence and proportion of apoptotic cells was found dependent on Triphala concentration. MCF-7 cells treated with Triphala when subjected to single cell gel electrophoresis, revealed a pattern of DNA damage, characteristic of apoptosis. Studies on Triphala treated MCF-7 and barcl-95 cells showed significant increase in intracellular reactive oxygen species (ROS) in a concentration dependent manner. ROS increase was, however, found to be insignificant in MCF-10 F as well as in murine spleen and liver normal cells. In vivo, direct oral feeding of Triphala to mice (40 mg/kg body weight) transplanted with barcl-95 produced significant reduction in tumor growth as evaluated by tumor volume measurement. It was also found that apoptosis was significantly higher in the excised tumor tissue of Triphala fed mice as compared to the control, suggesting the involvement of apoptosis in tumor growth reduction. These results suggest that Triphala possessed ability to induce cytotoxicity in tumor cells but spared the normal cells. The differential effect of Triphala on normal and tumor cells seems to be related to its ability to evoke differential response in intracellular ROS generation. The differential response of normal and tumor cells to Triphala in vitro and the substantial regression of transplanted tumor in mice fed with Triphala points to its potential use as an anticancer drug for clinical treatment.\",\n \"title\": \"Potential of traditional ayurvedic formulation, Triphala, as a novel anticancer drug.\"\n },\n {\n \"docid\": \"MED-948\",\n \"text\": \"Sprouted vegetable seeds used as food have been implicated as sources of outbreaks of Salmonella and Escherichia coli O157:H7 infections. We profiled the microbiological quality of sprouts and seeds sold at retail shops in Seoul, Korea. Ninety samples of radish sprouts and mixed sprouts purchased at department stores, supermarkets, and traditional markets and 96 samples of radish, alfalfa, and turnip seeds purchased from online stores were analyzed to determine the number of total aerobic bacteria (TAB) and molds or yeasts (MY) and the incidence of Salmonella, E. coli O157:H7, and Enterobacter sakazakii. Significantly higher numbers of TAB (7.52 log CFU/g) and MY (7.36 log CFU/g) were present on mixed sprouts than on radish sprouts (6.97 and 6.50 CFU/g, respectively). Populations of TAB and MY on the sprouts were not significantly affected by location of purchase. Radish seeds contained TAB and MY populations of 4.08 and 2.42 log CFU/g, respectively, whereas populations of TAB were only 2.54 to 2.84 log CFU/g and populations of MY were 0.82 to 1.69 log CFU/g on alfalfa and turnip seeds, respectively. Salmonella and E. coli O157:H7 were not detected on any of the sprout and seed samples tested. E. sakazakii was not found on seeds, but 13.3% of the mixed sprout samples contained this potentially pathogenic bacterium.\",\n \"title\": \"Microbiological examination of vegetable seed sprouts in Korea.\"\n }\n]"}}},{"rowIdx":2586,"cells":{"query_id":{"kind":"string","value":"189500"},"query":{"kind":"string","value":"Karl Malone played for the Los Angeles Lakers."},"positive_passages":{"kind":"list like","value":[{"docid":"Karl_Malone","text":"Karl Anthony Malone ( born July 24 , 1963 ) is an American retired professional basketball player . Nicknamed `` The Mailman '' , Malone played the power forward position and spent his first 18 seasons ( 1985 -- 2003 ) in the National Basketball Association ( NBA ) with the Utah Jazz and formed a formidable duo with his teammate John Stockton . Malone also played one season for the Los Angeles Lakers . Malone was a two-time NBA Most Valuable Player , a 14-time NBA All-Star , and an 11-time member of the All-NBA first team . He scored the second most career points in NBA history ( 36,928 ) ( second behind Kareem Abdul-Jabbar ) , and holds the records for most free throws attempted and made , in addition to co-holding the record for the most first team All-NBA elections in history ( tied with Kobe Bryant and LeBron James ) . He is considered one of the best power forwards in NBA history . Malone played college basketball at Louisiana Tech University . In his three seasons with Louisiana Tech , he helped the Bulldogs basketball team to its first-ever NCAA tournament in 1984 and to first place in the Southland Conference in 1985 . The Utah Jazz drafted Malone in 1985 with the 13th overall pick in the first round . Malone appeared in the playoffs every season in his career , including the NBA Finals in 1997 and 1998 with the Jazz . He played his final season with the Los Angeles Lakers , with whom he played his third Finals in 2004 . However , Malone has the most career postseason losses of any NBA player ever , with 95 . Malone also competed with the United States national team in the Summer Olympic Games of 1992 and 1996 ; in both years he won gold medals . After retiring from the NBA , Malone joined the staff of the Louisiana Tech Bulldogs basketball team in 2007 and was inducted into the Naismith Memorial Basketball Hall of Fame in 2010 ( twice -- for his individual career , and as a member of the 1992 United States men 's Olympic basketball team ) .","title":""}],"string":"[\n {\n \"docid\": \"Karl_Malone\",\n \"text\": \"Karl Anthony Malone ( born July 24 , 1963 ) is an American retired professional basketball player . Nicknamed `` The Mailman '' , Malone played the power forward position and spent his first 18 seasons ( 1985 -- 2003 ) in the National Basketball Association ( NBA ) with the Utah Jazz and formed a formidable duo with his teammate John Stockton . Malone also played one season for the Los Angeles Lakers . Malone was a two-time NBA Most Valuable Player , a 14-time NBA All-Star , and an 11-time member of the All-NBA first team . He scored the second most career points in NBA history ( 36,928 ) ( second behind Kareem Abdul-Jabbar ) , and holds the records for most free throws attempted and made , in addition to co-holding the record for the most first team All-NBA elections in history ( tied with Kobe Bryant and LeBron James ) . He is considered one of the best power forwards in NBA history . Malone played college basketball at Louisiana Tech University . In his three seasons with Louisiana Tech , he helped the Bulldogs basketball team to its first-ever NCAA tournament in 1984 and to first place in the Southland Conference in 1985 . The Utah Jazz drafted Malone in 1985 with the 13th overall pick in the first round . Malone appeared in the playoffs every season in his career , including the NBA Finals in 1997 and 1998 with the Jazz . He played his final season with the Los Angeles Lakers , with whom he played his third Finals in 2004 . However , Malone has the most career postseason losses of any NBA player ever , with 95 . Malone also competed with the United States national team in the Summer Olympic Games of 1992 and 1996 ; in both years he won gold medals . After retiring from the NBA , Malone joined the staff of the Louisiana Tech Bulldogs basketball team in 2007 and was inducted into the Naismith Memorial Basketball Hall of Fame in 2010 ( twice -- for his individual career , and as a member of the 1992 United States men 's Olympic basketball team ) .\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"2003–04_Los_Angeles_Lakers_season","text":"The 2003 -- 04 NBA season was the Lakers ' 56th season in the NBA and 44th in the city of Los Angeles . During the offseason , the Lakers signed veteran free agents and former All-Stars Karl Malone and Gary Payton , who were recruited by Superstar center Shaquille O'Neal , plus re-signing free agent Horace Grant . Payton struggled with coach Phil Jackson 's triangle offense , which limited his ball-handling and post-up opportunities . The off-season is notable for seeing Superstar guard Kobe Bryant getting accused of sexual assault in Colorado , which proved to be an ongoing distraction during the season . The Lake Show started the season 18-3 . However , they ran into struggles when Malone went down with a knee injury in December , soon followed by ailments to Shaq and Kobe . The `` Big Four '' of O'Neal , Bryant , Malone , and Payton played in only 20 games together . Despite all of this , the injury-depleted Lakers still managed a 56 -- 26 record and entered the playoffs as the number 2 seed in the Western Conference . They defeated a Houston Rockets team featuring Steve Francis and a young Yao Ming in five games in the first round . The second round pitted the Lakers against the defending NBA champions the San Antonio Spurs , who defeated the Lakers in last year 's playoffs . Though the Spurs took the first two games , the Lakers won the next four games , including Derek Fisher 's miracle shot with 0.4 seconds left in Game 5 ( a 74 -- 73 Lakers victory ) and a Game 6 88 -- 76 victory at home to advance to the Western Conference Finals against the Kevin Garnett-led Minnesota Timberwolves . The Lakers managed to get through a tough Minnesota team , defeating them in six games to advance to the NBA Finals where they would meet the Detroit Pistons . Though the Lakers were heavily favored to win the title , the heavy-underdog Pistons proved too much for the Lakers as they easily went on to win the series in five games . Game 4 of the NBA Finals was Karl Malone 's final NBA game as injuries forced him to sit out the fifth and final game of the series . Grant also retired the following season . Game 5 was the last time that O'Neal and Bryant would play together as teammates as O'Neal would be traded to the Miami Heat following the season after an acrimonious relationship between the duo . Meanwhile , Fisher signed as a free agent with the Golden State Warriors and Payton , who only spent one season with the Lakers , and Rick Fox were both traded to the Boston Celtics . For head coach Phil Jackson , he left the team at the conclusion of the Finals and later wrote a book about the team 's season in which he voiced disdain for Kobe Bryant , calling him `` uncoachable '' . 2004 was the first time the Lakers had lost the NBA Finals under Jackson . He returned for the 2005-06 season and led the team to another NBA Finals appearance in 2008 , where they fell to the Boston Celtics in six games . However , the Lakers won two more titles the following two seasons before Jackson retired from coaching in 2011 .","title":""},{"docid":"2004–05_Los_Angeles_Lakers_season","text":"The 2004 -- 05 Los Angeles Lakers season was the 57th in the National Basketball Association ( NBA ) and 59th overall . The Los Angeles Lakers finished fifth in the Pacific Division . The season is best remembered as a tough one for the Lakers , starting with a crushing defeat to the Detroit Pistons in last year 's NBA Finals in five games despite being the heavily favored team to win the Finals , winning only 34 games , missing the playoffs for the first time in 11 years . The off-season marked changes for the Lakers , who lost several members from the famed 2004 team : Rick Fox and Gary Payton were traded to the Boston Celtics , but Fox would retire before the season instead of suiting up for Boston , Shaquille O'Neal was traded to the Miami Heat in exchange for Brian Grant , Caron Butler , and Lamar Odom after bad blood between himself and teammate Kobe Bryant culminated after the loss to the Detroit Pistons in the NBA Finals , Derek Fisher left for the Golden State Warriors , though he would return to the Lakers in 2007 and would eventually win two more championships in 2009 and 2010 , and Karl Malone retired in February 2005 after spending half of the season unsigned . The team hired Rudy Tomjanovich , who was well known for his tenure with the Houston Rockets , to be their new head coach for the upcoming season . But midseason , Tomjanovich once again resigned and Frank Hamblen took over for the rest of the season . Kobe Bryant , for the sixth time in his career , did not make the All-NBA First Team .","title":""},{"docid":"The_Last_Season:_A_Team_in_Search_of_Its_Soul","text":"The Last Season : A Team in Search of Its Soul is a book by the former American basketball coach Phil Jackson , originally published by the Penguin Press in 2004 . The book deals with the ups and downs of the Los Angeles Lakers ' 2003-04 season and offers Jackson 's insight into the team 's season that ended in a breakup but not a championship , despite boasting four potential future Hall of Famers : Shaquille O'Neal , Kobe Bryant , Karl Malone and Gary Payton .","title":""},{"docid":"1988_NBA_All-Star_Game","text":"The 38th National Basketball Association All-Star Game was played on February 7 , 1988 , at Chicago Stadium in Chicago . The East won the game 138-133 and Michael Jordan ( who scored a game-high 40 points ) was named the game 's MVP . The Eastern Conference team featured Jordan and Dominique Wilkins , who had faced each other the preceding night in the slam dunk contest , along with Boston Celtics trio Larry Bird , Danny Ainge and Kevin McHale , plus Patrick Ewing of the New York Knicks , Maurice Cheeks and Charles Barkley of the Philadelphia 76ers , Moses Malone of the Washington Bullets , Isiah Thomas of the Detroit Pistons , Doc Rivers of the Atlanta Hawks , and Brad Daugherty of the Cleveland Cavaliers . The Western Conference team was led by Magic Johnson of the Los Angeles Lakers , Clyde Drexler of the Portland Trail Blazers , the Utah Jazz 's power forward Karl Malone and the Houston Rockets ' center Akeem Olajuwon . Joining them were James Worthy and Kareem Abdul-Jabbar of the Lakers , Fat Lever and Alex English of the Denver Nuggets , Xavier McDaniel of the Seattle SuperSonics , Alvin Robertson of the San Antonio Spurs and Mark Aguirre and James Donaldson of the Dallas Mavericks . In this game , Abdul-Jabbar would become the all-time leading scorer in NBA All-Star Game history , a distinction he held for 15 years . The Eastern Conference was coached by Mike Fratello of the Atlanta Hawks , and the Western Conference by Pat Riley of the Lakers . The game was telecast by CBS Sports , with Dick Stockton and Billy Cunningham commentating , and Pat O'Brien and Lesley Visser reporting from the sidelines . On radio , ABC Radio broadcast their fourth consecutive All-Star game , with Lakers announcer Chick Hearn working alongside Celtics announcer Johnny Most , and the two trading roles on play-by-play and color analysis . ABC 's regular NBA announcer Fred Manfra served as a sideline reporter .","title":""},{"docid":"2001–02_Utah_Jazz_season","text":"The 2001 -- 02 NBA season was the Jazz 's 28th season in the National Basketball Association , and 23rd season in Salt Lake City , Utah . During the offseason , the Jazz signed free agent John Amaechi . John Stockton continued to set new standards with 15,000 career assists and 3,000 career steals , as Karl Malone scored his 34,000 th career point . However , the Jazz began to show their age as they played mediocre basketball all season finishing fourth in the Midwest Division with a 44 -- 38 record . The Jazz also beat the Los Angeles Lakers ' record of sixteen consecutive winning seasons , set between 1976 -- 77 and 1991 -- 92 . Malone was selected for the 2002 NBA All-Star Game , but did not play due to an injury . Rookie Andre Kirilenko was selected to the All-Rookie First Team . In the first round of the playoffs , they lost in four games to the Sacramento Kings . Following the season , Bryon Russell signed as a free agent with the Washington Wizards , Donyell Marshall signed with the Chicago Bulls and John Starks retired .","title":""},{"docid":"2001–02_Los_Angeles_Lakers_season","text":"The 2001 -- 02 NBA season was the Lakers ' 54th season in the National Basketball Association , and 42nd in the city of Los Angeles . During the offseason , the Lakers signed All-Star guard Mitch Richmond and free agent Samaki Walker , while acquiring Lindsey Hunter from the Milwaukee Bucks . The team got off to a fast start winning 16 of their first 17 games , and finished second in the Pacific Division with a 58 -- 24 record . Kobe Bryant and Shaquille O'Neal were both selected for the 2002 NBA All-Star Game in which Bryant won MVP honors , but O'Neal did not participate in the All-Star game due to an injury . After sweeping the Portland Trail Blazers 3 -- 0 in the first round of the playoffs , then defeating the San Antonio Spurs 4 -- 1 in the semifinals , the Lakers where pushed to the brink once more in the Western Conference Finals by their archrivals the Sacramento Kings , who they narrowly defeated in a deciding seventh game . They then went on to win the NBA Finals , defeating and sweeping the New Jersey Nets in four straight games for their second three-peat in franchise history , the first since 1952 -- 54 . Following the season , Richmond retired and Hunter was traded to the Toronto Raptors . This would be the third and final consecutive NBA Championship the Lakers won in the early 2000s , as in the next season , their quest for a fourth consecutive NBA Championship ended with a playoff elimination by the San Antonio Spurs in six games in the semifinals , who would then go on to win the NBA Finals that season and their second NBA Championship . Although the Lakers returned to the Finals in 2004 , the Lakers would lose to the Detroit Pistons in five games , despite being the heavy favorites to win and having former All-Stars and veterans Gary Payton and Karl Malone , leading to O'Neal 's departure from the Lakers amidst boiling points between the Lakers staff and management and Kobe Bryant , culminating in his trade to the Miami Heat , ending the early 2000s Lakers dynasty . The Lakers would not win another title until 2009 , in which they defeated the Orlando Magic in five games .","title":""},{"docid":"2002–03_Utah_Jazz_season","text":"The 2002 -- 03 NBA season was the Jazz 's 29th season in the National Basketball Association , and 24th season in Salt Lake City , Utah . During the offseason , the Jazz signed free agents Matt Harpring , Calbert Cheaney and Mark Jackson . The team finished third in the Midwest Division with a 47 -- 35 record , and qualified for the playoffs for the twentieth straight season . However , the Jazz once again failed to make it out of the first round , losing to the Sacramento Kings in five games . This season also marked the end of the Stockton and Malone era . John Stockton and Karl Malone were both given a long standing ovation after Game 4 at the Delta Center , and another one after Game 5 at the ARCO Arena . Following the season , Stockton retired while Malone signed as a free agent with the Los Angeles Lakers . Also following the season , Cheaney signed with the Golden State Warriors and Jackson was released . The Jazz would not return to the playoffs until 2007 .","title":""},{"docid":"2003–04_San_Antonio_Spurs_season","text":"The 2003-04 NBA season was the Spurs ' 28th season in the NBA , the 31st in San Antonio , and 37th season as a franchise . During the offseason , the Spurs acquired Hedo Turkoglu from the Sacramento Kings in a three-team trade and signed free agent Robert Horry . Despite the retirement of David Robinson , the Spurs still managed a 57 -- 25 record , finishing 3rd in the West . They swept the Memphis Grizzlies in four straight games in the first round , and though the Spurs took the first two games in a second round rematch against the team they eliminated in the previous season 's semifinals and eventual Western Conference champion Los Angeles Lakers , led by their `` big four '' of Karl Malone , Shaquille O'Neal , Kobe Bryant , and Gary Payton , the Lakers responded by taking the next four games to eliminate the defending champions . Following the season , Turkoglu signed as a free agent with the Orlando Magic .","title":""},{"docid":"List_of_National_Basketball_Association_franchise_career_scoring_leaders","text":"The National Basketball Association ( NBA ) is a professional men 's basketball league , consisting of 30 teams in North America ( 29 in the United States and one in Canada ) . The NBA was founded in New York City on June 6 , 1946 , as the Basketball Association of America ( BAA ) . It adopted the name National Basketball Association at the start of the 1949 -- 50 season when it merged with the National Basketball League ( NBL ) . The NBA is an active member of USA Basketball , which is recognized by the International Basketball Federation ( FIBA ) as the National Governing Body ( NGB ) for basketball in the country . The league is considered to be one of the four major professional sports leagues of North America . There have been 15 defunct franchises in NBA history . In basketball , points are the sum of the score accumulated through free throw or field goal . The NBA introduced three-point field goals in the 1979 -- 80 season as a bonus for field goals made from a longer distance . Karl Malone scored 36,374 points with the Utah Jazz , the most points by a player for a single franchise . Kareem Abdul-Jabbar , the NBA 's all-time leading scorer , is the Milwaukee Bucks leader with 14,211 points . He scored more points with the Los Angeles Lakers ( 24,176 ) , where he ranks third in Lakers ' history . Kobe Bryant leads the Lakers , scoring the most points in the NBA while playing for only one team in an entire career . Dirk Nowitzki of the Dallas Mavericks is second behind Bryant in scoring while playing for only one team . Statistics accurate as of the conclusion of the regular 2016 -- 17 NBA season .","title":""},{"docid":"Los_Angeles_Lakers","text":"The Los Angeles Lakers are an American professional basketball team based in Los Angeles . The Lakers compete in the National Basketball Association ( NBA ) , as a member of the league 's Western Conference Pacific Division . The Lakers play their home games at Staples Center , an arena shared with the NBA 's Los Angeles Clippers , the Los Angeles Sparks of the Women 's National Basketball Association , and the Los Angeles Kings of the National Hockey League . The Lakers are one of the most successful teams in the history of the NBA , and have won 16 NBA championships , their last being in 2010 . As of 2015 , the Lakers are the second most valuable franchise in the NBA according to Forbes , having an estimated value of $ 2.7 billion . The franchise began with the 1947 purchase of a disbanded team , the Detroit Gems of the National Basketball League ( NBL ) . The new team began playing in Minneapolis , calling themselves the Minneapolis Lakers in honor of the state 's nickname , `` Land of 10,000 Lakes '' . Initially a member of the NBL , the Lakers won the 1948 NBL championship before joining the rival Basketball Association of America and winning five of the next six BAA and NBA championships in Minneapolis after the NBA formed in 1949 . The team was propelled by center George Mikan , who is described by the NBA 's official website as the league 's `` first superstar '' . After struggling financially in the late 1950s following Mikan 's retirement , they relocated to Los Angeles before the 1960 -- 61 season . Led by Hall of Famers Elgin Baylor and Jerry West , Los Angeles made the NBA Finals six times in the 1960s , but lost each series to the Boston Celtics , beginning their long and storied rivalry . In 1968 , the Lakers acquired four-time NBA Most Valuable Player ( MVP ) Wilt Chamberlain to play center , and after losing in the Finals in 1969 and 1970 , they won their sixth NBA title -- and first in Los Angeles -- in 1972 , led by new head coach Bill Sharman . After the retirement of West and Chamberlain , the team acquired another center , Kareem Abdul-Jabbar , who had won multiple MVP awards , but was unable to make the Finals in the late 1970s . The 1980s Lakers were nicknamed `` Showtime '' due to their Magic Johnson-led fast break-offense , and won five championships in a 9-year span , including their first ever Finals championship against the Celtics in 1985 . This team featured Hall of Famers in Johnson , Abdul-Jabbar , and James Worthy , and a Hall of Fame coach , Pat Riley . After Abdul-Jabbar and Johnson 's retirement , the team struggled in the early 1990s before acquiring Shaquille O'Neal and Kobe Bryant in 1996 . Led by O'Neal , Bryant , and another Hall of Fame coach , Phil Jackson , Los Angeles won three consecutive titles between 2000 to 2002 , securing the franchise its second `` three-peat '' . After losing both the 2004 and 2008 NBA Finals , the Lakers won two more championships by defeating the Orlando Magic in 2009 and Boston in 2010 . The Lakers hold the record for NBA 's longest winning streak , 33 straight games , set during the 1971 -- 72 season . 21 Hall of Famers have played for Los Angeles , while four have coached the team . Four Lakers -- Abdul-Jabbar , Johnson , O'Neal , and Bryant -- have won the NBA MVP Award for a total of eight awards .","title":""},{"docid":"Los_Angeles_Lakers_accomplishments_and_records","text":"This page details the all-time statistics , records , and other achievements pertaining to the Los Angeles Lakers . The Los Angeles Lakers are an American professional basketball team currently playing in the National Basketball Association .","title":""},{"docid":"1982–83_Los_Angeles_Lakers_season","text":"In the 1982-83 NBA season , the Lakers were attempting to become the first team since the Boston Celtics in 1969 to repeat as NBA Champions . However , on April 10 , 1983 , rookie James Worthy injured his leg while attempting a putback in a home loss against Phoenix , ending his rookie season . Even without Worthy for the playoffs , the Lakers did make it to the NBA Finals , only to be swept in four games by the Julius Erving and Moses Malone led Philadelphia 76ers .","title":""},{"docid":"1987_NBA_All-Star_Game","text":"The 37th National Basketball Association All-Star Game was played on February 8 , 1987 , at Seattle 's Kingdome . Seattle SuperSonics power forward Tom Chambers was the game 's MVP . The Eastern Conference team consisted of the Washington Bullets ' Moses Malone and Jeff Malone , the Philadelphia 76ers ' Julius Erving , Maurice Cheeks and Charles Barkley , the Boston Celtics ' Larry Bird , Robert Parish and Kevin McHale , the Detroit Pistons ' Isiah Thomas and Bill Laimbeer , the Atlanta Hawks ' Dominique Wilkins and the Chicago Bulls ' Michael Jordan . In addition to game MVP Tom Chambers , the Western Conference team featured the Los Angeles Lakers ' Magic Johnson , James Worthy and Kareem Abdul-Jabbar , the Golden State Warriors ' Sleepy Floyd and Joe Barry Carroll , the Dallas Mavericks ' Rolando Blackman and Mark Aguirre , the San Antonio Spurs ' Alvin Robertson , the Phoenix Suns ' Walter Davis , the Denver Nuggets ' Alex English and the Houston Rockets ' Akeem Olajuwon . Houston 's Ralph Sampson was selected but unable to play due to injury . The coach of the Eastern team was Boston 's K.C. Jones . The coach of the Western team was the Lakers ' Pat Riley .","title":""},{"docid":"2011_NBA_All-Star_Game","text":"The 2011 NBA All-Star Game was an exhibition basketball game that was played on February 20 , 2011 at Staples Center in Los Angeles , California , home of the Los Angeles Clippers and the Los Angeles Lakers . This game was the 60th edition of the National Basketball Association ( NBA ) All-Star Game and was played during the 2010 -- 11 NBA season . The Los Angeles Clippers and Los Angeles Lakers served as the hosts . The Clippers and Lakers were both awarded the All-Star Game in an announcement by commissioner David Stern on June 9 , 2009 . This was the second time that the Staples Center had hosted the All-Star Game ; the arena had previously hosted the event in 2004 . This will be the fifth time that Los Angeles had hosted the All-Star Game ; before Staples Center opened in 1999 , the city had previously hosted the event in 1963 , 1972 , and 1983 . Rihanna , Kanye West and Drake were the halftime performers , while Keri Hilson , Lenny Kravitz and Bruno Mars were the entertainment for pre-show festivities .","title":""},{"docid":"1983_NBA_Playoffs","text":"The 1983 NBA Playoffs was the postseason tournament of the National Basketball Association 's 1982 -- 83 season . This was the final postseason using the 12-team format , before the NBA expanded the postseason to 16 teams the next season . The tournament concluded with the Eastern Conference champion Philadelphia 76ers defeating the Western Conference champion Los Angeles Lakers 4 games to 0 in the NBA Finals . Moses Malone was named NBA Finals MVP . Malone made a famous prediction about the Sixers ' chances prior to the playoffs , saying `` Fo ' , fo ' , fo ' '' -- predicting that the Sixers would win 4 games in each of the three series they would play . They nearly accomplished a sweep of all three rounds , only losing one game ( to Milwaukee in the Eastern Conference Finals ) en route to the championship . The Sixers set a record for highest winning percentage in the playoffs that was not broken until the Lakers went 15 -- 1 in 2001 . The Lakers ' mark , however , came after the expansion to the current 16-team , four-round playoff format , which was first implemented in the 1984 playoffs , while the Sixers avoided the first round by virtue of their top seeding . It was the third time in four years that the Lakers and 76ers had met in the NBA Finals , with the Lakers winning the previous two series . After missing the playoffs the previous year , the Blazers began a string of 21 straight playoff appearances in 1983 lasting until 2003 . They made the playoffs 25 out of 26 years from their title-winning season of 1977 -- 2003 . The record was just one season shy of the 22-year playoff run set by the Syracuse Nationals/Philadelphia 76ers from 1950 -- 1971 . The Celtics were swept out of the playoffs for the first time in team history , losing 4 -- 0 to the Bucks in the second round . This was the Spurs ' last appearance in the Conference Finals until 1995 . However , for players such as George Gervin and Artis Gilmore , the 6-game loss to the Lakers was the last chance they got at reaching the NBA Finals , let alone an NBA Championship ( Gilmore did return to the conference finals with the Celtics in 1988 , but played sparingly ) .","title":""},{"docid":"Lakers–Clippers_rivalry","text":"The Los Angeles Lakers and Los Angeles Clippers are rival teams in the National Basketball Association ( NBA ) . The two Pacific Division teams both play their home games at Staples Center in Los Angeles , inspiring their matchups to sometimes be called the `` Hallway Series '' . The Lakers relocated from Minneapolis in 1960 , while the Clippers moved from San Diego in 1984 . Los Angeles fans have historically favored the Lakers . But the Clippers have sold out every home game at Staples Center since Feb. 2011 and entered the 2016-17 season with the sixth-longest active sellout streak in the NBA . The Lakers have won 11 of their 16 NBA championships since moving to Los Angeles . Meanwhile , the Clippers have made the playoffs only nine times since 1984 and were long considered the laughingstock of the NBA ; in the history of the franchise , they have never advanced past the second round of the playoffs . Some contended that the term rivalry was inaccurate until the Clippers became more successful . For the first time in 20 years , the Clippers won the season series against the Lakers in 2012 -- 13 . This was the first of five straight season series victories for the Clippers , which included season sweeps in both 2014-15 and 2015-16 . With the Clippers ' 3-1 series win in 2016-17 , the Lakers have now won the season series just four times in the past 13 seasons , with five Clippers wins , four Lakers wins , and four ties . The Lakers hold a 99 -- 47 advantage in the all-time series against the Clippers . The two teams have never met in the playoffs .","title":""},{"docid":"Los_Angeles_Clippers","text":"The Los Angeles Clippers , often abbreviated as the LA Clippers , are an American men 's professional basketball team based in Los Angeles . The Clippers compete in the National Basketball Association ( NBA ) as a member of the league 's Western Conference Pacific Division . The Clippers play their home games at Staples Center in downtown Los Angeles , an arena shared with the Los Angeles Lakers of the NBA , the Los Angeles Sparks of the Women 's National Basketball Association ( WNBA ) , and the Los Angeles Kings of the National Hockey League ( NHL ) . The franchise was founded in 1970 as the Buffalo Braves , one of three expansion teams to join the NBA that year . The Braves moved from Buffalo , New York to San Diego , California in 1978 and became known as the San Diego Clippers . In 1984 , the Clippers moved to Los Angeles . Through much of its history , the franchise failed to see significant regular season or playoff success . The Clippers were frequently seen as an example of a perennial loser in American professional sports , drawing unfavorable comparisons to the historically successful Lakers , with whom they have shared a market since 1984 and an arena since 1999 . The Clippers ' fortunes turned in the early 2010s with the acquisition of core players Blake Griffin , DeAndre Jordan , and Chris Paul . In 2013 , the franchise won its first division title , as the team made the playoffs for the ninth time in franchise history and the third time in the previous eight seasons . They also added to their budding rivalry with the Lakers , as they finished with a better record than the Lakers for the fifth time and won the season series for the second time since moving to Los Angeles in 1984 , this time in a sweep . They repeated as division champions in 2014 .","title":""},{"docid":"Lakers–Pistons_rivalry","text":"The Lakers -- Pistons rivalry is an American professional basketball rivalry between the Los Angeles Lakers and Detroit Pistons . This rivalry , which was showcased 3 times in the NBA Finals ( 1988 , 1989 , 2004 ) , pitted the high-flying , All-Star filled Lakers teams against the blue collar , team-first oriented Pistons squads . Despite playing the role of underdog in all 3 of their final round meetings with Los Angeles , Detroit enjoyed significant success against the Lakers , claiming the NBA title against them twice .","title":""},{"docid":"List_of_Los_Angeles_Lakers_seasons","text":"The Los Angeles Lakers are a professional basketball team based in Los Angeles , California that competes in the National Basketball Association ( NBA ) , which was formerly called the Basketball Association of America ( BAA ) . Since 1999 , the Lakers have played their home games at Staples Center . The Lakers ' franchise was founded in 1947 in Minneapolis , Minnesota . The first owners purchased the disbanded Gems from Detroit , Michigan , then renamed and moved the team . It was in Minneapolis where the Lakers received their official title from Minnesota 's nickname , Land of 10,000 Lakes . The Lakers won five championships before relocating to Los Angeles for the 1960 -- 61 NBA season . The Lakers went on to lose all of their eight appearances in the NBA Finals in the 1960s , despite the presence of Elgin Baylor and Jerry West . In , the Lakers compiled a 33-game winning streak , the longest streak in U.S. professional team sports , and won their sixth title , under coach Bill Sharman . The Lakers ' popularity soared in the 1980s when they won five additional championships during a nine-year span with the help of Hall of Famers Magic Johnson , Kareem Abdul-Jabbar , James Worthy and coach Pat Riley , the franchise 's all-time leader in both regular season and playoff games coached and wins . Two of those championships during that span were against their arch-rivals , the Boston Celtics . With the help of Shaquille O'Neal , Kobe Bryant , and Hall of Fame coach Phil Jackson , the Lakers played in seven NBA Finals between 2000 and 2010 , winning three of them consecutively from 2000 to 2002 , losing the next two in 2004 and 2008 , and winning in 2009 and 2010 ; the last three appearances were without O'Neal . The Lakers hold records for having ( at the end of the 2014 -- 15 NBA season ) the most wins ( 3,125 ) , the highest winning percentage ( .620 ) , the most NBA Finals appearances ( 31 ) of any NBA franchise , second-fewest non-playoff seasons with seven and are second NBA championships with 16 , behind the Boston Celtics ' 17 .","title":""},{"docid":"Los_Angeles_Lakers_all-time_roster","text":"The Los Angeles Lakers are an American professional basketball team based in Los Angeles , California . They play in the Pacific Division of the Western Conference in the National Basketball Association ( NBA ) . The Lakers ' franchise was founded in 1947 in Detroit , Michigan before moving to Minneapolis , Minnesota , where the team got its official title from the state 's nickname , `` Land of 10,000 Lakes '' . The Minneapolis Lakers won five NBA Finals before relocating to Los Angeles in the 1960 -- 61 NBA season , becoming the first West Coast team in league history . In the 1960s , the Lakers reached the NBA Finals six times , but lost every series to the Boston Celtics , beginning their long and storied rivalry . In 1972 , with future Hall of Famers Wilt Chamberlain , Gail Goodrich , and Jerry West , the Lakers compiled a 33-game winning streak , the longest streak in U.S. professional team sports , and won their sixth title under coach Bill Sharman . The Lakers ' popularity soared in the 1980s when they won five additional championships during a nine-year span with the help of Hall of Famers Magic Johnson , Kareem Abdul-Jabbar , James Worthy and coach Pat Riley , the franchise 's all-time leader in both regular season and playoff games coached and wins . Two of those championships during that span were against their arch-rivals , the Boston Celtics . With the team of Shaquille O'Neal , Kobe Bryant , Toby Tincher , and Hall of Fame coach Phil Jackson , the Lakers played in four of the first five NBA Finals of the 21st century ; winning three consecutively from 2000 to 2002 , and losing the fourth in 2004 . The Lakers would then conclude the decade with three straight Finals appearances ; losing to the Boston Celtics in 2008 but then prevailing with back-to-back championships against the Orlando Magic in 2009 and the Boston Celtics in 2010 . The 2010 championship marks the 16th NBA championship in Lakers franchise history . There have been 339 past and current players who has appeared in at least one game for the Lakers franchise . __ NOTOC __","title":""},{"docid":"List_of_Los_Angeles_Lakers_head_coaches","text":"The Los Angeles Lakers are an American professional basketball team based in Los Angeles , California , formerly known as the Minneapolis Lakers from 1948 to 1960 . They play in the Pacific Division of the Western Conference in the National Basketball Association ( NBA ) The Lakers have played their home games at the Staples Center since 1999 . The franchise took its official name from Minnesota 's nickname , the Land of 10,000 Lakes . At the time the name was revealed , the Lakers were in Minneapolis . In their franchise history , the team has only missed the NBA playoffs five times . According to Forbes magazine , the Lakers are the second most valuable basketball franchise in the NBA , valued at approximately US$ 1 billion , surpassed only by the New York Knicks . The Lakers are majority-owned by Jerry Buss 's family trust , while Mitch Kupchak is the general manager . There have been 24 head coaches for the Lakers since joining the NBA . The franchise 's first head coach while in the NBA was John Kundla , who coached for 11 seasons with the Lakers . The Lakers won four additional NBA championships in the next five years under Kundla . Phil Jackson is the franchise 's all-time leader for the most regular-season games coached ( 820 ) , most playoff games coached ( 181 ) , most regular-season game wins ( 553 ) , and most playoff wins ( 118 ) . The Lakers have won 16 championships ; five with Kundla , five with Phil Jackson , four with Riley , one with Bill Sharman , and one with Paul Westhead . With the Lakers , Sharman , Riley , and Del Harris have won the NBA Coach of the Year Award , in , , and respectively . Kundla , Bill Sharman , Riley and Jackson have been inducted into the Basketball Hall of Fame as a coach . George Mikan , Jim Pollard , Jerry West , Riley , Magic Johnson , Kurt Rambis , Byron Scott and Luke Walton have all played and head coached for the Lakers .","title":""},{"docid":"List_of_Los_Angeles_Lakers_first_and_second_round_draft_picks","text":"The Los Angeles Lakers joined the National Basketball Association ( NBA ) in the 1948 -- 49 BAA season as the Minneapolis Lakers , but moved to Los Angeles for the 1959 -- 60 NBA season , where they have been located ever since . They play their home games at Staples Center , which they share with fellow NBA team the Los Angeles Clippers . The Minneapolis Lakers took its official name from Minnesota 's nickname , Land of 10,000 Lakes . The NBA started as the Basketball Association of America ( BAA ) . To help teams acquire local players , territorial picks were instituted from its inception in 1950 until 1965 . Territorial picks were used as a type of special draft choice used in the NBA Draft . Prior to the league 's draft , a team could forfeit its first round draft pick and select a player from within 50 mi . Territorial picks were then eliminated when the draft was revamped in 1966 . Before the 1989 NBA draft , the draft had more than two rounds . After 1989 , the NBA agreed with the National Basketball Players ' Association to limit drafts to two rounds . Teams can also trade their picks , so some years a team could have more than or less than two picks . The Lakers selected Chuck Hanger with their first pick , ninth overall in the 1948 BAA draft . The Lakers got their first overall draft pick in 1958 by choosing Elgin Baylor , who went on to be selected as the only NBA Rookie of the Year to be on the Lakers . The Lakers also drafted Magic Johnson in 1979 with their second first overall pick , who was rated the greatest NBA point guard of all time by ESPN in 2007 . The Lakers had no first round draft picks in 1967 , 1976 , 1978 , 1980 , 2008 , 2010 , 2011 , 2012 and 2013 . The Lakers had no first or second round draft picks from 1983 , 1987 , and 2001 . Throughout the years , the Lakers had traded away some of their picks as well as traded for other teams ' picks . As a result of the various trades , the Los Angeles Lakers had five first and second round picks in 1979 .","title":""},{"docid":"Spectrum_SportsNet_(Los_Angeles)","text":"Spectrum SportsNet and Spectrum Deportes , formerly Time Warner Cable SportsNet and Time Warner Cable Deportes , ( abbreviated as TWC SportsNet and TWC Deportes ) are American regional sports cable and satellite television networks that are owned by Charter Communications through its acquisition of Time Warner Cable in May 2016 , with the Los Angeles Lakers maintaining editorial control over the content , including team-assigned reporters and anchors , as well as team-related programming . The networks are based near the Lakers ' team headquarters in the Los Angeles suburb of El Segundo , California . Spectrum SportsNet -- which broadcasts in English -- and Spectrum Deportes -- which is the first U.S. regional sports network with a 24-hour Spanish feed -- launched at 7:00 p.m. Pacific Time on October 1 , 2012 . Spectrum SportsNet and Spectrum Deportes serve the Los Angeles and San Diego metropolitan areas , the Coachella Valley , the Central Coast of California , Las Vegas , and Hawaii . Lakers game broadcasts serve as the centerpiece of both networks . Spectrum SportsNet and Spectrum Deportes have been the exclusive home of all Lakers games that are not televised nationally since the 2012 -- 13 NBA season . Other sports events aired on the networks include Los Angeles Galaxy soccer and Los Angeles Sparks basketball games . Game broadcasts are carried in high definition in both English and Spanish . A Korean language audio track is also provided via the second audio program function available on most television sets and cable receiver boxes ; as a result , Spectrum SportsNet holds the distinction of being the first English-language television network to offer Asian-language play-by-play audio of sporting events .","title":""},{"docid":"1997–98_Utah_Jazz_season","text":"The 1997 -- 98 NBA season was the Jazz 's 24th season in the National Basketball Association , and 19th season in Salt Lake City , Utah . Without John Stockton for the first 18 games due to a knee injury , the Jazz slowly got off to an 11 -- 7 start to the season . However , Stockton would eventually return as the Jazz won 31 of their final 36 games after the All-Star break , and finished first place in the Midwest Division with a 62 -- 20 record . The Jazz 's top scorer Karl Malone , who averaged 27.0 points per game , was part of a Jazz offense that had two other players , Stockton and Jeff Hornacek , averaging double-digits in points . Malone was the only member of the team to play in the 1998 NBA All-Star Game . In the first round of the playoffs , the Jazz trailed 2 -- 1 to the 8th-seeded Houston Rockets . However , they won the series in five games . In the semifinals , they defeated the San Antonio Spurs in five games . After that , the Jazz swept the Los Angeles Lakers in the Western Conference Finals in four straight games to advance to the NBA Finals for the second consecutive year , and once again , met the Chicago Bulls in a rematch of last year 's NBA Finals , in which they lost to the Bulls in six games . In the Finals , just like last year 's NBA Finals , they lost in six games to the Chicago Bulls . Following the season , Antoine Carr signed as a free agent with the Houston Rockets , and Chris Morris signed with the Phoenix Suns . The team 's season roster is featured in the video games NBA 2K16 and NBA 2K17 .","title":""},{"docid":"1972_NBA_Finals","text":"The 1972 NBA Finals was the championship series played at the conclusion of the 1971 -- 72 National Basketball Association ( NBA ) season . The Western Conference champion Los Angeles Lakers defeated the Eastern Conference champion New York Knicks in five games . The Los Angeles Lakers got their first NBA championship since the Lakers moved to Los Angeles from Minneapolis . This season 's edition of the Los Angeles Lakers had won an NBA-record 69 regular season games , including 33 wins in a row . They were led by Wilt Chamberlain , the NBA 's top rebounder that season . Guards Gail Goodrich and Jerry West were each among the NBA 's top ten scorers that season , spearheading the NBA 's top offense at 121 points per game . West also led the NBA in assists . The Lakers as a team led all NBA teams in rebounds and assists that season . Los Angeles had swept a solid 57-win Chicago Bulls team in the playoff 's opening round , then defeated the defending champion Milwaukee Bucks ( record of 63-19 ) in six games to win the Western Conference . That historic series had matched Chamberlain against Kareem Abdul-Jabbar , and West against Oscar Robertson . Having defeated tough Milwaukee , 48-win New York figured to be an easy formality for the Lakers . New York was a top defensive team that allowed just 98.2 points per game and made 47 % of their shots as a team . They had defeated the 38-win Baltimore Bullets and then upset the 56-win Boston Celtics to win the Eastern Conference final .","title":""},{"docid":"1984_NBA_Finals","text":"The 1984 NBA Finals , also known as Showdown ' 84 , was the championship round of the 1983-84 NBA season . In 1984 , the Boston Celtics defeated the Los Angeles Lakers in a seven-game Finals , winning Game 7 111-102 . Larry Bird averaged 27 points and 14 rebounds a game during the series , earning the Finals Most Valuable Player ( MVP ) . Bird was also named the league regular season MVP for that year . This series was the long-awaited rematch of the Los Angeles Lakers and Boston Celtics after their rivalry was revived in 1979 with the Magic Johnson-Larry Bird pair entering the league . After the Lakers won Game 1 , a crucial steal in Game 2 led to a tie game and the Celtics were able to win in overtime to tie the series . The Lakers won Game 3 easily and almost won Game 4 , but were again thwarted . Now tied 2-2 , the Lakers and Celtics each held serve at their home court to send the series to Boston for Game 7 . Game 5 was a classic , with Bird coming up with a huge game in one of the ( literally ) hottest games ever ( 97 ° F ) in the non-air conditioned Boston Garden . Game 7 was also contested in hot temperatures that hovered around 91 ° F . The score was close but the contest eventually went to the Celtics . Cedric Maxwell scored 24 points against the Los Angeles Lakers in the decisive Game 7 victory . Los Angeles won all three games played on Sunday afternoons . Boston won the games played on Tuesday night , Wednesday night , Thursday night , and Friday night . The Series schedule was an odd schedule , due entirely to the whims of television . Game One was played on a Sunday afternoon in Boston , about 36 hours after the Lakers had eliminated the Phoenix Suns in the Western Finals . The teams then had three plus days off , not playing until Thursday night . Then , after Game 3 on Sunday afternoon in Los Angeles , the teams had two plus days off , not playing again until Wednesday night . That in turn started a wearying back-and-forth across the country ... Wednesday night at LA , Friday night at Boston , Sunday afternoon at LA , and Tuesday night at Boston ... to end the series . The following year , the Finals format switched to 2-3-2 , where Games 1 , 2 , 6 , and 7 were hosted by the team with the best record . The change in format came after Red Auerbach complained about the constant travelling during the finals . The 2-2-1-1-1 format would return for the 2014 NBA Finals .","title":""},{"docid":"Laker_Band","text":"The Los Angeles Laker Band is a subset of the USC Trojan Marching Band that plays at Lakers home games . Created in 1979 at the request of Lakers owner Dr. Jerry Buss , this brass and rhythm ensemble performs at every Laker home game , including the playoffs , and regularly performs the national anthem before the game on the Staples Center court . The group is the only one of its kind in the NBA : a dedicated band that performs at every game in its own section . The band sits and performs in section 308 . The Laker Band comprises nine trumpets , six or seven trombones , a bass guitar , and a drum set . The band has been featured in the championship parade in downtown Los Angeles when the Lakers win the NBA title . Band members and the Laker Girls ride atop firetrucks for the parade down Figueroa Blvd. .","title":""},{"docid":"1991–92_Portland_Trail_Blazers_season","text":"The 1991 -- 92 NBA season was the 22nd season for the Portland Trail Blazers in the National Basketball Association . After losing three of their first four games , the Blazers would quickly recover as they continued to lead the way in the West posting a 57 -- 25 record , earning their second straight Pacific Division championship and 10th consecutive trip to the NBA Playoffs . Clyde Drexler led the way averaging 25.0 points per game while being named to the All-NBA First Team , selected for the 1992 NBA All-Star Game , and finishing a distant second to Michael Jordan in the MVP ballot . The Blazers began their postseason run by defeating the Los Angeles Lakers 3 -- 1 in the first round , eliminating the Lakers for the first time since Portland 's championship season of 1977 ; the Lakers had beaten the Blazers in four playoff series since then , including most recently the 1991 Western Conference Finals . The Blazers proceeded to defeat the Phoenix Suns 4 -- 1 in the second round and Karl Malone 's Utah Jazz 4 -- 2 in the Western Conference Finals , earning their second trip to the NBA Finals in three years , and a matchup with the defending champion Chicago Bulls . The Blazers ' dream of winning their second NBA title , however , was stifled by the Michael Jordan and Scottie Pippen-led Bulls , who defeated the Blazers 4 -- 2 and won their second straight NBA title . Following the season , Danny Ainge signed as a free agent with the Phoenix Suns . For the season , the Blazers changed their logo and uniforms . Both would last until 2002 .","title":""},{"docid":"1991–92_Los_Angeles_Lakers_season","text":"The 1991 -- 92 NBA season was the Lakers ' 44th season in the National Basketball Association , and 32nd in the city of Los Angeles . This was the start of a new era for the Los Angeles Lakers , as they had to cope with the sudden retirement of their longtime superstar , Magic Johnson , due to an HIV infection . However , he would make a brief return playing in the 1992 NBA All-Star Game winning the All-Star MVP award . During the offseason , the Lakers acquired Sedale Threatt from the Seattle SuperSonics . Without Johnson for the first time since 1979 , the Lakers won 10 of their first 13 games including a nine-game winning streak . However , they struggled in February losing seven straight games with a 3 -- 9 record during the month . The Lakers struggled to make the playoffs as they finished sixth in the Pacific Division with a 43 -- 39 record . It would be considered their worst record since the 1975 -- 76 season . As the # 8 seed in the Western Conference , the Lakers were eliminated from the first round of the NBA playoffs in four games by the Portland Trail Blazers . Following the season , Mike Dunleavy left and took a coaching job with the Milwaukee Bucks .","title":""},{"docid":"Andrew_Bynum","text":"Andrew Bynum ( born October 27 , 1987 ) is an American professional basketball player who is currently a free agent . Bynum has played for the Los Angeles Lakers , Cleveland Cavaliers , and Indiana Pacers of the National Basketball Association ( NBA ) . The 7 ft center is a two-time NBA champion , winning in 2009 and 2010 with the Lakers . He was named an All-Star and was selected to the All-NBA team in 2012 . Bynum was an All-American player in high school before he decided to forgo college and enter the 2005 NBA draft . He was selected with the 10th overall pick by the Los Angeles Lakers , and he became the youngest player ever to play in an NBA game . In 2012 , he was traded after 7 seasons with the Lakers to the Philadelphia 76ers as part of a four-team deal that also sent All-Star center Dwight Howard to Los Angeles . Bynum missed the entire 2012 -- 13 season because of knee problems . He signed as a free agent with Cleveland , where he briefly played before being traded to the Chicago Bulls , who subsequently released him . He then signed with the Indiana Pacers for the remainder of the 2013 -- 14 season .","title":""}],"string":"[\n {\n \"docid\": \"2003–04_Los_Angeles_Lakers_season\",\n \"text\": \"The 2003 -- 04 NBA season was the Lakers ' 56th season in the NBA and 44th in the city of Los Angeles . During the offseason , the Lakers signed veteran free agents and former All-Stars Karl Malone and Gary Payton , who were recruited by Superstar center Shaquille O'Neal , plus re-signing free agent Horace Grant . Payton struggled with coach Phil Jackson 's triangle offense , which limited his ball-handling and post-up opportunities . The off-season is notable for seeing Superstar guard Kobe Bryant getting accused of sexual assault in Colorado , which proved to be an ongoing distraction during the season . The Lake Show started the season 18-3 . However , they ran into struggles when Malone went down with a knee injury in December , soon followed by ailments to Shaq and Kobe . The `` Big Four '' of O'Neal , Bryant , Malone , and Payton played in only 20 games together . Despite all of this , the injury-depleted Lakers still managed a 56 -- 26 record and entered the playoffs as the number 2 seed in the Western Conference . They defeated a Houston Rockets team featuring Steve Francis and a young Yao Ming in five games in the first round . The second round pitted the Lakers against the defending NBA champions the San Antonio Spurs , who defeated the Lakers in last year 's playoffs . Though the Spurs took the first two games , the Lakers won the next four games , including Derek Fisher 's miracle shot with 0.4 seconds left in Game 5 ( a 74 -- 73 Lakers victory ) and a Game 6 88 -- 76 victory at home to advance to the Western Conference Finals against the Kevin Garnett-led Minnesota Timberwolves . The Lakers managed to get through a tough Minnesota team , defeating them in six games to advance to the NBA Finals where they would meet the Detroit Pistons . Though the Lakers were heavily favored to win the title , the heavy-underdog Pistons proved too much for the Lakers as they easily went on to win the series in five games . Game 4 of the NBA Finals was Karl Malone 's final NBA game as injuries forced him to sit out the fifth and final game of the series . Grant also retired the following season . Game 5 was the last time that O'Neal and Bryant would play together as teammates as O'Neal would be traded to the Miami Heat following the season after an acrimonious relationship between the duo . Meanwhile , Fisher signed as a free agent with the Golden State Warriors and Payton , who only spent one season with the Lakers , and Rick Fox were both traded to the Boston Celtics . For head coach Phil Jackson , he left the team at the conclusion of the Finals and later wrote a book about the team 's season in which he voiced disdain for Kobe Bryant , calling him `` uncoachable '' . 2004 was the first time the Lakers had lost the NBA Finals under Jackson . He returned for the 2005-06 season and led the team to another NBA Finals appearance in 2008 , where they fell to the Boston Celtics in six games . However , the Lakers won two more titles the following two seasons before Jackson retired from coaching in 2011 .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"2004–05_Los_Angeles_Lakers_season\",\n \"text\": \"The 2004 -- 05 Los Angeles Lakers season was the 57th in the National Basketball Association ( NBA ) and 59th overall . The Los Angeles Lakers finished fifth in the Pacific Division . The season is best remembered as a tough one for the Lakers , starting with a crushing defeat to the Detroit Pistons in last year 's NBA Finals in five games despite being the heavily favored team to win the Finals , winning only 34 games , missing the playoffs for the first time in 11 years . The off-season marked changes for the Lakers , who lost several members from the famed 2004 team : Rick Fox and Gary Payton were traded to the Boston Celtics , but Fox would retire before the season instead of suiting up for Boston , Shaquille O'Neal was traded to the Miami Heat in exchange for Brian Grant , Caron Butler , and Lamar Odom after bad blood between himself and teammate Kobe Bryant culminated after the loss to the Detroit Pistons in the NBA Finals , Derek Fisher left for the Golden State Warriors , though he would return to the Lakers in 2007 and would eventually win two more championships in 2009 and 2010 , and Karl Malone retired in February 2005 after spending half of the season unsigned . The team hired Rudy Tomjanovich , who was well known for his tenure with the Houston Rockets , to be their new head coach for the upcoming season . But midseason , Tomjanovich once again resigned and Frank Hamblen took over for the rest of the season . Kobe Bryant , for the sixth time in his career , did not make the All-NBA First Team .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"The_Last_Season:_A_Team_in_Search_of_Its_Soul\",\n \"text\": \"The Last Season : A Team in Search of Its Soul is a book by the former American basketball coach Phil Jackson , originally published by the Penguin Press in 2004 . The book deals with the ups and downs of the Los Angeles Lakers ' 2003-04 season and offers Jackson 's insight into the team 's season that ended in a breakup but not a championship , despite boasting four potential future Hall of Famers : Shaquille O'Neal , Kobe Bryant , Karl Malone and Gary Payton .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1988_NBA_All-Star_Game\",\n \"text\": \"The 38th National Basketball Association All-Star Game was played on February 7 , 1988 , at Chicago Stadium in Chicago . The East won the game 138-133 and Michael Jordan ( who scored a game-high 40 points ) was named the game 's MVP . The Eastern Conference team featured Jordan and Dominique Wilkins , who had faced each other the preceding night in the slam dunk contest , along with Boston Celtics trio Larry Bird , Danny Ainge and Kevin McHale , plus Patrick Ewing of the New York Knicks , Maurice Cheeks and Charles Barkley of the Philadelphia 76ers , Moses Malone of the Washington Bullets , Isiah Thomas of the Detroit Pistons , Doc Rivers of the Atlanta Hawks , and Brad Daugherty of the Cleveland Cavaliers . The Western Conference team was led by Magic Johnson of the Los Angeles Lakers , Clyde Drexler of the Portland Trail Blazers , the Utah Jazz 's power forward Karl Malone and the Houston Rockets ' center Akeem Olajuwon . Joining them were James Worthy and Kareem Abdul-Jabbar of the Lakers , Fat Lever and Alex English of the Denver Nuggets , Xavier McDaniel of the Seattle SuperSonics , Alvin Robertson of the San Antonio Spurs and Mark Aguirre and James Donaldson of the Dallas Mavericks . In this game , Abdul-Jabbar would become the all-time leading scorer in NBA All-Star Game history , a distinction he held for 15 years . The Eastern Conference was coached by Mike Fratello of the Atlanta Hawks , and the Western Conference by Pat Riley of the Lakers . The game was telecast by CBS Sports , with Dick Stockton and Billy Cunningham commentating , and Pat O'Brien and Lesley Visser reporting from the sidelines . On radio , ABC Radio broadcast their fourth consecutive All-Star game , with Lakers announcer Chick Hearn working alongside Celtics announcer Johnny Most , and the two trading roles on play-by-play and color analysis . ABC 's regular NBA announcer Fred Manfra served as a sideline reporter .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"2001–02_Utah_Jazz_season\",\n \"text\": \"The 2001 -- 02 NBA season was the Jazz 's 28th season in the National Basketball Association , and 23rd season in Salt Lake City , Utah . During the offseason , the Jazz signed free agent John Amaechi . John Stockton continued to set new standards with 15,000 career assists and 3,000 career steals , as Karl Malone scored his 34,000 th career point . However , the Jazz began to show their age as they played mediocre basketball all season finishing fourth in the Midwest Division with a 44 -- 38 record . The Jazz also beat the Los Angeles Lakers ' record of sixteen consecutive winning seasons , set between 1976 -- 77 and 1991 -- 92 . Malone was selected for the 2002 NBA All-Star Game , but did not play due to an injury . Rookie Andre Kirilenko was selected to the All-Rookie First Team . In the first round of the playoffs , they lost in four games to the Sacramento Kings . Following the season , Bryon Russell signed as a free agent with the Washington Wizards , Donyell Marshall signed with the Chicago Bulls and John Starks retired .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"2001–02_Los_Angeles_Lakers_season\",\n \"text\": \"The 2001 -- 02 NBA season was the Lakers ' 54th season in the National Basketball Association , and 42nd in the city of Los Angeles . During the offseason , the Lakers signed All-Star guard Mitch Richmond and free agent Samaki Walker , while acquiring Lindsey Hunter from the Milwaukee Bucks . The team got off to a fast start winning 16 of their first 17 games , and finished second in the Pacific Division with a 58 -- 24 record . Kobe Bryant and Shaquille O'Neal were both selected for the 2002 NBA All-Star Game in which Bryant won MVP honors , but O'Neal did not participate in the All-Star game due to an injury . After sweeping the Portland Trail Blazers 3 -- 0 in the first round of the playoffs , then defeating the San Antonio Spurs 4 -- 1 in the semifinals , the Lakers where pushed to the brink once more in the Western Conference Finals by their archrivals the Sacramento Kings , who they narrowly defeated in a deciding seventh game . They then went on to win the NBA Finals , defeating and sweeping the New Jersey Nets in four straight games for their second three-peat in franchise history , the first since 1952 -- 54 . Following the season , Richmond retired and Hunter was traded to the Toronto Raptors . This would be the third and final consecutive NBA Championship the Lakers won in the early 2000s , as in the next season , their quest for a fourth consecutive NBA Championship ended with a playoff elimination by the San Antonio Spurs in six games in the semifinals , who would then go on to win the NBA Finals that season and their second NBA Championship . Although the Lakers returned to the Finals in 2004 , the Lakers would lose to the Detroit Pistons in five games , despite being the heavy favorites to win and having former All-Stars and veterans Gary Payton and Karl Malone , leading to O'Neal 's departure from the Lakers amidst boiling points between the Lakers staff and management and Kobe Bryant , culminating in his trade to the Miami Heat , ending the early 2000s Lakers dynasty . The Lakers would not win another title until 2009 , in which they defeated the Orlando Magic in five games .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"2002–03_Utah_Jazz_season\",\n \"text\": \"The 2002 -- 03 NBA season was the Jazz 's 29th season in the National Basketball Association , and 24th season in Salt Lake City , Utah . During the offseason , the Jazz signed free agents Matt Harpring , Calbert Cheaney and Mark Jackson . The team finished third in the Midwest Division with a 47 -- 35 record , and qualified for the playoffs for the twentieth straight season . However , the Jazz once again failed to make it out of the first round , losing to the Sacramento Kings in five games . This season also marked the end of the Stockton and Malone era . John Stockton and Karl Malone were both given a long standing ovation after Game 4 at the Delta Center , and another one after Game 5 at the ARCO Arena . Following the season , Stockton retired while Malone signed as a free agent with the Los Angeles Lakers . Also following the season , Cheaney signed with the Golden State Warriors and Jackson was released . The Jazz would not return to the playoffs until 2007 .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"2003–04_San_Antonio_Spurs_season\",\n \"text\": \"The 2003-04 NBA season was the Spurs ' 28th season in the NBA , the 31st in San Antonio , and 37th season as a franchise . During the offseason , the Spurs acquired Hedo Turkoglu from the Sacramento Kings in a three-team trade and signed free agent Robert Horry . Despite the retirement of David Robinson , the Spurs still managed a 57 -- 25 record , finishing 3rd in the West . They swept the Memphis Grizzlies in four straight games in the first round , and though the Spurs took the first two games in a second round rematch against the team they eliminated in the previous season 's semifinals and eventual Western Conference champion Los Angeles Lakers , led by their `` big four '' of Karl Malone , Shaquille O'Neal , Kobe Bryant , and Gary Payton , the Lakers responded by taking the next four games to eliminate the defending champions . Following the season , Turkoglu signed as a free agent with the Orlando Magic .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"List_of_National_Basketball_Association_franchise_career_scoring_leaders\",\n \"text\": \"The National Basketball Association ( NBA ) is a professional men 's basketball league , consisting of 30 teams in North America ( 29 in the United States and one in Canada ) . The NBA was founded in New York City on June 6 , 1946 , as the Basketball Association of America ( BAA ) . It adopted the name National Basketball Association at the start of the 1949 -- 50 season when it merged with the National Basketball League ( NBL ) . The NBA is an active member of USA Basketball , which is recognized by the International Basketball Federation ( FIBA ) as the National Governing Body ( NGB ) for basketball in the country . The league is considered to be one of the four major professional sports leagues of North America . There have been 15 defunct franchises in NBA history . In basketball , points are the sum of the score accumulated through free throw or field goal . The NBA introduced three-point field goals in the 1979 -- 80 season as a bonus for field goals made from a longer distance . Karl Malone scored 36,374 points with the Utah Jazz , the most points by a player for a single franchise . Kareem Abdul-Jabbar , the NBA 's all-time leading scorer , is the Milwaukee Bucks leader with 14,211 points . He scored more points with the Los Angeles Lakers ( 24,176 ) , where he ranks third in Lakers ' history . Kobe Bryant leads the Lakers , scoring the most points in the NBA while playing for only one team in an entire career . Dirk Nowitzki of the Dallas Mavericks is second behind Bryant in scoring while playing for only one team . Statistics accurate as of the conclusion of the regular 2016 -- 17 NBA season .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Los_Angeles_Lakers\",\n \"text\": \"The Los Angeles Lakers are an American professional basketball team based in Los Angeles . The Lakers compete in the National Basketball Association ( NBA ) , as a member of the league 's Western Conference Pacific Division . The Lakers play their home games at Staples Center , an arena shared with the NBA 's Los Angeles Clippers , the Los Angeles Sparks of the Women 's National Basketball Association , and the Los Angeles Kings of the National Hockey League . The Lakers are one of the most successful teams in the history of the NBA , and have won 16 NBA championships , their last being in 2010 . As of 2015 , the Lakers are the second most valuable franchise in the NBA according to Forbes , having an estimated value of $ 2.7 billion . The franchise began with the 1947 purchase of a disbanded team , the Detroit Gems of the National Basketball League ( NBL ) . The new team began playing in Minneapolis , calling themselves the Minneapolis Lakers in honor of the state 's nickname , `` Land of 10,000 Lakes '' . Initially a member of the NBL , the Lakers won the 1948 NBL championship before joining the rival Basketball Association of America and winning five of the next six BAA and NBA championships in Minneapolis after the NBA formed in 1949 . The team was propelled by center George Mikan , who is described by the NBA 's official website as the league 's `` first superstar '' . After struggling financially in the late 1950s following Mikan 's retirement , they relocated to Los Angeles before the 1960 -- 61 season . Led by Hall of Famers Elgin Baylor and Jerry West , Los Angeles made the NBA Finals six times in the 1960s , but lost each series to the Boston Celtics , beginning their long and storied rivalry . In 1968 , the Lakers acquired four-time NBA Most Valuable Player ( MVP ) Wilt Chamberlain to play center , and after losing in the Finals in 1969 and 1970 , they won their sixth NBA title -- and first in Los Angeles -- in 1972 , led by new head coach Bill Sharman . After the retirement of West and Chamberlain , the team acquired another center , Kareem Abdul-Jabbar , who had won multiple MVP awards , but was unable to make the Finals in the late 1970s . The 1980s Lakers were nicknamed `` Showtime '' due to their Magic Johnson-led fast break-offense , and won five championships in a 9-year span , including their first ever Finals championship against the Celtics in 1985 . This team featured Hall of Famers in Johnson , Abdul-Jabbar , and James Worthy , and a Hall of Fame coach , Pat Riley . After Abdul-Jabbar and Johnson 's retirement , the team struggled in the early 1990s before acquiring Shaquille O'Neal and Kobe Bryant in 1996 . Led by O'Neal , Bryant , and another Hall of Fame coach , Phil Jackson , Los Angeles won three consecutive titles between 2000 to 2002 , securing the franchise its second `` three-peat '' . After losing both the 2004 and 2008 NBA Finals , the Lakers won two more championships by defeating the Orlando Magic in 2009 and Boston in 2010 . The Lakers hold the record for NBA 's longest winning streak , 33 straight games , set during the 1971 -- 72 season . 21 Hall of Famers have played for Los Angeles , while four have coached the team . Four Lakers -- Abdul-Jabbar , Johnson , O'Neal , and Bryant -- have won the NBA MVP Award for a total of eight awards .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Los_Angeles_Lakers_accomplishments_and_records\",\n \"text\": \"This page details the all-time statistics , records , and other achievements pertaining to the Los Angeles Lakers . The Los Angeles Lakers are an American professional basketball team currently playing in the National Basketball Association .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1982–83_Los_Angeles_Lakers_season\",\n \"text\": \"In the 1982-83 NBA season , the Lakers were attempting to become the first team since the Boston Celtics in 1969 to repeat as NBA Champions . However , on April 10 , 1983 , rookie James Worthy injured his leg while attempting a putback in a home loss against Phoenix , ending his rookie season . Even without Worthy for the playoffs , the Lakers did make it to the NBA Finals , only to be swept in four games by the Julius Erving and Moses Malone led Philadelphia 76ers .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1987_NBA_All-Star_Game\",\n \"text\": \"The 37th National Basketball Association All-Star Game was played on February 8 , 1987 , at Seattle 's Kingdome . Seattle SuperSonics power forward Tom Chambers was the game 's MVP . The Eastern Conference team consisted of the Washington Bullets ' Moses Malone and Jeff Malone , the Philadelphia 76ers ' Julius Erving , Maurice Cheeks and Charles Barkley , the Boston Celtics ' Larry Bird , Robert Parish and Kevin McHale , the Detroit Pistons ' Isiah Thomas and Bill Laimbeer , the Atlanta Hawks ' Dominique Wilkins and the Chicago Bulls ' Michael Jordan . In addition to game MVP Tom Chambers , the Western Conference team featured the Los Angeles Lakers ' Magic Johnson , James Worthy and Kareem Abdul-Jabbar , the Golden State Warriors ' Sleepy Floyd and Joe Barry Carroll , the Dallas Mavericks ' Rolando Blackman and Mark Aguirre , the San Antonio Spurs ' Alvin Robertson , the Phoenix Suns ' Walter Davis , the Denver Nuggets ' Alex English and the Houston Rockets ' Akeem Olajuwon . Houston 's Ralph Sampson was selected but unable to play due to injury . The coach of the Eastern team was Boston 's K.C. Jones . The coach of the Western team was the Lakers ' Pat Riley .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"2011_NBA_All-Star_Game\",\n \"text\": \"The 2011 NBA All-Star Game was an exhibition basketball game that was played on February 20 , 2011 at Staples Center in Los Angeles , California , home of the Los Angeles Clippers and the Los Angeles Lakers . This game was the 60th edition of the National Basketball Association ( NBA ) All-Star Game and was played during the 2010 -- 11 NBA season . The Los Angeles Clippers and Los Angeles Lakers served as the hosts . The Clippers and Lakers were both awarded the All-Star Game in an announcement by commissioner David Stern on June 9 , 2009 . This was the second time that the Staples Center had hosted the All-Star Game ; the arena had previously hosted the event in 2004 . This will be the fifth time that Los Angeles had hosted the All-Star Game ; before Staples Center opened in 1999 , the city had previously hosted the event in 1963 , 1972 , and 1983 . Rihanna , Kanye West and Drake were the halftime performers , while Keri Hilson , Lenny Kravitz and Bruno Mars were the entertainment for pre-show festivities .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1983_NBA_Playoffs\",\n \"text\": \"The 1983 NBA Playoffs was the postseason tournament of the National Basketball Association 's 1982 -- 83 season . This was the final postseason using the 12-team format , before the NBA expanded the postseason to 16 teams the next season . The tournament concluded with the Eastern Conference champion Philadelphia 76ers defeating the Western Conference champion Los Angeles Lakers 4 games to 0 in the NBA Finals . Moses Malone was named NBA Finals MVP . Malone made a famous prediction about the Sixers ' chances prior to the playoffs , saying `` Fo ' , fo ' , fo ' '' -- predicting that the Sixers would win 4 games in each of the three series they would play . They nearly accomplished a sweep of all three rounds , only losing one game ( to Milwaukee in the Eastern Conference Finals ) en route to the championship . The Sixers set a record for highest winning percentage in the playoffs that was not broken until the Lakers went 15 -- 1 in 2001 . The Lakers ' mark , however , came after the expansion to the current 16-team , four-round playoff format , which was first implemented in the 1984 playoffs , while the Sixers avoided the first round by virtue of their top seeding . It was the third time in four years that the Lakers and 76ers had met in the NBA Finals , with the Lakers winning the previous two series . After missing the playoffs the previous year , the Blazers began a string of 21 straight playoff appearances in 1983 lasting until 2003 . They made the playoffs 25 out of 26 years from their title-winning season of 1977 -- 2003 . The record was just one season shy of the 22-year playoff run set by the Syracuse Nationals/Philadelphia 76ers from 1950 -- 1971 . The Celtics were swept out of the playoffs for the first time in team history , losing 4 -- 0 to the Bucks in the second round . This was the Spurs ' last appearance in the Conference Finals until 1995 . However , for players such as George Gervin and Artis Gilmore , the 6-game loss to the Lakers was the last chance they got at reaching the NBA Finals , let alone an NBA Championship ( Gilmore did return to the conference finals with the Celtics in 1988 , but played sparingly ) .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Lakers–Clippers_rivalry\",\n \"text\": \"The Los Angeles Lakers and Los Angeles Clippers are rival teams in the National Basketball Association ( NBA ) . The two Pacific Division teams both play their home games at Staples Center in Los Angeles , inspiring their matchups to sometimes be called the `` Hallway Series '' . The Lakers relocated from Minneapolis in 1960 , while the Clippers moved from San Diego in 1984 . Los Angeles fans have historically favored the Lakers . But the Clippers have sold out every home game at Staples Center since Feb. 2011 and entered the 2016-17 season with the sixth-longest active sellout streak in the NBA . The Lakers have won 11 of their 16 NBA championships since moving to Los Angeles . Meanwhile , the Clippers have made the playoffs only nine times since 1984 and were long considered the laughingstock of the NBA ; in the history of the franchise , they have never advanced past the second round of the playoffs . Some contended that the term rivalry was inaccurate until the Clippers became more successful . For the first time in 20 years , the Clippers won the season series against the Lakers in 2012 -- 13 . This was the first of five straight season series victories for the Clippers , which included season sweeps in both 2014-15 and 2015-16 . With the Clippers ' 3-1 series win in 2016-17 , the Lakers have now won the season series just four times in the past 13 seasons , with five Clippers wins , four Lakers wins , and four ties . The Lakers hold a 99 -- 47 advantage in the all-time series against the Clippers . The two teams have never met in the playoffs .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Los_Angeles_Clippers\",\n \"text\": \"The Los Angeles Clippers , often abbreviated as the LA Clippers , are an American men 's professional basketball team based in Los Angeles . The Clippers compete in the National Basketball Association ( NBA ) as a member of the league 's Western Conference Pacific Division . The Clippers play their home games at Staples Center in downtown Los Angeles , an arena shared with the Los Angeles Lakers of the NBA , the Los Angeles Sparks of the Women 's National Basketball Association ( WNBA ) , and the Los Angeles Kings of the National Hockey League ( NHL ) . The franchise was founded in 1970 as the Buffalo Braves , one of three expansion teams to join the NBA that year . The Braves moved from Buffalo , New York to San Diego , California in 1978 and became known as the San Diego Clippers . In 1984 , the Clippers moved to Los Angeles . Through much of its history , the franchise failed to see significant regular season or playoff success . The Clippers were frequently seen as an example of a perennial loser in American professional sports , drawing unfavorable comparisons to the historically successful Lakers , with whom they have shared a market since 1984 and an arena since 1999 . The Clippers ' fortunes turned in the early 2010s with the acquisition of core players Blake Griffin , DeAndre Jordan , and Chris Paul . In 2013 , the franchise won its first division title , as the team made the playoffs for the ninth time in franchise history and the third time in the previous eight seasons . They also added to their budding rivalry with the Lakers , as they finished with a better record than the Lakers for the fifth time and won the season series for the second time since moving to Los Angeles in 1984 , this time in a sweep . They repeated as division champions in 2014 .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Lakers–Pistons_rivalry\",\n \"text\": \"The Lakers -- Pistons rivalry is an American professional basketball rivalry between the Los Angeles Lakers and Detroit Pistons . This rivalry , which was showcased 3 times in the NBA Finals ( 1988 , 1989 , 2004 ) , pitted the high-flying , All-Star filled Lakers teams against the blue collar , team-first oriented Pistons squads . Despite playing the role of underdog in all 3 of their final round meetings with Los Angeles , Detroit enjoyed significant success against the Lakers , claiming the NBA title against them twice .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"List_of_Los_Angeles_Lakers_seasons\",\n \"text\": \"The Los Angeles Lakers are a professional basketball team based in Los Angeles , California that competes in the National Basketball Association ( NBA ) , which was formerly called the Basketball Association of America ( BAA ) . Since 1999 , the Lakers have played their home games at Staples Center . The Lakers ' franchise was founded in 1947 in Minneapolis , Minnesota . The first owners purchased the disbanded Gems from Detroit , Michigan , then renamed and moved the team . It was in Minneapolis where the Lakers received their official title from Minnesota 's nickname , Land of 10,000 Lakes . The Lakers won five championships before relocating to Los Angeles for the 1960 -- 61 NBA season . The Lakers went on to lose all of their eight appearances in the NBA Finals in the 1960s , despite the presence of Elgin Baylor and Jerry West . In , the Lakers compiled a 33-game winning streak , the longest streak in U.S. professional team sports , and won their sixth title , under coach Bill Sharman . The Lakers ' popularity soared in the 1980s when they won five additional championships during a nine-year span with the help of Hall of Famers Magic Johnson , Kareem Abdul-Jabbar , James Worthy and coach Pat Riley , the franchise 's all-time leader in both regular season and playoff games coached and wins . Two of those championships during that span were against their arch-rivals , the Boston Celtics . With the help of Shaquille O'Neal , Kobe Bryant , and Hall of Fame coach Phil Jackson , the Lakers played in seven NBA Finals between 2000 and 2010 , winning three of them consecutively from 2000 to 2002 , losing the next two in 2004 and 2008 , and winning in 2009 and 2010 ; the last three appearances were without O'Neal . The Lakers hold records for having ( at the end of the 2014 -- 15 NBA season ) the most wins ( 3,125 ) , the highest winning percentage ( .620 ) , the most NBA Finals appearances ( 31 ) of any NBA franchise , second-fewest non-playoff seasons with seven and are second NBA championships with 16 , behind the Boston Celtics ' 17 .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Los_Angeles_Lakers_all-time_roster\",\n \"text\": \"The Los Angeles Lakers are an American professional basketball team based in Los Angeles , California . They play in the Pacific Division of the Western Conference in the National Basketball Association ( NBA ) . The Lakers ' franchise was founded in 1947 in Detroit , Michigan before moving to Minneapolis , Minnesota , where the team got its official title from the state 's nickname , `` Land of 10,000 Lakes '' . The Minneapolis Lakers won five NBA Finals before relocating to Los Angeles in the 1960 -- 61 NBA season , becoming the first West Coast team in league history . In the 1960s , the Lakers reached the NBA Finals six times , but lost every series to the Boston Celtics , beginning their long and storied rivalry . In 1972 , with future Hall of Famers Wilt Chamberlain , Gail Goodrich , and Jerry West , the Lakers compiled a 33-game winning streak , the longest streak in U.S. professional team sports , and won their sixth title under coach Bill Sharman . The Lakers ' popularity soared in the 1980s when they won five additional championships during a nine-year span with the help of Hall of Famers Magic Johnson , Kareem Abdul-Jabbar , James Worthy and coach Pat Riley , the franchise 's all-time leader in both regular season and playoff games coached and wins . Two of those championships during that span were against their arch-rivals , the Boston Celtics . With the team of Shaquille O'Neal , Kobe Bryant , Toby Tincher , and Hall of Fame coach Phil Jackson , the Lakers played in four of the first five NBA Finals of the 21st century ; winning three consecutively from 2000 to 2002 , and losing the fourth in 2004 . The Lakers would then conclude the decade with three straight Finals appearances ; losing to the Boston Celtics in 2008 but then prevailing with back-to-back championships against the Orlando Magic in 2009 and the Boston Celtics in 2010 . The 2010 championship marks the 16th NBA championship in Lakers franchise history . There have been 339 past and current players who has appeared in at least one game for the Lakers franchise . __ NOTOC __\",\n \"title\": \"\"\n },\n {\n \"docid\": \"List_of_Los_Angeles_Lakers_head_coaches\",\n \"text\": \"The Los Angeles Lakers are an American professional basketball team based in Los Angeles , California , formerly known as the Minneapolis Lakers from 1948 to 1960 . They play in the Pacific Division of the Western Conference in the National Basketball Association ( NBA ) The Lakers have played their home games at the Staples Center since 1999 . The franchise took its official name from Minnesota 's nickname , the Land of 10,000 Lakes . At the time the name was revealed , the Lakers were in Minneapolis . In their franchise history , the team has only missed the NBA playoffs five times . According to Forbes magazine , the Lakers are the second most valuable basketball franchise in the NBA , valued at approximately US$ 1 billion , surpassed only by the New York Knicks . The Lakers are majority-owned by Jerry Buss 's family trust , while Mitch Kupchak is the general manager . There have been 24 head coaches for the Lakers since joining the NBA . The franchise 's first head coach while in the NBA was John Kundla , who coached for 11 seasons with the Lakers . The Lakers won four additional NBA championships in the next five years under Kundla . Phil Jackson is the franchise 's all-time leader for the most regular-season games coached ( 820 ) , most playoff games coached ( 181 ) , most regular-season game wins ( 553 ) , and most playoff wins ( 118 ) . The Lakers have won 16 championships ; five with Kundla , five with Phil Jackson , four with Riley , one with Bill Sharman , and one with Paul Westhead . With the Lakers , Sharman , Riley , and Del Harris have won the NBA Coach of the Year Award , in , , and respectively . Kundla , Bill Sharman , Riley and Jackson have been inducted into the Basketball Hall of Fame as a coach . George Mikan , Jim Pollard , Jerry West , Riley , Magic Johnson , Kurt Rambis , Byron Scott and Luke Walton have all played and head coached for the Lakers .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"List_of_Los_Angeles_Lakers_first_and_second_round_draft_picks\",\n \"text\": \"The Los Angeles Lakers joined the National Basketball Association ( NBA ) in the 1948 -- 49 BAA season as the Minneapolis Lakers , but moved to Los Angeles for the 1959 -- 60 NBA season , where they have been located ever since . They play their home games at Staples Center , which they share with fellow NBA team the Los Angeles Clippers . The Minneapolis Lakers took its official name from Minnesota 's nickname , Land of 10,000 Lakes . The NBA started as the Basketball Association of America ( BAA ) . To help teams acquire local players , territorial picks were instituted from its inception in 1950 until 1965 . Territorial picks were used as a type of special draft choice used in the NBA Draft . Prior to the league 's draft , a team could forfeit its first round draft pick and select a player from within 50 mi . Territorial picks were then eliminated when the draft was revamped in 1966 . Before the 1989 NBA draft , the draft had more than two rounds . After 1989 , the NBA agreed with the National Basketball Players ' Association to limit drafts to two rounds . Teams can also trade their picks , so some years a team could have more than or less than two picks . The Lakers selected Chuck Hanger with their first pick , ninth overall in the 1948 BAA draft . The Lakers got their first overall draft pick in 1958 by choosing Elgin Baylor , who went on to be selected as the only NBA Rookie of the Year to be on the Lakers . The Lakers also drafted Magic Johnson in 1979 with their second first overall pick , who was rated the greatest NBA point guard of all time by ESPN in 2007 . The Lakers had no first round draft picks in 1967 , 1976 , 1978 , 1980 , 2008 , 2010 , 2011 , 2012 and 2013 . The Lakers had no first or second round draft picks from 1983 , 1987 , and 2001 . Throughout the years , the Lakers had traded away some of their picks as well as traded for other teams ' picks . As a result of the various trades , the Los Angeles Lakers had five first and second round picks in 1979 .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Spectrum_SportsNet_(Los_Angeles)\",\n \"text\": \"Spectrum SportsNet and Spectrum Deportes , formerly Time Warner Cable SportsNet and Time Warner Cable Deportes , ( abbreviated as TWC SportsNet and TWC Deportes ) are American regional sports cable and satellite television networks that are owned by Charter Communications through its acquisition of Time Warner Cable in May 2016 , with the Los Angeles Lakers maintaining editorial control over the content , including team-assigned reporters and anchors , as well as team-related programming . The networks are based near the Lakers ' team headquarters in the Los Angeles suburb of El Segundo , California . Spectrum SportsNet -- which broadcasts in English -- and Spectrum Deportes -- which is the first U.S. regional sports network with a 24-hour Spanish feed -- launched at 7:00 p.m. Pacific Time on October 1 , 2012 . Spectrum SportsNet and Spectrum Deportes serve the Los Angeles and San Diego metropolitan areas , the Coachella Valley , the Central Coast of California , Las Vegas , and Hawaii . Lakers game broadcasts serve as the centerpiece of both networks . Spectrum SportsNet and Spectrum Deportes have been the exclusive home of all Lakers games that are not televised nationally since the 2012 -- 13 NBA season . Other sports events aired on the networks include Los Angeles Galaxy soccer and Los Angeles Sparks basketball games . Game broadcasts are carried in high definition in both English and Spanish . A Korean language audio track is also provided via the second audio program function available on most television sets and cable receiver boxes ; as a result , Spectrum SportsNet holds the distinction of being the first English-language television network to offer Asian-language play-by-play audio of sporting events .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1997–98_Utah_Jazz_season\",\n \"text\": \"The 1997 -- 98 NBA season was the Jazz 's 24th season in the National Basketball Association , and 19th season in Salt Lake City , Utah . Without John Stockton for the first 18 games due to a knee injury , the Jazz slowly got off to an 11 -- 7 start to the season . However , Stockton would eventually return as the Jazz won 31 of their final 36 games after the All-Star break , and finished first place in the Midwest Division with a 62 -- 20 record . The Jazz 's top scorer Karl Malone , who averaged 27.0 points per game , was part of a Jazz offense that had two other players , Stockton and Jeff Hornacek , averaging double-digits in points . Malone was the only member of the team to play in the 1998 NBA All-Star Game . In the first round of the playoffs , the Jazz trailed 2 -- 1 to the 8th-seeded Houston Rockets . However , they won the series in five games . In the semifinals , they defeated the San Antonio Spurs in five games . After that , the Jazz swept the Los Angeles Lakers in the Western Conference Finals in four straight games to advance to the NBA Finals for the second consecutive year , and once again , met the Chicago Bulls in a rematch of last year 's NBA Finals , in which they lost to the Bulls in six games . In the Finals , just like last year 's NBA Finals , they lost in six games to the Chicago Bulls . Following the season , Antoine Carr signed as a free agent with the Houston Rockets , and Chris Morris signed with the Phoenix Suns . The team 's season roster is featured in the video games NBA 2K16 and NBA 2K17 .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1972_NBA_Finals\",\n \"text\": \"The 1972 NBA Finals was the championship series played at the conclusion of the 1971 -- 72 National Basketball Association ( NBA ) season . The Western Conference champion Los Angeles Lakers defeated the Eastern Conference champion New York Knicks in five games . The Los Angeles Lakers got their first NBA championship since the Lakers moved to Los Angeles from Minneapolis . This season 's edition of the Los Angeles Lakers had won an NBA-record 69 regular season games , including 33 wins in a row . They were led by Wilt Chamberlain , the NBA 's top rebounder that season . Guards Gail Goodrich and Jerry West were each among the NBA 's top ten scorers that season , spearheading the NBA 's top offense at 121 points per game . West also led the NBA in assists . The Lakers as a team led all NBA teams in rebounds and assists that season . Los Angeles had swept a solid 57-win Chicago Bulls team in the playoff 's opening round , then defeated the defending champion Milwaukee Bucks ( record of 63-19 ) in six games to win the Western Conference . That historic series had matched Chamberlain against Kareem Abdul-Jabbar , and West against Oscar Robertson . Having defeated tough Milwaukee , 48-win New York figured to be an easy formality for the Lakers . New York was a top defensive team that allowed just 98.2 points per game and made 47 % of their shots as a team . They had defeated the 38-win Baltimore Bullets and then upset the 56-win Boston Celtics to win the Eastern Conference final .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1984_NBA_Finals\",\n \"text\": \"The 1984 NBA Finals , also known as Showdown ' 84 , was the championship round of the 1983-84 NBA season . In 1984 , the Boston Celtics defeated the Los Angeles Lakers in a seven-game Finals , winning Game 7 111-102 . Larry Bird averaged 27 points and 14 rebounds a game during the series , earning the Finals Most Valuable Player ( MVP ) . Bird was also named the league regular season MVP for that year . This series was the long-awaited rematch of the Los Angeles Lakers and Boston Celtics after their rivalry was revived in 1979 with the Magic Johnson-Larry Bird pair entering the league . After the Lakers won Game 1 , a crucial steal in Game 2 led to a tie game and the Celtics were able to win in overtime to tie the series . The Lakers won Game 3 easily and almost won Game 4 , but were again thwarted . Now tied 2-2 , the Lakers and Celtics each held serve at their home court to send the series to Boston for Game 7 . Game 5 was a classic , with Bird coming up with a huge game in one of the ( literally ) hottest games ever ( 97 ° F ) in the non-air conditioned Boston Garden . Game 7 was also contested in hot temperatures that hovered around 91 ° F . The score was close but the contest eventually went to the Celtics . Cedric Maxwell scored 24 points against the Los Angeles Lakers in the decisive Game 7 victory . Los Angeles won all three games played on Sunday afternoons . Boston won the games played on Tuesday night , Wednesday night , Thursday night , and Friday night . The Series schedule was an odd schedule , due entirely to the whims of television . Game One was played on a Sunday afternoon in Boston , about 36 hours after the Lakers had eliminated the Phoenix Suns in the Western Finals . The teams then had three plus days off , not playing until Thursday night . Then , after Game 3 on Sunday afternoon in Los Angeles , the teams had two plus days off , not playing again until Wednesday night . That in turn started a wearying back-and-forth across the country ... Wednesday night at LA , Friday night at Boston , Sunday afternoon at LA , and Tuesday night at Boston ... to end the series . The following year , the Finals format switched to 2-3-2 , where Games 1 , 2 , 6 , and 7 were hosted by the team with the best record . The change in format came after Red Auerbach complained about the constant travelling during the finals . The 2-2-1-1-1 format would return for the 2014 NBA Finals .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Laker_Band\",\n \"text\": \"The Los Angeles Laker Band is a subset of the USC Trojan Marching Band that plays at Lakers home games . Created in 1979 at the request of Lakers owner Dr. Jerry Buss , this brass and rhythm ensemble performs at every Laker home game , including the playoffs , and regularly performs the national anthem before the game on the Staples Center court . The group is the only one of its kind in the NBA : a dedicated band that performs at every game in its own section . The band sits and performs in section 308 . The Laker Band comprises nine trumpets , six or seven trombones , a bass guitar , and a drum set . The band has been featured in the championship parade in downtown Los Angeles when the Lakers win the NBA title . Band members and the Laker Girls ride atop firetrucks for the parade down Figueroa Blvd. .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1991–92_Portland_Trail_Blazers_season\",\n \"text\": \"The 1991 -- 92 NBA season was the 22nd season for the Portland Trail Blazers in the National Basketball Association . After losing three of their first four games , the Blazers would quickly recover as they continued to lead the way in the West posting a 57 -- 25 record , earning their second straight Pacific Division championship and 10th consecutive trip to the NBA Playoffs . Clyde Drexler led the way averaging 25.0 points per game while being named to the All-NBA First Team , selected for the 1992 NBA All-Star Game , and finishing a distant second to Michael Jordan in the MVP ballot . The Blazers began their postseason run by defeating the Los Angeles Lakers 3 -- 1 in the first round , eliminating the Lakers for the first time since Portland 's championship season of 1977 ; the Lakers had beaten the Blazers in four playoff series since then , including most recently the 1991 Western Conference Finals . The Blazers proceeded to defeat the Phoenix Suns 4 -- 1 in the second round and Karl Malone 's Utah Jazz 4 -- 2 in the Western Conference Finals , earning their second trip to the NBA Finals in three years , and a matchup with the defending champion Chicago Bulls . The Blazers ' dream of winning their second NBA title , however , was stifled by the Michael Jordan and Scottie Pippen-led Bulls , who defeated the Blazers 4 -- 2 and won their second straight NBA title . Following the season , Danny Ainge signed as a free agent with the Phoenix Suns . For the season , the Blazers changed their logo and uniforms . Both would last until 2002 .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1991–92_Los_Angeles_Lakers_season\",\n \"text\": \"The 1991 -- 92 NBA season was the Lakers ' 44th season in the National Basketball Association , and 32nd in the city of Los Angeles . This was the start of a new era for the Los Angeles Lakers , as they had to cope with the sudden retirement of their longtime superstar , Magic Johnson , due to an HIV infection . However , he would make a brief return playing in the 1992 NBA All-Star Game winning the All-Star MVP award . During the offseason , the Lakers acquired Sedale Threatt from the Seattle SuperSonics . Without Johnson for the first time since 1979 , the Lakers won 10 of their first 13 games including a nine-game winning streak . However , they struggled in February losing seven straight games with a 3 -- 9 record during the month . The Lakers struggled to make the playoffs as they finished sixth in the Pacific Division with a 43 -- 39 record . It would be considered their worst record since the 1975 -- 76 season . As the # 8 seed in the Western Conference , the Lakers were eliminated from the first round of the NBA playoffs in four games by the Portland Trail Blazers . Following the season , Mike Dunleavy left and took a coaching job with the Milwaukee Bucks .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Andrew_Bynum\",\n \"text\": \"Andrew Bynum ( born October 27 , 1987 ) is an American professional basketball player who is currently a free agent . Bynum has played for the Los Angeles Lakers , Cleveland Cavaliers , and Indiana Pacers of the National Basketball Association ( NBA ) . The 7 ft center is a two-time NBA champion , winning in 2009 and 2010 with the Lakers . He was named an All-Star and was selected to the All-NBA team in 2012 . Bynum was an All-American player in high school before he decided to forgo college and enter the 2005 NBA draft . He was selected with the 10th overall pick by the Los Angeles Lakers , and he became the youngest player ever to play in an NBA game . In 2012 , he was traded after 7 seasons with the Lakers to the Philadelphia 76ers as part of a four-team deal that also sent All-Star center Dwight Howard to Los Angeles . Bynum missed the entire 2012 -- 13 season because of knee problems . He signed as a free agent with Cleveland , where he briefly played before being traded to the Chicago Bulls , who subsequently released him . He then signed with the Indiana Pacers for the remainder of the 2013 -- 14 season .\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":2587,"cells":{"query_id":{"kind":"string","value":"1703"},"query":{"kind":"string","value":"Is it possible to borrow money to accrue interest, and then use that interest to pay back the borrower + fees?"},"positive_passages":{"kind":"list like","value":[{"docid":"149723","text":"\"With (1), it's rather confusing as to where \"\"interest\"\" refers to what you're paying and where it refers to what you're being paid, and it's confusing what you expect the numbers to work out to be. If you have to pay normal interest on top of sharing the interest you receive, then you're losing money. If the lending bank is receiving less interest than the going market rate, then they're losing money. If the bank you've deposited the money with is paying more than the going market rate, they're losing money. I don't see how you imagine a scenario where someone isn't losing money. For (2) and (3), you're buying stocks on margin, which certainly is something that happens, but you'll have to get an account that is specifically for margin trading. It's a specific type of credit with specific rules, and you if you want to engage in this sort of trading, you should go through established channels rather than trying to convert a regular loan into margin trading. If you get a personal loan that isn't specifically for margin trading, and buy stocks with the money, and the stocks tank, you can be in serious trouble. (If you do it through margin trading, it's still very risky, but not nearly as risky as trying to game the system. In some cases, doing this makes you not only civilly but criminally liable.) The lending bank absolutely can lose if your stocks tank, since then there will be nothing backing up the loan.\"","title":""},{"docid":"121590","text":"\"There are many flaws with your idea. Say I want to borrow $225,000.00 to accrue interest on a 1.20% APY account. I promise ... that I cannot withdraw nor touch the account by legal contract. If you break the contract and lose the money, the lender is out the money. They can take you to court and will win, but if you don't have the money, then they don't get paid. (You can't squeeze water out of a rock even if a judge orders you to.) By sharing the interest with me on a loan, they keep a percentage that they'd normally get... If you're \"\"investing\"\" the money at 1.2%, and the lender gets some amount less than that, then they are getting much less than they \"\"normally\"\" get. Lenders typically get somewhere from 5-15% on loans. The money can also be used to fund a stock/trading account. Regardless of whether I profit, I pay interest on the loan and split the profit shares 24/7. How can the lender lose with legal enforcing? Again, if you lose the money, no amount of legal enforcing can force you to pay money that you don't have. Even if you go to jail for fraud the lender still doesn't get paid. Simply, no bank would ever agree to this.\"","title":""},{"docid":"392980","text":"\"Your plan as proposed will not work, because it goes against how banks make money. Banks make money in two ways: (1) Fees [including account fees, investment advice fees, mortgage application fees, etc.]; and (2) Interest Rate Spread. They borrow money for x%, and they lend it out for x+y%. In a simple form, someone gives the bank a deposit, and earns 1%. The bank turns around to the next person in line and loans the money to them for 4%. You are asking them to turn the interest rate spread into a cost instead of their main source of profit: You are asking the bank to borrow money from another person paying them 1.2% interest, and then loan the money to you, paying you 0.6% interest and keeping 0.6% for themselves. The bank would lose money doing this. Technically yes, you can borrow from a bank and invest it in something earning above the 4% interest they will charge you. You can then pay the bank's interest off of your earnings, and make some profit for yourself. BUT this carries an inherent risk: If your investment loses money, you still owe the bank, effectively increasing the negative impact of your investment. This tactic is called \"\"Leveraging\"\"; you can look it up on this site or on google. It is not something you should do if you do not fully understand the risks you are taking on. Given that you are asking this question, I would suggest tactfully that you are not yet well informed enough to make this sort of investment. You run serious risk of losing everything if you over-leverage (assuming the banks will even lend you money in the first place).\"","title":""},{"docid":"52343","text":"No. The WSJ prime rate is 4.25%, even the Fed prime rate is 1.75%, way above the 1.20% you'll be making from your savings account. If you are high worth individual with great credit history, the bank might give you a personal loan at 4.25%. They won't care what you do with it as long as they get their payments. If you are not that creditworthy, they'll ask for a collateral, you can mortgage your house for example. It ends up being the sames thing, you get your money and do what you want with it. If you can make more than the interest rate the bank gave you, great, you made profit. The bank however won't agree to lend you money at 0.6% (1/2 of the 1.2% APY your savings account will bring). Why would they when they can loan that at prime rate of 4.25%?? The closest you can get to something like this is if you are a hot-shot wall street money manager with track record of making big profits. In that case the bank might put some money in your fund for you to manage, but that's not something a regular person can do.","title":""}],"string":"[\n {\n \"docid\": \"149723\",\n \"text\": \"\\\"With (1), it's rather confusing as to where \\\"\\\"interest\\\"\\\" refers to what you're paying and where it refers to what you're being paid, and it's confusing what you expect the numbers to work out to be. If you have to pay normal interest on top of sharing the interest you receive, then you're losing money. If the lending bank is receiving less interest than the going market rate, then they're losing money. If the bank you've deposited the money with is paying more than the going market rate, they're losing money. I don't see how you imagine a scenario where someone isn't losing money. For (2) and (3), you're buying stocks on margin, which certainly is something that happens, but you'll have to get an account that is specifically for margin trading. It's a specific type of credit with specific rules, and you if you want to engage in this sort of trading, you should go through established channels rather than trying to convert a regular loan into margin trading. If you get a personal loan that isn't specifically for margin trading, and buy stocks with the money, and the stocks tank, you can be in serious trouble. (If you do it through margin trading, it's still very risky, but not nearly as risky as trying to game the system. In some cases, doing this makes you not only civilly but criminally liable.) The lending bank absolutely can lose if your stocks tank, since then there will be nothing backing up the loan.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"121590\",\n \"text\": \"\\\"There are many flaws with your idea. Say I want to borrow $225,000.00 to accrue interest on a 1.20% APY account. I promise ... that I cannot withdraw nor touch the account by legal contract. If you break the contract and lose the money, the lender is out the money. They can take you to court and will win, but if you don't have the money, then they don't get paid. (You can't squeeze water out of a rock even if a judge orders you to.) By sharing the interest with me on a loan, they keep a percentage that they'd normally get... If you're \\\"\\\"investing\\\"\\\" the money at 1.2%, and the lender gets some amount less than that, then they are getting much less than they \\\"\\\"normally\\\"\\\" get. Lenders typically get somewhere from 5-15% on loans. The money can also be used to fund a stock/trading account. Regardless of whether I profit, I pay interest on the loan and split the profit shares 24/7. How can the lender lose with legal enforcing? Again, if you lose the money, no amount of legal enforcing can force you to pay money that you don't have. Even if you go to jail for fraud the lender still doesn't get paid. Simply, no bank would ever agree to this.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"392980\",\n \"text\": \"\\\"Your plan as proposed will not work, because it goes against how banks make money. Banks make money in two ways: (1) Fees [including account fees, investment advice fees, mortgage application fees, etc.]; and (2) Interest Rate Spread. They borrow money for x%, and they lend it out for x+y%. In a simple form, someone gives the bank a deposit, and earns 1%. The bank turns around to the next person in line and loans the money to them for 4%. You are asking them to turn the interest rate spread into a cost instead of their main source of profit: You are asking the bank to borrow money from another person paying them 1.2% interest, and then loan the money to you, paying you 0.6% interest and keeping 0.6% for themselves. The bank would lose money doing this. Technically yes, you can borrow from a bank and invest it in something earning above the 4% interest they will charge you. You can then pay the bank's interest off of your earnings, and make some profit for yourself. BUT this carries an inherent risk: If your investment loses money, you still owe the bank, effectively increasing the negative impact of your investment. This tactic is called \\\"\\\"Leveraging\\\"\\\"; you can look it up on this site or on google. It is not something you should do if you do not fully understand the risks you are taking on. Given that you are asking this question, I would suggest tactfully that you are not yet well informed enough to make this sort of investment. You run serious risk of losing everything if you over-leverage (assuming the banks will even lend you money in the first place).\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"52343\",\n \"text\": \"No. The WSJ prime rate is 4.25%, even the Fed prime rate is 1.75%, way above the 1.20% you'll be making from your savings account. If you are high worth individual with great credit history, the bank might give you a personal loan at 4.25%. They won't care what you do with it as long as they get their payments. If you are not that creditworthy, they'll ask for a collateral, you can mortgage your house for example. It ends up being the sames thing, you get your money and do what you want with it. If you can make more than the interest rate the bank gave you, great, you made profit. The bank however won't agree to lend you money at 0.6% (1/2 of the 1.2% APY your savings account will bring). Why would they when they can loan that at prime rate of 4.25%?? The closest you can get to something like this is if you are a hot-shot wall street money manager with track record of making big profits. In that case the bank might put some money in your fund for you to manage, but that's not something a regular person can do.\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"550457","text":"\"Outstanding principal balance is the amount you owe at any given time, not including the amount of interest you need to pay as soon as possible. The \"\"capitalized interest\"\" shown is consistent with an average of 13.5 months between when each dollar is borrowed and when the repayment period begins. Suppose you borrow the first half of the money on September 1, 2017 and the second half of the money on February 1, 2017 (5 months later). At that point, half the money has been accruing interest for 5 months. On January 1, 2018, half the money accrued interest for 16 months, and half the money accrued interest for 11 months. The lender now expects you to start repaying the loan, with the first payment due at the end of January 2018 or the beginning of February 2018. If you make the minimum payments on time, the lender expects you to make 120 monthly payments. The last monthly payment would be at the end of December 2027 or the beginning of January 2028. The lender (or the website) should provide details about the actual payment plan, grace periods, provisions for handling inability to pay due to unemployment, and other terms. In the United States, most installment loans pretend that (for purposes of calculating interest) every month has 30 days -- even February and July! Each month, 1/12 of the \"\"annual percentage rate\"\" (APR) is charged as interest. If you do the compounding, a 6.8 percent APR corresponds to (1 + 0.068 / 12)^12 - 1 = 7.016 percent \"\"annual percentage yield\"\" (APY). Also, the APR is understated. The 6.8 percent applies to the full balance (including the loan fees), even though the borrower only gets the amount minus the loan fees. The 6.8 percent rate is useful for doing calculations after the loan fees have been charged, though. These calculations include the capitalized interest and the monthly payment amounts. A true calculation of the APR would take the loan fees into account, and give a higher number than 6.8 percent. But the corrected APR would not be useful for calculating the capitalized interest, nor for calculating the monthly payment amounts.\"","title":""},{"docid":"444941","text":"\"This election only applies to payments that you make within 120 days of your having received loan money. These wouldn't be required payments, which is why they are called \"\"early\"\" payments. For example, let's say that you've just received $10,000 from your lender for a new loan. One month later, you pay $500 back. This election decides how that $500 will be applied. The first choice, \"\"Apply as Refund,\"\" means that you are essentially returning some of the money that you initially borrowed. It's like you never borrowed it. Instead of a $10,000 loan, it is now a $9,500 loan. The accrued interest will be recalculated for the new loan amount. The second choice, \"\"Apply as Payment,\"\" means that your payment will first be applied to any interest that has accrued, then applied to the principal. While you are in school, you don't need to make payments on student loans. However, interest is accruing from the day you get the money. This interest is simple interest, which means that the interest is only based on the loan principal; the interest is not compounding, and you are not paying interest on interest. After you leave school and your grace period expires, you enter repayment, and you have to start making payments. At this point, all the interest that has accrued from the time you first received the money until now is capitalized. This means that the interest is added to your loan principal, and interest will now be calculated on this new, larger amount. To avoid this, you can pay the interest as you go before it is capitalized, which will save you from having to pay even more interest later on. As to which method is better, just as they told you right on the form, the \"\"Apply as Refund\"\" method will save you the most money in the long run. However, as I said at the beginning, this election only applies if you make a payment within 120 days from receiving loan funds. Since you are already out of school and in repayment, I don't think it matters at all what you select here. For any students reading this and thinking about loans, I want to issue a warning. Student loans can ruin people later in life. If you truly feel that taking out a loan is the only way you'll be able to get the education you need, minimize these as much as possible. Borrow as little as possible, pay as much as you can as early as you can, and plan on knocking these out ASAP. Great Lakes has a few pages that discuss these topics:\"","title":""},{"docid":"503723","text":"When you pay off a loan early, you pay the remaining principal, and you save all of the remaining interest. So you do save on interest, but it's the interest you would have paid in the future, not the interest you have paid in the past. (Your remaining balance when you pay off the loan only includes the principal, not the projected interest.) Interest is a factor of the amount borrowed, the interest rate and the amount of time you borrow the money. The sooner you repay the money, the less interest you pay. Imagine if you had taken a 30 year loan at 4% interest but were allowed to make no payments until the loan term ended. If you waited 15 years to make your first payment, you wouldn't owe the same money as if you'd made payments every month. No, instead of owing ~$64k, you'd owe ~$182k, because you had borrowed $100k for 15 years (plus the interest due) rather than borrowing a declining sum. So that's why you don't get a refund on interest for previous months. If you had started with a 16 year loan, then you would have been paying more principal every month, and your monthly amount due would have been higher to reflect that. As you paid the principal off faster, the interest each month would drop faster. Paying a huge portion of the principal at the end of the loan is not the same as steadily paying it down in the same time frame. You will pay a lot more interest in the former case, and rightfully so. It might help to consider a credit card payment in comparison. If you run up a balance and pay only the minimum each month, you pay a lot of interest over time, because your principal goes down slowly. If you suddenly pay off your credit card, you don't have to pay any more interest, but you also don't get any interest back for previous months. That's because the interest accrued each month is based on your current balance, just like your mortgage. The minimum payments are calculated differently, but the interest accrued each month uses essentially the same mechanism.","title":""},{"docid":"436331","text":"I suggest rolling it over to the 401(k) with your new employer. Particularly if they match any percentage of your contribution, it would be in your interest to take as much of that money as possible. When it comes to borrowing money from your 401(k), it looks like the issues AbraCadaver mentioned only apply if you don't pay back the money (http://www.kiplinger.com/article/real-estate/T010-C000-S002-borrowing-from-your-retirement-plan-to-buy-a-home.html). The reasonable argument against taking money out of your 401(k) to buy a home is that it leaves a dent in your retirement nest egg (and its earning power) during key earning years. On the plus side for borrowing from your 401(k), it's very low interest--and it's interest you're paying back to yourself over a 5-year period. At its current value, the most you could borrow from your 401(k) is $35K. If you're fortunate in where you live, that could be most or all of the downpayment. In my own experience, my wife borrowed against her 401(k) balance for the earnest money when we purchased a new home. Fortunately for us, an investor snapped up my previous home within 4 days of us listing it, so she was able to pay back her loan in full right away.","title":""},{"docid":"293897","text":"\"Let me run some simplistic numbers, ignoring inflation. You have the opportunity to borrow up to 51K. What matters (and varies) is your postgraduation salary. Case 1 - you make 22K after graduation. You pay back 90 a year for 30 years, paying off at most 2700 of the loan. In this case, whether you borrow 2,800 or 28,000 makes no difference to the paying-off. You would do best to borrow as much as you possibly can, treating it as a grant. Case 2 - you make 100K after graduation. You pay back over 7K a year. If you borrowed the full 51, after 7 or 8 years it would be paid off (yeah, yeah, inflation, interest, but maybe that might make it 9 years.) In this case, the more you borrow the more you have to pay back, but you can easily pay it back, so you don't care. Invest your sponsorships and savings into something long term since you know you won't be needing to draw on them. Case 3 - you make 30K after graduation. Here, the payments you have to make actually impact how much disposable income you have. You pay back 810 a year, and over 30 years that's about 25K of principal. It will be less if you account for some (even most) of the payment going to interest, not principal. Anything you borrow above 25K (or the lower, more accurate amount) is \"\"free\"\". If you borrow substantially less than that (by using your sponsorship, savings, and summer job) you may be able to stop paying sooner than 30 years. But even if you borrow only 12K (or half the more accurate number), it will still be 15 years of payments. Running slightly more realistic versions of these calculations where your salary goes up, and you take interest into account, I think you will discover, for each possible salary path, a number that represents how much of your loan is really loan: everything above that is actually a grant you do not pay back. The less you are likely to make, the more of it is really grant. On top of that, it seems to me that no matter the loan/grant ratio, \"\"borrow as much as you can from this rather bizarre source\"\" appears to be the correct answer. In the cases where it's all loan, you have a lot of income and don't care much about this loan payment. Borrowing the whole 51K lets you invest all the money you get while you're a student, and you can use the returns on those investments to make the loan payments.\"","title":""},{"docid":"559745","text":"\"@fredsbend, Hope this helps! \"\"I understand that a reverse mortgage can be paid out in two ways: A lump sum and monthly payments. I figure that if you take the lump sum, eventually, the bank wants you to start paying it back.\"\" Answer: Actually, there are 3 payout options, or 4 if you consider a combination payout as another one. There's a lump sum, a line of credit, or the monthly payout, or a combination. \"\"I figure that if you take the monthly payments, eventually, the bank stops paying out and wants you to pay it back. In both situations, interest accrues and this is how the bank makes money off of the deal\"\". Answer: The only time the monthly payments would stop would be if the borrower defaults on the lenders' terms or they no longer live at home. You are right though, and interest does accrue on whichever payment is decided on. I'm not sure how the lender makes money, probably by the interest, but I know borrowers are protected against high rates and owing more than your house. Here's an article I found that goes over the protections more in detail: https://www.americanadvisorsgroup.com/news/6-consumer-protections-reverse-mortgage-loan-borrowers. \"\"But what determines when you have to begin paying back the reverse mortgage? Some sources online seem to say that it's based only on if you die or would like to sell/move. That can't be right in all situations, because you could end up with a massive debt on a property more than its value.\"\" Answer: There are a lot of protections or regulations in place to protect anyone who takes out a reverse mortgage. One being, you can't owe MORE than your house is valued at during the time of repayment, a reverse mortgage is a non-recourse loan. In the instance that your house is less than you owe, you either sell the home and the proceeds are used to pay the loan and you keep the rest OR if you owe more than the house proceeds of the home go to the lender. Either way, you're not left paying for a \"\"mortgage\"\" without the house. In the case the parent, grandparent passes, then the heirs would have a choice of either paying back the reverse mortgage in payments, OR they can sell the house, heirs are protected during this as well to make sure they're not left with major debt in case of anything. Is there a formula to figure out when the bank stops the monthly payments and then wants it back? **Answer:**The amount becomes due if loan terms are not met, but the lender will discuss the options if it comes to that. Is there a different formula for when the lump sum would have to be paid back?\"\" Answer: Each payout option has the same terms and the same pay back terms. As long as terms are met, the lender can't ask for early repayment.\"","title":""},{"docid":"479240","text":"I like the answers others gave, if it's some substantial debt you definitely could go the bankruptcy route but it damages your future, also it's morally unethical to borrow all that money and not intend to pay. Second, if you can pay off the entire balance and clear out the 23% interest than I'd do that first. One less bill to concern yourself with. Now let's say you've been making $100 payments monthly on each card (my assumption for this examples sale) now instead of paying $100 to the remaining cards balance each month and saving the other $100, pay $200 against the remaining credit cards balance. By not taking home any money this way you are tackling the liability that is costing you money every month. Unless you have a great investment opportunity on that remaining $1000 or haven't created much of an emergency fund yet, I'd consider putting more of that money towards the debt. Gaining 0.01% on savings interest still means you're eating 25.99% in debt monthly. If you're able to I'd venture out to open a zero interest card and do a balance transfer over to that new card, there will be a minimal transfer fee but you may get some cash back out of it and also that zero interest for a year would help hold off more interest accruing while you're tackling the balance.","title":""},{"docid":"171339","text":"\"One of the factors of a credit score is the \"\"length of time revolving accounts have been established\"\". Having a credit card with any line of credit will help in this regard. The account will age regardless of your use or utilization. If you are having issues with credit limits and no credit history, you may have trouble getting financing for the purchase. You should be sure you're approved for financing, and not just that the financing option is \"\"available\"\" (potentially with the caveat of \"\"for well qualified borrowers\"\"). Generally, if you've gotten approved for financing, that will come in the form of another credit card account (many contracting and plumbing companies will do this in hopes you will use the card for future purchases) or a bank loan account (more common for auto and home loans). With the credit card account, you might be able to perform a balance transfer, but there are usually fees associated with that. For bank loan accounts, you probably can't pay that off with a credit card. You'll need to transfer money to the account via ACH or send in a check. In short: I wouldn't bet on paying with your current credit card to get any benefit. IANAL. Utilizing promotional offers, whether interest-free for __ months, no balance transfer fees, or whatever, and passing your debt around is not illegal, not fraudulent, and in many cases advised (this is a link), though that is more for people to distribute utilization across multiple cards, and to minimize interest accrued. Many people, myself included, use a credit card for purchasing EVERYTHING, then pay it off in full every month (or sometimes immediately) to reap the benefit of cash back rewards and other cardholder benefits. I've also made a major payment (tuition, actually) on a Discover card, and opened up a new Visa card with 18-months of no interest and no balance transfer fees to let the bill sit for 12 months while I finished school and got a job.\"","title":""},{"docid":"360003","text":"My opinion is that in general, it is probably not a good idea to borrow at a cost in order to make your RRSP contribution. Banks, of course, have an interest in loaning you money. Don't expect their literature to be objective on the matter! They are selling you a product and the advice is biased. What better way to double-dip than to get guaranteed interest payments from you, as well as ongoing fees for (probably also) getting your loan money invested in their high-fee mutual funds? A year's RRSP contribution room allowance isn't use it or lose it — unlike 401k contribution allowances in the U.S.. That is, unused RRSP contribution room accumulates and you can take advantage of it in later years. If we couldn't carry our RRSP contribution room over, I might feel different about the general case for RRSP loans. Yet there are two specific cases I can think of where it may make sense to borrow and pay back: (a possible case) ... if your tax rate is currently in a high bracket (e.g. 46%), and you anticipate being in a lower income and bracket next year (e.g. 35%), then it would make sense to take advantage of the higher tax savings in the current tax year. If you waited until the following year to take the deduction, you'd lose out on 11% of the deducted amount. For a typical person whose income is level or increasing from year to year, this isn't likely to be applicable, but it could help somebody who is going on leave or otherwise has irregular income. (a foolish case) ... if you knew, somehow, that you could realize a return on your invested RRSP money exceeding the pre-tax earnings required to pay the interest on the RRSP loan. However, I would suggest this is foolish bet to make. The interest you pay is guaranteed, but the return you are expected to get is probably not (or if it is, it is probably a return lower than what your bank wants to charge on the loan.) If for some reason it does make sense for you, take the money and invest it somewhere better than the high-fee mutual funds the bank is also pushing.","title":""},{"docid":"365342","text":"If you intend to flip this property, you might consider either a construction loan or private money. A construction loan allows you to borrow from a bank against the value of the finished house a little at a time. As each stage of the construction/repairs are completed, the bank releases more funds to you. Interest accrues during the construction, but no payments need to be made until the construction/repairs are complete. Private money works in a similar manner, but the full amount can be released to you at once so you can get the repairs done more quickly. The interest rate will be higher. If you are flipping, then this higher interest rate is simply a cost of doing business. Since it's a private loan, you ca structure the deal any way you want. Perhaps accruing interest until the property is sold and then paying it back as a single balloon payment on sale of the property. To find private money, contact a mortgage broker and tell them what you have in mind. If you're intending to keep the property for yourself, private money is still an option. Once the repairs are complete, have the bank reassess the property value and refinance based on the new amount. Pay back the private loan with equity pulled from the house and all the shiny new repairs.","title":""},{"docid":"150607","text":"\"In England, currently and for most of the last fifty years, the standard length of the mortgage term is 25 years. A mortgage can be either a capital-and-interest mortgage, or interest-only. In the former, you pay off part of the original loan each month, plus the interest on the amount borrowed. In the latter, you only pay interest each month, and the original amount borrowed never reduces: you pay premiums on a life insurance policy, additionally, which is designed to pay off the original sum borrowed at the end of the 25 years. No one in England thinks that a 25 year loan has any drawbacks. The main point to appreciate is that the longer the period of the loan, the less you need to pay each month, because you are repaying the original loan - the capital - over a longer period of time. Thus, in principle, a mortgage is easier to repay the longer the term is, because the monthly payment is less. If you have a 12 year mortgage, you must pay back the original amount borrowed in half the time: the capital element in your payment each month is double what it would be if repaid over 25 years - i.e. if repaid over a period twice as long. Only if the borrower is less than 25 years away from retirement is a 25 years mortgage seen as a bad idea, by the lender - because, obviously, the lender relies on the borrower having an income sufficient to keep up the repayments. There are many complicating factors: an interest-only mortgage, where you pay back the original amount borrowed from the maturity proceeds from a life policy, puts you in a situation where the original capital sum never reduces, so you always pay the same each month. But on a straight repayment mortgage, the traditional type, you pay less and less each month as time goes by, for you are reducing the capital outstanding each month, and because that is reducing so is the amount of interest you pay each month (as this is calculated on the outstanding capital amount). There are snags to avoid, if you can. For example, some mortgage contracts impose penalties if the borrower repays more than the due monthly amount, hence in effect the borrower faces a - possibly heavy - financial penalty for early repayment of the loan. But not all mortgages include such a condition. If house prices are on a rising trend, the market value of the property will soon be worth considerably more than the amount owed on the mortgage, especially where the mortgage debt is reducing every month, as each repayment is made; so the bank or other lender will not be worried about lending over a 25 year term, because if it forecloses there should normally be no difficulty in recovering the outstanding amount from the sale proceeds. If the borrower falls behind on the repayments, or house prices fall, he may soon get into difficulties; but this could happen to anyone - it is not a particular problem of a 25 year term. Where a default in repayment occurs, the bank will often suggest lengthening the mortgage term, from 25 years to 30 years, in order to reduce the amount of the monthly repayment, as a means of helping the borrower. So longer terms than 25 years are in fact a positive solution in a case of financial difficulty. Of course, the longer the term the greater the amount that the borrower will pay in total. But the longer the term, the less he will pay each month - at least on a traditional capital-and-interest mortgage. So it is a question of balancing those two competing factors. As long as you do not have a mortgage condition that penalises the borrower for paying off the loan more quickly, it can make sense to have as long a term as possible, to begin with, which can be shortened by increasing the monthly repayment as fast as circumstances allow. In England, we used to have tax relief on mortgage payments, and so in times gone by it did make sense to let the mortgage run the full 25 years, in order to get maximum tax relief - the rules were very complex, but it tended to maximise your tax relief by paying over the longest possible period. But today, with no income tax relief given on mortgage payments, that is no longer a consideration in this country. The practical position is, of course, that you can never tell how long it might take you to pay off a mortgage. It is a gamble as to whether your income will rise in future years, and whether your job will last until your mortgage is paid off. You might fall ill, you might be made redundant, you might be demoted. Mortgage interest rates might rise. It is never possible to say that you \"\"can\"\" pay off the loan in a short time. If you hope to do so, the only matters that actually fall within your control are the conditions of the mortgage contract itself. Get a good lawyer. Tell him to watch out for early-redemption penalties. Get a good financial adviser. Tell him to work out what you will need to pay in additional premiums on your life policy if you are considering taking an interest-only mortgage. Try to fix your mortgage rate in the first few years, for as long as possible, so that in your most vulnerable period, with the greatest amount owing, you are insulated against unexpected interest rate fluctuations. Only the initial conditions can be controlled, so it might be prudent to take as long a term as possible, even though a prudent borrower will leave himself room to reduce that term, and a prudent lender will leave room to extend it, in case of unpredictable changes in the financial circumstances. In England, most lenders are, in my experience, reluctant to grant mortgages for less than 25 years. That is simply a policy. Rightly or wrongly, the borrower usually has no choice about the length of the mortgbage term. Hence, in the UK it can be difficult to find a choice of interest rates based on differing mortgage terms. I am aware that the situation in the USA is rather different, but if I personally were faced with the choice I would be uncomfortable about taking on a short term mortgage, because of the factors I have outlined above.\"","title":""},{"docid":"10873","text":"\"This answer is better served as a comment but I don't have enough rep. It is not guaranteed that they 'do not accrue interest while you are a full time student'. Some student loans can capitalize the interest - before pursuing leveraged investing, be sure that your student loan is not capitalizing. https://www.salliemae.com/student-loans/manage-your-private-student-loan/understand-student-loan-payments/learn-about-interest-and-capitalization/ Capitalized interest Capitalized interest is a second reason your loan may end up costing more than the amount you originally borrowed. Interest starts to accrue (grow) from the day your loan is disbursed (sent to you or your school). At certain points in time—when your separation or grace period ends, or at the end of forbearance or deferment—your Unpaid Interest may capitalize. That means it is added to your loan’s Current Principal. From that point, your interest will now be calculated on this new amount. That’s capitalized interest.\"\" https://www.navient.com/loan-customers/interest-and-taxes/how-student-loan-interest-works/ Capitalized Interest If you accrue interest while you are in school – as with Direct Unsubsidized, FFELP Unsubsidized, Direct and FFELP PLUS Loans, and Private Loans – you will have capitalized interest if it is unpaid. Unpaid accrued interest is added to the principal amount of your loan after you leave school and finish any applicable grace period. Simply put, there will be interest to be paid on both the principal of the loan and on the interest that has already accumulated. To minimize the effects of the capitalized interest on the amount you will pay overall, you can pay the interest during college instead of waiting until after graduation. That way, you start with the original principal balance (minus any fees) when you begin repayment.\"","title":""},{"docid":"543811","text":"\"I think to some extent you may be confusing the terms margin and leverage. From Investopedia Two concepts that are important to traders are margin and leverage. Margin is a loan extended by your broker that allows you to leverage the funds and securities in your account to enter larger trades. In order to use margin, you must open and be approved for a margin account. The loan is collateralized by the securities and cash in your margin account. The borrowed money doesn't come free, however; it has to be paid back with interest. If you are a day trader or scalper this may not be a concern; but if you are a swing trader, you can expect to pay between 5 and 10% interest on the borrowed money, or margin. Going hand-in-hand with margin is leverage; you use margin to create leverage. Leverage is the increased buying power that is available to margin account holders. Essentially, leverage allows you to pay less than full price for a trade, giving you the ability to enter larger positions than would be possible with your account funds alone. Leverage is expressed as a ratio. A 2:1 leverage, for example, means that you would be able to hold a position that is twice the value of your trading account. If you had $25,000 in your trading account with 2:1 leverage, you would be able to purchase $50,000 worth of stock. Margin refers to essentially buying with borrowed money. This must be paid back, with interest. You also may have a \"\"margin call\"\" forcing you to liquidate assets if you go beyond your margin limits. Leverage can be achieved in a number of ways when investing, one of which is investing with a margin account.\"","title":""},{"docid":"521418","text":"\"A credit card is basically a \"\"revolving\"\" loan, in which you're allowed to borrow up to a certain amount (the limit), and any time you borrow, you pay interest. If you were to *borrow* $100 to pay for something via a credit card, you'd have a $100 balance on the card. If you then pay $70 cash to the card, there would be $30 remaining. That $30 balance could accrue interest. The timing of that interest charge could vary. The 20% you've quoted is almost certainly \"\"APR,\"\" of which the \"\"A\"\" stands for \"\"annual,\"\" so that 20% would be an annual rate. It makes the most sense, mind you, to keep a minimal balance on a credit card, as the interest rate is higher than most other loans.\"","title":""},{"docid":"559618","text":"\"Somehow I just stumbled onto this thread... > You essentially robbed the person holding the debt (since you promised to pay it off). Depends on leverage, with fractional reserve lending. Banks are permitted to loan out 30x their actual assets, or more. If I have $1 but can loan out $30, and anything more than $1 gets paid back, I haven't lost any money. In addition, I can write off the amount defaulted, *and the government will pay me back* for certain types of loans. With student loans, since they are almost impossible to discharge, gov't will pursue the borrower for years and decades, and ultimately collect more interest. Here is an article on it: http://online.wsj.com/article/SB10001424052748704723104576061953842079760.html > According to Kantrowitz, the government stands to earn $2,010.44 more in interest from a $10,000 loan that defaulted than if it had been paid in full over a 20-year term, and $6,522.00 more than if it had been paid back in 10 years. Alan Collinge, founder of borrowers' rights advocacy Student Loan Justice, said the high recovery rates provide a \"\"perverted incentive\"\" for the government to allow loans to go into default. Kantrowitz estimates the recovery rate would need to fall to below 50% in order for default prevention efforts to become more lucrative than defaults themselves. Not to mention: http://studentloanjustice.org/defaults-making-money.html > So essentially, the Department is given a choice: Either do nothing and get nothing, or outlay cash with the knowledge that this outlay will realize a 22 percent return, ultimately (minus the governments cost of money and collection costs). From this perspective, it is clear that based solely on financial motivations, and without specific detailed knowledge of the loan (i.e. borrower characteristics, etc.), the chooser would clearly favor the default scenario, for not only the return, but perhaps the potential savings in subsidy payment as well, And don't forget the penalties accruing to the person defaulting; they will probably have to move out of the country in order to escape collection. And let's factor in the huge ROI the lender sees by creating an indentured servant class. Plus, the gov't will issue as much currency as it wants, to make *itself* whole. And how much of a loss IS the loss, when the whole of the loan amount went right back into the local economy, paying professors, janitors, landlords, grocery stores, etc.? And don't forget all THOSE taxes (income and sale) that the gov't collects. Government will collect ~30%-50% of the loan immediately as income and sales tax, plus a portion of it every time the money changes hands (I pay income tax, then use some of my after-tax money to pay you for a product or service, and you still have to pay tax on that money, and so on). So it's more complicated than having \"\"robbed the person holding the debt\"\". Banks at 30x leverage don't lose money as long as they get back 1/30th of the total amount lent out, including interest, fees, and penalties, before considering write-offs and government repayment. In fact, the point of over-leverage is so you CAN make loans that have risk attached. If you could only lend what you actually had, you would have to stay away from anything risky because it would be too easy to lose money. Having virtual $ to bet means you can serve market segments that have higher risk. This makes MORE money for the banks, that's why they do it. They are already playing with funny money, so they don't lose any even if you default and move to another country. And the money you \"\"spent\"\" has also made its way back to them in various amounts, such as your professor's mortgage payments, auto loan, etc. Your taking on debt already helped the bank get its OTHER loans repaid. So, roughly speaking, if you took out $90,000 and $3,000 of that made its way back to the bank through various means, they haven't lost any money, because it only cost them $3,000 actual dollars in the first place.\"","title":""},{"docid":"421743","text":"\"never carry a balance on a credit card. there is almost always a cheaper way to borrow money. the exception to that rule is when you are offered a 0% promotion on a credit card, but even then watch out for cash advance fees and how payments are applied (typically to promotional balances first). paying interest on daily spending is a bad idea. generally, the only time you should pay interest is on a home loan, car loan or education loan. basically that's because those loans can either allow you to reduce an expense (e.g. apartment rent, taxi fair), or increase your income (by getting a better job). you can try to make an argument about the utility of a dollar, but all sophistry aside you are better off investing than borrowing under normal circumstances. that said, using a credit card (with no annual fee) can build credit for a future car or home loan. the biggest advantage of a credit card is cash back. if you have good credit you can get a credit card that offers at least 1% cash back on every purchase. if you don't have good credit, using a credit card with no annual fee can be a good way to build credit until you can get approved for a 2% card (e.g. citi double cash). additionally, technically, you can get close to 10% cash back by chasing sign up bonuses. however, that requires applying for new cards frequently and keeping track of minimum spend etc. credit cards also protect you from fraud. if someone uses your debit card number, you can be short on cash until your bank fixes it. but if someone uses your credit card number, you can simply dispute the charge when you get the bill. you don't have to worry about how to make rent after an unexpected 2k$ charge. side note: it is a common mis-conception that credit card issuers only make money from cardholder interest and fees. card issuers make a lot of revenue from \"\"interchange fees\"\" paid by merchants every time you use your card. some issuers (e.g. amex) make a majority of their revenue from merchants.\"","title":""},{"docid":"249831","text":"\"Ditto mhoran_psprep. I'm not quite sure what you're asking. Where does the money come from? When someone starts a bank, they normally get together a bunch of investors -- perhaps people they know personally, perhaps they sell stock -- to raise initial capital. But most of the money in the bank comes from depositors. Fundamentally, what a bank does is take money from depositors and loan it to borrowers. (Banks also borrow money from other banks and from the government.) They charge the borrowers interest on the loan, and they pay depositors interest on their deposits. The difference between those two interest rates is where the bank gets their profit. Where does the money go when you pay it back? As mhoran_psprep said, some of it goes to pay interest to the depositors; some of it goes to pay the bank's expenses like employee salaries, cost of the building, etc; and some of it goes as profit to the owners or stockholders of the bank. If you're thinking, \"\"Wow, I'm paying back a whole lot more than I borrowed\"\", well, yes. But remember you're borrowing that money for 20 or 30 years. The bank isn't making very much money on the loan each year that you have it -- these days something like 4 or 5% in the U.S., I don't know what the going rates are in other countries.\"","title":""},{"docid":"42475","text":"\"The interest rate offered by a bond is called the nominal interest rate. The so-called real interest rate is the nominal interest rate minus the rate of inflation. If inflation is equal to or greater than the nominal rate at any given time, the REAL interest rate is zero or negative. We're talking about a ten year bond. It's possible for the real interest rate to be negative for one or two years of the bond's life, and positive for eight or nine. On the other hand, if we have a period of rising inflation, as in the 1970s, the inflation rate will exceed the (original) interest rate in most years, meaning that the real interest rate on the ten year bond will be negative over its whole life. People lost \"\"serious\"\" money on bonds (and loans) in the 1970s. In such situations, the BORROWERS make out. That is, they borrow money at low rates, earn inflation (plus a little more) pay back inflated dollars, and pocket the difference. For them, the money is \"\"free.\"\"\"","title":""},{"docid":"191508","text":"Forget about terms. Think about loans in terms of months. To simplify things, let's consider a $1000 loan with .3% interest per month. This looks like a ten month term, but it's equally reasonable to think about it on a month-to-month basis. In the first month, you borrowed $1000 and accrued $3 interest. With the $102 payment, that leaves $901 which you borrow for another month. So on and so forth. The payoff after five payments would by $503.54 ($502.03 principal plus $1.51 interest). You'd save $2.99 in interest after paying $13.54. The reason why most of the interest was already paid is that you already did most of the borrowing. You borrowed $502.03 for six months and about $100 each for five, four, three, two, and one month. So you borrowed about $4500 months (you borrowed $1000 for the first month, $901 for the second month, etc.). The total for a ten month $1000 loan is about $5500 months of borrowing. So you've done 9/11 of the borrowing. It's unsurprising that you've paid about 9/11 of the interest. If you did this as a six month loan instead, then the payments look different. Say You borrow $1000 for one month. Then 834 for one month. So on and so forth. Adding that together, you get about $168.50 * 21 or $3538.50 months borrowed. Since you only borrow about 7/9 as much, you should pay 7/9 the interest. And if we adding things up, we get $10.54 in interest, about 7/9 of $13.54. That's how I would expect your mortgage to work in the United States (and I'd expect it to be similar elsewhere). Mortgages are pretty straight-jacketed by federal and state regulations. I too once had a car loan that claimed that early payment didn't matter. But to get rid of the loan, I made extra payments. And they ended up crediting me with an early release. In fact, they rebated part of my last payment. I saved several hundred dollars through the early release. Perhaps your loan did not work the same way. Perhaps it did. But in any case, mortgages don't generally work like you describe.","title":""},{"docid":"239611","text":"\"The most important thing in my view is flexibility, to avoid running into problems. One useful thing in the UK would be an arranged overdraft. You go to your bank, and they'll agree that you can overdraw your account by a certain number of pounds, depending on your income etc. It will cost you a very high interest rate, but only for each day where you are overdrawn. So paying a bill two days before your salary comes in isn't too bad. Obviously avoid using the overdraft if you can, having an overdraft while not using it is free. It's meant for an emergency; being regularly overdrawn is expensive. But once it is arranged with your bank, an arranged overdraft is much much cheaper than bouncing cheques etc. and possibly high fees for overdrawing your account. And it takes the pressure of you. Now things to need before you get a loan (again, UK): The real interest rate that you are paying is called APR. That's the number that counts, and that cannot be manipulated. No \"\"payday loans\"\" to avoid getting yourself into deep, deep trouble. No loan sharks, obviously. If you buy things with \"\"interest free credit\"\", that's (a) included in the price, so you pay more, and (b) if you miss paying by one day they'll hit you with huge interest payments, and some will try this intentionally. Interest rate depends on loan amount. I once had to borrow 20% more than I needed because it reduced the interest rate by half... The 20% went straight into a savings account. Credit cards and overdrafts are much more expensive than loans. Mortgage is again cheaper than a loan usually. Make sure that you only use money from sources that charge the least amount. Make sure you pay back regularly so cheap sources stay available to you. Just do yourself a favour and if at all possible, spend less instead of getting a loan.\"","title":""},{"docid":"362468","text":"\"I've never heard of a loan product like that. Yes, if they keep the funds in an account, it is no risk to the bank, but they would essentially need to go through the loan process twice for the same loan: when you pick a house, they need to reevaluate everything, along with appraising and approving the house. Even if you did find a bank that would do this for you, there are a few problems with this scheme. You would be paying interest before you have a need for this money, negating the savings you might achieve if the interest rates go up. In addition, your \"\"balance\"\" will go down as \"\"payments\"\" are deducted from your loan, and when you finally find a home to buy, you might not have enough for the house you want. You'll need to borrow more than you need, which will further negate any possible savings. It is impossible to know how fast rates will climb. If I were you, I would stick to saving for your down payment, and just get the best rate you can when you are ready to buy. Another potential idea for you is to lock an interest rate. When you apply for a mortgage, the interest rate is often locked for as much as 60 days, to protect the borrower in the event that the rates go up. You could ask the bank if you can pay a fee to lock the rate even longer. I don't know if that is possible or not. And, of course, the fee would eat into your potential savings.\"","title":""},{"docid":"17110","text":"Because this is Money.SE and you're connecting it to offspring, I'd think about a discussion with them to get their agreements. From my perspective, anything (my wife and) I have will go to offspring in the end. As such, everything borrowed and not repaid simply reduces the estate by that much. Among multiple offspring, such reductions should be against the borrower rather than spreading it out. That should be accounted for in whatever will is created. This would be the discussion point. It might also be discussed how or even if any interest should accrue for unpaid amounts. If, for example, a 1% APR is agreed upon for unpaid loans, then the final principle+interest amount is taken off of the borrower's inheritance. Existing outstanding loans might (or might not!) be useful examples for sample calculations if desired or needed. (If nothing else, they might serve as reminders that loans were not forgotten.) By having such a discussion, you can show that you are trying to plan for a fair distribution of your estate, perhaps thereby sidestepping any concern about charging interest to offspring for repaid loans. At the same time, you're handing over some financial responsibility, giving them a power of personal choice, which seems to be a part of what you're concerned about. Once such a discussion is started, it's possible that any question of interest will resolve itself naturally. The discussion almost necessarily must include all offspring at once. One will find it harder to negotiate from a standpoint of pure self-interest without objection from another. Think beforehand about what will be said and about what responses might come. Think things through as much as you can.","title":""},{"docid":"22268","text":"\"They don't actually need to. They accept deposits for historical reasons and because they make money doing so, but there's nothing key to their business that requires them to do so. Here's a decent summary, but I'll explain in great detail below. By making loans, banks create money. This is what we mean when we say the monetary supply is endogenous. (At least if you believe Sir Mervyn King, who used to run England's central bank...) The only real checks on this are regulatory--capitalization requirements and reserve requirements, which impose a sort of tax on a bank's circulating loans. I'll get into that later. Let's start with Why should you believe that story--that loans create deposits? It seems like a bizarre assertion. But it actually matches how banks behave in practice. If you go borrow money from a bank, the loan officer will do many things. She'll want to look at your credit history. She'll want to look at your income and assets. She'll want to look at what kind of collateral or guarantees you're providing that the loan will be repaid. What she will not do is call down to the vaults and make sure that there's enough bills stacked up for them to lend out. Loans are judged based on a profitability function determined by the interest rate and the loan risk. If those add up to \"\"profitable\"\", the bank makes the loan. So the limiting factor on the loans a bank makes are the available creditworthy borrowers--not the bank's stock of cash. Further, the story makes sense because loans are how banks make money. If a bank that was short of money suddenly stopped making loans, it'd be screwed: no new loans = no way to make money to pay back depositors and also keep the lights on = no more bank. And the story is believable because of the way banks make so little effort to solicit commercial deposit business. Oh sure, they used to give you a free toaster if you opened an account; but now it's really quite challenging to find a no-fee checking account that doesn't impose a super-high deposit limit. And the interest paid on savings deposits is asymptotically approaching zero. If banks actually needed your deposits, they'd be making a lot more of effort to get them. I mean, they won't turn up their noses; your deposited allowance is a couple basis points cheaper to the bank than borrowing from the Fed; but banks seem to value small-potatoes depositors more as a source of fees and sales opportunities for services and consumer credit than as a source of cash. (It's a bit different if you get north of seven figures, but smaller depositors aren't really worth the hassle just for their cash.) This is where someone will mention the regulatory requirements of fractional reserve banking: banks are obliged by regulators to keep enough cash on hand to pay out a certain percentage of deposits. Note nothing about loans was said in that statement: this requirement does not serve as a check on the bank making bad loans, because the bank is ultimately liable to all its depositors for the full value of their deposits; it's more making sure they have enough liquidity to prevent bank runs, the self-fulfilling prophecy in which an undercapitalized bank could be forced into bankruptcy. As you noted in your question, banks can always borrow from the Fed at the Fed Discount Rate (or from other banks at the interbank overnight rate, which is a little lower) to meet this requirement. They do have to pledge collateral, but loans themselves are collateral, so this doesn't present much of a problem. In terms of paying off depositors if the bank should collapse (and minimizing the amount of FDIC insurance payout from the government), it's really capital requirements that are actually important. I.E. the bank has to have investors who don't have a right to be paid back and whose investment is on the hook if the bank goes belly-up. But that's just a safeguard for the depositors; it doesn't really have anything to do with loans other than that bad loans are the main reason a bank might go under. Banks, like any other private business, have assets (things of value) and liabilities (obligations to other people). But banking assets and liabilities are counterintuitive. The bank's assets are loans, because they are theoretically recoverable (the principal) and also generate a revenue stream (the interest payments). The money the bank holds in deposits is actually a liability, because it has to pay that money out to depositors on demand, and the deposited money will never (by itself) bring the bank any revenue at all. In fact, it's a drain, because the bank needs to pay interest to its depositors. (Well, they used to anyway.) So what happens when a bank makes a loan? From a balance sheet perspective, strangely enough, the answer is nothing at all. If I grant you a loan, the minute we shake hands and you sign the paperwork, a teller types on a keyboard and money appears in your account. Your account with my bank. My bank has simultaneously created an asset (the loan you now have to repay me) and an equal-sized liability (the funds I loaned you, which are now deposited in your account). I'll make money on the deal, because the interest you owe me is a much higher rate than the interest I pay on your deposits, or the rate I'd have to pay if I need to borrow cash to cover your withdrawal. (I might just have the cash on hand anyway from interest and origination fees and whatnot from previous loans.) From an accounting perspective, nothing has happened to my balance sheet, but suddenly you owe me closing costs and a stream of extraneous interest payments. (Nice work if you can get it...) Okay, so I've exhaustively demonstrated that I don't need to take deposits to make loans. But we live in a world where banks do! Here's a few reasons: You can probably think of more, but at the end of the day, a bank should be designed so that if every single (non-borrowing) depositor withdrew their deposits, the bank wouldn't collapse or cease to exist.\"","title":""},{"docid":"444637","text":"Putting debt out long means to borrow a sum of money paid back over a longer period of time than you could reasonably pay it back. It should be important to note that this advice only applies for fixed rate loans (meaning your rate can't change for the life of the loan without you explicitly changing it). The logic is that if you can borrow money when interest rates are really low, there is a good chance you can find an investment that has a return higher than the interest rate on the loan. It also means that when/if interest rates go up in the future, a simple savings account may even have a greater return than your loans interest. The advice suggests to borrow over a long period so you are paying less interest per payment, and gives you time to find a proper investment without having to pay too much interest during that time.","title":""},{"docid":"474318","text":"\"If the government prints money recklessly and causes inflation, people will come to expect inflation, and the value of the currency will plummet, and you'll end up like Zimbabwe where a trillion dollars won't buy a loaf of bread. If the government actually pays people for the money they borrow, they don't have this problem - and as it turns out, the US government can get pretty good rates on borrowing in general, in part because they're extraordinarily good about paying them back. (Also, inflation expectations are low, so people will accept 1-2% interest rates. If you expected inflation of 10%, you'd see people demanding something more like 12% interest rates.) (The downside of too much of this sort of borrowing is that it \"\"crowds out\"\" other borrowing, which may harm the economy. Who would lend money to / invest in a small business, if the government is paying good money and there's almost no risk at all?) Now, inflation can come into play afterward, if the Fed decides it needs to maintain \"\"easy money\"\" policies to stimulate the economy (because taxes are too high because we're paying off the debt, or because we've crowded out smaller borrowers, or something). -- In general, you can count on the the principle that if you, as the government, try to play too many games with people's money... well, people aren't stupid; they will eventually catch on, and adjust their behavior to compensate, and then you're right back where you started, but with less trust.\"","title":""},{"docid":"580147","text":"When you get a loan (car, home, student) the lending company (bank) give the (auto dealer, previous home owner, school) money. You as the borrow promise to pay this money back with interest. So in your case the 100,000 you borrow requires a payment for principal and interest of ~965 per month. After 240 payments you will have paid the bank ~231,605. So who got the ~131,000 in interest. The bank did. It was used to pay interest to the people who made deposits into the bank. It was also used to pay the expenses of the bank: salaries, retirement, rent, electricity, computers, etc. If the bank is a company with investors they may have to pay dividends to them to. Of course not all loans are successfully paid back, so some of the payment goes to cover the loans that are in default. In many cases loans are also refinanced, or the house is sold long before the 20-30 year term is up. In these cases the amount of interest received for that loan is much less than anticipated, but the good news is that it can be loaned out again.","title":""},{"docid":"285176","text":"The assumption that bonds have been issued with a negative coupon is not correct, or at least is has not occurred thus far. We'll look at this future possibility in the final paragraph. For now, lets look at the current bond market. The issuance of government bonds which carry a negative gross redemption yield is the result of governments issuing bonds at an issue price which exceed the nominal/redemption price and any coupon yield receivable over the life of the bond. I can find no instances of bonds with a negative coupon, though many have tiny positive coupon yields. The short seller of a bond with a negative gross redemption yield will be liable to pay the buyer the interest amount determined by the coupon. If the short seller has borrowed the bonds in order to sell them, then the short seller will receive the interest due from the lender to offset the interest paid to the buyer. If the short seller has not borrowed the bonds, but has sold them using some sort of synthetic contract such as a Contract for Difference, then the short seller will pay the coupon without receiving any offsetting payment. I thought this was an interesting question and it will be interesting to see if, at some time in the future, governments do ever issue bonds with a negative coupon. To date, this does not appear to have happened. So what would happen if we assume that a government issues a bond with a negative coupon. The buyer of the bond would be required to pay the equivalent yield to the government according to the bond contract specification. If an investor sells short such a bond, they would then become entitled to receive the interest from the buyer. If they have borrowed the bonds in order to sell them short, then they would pay any interest received back to the lender - this chain should eventually end with the ultimate owner/lender paying the government their dues. If they have sold short using a synthetic contract, then presumably they would keep the interest from themselves.","title":""},{"docid":"41312","text":"You must mean the current debt ceiling debacle. The meaning of it is: US government is constantly borrowing money (by issuing treasury bonds) and constantly repaying some of the bonds that come to maturity, and also has other obligations it has to meet by law all the time - such as Social Security checks, bonds interest, federal employees' salaries and pensions, etc. By law, total amount of money that can be borrowed at the same time is capped. That means, there can be situation where the government needs to borrow money to pay, say, interest on existing bonds, but can not, since the limit is reached. Such situation is called a default, since the government promised to pay the interest, but is unable to do so. That does not mean the government has no money at all and will completely collapse or couldn't raise money on the market if it were permitted by law to do so (currently, the market is completely willing to buy the debt issued by US government, and with interest that is not very high, though of course that may change). It also does not mean the economy ceases to function, dollars cease to have value or banks instantly go bankrupt. But if the government breaks its promises to investors, it has various consequences such as raising the costs of borrowing in the future. Breaking promises to other people - like Social Security recipients - would also look bad and probably hurt many of them. Going back to your bank account, most probably nothing would happen to the money you store there. Even if the bank had invested 100% of the money in US treasury bonds (which doesn't really happen) they still can be sold on the open market, even if with some discount in the event of credit rating downgrade, so most probably your account would not be affected. As stated in another answer, even if the fallout of all these calamities causes a bank to fail, there's FDIC and if your money is under insured maximums you'll be getting your money back. But if your bank is one of the big ones, nothing of the sort would happen anyway - as we have seen in the past years, government would do practically anything to not allow any big bank failures.","title":""},{"docid":"28809","text":"\"Most likely that's the amount of interest that accrued on the loan while you were in school. If you had paid that amount before 6/21, you would have just paid off accrued interest and your loan balance would have stayed the same. Since you did not pay the interest, it will be added to your loan balance and you will just pay it off as part of the loan (plus compounded interest). If you pay off your loan at 5% over 30 years (hopefully you won't, but that's what they're amortized for), that $350 will compound and become $1,563. Essentially you're \"\"borrowing\"\" $350 at 5% interest for 30 years. Hopefully that motivates you to pay it off sooner that that...\"","title":""},{"docid":"557324","text":"There are a few reasons, particularly for businesses. The first is opportunity cost. That chunk of money they have could be used to get higher returns somewhere else. If they can borrow from a bank at low interest rates to finance their ongoing operations, they can use their cash to get a higher return somewhere else. The second is credit rating. For public companies, ratings companies give high emphasis to companies with large reserves. This strengthens their ability to pay back the loan should it become necessary. A good credit rating in turn let's the company borrow money at lower rates. When a company can borrow money at low rates, it circles back to the first point where they can now put their reserves to better use. The third is leverage. Companies can use the cash they have built up to leverage into a larger investment. Assuming the investment works out, it will pay for the cost of borrowing over time. For instance let's say I have $1 million to invest. I can pay all cash for a $1 million apartment building or I can leverage that into a $3 million building. Assuming I run it well, the tenants will pay for the cost of borrowing $2 million and at the end of the term I'll be left with my $3 million building.","title":""}],"string":"[\n {\n \"docid\": \"550457\",\n \"text\": \"\\\"Outstanding principal balance is the amount you owe at any given time, not including the amount of interest you need to pay as soon as possible. The \\\"\\\"capitalized interest\\\"\\\" shown is consistent with an average of 13.5 months between when each dollar is borrowed and when the repayment period begins. Suppose you borrow the first half of the money on September 1, 2017 and the second half of the money on February 1, 2017 (5 months later). At that point, half the money has been accruing interest for 5 months. On January 1, 2018, half the money accrued interest for 16 months, and half the money accrued interest for 11 months. The lender now expects you to start repaying the loan, with the first payment due at the end of January 2018 or the beginning of February 2018. If you make the minimum payments on time, the lender expects you to make 120 monthly payments. The last monthly payment would be at the end of December 2027 or the beginning of January 2028. The lender (or the website) should provide details about the actual payment plan, grace periods, provisions for handling inability to pay due to unemployment, and other terms. In the United States, most installment loans pretend that (for purposes of calculating interest) every month has 30 days -- even February and July! Each month, 1/12 of the \\\"\\\"annual percentage rate\\\"\\\" (APR) is charged as interest. If you do the compounding, a 6.8 percent APR corresponds to (1 + 0.068 / 12)^12 - 1 = 7.016 percent \\\"\\\"annual percentage yield\\\"\\\" (APY). Also, the APR is understated. The 6.8 percent applies to the full balance (including the loan fees), even though the borrower only gets the amount minus the loan fees. The 6.8 percent rate is useful for doing calculations after the loan fees have been charged, though. These calculations include the capitalized interest and the monthly payment amounts. A true calculation of the APR would take the loan fees into account, and give a higher number than 6.8 percent. But the corrected APR would not be useful for calculating the capitalized interest, nor for calculating the monthly payment amounts.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"444941\",\n \"text\": \"\\\"This election only applies to payments that you make within 120 days of your having received loan money. These wouldn't be required payments, which is why they are called \\\"\\\"early\\\"\\\" payments. For example, let's say that you've just received $10,000 from your lender for a new loan. One month later, you pay $500 back. This election decides how that $500 will be applied. The first choice, \\\"\\\"Apply as Refund,\\\"\\\" means that you are essentially returning some of the money that you initially borrowed. It's like you never borrowed it. Instead of a $10,000 loan, it is now a $9,500 loan. The accrued interest will be recalculated for the new loan amount. The second choice, \\\"\\\"Apply as Payment,\\\"\\\" means that your payment will first be applied to any interest that has accrued, then applied to the principal. While you are in school, you don't need to make payments on student loans. However, interest is accruing from the day you get the money. This interest is simple interest, which means that the interest is only based on the loan principal; the interest is not compounding, and you are not paying interest on interest. After you leave school and your grace period expires, you enter repayment, and you have to start making payments. At this point, all the interest that has accrued from the time you first received the money until now is capitalized. This means that the interest is added to your loan principal, and interest will now be calculated on this new, larger amount. To avoid this, you can pay the interest as you go before it is capitalized, which will save you from having to pay even more interest later on. As to which method is better, just as they told you right on the form, the \\\"\\\"Apply as Refund\\\"\\\" method will save you the most money in the long run. However, as I said at the beginning, this election only applies if you make a payment within 120 days from receiving loan funds. Since you are already out of school and in repayment, I don't think it matters at all what you select here. For any students reading this and thinking about loans, I want to issue a warning. Student loans can ruin people later in life. If you truly feel that taking out a loan is the only way you'll be able to get the education you need, minimize these as much as possible. Borrow as little as possible, pay as much as you can as early as you can, and plan on knocking these out ASAP. Great Lakes has a few pages that discuss these topics:\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"503723\",\n \"text\": \"When you pay off a loan early, you pay the remaining principal, and you save all of the remaining interest. So you do save on interest, but it's the interest you would have paid in the future, not the interest you have paid in the past. (Your remaining balance when you pay off the loan only includes the principal, not the projected interest.) Interest is a factor of the amount borrowed, the interest rate and the amount of time you borrow the money. The sooner you repay the money, the less interest you pay. Imagine if you had taken a 30 year loan at 4% interest but were allowed to make no payments until the loan term ended. If you waited 15 years to make your first payment, you wouldn't owe the same money as if you'd made payments every month. No, instead of owing ~$64k, you'd owe ~$182k, because you had borrowed $100k for 15 years (plus the interest due) rather than borrowing a declining sum. So that's why you don't get a refund on interest for previous months. If you had started with a 16 year loan, then you would have been paying more principal every month, and your monthly amount due would have been higher to reflect that. As you paid the principal off faster, the interest each month would drop faster. Paying a huge portion of the principal at the end of the loan is not the same as steadily paying it down in the same time frame. You will pay a lot more interest in the former case, and rightfully so. It might help to consider a credit card payment in comparison. If you run up a balance and pay only the minimum each month, you pay a lot of interest over time, because your principal goes down slowly. If you suddenly pay off your credit card, you don't have to pay any more interest, but you also don't get any interest back for previous months. That's because the interest accrued each month is based on your current balance, just like your mortgage. The minimum payments are calculated differently, but the interest accrued each month uses essentially the same mechanism.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"436331\",\n \"text\": \"I suggest rolling it over to the 401(k) with your new employer. Particularly if they match any percentage of your contribution, it would be in your interest to take as much of that money as possible. When it comes to borrowing money from your 401(k), it looks like the issues AbraCadaver mentioned only apply if you don't pay back the money (http://www.kiplinger.com/article/real-estate/T010-C000-S002-borrowing-from-your-retirement-plan-to-buy-a-home.html). The reasonable argument against taking money out of your 401(k) to buy a home is that it leaves a dent in your retirement nest egg (and its earning power) during key earning years. On the plus side for borrowing from your 401(k), it's very low interest--and it's interest you're paying back to yourself over a 5-year period. At its current value, the most you could borrow from your 401(k) is $35K. If you're fortunate in where you live, that could be most or all of the downpayment. In my own experience, my wife borrowed against her 401(k) balance for the earnest money when we purchased a new home. Fortunately for us, an investor snapped up my previous home within 4 days of us listing it, so she was able to pay back her loan in full right away.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"293897\",\n \"text\": \"\\\"Let me run some simplistic numbers, ignoring inflation. You have the opportunity to borrow up to 51K. What matters (and varies) is your postgraduation salary. Case 1 - you make 22K after graduation. You pay back 90 a year for 30 years, paying off at most 2700 of the loan. In this case, whether you borrow 2,800 or 28,000 makes no difference to the paying-off. You would do best to borrow as much as you possibly can, treating it as a grant. Case 2 - you make 100K after graduation. You pay back over 7K a year. If you borrowed the full 51, after 7 or 8 years it would be paid off (yeah, yeah, inflation, interest, but maybe that might make it 9 years.) In this case, the more you borrow the more you have to pay back, but you can easily pay it back, so you don't care. Invest your sponsorships and savings into something long term since you know you won't be needing to draw on them. Case 3 - you make 30K after graduation. Here, the payments you have to make actually impact how much disposable income you have. You pay back 810 a year, and over 30 years that's about 25K of principal. It will be less if you account for some (even most) of the payment going to interest, not principal. Anything you borrow above 25K (or the lower, more accurate amount) is \\\"\\\"free\\\"\\\". If you borrow substantially less than that (by using your sponsorship, savings, and summer job) you may be able to stop paying sooner than 30 years. But even if you borrow only 12K (or half the more accurate number), it will still be 15 years of payments. Running slightly more realistic versions of these calculations where your salary goes up, and you take interest into account, I think you will discover, for each possible salary path, a number that represents how much of your loan is really loan: everything above that is actually a grant you do not pay back. The less you are likely to make, the more of it is really grant. On top of that, it seems to me that no matter the loan/grant ratio, \\\"\\\"borrow as much as you can from this rather bizarre source\\\"\\\" appears to be the correct answer. In the cases where it's all loan, you have a lot of income and don't care much about this loan payment. Borrowing the whole 51K lets you invest all the money you get while you're a student, and you can use the returns on those investments to make the loan payments.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"559745\",\n \"text\": \"\\\"@fredsbend, Hope this helps! \\\"\\\"I understand that a reverse mortgage can be paid out in two ways: A lump sum and monthly payments. I figure that if you take the lump sum, eventually, the bank wants you to start paying it back.\\\"\\\" Answer: Actually, there are 3 payout options, or 4 if you consider a combination payout as another one. There's a lump sum, a line of credit, or the monthly payout, or a combination. \\\"\\\"I figure that if you take the monthly payments, eventually, the bank stops paying out and wants you to pay it back. In both situations, interest accrues and this is how the bank makes money off of the deal\\\"\\\". Answer: The only time the monthly payments would stop would be if the borrower defaults on the lenders' terms or they no longer live at home. You are right though, and interest does accrue on whichever payment is decided on. I'm not sure how the lender makes money, probably by the interest, but I know borrowers are protected against high rates and owing more than your house. Here's an article I found that goes over the protections more in detail: https://www.americanadvisorsgroup.com/news/6-consumer-protections-reverse-mortgage-loan-borrowers. \\\"\\\"But what determines when you have to begin paying back the reverse mortgage? Some sources online seem to say that it's based only on if you die or would like to sell/move. That can't be right in all situations, because you could end up with a massive debt on a property more than its value.\\\"\\\" Answer: There are a lot of protections or regulations in place to protect anyone who takes out a reverse mortgage. One being, you can't owe MORE than your house is valued at during the time of repayment, a reverse mortgage is a non-recourse loan. In the instance that your house is less than you owe, you either sell the home and the proceeds are used to pay the loan and you keep the rest OR if you owe more than the house proceeds of the home go to the lender. Either way, you're not left paying for a \\\"\\\"mortgage\\\"\\\" without the house. In the case the parent, grandparent passes, then the heirs would have a choice of either paying back the reverse mortgage in payments, OR they can sell the house, heirs are protected during this as well to make sure they're not left with major debt in case of anything. Is there a formula to figure out when the bank stops the monthly payments and then wants it back? **Answer:**The amount becomes due if loan terms are not met, but the lender will discuss the options if it comes to that. Is there a different formula for when the lump sum would have to be paid back?\\\"\\\" Answer: Each payout option has the same terms and the same pay back terms. As long as terms are met, the lender can't ask for early repayment.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"479240\",\n \"text\": \"I like the answers others gave, if it's some substantial debt you definitely could go the bankruptcy route but it damages your future, also it's morally unethical to borrow all that money and not intend to pay. Second, if you can pay off the entire balance and clear out the 23% interest than I'd do that first. One less bill to concern yourself with. Now let's say you've been making $100 payments monthly on each card (my assumption for this examples sale) now instead of paying $100 to the remaining cards balance each month and saving the other $100, pay $200 against the remaining credit cards balance. By not taking home any money this way you are tackling the liability that is costing you money every month. Unless you have a great investment opportunity on that remaining $1000 or haven't created much of an emergency fund yet, I'd consider putting more of that money towards the debt. Gaining 0.01% on savings interest still means you're eating 25.99% in debt monthly. If you're able to I'd venture out to open a zero interest card and do a balance transfer over to that new card, there will be a minimal transfer fee but you may get some cash back out of it and also that zero interest for a year would help hold off more interest accruing while you're tackling the balance.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"171339\",\n \"text\": \"\\\"One of the factors of a credit score is the \\\"\\\"length of time revolving accounts have been established\\\"\\\". Having a credit card with any line of credit will help in this regard. The account will age regardless of your use or utilization. If you are having issues with credit limits and no credit history, you may have trouble getting financing for the purchase. You should be sure you're approved for financing, and not just that the financing option is \\\"\\\"available\\\"\\\" (potentially with the caveat of \\\"\\\"for well qualified borrowers\\\"\\\"). Generally, if you've gotten approved for financing, that will come in the form of another credit card account (many contracting and plumbing companies will do this in hopes you will use the card for future purchases) or a bank loan account (more common for auto and home loans). With the credit card account, you might be able to perform a balance transfer, but there are usually fees associated with that. For bank loan accounts, you probably can't pay that off with a credit card. You'll need to transfer money to the account via ACH or send in a check. In short: I wouldn't bet on paying with your current credit card to get any benefit. IANAL. Utilizing promotional offers, whether interest-free for __ months, no balance transfer fees, or whatever, and passing your debt around is not illegal, not fraudulent, and in many cases advised (this is a link), though that is more for people to distribute utilization across multiple cards, and to minimize interest accrued. Many people, myself included, use a credit card for purchasing EVERYTHING, then pay it off in full every month (or sometimes immediately) to reap the benefit of cash back rewards and other cardholder benefits. I've also made a major payment (tuition, actually) on a Discover card, and opened up a new Visa card with 18-months of no interest and no balance transfer fees to let the bill sit for 12 months while I finished school and got a job.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"360003\",\n \"text\": \"My opinion is that in general, it is probably not a good idea to borrow at a cost in order to make your RRSP contribution. Banks, of course, have an interest in loaning you money. Don't expect their literature to be objective on the matter! They are selling you a product and the advice is biased. What better way to double-dip than to get guaranteed interest payments from you, as well as ongoing fees for (probably also) getting your loan money invested in their high-fee mutual funds? A year's RRSP contribution room allowance isn't use it or lose it — unlike 401k contribution allowances in the U.S.. That is, unused RRSP contribution room accumulates and you can take advantage of it in later years. If we couldn't carry our RRSP contribution room over, I might feel different about the general case for RRSP loans. Yet there are two specific cases I can think of where it may make sense to borrow and pay back: (a possible case) ... if your tax rate is currently in a high bracket (e.g. 46%), and you anticipate being in a lower income and bracket next year (e.g. 35%), then it would make sense to take advantage of the higher tax savings in the current tax year. If you waited until the following year to take the deduction, you'd lose out on 11% of the deducted amount. For a typical person whose income is level or increasing from year to year, this isn't likely to be applicable, but it could help somebody who is going on leave or otherwise has irregular income. (a foolish case) ... if you knew, somehow, that you could realize a return on your invested RRSP money exceeding the pre-tax earnings required to pay the interest on the RRSP loan. However, I would suggest this is foolish bet to make. The interest you pay is guaranteed, but the return you are expected to get is probably not (or if it is, it is probably a return lower than what your bank wants to charge on the loan.) If for some reason it does make sense for you, take the money and invest it somewhere better than the high-fee mutual funds the bank is also pushing.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"365342\",\n \"text\": \"If you intend to flip this property, you might consider either a construction loan or private money. A construction loan allows you to borrow from a bank against the value of the finished house a little at a time. As each stage of the construction/repairs are completed, the bank releases more funds to you. Interest accrues during the construction, but no payments need to be made until the construction/repairs are complete. Private money works in a similar manner, but the full amount can be released to you at once so you can get the repairs done more quickly. The interest rate will be higher. If you are flipping, then this higher interest rate is simply a cost of doing business. Since it's a private loan, you ca structure the deal any way you want. Perhaps accruing interest until the property is sold and then paying it back as a single balloon payment on sale of the property. To find private money, contact a mortgage broker and tell them what you have in mind. If you're intending to keep the property for yourself, private money is still an option. Once the repairs are complete, have the bank reassess the property value and refinance based on the new amount. Pay back the private loan with equity pulled from the house and all the shiny new repairs.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"150607\",\n \"text\": \"\\\"In England, currently and for most of the last fifty years, the standard length of the mortgage term is 25 years. A mortgage can be either a capital-and-interest mortgage, or interest-only. In the former, you pay off part of the original loan each month, plus the interest on the amount borrowed. In the latter, you only pay interest each month, and the original amount borrowed never reduces: you pay premiums on a life insurance policy, additionally, which is designed to pay off the original sum borrowed at the end of the 25 years. No one in England thinks that a 25 year loan has any drawbacks. The main point to appreciate is that the longer the period of the loan, the less you need to pay each month, because you are repaying the original loan - the capital - over a longer period of time. Thus, in principle, a mortgage is easier to repay the longer the term is, because the monthly payment is less. If you have a 12 year mortgage, you must pay back the original amount borrowed in half the time: the capital element in your payment each month is double what it would be if repaid over 25 years - i.e. if repaid over a period twice as long. Only if the borrower is less than 25 years away from retirement is a 25 years mortgage seen as a bad idea, by the lender - because, obviously, the lender relies on the borrower having an income sufficient to keep up the repayments. There are many complicating factors: an interest-only mortgage, where you pay back the original amount borrowed from the maturity proceeds from a life policy, puts you in a situation where the original capital sum never reduces, so you always pay the same each month. But on a straight repayment mortgage, the traditional type, you pay less and less each month as time goes by, for you are reducing the capital outstanding each month, and because that is reducing so is the amount of interest you pay each month (as this is calculated on the outstanding capital amount). There are snags to avoid, if you can. For example, some mortgage contracts impose penalties if the borrower repays more than the due monthly amount, hence in effect the borrower faces a - possibly heavy - financial penalty for early repayment of the loan. But not all mortgages include such a condition. If house prices are on a rising trend, the market value of the property will soon be worth considerably more than the amount owed on the mortgage, especially where the mortgage debt is reducing every month, as each repayment is made; so the bank or other lender will not be worried about lending over a 25 year term, because if it forecloses there should normally be no difficulty in recovering the outstanding amount from the sale proceeds. If the borrower falls behind on the repayments, or house prices fall, he may soon get into difficulties; but this could happen to anyone - it is not a particular problem of a 25 year term. Where a default in repayment occurs, the bank will often suggest lengthening the mortgage term, from 25 years to 30 years, in order to reduce the amount of the monthly repayment, as a means of helping the borrower. So longer terms than 25 years are in fact a positive solution in a case of financial difficulty. Of course, the longer the term the greater the amount that the borrower will pay in total. But the longer the term, the less he will pay each month - at least on a traditional capital-and-interest mortgage. So it is a question of balancing those two competing factors. As long as you do not have a mortgage condition that penalises the borrower for paying off the loan more quickly, it can make sense to have as long a term as possible, to begin with, which can be shortened by increasing the monthly repayment as fast as circumstances allow. In England, we used to have tax relief on mortgage payments, and so in times gone by it did make sense to let the mortgage run the full 25 years, in order to get maximum tax relief - the rules were very complex, but it tended to maximise your tax relief by paying over the longest possible period. But today, with no income tax relief given on mortgage payments, that is no longer a consideration in this country. The practical position is, of course, that you can never tell how long it might take you to pay off a mortgage. It is a gamble as to whether your income will rise in future years, and whether your job will last until your mortgage is paid off. You might fall ill, you might be made redundant, you might be demoted. Mortgage interest rates might rise. It is never possible to say that you \\\"\\\"can\\\"\\\" pay off the loan in a short time. If you hope to do so, the only matters that actually fall within your control are the conditions of the mortgage contract itself. Get a good lawyer. Tell him to watch out for early-redemption penalties. Get a good financial adviser. Tell him to work out what you will need to pay in additional premiums on your life policy if you are considering taking an interest-only mortgage. Try to fix your mortgage rate in the first few years, for as long as possible, so that in your most vulnerable period, with the greatest amount owing, you are insulated against unexpected interest rate fluctuations. Only the initial conditions can be controlled, so it might be prudent to take as long a term as possible, even though a prudent borrower will leave himself room to reduce that term, and a prudent lender will leave room to extend it, in case of unpredictable changes in the financial circumstances. In England, most lenders are, in my experience, reluctant to grant mortgages for less than 25 years. That is simply a policy. Rightly or wrongly, the borrower usually has no choice about the length of the mortgbage term. Hence, in the UK it can be difficult to find a choice of interest rates based on differing mortgage terms. I am aware that the situation in the USA is rather different, but if I personally were faced with the choice I would be uncomfortable about taking on a short term mortgage, because of the factors I have outlined above.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"10873\",\n \"text\": \"\\\"This answer is better served as a comment but I don't have enough rep. It is not guaranteed that they 'do not accrue interest while you are a full time student'. Some student loans can capitalize the interest - before pursuing leveraged investing, be sure that your student loan is not capitalizing. https://www.salliemae.com/student-loans/manage-your-private-student-loan/understand-student-loan-payments/learn-about-interest-and-capitalization/ Capitalized interest Capitalized interest is a second reason your loan may end up costing more than the amount you originally borrowed. Interest starts to accrue (grow) from the day your loan is disbursed (sent to you or your school). At certain points in time—when your separation or grace period ends, or at the end of forbearance or deferment—your Unpaid Interest may capitalize. That means it is added to your loan’s Current Principal. From that point, your interest will now be calculated on this new amount. That’s capitalized interest.\\\"\\\" https://www.navient.com/loan-customers/interest-and-taxes/how-student-loan-interest-works/ Capitalized Interest If you accrue interest while you are in school – as with Direct Unsubsidized, FFELP Unsubsidized, Direct and FFELP PLUS Loans, and Private Loans – you will have capitalized interest if it is unpaid. Unpaid accrued interest is added to the principal amount of your loan after you leave school and finish any applicable grace period. Simply put, there will be interest to be paid on both the principal of the loan and on the interest that has already accumulated. To minimize the effects of the capitalized interest on the amount you will pay overall, you can pay the interest during college instead of waiting until after graduation. That way, you start with the original principal balance (minus any fees) when you begin repayment.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"543811\",\n \"text\": \"\\\"I think to some extent you may be confusing the terms margin and leverage. From Investopedia Two concepts that are important to traders are margin and leverage. Margin is a loan extended by your broker that allows you to leverage the funds and securities in your account to enter larger trades. In order to use margin, you must open and be approved for a margin account. The loan is collateralized by the securities and cash in your margin account. The borrowed money doesn't come free, however; it has to be paid back with interest. If you are a day trader or scalper this may not be a concern; but if you are a swing trader, you can expect to pay between 5 and 10% interest on the borrowed money, or margin. Going hand-in-hand with margin is leverage; you use margin to create leverage. Leverage is the increased buying power that is available to margin account holders. Essentially, leverage allows you to pay less than full price for a trade, giving you the ability to enter larger positions than would be possible with your account funds alone. Leverage is expressed as a ratio. A 2:1 leverage, for example, means that you would be able to hold a position that is twice the value of your trading account. If you had $25,000 in your trading account with 2:1 leverage, you would be able to purchase $50,000 worth of stock. Margin refers to essentially buying with borrowed money. This must be paid back, with interest. You also may have a \\\"\\\"margin call\\\"\\\" forcing you to liquidate assets if you go beyond your margin limits. Leverage can be achieved in a number of ways when investing, one of which is investing with a margin account.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"521418\",\n \"text\": \"\\\"A credit card is basically a \\\"\\\"revolving\\\"\\\" loan, in which you're allowed to borrow up to a certain amount (the limit), and any time you borrow, you pay interest. If you were to *borrow* $100 to pay for something via a credit card, you'd have a $100 balance on the card. If you then pay $70 cash to the card, there would be $30 remaining. That $30 balance could accrue interest. The timing of that interest charge could vary. The 20% you've quoted is almost certainly \\\"\\\"APR,\\\"\\\" of which the \\\"\\\"A\\\"\\\" stands for \\\"\\\"annual,\\\"\\\" so that 20% would be an annual rate. It makes the most sense, mind you, to keep a minimal balance on a credit card, as the interest rate is higher than most other loans.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"559618\",\n \"text\": \"\\\"Somehow I just stumbled onto this thread... > You essentially robbed the person holding the debt (since you promised to pay it off). Depends on leverage, with fractional reserve lending. Banks are permitted to loan out 30x their actual assets, or more. If I have $1 but can loan out $30, and anything more than $1 gets paid back, I haven't lost any money. In addition, I can write off the amount defaulted, *and the government will pay me back* for certain types of loans. With student loans, since they are almost impossible to discharge, gov't will pursue the borrower for years and decades, and ultimately collect more interest. Here is an article on it: http://online.wsj.com/article/SB10001424052748704723104576061953842079760.html > According to Kantrowitz, the government stands to earn $2,010.44 more in interest from a $10,000 loan that defaulted than if it had been paid in full over a 20-year term, and $6,522.00 more than if it had been paid back in 10 years. Alan Collinge, founder of borrowers' rights advocacy Student Loan Justice, said the high recovery rates provide a \\\"\\\"perverted incentive\\\"\\\" for the government to allow loans to go into default. Kantrowitz estimates the recovery rate would need to fall to below 50% in order for default prevention efforts to become more lucrative than defaults themselves. Not to mention: http://studentloanjustice.org/defaults-making-money.html > So essentially, the Department is given a choice: Either do nothing and get nothing, or outlay cash with the knowledge that this outlay will realize a 22 percent return, ultimately (minus the governments cost of money and collection costs). From this perspective, it is clear that based solely on financial motivations, and without specific detailed knowledge of the loan (i.e. borrower characteristics, etc.), the chooser would clearly favor the default scenario, for not only the return, but perhaps the potential savings in subsidy payment as well, And don't forget the penalties accruing to the person defaulting; they will probably have to move out of the country in order to escape collection. And let's factor in the huge ROI the lender sees by creating an indentured servant class. Plus, the gov't will issue as much currency as it wants, to make *itself* whole. And how much of a loss IS the loss, when the whole of the loan amount went right back into the local economy, paying professors, janitors, landlords, grocery stores, etc.? And don't forget all THOSE taxes (income and sale) that the gov't collects. Government will collect ~30%-50% of the loan immediately as income and sales tax, plus a portion of it every time the money changes hands (I pay income tax, then use some of my after-tax money to pay you for a product or service, and you still have to pay tax on that money, and so on). So it's more complicated than having \\\"\\\"robbed the person holding the debt\\\"\\\". Banks at 30x leverage don't lose money as long as they get back 1/30th of the total amount lent out, including interest, fees, and penalties, before considering write-offs and government repayment. In fact, the point of over-leverage is so you CAN make loans that have risk attached. If you could only lend what you actually had, you would have to stay away from anything risky because it would be too easy to lose money. Having virtual $ to bet means you can serve market segments that have higher risk. This makes MORE money for the banks, that's why they do it. They are already playing with funny money, so they don't lose any even if you default and move to another country. And the money you \\\"\\\"spent\\\"\\\" has also made its way back to them in various amounts, such as your professor's mortgage payments, auto loan, etc. Your taking on debt already helped the bank get its OTHER loans repaid. So, roughly speaking, if you took out $90,000 and $3,000 of that made its way back to the bank through various means, they haven't lost any money, because it only cost them $3,000 actual dollars in the first place.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"421743\",\n \"text\": \"\\\"never carry a balance on a credit card. there is almost always a cheaper way to borrow money. the exception to that rule is when you are offered a 0% promotion on a credit card, but even then watch out for cash advance fees and how payments are applied (typically to promotional balances first). paying interest on daily spending is a bad idea. generally, the only time you should pay interest is on a home loan, car loan or education loan. basically that's because those loans can either allow you to reduce an expense (e.g. apartment rent, taxi fair), or increase your income (by getting a better job). you can try to make an argument about the utility of a dollar, but all sophistry aside you are better off investing than borrowing under normal circumstances. that said, using a credit card (with no annual fee) can build credit for a future car or home loan. the biggest advantage of a credit card is cash back. if you have good credit you can get a credit card that offers at least 1% cash back on every purchase. if you don't have good credit, using a credit card with no annual fee can be a good way to build credit until you can get approved for a 2% card (e.g. citi double cash). additionally, technically, you can get close to 10% cash back by chasing sign up bonuses. however, that requires applying for new cards frequently and keeping track of minimum spend etc. credit cards also protect you from fraud. if someone uses your debit card number, you can be short on cash until your bank fixes it. but if someone uses your credit card number, you can simply dispute the charge when you get the bill. you don't have to worry about how to make rent after an unexpected 2k$ charge. side note: it is a common mis-conception that credit card issuers only make money from cardholder interest and fees. card issuers make a lot of revenue from \\\"\\\"interchange fees\\\"\\\" paid by merchants every time you use your card. some issuers (e.g. amex) make a majority of their revenue from merchants.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"249831\",\n \"text\": \"\\\"Ditto mhoran_psprep. I'm not quite sure what you're asking. Where does the money come from? When someone starts a bank, they normally get together a bunch of investors -- perhaps people they know personally, perhaps they sell stock -- to raise initial capital. But most of the money in the bank comes from depositors. Fundamentally, what a bank does is take money from depositors and loan it to borrowers. (Banks also borrow money from other banks and from the government.) They charge the borrowers interest on the loan, and they pay depositors interest on their deposits. The difference between those two interest rates is where the bank gets their profit. Where does the money go when you pay it back? As mhoran_psprep said, some of it goes to pay interest to the depositors; some of it goes to pay the bank's expenses like employee salaries, cost of the building, etc; and some of it goes as profit to the owners or stockholders of the bank. If you're thinking, \\\"\\\"Wow, I'm paying back a whole lot more than I borrowed\\\"\\\", well, yes. But remember you're borrowing that money for 20 or 30 years. The bank isn't making very much money on the loan each year that you have it -- these days something like 4 or 5% in the U.S., I don't know what the going rates are in other countries.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"42475\",\n \"text\": \"\\\"The interest rate offered by a bond is called the nominal interest rate. The so-called real interest rate is the nominal interest rate minus the rate of inflation. If inflation is equal to or greater than the nominal rate at any given time, the REAL interest rate is zero or negative. We're talking about a ten year bond. It's possible for the real interest rate to be negative for one or two years of the bond's life, and positive for eight or nine. On the other hand, if we have a period of rising inflation, as in the 1970s, the inflation rate will exceed the (original) interest rate in most years, meaning that the real interest rate on the ten year bond will be negative over its whole life. People lost \\\"\\\"serious\\\"\\\" money on bonds (and loans) in the 1970s. In such situations, the BORROWERS make out. That is, they borrow money at low rates, earn inflation (plus a little more) pay back inflated dollars, and pocket the difference. For them, the money is \\\"\\\"free.\\\"\\\"\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"191508\",\n \"text\": \"Forget about terms. Think about loans in terms of months. To simplify things, let's consider a $1000 loan with .3% interest per month. This looks like a ten month term, but it's equally reasonable to think about it on a month-to-month basis. In the first month, you borrowed $1000 and accrued $3 interest. With the $102 payment, that leaves $901 which you borrow for another month. So on and so forth. The payoff after five payments would by $503.54 ($502.03 principal plus $1.51 interest). You'd save $2.99 in interest after paying $13.54. The reason why most of the interest was already paid is that you already did most of the borrowing. You borrowed $502.03 for six months and about $100 each for five, four, three, two, and one month. So you borrowed about $4500 months (you borrowed $1000 for the first month, $901 for the second month, etc.). The total for a ten month $1000 loan is about $5500 months of borrowing. So you've done 9/11 of the borrowing. It's unsurprising that you've paid about 9/11 of the interest. If you did this as a six month loan instead, then the payments look different. Say You borrow $1000 for one month. Then 834 for one month. So on and so forth. Adding that together, you get about $168.50 * 21 or $3538.50 months borrowed. Since you only borrow about 7/9 as much, you should pay 7/9 the interest. And if we adding things up, we get $10.54 in interest, about 7/9 of $13.54. That's how I would expect your mortgage to work in the United States (and I'd expect it to be similar elsewhere). Mortgages are pretty straight-jacketed by federal and state regulations. I too once had a car loan that claimed that early payment didn't matter. But to get rid of the loan, I made extra payments. And they ended up crediting me with an early release. In fact, they rebated part of my last payment. I saved several hundred dollars through the early release. Perhaps your loan did not work the same way. Perhaps it did. But in any case, mortgages don't generally work like you describe.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"239611\",\n \"text\": \"\\\"The most important thing in my view is flexibility, to avoid running into problems. One useful thing in the UK would be an arranged overdraft. You go to your bank, and they'll agree that you can overdraw your account by a certain number of pounds, depending on your income etc. It will cost you a very high interest rate, but only for each day where you are overdrawn. So paying a bill two days before your salary comes in isn't too bad. Obviously avoid using the overdraft if you can, having an overdraft while not using it is free. It's meant for an emergency; being regularly overdrawn is expensive. But once it is arranged with your bank, an arranged overdraft is much much cheaper than bouncing cheques etc. and possibly high fees for overdrawing your account. And it takes the pressure of you. Now things to need before you get a loan (again, UK): The real interest rate that you are paying is called APR. That's the number that counts, and that cannot be manipulated. No \\\"\\\"payday loans\\\"\\\" to avoid getting yourself into deep, deep trouble. No loan sharks, obviously. If you buy things with \\\"\\\"interest free credit\\\"\\\", that's (a) included in the price, so you pay more, and (b) if you miss paying by one day they'll hit you with huge interest payments, and some will try this intentionally. Interest rate depends on loan amount. I once had to borrow 20% more than I needed because it reduced the interest rate by half... The 20% went straight into a savings account. Credit cards and overdrafts are much more expensive than loans. Mortgage is again cheaper than a loan usually. Make sure that you only use money from sources that charge the least amount. Make sure you pay back regularly so cheap sources stay available to you. Just do yourself a favour and if at all possible, spend less instead of getting a loan.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"362468\",\n \"text\": \"\\\"I've never heard of a loan product like that. Yes, if they keep the funds in an account, it is no risk to the bank, but they would essentially need to go through the loan process twice for the same loan: when you pick a house, they need to reevaluate everything, along with appraising and approving the house. Even if you did find a bank that would do this for you, there are a few problems with this scheme. You would be paying interest before you have a need for this money, negating the savings you might achieve if the interest rates go up. In addition, your \\\"\\\"balance\\\"\\\" will go down as \\\"\\\"payments\\\"\\\" are deducted from your loan, and when you finally find a home to buy, you might not have enough for the house you want. You'll need to borrow more than you need, which will further negate any possible savings. It is impossible to know how fast rates will climb. If I were you, I would stick to saving for your down payment, and just get the best rate you can when you are ready to buy. Another potential idea for you is to lock an interest rate. When you apply for a mortgage, the interest rate is often locked for as much as 60 days, to protect the borrower in the event that the rates go up. You could ask the bank if you can pay a fee to lock the rate even longer. I don't know if that is possible or not. And, of course, the fee would eat into your potential savings.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"17110\",\n \"text\": \"Because this is Money.SE and you're connecting it to offspring, I'd think about a discussion with them to get their agreements. From my perspective, anything (my wife and) I have will go to offspring in the end. As such, everything borrowed and not repaid simply reduces the estate by that much. Among multiple offspring, such reductions should be against the borrower rather than spreading it out. That should be accounted for in whatever will is created. This would be the discussion point. It might also be discussed how or even if any interest should accrue for unpaid amounts. If, for example, a 1% APR is agreed upon for unpaid loans, then the final principle+interest amount is taken off of the borrower's inheritance. Existing outstanding loans might (or might not!) be useful examples for sample calculations if desired or needed. (If nothing else, they might serve as reminders that loans were not forgotten.) By having such a discussion, you can show that you are trying to plan for a fair distribution of your estate, perhaps thereby sidestepping any concern about charging interest to offspring for repaid loans. At the same time, you're handing over some financial responsibility, giving them a power of personal choice, which seems to be a part of what you're concerned about. Once such a discussion is started, it's possible that any question of interest will resolve itself naturally. The discussion almost necessarily must include all offspring at once. One will find it harder to negotiate from a standpoint of pure self-interest without objection from another. Think beforehand about what will be said and about what responses might come. Think things through as much as you can.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"22268\",\n \"text\": \"\\\"They don't actually need to. They accept deposits for historical reasons and because they make money doing so, but there's nothing key to their business that requires them to do so. Here's a decent summary, but I'll explain in great detail below. By making loans, banks create money. This is what we mean when we say the monetary supply is endogenous. (At least if you believe Sir Mervyn King, who used to run England's central bank...) The only real checks on this are regulatory--capitalization requirements and reserve requirements, which impose a sort of tax on a bank's circulating loans. I'll get into that later. Let's start with Why should you believe that story--that loans create deposits? It seems like a bizarre assertion. But it actually matches how banks behave in practice. If you go borrow money from a bank, the loan officer will do many things. She'll want to look at your credit history. She'll want to look at your income and assets. She'll want to look at what kind of collateral or guarantees you're providing that the loan will be repaid. What she will not do is call down to the vaults and make sure that there's enough bills stacked up for them to lend out. Loans are judged based on a profitability function determined by the interest rate and the loan risk. If those add up to \\\"\\\"profitable\\\"\\\", the bank makes the loan. So the limiting factor on the loans a bank makes are the available creditworthy borrowers--not the bank's stock of cash. Further, the story makes sense because loans are how banks make money. If a bank that was short of money suddenly stopped making loans, it'd be screwed: no new loans = no way to make money to pay back depositors and also keep the lights on = no more bank. And the story is believable because of the way banks make so little effort to solicit commercial deposit business. Oh sure, they used to give you a free toaster if you opened an account; but now it's really quite challenging to find a no-fee checking account that doesn't impose a super-high deposit limit. And the interest paid on savings deposits is asymptotically approaching zero. If banks actually needed your deposits, they'd be making a lot more of effort to get them. I mean, they won't turn up their noses; your deposited allowance is a couple basis points cheaper to the bank than borrowing from the Fed; but banks seem to value small-potatoes depositors more as a source of fees and sales opportunities for services and consumer credit than as a source of cash. (It's a bit different if you get north of seven figures, but smaller depositors aren't really worth the hassle just for their cash.) This is where someone will mention the regulatory requirements of fractional reserve banking: banks are obliged by regulators to keep enough cash on hand to pay out a certain percentage of deposits. Note nothing about loans was said in that statement: this requirement does not serve as a check on the bank making bad loans, because the bank is ultimately liable to all its depositors for the full value of their deposits; it's more making sure they have enough liquidity to prevent bank runs, the self-fulfilling prophecy in which an undercapitalized bank could be forced into bankruptcy. As you noted in your question, banks can always borrow from the Fed at the Fed Discount Rate (or from other banks at the interbank overnight rate, which is a little lower) to meet this requirement. They do have to pledge collateral, but loans themselves are collateral, so this doesn't present much of a problem. In terms of paying off depositors if the bank should collapse (and minimizing the amount of FDIC insurance payout from the government), it's really capital requirements that are actually important. I.E. the bank has to have investors who don't have a right to be paid back and whose investment is on the hook if the bank goes belly-up. But that's just a safeguard for the depositors; it doesn't really have anything to do with loans other than that bad loans are the main reason a bank might go under. Banks, like any other private business, have assets (things of value) and liabilities (obligations to other people). But banking assets and liabilities are counterintuitive. The bank's assets are loans, because they are theoretically recoverable (the principal) and also generate a revenue stream (the interest payments). The money the bank holds in deposits is actually a liability, because it has to pay that money out to depositors on demand, and the deposited money will never (by itself) bring the bank any revenue at all. In fact, it's a drain, because the bank needs to pay interest to its depositors. (Well, they used to anyway.) So what happens when a bank makes a loan? From a balance sheet perspective, strangely enough, the answer is nothing at all. If I grant you a loan, the minute we shake hands and you sign the paperwork, a teller types on a keyboard and money appears in your account. Your account with my bank. My bank has simultaneously created an asset (the loan you now have to repay me) and an equal-sized liability (the funds I loaned you, which are now deposited in your account). I'll make money on the deal, because the interest you owe me is a much higher rate than the interest I pay on your deposits, or the rate I'd have to pay if I need to borrow cash to cover your withdrawal. (I might just have the cash on hand anyway from interest and origination fees and whatnot from previous loans.) From an accounting perspective, nothing has happened to my balance sheet, but suddenly you owe me closing costs and a stream of extraneous interest payments. (Nice work if you can get it...) Okay, so I've exhaustively demonstrated that I don't need to take deposits to make loans. But we live in a world where banks do! Here's a few reasons: You can probably think of more, but at the end of the day, a bank should be designed so that if every single (non-borrowing) depositor withdrew their deposits, the bank wouldn't collapse or cease to exist.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"444637\",\n \"text\": \"Putting debt out long means to borrow a sum of money paid back over a longer period of time than you could reasonably pay it back. It should be important to note that this advice only applies for fixed rate loans (meaning your rate can't change for the life of the loan without you explicitly changing it). The logic is that if you can borrow money when interest rates are really low, there is a good chance you can find an investment that has a return higher than the interest rate on the loan. It also means that when/if interest rates go up in the future, a simple savings account may even have a greater return than your loans interest. The advice suggests to borrow over a long period so you are paying less interest per payment, and gives you time to find a proper investment without having to pay too much interest during that time.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"474318\",\n \"text\": \"\\\"If the government prints money recklessly and causes inflation, people will come to expect inflation, and the value of the currency will plummet, and you'll end up like Zimbabwe where a trillion dollars won't buy a loaf of bread. If the government actually pays people for the money they borrow, they don't have this problem - and as it turns out, the US government can get pretty good rates on borrowing in general, in part because they're extraordinarily good about paying them back. (Also, inflation expectations are low, so people will accept 1-2% interest rates. If you expected inflation of 10%, you'd see people demanding something more like 12% interest rates.) (The downside of too much of this sort of borrowing is that it \\\"\\\"crowds out\\\"\\\" other borrowing, which may harm the economy. Who would lend money to / invest in a small business, if the government is paying good money and there's almost no risk at all?) Now, inflation can come into play afterward, if the Fed decides it needs to maintain \\\"\\\"easy money\\\"\\\" policies to stimulate the economy (because taxes are too high because we're paying off the debt, or because we've crowded out smaller borrowers, or something). -- In general, you can count on the the principle that if you, as the government, try to play too many games with people's money... well, people aren't stupid; they will eventually catch on, and adjust their behavior to compensate, and then you're right back where you started, but with less trust.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"580147\",\n \"text\": \"When you get a loan (car, home, student) the lending company (bank) give the (auto dealer, previous home owner, school) money. You as the borrow promise to pay this money back with interest. So in your case the 100,000 you borrow requires a payment for principal and interest of ~965 per month. After 240 payments you will have paid the bank ~231,605. So who got the ~131,000 in interest. The bank did. It was used to pay interest to the people who made deposits into the bank. It was also used to pay the expenses of the bank: salaries, retirement, rent, electricity, computers, etc. If the bank is a company with investors they may have to pay dividends to them to. Of course not all loans are successfully paid back, so some of the payment goes to cover the loans that are in default. In many cases loans are also refinanced, or the house is sold long before the 20-30 year term is up. In these cases the amount of interest received for that loan is much less than anticipated, but the good news is that it can be loaned out again.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"285176\",\n \"text\": \"The assumption that bonds have been issued with a negative coupon is not correct, or at least is has not occurred thus far. We'll look at this future possibility in the final paragraph. For now, lets look at the current bond market. The issuance of government bonds which carry a negative gross redemption yield is the result of governments issuing bonds at an issue price which exceed the nominal/redemption price and any coupon yield receivable over the life of the bond. I can find no instances of bonds with a negative coupon, though many have tiny positive coupon yields. The short seller of a bond with a negative gross redemption yield will be liable to pay the buyer the interest amount determined by the coupon. If the short seller has borrowed the bonds in order to sell them, then the short seller will receive the interest due from the lender to offset the interest paid to the buyer. If the short seller has not borrowed the bonds, but has sold them using some sort of synthetic contract such as a Contract for Difference, then the short seller will pay the coupon without receiving any offsetting payment. I thought this was an interesting question and it will be interesting to see if, at some time in the future, governments do ever issue bonds with a negative coupon. To date, this does not appear to have happened. So what would happen if we assume that a government issues a bond with a negative coupon. The buyer of the bond would be required to pay the equivalent yield to the government according to the bond contract specification. If an investor sells short such a bond, they would then become entitled to receive the interest from the buyer. If they have borrowed the bonds in order to sell them short, then they would pay any interest received back to the lender - this chain should eventually end with the ultimate owner/lender paying the government their dues. If they have sold short using a synthetic contract, then presumably they would keep the interest from themselves.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"41312\",\n \"text\": \"You must mean the current debt ceiling debacle. The meaning of it is: US government is constantly borrowing money (by issuing treasury bonds) and constantly repaying some of the bonds that come to maturity, and also has other obligations it has to meet by law all the time - such as Social Security checks, bonds interest, federal employees' salaries and pensions, etc. By law, total amount of money that can be borrowed at the same time is capped. That means, there can be situation where the government needs to borrow money to pay, say, interest on existing bonds, but can not, since the limit is reached. Such situation is called a default, since the government promised to pay the interest, but is unable to do so. That does not mean the government has no money at all and will completely collapse or couldn't raise money on the market if it were permitted by law to do so (currently, the market is completely willing to buy the debt issued by US government, and with interest that is not very high, though of course that may change). It also does not mean the economy ceases to function, dollars cease to have value or banks instantly go bankrupt. But if the government breaks its promises to investors, it has various consequences such as raising the costs of borrowing in the future. Breaking promises to other people - like Social Security recipients - would also look bad and probably hurt many of them. Going back to your bank account, most probably nothing would happen to the money you store there. Even if the bank had invested 100% of the money in US treasury bonds (which doesn't really happen) they still can be sold on the open market, even if with some discount in the event of credit rating downgrade, so most probably your account would not be affected. As stated in another answer, even if the fallout of all these calamities causes a bank to fail, there's FDIC and if your money is under insured maximums you'll be getting your money back. But if your bank is one of the big ones, nothing of the sort would happen anyway - as we have seen in the past years, government would do practically anything to not allow any big bank failures.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"28809\",\n \"text\": \"\\\"Most likely that's the amount of interest that accrued on the loan while you were in school. If you had paid that amount before 6/21, you would have just paid off accrued interest and your loan balance would have stayed the same. Since you did not pay the interest, it will be added to your loan balance and you will just pay it off as part of the loan (plus compounded interest). If you pay off your loan at 5% over 30 years (hopefully you won't, but that's what they're amortized for), that $350 will compound and become $1,563. Essentially you're \\\"\\\"borrowing\\\"\\\" $350 at 5% interest for 30 years. Hopefully that motivates you to pay it off sooner that that...\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"557324\",\n \"text\": \"There are a few reasons, particularly for businesses. The first is opportunity cost. That chunk of money they have could be used to get higher returns somewhere else. If they can borrow from a bank at low interest rates to finance their ongoing operations, they can use their cash to get a higher return somewhere else. The second is credit rating. For public companies, ratings companies give high emphasis to companies with large reserves. This strengthens their ability to pay back the loan should it become necessary. A good credit rating in turn let's the company borrow money at lower rates. When a company can borrow money at low rates, it circles back to the first point where they can now put their reserves to better use. The third is leverage. Companies can use the cash they have built up to leverage into a larger investment. Assuming the investment works out, it will pay for the cost of borrowing over time. For instance let's say I have $1 million to invest. I can pay all cash for a $1 million apartment building or I can leverage that into a $3 million building. Assuming I run it well, the tenants will pay for the cost of borrowing $2 million and at the end of the term I'll be left with my $3 million building.\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":2588,"cells":{"query_id":{"kind":"string","value":"771"},"query":{"kind":"string","value":"Metastatic colorectal cancer treated with a single agent fluoropyrimidines resulted in similar efficacy and better quality of life when compared with oxaliplatin-based chemotherapy in elderly patients."},"positive_passages":{"kind":"list like","value":[{"docid":"15476777","text":"BACKGROUND Elderly and frail patients with cancer, although often treated with chemotherapy, are under-represented in clinical trials. We designed FOCUS2 to investigate reduced-dose chemotherapy options and to seek objective predictors of outcome in frail patients with advanced colorectal cancer. METHODS We undertook an open, 2 × 2 factorial trial in 61 UK centres for patients with previously untreated advanced colorectal cancer who were considered unfit for full-dose chemotherapy. After comprehensive health assessment (CHA), patients were randomly assigned by minimisation to: 48-h intravenous fluorouracil with levofolinate (group A); oxaliplatin and fluorouracil (group B); capecitabine (group C); or oxaliplatin and capecitabine (group D). Treatment allocation was not masked. Starting doses were 80% of standard doses, with discretionary escalation to full dose after 6 weeks. The two primary outcome measures were: addition of oxaliplatin ([A vs B] + [C vs D]), assessed with progression-free survival (PFS); and substitution of fluorouracil with capecitabine ([A vs C] + [B vs D]), assessed by change from baseline to 12 weeks in global quality of life (QoL). Analysis was by intention to treat. Baseline clinical and CHA data were modelled against outcomes with a novel composite measure, overall treatment utility (OTU). This study is registered, number ISRCTN21221452. FINDINGS 459 patients were randomly assigned (115 to each of groups A-C, 114 to group D). Factorial comparison of addition of oxaliplatin versus no addition suggested some improvement in PFS, but the finding was not significant (median 5·8 months [IQR 3·3-7·5] vs 4·5 months [2·8-6·4]; hazard ratio 0·84, 95% CI 0·69-1·01, p=0·07). Replacement of fluorouracil with capecitabine did not improve global QoL: 69 of 124 (56%) patients receiving fluorouracil reported improvement in global QoL compared with 69 of 123 (56%) receiving capecitabine. The risk of having any grade 3 or worse toxic effect was not significantly increased with oxaliplatin (83/219 [38%] vs 70/221 [32%]; p=0·17), but was higher with capecitabine than with fluorouracil (88/222 [40%] vs 65/218 [30%]; p=0·03). In multivariable analysis, fewer baseline symptoms (odds ratio 1·32, 95% CI 1·14-1·52), less widespread disease (1·51, 1·05-2·19), and use of oxaliplatin (0·57, 0·39-0·82) were predictive of better OTU. INTERPRETATION FOCUS2 shows that with an appropriate design, including reduced starting doses of chemotherapy, frail and elderly patients can participate in a randomised controlled trial. On balance, a combination including oxaliplatin was preferable to single-agent fluoropyrimidines, although the primary endpoint of PFS was not met. Capecitabine did not improve QoL compared with fluorouracil. Comprehensive baseline assessment holds promise as an objective predictor of treatment benefit. FUNDING Cancer Research UK and the Medical Research Council.","title":"Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial"}],"string":"[\n {\n \"docid\": \"15476777\",\n \"text\": \"BACKGROUND Elderly and frail patients with cancer, although often treated with chemotherapy, are under-represented in clinical trials. We designed FOCUS2 to investigate reduced-dose chemotherapy options and to seek objective predictors of outcome in frail patients with advanced colorectal cancer. METHODS We undertook an open, 2 × 2 factorial trial in 61 UK centres for patients with previously untreated advanced colorectal cancer who were considered unfit for full-dose chemotherapy. After comprehensive health assessment (CHA), patients were randomly assigned by minimisation to: 48-h intravenous fluorouracil with levofolinate (group A); oxaliplatin and fluorouracil (group B); capecitabine (group C); or oxaliplatin and capecitabine (group D). Treatment allocation was not masked. Starting doses were 80% of standard doses, with discretionary escalation to full dose after 6 weeks. The two primary outcome measures were: addition of oxaliplatin ([A vs B] + [C vs D]), assessed with progression-free survival (PFS); and substitution of fluorouracil with capecitabine ([A vs C] + [B vs D]), assessed by change from baseline to 12 weeks in global quality of life (QoL). Analysis was by intention to treat. Baseline clinical and CHA data were modelled against outcomes with a novel composite measure, overall treatment utility (OTU). This study is registered, number ISRCTN21221452. FINDINGS 459 patients were randomly assigned (115 to each of groups A-C, 114 to group D). Factorial comparison of addition of oxaliplatin versus no addition suggested some improvement in PFS, but the finding was not significant (median 5·8 months [IQR 3·3-7·5] vs 4·5 months [2·8-6·4]; hazard ratio 0·84, 95% CI 0·69-1·01, p=0·07). Replacement of fluorouracil with capecitabine did not improve global QoL: 69 of 124 (56%) patients receiving fluorouracil reported improvement in global QoL compared with 69 of 123 (56%) receiving capecitabine. The risk of having any grade 3 or worse toxic effect was not significantly increased with oxaliplatin (83/219 [38%] vs 70/221 [32%]; p=0·17), but was higher with capecitabine than with fluorouracil (88/222 [40%] vs 65/218 [30%]; p=0·03). In multivariable analysis, fewer baseline symptoms (odds ratio 1·32, 95% CI 1·14-1·52), less widespread disease (1·51, 1·05-2·19), and use of oxaliplatin (0·57, 0·39-0·82) were predictive of better OTU. INTERPRETATION FOCUS2 shows that with an appropriate design, including reduced starting doses of chemotherapy, frail and elderly patients can participate in a randomised controlled trial. On balance, a combination including oxaliplatin was preferable to single-agent fluoropyrimidines, although the primary endpoint of PFS was not met. Capecitabine did not improve QoL compared with fluorouracil. Comprehensive baseline assessment holds promise as an objective predictor of treatment benefit. FUNDING Cancer Research UK and the Medical Research Council.\",\n \"title\": \"Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"2492146","text":"Metastatic colorectal cancer (mCRC) is increasingly treated using targeted therapies. Post-marketing safety of these agents is understudied, especially in the elderly. This study aimed to compare, according to age, the adverse drug reactions (ADRs) of targeted therapies used for mCRC in real life. An extraction of VigiBase, which contains World Health Organization individual case safety reports (ICSRs), was performed. All ADR reports with aflibercept, bevacizumab, cetuximab, panitumumab, or regorafenib used in CRC were considered. For all drugs, chi-square tests were used to compare frequencies of serious ADRs between patients aged ≥75 and <75 years. For selected ADRs and each drug, the drug-ADR association compared to other anticancer drugs was estimated through the proportional reporting ratio (PRR) in both age groups. There were 21,565 ICSRs included, among which 74% were serious and 11% were fatal. Median age was 64 years (Inter Quartile Range = 56–71) and 15% of patients were aged ≥75; 57% were male. Serious ICSRs accounted for 47,292 ADRs. Neutropenia was not more reported in elderly for all drugs while diarrhea was more reported in elderly for panitumumab. Cardiac disorders were more reported in elderly patients, in particular heart failure, especially for bevacizumab, cetuximab, and regorafenib, as were respiratory, thoracic, and mediastinal disorders. Most of PRR were not different between the two groups, except encephalopathies, which were significantly associated with bevacizumab in the elderly only. ADRs related to targeted therapies used for mCRC treatment were different across age groups; yet, not systematically more reported or worse in elderly patients. Selected elderly patients could, therefore, be treated with these targeted therapies.","title":"Comparative Safety of Targeted Therapies for Metastatic Colorectal Cancer between Elderly and Younger Patients: a Study Using the International Pharmacovigilance Database"},{"docid":"13256155","text":"BACKGROUND Molecularly targeted agents have been reported to have anti-tumour activity for patients whose tumours harbour the matching molecular alteration. These results have led to increased off-label use of molecularly targeted agents on the basis of identified molecular alterations. We assessed the efficacy of several molecularly targeted agents marketed in France, which were chosen on the basis of tumour molecular profiling but used outside their indications, in patients with advanced cancer for whom standard-of-care therapy had failed. METHODS The open-label, randomised, controlled phase 2 SHIVA trial was done at eight French academic centres. We included adult patients with any kind of metastatic solid tumour refractory to standard of care, provided they had an Eastern Cooperative Oncology Group performance status of 0 or 1, disease that was accessible for a biopsy or resection of a metastatic site, and at least one measurable lesion. The molecular profile of each patient's tumour was established with a mandatory biopsy of a metastatic tumour and large-scale genomic testing. We only included patients for whom a molecular alteration was identified within one of three molecular pathways (hormone receptor, PI3K/AKT/mTOR, RAF/MEK), which could be matched to one of ten regimens including 11 available molecularly targeted agents (erlotinib, lapatinib plus trastuzumab, sorafenib, imatinib, dasatinib, vemurafenib, everolimus, abiraterone, letrozole, tamoxifen). We randomly assigned these patients (1:1) to receive a matched molecularly targeted agent (experimental group) or treatment at physician's choice (control group) by central block randomisation (blocks of size six). Randomisation was done centrally with a web-based response system and was stratified according to the Royal Marsden Hospital prognostic score (0 or 1 vs 2 or 3) and the altered molecular pathway. Clinicians and patients were not masked to treatment allocation. Treatments in both groups were given in accordance with the approved product information and standard practice protocols at each institution and were continued until evidence of disease progression. The primary endpoint was progression-free survival in the intention-to-treat population, which was not assessed by independent central review. We assessed safety in any patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT01771458. FINDINGS Between Oct 4, 2012, and July 11, 2014, we screened 741 patients with any tumour type. 293 (40%) patients had at least one molecular alteration matching one of the 10 available regimens. At the time of data cutoff, Jan 20, 2015, 195 (26%) patients had been randomly assigned, with 99 in the experimental group and 96 in the control group. All patients in the experimental group started treatment, as did 92 in the control group. Two patients in the control group received a molecularly targeted agent: both were included in their assigned group for efficacy analyses, the patient who received an agent that was allowed in the experimental group was included in the experimental group for the purposes of safety analyses, while the other patient, who received a molecularly targeted agent and chemotherapy, was kept in the control group for safety analyses. Median follow-up was 11·3 months (IQR 5·8-11·6) in the experimental group and 11·3 months (8·1-11·6) in the control group at the time of the primary analysis of progression-free survival. Median progression-free survival was 2·3 months (95% CI 1·7-3·8) in the experimental group versus 2·0 months (1·8-2·1) in the control group (hazard ratio 0·88, 95% CI 0·65-1·19, p=0·41). In the safety population, 43 (43%) of 100 patients treated with a molecularly targeted agent and 32 (35%) of 91 patients treated with cytotoxic chemotherapy had grade 3-4 adverse events (p=0·30). INTERPRETATION The use of molecularly targeted agents outside their indications does not improve progression-free survival compared with treatment at physician's choice in heavily pretreated patients with cancer. Off-label use of molecularly targeted agents should be discouraged, but enrolment in clinical trials should be encouraged to assess predictive biomarkers of efficacy.","title":"Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial."},{"docid":"20606520","text":"OBJECTIVES To assess mortality, quality of life (QOL), and quality-adjusted life-years (QALYs) for critically ill elderly patients. DESIGN Cross-sectional survey. SETTING A ten-bed medical-surgical intensive care unit (ICU) in a tertiary care university hospital. PATIENTS The study group included 882 elderly patients (> or =65 yrs of age) and 1,827 controls (<65 yrs of age) treated during the period of 1995 to 2000. INTERVENTION None. MEASUREMENTS AND MAIN RESULTS Mortality was assessed during the ICU and hospital stays, and 12, 24, and 36 months after ICU discharge. The cumulative 3-yr mortality rate among the elderly (57%) was higher (p < .05) than that among the controls (40%). The majority (66%) of the elderly nonsurvivors died within 1 month after intensive care discharge. All elderly patients with day-1 Sequential Organ Failure (SOFA) scores >15 died during the ICU stay. QOL was assessed with EQ-5D and RAND-36 measures from 10 months to 7 yrs after discharge. The majority (88%) of the elderly survivors assessed their present health state as good or satisfactory; 66% found it to be similar or better than 12 months earlier, and 48% similar or better than their preadmission state. QOL measures by RAND-36 revealed that aging decreased their competencies most in physical functioning, physical role limitations, and vitality, but the elderly had better values in mental health than the controls. However, QALYs of the elderly respondents were 21% to 35% lower than the mean QALY minus 2 sd units of the age- and gender-adjusted general population. CONCLUSIONS High age alone is not a valid reason to refuse intensive care, but the benefits perceived by intensive care seem to decrease with aging, if reflected as QALYs. However, 97% of the elderly survivors lived at home and 88% of them considered their QOL satisfactory or good after hospital discharge. Therefore, more reliable information on the outcome for the elderly is clearly needed.","title":"Long-term survival, quality of life, and quality-adjusted life-years among critically ill elderly patients."},{"docid":"7165938","text":"PURPOSE The circadian clock gene Bmal1 is involved in cancer cell proliferation and DNA damage sensitivity. The aim of this study was to explore the effect of Bmal1 on oxaliplatin sensitivity and to determine its clinical significance in colorectal cancer. EXPERIMENTAL DESIGN Three colorectal cancer cell lines, HCT116, THC8307 and HT29, were used. The Bmal1-mediated control of colorectal cancer cell proliferation was tested in vitro and in vivo. MTT and colony formation assays were performed to determine the sensitivity of colorectal cancer cells to oxaliplatin. Flow cytometry was used to examine changes in the cell-cycle distribution and apoptosis rate. Proteins expressed downstream of Bmal1 upon its overexpression were determined by Western blotting. Immunohistochemistry was used to analyze Bmal1 expression in 82 archived colorectal cancer tumors from patients treated with oxaliplatin-based regimens. RESULTS Bmal1 overexpression inhibited colorectal cancer cell proliferation and increased colorectal cancer sensitivity to oxaliplatin in three colorectal cancer cell lines and HCT116 cells model in vivo. Furthermore, the overall survival of patients with colorectal cancer with high Bmal1 levels in their primary tumors was significantly longer than that of patients with low Bmal1 levels (27 vs. 19 months; P = 0.043). The progression-free survival of patients with high Bmal1 expression was also significantly longer than that of patients with low Bmal1 expression (11 vs. 5 months; P = 0.015). Mechanistically, the effect of Bmal1 was associated with its ability to regulate G2-M arrest by activating the ATM pathway. CONCLUSION Bmal1 shows the potential as a novel prognostic biomarker and may represent a new therapeutic target in colorectal cancer.","title":"Overexpression of the circadian clock gene Bmal1 increases sensitivity to oxaliplatin in colorectal cancer."},{"docid":"9929089","text":"BACKGROUND Patients with advanced or metastatic non-small cell lung cancer (NSCLC) can develop acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib. Here, we report the successful treatment with alternating chemotherapy and TKIs of two cases of advanced NSCLC who developed resistance to TKI. CASE PRESENTATION Two patients with advanced or metastatic NSCLC were treated with palliative chemotherapy followed by erlotinib/gefitinib. When TKI therapy failed, two cycles of chemotherapy were provided, which were followed by re-challenge with erlotinib or gefitinib. CONCLUSION NSCLC patients with acquired TKI resistance should be managed aggressively whenever possible. Subsequent chemotherapy and target treatment is one of the reasonable choices for those with an initial dramatic clinical response with erlotinib/gefitinib treatment. Further studies are warranted to substantiate the association of erlotinib /gefitinib treatment with the efficacy of NSCLC patients with acquired TKI failure.","title":"Subsequent chemotherapy reverses acquired tyrosine kinase inhibitor resistance and restores response to tyrosine kinase inhibitor in advanced non-small-cell lung cancer"},{"docid":"24974080","text":"New blood vessel formation (angiogenesis) is a fundamental event in the process of tumor growth and metastatic dissemination. Hence, the molecular basis of tumor angiogenesis has been of keen interest in the field of cancer research. The vascular endothelial growth factor (VEGF) pathway is well established as one of the key regulators of this process. The VEGF/VEGF-receptor axis is composed of multiple ligands and receptors with overlapping and distinct ligand-receptor binding specificities, cell-type expression, and function. Activation of the VEGF-receptor pathway triggers a network of signaling processes that promote endothelial cell growth, migration, and survival from pre-existing vasculature. In addition, VEGF mediates vessel permeability, and has been associated with malignant effusions. More recently, an important role for VEGF has emerged in mobilization of endothelial progenitor cells from the bone marrow to distant sites of neovascularization. The well-established role of VEGF in promoting tumor angiogenesis and the pathogenesis of human cancers has led to the rational design and development of agents that selectively target this pathway. Studies with various anti-VEGF/VEGF-receptor therapies have shown that these agents can potently inhibit angiogenesis and tumor growth in preclinical models. Recently, an anti-VEGF antibody (bevacizumab), when used in combination with chemotherapy, was shown to significantly improve survival and response rates in patients with metastatic colorectal cancer and thus, validate VEGF pathway inhibitors as an important new treatment modality in cancer therapy.","title":"Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis."},{"docid":"24873253","text":"Patients with metastatic bone disease are at risk for developing skeletal-related events that can negatively influence quality of life, contributing to loss of autonomy and functional capabilities. Bisphosphonates have become an important component in the treatment of patients with bone metastases as they delay the onset and reduce the risk of skeletal-related events and also palliate or control bone pain in multiple cancer types, thus preserving quality of life. Zoledronic acid has proven efficacy and safety in patients with bone lesions from breast cancer, prostate cancer, lung cancer, and other solid tumors, as well as in patients with multiple myeloma. Current data suggest that early treatment with zoledronic acid (before the onset of bone pain) may provide additional clinical benefits and also positive effects on survival in subsets of patients who have elevated levels of N-telopeptide of type I collagen (NTX), a biochemical marker of bone resorption. Studies have shown that in patients with breast cancer, prostate cancer, lung cancer, or other solid tumors, normalization of elevated levels of NTX was observed in the majority of patients who received zoledronic acid. Furthermore, normalization of NTX values correlated with extended survival.","title":"Clinical benefits and considerations of bisphosphonate treatment in metastatic bone disease."},{"docid":"25589047","text":"CONTEXT Fatal adverse events (FAEs) have been reported in cancer patients treated with the widely used angiogenesis inhibitor bevacizumab in combination with chemotherapy. Currently, the role of bevacizumab in treatment-related mortality is not clear. OBJECTIVE To perform a systematic review and meta-analysis of published randomized controlled trials (RCTs) to determine the overall risk of FAEs associated with bevacizumab. DATA SOURCES PubMed, EMBASE, and Web of Science databases as well as abstracts presented at American Society of Clinical Oncology conferences from January 1966 to October 2010 were searched to identify relevant studies. STUDY SELECTION AND DATA EXTRACTION Eligible studies included prospective RCTs in which bevacizumab in combination with chemotherapy or biological therapy was compared with chemotherapy or biological therapy alone. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. DATA SYNTHESIS A total of 10,217 patients with a variety of advanced solid tumors from 16 RCTs were included in the analysis. The overall incidence of FAEs with bevacizumab was 2.5% (95% CI, 1.7%-3.9%). Compared with chemotherapy alone, the addition of bevacizumab was associated with an increased risk of FAEs, with an RR of 1.46 (95% CI, 1.09-1.94; P = .01; incidence, 2.5% vs 1.7%). This association varied significantly with chemotherapeutic agents (P = .045) but not with tumor types (P = .13) or bevacizumab doses (P = .16). Bevacizumab was associated with an increased risk of FAEs in patients receiving taxanes or platinum agents (RR, 3.49; 95% CI, 1.82-6.66; incidence, 3.3% vs 1.0%) but was not associated with increased risk of FAEs when used in conjunction with other agents (RR, 0.85; 95% CI, 0.25-2.88; incidence, 0.8% vs 0.9%). The most common causes of FAEs were hemorrhage (23.5%), neutropenia (12.2%), and gastrointestinal tract perforation (7.1%). CONCLUSION In a meta-analysis of RCTs, bevacizumab in combination with chemotherapy or biological therapy, compared with chemotherapy alone, was associated with increased treatment-related mortality.","title":"Treatment-related mortality with bevacizumab in cancer patients: a meta-analysis."},{"docid":"9558539","text":"Cancer stem cells drive tumor formation and metastasis, but how they acquire metastatic traits is not well understood. Here, we show that all colorectal cancer stem cells (CR-CSCs) express CD44v6, which is required for their migration and generation of metastatic tumors. CD44v6 expression is low in primary tumors but demarcated clonogenic CR-CSC populations. Cytokines hepatocyte growth factor (HGF), osteopontin (OPN), and stromal-derived factor 1α (SDF-1), secreted from tumor associated cells, increase CD44v6 expression in CR-CSCs by activating the Wnt/β-catenin pathway, which promotes migration and metastasis. CD44v6(-) progenitor cells do not give rise to metastatic lesions but, when treated with cytokines, acquire CD44v6 expression and metastatic capacity. Importantly, phosphatidylinositol 3-kinase (PI3K) inhibition selectively killed CD44v6 CR-CSCs and reduced metastatic growth. In patient cohorts, low levels of CD44v6 predict increased probability of survival. Thus, the metastatic process in colorectal cancer is initiated by CSCs through the expression of CD44v6, which is both a functional biomarker and therapeutic target.","title":"CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis."},{"docid":"20127522","text":"PURPOSE Five or more circulating tumor cells (CTCs) per 7.5 mL of blood predicts for poorer progression-free survival (PFS) in patients with metastatic breast cancer (MBC). We conducted a prospective study to demonstrate that CTC results correlate strongly with radiographic disease progression at the time of and in advance of imaging. PATIENTS AND METHODS Serial CTC levels were obtained in patients starting a new treatment regimen for progressive, radiographically measurable MBC. Peripheral blood was collected for CTC enumeration at baseline and at 3- to 4-week intervals. Clinical outcomes were based on radiographic studies performed in 9- to 12-week intervals. RESULTS Sixty-eight patients were evaluable for the CTC-imaging correlations, and 74 patients were evaluable for the PFS analysis. Median follow-up was 13.3 months. A statistically significant correlation was demonstrated between CTC levels and radiographic disease progression in patients receiving chemotherapy or endocrine therapy. This correlation applied to CTC results obtained at the time of imaging (odds ratio [OR], 6.3), 3 to 5 weeks before imaging (OR, 3.1), and 7 to 9 weeks before imaging (OR, 4.9). Results from analyses stratified by type of therapy remained statistically significant. Shorter PFS was observed for patients with five or more CTCs at 3 to 5 weeks and at 7 to 9 weeks after the start of treatment. CONCLUSION We provide, to our knowledge, the first evidence of a strong correlation between CTC results and radiographic disease progression in patients receiving chemotherapy or endocrine therapy for MBC. These findings support the role of CTC enumeration as an adjunct to standard methods of monitoring disease status in MBC.","title":"Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer."},{"docid":"6334188","text":"BACKGROUND Chemotherapy-induced febrile neutropenia (FN) is a clinically important complication that affects patient outcome by delaying chemotherapy doses or reducing dose intensity. Risk of FN depends on chemotherapy- and patient-level factors. We sought to determine the effects of chronic comorbidities on risk of FN. DESIGN We conducted a cohort study to examine the association between a variety of chronic comorbidities and risk of FN in patients diagnosed with six types of cancer (non-Hodgkin lymphoma and breast, colorectal, lung, ovary, and gastric cancer) from 2000 to 2009 who were treated with chemotherapy at Kaiser Permanente Southern California, a large managed care organization. We excluded those patients who received primary prophylactic granulocyte colony-stimulating factor. History of comorbidities and FN events were identified using electronic medical records. Cox models adjusting for propensity score, stratified by cancer type, were used to determine the association between comorbid conditions and FN. Models that additionally adjusted for cancer stage, baseline neutrophil count, chemotherapy regimen, and dose reduction were also evaluated. RESULTS A total of 19 160 patients with mean age of 60 years were included; 963 (5.0%) developed FN in the first chemotherapy cycle. Chronic obstructive pulmonary disease [hazard ratio (HR) = 1.30 (1.07-1.57)], congestive heart failure [HR = 1.43 (1.00-1.98)], HIV infection [HR = 3.40 (1.90-5.63)], autoimmune disease [HR = 2.01 (1.10-3.33)], peptic ulcer disease [HR = 1.57 (1.05-2.26)], renal disease [HR = 1.60 (1.21-2.09)], and thyroid disorder [HR = 1.32 (1.06-1.64)] were all associated with a significantly increased FN risk. CONCLUSIONS These results provide evidence that history of several chronic comorbidities increases risk of FN, which should be considered when managing patients during chemotherapy.","title":"History of chronic comorbidity and risk of chemotherapy-induced febrile neutropenia in cancer patients not receiving G-CSF prophylaxis."},{"docid":"22635278","text":"From April 1986 to September 2000, 122 MRCC patients were treated by monthly intralymphatic injections (containing a mean of 573 IL-2 U and 26 x 10(6) LAK cells) and i.m. administration of IFN and TF; 71 patients also received a 3-day cycle of monthly IL-2 inhalations with a mean of 998 daily U. MRCC cases not treated by immunotherapy (n = 89) represent our historical controls. Adverse clinical side effects related to treatment were negligible. CR (n = 11) and PR (n = 13) were noticed in 24/122 patients. Of 24 responding patients, 17 resumed progression, whereas 7 remain in remission 11-69 months later. The overall median survival of treated patients (28 months) was 3.5-fold higher than the median survival of historical controls (7.5 months), and a Kaplan-Meier curve showed 25% survival 11 years after the beginning of immunotherapy. Apparently, the addition of IL-2 by inhalation improved survival. The present immunotherapy protocol appears to be efficacious, safe, devoid of adverse side effects, far less costly than others and able to offer a good quality of life to MRCC patients; if confirmed in a multicenter trial, it could set the basis for developing low-dose immunomodulatory treatments.","title":"Immunotherapy of metastatic kidney cancer."},{"docid":"5912283","text":"CONTEXT Insomnia is a common condition in older adults and is associated with a number of adverse medical, social, and psychological consequences. Previous research has suggested beneficial outcomes of both psychological and pharmacological treatments, but blinded placebo-controlled trials comparing the effects of these treatments are lacking. OBJECTIVE To examine short- and long-term clinical efficacy of cognitive behavioral therapy (CBT) and pharmacological treatment in older adults experiencing chronic primary insomnia. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blinded, placebo-controlled trial of 46 adults (mean age, 60.8 y; 22 women) with chronic primary insomnia conducted between January 2004 and December 2005 in a single Norwegian university-based outpatient clinic for adults and elderly patients. INTERVENTION CBT (sleep hygiene, sleep restriction, stimulus control, cognitive therapy, and relaxation; n = 18), sleep medication (7.5-mg zopiclone each night; n = 16), or placebo medication (n = 12). All treatment duration was 6 weeks, and the 2 active treatments were followed up at 6 months. MAIN OUTCOME MEASURES Ambulant clinical polysomnographic data and sleep diaries were used to determine total wake time, total sleep time, sleep efficiency, and slow-wave sleep (only assessed using polysomnography) on all 3 assessment points. RESULTS CBT resulted in improved short- and long-term outcomes compared with zopiclone on 3 out of 4 outcome measures. For most outcomes, zopiclone did not differ from placebo. Participants receiving CBT improved their sleep efficiency from 81.4% at pretreatment to 90.1% at 6-month follow-up compared with a decrease from 82.3% to 81.9% in the zopiclone group. Participants in the CBT group spent much more time in slow-wave sleep (stages 3 and 4) compared with those in other groups, and spent less time awake during the night. Total sleep time was similar in all 3 groups; at 6 months, patients receiving CBT had better sleep efficiency using polysomnography than those taking zopiclone. CONCLUSION These results suggest that interventions based on CBT are superior to zopiclone treatment both in short- and long-term management of insomnia in older adults. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00295386.","title":"Cognitive behavioral therapy vs zopiclone for treatment of chronic primary insomnia in older adults: a randomized controlled trial."},{"docid":"24341590","text":"CONTEXT The growth inhibitory effect of tamoxifen, which is used for the treatment of hormone receptor-positive breast cancer, is mediated by its metabolites, 4-hydroxytamoxifen and endoxifen. The formation of active metabolites is catalyzed by the polymorphic cytochrome P450 2D6 (CYP2D6) enzyme. OBJECTIVE To determine whether CYP2D6 variation is associated with clinical outcomes in women receiving adjuvant tamoxifen. DESIGN, SETTING, AND PATIENTS Retrospective analysis of German and US cohorts of patients treated with adjuvant tamoxifen for early stage breast cancer. The 1325 patients had diagnoses between 1986 and 2005 of stage I through III breast cancer and were mainly postmenopausal (95.4%). Last follow-up was in December 2008; inclusion criteria were hormone receptor positivity, no metastatic disease at diagnosis, adjuvant tamoxifen therapy, and no chemotherapy. DNA from tumor tissue or blood was genotyped for CYP2D6 variants associated with reduced (*10, *41) or absent (*3, *4, *5) enzyme activity. Women were classified as having an extensive (n=609), heterozygous extensive/intermediate (n=637), or poor (n=79) CYP2D6 metabolism. MAIN OUTCOME MEASURES Time to recurrence, event-free survival, disease-free survival, and overall survival. RESULTS Median follow-up was 6.3 years. At 9 years of follow-up, the recurrence rates were 14.9% for extensive metabolizers, 20.9% for heterozygous extensive/intermediate metabolizers, and 29.0% for poor metabolizers, and all-cause mortality rates were 16.7%, 18.0%, and 22.8%, respectively. Compared with extensive metabolizers, there was a significantly increased risk of recurrence for heterozygous extensive/intermediate metabolizers (time to recurrence adjusted hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.04-1.90) and for poor metabolizers (time to recurrence HR, 1.90; 95% CI, 1.10-3.28). Compared with extensive metabolizers, those with decreased CYP2D6 activity (heterozygous extensive/intermediate and poor metabolism) had worse event-free survival (HR, 1.33; 95% CI, 1.06-1.68) and disease-free survival (HR, 1.29; 95% CI, 1.03-1.61), but there was no significant difference in overall survival (HR, 1.15; 95% CI, 0.88-1.51). CONCLUSION Among women with breast cancer treated with tamoxifen, there was an association between CYP2D6 variation and clinical outcomes, such that the presence of 2 functional CYP2D6 alleles was associated with better clinical outcomes and the presence of nonfunctional or reduced-function alleles with worse outcomes.","title":"Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen."},{"docid":"42731834","text":"Functional studies on colorectal cancer cells indicated a protective role of the interferon-inducible dsDNA sensor Absent in Melanoma 2 (AIM2) in cancer progression. Given that a high mutation rate and lack of AIM2 expression was previously detected in a subset of colorectal cancers, we here investigated the association of AIM2 expression in tumor cells and patient prognosis (5-year follow-up). A tissue microarray analysis of 476 matched tissue pairs (colorectal tumor and adjacent normal colon epithelium) was performed by two independent observers. Samples from 62 patients were excluded because of missing follow-up information or due to neo-adjuvant therapy before tissue sampling. Out of the remaining 414 tissue pairs, 279 (67.4%) displayed reduced AIM2 expression in cancer cells when compared to epithelial cells of their normal counterpart. Thirty-eight patients (9.18%) had completely lost AIM2 expression in tumor cells. After adjustment for sex, age, cancer stage, tumor site, tumor grade and chemotherapy, complete lack of AIM2 expression was associated with an up to 3-fold increase in overall mortality (HR=2.40; 95% CI=1.44-3.99) and disease specific mortality (HR=3.14; 95% CI=1.75-5.65) in comparison to AIM2-positive tumor samples. Our results demonstrate that lack of AIM2 expression is closely associated with poor outcome in colorectal cancer. The data thus strongly substantiate a protective role of AIM2 against progression of colorectal tumors. Further studies are required to assess whether lack of AIM2 expression may be used as a biomarker for the identification of colorectal cancer patients with poor prognosis.","title":"Lack of Absent in Melanoma 2 (AIM2) expression in tumor cells is closely associated with poor survival in colorectal cancer patients."},{"docid":"25690516","text":"The aim of the study was to evaluate whether treatment with recombinant human growth hormone (rhGH) affects the quality of life of young adults who were diagnosed as idiopathic short stature (ISS) during childhood, and whether their quality of life and aspects of the personality are different from normal. Experiences and expectations concerning rhGH treatment of the subjects and their parents were also investigated. Eighty-nine subjects were included into the study: 24 subjects (16M, 8F) were treated with rhGH from childhood, whereas 65 subjects (40M, 25F) were never treated. At the time of the interview all subjects had attained final height [mean (SD) -2.3 (0.9) SDS for Dutch references], and the age of the treated subjects was 20.5 (1.0) y, and 25.7 (3.5) y of the control subjects (p < 0.001). The level of education was similar, but the treated subjects had less often a partner compared to the control subjects (adjusted for age and gender, p < 0.001). The Nottingham Health Profile and Short Form 36 Health Survey showed no difference in general health state between treated and control subjects, and the healthy Dutch age-specific references (norm group). Although 74% of the subjects reported one or more negative events related to their height, and 61% would like to be taller, only 22% and 11% were willing to trade-off at Time Trade-Off and Standard Gamble, respectively. The personality of the subjects, which was measured by the Minnesota Multiphasic Personality Inventory, was not different from the norm group. The satisfaction with the rhGH treatment was high, as it had caused 12 (8) cm and 13 (7) cm gain in final height according to the subjects and parents, respectively. Based on initial predicted adult height (Bayley & Pinneau), this gain was only 3.3 (5.6) cm. We concluded that although the treated subjects had a partner less often when compared to the control subjects, the quality of life of subjects with ISS at adult age is normal and appears not to be affected by rhGH therapy, The treated subjects were very satisfied with the treatment, probably by overestimation of the final height gain.","title":"Quality of life of young adults with idiopathic short stature: effect of growth hormone treatment. Dutch Growth Hormone Working Group."},{"docid":"15041758","text":"OBJECTIVE To evaluate the effectiveness of integrated care for chronic physical diseases and depression in reducing disability and improving quality of life. DESIGN A randomised controlled trial of multi-condition collaborative care for depression and poorly controlled diabetes and/or risk factors for coronary heart disease compared with usual care among middle aged and elderly people SETTING Fourteen primary care clinics in Seattle, Washington. PARTICIPANTS Patients with diabetes or coronary heart disease, or both, and blood pressure above 140/90 mm Hg, low density lipoprotein concentration >3.37 mmol/L, or glycated haemoglobin 8.5% or higher, and PHQ-9 depression scores of ≥ 10. INTERVENTION A 12 month intervention to improve depression, glycaemic control, blood pressure, and lipid control by integrating a \"treat to target\" programme for diabetes and risk factors for coronary heart disease with collaborative care for depression. The intervention combined self management support, monitoring of disease control, and pharmacotherapy to control depression, hyperglycaemia, hypertension, and hyperlipidaemia. MAIN OUTCOME MEASURES Social role disability (Sheehan disability scale), global quality of life rating, and World Health Organization disability assessment schedule (WHODAS-2) scales to measure disabilities in activities of daily living (mobility, self care, household maintenance). RESULTS Of 214 patients enrolled (106 intervention and 108 usual care), disability and quality of life measures were obtained for 97 intervention patients at six months (92%) and 92 at 12 months (87%), and for 96 usual care patients at six months (89%) and 92 at 12 months (85%). Improvements from baseline on the Sheehan disability scale (-0.9, 95% confidence interval -1.5 to -0.2; P = 0.006) and global quality of life rating (0.7, 0.2 to 1.2; P = 0.005) were significantly greater at six and 12 months in patients in the intervention group. There was a trend toward greater improvement in disabilities in activities of daily living (-1.5, -3.3 to 0.4; P = 0.10). CONCLUSIONS Integrated care that covers chronic physical disease and comorbid depression can reduce social role disability and enhance global quality of life. Trial registration Clinical Trials NCT00468676.","title":"Functional outcomes of multi-condition collaborative care and successful ageing: results of randomised trial"},{"docid":"52180874","text":"OBJECTIVE To evaluate the relative efficacy of programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors versus conventional drugs in patients with cancer that were PD-L1 positive and PD-L1 negative. DESIGN Meta-analysis of randomised controlled trials. DATA SOURCES PubMed, Embase, Cochrane database, and conference abstracts presented at the American Society of Clinical Oncology and European Society of Medical Oncology up to March 2018. REVIEW METHODS Studies of PD-1 or PD-L1 inhibitors (avelumab, atezolizumab, durvalumab, nivolumab, and pembrolizumab) that had available hazard ratios for death based on PD-L1 positivity or negativity were included. The threshold for PD-L1 positivity or negativity was that PD-L1 stained cell accounted for 1% of tumour cells, or tumour and immune cells, assayed by immunohistochemistry staining methods. RESULTS 4174 patients with advanced or metastatic cancers from eight randomised controlled trials were included in this study. Compared with conventional agents, PD-1 or PD-L1 inhibitors were associated with significantly prolonged overall survival in both patients that were PD-L1 positive (n=2254, hazard ratio 0.66, 95% confidence interval 0.59 to 0.74) and PD-L1 negative (1920, 0.80, 0.71 to 0.90). However, the efficacies of PD-1 or PD-L1 blockade treatment in patients that were PD-L1 positive and PD-L1 negative were significantly different (P=0.02 for interaction). Additionally, in both patients that were PD-L1 positive and PD-L1 negative, the long term clinical benefits from PD-1 or PD-L1 blockade were observed consistently across interventional agent, cancer histotype, method of randomisation stratification, type of immunohistochemical scoring system, drug target, type of control group, and median follow-up time. CONCLUSIONS PD-1 or PD-L1 blockade therapy is a preferable treatment option over conventional therapy for both patients that are PD-L1 positive and PD-L1 negative. This finding suggests that PD-L1 expression status alone is insufficient in determining which patients should be offered PD-1 or PD-L1 blockade therapy.","title":"Efficacy of PD-1 or PD-L1 inhibitors and PD-L1 expression status in cancer: meta-analysis"},{"docid":"52188256","text":"This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.","title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries."},{"docid":"24575065","text":"CONTEXT The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) altered reimbursements for outpatient chemotherapy drugs and drug administration services. Anecdotal reports suggest that these adjustments may have negatively affected access to chemotherapy for Medicare beneficiaries. OBJECTIVE To compare patient wait times and travel distances for chemotherapy before and after the enactment of the MMA. DESIGN, SETTING, AND PATIENTS Analysis of a nationally representative 5% sample of claims from the Centers for Medicare & Medicaid Services for the period 2003 through 2006. Patients were Medicare beneficiaries with incident breast cancer, colorectal cancer, leukemia, lung cancer, or lymphoma who received chemotherapy in inpatient hospital, institutional outpatient, or physician office settings. MAIN OUTCOME MEASURES Days from incident diagnosis to first chemotherapy visit and distance traveled for treatment, controlling for age, sex, race/ethnicity, cancer type, geographic region, comorbid conditions, and year of diagnosis and treatment. RESULTS There were 5082 incident cases of breast cancer, colorectal cancer, leukemia, lung cancer, or lymphoma in 2003; 5379 cases in 2004; 5116 cases in 2005; and 5288 cases in 2006. Approximately 70% of patients received treatment in physician office settings in each year. Although the distribution of treatment settings in 2004 and 2005 was not significantly different from 2003 (P = .24 and P = .72, respectively), there was a small but significant change from 2003 to 2006 (P = .02). The proportion of patients receiving chemotherapy in inpatient settings decreased from 10.2% in 2003 to 8.8% in 2006 (P = .03), and the proportion in institutional outpatient settings increased from 21.1% to 22.5% (P = .004). The proportion in physician offices remained at 68.7% (P = .29). The median time from diagnosis to initial chemotherapy visit was 28 days in 2003, 27 days in 2004, 29 days in 2005, and 28 days in 2006. In multivariate analyses, average wait times for chemotherapy were 1.96 days longer in 2005 than in 2003 (95% confidence interval [CI], 0.11-3.80 days; P = .04) but not significantly different in 2006 (0.88 days; 95% CI, -0.96 to 2.71 days; P = .35). Median travel distance was 7 miles (11.2 km) in 2003 and 8 miles (12.8 km) in 2004 through 2006. After adjustment, average travel distance remained slightly longer in 2004 (1.47 miles [2.35 km]; 95% CI, 0.87-2.07 miles [1.39-3.31 km]; P < .001), 2005 (1.19 miles [1.90 km]; 95% CI, 0.58-1.80 miles [0.93-2.88 km]; P < .001), and 2006 (1.30 miles [2.08 km]; 95% CI, 0.69-1.90 miles [1.10-3.04 km]; P < .001) compared with 2003. CONCLUSION There have not been major changes in travel distance and patient wait times for chemotherapy in the Medicare population since 2003, the year before MMA-related changes in reimbursement.","title":"Association between the Medicare Modernization Act of 2003 and patient wait times and travel distance for chemotherapy."},{"docid":"5151024","text":"BACKGROUND The diagnosis of hypertension has traditionally been based on blood-pressure measurements in the clinic, but home and ambulatory measurements better correlate with cardiovascular outcome, and ambulatory monitoring is more accurate than both clinic and home monitoring in diagnosing hypertension. We aimed to compare the cost-effectiveness of different diagnostic strategies for hypertension. METHODS We did a Markov model-based probabilistic cost-effectiveness analysis. We used a hypothetical primary-care population aged 40 years or older with a screening blood-pressure measurement greater than 140/90 mm Hg and risk-factor prevalence equivalent to the general population. We compared three diagnostic strategies-further blood pressure measurement in the clinic, at home, and with an ambulatory monitor-in terms of lifetime costs, quality-adjusted life years, and cost-effectiveness. FINDINGS Ambulatory monitoring was the most cost-effective strategy for the diagnosis of hypertension for men and women of all ages. It was cost-saving for all groups (from -£56 [95% CI -105 to -10] in men aged 75 years to -£323 [-389 to -222] in women aged 40 years) and resulted in more quality-adjusted life years for men and women older than 50 years (from 0·006 [0·000 to 0·015] for women aged 60 years to 0·022 [0·012 to 0·035] for men aged 70 years). This finding was robust when assessed with a wide range of deterministic sensitivity analyses around the base case, but was sensitive if home monitoring was judged to have equal test performance to ambulatory monitoring or if treatment was judged effective irrespective of whether an individual was hypertensive. INTERPRETATION Ambulatory monitoring as a diagnostic strategy for hypertension after an initial raised reading in the clinic would reduce misdiagnosis and save costs. Additional costs from ambulatory monitoring are counterbalanced by cost savings from better targeted treatment. Ambulatory monitoring is recommended for most patients before the start of antihypertensive drugs. FUNDING National Institute for Health Research and the National Institute for Health and Clinical Excellence.","title":"Cost-effectiveness of options for the diagnosis of high blood pressure in primary care: a modelling study."},{"docid":"20610557","text":"In recent years, the immune-potentiating effects of some widely used chemotherapeutic agents have been increasingly appreciated. This provides a rationale for combining conventional chemotherapy with immunotherapy strategies to achieve durable therapeutic benefits. Previous studies have implicated the immunomodulatory effects of melphalan, an alkylating agent commonly used to treat multiple myeloma, but the underlying mechanisms remain obscure. In the present study, we investigated the impact of melphalan on endogenous immune cells as well as adoptively transferred tumor-specific CD4(+) T cells in tumor-bearing mice. We showed that melphalan treatment resulted in a rapid burst of inflammatory cytokines and chemokines during the cellular recovery phase after melphalan-induced myelodepletion and leukodepletion. After melphalan treatment, tumor cells exhibited characteristics of immunogenic cell death, including membrane translocation of the endoplasmic reticulum-resident calreticulin and extracellular release of high-mobility group box 1. Additionally, there was enhanced tumor Ag uptake by dendritic cells in the tumor-draining lymph node. Consistent with these immunomodulatory effects, melphalan treatment of tumor-bearing mice led to the activation of the endogenous CD8(+) T cells and, more importantly, effectively drove the clonal expansion and effector differentiation of adoptively transferred tumor-specific CD4(+) T cells. Notably, the combination of melphalan and CD4(+) T cell adoptive cell therapy was more efficacious than either treatment alone in prolonging the survival of mice with advanced B cell lymphomas or colorectal tumors. These findings provide mechanistic insights into melphalan's immunostimulatory effects and demonstrate the therapeutic potential of combining melphalan with adoptive cell therapy utilizing antitumor CD4(+) T cells.","title":"Alkylating agent melphalan augments the efficacy of adoptive immunotherapy using tumor-specific CD4+ T cells."},{"docid":"195680777","text":"BACKGROUND Moderate differences in efficacy between adjuvant chemotherapy regimens for breast cancer are plausible, and could affect treatment choices. We sought any such differences. METHODS We undertook individual-patient-data meta-analyses of the randomised trials comparing: any taxane-plus-anthracycline-based regimen versus the same, or more, non-taxane chemotherapy (n=44,000); one anthracycline-based regimen versus another (n=7000) or versus cyclophosphamide, methotrexate, and fluorouracil (CMF; n=18,000); and polychemotherapy versus no chemotherapy (n=32,000). The scheduled dosages of these three drugs and of the anthracyclines doxorubicin (A) and epirubicin (E) were used to define standard CMF, standard 4AC, and CAF and CEF. Log-rank breast cancer mortality rate ratios (RRs) are reported. FINDINGS In trials adding four separate cycles of a taxane to a fixed anthracycline-based control regimen, extending treatment duration, breast cancer mortality was reduced (RR 0·86, SE 0·04, two-sided significance [2p]=0·0005). In trials with four such extra cycles of a taxane counterbalanced in controls by extra cycles of other cytotoxic drugs, roughly doubling non-taxane dosage, there was no significant difference (RR 0·94, SE 0·06, 2p=0·33). Trials with CMF-treated controls showed that standard 4AC and standard CMF were equivalent (RR 0·98, SE 0·05, 2p=0·67), but that anthracycline-based regimens with substantially higher cumulative dosage than standard 4AC (eg, CAF or CEF) were superior to standard CMF (RR 0·78, SE 0·06, 2p=0·0004). Trials versus no chemotherapy also suggested greater mortality reductions with CAF (RR 0·64, SE 0·09, 2p<0·0001) than with standard 4AC (RR 0·78, SE 0·09, 2p=0·01) or standard CMF (RR 0·76, SE 0·05, 2p<0·0001). In all meta-analyses involving taxane-based or anthracycline-based regimens, proportional risk reductions were little affected by age, nodal status, tumour diameter or differentiation (moderate or poor; few were well differentiated), oestrogen receptor status, or tamoxifen use. Hence, largely independently of age (up to at least 70 years) or the tumour characteristics currently available to us for the patients selected to be in these trials, some taxane-plus-anthracycline-based or higher-cumulative-dosage anthracycline-based regimens (not requiring stem cells) reduced breast cancer mortality by, on average, about one-third. 10-year overall mortality differences paralleled breast cancer mortality differences, despite taxane, anthracycline, and other toxicities. INTERPRETATION 10-year gains from a one-third breast cancer mortality reduction depend on absolute risks without chemotherapy (which, for oestrogen-receptor-positive disease, are the risks remaining with appropriate endocrine therapy). Low absolute risk implies low absolute benefit, but information was lacking about tumour gene expression markers or quantitative immunohistochemistry that might help to predict risk, chemosensitivity, or both. FUNDING Cancer Research UK; British Heart Foundation; UK Medical Research Council.","title":"Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials."},{"docid":"32852283","text":"BACKGROUND Although zoledronic acid (ZOL), a third-generation nitrogen-containing bisphosphonate, has been identified as an attractive therapeutic agent against breast cancer, prostate cancer, multiple myeloma as well as small-cell lung cancer (SCLC), as best as we are aware, the anti-tumor effect of ZOL upon non-small-cell lung cancer (NSCLC) remains to be effectively investigated. This study examined the effects of ZOL upon the line-1 tumor cell, using a murine lung adenocarcinoma cell line similar to the behavior of human lung adenocarcinoma. METHODS We investigated the anti-tumor effects of ZOL (3-100 microM) on line-1 tumor cells in vitro, including cellular proliferation, by means of an MTT assay, cell-cycle analysis by flow cytometry and by assessing the level of apoptosis by annexin V/propidium iodide (PI) and 4'-6-diamidino-2-phenylindole (DAPI) staining. Further, we evaluated the growth and survival of line-1 tumor cells following ZOL treatment (1 microg/kg/week) using an animal model. We also examined the in vivo cell-cycle pattern using lacZ-expressing line-1 cells (line-1/lacZ). RESULTS ZOL significantly slowed the line-1 tumor growth in a dose-dependent manner in vitro. The treated line-1 tumor cells typically arrested at the S/G2/M-phase of the cell-cycle following ZOL exposure, but no apoptotic cells could be detected by either annexin V/PI or DAPI staining. When the ZOL was washed out, the drug-inhibited cells continued to proliferate again and the cell-cycle prolongation elicited earlier by the drug, then disappeared. Within 72-96 h following drug removal, the cell-cycle of the treated cells revealed a similar distribution to that of the untreated controls. In vivo studies demonstrated that ZOL significantly slowed the line-1 tumor growth. Indeed, mice lived significantly longer when they had been ZOL-treated than was the case for untreated mice (p<0.05). Using line-1/lacZ cells, the in vivo cell-cycle distribution of line-1 tumor cells subsequent to ZOL exposure revealed S/G2/M-phase arrest that was identical to the in vitro culture. CONCLUSIONS ZOL maintains the potential to reduce tumor burden and prolong survival for murine pulmonary adenocarcinoma. The flow cytometrical analysis of cell-cycle demonstrated that ZOL induces no apoptosis but is able to arrest line-1 tumor cells at the S/G2/M-phase. Although the clinical relevance of these results warrants verification for human lung cancer patients, ZOL combined with chemotherapy and/or radiotherapy appears to be a new therapeutic strategy for the effective treatment of NSCLC.","title":"Zoledronic acid is unable to induce apoptosis, but slows tumor growth and prolongs survival for non-small-cell lung cancers."},{"docid":"2328272","text":"INTRODUCTION With the growing number of adult cancer survivors, there is increasing need for information that links potential late and long term effects with specific treatment regimens. Few adult cancer patients are treated on clinical trials; however, patients previously enrolled in these trials are an important source of information about treatment-related late effects. METHODS Focusing on colorectal cancer survivors, we used the database from five phase III randomized clinical trials from the National Surgical Adjuvant Breast & Bowel Project (NSABP) to recruit and enroll long term survivors in a study of late health outcomes and quality of life. We describe the challenges to recruitment of patients more than 5 -20 years after treatment. RESULTS Sixty-five NSABP treatment sites were invited to enroll patients in the study. Sixty participated with the potential to recruit 2,408 patients. We received registration forms on only 976 patients (41%) of whom 744 (76%) expressed interest in participating and 708 completed interviews (95% of those expressing interest; 29% of total potential sample). There were multiple barriers to recruitment (difficulty locating patients, lack of institutional commitment, lack of patient interest). CONCLUSIONS Patients treated on clinical trials are an important potential source for examining the late effects of cancer treatments. Retrospective recruitment has substantial limitations. In the future, mechanisms should be established for prospective long-term follow-up to identify and understand the frequency and type of late effects associated with cancer treatments. IMPLICATIONS FOR CANCER SURVIVORS As cancer patients are living longer, it will be important to learn from participants in clinical trials whether or not specific treatment regimens are associated with any serious late effects.","title":"Cancer survivorship research: the challenge of recruiting adult long term cancer survivors from a cooperative clinical trials group"},{"docid":"32421068","text":"Objective To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe. Design Retrospective cohort study. Setting Publicly accessible regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013.Main outcome measures Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after market entry. Validated European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) used to assess the clinical value of the reported gains in published studies of cancer drugs. Results From 2009 to 2013, the EMA approved the use of 48 cancer drugs for 68 indications. Of these, eight indications (12%) were approved on the basis of a single arm study. At the time of market approval, there was significant prolongation of survival in 24 of the 68 (35%). The magnitude of the benefit on overall survival ranged from 1.0 to 5.8 months (median 2.7 months). At the time of market approval, there was an improvement in quality of life in seven of 68 indications (10%). Out of 44 indications for which there was no evidence of a survival gain at the time of market authorisation, in the subsequent postmarketing period there was evidence for extension of life in three (7%) and reported benefit on quality of life in five (11%). Of the 68 cancer indications with EMA approval, and with a median of 5.4 years' follow-up (minimum 3.3 years, maximum 8.1 years), only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (49%) remained uncertain. Of 23 indications associated with a survival benefit that could be scored with the ESMO-MCBS tool, the benefit was judged to be clinically meaningful in less than half (11/23, 48%).Conclusions This systematic evaluation of oncology approvals by the EMA in 2009-13 shows that most drugs entered the market without evidence of benefit on survival or quality of life. At a minimum of 3.3 years after market entry, there was still no conclusive evidence that these drugs either extended or improved life for most cancer indications. When there were survival gains over existing treatment options or placebo, they were often marginal.","title":"Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13"},{"docid":"26067999","text":"The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms. It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment. The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms. Summary of Recommendation and Evidence The USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) See the Clinical Considerations section for suggestions for implementation in practice. See the Figure for a summary of the recommendation and suggestions for clinical practice. Figure. Screening for lung cancer: clinical summary of U.S. Preventive Services Task Force recommendation. Appendix Table 1 describes the USPSTF grades, and Appendix Table 2 describes the USPSTF classification of levels of certainty about net benefit. Appendix Table 1. What the USPSTF Grades Mean and Suggestions for Practice Appendix Table 2. USPSTF Levels of Certainty Regarding Net Benefit Supplement. Consumer Fact Sheet. Rationale Importance Lung cancer is the third most common cancer and the leading cause of cancer-related death in the United States (1). The most important risk factor for lung cancer is smoking, which results in approximately 85% of all U.S. lung cancer cases (2). Although the prevalence of smoking has decreased, approximately 37% of U.S. adults are current or former smokers (2). The incidence of lung cancer increases with age and occurs most commonly in persons aged 55 years or older. Increasing age and cumulative exposure to tobacco smoke are the 2 most common risk factors for lung cancer. Lung cancer has a poor prognosis, and nearly 90% of persons with lung cancer die of the disease. However, early-stage nonsmall cell lung cancer (NSCLC) has a better prognosis and can be treated with surgical resection. Detection Most lung cancer cases are NSCLC, and most screening programs focus on the detection and treatment of early-stage NSCLC. Although chest radiography and sputum cytologic evaluation have been used to screen for lung cancer, LDCT has greater sensitivity for detecting early-stage cancer (3). Benefits of Detection and Early Treatment Although lung cancer screening is not an alternative to smoking cessation, the USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancerrelated deaths. Direct evidence from a large, well-conducted, randomized, controlled trial (RCT) provides moderate certainty of the benefit of lung cancer screening with LDCT in this population (4). The magnitude of benefit to the person depends on that person's risk for lung cancer because those who are at highest risk are most likely to benefit. Screening cannot prevent most lung cancerrelated deaths, and smoking cessation remains essential. Harms of Detection and Early Intervention and Treatment The harms associated with LDCT screening include false-negative and false-positive results, incidental findings, overdiagnosis, and radiation exposure. False-positive LDCT results occur in a substantial proportion of screened persons; 95% of all positive results do not lead to a diagnosis of cancer. In a high-quality screening program, further imaging can resolve most false-positive results; however, some patients may require invasive procedures. The USPSTF found insufficient evidence on the harms associated with incidental findings. Overdiagnosis of lung cancer occurs, but its precise magnitude is uncertain. A modeling study performed for the USPSTF estimated that 10% to 12% of screen-detected cancer cases are overdiagnosedthat is, they would not have been detected in the patient's lifetime without screening. Radiation harms, including cancer resulting from cumulative exposure to radiation, vary depending on the age at the start of screening; the number of scans received; and the person's exposure to other sources of radiation, particularly other medical imaging. USPSTF Assessment The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT is of moderate net benefit in asymptomatic persons who are at high risk for lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. The moderate net benefit of screening depends on limiting screening to persons who are at high risk, the accuracy of image interpretation being similar to that found in the NLST (National Lung Screening Trial), and the resolution of most false-positive results without invasive procedures (4). Clinical Considerations Patient Population Under Consideration The risk for lung cancer increases with age and cumulative exposure to tobacco smoke and decreases with time since quitting smoking. The best evidence for the benefit of screening comes from the NLST, which enrolled adults aged 55 to 74 years who had at least a 30 pack-year smoking history and were current smokers or had quit within the past 15 years. As with all screening trials, the NLST tested a specific intervention over a finite period. Because initial eligibility extended through age 74 years and participants received 3 annual screening computed tomographic scans, the oldest participants in the trial were aged 77 years. The USPSTF used modeling studies to predict the benefits and harms of screening programs that use different screening intervals, age ranges, smoking histories, and times since quitting. A program that annually screens adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years is projected to have a reasonable balance of benefits and harms. The model assumes that persons who achieve 15 years of smoking cessation during the screening program discontinue screening. This model predicts the outcomes of continuing the screening program used in the NLST through age 80 years. Screening may not be appropriate for patients with substantial comorbid conditions, particularly those at the upper end of the screening age range. The NLST excluded persons who were unlikely to complete curative lung cancer surgery and those with medical conditions that posed a substantial risk for death during the 8-year trial. The baseline characteristics of the NLST showed a relatively healthy sample, and fewer than 10% of enrolled participants were older than 70 years (5). Persons with serious comorbid conditions may experience net harm, no net benefit, or at least substantially less net benefit. Similarly, persons who are unwilling to have curative lung surgery are unlikely to benefit from a screening program. Assessment of Risk Age, total exposure to tobacco smoke, and years since quitting smoking are important risk factors for lung cancer and were used to determine eligibility in the NLST. Other risk factors include specific occupational exposures, radon exposure, family history, and history of pulmonary fibrosis or chronic obstructive lung disease. The incidence of lung cancer is relatively low in persons younger than 50 years but increases with age, especially after age 60 years. In current and former smokers, age-specific incidence rates increase with age and cumulative exposure to tobacco smoke. Smoking cessation substantially reduces a person's risk for developing and dying of lung cancer. Among persons enrolled in the NLST, those who were at highest risk because of additional risk factors or a greater cumulative exposure to tobacco smoke experienced most of the benefit (6). A validated multivariate model showed that persons in the highest 60% of risk accounted for 88% of all deaths preventable by screening. Screening Tests Low-dose computed tomography has shown high sensitivity and acceptable specificity for the detection of lung cancer in high-risk persons. Chest radiography and sputum cytologic evaluation have not shown adequate sensitivity or specificity as screening tests. Therefore, LDCT is currently the only recommended screening test for lung cancer. Treatment Surgical resection is the current standard of care for localized NSCLC. This type of cancer is treated with surgical resection when possible and also with radiation and chemotherapy. Annual LDCT screening may not be useful for patients with life-limiting comorbid conditions or poor functional status who may not be candidates for surgery. Other Approaches to Prevention Smoking cessation is the most important intervention to prevent NSCLC. Advising smokers to stop smoking and preventing nonsmokers from being exposed to tobacco smoke are the most effective ways to decrease the morbidity and mortality associated with lung cancer. Current smokers should be informed of their continuing risk for lung cancer and offered cessation treatments. Screening with LDCT should be viewed as an adjunct to tobacco cessation interventions. Useful Resources Clinicians have many resources to help patients stop smoking. The Centers for Disease Control and Prevention has developed a Web site with many such resources, including information on tobacco quit lines, available in several languages (www.cdc.gov/tobacco/campaign/tips). Quit l","title":"Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation Statement"},{"docid":"6407356","text":"Coxibs, including celecoxib, and other nonsteroidal anti-inflammatory drugs (NSAID), including aspirin, are among the most promising cancer chemopreventive agents in development today. This article examines the data on the efficacy of these agents in animal model studies of cancer prevention carried out by the authors. The studies evaluated here are restricted to our rodent models of colon/intestinal, bladder, and nonmelanoma skin cancer, in which celecoxib and other NSAIDs were administered as either cancer preventive or therapeutic agents. These studies may shed light on several questions. Is celecoxib unique compared with other NSAIDs, and if so, what implications would this have for human use? Are standard NSAIDs (which inhibit both COX-1 and COX-2) as effective as celecoxib in animal studies? Is the efficacy of celecoxib in particular or NSAIDs in general due to their off-target effects or to their effects on COX-1 and COX-2? What is the likely efficacy of low-dose aspirin? Some questions raised by human trials and epidemiology are discussed and related to our observations in animal model studies. We also discuss the problem of cardiovascular (CV) events associated with coxibs and certain other NSAIDs and whether results in animal models are predictive of efficacy in humans. On the basis of epidemiologic studies and its CV profile, aspirin seems to be the most promising NSAID for preventing human colorectal, bladder, and skin cancer, although the animal data for aspirin are less clear. A comprehensive understanding of the results of coxibs and other NSAIDs in animal studies may help inform and shape human trials of these commonly employed, relatively inexpensive, and highly effective compounds.","title":"Coxibs and other nonsteroidal anti-inflammatory drugs in animal models of cancer chemoprevention."},{"docid":"38886345","text":"BACKGROUND JX-594 is a targeted oncolytic poxvirus designed to selectively replicate in and destroy cancer cells with cell-cycle abnormalities and epidermal growth factor receptor (EGFR)-ras pathway activation. Direct oncolysis plus granulocyte-macrophage colony-stimulating factor (GM-CSF) expression also stimulates shutdown of tumour vasculature and antitumoral immunity. We aimed to assess intratumoral injection of JX-594 in patients with refractory primary or metastatic liver cancer. METHODS Between Jan 4, 2006, and July 4, 2007, 14 patients with histologically confirmed refractory primary or metastatic liver tumours (up to 10.9 cm total diameter) that were amenable to image-guided intratumoral injections were enrolled into this non-comparative, open-label, phase I dose-escalation trial (standard 3x3 design; two to six patients for each dose with 12-18 estimated total patients). Patients received one of four doses of intratumoral JX-594 (10(8) plaque-forming units [pfu], 3x10(8) pfu, 10(9) pfu, or 3x10(9) pfu) every 3 weeks at Dong-A University Hospital (Busan, South Korea). Patients were monitored after treatment for at least 48 h in hospital and for at least 4 weeks as out-patients. Adverse event-monitoring according to the National Cancer Institute Common Toxicity Criteria (version 3) and standard laboratory toxicity grading for haematology, liver and renal function, coagulation studies, serum chemistry, and urinalysis were done. The primary aims were to ascertain the maximum-tolerated dose (MTD) and safety of JX-594 treatment. Data were also collected on pharmacokinetics, pharmacodynamics, and efficacy. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00629759. FINDINGS Of 22 patients with liver tumours who were assessed for eligibility, eight patients did not meet inclusion criteria. Therefore, 14 patients, including those with hepatocellular, colorectal, melanoma, and lung cancer, were enrolled. Patients were heavily pretreated (5.6 previous treatments, SD 2.8, range 2.0-12.0) and had large tumours (7.0 cm diameter, SD 2.7, range 1.8-10.9). Patients received a mean of 3.4 (SD 2.2, range 1.0-8.0) cycles of JX-594. All patients were evaluable for toxicity. All patients experienced grade I-III flu-like symptoms, and four had transient grade I-III dose-related thrombocytopenia. Grade III hyperbilirubinaemia was dose-limiting in both patients at the highest dose; the MTD was therefore 1x10(9) pfu. JX-594 replication-dependent dissemination in blood was shown, with resultant infection of non-injected tumour sites. GM-CSF expression resulted in grade I-III increases in neutrophil counts in four of six patients at the MTD. Tumour responses were shown in injected and non-injected tumours. Ten patients were radiographically evaluable for objective responses; non-evaluable patients had contraindications to contrast medium (n=2) or no post-treatment scans (n=2). According to Response Evaluation Criteria in Solid Tumors (RECIST), three patients had partial response, six had stable disease, and one had progressive disease. INTERPRETATION Intratumoral injection of JX-594 into primary or metastatic liver tumours was generally well-tolerated. Direct hyperbilirubinaemia was the dose-limiting toxicity. Safety was acceptable in the context of JX-594 replication, GM-CSF expression, systemic dissemination, and JX-594 had anti-tumoral effects against several refractory carcinomas. Phase II trials are now underway.","title":"Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial."},{"docid":"35301079","text":"BACKGROUND In uveal melanoma (UM) with metastatic disease limited to the liver, the effect of an intrahepatic treatment on survival is unknown. We investigated prospectively the efficacy and toxicity of hepatic intra-arterial (HIA) versus systemic (IV) fotemustine in patients with liver metastases from UM. PATIENTS AND METHODS Patients were randomly assigned to receive either IV or HIA fotemustine at 100 mg/m(2) on days 1, 8, 15 (and 22 in HIA arm only) as induction, and after a 5-week rest period every 3 weeks as maintenance. Primary end point was overall survival (OS). Response rate (RR), progression-free survival (PFS) and safety were secondary end points. RESULTS Accrual was stopped after randomization of 171 patients based on the results of a futility OS analysis. A total of 155 patients died and 16 were still alive [median follow-up 1.6 years (range 0.25-6 years)]. HIA did not improve OS (median 14.6 months) when compared with the IV arm (median 13.8 months), hazard ratio (HR) 1.09; 95% confidence interval (CI) 0.79-1.50, log-rank P = 0.59. However, there was a significant benefit on PFS for HIA compared with IV with a median of 4.5 versus 3.5 months, respectively (HR 0.62; 95% CI 0.45-0.84, log-rank P = 0.002). The 1-year PFS rate was 24% in the HIA arm versus 8% in the IV arm. An improved RR was seen in the HIA (10.5%) compared with IV treatment (2.4%). In the IV arm, the most frequent grade ≥3 toxicity was thrombocytopenia (42.1%) and neutropenia (62.6%), compared with 21.2% and 28.7% in the HIA arm. The main grade ≥3 toxicity related to HIA was catheter complications (12%) and liver toxicity (4.5%) apart from two toxic deaths. CONCLUSION HIA treatment with fotemustine did not translate into an improved OS compared with IV treatment, despite better RR and PFS. Intrahepatic treatment should still be considered as experimental. EUDRACT NUMBER AND CLINICALTRIALSGOV IDENTIFIER 2004-002245-12 and NCT00110123.","title":"Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial."}],"string":"[\n {\n \"docid\": \"2492146\",\n \"text\": \"Metastatic colorectal cancer (mCRC) is increasingly treated using targeted therapies. Post-marketing safety of these agents is understudied, especially in the elderly. This study aimed to compare, according to age, the adverse drug reactions (ADRs) of targeted therapies used for mCRC in real life. An extraction of VigiBase, which contains World Health Organization individual case safety reports (ICSRs), was performed. All ADR reports with aflibercept, bevacizumab, cetuximab, panitumumab, or regorafenib used in CRC were considered. For all drugs, chi-square tests were used to compare frequencies of serious ADRs between patients aged ≥75 and <75 years. For selected ADRs and each drug, the drug-ADR association compared to other anticancer drugs was estimated through the proportional reporting ratio (PRR) in both age groups. There were 21,565 ICSRs included, among which 74% were serious and 11% were fatal. Median age was 64 years (Inter Quartile Range = 56–71) and 15% of patients were aged ≥75; 57% were male. Serious ICSRs accounted for 47,292 ADRs. Neutropenia was not more reported in elderly for all drugs while diarrhea was more reported in elderly for panitumumab. Cardiac disorders were more reported in elderly patients, in particular heart failure, especially for bevacizumab, cetuximab, and regorafenib, as were respiratory, thoracic, and mediastinal disorders. Most of PRR were not different between the two groups, except encephalopathies, which were significantly associated with bevacizumab in the elderly only. ADRs related to targeted therapies used for mCRC treatment were different across age groups; yet, not systematically more reported or worse in elderly patients. Selected elderly patients could, therefore, be treated with these targeted therapies.\",\n \"title\": \"Comparative Safety of Targeted Therapies for Metastatic Colorectal Cancer between Elderly and Younger Patients: a Study Using the International Pharmacovigilance Database\"\n },\n {\n \"docid\": \"13256155\",\n \"text\": \"BACKGROUND Molecularly targeted agents have been reported to have anti-tumour activity for patients whose tumours harbour the matching molecular alteration. These results have led to increased off-label use of molecularly targeted agents on the basis of identified molecular alterations. We assessed the efficacy of several molecularly targeted agents marketed in France, which were chosen on the basis of tumour molecular profiling but used outside their indications, in patients with advanced cancer for whom standard-of-care therapy had failed. METHODS The open-label, randomised, controlled phase 2 SHIVA trial was done at eight French academic centres. We included adult patients with any kind of metastatic solid tumour refractory to standard of care, provided they had an Eastern Cooperative Oncology Group performance status of 0 or 1, disease that was accessible for a biopsy or resection of a metastatic site, and at least one measurable lesion. The molecular profile of each patient's tumour was established with a mandatory biopsy of a metastatic tumour and large-scale genomic testing. We only included patients for whom a molecular alteration was identified within one of three molecular pathways (hormone receptor, PI3K/AKT/mTOR, RAF/MEK), which could be matched to one of ten regimens including 11 available molecularly targeted agents (erlotinib, lapatinib plus trastuzumab, sorafenib, imatinib, dasatinib, vemurafenib, everolimus, abiraterone, letrozole, tamoxifen). We randomly assigned these patients (1:1) to receive a matched molecularly targeted agent (experimental group) or treatment at physician's choice (control group) by central block randomisation (blocks of size six). Randomisation was done centrally with a web-based response system and was stratified according to the Royal Marsden Hospital prognostic score (0 or 1 vs 2 or 3) and the altered molecular pathway. Clinicians and patients were not masked to treatment allocation. Treatments in both groups were given in accordance with the approved product information and standard practice protocols at each institution and were continued until evidence of disease progression. The primary endpoint was progression-free survival in the intention-to-treat population, which was not assessed by independent central review. We assessed safety in any patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT01771458. FINDINGS Between Oct 4, 2012, and July 11, 2014, we screened 741 patients with any tumour type. 293 (40%) patients had at least one molecular alteration matching one of the 10 available regimens. At the time of data cutoff, Jan 20, 2015, 195 (26%) patients had been randomly assigned, with 99 in the experimental group and 96 in the control group. All patients in the experimental group started treatment, as did 92 in the control group. Two patients in the control group received a molecularly targeted agent: both were included in their assigned group for efficacy analyses, the patient who received an agent that was allowed in the experimental group was included in the experimental group for the purposes of safety analyses, while the other patient, who received a molecularly targeted agent and chemotherapy, was kept in the control group for safety analyses. Median follow-up was 11·3 months (IQR 5·8-11·6) in the experimental group and 11·3 months (8·1-11·6) in the control group at the time of the primary analysis of progression-free survival. Median progression-free survival was 2·3 months (95% CI 1·7-3·8) in the experimental group versus 2·0 months (1·8-2·1) in the control group (hazard ratio 0·88, 95% CI 0·65-1·19, p=0·41). In the safety population, 43 (43%) of 100 patients treated with a molecularly targeted agent and 32 (35%) of 91 patients treated with cytotoxic chemotherapy had grade 3-4 adverse events (p=0·30). INTERPRETATION The use of molecularly targeted agents outside their indications does not improve progression-free survival compared with treatment at physician's choice in heavily pretreated patients with cancer. Off-label use of molecularly targeted agents should be discouraged, but enrolment in clinical trials should be encouraged to assess predictive biomarkers of efficacy.\",\n \"title\": \"Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial.\"\n },\n {\n \"docid\": \"20606520\",\n \"text\": \"OBJECTIVES To assess mortality, quality of life (QOL), and quality-adjusted life-years (QALYs) for critically ill elderly patients. DESIGN Cross-sectional survey. SETTING A ten-bed medical-surgical intensive care unit (ICU) in a tertiary care university hospital. PATIENTS The study group included 882 elderly patients (> or =65 yrs of age) and 1,827 controls (<65 yrs of age) treated during the period of 1995 to 2000. INTERVENTION None. MEASUREMENTS AND MAIN RESULTS Mortality was assessed during the ICU and hospital stays, and 12, 24, and 36 months after ICU discharge. The cumulative 3-yr mortality rate among the elderly (57%) was higher (p < .05) than that among the controls (40%). The majority (66%) of the elderly nonsurvivors died within 1 month after intensive care discharge. All elderly patients with day-1 Sequential Organ Failure (SOFA) scores >15 died during the ICU stay. QOL was assessed with EQ-5D and RAND-36 measures from 10 months to 7 yrs after discharge. The majority (88%) of the elderly survivors assessed their present health state as good or satisfactory; 66% found it to be similar or better than 12 months earlier, and 48% similar or better than their preadmission state. QOL measures by RAND-36 revealed that aging decreased their competencies most in physical functioning, physical role limitations, and vitality, but the elderly had better values in mental health than the controls. However, QALYs of the elderly respondents were 21% to 35% lower than the mean QALY minus 2 sd units of the age- and gender-adjusted general population. CONCLUSIONS High age alone is not a valid reason to refuse intensive care, but the benefits perceived by intensive care seem to decrease with aging, if reflected as QALYs. However, 97% of the elderly survivors lived at home and 88% of them considered their QOL satisfactory or good after hospital discharge. Therefore, more reliable information on the outcome for the elderly is clearly needed.\",\n \"title\": \"Long-term survival, quality of life, and quality-adjusted life-years among critically ill elderly patients.\"\n },\n {\n \"docid\": \"7165938\",\n \"text\": \"PURPOSE The circadian clock gene Bmal1 is involved in cancer cell proliferation and DNA damage sensitivity. The aim of this study was to explore the effect of Bmal1 on oxaliplatin sensitivity and to determine its clinical significance in colorectal cancer. EXPERIMENTAL DESIGN Three colorectal cancer cell lines, HCT116, THC8307 and HT29, were used. The Bmal1-mediated control of colorectal cancer cell proliferation was tested in vitro and in vivo. MTT and colony formation assays were performed to determine the sensitivity of colorectal cancer cells to oxaliplatin. Flow cytometry was used to examine changes in the cell-cycle distribution and apoptosis rate. Proteins expressed downstream of Bmal1 upon its overexpression were determined by Western blotting. Immunohistochemistry was used to analyze Bmal1 expression in 82 archived colorectal cancer tumors from patients treated with oxaliplatin-based regimens. RESULTS Bmal1 overexpression inhibited colorectal cancer cell proliferation and increased colorectal cancer sensitivity to oxaliplatin in three colorectal cancer cell lines and HCT116 cells model in vivo. Furthermore, the overall survival of patients with colorectal cancer with high Bmal1 levels in their primary tumors was significantly longer than that of patients with low Bmal1 levels (27 vs. 19 months; P = 0.043). The progression-free survival of patients with high Bmal1 expression was also significantly longer than that of patients with low Bmal1 expression (11 vs. 5 months; P = 0.015). Mechanistically, the effect of Bmal1 was associated with its ability to regulate G2-M arrest by activating the ATM pathway. CONCLUSION Bmal1 shows the potential as a novel prognostic biomarker and may represent a new therapeutic target in colorectal cancer.\",\n \"title\": \"Overexpression of the circadian clock gene Bmal1 increases sensitivity to oxaliplatin in colorectal cancer.\"\n },\n {\n \"docid\": \"9929089\",\n \"text\": \"BACKGROUND Patients with advanced or metastatic non-small cell lung cancer (NSCLC) can develop acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib. Here, we report the successful treatment with alternating chemotherapy and TKIs of two cases of advanced NSCLC who developed resistance to TKI. CASE PRESENTATION Two patients with advanced or metastatic NSCLC were treated with palliative chemotherapy followed by erlotinib/gefitinib. When TKI therapy failed, two cycles of chemotherapy were provided, which were followed by re-challenge with erlotinib or gefitinib. CONCLUSION NSCLC patients with acquired TKI resistance should be managed aggressively whenever possible. Subsequent chemotherapy and target treatment is one of the reasonable choices for those with an initial dramatic clinical response with erlotinib/gefitinib treatment. Further studies are warranted to substantiate the association of erlotinib /gefitinib treatment with the efficacy of NSCLC patients with acquired TKI failure.\",\n \"title\": \"Subsequent chemotherapy reverses acquired tyrosine kinase inhibitor resistance and restores response to tyrosine kinase inhibitor in advanced non-small-cell lung cancer\"\n },\n {\n \"docid\": \"24974080\",\n \"text\": \"New blood vessel formation (angiogenesis) is a fundamental event in the process of tumor growth and metastatic dissemination. Hence, the molecular basis of tumor angiogenesis has been of keen interest in the field of cancer research. The vascular endothelial growth factor (VEGF) pathway is well established as one of the key regulators of this process. The VEGF/VEGF-receptor axis is composed of multiple ligands and receptors with overlapping and distinct ligand-receptor binding specificities, cell-type expression, and function. Activation of the VEGF-receptor pathway triggers a network of signaling processes that promote endothelial cell growth, migration, and survival from pre-existing vasculature. In addition, VEGF mediates vessel permeability, and has been associated with malignant effusions. More recently, an important role for VEGF has emerged in mobilization of endothelial progenitor cells from the bone marrow to distant sites of neovascularization. The well-established role of VEGF in promoting tumor angiogenesis and the pathogenesis of human cancers has led to the rational design and development of agents that selectively target this pathway. Studies with various anti-VEGF/VEGF-receptor therapies have shown that these agents can potently inhibit angiogenesis and tumor growth in preclinical models. Recently, an anti-VEGF antibody (bevacizumab), when used in combination with chemotherapy, was shown to significantly improve survival and response rates in patients with metastatic colorectal cancer and thus, validate VEGF pathway inhibitors as an important new treatment modality in cancer therapy.\",\n \"title\": \"Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis.\"\n },\n {\n \"docid\": \"24873253\",\n \"text\": \"Patients with metastatic bone disease are at risk for developing skeletal-related events that can negatively influence quality of life, contributing to loss of autonomy and functional capabilities. Bisphosphonates have become an important component in the treatment of patients with bone metastases as they delay the onset and reduce the risk of skeletal-related events and also palliate or control bone pain in multiple cancer types, thus preserving quality of life. Zoledronic acid has proven efficacy and safety in patients with bone lesions from breast cancer, prostate cancer, lung cancer, and other solid tumors, as well as in patients with multiple myeloma. Current data suggest that early treatment with zoledronic acid (before the onset of bone pain) may provide additional clinical benefits and also positive effects on survival in subsets of patients who have elevated levels of N-telopeptide of type I collagen (NTX), a biochemical marker of bone resorption. Studies have shown that in patients with breast cancer, prostate cancer, lung cancer, or other solid tumors, normalization of elevated levels of NTX was observed in the majority of patients who received zoledronic acid. Furthermore, normalization of NTX values correlated with extended survival.\",\n \"title\": \"Clinical benefits and considerations of bisphosphonate treatment in metastatic bone disease.\"\n },\n {\n \"docid\": \"25589047\",\n \"text\": \"CONTEXT Fatal adverse events (FAEs) have been reported in cancer patients treated with the widely used angiogenesis inhibitor bevacizumab in combination with chemotherapy. Currently, the role of bevacizumab in treatment-related mortality is not clear. OBJECTIVE To perform a systematic review and meta-analysis of published randomized controlled trials (RCTs) to determine the overall risk of FAEs associated with bevacizumab. DATA SOURCES PubMed, EMBASE, and Web of Science databases as well as abstracts presented at American Society of Clinical Oncology conferences from January 1966 to October 2010 were searched to identify relevant studies. STUDY SELECTION AND DATA EXTRACTION Eligible studies included prospective RCTs in which bevacizumab in combination with chemotherapy or biological therapy was compared with chemotherapy or biological therapy alone. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. DATA SYNTHESIS A total of 10,217 patients with a variety of advanced solid tumors from 16 RCTs were included in the analysis. The overall incidence of FAEs with bevacizumab was 2.5% (95% CI, 1.7%-3.9%). Compared with chemotherapy alone, the addition of bevacizumab was associated with an increased risk of FAEs, with an RR of 1.46 (95% CI, 1.09-1.94; P = .01; incidence, 2.5% vs 1.7%). This association varied significantly with chemotherapeutic agents (P = .045) but not with tumor types (P = .13) or bevacizumab doses (P = .16). Bevacizumab was associated with an increased risk of FAEs in patients receiving taxanes or platinum agents (RR, 3.49; 95% CI, 1.82-6.66; incidence, 3.3% vs 1.0%) but was not associated with increased risk of FAEs when used in conjunction with other agents (RR, 0.85; 95% CI, 0.25-2.88; incidence, 0.8% vs 0.9%). The most common causes of FAEs were hemorrhage (23.5%), neutropenia (12.2%), and gastrointestinal tract perforation (7.1%). CONCLUSION In a meta-analysis of RCTs, bevacizumab in combination with chemotherapy or biological therapy, compared with chemotherapy alone, was associated with increased treatment-related mortality.\",\n \"title\": \"Treatment-related mortality with bevacizumab in cancer patients: a meta-analysis.\"\n },\n {\n \"docid\": \"9558539\",\n \"text\": \"Cancer stem cells drive tumor formation and metastasis, but how they acquire metastatic traits is not well understood. Here, we show that all colorectal cancer stem cells (CR-CSCs) express CD44v6, which is required for their migration and generation of metastatic tumors. CD44v6 expression is low in primary tumors but demarcated clonogenic CR-CSC populations. Cytokines hepatocyte growth factor (HGF), osteopontin (OPN), and stromal-derived factor 1α (SDF-1), secreted from tumor associated cells, increase CD44v6 expression in CR-CSCs by activating the Wnt/β-catenin pathway, which promotes migration and metastasis. CD44v6(-) progenitor cells do not give rise to metastatic lesions but, when treated with cytokines, acquire CD44v6 expression and metastatic capacity. Importantly, phosphatidylinositol 3-kinase (PI3K) inhibition selectively killed CD44v6 CR-CSCs and reduced metastatic growth. In patient cohorts, low levels of CD44v6 predict increased probability of survival. Thus, the metastatic process in colorectal cancer is initiated by CSCs through the expression of CD44v6, which is both a functional biomarker and therapeutic target.\",\n \"title\": \"CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis.\"\n },\n {\n \"docid\": \"20127522\",\n \"text\": \"PURPOSE Five or more circulating tumor cells (CTCs) per 7.5 mL of blood predicts for poorer progression-free survival (PFS) in patients with metastatic breast cancer (MBC). We conducted a prospective study to demonstrate that CTC results correlate strongly with radiographic disease progression at the time of and in advance of imaging. PATIENTS AND METHODS Serial CTC levels were obtained in patients starting a new treatment regimen for progressive, radiographically measurable MBC. Peripheral blood was collected for CTC enumeration at baseline and at 3- to 4-week intervals. Clinical outcomes were based on radiographic studies performed in 9- to 12-week intervals. RESULTS Sixty-eight patients were evaluable for the CTC-imaging correlations, and 74 patients were evaluable for the PFS analysis. Median follow-up was 13.3 months. A statistically significant correlation was demonstrated between CTC levels and radiographic disease progression in patients receiving chemotherapy or endocrine therapy. This correlation applied to CTC results obtained at the time of imaging (odds ratio [OR], 6.3), 3 to 5 weeks before imaging (OR, 3.1), and 7 to 9 weeks before imaging (OR, 4.9). Results from analyses stratified by type of therapy remained statistically significant. Shorter PFS was observed for patients with five or more CTCs at 3 to 5 weeks and at 7 to 9 weeks after the start of treatment. CONCLUSION We provide, to our knowledge, the first evidence of a strong correlation between CTC results and radiographic disease progression in patients receiving chemotherapy or endocrine therapy for MBC. These findings support the role of CTC enumeration as an adjunct to standard methods of monitoring disease status in MBC.\",\n \"title\": \"Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer.\"\n },\n {\n \"docid\": \"6334188\",\n \"text\": \"BACKGROUND Chemotherapy-induced febrile neutropenia (FN) is a clinically important complication that affects patient outcome by delaying chemotherapy doses or reducing dose intensity. Risk of FN depends on chemotherapy- and patient-level factors. We sought to determine the effects of chronic comorbidities on risk of FN. DESIGN We conducted a cohort study to examine the association between a variety of chronic comorbidities and risk of FN in patients diagnosed with six types of cancer (non-Hodgkin lymphoma and breast, colorectal, lung, ovary, and gastric cancer) from 2000 to 2009 who were treated with chemotherapy at Kaiser Permanente Southern California, a large managed care organization. We excluded those patients who received primary prophylactic granulocyte colony-stimulating factor. History of comorbidities and FN events were identified using electronic medical records. Cox models adjusting for propensity score, stratified by cancer type, were used to determine the association between comorbid conditions and FN. Models that additionally adjusted for cancer stage, baseline neutrophil count, chemotherapy regimen, and dose reduction were also evaluated. RESULTS A total of 19 160 patients with mean age of 60 years were included; 963 (5.0%) developed FN in the first chemotherapy cycle. Chronic obstructive pulmonary disease [hazard ratio (HR) = 1.30 (1.07-1.57)], congestive heart failure [HR = 1.43 (1.00-1.98)], HIV infection [HR = 3.40 (1.90-5.63)], autoimmune disease [HR = 2.01 (1.10-3.33)], peptic ulcer disease [HR = 1.57 (1.05-2.26)], renal disease [HR = 1.60 (1.21-2.09)], and thyroid disorder [HR = 1.32 (1.06-1.64)] were all associated with a significantly increased FN risk. CONCLUSIONS These results provide evidence that history of several chronic comorbidities increases risk of FN, which should be considered when managing patients during chemotherapy.\",\n \"title\": \"History of chronic comorbidity and risk of chemotherapy-induced febrile neutropenia in cancer patients not receiving G-CSF prophylaxis.\"\n },\n {\n \"docid\": \"22635278\",\n \"text\": \"From April 1986 to September 2000, 122 MRCC patients were treated by monthly intralymphatic injections (containing a mean of 573 IL-2 U and 26 x 10(6) LAK cells) and i.m. administration of IFN and TF; 71 patients also received a 3-day cycle of monthly IL-2 inhalations with a mean of 998 daily U. MRCC cases not treated by immunotherapy (n = 89) represent our historical controls. Adverse clinical side effects related to treatment were negligible. CR (n = 11) and PR (n = 13) were noticed in 24/122 patients. Of 24 responding patients, 17 resumed progression, whereas 7 remain in remission 11-69 months later. The overall median survival of treated patients (28 months) was 3.5-fold higher than the median survival of historical controls (7.5 months), and a Kaplan-Meier curve showed 25% survival 11 years after the beginning of immunotherapy. Apparently, the addition of IL-2 by inhalation improved survival. The present immunotherapy protocol appears to be efficacious, safe, devoid of adverse side effects, far less costly than others and able to offer a good quality of life to MRCC patients; if confirmed in a multicenter trial, it could set the basis for developing low-dose immunomodulatory treatments.\",\n \"title\": \"Immunotherapy of metastatic kidney cancer.\"\n },\n {\n \"docid\": \"5912283\",\n \"text\": \"CONTEXT Insomnia is a common condition in older adults and is associated with a number of adverse medical, social, and psychological consequences. Previous research has suggested beneficial outcomes of both psychological and pharmacological treatments, but blinded placebo-controlled trials comparing the effects of these treatments are lacking. OBJECTIVE To examine short- and long-term clinical efficacy of cognitive behavioral therapy (CBT) and pharmacological treatment in older adults experiencing chronic primary insomnia. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blinded, placebo-controlled trial of 46 adults (mean age, 60.8 y; 22 women) with chronic primary insomnia conducted between January 2004 and December 2005 in a single Norwegian university-based outpatient clinic for adults and elderly patients. INTERVENTION CBT (sleep hygiene, sleep restriction, stimulus control, cognitive therapy, and relaxation; n = 18), sleep medication (7.5-mg zopiclone each night; n = 16), or placebo medication (n = 12). All treatment duration was 6 weeks, and the 2 active treatments were followed up at 6 months. MAIN OUTCOME MEASURES Ambulant clinical polysomnographic data and sleep diaries were used to determine total wake time, total sleep time, sleep efficiency, and slow-wave sleep (only assessed using polysomnography) on all 3 assessment points. RESULTS CBT resulted in improved short- and long-term outcomes compared with zopiclone on 3 out of 4 outcome measures. For most outcomes, zopiclone did not differ from placebo. Participants receiving CBT improved their sleep efficiency from 81.4% at pretreatment to 90.1% at 6-month follow-up compared with a decrease from 82.3% to 81.9% in the zopiclone group. Participants in the CBT group spent much more time in slow-wave sleep (stages 3 and 4) compared with those in other groups, and spent less time awake during the night. Total sleep time was similar in all 3 groups; at 6 months, patients receiving CBT had better sleep efficiency using polysomnography than those taking zopiclone. CONCLUSION These results suggest that interventions based on CBT are superior to zopiclone treatment both in short- and long-term management of insomnia in older adults. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00295386.\",\n \"title\": \"Cognitive behavioral therapy vs zopiclone for treatment of chronic primary insomnia in older adults: a randomized controlled trial.\"\n },\n {\n \"docid\": \"24341590\",\n \"text\": \"CONTEXT The growth inhibitory effect of tamoxifen, which is used for the treatment of hormone receptor-positive breast cancer, is mediated by its metabolites, 4-hydroxytamoxifen and endoxifen. The formation of active metabolites is catalyzed by the polymorphic cytochrome P450 2D6 (CYP2D6) enzyme. OBJECTIVE To determine whether CYP2D6 variation is associated with clinical outcomes in women receiving adjuvant tamoxifen. DESIGN, SETTING, AND PATIENTS Retrospective analysis of German and US cohorts of patients treated with adjuvant tamoxifen for early stage breast cancer. The 1325 patients had diagnoses between 1986 and 2005 of stage I through III breast cancer and were mainly postmenopausal (95.4%). Last follow-up was in December 2008; inclusion criteria were hormone receptor positivity, no metastatic disease at diagnosis, adjuvant tamoxifen therapy, and no chemotherapy. DNA from tumor tissue or blood was genotyped for CYP2D6 variants associated with reduced (*10, *41) or absent (*3, *4, *5) enzyme activity. Women were classified as having an extensive (n=609), heterozygous extensive/intermediate (n=637), or poor (n=79) CYP2D6 metabolism. MAIN OUTCOME MEASURES Time to recurrence, event-free survival, disease-free survival, and overall survival. RESULTS Median follow-up was 6.3 years. At 9 years of follow-up, the recurrence rates were 14.9% for extensive metabolizers, 20.9% for heterozygous extensive/intermediate metabolizers, and 29.0% for poor metabolizers, and all-cause mortality rates were 16.7%, 18.0%, and 22.8%, respectively. Compared with extensive metabolizers, there was a significantly increased risk of recurrence for heterozygous extensive/intermediate metabolizers (time to recurrence adjusted hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.04-1.90) and for poor metabolizers (time to recurrence HR, 1.90; 95% CI, 1.10-3.28). Compared with extensive metabolizers, those with decreased CYP2D6 activity (heterozygous extensive/intermediate and poor metabolism) had worse event-free survival (HR, 1.33; 95% CI, 1.06-1.68) and disease-free survival (HR, 1.29; 95% CI, 1.03-1.61), but there was no significant difference in overall survival (HR, 1.15; 95% CI, 0.88-1.51). CONCLUSION Among women with breast cancer treated with tamoxifen, there was an association between CYP2D6 variation and clinical outcomes, such that the presence of 2 functional CYP2D6 alleles was associated with better clinical outcomes and the presence of nonfunctional or reduced-function alleles with worse outcomes.\",\n \"title\": \"Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen.\"\n },\n {\n \"docid\": \"42731834\",\n \"text\": \"Functional studies on colorectal cancer cells indicated a protective role of the interferon-inducible dsDNA sensor Absent in Melanoma 2 (AIM2) in cancer progression. Given that a high mutation rate and lack of AIM2 expression was previously detected in a subset of colorectal cancers, we here investigated the association of AIM2 expression in tumor cells and patient prognosis (5-year follow-up). A tissue microarray analysis of 476 matched tissue pairs (colorectal tumor and adjacent normal colon epithelium) was performed by two independent observers. Samples from 62 patients were excluded because of missing follow-up information or due to neo-adjuvant therapy before tissue sampling. Out of the remaining 414 tissue pairs, 279 (67.4%) displayed reduced AIM2 expression in cancer cells when compared to epithelial cells of their normal counterpart. Thirty-eight patients (9.18%) had completely lost AIM2 expression in tumor cells. After adjustment for sex, age, cancer stage, tumor site, tumor grade and chemotherapy, complete lack of AIM2 expression was associated with an up to 3-fold increase in overall mortality (HR=2.40; 95% CI=1.44-3.99) and disease specific mortality (HR=3.14; 95% CI=1.75-5.65) in comparison to AIM2-positive tumor samples. Our results demonstrate that lack of AIM2 expression is closely associated with poor outcome in colorectal cancer. The data thus strongly substantiate a protective role of AIM2 against progression of colorectal tumors. Further studies are required to assess whether lack of AIM2 expression may be used as a biomarker for the identification of colorectal cancer patients with poor prognosis.\",\n \"title\": \"Lack of Absent in Melanoma 2 (AIM2) expression in tumor cells is closely associated with poor survival in colorectal cancer patients.\"\n },\n {\n \"docid\": \"25690516\",\n \"text\": \"The aim of the study was to evaluate whether treatment with recombinant human growth hormone (rhGH) affects the quality of life of young adults who were diagnosed as idiopathic short stature (ISS) during childhood, and whether their quality of life and aspects of the personality are different from normal. Experiences and expectations concerning rhGH treatment of the subjects and their parents were also investigated. Eighty-nine subjects were included into the study: 24 subjects (16M, 8F) were treated with rhGH from childhood, whereas 65 subjects (40M, 25F) were never treated. At the time of the interview all subjects had attained final height [mean (SD) -2.3 (0.9) SDS for Dutch references], and the age of the treated subjects was 20.5 (1.0) y, and 25.7 (3.5) y of the control subjects (p < 0.001). The level of education was similar, but the treated subjects had less often a partner compared to the control subjects (adjusted for age and gender, p < 0.001). The Nottingham Health Profile and Short Form 36 Health Survey showed no difference in general health state between treated and control subjects, and the healthy Dutch age-specific references (norm group). Although 74% of the subjects reported one or more negative events related to their height, and 61% would like to be taller, only 22% and 11% were willing to trade-off at Time Trade-Off and Standard Gamble, respectively. The personality of the subjects, which was measured by the Minnesota Multiphasic Personality Inventory, was not different from the norm group. The satisfaction with the rhGH treatment was high, as it had caused 12 (8) cm and 13 (7) cm gain in final height according to the subjects and parents, respectively. Based on initial predicted adult height (Bayley & Pinneau), this gain was only 3.3 (5.6) cm. We concluded that although the treated subjects had a partner less often when compared to the control subjects, the quality of life of subjects with ISS at adult age is normal and appears not to be affected by rhGH therapy, The treated subjects were very satisfied with the treatment, probably by overestimation of the final height gain.\",\n \"title\": \"Quality of life of young adults with idiopathic short stature: effect of growth hormone treatment. Dutch Growth Hormone Working Group.\"\n },\n {\n \"docid\": \"15041758\",\n \"text\": \"OBJECTIVE To evaluate the effectiveness of integrated care for chronic physical diseases and depression in reducing disability and improving quality of life. DESIGN A randomised controlled trial of multi-condition collaborative care for depression and poorly controlled diabetes and/or risk factors for coronary heart disease compared with usual care among middle aged and elderly people SETTING Fourteen primary care clinics in Seattle, Washington. PARTICIPANTS Patients with diabetes or coronary heart disease, or both, and blood pressure above 140/90 mm Hg, low density lipoprotein concentration >3.37 mmol/L, or glycated haemoglobin 8.5% or higher, and PHQ-9 depression scores of ≥ 10. INTERVENTION A 12 month intervention to improve depression, glycaemic control, blood pressure, and lipid control by integrating a \\\"treat to target\\\" programme for diabetes and risk factors for coronary heart disease with collaborative care for depression. The intervention combined self management support, monitoring of disease control, and pharmacotherapy to control depression, hyperglycaemia, hypertension, and hyperlipidaemia. MAIN OUTCOME MEASURES Social role disability (Sheehan disability scale), global quality of life rating, and World Health Organization disability assessment schedule (WHODAS-2) scales to measure disabilities in activities of daily living (mobility, self care, household maintenance). RESULTS Of 214 patients enrolled (106 intervention and 108 usual care), disability and quality of life measures were obtained for 97 intervention patients at six months (92%) and 92 at 12 months (87%), and for 96 usual care patients at six months (89%) and 92 at 12 months (85%). Improvements from baseline on the Sheehan disability scale (-0.9, 95% confidence interval -1.5 to -0.2; P = 0.006) and global quality of life rating (0.7, 0.2 to 1.2; P = 0.005) were significantly greater at six and 12 months in patients in the intervention group. There was a trend toward greater improvement in disabilities in activities of daily living (-1.5, -3.3 to 0.4; P = 0.10). CONCLUSIONS Integrated care that covers chronic physical disease and comorbid depression can reduce social role disability and enhance global quality of life. Trial registration Clinical Trials NCT00468676.\",\n \"title\": \"Functional outcomes of multi-condition collaborative care and successful ageing: results of randomised trial\"\n },\n {\n \"docid\": \"52180874\",\n \"text\": \"OBJECTIVE To evaluate the relative efficacy of programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors versus conventional drugs in patients with cancer that were PD-L1 positive and PD-L1 negative. DESIGN Meta-analysis of randomised controlled trials. DATA SOURCES PubMed, Embase, Cochrane database, and conference abstracts presented at the American Society of Clinical Oncology and European Society of Medical Oncology up to March 2018. REVIEW METHODS Studies of PD-1 or PD-L1 inhibitors (avelumab, atezolizumab, durvalumab, nivolumab, and pembrolizumab) that had available hazard ratios for death based on PD-L1 positivity or negativity were included. The threshold for PD-L1 positivity or negativity was that PD-L1 stained cell accounted for 1% of tumour cells, or tumour and immune cells, assayed by immunohistochemistry staining methods. RESULTS 4174 patients with advanced or metastatic cancers from eight randomised controlled trials were included in this study. Compared with conventional agents, PD-1 or PD-L1 inhibitors were associated with significantly prolonged overall survival in both patients that were PD-L1 positive (n=2254, hazard ratio 0.66, 95% confidence interval 0.59 to 0.74) and PD-L1 negative (1920, 0.80, 0.71 to 0.90). However, the efficacies of PD-1 or PD-L1 blockade treatment in patients that were PD-L1 positive and PD-L1 negative were significantly different (P=0.02 for interaction). Additionally, in both patients that were PD-L1 positive and PD-L1 negative, the long term clinical benefits from PD-1 or PD-L1 blockade were observed consistently across interventional agent, cancer histotype, method of randomisation stratification, type of immunohistochemical scoring system, drug target, type of control group, and median follow-up time. CONCLUSIONS PD-1 or PD-L1 blockade therapy is a preferable treatment option over conventional therapy for both patients that are PD-L1 positive and PD-L1 negative. This finding suggests that PD-L1 expression status alone is insufficient in determining which patients should be offered PD-1 or PD-L1 blockade therapy.\",\n \"title\": \"Efficacy of PD-1 or PD-L1 inhibitors and PD-L1 expression status in cancer: meta-analysis\"\n },\n {\n \"docid\": \"52188256\",\n \"text\": \"This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.\",\n \"title\": \"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.\"\n },\n {\n \"docid\": \"24575065\",\n \"text\": \"CONTEXT The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) altered reimbursements for outpatient chemotherapy drugs and drug administration services. Anecdotal reports suggest that these adjustments may have negatively affected access to chemotherapy for Medicare beneficiaries. OBJECTIVE To compare patient wait times and travel distances for chemotherapy before and after the enactment of the MMA. DESIGN, SETTING, AND PATIENTS Analysis of a nationally representative 5% sample of claims from the Centers for Medicare & Medicaid Services for the period 2003 through 2006. Patients were Medicare beneficiaries with incident breast cancer, colorectal cancer, leukemia, lung cancer, or lymphoma who received chemotherapy in inpatient hospital, institutional outpatient, or physician office settings. MAIN OUTCOME MEASURES Days from incident diagnosis to first chemotherapy visit and distance traveled for treatment, controlling for age, sex, race/ethnicity, cancer type, geographic region, comorbid conditions, and year of diagnosis and treatment. RESULTS There were 5082 incident cases of breast cancer, colorectal cancer, leukemia, lung cancer, or lymphoma in 2003; 5379 cases in 2004; 5116 cases in 2005; and 5288 cases in 2006. Approximately 70% of patients received treatment in physician office settings in each year. Although the distribution of treatment settings in 2004 and 2005 was not significantly different from 2003 (P = .24 and P = .72, respectively), there was a small but significant change from 2003 to 2006 (P = .02). The proportion of patients receiving chemotherapy in inpatient settings decreased from 10.2% in 2003 to 8.8% in 2006 (P = .03), and the proportion in institutional outpatient settings increased from 21.1% to 22.5% (P = .004). The proportion in physician offices remained at 68.7% (P = .29). The median time from diagnosis to initial chemotherapy visit was 28 days in 2003, 27 days in 2004, 29 days in 2005, and 28 days in 2006. In multivariate analyses, average wait times for chemotherapy were 1.96 days longer in 2005 than in 2003 (95% confidence interval [CI], 0.11-3.80 days; P = .04) but not significantly different in 2006 (0.88 days; 95% CI, -0.96 to 2.71 days; P = .35). Median travel distance was 7 miles (11.2 km) in 2003 and 8 miles (12.8 km) in 2004 through 2006. After adjustment, average travel distance remained slightly longer in 2004 (1.47 miles [2.35 km]; 95% CI, 0.87-2.07 miles [1.39-3.31 km]; P < .001), 2005 (1.19 miles [1.90 km]; 95% CI, 0.58-1.80 miles [0.93-2.88 km]; P < .001), and 2006 (1.30 miles [2.08 km]; 95% CI, 0.69-1.90 miles [1.10-3.04 km]; P < .001) compared with 2003. CONCLUSION There have not been major changes in travel distance and patient wait times for chemotherapy in the Medicare population since 2003, the year before MMA-related changes in reimbursement.\",\n \"title\": \"Association between the Medicare Modernization Act of 2003 and patient wait times and travel distance for chemotherapy.\"\n },\n {\n \"docid\": \"5151024\",\n \"text\": \"BACKGROUND The diagnosis of hypertension has traditionally been based on blood-pressure measurements in the clinic, but home and ambulatory measurements better correlate with cardiovascular outcome, and ambulatory monitoring is more accurate than both clinic and home monitoring in diagnosing hypertension. We aimed to compare the cost-effectiveness of different diagnostic strategies for hypertension. METHODS We did a Markov model-based probabilistic cost-effectiveness analysis. We used a hypothetical primary-care population aged 40 years or older with a screening blood-pressure measurement greater than 140/90 mm Hg and risk-factor prevalence equivalent to the general population. We compared three diagnostic strategies-further blood pressure measurement in the clinic, at home, and with an ambulatory monitor-in terms of lifetime costs, quality-adjusted life years, and cost-effectiveness. FINDINGS Ambulatory monitoring was the most cost-effective strategy for the diagnosis of hypertension for men and women of all ages. It was cost-saving for all groups (from -£56 [95% CI -105 to -10] in men aged 75 years to -£323 [-389 to -222] in women aged 40 years) and resulted in more quality-adjusted life years for men and women older than 50 years (from 0·006 [0·000 to 0·015] for women aged 60 years to 0·022 [0·012 to 0·035] for men aged 70 years). This finding was robust when assessed with a wide range of deterministic sensitivity analyses around the base case, but was sensitive if home monitoring was judged to have equal test performance to ambulatory monitoring or if treatment was judged effective irrespective of whether an individual was hypertensive. INTERPRETATION Ambulatory monitoring as a diagnostic strategy for hypertension after an initial raised reading in the clinic would reduce misdiagnosis and save costs. Additional costs from ambulatory monitoring are counterbalanced by cost savings from better targeted treatment. Ambulatory monitoring is recommended for most patients before the start of antihypertensive drugs. FUNDING National Institute for Health Research and the National Institute for Health and Clinical Excellence.\",\n \"title\": \"Cost-effectiveness of options for the diagnosis of high blood pressure in primary care: a modelling study.\"\n },\n {\n \"docid\": \"20610557\",\n \"text\": \"In recent years, the immune-potentiating effects of some widely used chemotherapeutic agents have been increasingly appreciated. This provides a rationale for combining conventional chemotherapy with immunotherapy strategies to achieve durable therapeutic benefits. Previous studies have implicated the immunomodulatory effects of melphalan, an alkylating agent commonly used to treat multiple myeloma, but the underlying mechanisms remain obscure. In the present study, we investigated the impact of melphalan on endogenous immune cells as well as adoptively transferred tumor-specific CD4(+) T cells in tumor-bearing mice. We showed that melphalan treatment resulted in a rapid burst of inflammatory cytokines and chemokines during the cellular recovery phase after melphalan-induced myelodepletion and leukodepletion. After melphalan treatment, tumor cells exhibited characteristics of immunogenic cell death, including membrane translocation of the endoplasmic reticulum-resident calreticulin and extracellular release of high-mobility group box 1. Additionally, there was enhanced tumor Ag uptake by dendritic cells in the tumor-draining lymph node. Consistent with these immunomodulatory effects, melphalan treatment of tumor-bearing mice led to the activation of the endogenous CD8(+) T cells and, more importantly, effectively drove the clonal expansion and effector differentiation of adoptively transferred tumor-specific CD4(+) T cells. Notably, the combination of melphalan and CD4(+) T cell adoptive cell therapy was more efficacious than either treatment alone in prolonging the survival of mice with advanced B cell lymphomas or colorectal tumors. These findings provide mechanistic insights into melphalan's immunostimulatory effects and demonstrate the therapeutic potential of combining melphalan with adoptive cell therapy utilizing antitumor CD4(+) T cells.\",\n \"title\": \"Alkylating agent melphalan augments the efficacy of adoptive immunotherapy using tumor-specific CD4+ T cells.\"\n },\n {\n \"docid\": \"195680777\",\n \"text\": \"BACKGROUND Moderate differences in efficacy between adjuvant chemotherapy regimens for breast cancer are plausible, and could affect treatment choices. We sought any such differences. METHODS We undertook individual-patient-data meta-analyses of the randomised trials comparing: any taxane-plus-anthracycline-based regimen versus the same, or more, non-taxane chemotherapy (n=44,000); one anthracycline-based regimen versus another (n=7000) or versus cyclophosphamide, methotrexate, and fluorouracil (CMF; n=18,000); and polychemotherapy versus no chemotherapy (n=32,000). The scheduled dosages of these three drugs and of the anthracyclines doxorubicin (A) and epirubicin (E) were used to define standard CMF, standard 4AC, and CAF and CEF. Log-rank breast cancer mortality rate ratios (RRs) are reported. FINDINGS In trials adding four separate cycles of a taxane to a fixed anthracycline-based control regimen, extending treatment duration, breast cancer mortality was reduced (RR 0·86, SE 0·04, two-sided significance [2p]=0·0005). In trials with four such extra cycles of a taxane counterbalanced in controls by extra cycles of other cytotoxic drugs, roughly doubling non-taxane dosage, there was no significant difference (RR 0·94, SE 0·06, 2p=0·33). Trials with CMF-treated controls showed that standard 4AC and standard CMF were equivalent (RR 0·98, SE 0·05, 2p=0·67), but that anthracycline-based regimens with substantially higher cumulative dosage than standard 4AC (eg, CAF or CEF) were superior to standard CMF (RR 0·78, SE 0·06, 2p=0·0004). Trials versus no chemotherapy also suggested greater mortality reductions with CAF (RR 0·64, SE 0·09, 2p<0·0001) than with standard 4AC (RR 0·78, SE 0·09, 2p=0·01) or standard CMF (RR 0·76, SE 0·05, 2p<0·0001). In all meta-analyses involving taxane-based or anthracycline-based regimens, proportional risk reductions were little affected by age, nodal status, tumour diameter or differentiation (moderate or poor; few were well differentiated), oestrogen receptor status, or tamoxifen use. Hence, largely independently of age (up to at least 70 years) or the tumour characteristics currently available to us for the patients selected to be in these trials, some taxane-plus-anthracycline-based or higher-cumulative-dosage anthracycline-based regimens (not requiring stem cells) reduced breast cancer mortality by, on average, about one-third. 10-year overall mortality differences paralleled breast cancer mortality differences, despite taxane, anthracycline, and other toxicities. INTERPRETATION 10-year gains from a one-third breast cancer mortality reduction depend on absolute risks without chemotherapy (which, for oestrogen-receptor-positive disease, are the risks remaining with appropriate endocrine therapy). Low absolute risk implies low absolute benefit, but information was lacking about tumour gene expression markers or quantitative immunohistochemistry that might help to predict risk, chemosensitivity, or both. FUNDING Cancer Research UK; British Heart Foundation; UK Medical Research Council.\",\n \"title\": \"Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials.\"\n },\n {\n \"docid\": \"32852283\",\n \"text\": \"BACKGROUND Although zoledronic acid (ZOL), a third-generation nitrogen-containing bisphosphonate, has been identified as an attractive therapeutic agent against breast cancer, prostate cancer, multiple myeloma as well as small-cell lung cancer (SCLC), as best as we are aware, the anti-tumor effect of ZOL upon non-small-cell lung cancer (NSCLC) remains to be effectively investigated. This study examined the effects of ZOL upon the line-1 tumor cell, using a murine lung adenocarcinoma cell line similar to the behavior of human lung adenocarcinoma. METHODS We investigated the anti-tumor effects of ZOL (3-100 microM) on line-1 tumor cells in vitro, including cellular proliferation, by means of an MTT assay, cell-cycle analysis by flow cytometry and by assessing the level of apoptosis by annexin V/propidium iodide (PI) and 4'-6-diamidino-2-phenylindole (DAPI) staining. Further, we evaluated the growth and survival of line-1 tumor cells following ZOL treatment (1 microg/kg/week) using an animal model. We also examined the in vivo cell-cycle pattern using lacZ-expressing line-1 cells (line-1/lacZ). RESULTS ZOL significantly slowed the line-1 tumor growth in a dose-dependent manner in vitro. The treated line-1 tumor cells typically arrested at the S/G2/M-phase of the cell-cycle following ZOL exposure, but no apoptotic cells could be detected by either annexin V/PI or DAPI staining. When the ZOL was washed out, the drug-inhibited cells continued to proliferate again and the cell-cycle prolongation elicited earlier by the drug, then disappeared. Within 72-96 h following drug removal, the cell-cycle of the treated cells revealed a similar distribution to that of the untreated controls. In vivo studies demonstrated that ZOL significantly slowed the line-1 tumor growth. Indeed, mice lived significantly longer when they had been ZOL-treated than was the case for untreated mice (p<0.05). Using line-1/lacZ cells, the in vivo cell-cycle distribution of line-1 tumor cells subsequent to ZOL exposure revealed S/G2/M-phase arrest that was identical to the in vitro culture. CONCLUSIONS ZOL maintains the potential to reduce tumor burden and prolong survival for murine pulmonary adenocarcinoma. The flow cytometrical analysis of cell-cycle demonstrated that ZOL induces no apoptosis but is able to arrest line-1 tumor cells at the S/G2/M-phase. Although the clinical relevance of these results warrants verification for human lung cancer patients, ZOL combined with chemotherapy and/or radiotherapy appears to be a new therapeutic strategy for the effective treatment of NSCLC.\",\n \"title\": \"Zoledronic acid is unable to induce apoptosis, but slows tumor growth and prolongs survival for non-small-cell lung cancers.\"\n },\n {\n \"docid\": \"2328272\",\n \"text\": \"INTRODUCTION With the growing number of adult cancer survivors, there is increasing need for information that links potential late and long term effects with specific treatment regimens. Few adult cancer patients are treated on clinical trials; however, patients previously enrolled in these trials are an important source of information about treatment-related late effects. METHODS Focusing on colorectal cancer survivors, we used the database from five phase III randomized clinical trials from the National Surgical Adjuvant Breast & Bowel Project (NSABP) to recruit and enroll long term survivors in a study of late health outcomes and quality of life. We describe the challenges to recruitment of patients more than 5 -20 years after treatment. RESULTS Sixty-five NSABP treatment sites were invited to enroll patients in the study. Sixty participated with the potential to recruit 2,408 patients. We received registration forms on only 976 patients (41%) of whom 744 (76%) expressed interest in participating and 708 completed interviews (95% of those expressing interest; 29% of total potential sample). There were multiple barriers to recruitment (difficulty locating patients, lack of institutional commitment, lack of patient interest). CONCLUSIONS Patients treated on clinical trials are an important potential source for examining the late effects of cancer treatments. Retrospective recruitment has substantial limitations. In the future, mechanisms should be established for prospective long-term follow-up to identify and understand the frequency and type of late effects associated with cancer treatments. IMPLICATIONS FOR CANCER SURVIVORS As cancer patients are living longer, it will be important to learn from participants in clinical trials whether or not specific treatment regimens are associated with any serious late effects.\",\n \"title\": \"Cancer survivorship research: the challenge of recruiting adult long term cancer survivors from a cooperative clinical trials group\"\n },\n {\n \"docid\": \"32421068\",\n \"text\": \"Objective To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe. Design Retrospective cohort study. Setting Publicly accessible regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013.Main outcome measures Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after market entry. Validated European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) used to assess the clinical value of the reported gains in published studies of cancer drugs. Results From 2009 to 2013, the EMA approved the use of 48 cancer drugs for 68 indications. Of these, eight indications (12%) were approved on the basis of a single arm study. At the time of market approval, there was significant prolongation of survival in 24 of the 68 (35%). The magnitude of the benefit on overall survival ranged from 1.0 to 5.8 months (median 2.7 months). At the time of market approval, there was an improvement in quality of life in seven of 68 indications (10%). Out of 44 indications for which there was no evidence of a survival gain at the time of market authorisation, in the subsequent postmarketing period there was evidence for extension of life in three (7%) and reported benefit on quality of life in five (11%). Of the 68 cancer indications with EMA approval, and with a median of 5.4 years' follow-up (minimum 3.3 years, maximum 8.1 years), only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (49%) remained uncertain. Of 23 indications associated with a survival benefit that could be scored with the ESMO-MCBS tool, the benefit was judged to be clinically meaningful in less than half (11/23, 48%).Conclusions This systematic evaluation of oncology approvals by the EMA in 2009-13 shows that most drugs entered the market without evidence of benefit on survival or quality of life. At a minimum of 3.3 years after market entry, there was still no conclusive evidence that these drugs either extended or improved life for most cancer indications. When there were survival gains over existing treatment options or placebo, they were often marginal.\",\n \"title\": \"Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13\"\n },\n {\n \"docid\": \"26067999\",\n \"text\": \"The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms. It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment. The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms. Summary of Recommendation and Evidence The USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) See the Clinical Considerations section for suggestions for implementation in practice. See the Figure for a summary of the recommendation and suggestions for clinical practice. Figure. Screening for lung cancer: clinical summary of U.S. Preventive Services Task Force recommendation. Appendix Table 1 describes the USPSTF grades, and Appendix Table 2 describes the USPSTF classification of levels of certainty about net benefit. Appendix Table 1. What the USPSTF Grades Mean and Suggestions for Practice Appendix Table 2. USPSTF Levels of Certainty Regarding Net Benefit Supplement. Consumer Fact Sheet. Rationale Importance Lung cancer is the third most common cancer and the leading cause of cancer-related death in the United States (1). The most important risk factor for lung cancer is smoking, which results in approximately 85% of all U.S. lung cancer cases (2). Although the prevalence of smoking has decreased, approximately 37% of U.S. adults are current or former smokers (2). The incidence of lung cancer increases with age and occurs most commonly in persons aged 55 years or older. Increasing age and cumulative exposure to tobacco smoke are the 2 most common risk factors for lung cancer. Lung cancer has a poor prognosis, and nearly 90% of persons with lung cancer die of the disease. However, early-stage nonsmall cell lung cancer (NSCLC) has a better prognosis and can be treated with surgical resection. Detection Most lung cancer cases are NSCLC, and most screening programs focus on the detection and treatment of early-stage NSCLC. Although chest radiography and sputum cytologic evaluation have been used to screen for lung cancer, LDCT has greater sensitivity for detecting early-stage cancer (3). Benefits of Detection and Early Treatment Although lung cancer screening is not an alternative to smoking cessation, the USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancerrelated deaths. Direct evidence from a large, well-conducted, randomized, controlled trial (RCT) provides moderate certainty of the benefit of lung cancer screening with LDCT in this population (4). The magnitude of benefit to the person depends on that person's risk for lung cancer because those who are at highest risk are most likely to benefit. Screening cannot prevent most lung cancerrelated deaths, and smoking cessation remains essential. Harms of Detection and Early Intervention and Treatment The harms associated with LDCT screening include false-negative and false-positive results, incidental findings, overdiagnosis, and radiation exposure. False-positive LDCT results occur in a substantial proportion of screened persons; 95% of all positive results do not lead to a diagnosis of cancer. In a high-quality screening program, further imaging can resolve most false-positive results; however, some patients may require invasive procedures. The USPSTF found insufficient evidence on the harms associated with incidental findings. Overdiagnosis of lung cancer occurs, but its precise magnitude is uncertain. A modeling study performed for the USPSTF estimated that 10% to 12% of screen-detected cancer cases are overdiagnosedthat is, they would not have been detected in the patient's lifetime without screening. Radiation harms, including cancer resulting from cumulative exposure to radiation, vary depending on the age at the start of screening; the number of scans received; and the person's exposure to other sources of radiation, particularly other medical imaging. USPSTF Assessment The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT is of moderate net benefit in asymptomatic persons who are at high risk for lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. The moderate net benefit of screening depends on limiting screening to persons who are at high risk, the accuracy of image interpretation being similar to that found in the NLST (National Lung Screening Trial), and the resolution of most false-positive results without invasive procedures (4). Clinical Considerations Patient Population Under Consideration The risk for lung cancer increases with age and cumulative exposure to tobacco smoke and decreases with time since quitting smoking. The best evidence for the benefit of screening comes from the NLST, which enrolled adults aged 55 to 74 years who had at least a 30 pack-year smoking history and were current smokers or had quit within the past 15 years. As with all screening trials, the NLST tested a specific intervention over a finite period. Because initial eligibility extended through age 74 years and participants received 3 annual screening computed tomographic scans, the oldest participants in the trial were aged 77 years. The USPSTF used modeling studies to predict the benefits and harms of screening programs that use different screening intervals, age ranges, smoking histories, and times since quitting. A program that annually screens adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years is projected to have a reasonable balance of benefits and harms. The model assumes that persons who achieve 15 years of smoking cessation during the screening program discontinue screening. This model predicts the outcomes of continuing the screening program used in the NLST through age 80 years. Screening may not be appropriate for patients with substantial comorbid conditions, particularly those at the upper end of the screening age range. The NLST excluded persons who were unlikely to complete curative lung cancer surgery and those with medical conditions that posed a substantial risk for death during the 8-year trial. The baseline characteristics of the NLST showed a relatively healthy sample, and fewer than 10% of enrolled participants were older than 70 years (5). Persons with serious comorbid conditions may experience net harm, no net benefit, or at least substantially less net benefit. Similarly, persons who are unwilling to have curative lung surgery are unlikely to benefit from a screening program. Assessment of Risk Age, total exposure to tobacco smoke, and years since quitting smoking are important risk factors for lung cancer and were used to determine eligibility in the NLST. Other risk factors include specific occupational exposures, radon exposure, family history, and history of pulmonary fibrosis or chronic obstructive lung disease. The incidence of lung cancer is relatively low in persons younger than 50 years but increases with age, especially after age 60 years. In current and former smokers, age-specific incidence rates increase with age and cumulative exposure to tobacco smoke. Smoking cessation substantially reduces a person's risk for developing and dying of lung cancer. Among persons enrolled in the NLST, those who were at highest risk because of additional risk factors or a greater cumulative exposure to tobacco smoke experienced most of the benefit (6). A validated multivariate model showed that persons in the highest 60% of risk accounted for 88% of all deaths preventable by screening. Screening Tests Low-dose computed tomography has shown high sensitivity and acceptable specificity for the detection of lung cancer in high-risk persons. Chest radiography and sputum cytologic evaluation have not shown adequate sensitivity or specificity as screening tests. Therefore, LDCT is currently the only recommended screening test for lung cancer. Treatment Surgical resection is the current standard of care for localized NSCLC. This type of cancer is treated with surgical resection when possible and also with radiation and chemotherapy. Annual LDCT screening may not be useful for patients with life-limiting comorbid conditions or poor functional status who may not be candidates for surgery. Other Approaches to Prevention Smoking cessation is the most important intervention to prevent NSCLC. Advising smokers to stop smoking and preventing nonsmokers from being exposed to tobacco smoke are the most effective ways to decrease the morbidity and mortality associated with lung cancer. Current smokers should be informed of their continuing risk for lung cancer and offered cessation treatments. Screening with LDCT should be viewed as an adjunct to tobacco cessation interventions. Useful Resources Clinicians have many resources to help patients stop smoking. The Centers for Disease Control and Prevention has developed a Web site with many such resources, including information on tobacco quit lines, available in several languages (www.cdc.gov/tobacco/campaign/tips). Quit l\",\n \"title\": \"Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation Statement\"\n },\n {\n \"docid\": \"6407356\",\n \"text\": \"Coxibs, including celecoxib, and other nonsteroidal anti-inflammatory drugs (NSAID), including aspirin, are among the most promising cancer chemopreventive agents in development today. This article examines the data on the efficacy of these agents in animal model studies of cancer prevention carried out by the authors. The studies evaluated here are restricted to our rodent models of colon/intestinal, bladder, and nonmelanoma skin cancer, in which celecoxib and other NSAIDs were administered as either cancer preventive or therapeutic agents. These studies may shed light on several questions. Is celecoxib unique compared with other NSAIDs, and if so, what implications would this have for human use? Are standard NSAIDs (which inhibit both COX-1 and COX-2) as effective as celecoxib in animal studies? Is the efficacy of celecoxib in particular or NSAIDs in general due to their off-target effects or to their effects on COX-1 and COX-2? What is the likely efficacy of low-dose aspirin? Some questions raised by human trials and epidemiology are discussed and related to our observations in animal model studies. We also discuss the problem of cardiovascular (CV) events associated with coxibs and certain other NSAIDs and whether results in animal models are predictive of efficacy in humans. On the basis of epidemiologic studies and its CV profile, aspirin seems to be the most promising NSAID for preventing human colorectal, bladder, and skin cancer, although the animal data for aspirin are less clear. A comprehensive understanding of the results of coxibs and other NSAIDs in animal studies may help inform and shape human trials of these commonly employed, relatively inexpensive, and highly effective compounds.\",\n \"title\": \"Coxibs and other nonsteroidal anti-inflammatory drugs in animal models of cancer chemoprevention.\"\n },\n {\n \"docid\": \"38886345\",\n \"text\": \"BACKGROUND JX-594 is a targeted oncolytic poxvirus designed to selectively replicate in and destroy cancer cells with cell-cycle abnormalities and epidermal growth factor receptor (EGFR)-ras pathway activation. Direct oncolysis plus granulocyte-macrophage colony-stimulating factor (GM-CSF) expression also stimulates shutdown of tumour vasculature and antitumoral immunity. We aimed to assess intratumoral injection of JX-594 in patients with refractory primary or metastatic liver cancer. METHODS Between Jan 4, 2006, and July 4, 2007, 14 patients with histologically confirmed refractory primary or metastatic liver tumours (up to 10.9 cm total diameter) that were amenable to image-guided intratumoral injections were enrolled into this non-comparative, open-label, phase I dose-escalation trial (standard 3x3 design; two to six patients for each dose with 12-18 estimated total patients). Patients received one of four doses of intratumoral JX-594 (10(8) plaque-forming units [pfu], 3x10(8) pfu, 10(9) pfu, or 3x10(9) pfu) every 3 weeks at Dong-A University Hospital (Busan, South Korea). Patients were monitored after treatment for at least 48 h in hospital and for at least 4 weeks as out-patients. Adverse event-monitoring according to the National Cancer Institute Common Toxicity Criteria (version 3) and standard laboratory toxicity grading for haematology, liver and renal function, coagulation studies, serum chemistry, and urinalysis were done. The primary aims were to ascertain the maximum-tolerated dose (MTD) and safety of JX-594 treatment. Data were also collected on pharmacokinetics, pharmacodynamics, and efficacy. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00629759. FINDINGS Of 22 patients with liver tumours who were assessed for eligibility, eight patients did not meet inclusion criteria. Therefore, 14 patients, including those with hepatocellular, colorectal, melanoma, and lung cancer, were enrolled. Patients were heavily pretreated (5.6 previous treatments, SD 2.8, range 2.0-12.0) and had large tumours (7.0 cm diameter, SD 2.7, range 1.8-10.9). Patients received a mean of 3.4 (SD 2.2, range 1.0-8.0) cycles of JX-594. All patients were evaluable for toxicity. All patients experienced grade I-III flu-like symptoms, and four had transient grade I-III dose-related thrombocytopenia. Grade III hyperbilirubinaemia was dose-limiting in both patients at the highest dose; the MTD was therefore 1x10(9) pfu. JX-594 replication-dependent dissemination in blood was shown, with resultant infection of non-injected tumour sites. GM-CSF expression resulted in grade I-III increases in neutrophil counts in four of six patients at the MTD. Tumour responses were shown in injected and non-injected tumours. Ten patients were radiographically evaluable for objective responses; non-evaluable patients had contraindications to contrast medium (n=2) or no post-treatment scans (n=2). According to Response Evaluation Criteria in Solid Tumors (RECIST), three patients had partial response, six had stable disease, and one had progressive disease. INTERPRETATION Intratumoral injection of JX-594 into primary or metastatic liver tumours was generally well-tolerated. Direct hyperbilirubinaemia was the dose-limiting toxicity. Safety was acceptable in the context of JX-594 replication, GM-CSF expression, systemic dissemination, and JX-594 had anti-tumoral effects against several refractory carcinomas. Phase II trials are now underway.\",\n \"title\": \"Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial.\"\n },\n {\n \"docid\": \"35301079\",\n \"text\": \"BACKGROUND In uveal melanoma (UM) with metastatic disease limited to the liver, the effect of an intrahepatic treatment on survival is unknown. We investigated prospectively the efficacy and toxicity of hepatic intra-arterial (HIA) versus systemic (IV) fotemustine in patients with liver metastases from UM. PATIENTS AND METHODS Patients were randomly assigned to receive either IV or HIA fotemustine at 100 mg/m(2) on days 1, 8, 15 (and 22 in HIA arm only) as induction, and after a 5-week rest period every 3 weeks as maintenance. Primary end point was overall survival (OS). Response rate (RR), progression-free survival (PFS) and safety were secondary end points. RESULTS Accrual was stopped after randomization of 171 patients based on the results of a futility OS analysis. A total of 155 patients died and 16 were still alive [median follow-up 1.6 years (range 0.25-6 years)]. HIA did not improve OS (median 14.6 months) when compared with the IV arm (median 13.8 months), hazard ratio (HR) 1.09; 95% confidence interval (CI) 0.79-1.50, log-rank P = 0.59. However, there was a significant benefit on PFS for HIA compared with IV with a median of 4.5 versus 3.5 months, respectively (HR 0.62; 95% CI 0.45-0.84, log-rank P = 0.002). The 1-year PFS rate was 24% in the HIA arm versus 8% in the IV arm. An improved RR was seen in the HIA (10.5%) compared with IV treatment (2.4%). In the IV arm, the most frequent grade ≥3 toxicity was thrombocytopenia (42.1%) and neutropenia (62.6%), compared with 21.2% and 28.7% in the HIA arm. The main grade ≥3 toxicity related to HIA was catheter complications (12%) and liver toxicity (4.5%) apart from two toxic deaths. CONCLUSION HIA treatment with fotemustine did not translate into an improved OS compared with IV treatment, despite better RR and PFS. Intrahepatic treatment should still be considered as experimental. EUDRACT NUMBER AND CLINICALTRIALSGOV IDENTIFIER 2004-002245-12 and NCT00110123.\",\n \"title\": \"Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial.\"\n }\n]"}}},{"rowIdx":2589,"cells":{"query_id":{"kind":"string","value":"835"},"query":{"kind":"string","value":"NR5A2 does not play a role in development of endometrial tissues."},"positive_passages":{"kind":"list like","value":[{"docid":"15928989","text":"Successful pregnancy requires coordination of an array of signals and factors from multiple tissues. One such element, liver receptor homolog-1 (Lrh-1), is an orphan nuclear receptor that regulates metabolism and hormone synthesis. It is strongly expressed in granulosa cells of ovarian follicles and in the corpus luteum of rodents and humans. Germline ablation of Nr5a2 (also called Lrh-1), the gene coding for Lrh-1, in mice is embryonically lethal at gastrulation. Depletion of Lrh-1 in the ovarian follicle shows that it regulates genes required for both steroid synthesis and ovulation. To study the effects of Lrh-1 on mouse gestation, we genetically disrupted its expression in the corpus luteum, resulting in luteal insufficiency. Hormone replacement permitted embryo implantation but was followed by gestational failure with impaired endometrial decidualization, compromised placental formation, fetal growth retardation and fetal death. Lrh-1 is also expressed in the mouse and human endometrium, and in a primary culture of human endometrial stromal cells, reduction of NR5A2 transcript abundance by RNA interference abrogated decidualization. These findings show that Lrh-1 is necessary for maintenance of the corpus luteum, for promotion of decidualization and for formation of the placenta. It therefore has multiple, indispensible roles in establishing and sustaining pregnancy.","title":"Liver receptor homolog-1 is essential for pregnancy"}],"string":"[\n {\n \"docid\": \"15928989\",\n \"text\": \"Successful pregnancy requires coordination of an array of signals and factors from multiple tissues. One such element, liver receptor homolog-1 (Lrh-1), is an orphan nuclear receptor that regulates metabolism and hormone synthesis. It is strongly expressed in granulosa cells of ovarian follicles and in the corpus luteum of rodents and humans. Germline ablation of Nr5a2 (also called Lrh-1), the gene coding for Lrh-1, in mice is embryonically lethal at gastrulation. Depletion of Lrh-1 in the ovarian follicle shows that it regulates genes required for both steroid synthesis and ovulation. To study the effects of Lrh-1 on mouse gestation, we genetically disrupted its expression in the corpus luteum, resulting in luteal insufficiency. Hormone replacement permitted embryo implantation but was followed by gestational failure with impaired endometrial decidualization, compromised placental formation, fetal growth retardation and fetal death. Lrh-1 is also expressed in the mouse and human endometrium, and in a primary culture of human endometrial stromal cells, reduction of NR5A2 transcript abundance by RNA interference abrogated decidualization. These findings show that Lrh-1 is necessary for maintenance of the corpus luteum, for promotion of decidualization and for formation of the placenta. It therefore has multiple, indispensible roles in establishing and sustaining pregnancy.\",\n \"title\": \"Liver receptor homolog-1 is essential for pregnancy\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"1780819","text":"BACKGROUND Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development. METHODS AND FINDINGS Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64) and control samples (n = 23) revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma) is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A). Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to develop precancerous endometrial lesions with increasing age, and these lesions also demonstrated a lack of PTEN expression. CONCLUSIONS HAND2 methylation is a common and crucial molecular alteration in endometrial cancer that could potentially be employed as a biomarker for early detection of endometrial cancer and as a predictor of treatment response. The true clinical utility of HAND2 DNA methylation, however, requires further validation in prospective studies. Please see later in the article for the Editors' Summary.","title":"Role of DNA Methylation and Epigenetic Silencing of HAND2 in Endometrial Cancer Development"},{"docid":"6121668","text":"OBJECTIVES To investigate the expressions of survivin and Cyclooxygenase-2 (COX-2), and their possible correlations in the development of endometrial adenocarcinoma (EC). We also looked at their association with classical prognostic factors in EC. To our knowledge, this is the first time survivin expression is investigated in terms of its relation to COX-2 in the developmental pathway of EC. METHODS Archived tissue samples of 50 EC, 30 endometrial hyperplasia and 20 proliferative endometrium were selected and immunohistochemically analyzed for survivin and COX-2 expression. RESULTS Both survivin and COX-2 were overexpressed in hyperplasia and endometrial adenocarcinoma cases compared to proliferative endometrium, which was statistically significant (p=0.01, p=0.02, respectively). Among EC cases, survivin and COX-2 were strongly positive in 38 (76%) and 30 (60%) patients, respectively. Furthermore, we found survivin and COX-2 to be positively correlated, which was also statistically significant (p=0.0001, r=0.46). Neither survivin nor COX-2 expression was correlated with classical prognostic factors of endometrial carcinoma such as myometrial invasion, grade or lymph node metastasis (p>0.05). Neither COX-2 nor survivin had an impact on overall survival (p>0.05). CONCLUSIONS Both survivin and COX-2 are overexpressed, and they seem to be early events in the occurrence of EC. Moreover, protein products of these two genes are positively correlated. COX-2 and survivin might share a common molecular pathway or enhance each other's actions in the developmental pathway of EC. Molecular basis of such a relationship should be further investigated in endometrial carcinogenesis.","title":"COX-2 and survivin are overexpressed and positively correlated in endometrial carcinoma."},{"docid":"30369606","text":"Obtaining primary human endometrial stromal cells (HESCs) for in vitro studies is limited by the scarcity of adequate human material and the inability to passage these cells in culture for long periods. Immortalization of these cells would greatly facilitate studies; however, the process of immortalization often results in abnormal karyotypes and aberrant functional characteristics. To meet this need, we have introduced telomerase into cultured HESCs to prevent the normal shortening of telomeres observed in adult somatic cells during mitosis. We have now developed and analyzed a newly immortalized HESC line that contains no clonal chromosomal structural or numerical abnormalities. In addition, when compared with the primary unpassaged parent cells, the new cell line displayed similar biochemical endpoints after treatment with ovarian steroids. Classical decidualization response to estradiol plus medroxyprogesterone acetate were seen in both morphologically, and progestin was seen to induce or regulate the expression of IGF binding protein-1, fibronectin, prolactin, tissue factor, plasminogen activator inhibitor-1, and Fas/Fas ligand. In summary, an immortalized HESC line has been developed that is karyotypically, morphologically, and phenotypically similar to the primary parent cells, and it is a powerful and consistent resource for in vitro work.","title":"A novel immortalized human endometrial stromal cell line with normal progestational response."},{"docid":"24707550","text":"Macrophages play a pivotal role in innate and acquired immune responses to Schistosoma mansoni. Classical (M1) or alternative (M2) activation states of these cells further delineate their roles in tissue damage through innate immunity or fibrotic remodeling, respectively. In the present study, we addressed the following question: Does systemic Th2-type cytokine polarization evoked by S. mansoni affect macrophage differentiation and activation? To this end, we analyzed bone marrow-derived macrophages from mice with S. mansoni egg-induced pulmonary granulomas and unchallenged (or naïve) mice to determine their activation state and their response to specific TLR agonists, including S. mansoni egg antigens. Unlike naïve macrophages, macrophages from Th2-polarized mice constitutively expressed significantly higher \"found in inflammatory zone-1\" (FIZZ1) and ST2 (M2 markers) and significantly lower NO synthase 2, CCL3, MIP-2, TNF-alpha, and IL-12 (M1 markers). Also, compared with naïve macrophages, Th2-polarized macrophages exhibited enhanced responses to the presence of specific TLR agonists, which consistently induced significantly higher levels of gene and protein levels for M2 and M1 markers in these cells. Together, these data show that signals received by bone marrow precursors during S. mansoni egg-induced granuloma responses dynamically alter the development of macrophages and enhance the TLR responsiveness of these cells, which may ultimately have a significant effect on the pulmonary granulomatous response.","title":"A systemic granulomatous response to Schistosoma mansoni eggs alters responsiveness of bone-marrow-derived macrophages to Toll-like receptor agonists."},{"docid":"8771704","text":"Acute skeletal muscle injury triggers an expansion of fibro/adipogenic progenitors (FAPs) and a transient stage of fibrogenesis characterized by extracellular matrix deposition. While the perpetuation of such phase can lead to permanent tissue scarring, the consequences of its suppression remain to be studied. Using a model of acute muscle damage we were able to determine that pharmacological inhibition of FAP expansion by Nilotinib, a tyrosine kinase inhibitor with potent antifibrotic activity, exerts a detrimental effect on myogenesis during regeneration. We found that Nilotinib inhibits the damage-induced expansion of satellite cells in vivo, but it does not affect in vitro proliferation, suggesting a non cell-autonomous effect. Nilotinib impairs regenerative fibrogenesis by preventing the injury-triggered expansion and differentiation of resident CD45(-):CD31(-):α7integrin(-):Sca1(+) mesenchymal FAPs. Our data support the notion that the expansion of FAPs and transient fibrogenesis observed during regeneration play an important trophic role toward tissue-specific stem cells.","title":"Pharmacological blockage of fibro/adipogenic progenitor expansion and suppression of regenerative fibrogenesis is associated with impaired skeletal muscle regeneration."},{"docid":"45015767","text":"BACKGROUND Adenocarcinoma of the endometrium is the most common gynecologic malignancy in the United States, accounting for approximately 36,000 diagnoses of invasive carcinoma annually. The most common histologic type, endometrioid adenocarcinoma (EC), accounts for 75-80% of patients. The objective of this work was to estimate the prevalence of concurrent carcinoma in women with a biopsy diagnosis of the precursor lesion, atypical endometrial hyperplasia (AEH). METHODS This prospective cohort study included women who had a community diagnosis of AEH. Diagnostic biopsy specimens were reviewed independently by three gynecologic pathologists who used International Society of Gynecologic Pathologists/World Health Organization criteria. Study participants underwent hysterectomy within 12 weeks of entry onto protocol without interval treatment. The hysterectomy slides also were reviewed by the study pathologists, and their findings were used in the subsequent analyses. RESULTS Between November 1998 and June 2003, 306 women were enrolled on the study. Of these, 17 women were not included in the analysis: Two patients had unreadable slides because of poor processing or insufficient tissue, 2 patients had only slides that were not endometrial, the slides for 5 patients were not available for review, and 8 of the hysterectomy specimens were excluded because they showed evidence of interval intervention, either progestin effect or ablation. In total, 289 patients were included in the current analysis. The study panel review of the AEH biopsy specimens was interpreted as follows: 74 of 289 specimens (25.6%) were diagnosed as less than AEH, 115 of 289 specimens (39.8%) were diagnosed as AEH, and 84 of 289 specimens (29.1%) were diagnosed as endometrial carcinoma. In 5.5% (16 of 289 specimens), there was no consensus on the biopsy diagnosis. The rate of concurrent endometrial carcinoma for analyzed specimens was 42.6% (123 of 289 specimens). Of these, 30.9% (38 of 123 specimens) were myoinvasive, and 10.6% (13 of 123 specimens) involved the outer 50% of the myometrium. Among the women who had hysterectomy specimens with carcinoma, 14 of 74 women (18.9%) had a study panel biopsy consensus diagnosis of less than AEH, 45 of 115 women (39.1%) had a study panel biopsy consensus diagnosis of AEH, and 54 of 84 women (64.3%) had a study panel diagnosis of carcinoma. Among women who had no consensus in their biopsy diagnosis, 10 of 16 women (62.5%) had carcinoma in their hysterectomy specimens. CONCLUSIONS The prevalence of endometrial carcinoma in patients who had a community hospital biopsy diagnosis of AEH was high (42.6%). When considering management strategies for women who have a biopsy diagnosis of AEH, clinicians and patients should take into account the considerable rate of concurrent carcinoma.","title":"Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study."},{"docid":"10889845","text":"Obesity and insulin resistance, the key features of metabolic syndrome, are closely associated with a state of chronic, low-grade inflammation characterized by abnormal macrophage infiltration into adipose tissues. Although it has been reported that chemokines promote leukocyte migration by activating class IB phosphoinositide-3 kinase (PI3Kγ) in inflammatory states, little is known about the role of PI3Kγ in obesity-induced macrophage infiltration into tissues, systemic inflammation, and the development of insulin resistance. In the present study, we used murine models of both diet-induced and genetically induced obesity to examine the role of PI3Kγ in the accumulation of tissue macrophages and the development of obesity-induced insulin resistance. Mice lacking p110γ (Pik3cg(-/-)), the catalytic subunit of PI3Kγ, exhibited improved systemic insulin sensitivity with enhanced insulin signaling in the tissues of obese animals. In adipose tissues and livers of obese Pik3cg(-/-) mice, the numbers of infiltrated proinflammatory macrophages were markedly reduced, leading to suppression of inflammatory reactions in these tissues. Furthermore, bone marrow-specific deletion and pharmacological blockade of PI3Kγ also ameliorated obesity-induced macrophage infiltration and insulin resistance. These data suggest that PI3Kγ plays a crucial role in the development of both obesity-induced inflammation and systemic insulin resistance and that PI3Kγ can be a therapeutic target for type 2 diabetes.","title":"Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance."},{"docid":"15836115","text":"Mitochondrial morphological and ultrastructural changes occur during apoptosis and autophagy, but whether they are relevant in vivo for tissue response to damage is unclear. Here we investigate the role of the optic atrophy 1 (OPA1)-dependent cristae remodeling pathway in vivo and provide evidence that it regulates the response of multiple tissues to apoptotic, necrotic, and atrophic stimuli. Genetic inhibition of the cristae remodeling pathway in vivo does not affect development, but protects mice from denervation-induced muscular atrophy, ischemic heart and brain damage, as well as hepatocellular apoptosis. Mechanistically, OPA1-dependent mitochondrial cristae stabilization increases mitochondrial respiratory efficiency and blunts mitochondrial dysfunction, cytochrome c release, and reactive oxygen species production. Our results indicate that the OPA1-dependent cristae remodeling pathway is a fundamental, targetable determinant of tissue damage in vivo.","title":"The Opa1-Dependent Mitochondrial Cristae Remodeling Pathway Controls Atrophic, Apoptotic, and Ischemic Tissue Damage"},{"docid":"3210545","text":"BACKGROUND Three quarter of endometrial carcinomas are treated at early stage. Still, 15 to 20% of these patients experience recurrence, with little effect from systemic therapies. Homo sapiens v-Ki-ras2 Kirsten rat sarcoma viral oncogenes homologue (KRAS) mutations have been reported to have an important role in tumorigenesis for human cancers, but there is limited knowledge regarding clinical relevance of KRAS status in endometrial carcinomas. METHODS We have performed a comprehensive and integrated characterisation of genome-wide expression related to KRAS mutations and copy-number alterations in primary- and metastatic endometrial carcinoma lesions in relation to clinical and histopathological data. A primary investigation set and clinical validation set was applied, consisting of 414 primary tumours and 61 metastatic lesions totally. RESULTS Amplification and gain of KRAS present in 3% of the primary lesions and 18% of metastatic lesions correlated significantly with poor outcome, high International Federation of Gynaecology and Obstetrics stage, non-endometrioid subtype, high grade, aneuploidy, receptor loss and high KRAS mRNA levels, also found to be associated with aggressive phenotype. In contrast, KRAS mutations were present in 14.7% of primary lesions with no increase in metastatic lesions, and did not influence outcome, but was significantly associated with endometrioid subtype, low grade and obesity. CONCLUSION These results support that KRAS amplification and KRAS mRNA expression, both increasing from primary to metastatic lesions, are relevant for endometrial carcinoma disease progression.","title":"KRAS gene amplification and overexpression but not mutation associates with aggressive and metastatic endometrial cancer"},{"docid":"19485649","text":"Transmembrane cadherins are calcium-dependent intercellular adhesion molecules. Recently, they have also been shown to be sites of actin assembly during adhesive contact formation. However, the roles of actin assembly on transmembrane cadherins during development are not fully understood. We show here, using the developing ectoderm of the Xenopus embryo as a model, that F-actin assembly is a primary function of both N-cadherin in the neural ectoderm and E-cadherin in the non-neural (epidermal) ectoderm, and that each cadherin is essential for the characteristic morphogenetic movements of these two tissues. However, depletion of N-cadherin and E-cadherin did not cause dissociation in these tissues at the neurula stage, probably owing to the expression of C-cadherin in each tissue. Depletion of each of these cadherins is not rescued by the other, nor by the expression of C-cadherin, which is expressed in both tissues. One possible reason for this is that each cadherin is expressed in a different domain of the cell membrane. These data indicate the combinatorial nature of cadherin function, the fact that N- and E-cadherin play primary roles in F-actin assembly in addition to roles in cell adhesion, and that this function is specific to individual cadherins. They also show how cell adhesion and motility can be combined in morphogenetic tissue movements that generate the form and shape of the embryonic organs.","title":"N- and E-cadherins in Xenopus are specifically required in the neural and non-neural ectoderm, respectively, for F-actin assembly and morphogenetic movements."},{"docid":"29148743","text":"To determine the relative contributions of endothelial-derived nitric oxide (NO) vs. intravascular nitrogen oxide species in the regulation of human blood flow, we simultaneously measured forearm blood flow and arterial and venous levels of plasma nitrite, LMW-SNOs and HMW-SNOs, and red cell S-nitrosohemoglobin (SNO-Hb). Measurements were made at rest and during regional inhibition of NO synthesis, followed by forearm exercise. Surprisingly, we found significant circulating arterial-venous plasma nitrite gradients, providing a novel delivery source for intravascular NO. Further supporting the notion that circulating nitrite is bioactive, the consumption of nitrite increased significantly with exercise during the inhibition of regional endothelial synthesis of NO. The role of circulating S-nitrosothiols and SNO-Hb in the regulation of basal vascular tone is less certain. We found that low-molecular-weight S-nitrosothiols were undetectable and S-nitroso-albumin levels were two logs lower than previously reported. In fact, S-nitroso-albumin primarily formed in the venous circulation, even during NO synthase inhibition. Whereas SNO-Hb was measurable in the human circulation (brachial artery levels of 170 nM in whole blood), arterial-venous gradients were not significant, and delivery of NO from SNO-Hb was minimal. In conclusion, we present data that suggest (i) circulating nitrite is bioactive and provides a delivery gradient of intravascular NO, (ii) S-nitroso-albumin does not deliver NO from the lungs to the tissue but forms in the peripheral circulation, and (iii) SNO-Hb and S-nitrosothiols play a minimal role in the regulation of basal vascular tone, even during exercise stress.","title":"Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans."},{"docid":"20960682","text":"BACKGROUND & AIMS GS-9620, an oral agonist of toll-like receptor 7 (TLR7), is in clinical development for the treatment of chronic hepatitis B (CHB). GS-9620 was previously shown to induce prolonged suppression of serum viral DNA and antigens in the woodchuck and chimpanzee models of CHB. Herein, we investigated the molecular mechanisms that contribute to the antiviral response to GS-9620 using in vitro models of hepatitis B virus (HBV) infection. METHODS Cryopreserved primary human hepatocytes (PHH) and differentiated HepaRG (dHepaRG) cells were infected with HBV and treated with GS-9620, conditioned media from human peripheral blood mononuclear cells treated with GS-9620 (GS-9620 conditioned media [GS-9620-CM]), or other innate immune stimuli. The antiviral and transcriptional response to these agents was determined. RESULTS GS-9620 had no antiviral activity in HBV-infected PHH, consistent with low level TLR7 mRNA expression in human hepatocytes. In contrast, GS-9620-CM induced prolonged reduction of HBV DNA, RNA, and antigen levels in PHH and dHepaRG cells via a type I interferon (IFN)-dependent mechanism. GS-9620-CM did not reduce covalently closed circular DNA (cccDNA) levels in either cell type. Transcriptional profiling demonstrated that GS-9620-CM strongly induced various HBV restriction factors - although not APOBEC3A or the Smc5/6 complex - and indicated that established HBV infection does not modulate innate immune sensing or signaling in cryopreserved PHH. GS-9620-CM also induced expression of immunoproteasome subunits and enhanced presentation of an immunodominant viral peptide in HBV-infected PHH. CONCLUSIONS Type I IFN induced by GS-9620 durably suppressed HBV in human hepatocytes without reducing cccDNA levels. Moreover, HBV antigen presentation was enhanced, suggesting additional components of the TLR7-induced immune response played a role in the antiviral response to GS-9620 in animal models of CHB. LAY SUMMARY GS-9620 is a drug currently being tested in clinical trials for the treatment of chronic hepatitis B virus (HBV) infection. GS-9620 has previously been shown to suppress HBV in various animal models, but the underlying antiviral mechanisms were not completely understood. In this study, we determined that GS-9620 does not directly activate antiviral pathways in human liver cells, but can induce prolonged suppression of HBV via induction of an antiviral cytokine called interferon. However, interferon did not destroy the HBV genome, suggesting that other parts of the immune response (e.g. activation of immune cells that kill infected cells) also play an important role in the antiviral response to GS-9620.","title":"Toll-like receptor 7 agonist GS-9620 induces prolonged inhibition of HBV via a type I interferon-dependent mechanism."},{"docid":"18450716","text":"Adipose tissue dysfunction plays a pivotal role in the development of insulin resistance in obese individuals. Cell culture studies and gain-of-function mouse models suggest that canonical Wnt proteins modulate adipose tissue expansion. However, no genetic evidence supports a role for endogenous Wnt proteins in adipose tissue dysfunction, and the role of noncanonical Wnt signaling remains largely unexplored. Here we provide evidence from human, mouse, and cell culture studies showing that Wnt5a-mediated, noncanonical Wnt signaling contributes to obesity-associated metabolic dysfunction by increasing adipose tissue inflammation. Wnt5a expression is significantly upregulated in human visceral fat compared with subcutaneous fat in obese individuals. In obese mice, Wnt5a ablation ameliorates insulin resistance, in parallel with reductions in adipose tissue inflammation. Conversely, Wnt5a overexpression in myeloid cells augments adipose tissue inflammation and leads to greater impairments in glucose homeostasis. Wnt5a ablation or overexpression did not affect fat mass or adipocyte size. Mechanistically, Wnt5a promotes the expression of proinflammatory cytokines by macrophages in a Jun NH2-terminal kinase-dependent manner, leading to defective insulin signaling in adipocytes. Exogenous interleukin-6 administration restores insulin resistance in obese Wnt5a-deficient mice, suggesting a central role for this cytokine in Wnt5a-mediated metabolic dysfunction. Taken together, these results demonstrate that noncanonical Wnt signaling contributes to obesity-induced insulin resistance independent of adipose tissue expansion.","title":"Noncanonical Wnt Signaling Promotes Obesity-Induced Adipose Tissue Inflammation and Metabolic Dysfunction Independent of Adipose Tissue Expansion"},{"docid":"25263942","text":"Endometrial polyps are very common benign endometrial lesions, but their pathogenesis is poorly understood, except for a few studies indicating the possibility of benign stromal neoplasm. Although the histopathological diagnosis of endometrial polyp on a surgical specimen is straightforward, it is often difficult to differentiate endometrial polyp from endometrial hyperplasia on a biopsy or curettage specimen. Presently, there is no immunohistochemical marker helpful in this differential diagnosis. In this study, we examined p16 expression in 35 endometrial polyps and 33 cases of endometrial hyperplasia that included 16 simple hyperplasias, 14 complex atypical hyperplasias, and 3 complex hyperplasias without atypia. Stromal p16 expression differed significantly between the two groups; it was seen in 31 (89 %) endometrial polyps, but in only 1 (3 %) endometrial hyperplasia. The percentage of p16-positive stromal cells ranged from 10 to 90 % (mean, 47 %) and the positive cells tended to be distributed around glands. Six cases of endometrial hyperplasia within an endometrial polyp were also examined and all cases showed stromal p16 expression. There was no difference in glandular p16 expression between endometrial polyps 33 (94 %) and hyperplasia 27 (82 %). The p16-immunoreactivity was mostly confined to metaplastic epithelial cells in both groups. Stromal p16 expression might be a peculiar characteristic of endometrial polyp and constitute a useful marker for the diagnosis, especially in fragmented specimens from biopsy or curettage. Stromal p16 expression might be a reflection of p16-induced cellular senescence, which has been documented in several benign mesenchymal neoplasms.","title":"Stromal p16 expression differentiates endometrial polyp from endometrial hyperplasia"},{"docid":"14116046","text":"Retinoic acid-related orphan receptors RORα and RORγ play a regulatory role in lipid/glucose homeostasis and various immune functions, and have been implicated in metabolic syndrome and several inflammatory diseases. RORα-deficient mice are protected against age- and diet-induced obesity, hepatosteatosis, and insulin resistance. The resistance to hepatosteatosis in RORα-deficient mice is related to the reduced expression of several genes regulating lipid synthesis, transport, and storage. Adipose tissue-associated inflammation, which plays a critical role in the development of insulin resistance, is considerably diminished in RORα-deficient mice as indicated by the reduced infiltration of M1 macrophages and decreased expression of many proinflammatory genes. Deficiency in RORγ also protects against diet-induced insulin resistance by a mechanism that appears different from that in RORα deficiency. Recent studies indicated that RORs provide an important link between the circadian clock machinery and its regulation of metabolic genes and metabolic syndrome. As ligand-dependent transcription factors, RORs may provide novel therapeutic targets in the management of obesity and associated metabolic diseases, including hepatosteatosis, adipose tissue-associated inflammation, and insulin resistance.","title":"Retinoic acid-related orphan receptors α and γ: key regulators of lipid/glucose metabolism, inflammation, and insulin sensitivity"},{"docid":"22705234","text":"The African green monkey (AGM) is one of many African species endemically infected with simian immunodeficiency virus (SIV). Like the other natural hosts, AGMs do not succumb to AIDS and understanding the basis for this resistance to disease progression would be of enormous theoretical and practical importance. Early efforts by our group that concentrated on identifying immune mechanisms presumed to keep the virus under control failed to find any obvious candidates. The presumption of virus control was invalidated by the finding that SIVagm replicates in AGMs with the same vigor as HIV-1 does in humans. Focus therefore shifted to identifying possible immunopathologic features present in disease susceptible hosts but absent in the AGM natural host. The apparent immunologic tolerance of AGMs to the SIVagm core protein led to the development of a hypothesis implicating anti-Gag antibodies in the formation of immune complexes, virus trapping in the lymph nodes and immune dysfunction. The idea proved difficult to test in vivo and present work focuses on the possibility that Gag tolerance at the T-cell level plays an important role in preventing the catastrophic demise of the immune system characteristic of immunodeficiency virus infection of the heterologous primate host.","title":"The role of the immune response during SIVagm infection of the African green monkey natural host."},{"docid":"8538916","text":"The molecular chaperone CCT/TRiC plays a central role in maintaining cellular proteostasis as it mediates the folding of the major cytoskeletal proteins tubulins and actins. CCT/TRiC is also involved in the oncoprotein cyclin E, the Von Hippel-Lindau tumour suppressor protein, cyclin B and p21(ras) folding which strongly suggests that it is involved in cell proliferation and tumor genesis. To assess the involvement of CCT/TRiC in tumor genesis, we quantified its expression levels and activity in 18 cancer, one non-cancer human cell lines and a non-cancer human liver. We show that the expression levels of CCT/TRiC in cancer cell lines are higher than that in normal cells. However, CCT/TRiC activity does not always correlate with its expression levels. We therefore documented the expression levels of CCT/TRiC modulators and partners PhLP3, Hop/P60, prefoldin and Hsc/Hsp70. Our analysis reveals a functional interplay between molecular chaperones that might account for a precise modulation of CCT/TRiC activity in cell proliferation through changes in the cellular levels of prefoldin and/or Hsc/p70 and CCT/TRiC client protein availability. Our observation and approaches bring novel insights in the role of CCT/TRiC-mediated protein folding machinery in cancer cell development.","title":"The Cytosolic Chaperonin CCT/TRiC and Cancer Cell Proliferation"},{"docid":"16346504","text":"BACKGROUND Growth arrest-specific 5 (GAS5) was reported to be implicated and aberrantly express in multiple cancers. However, the expression and mechanism of action of GAS5 were largely poor understood in endometrial carcinoma. RESULTS According to the result of real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and flow cytometry analysis, we identified that GAS5 was down-regulated in endometrial cancer cells and stimulated the apoptosis of endometrial cancer cells. To investigate the expression of GAS5, PTEN and miR-103, RT-PCR was performed. And we found that the expression of PTEN was up-regulated when endometrial cancer cells overexpressed GAS5. The prediction of bioinformatics online revealed that GAS5 could bind to miR-103, which was further found to be regulated by GAS5. Finally, we found that miR-103 mimic could decrease the mRNA and protein levels of PTEN through luciferase reporter assay and western blotting, and GAS5 plasmid may reverse this regulation effect in endometrial cancer cells. CONCLUSION In summary, we demonstrate that GAS5 acts as an tumor suppressor lncRNA in endometrial cancer. Through inhibiting the expression of miR-103, GAS5 significantly enhanced the expression of PTEN to promote cancer cell apoptosis, and, thus, could be an important mediator in the pathogenesis of endometrial cancer.","title":"LncRNA-GAS5 induces PTEN expression through inhibiting miR-103 in endometrial cancer cells"},{"docid":"20456030","text":"Mitochondria play a pivotal role in energy metabolism, programmed cell death and oxidative stress. Mutated mitochondrial DNA in diseased cells compromises the structure of key enzyme complexes and, therefore, mitochondrial function, which leads to a myriad of health-related conditions such as cancer, neurodegenerative diseases, diabetes and aging. Early detection of mitochondrial and metabolic anomalies is an essential step towards effective diagnoses and therapeutic intervention. Reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) play important roles in a wide range of cellular oxidation-reduction reactions. Importantly, NADH and FAD are naturally fluorescent, which allows noninvasive imaging of metabolic activities of living cells and tissues. Furthermore, NADH and FAD autofluorescence, which can be excited using distinct wavelengths for complementary imaging methods and is sensitive to protein binding and local environment. This article highlights recent developments concerning intracellular NADH and FAD as potential biomarkers for metabolic and mitochondrial activities.","title":"Intracellular coenzymes as natural biomarkers for metabolic activities and mitochondrial anomalies."},{"docid":"23577867","text":"Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer.","title":"Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer."},{"docid":"1386103","text":"Tuberculosis, a major health problem in developing countries, has reemerged in recent years in many industrialized countries. The increased susceptibility of immunocompromised individuals to tuberculosis, and many experimental studies indicate that T cell-mediated immunity plays an important role in resistance. The lymphokine interferon gamma (IFN-gamma) is thought to be a principal mediator of macrophage activation and resistance to intracellular pathogens. Mice have been developed which fail to produce IFN-gamma (gko), because of a targeted disruption of the gene for IFN-gamma. Upon infection with Mycobacterium tuberculosis, although they develop granulomas, gko mice fail to produce reactive nitrogen intermediates and are unable to restrict the growth of the bacilli. In contrast to control mice, gko mice exhibit heightened tissue necrosis and succumb to a rapid and fatal course of tuberculosis that could be delayed, but not prevented, by treatment with exogenous recombinant IFN-gamma.","title":"An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection"},{"docid":"9239963","text":"Excessive exposure to estradiol represents the main risk factor for endometrial cancer. The abnormally high estradiol levels in the endometrium of women with endometrial cancer are most likely due to overproduction by the tumour itself. Endometrial cancer cells express the genes encoding the steroidogenic enzymes involved in estradiol synthesis. Here we used RT-PCR and Western blot to show that the nuclear receptors SF1 and LRH1, two well-known regulators of steroidogenic gene expression in gonadal and adrenal cells, are also expressed in endometrial cancer cell lines. By transient transfections, we found that SF1 and LRH1, but not the related nuclear receptor NUR77, can activate the promoters of three human steroidogenic genes: STAR, HSD3B2, and CYP19A1 PII. Similarly, forskolin but not PMA, could activate all three promoters. In addition, we found that both SF1 and LRH1 can transcriptionally cooperate with the AP-1 family members c-JUN and c-FOS, known to be associated with enhanced proliferation of endometrial carcinoma cells, to further enhance activation of the STAR, HSD3B2, and CYP19A1 PII promoters. All together, our data provide novel insights into the mechanisms of steroidogenic gene expression in endometrial cancer cells and thus in the regulation of estradiol biosynthesis by tumour cells.","title":"The nuclear receptors SF1 and LRH1 are expressed in endometrial cancer cells and regulate steroidogenic gene transcription by cooperating with AP-1 factors."},{"docid":"1428840","text":"BACKGROUND It has been suggested that identified risk factors for endometrial cancer operate through a single etiologic pathway, i.e., exposure to relatively high levels of unopposed estrogen (estrogen in the absence of progestins). Only a few studies, however, have addressed this issue directly. PURPOSE We assessed the risk of developing endometrial cancer among both premenopausal and postmenopausal women in relation to the circulating levels of steroid hormones and sex hormone-binding globulin (SHBG). The independent effect of hormones was assessed after adjustment for other known risk factors. METHODS The data used in the analysis are from a case-control study conducted in five geographic regions in the United States. Incident cases were newly diagnosed during the period from June 1, 1987, through May 15, 1990. The case patients, aged 20-74 years, were matched to control subjects by age, race, and geographic region. The community control subjects were obtained by random-digit-dialing procedures (for subjects 20-64 years old) and from files of the Health Care Financing Administration (for subjects > or = 65 years old). Additional control subjects who were having a hysterectomy performed for benign conditions were obtained from the participating centers. Women reporting use of exogenous estrogens or oral contraceptives within 6 months of interview were excluded, resulting in 68 case patients and 107 control subjects among premenopausal women and 208 case patients and 209 control subjects among postmenopausal women. The hormone analyses were performed on blood samples obtained from case patients or from hysterectomy control subjects before surgery. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of an unconditional logistic regression analysis after we controlled for matching variables and potential confounders. All P values were two-sided. RESULTS High circulating levels of androstenedione were associated with 3.6-fold and 2.8-fold increased risks among premenopausal and postmenopausal women, respectively, after adjustment for other factors (P for trend = .01 and < .001, respectively). Risks related to other hormone fractions varied by menopausal status. Among postmenopausal women, a reduced risk was associated with high SHBG levels and persisted after adjustment was made for obesity and other factors (OR = 0.51; 95% CI = 0.27-0.95). High estrone levels were associated with increased risk (OR = 3.8; 95% CI = 2.2-6.6), although adjustment for other risk factors (particularly body mass index) diminished the effect (OR = 2.2; 95% CI = 1.2-4.4). Albumin-bound estradiol (E2), a marker of the bioavailable fraction, also remained an important risk factor after adjustment was made for other factors (OR = 2.0; 95% CI = 1.0-3.9). In contrast, high concentrations of total, free, and albumin-bound E2 were unrelated to increased risk in premenopausal women. In both premenopausal and postmenopausal groups, risks associated with obesity and fat distribution were not affected by adjustment for hormones. CONCLUSION High endogenous levels of unopposed estrogen are related to increased risk of endometrial cancer, but their independence from other risk factors is inconsistent with being a common underlying biologic pathway through which all risk factors for endometrial cancer operate. IMPLICATIONS Further research should focus on alternative endocrinologic mechanisms for risk associated with obesity and body fat distribution and for the biologic relevance of the increased risk associated with androstenedione in both premenopausal and postmenopausal disease.","title":"Case-control study of endogenous steroid hormones and endometrial cancer."},{"docid":"3952288","text":"Aire-expressing medullary thymic epithelial cells (mTECs) play a key role in preventing autoimmunity by expressing tissue-restricted antigens to help purge the emerging T cell receptor repertoire of self-reactive specificities. Here we demonstrate a novel role for a CD4+3− inducer cell population, previously linked to development of organized secondary lymphoid structures and maintenance of T cell memory in the functional regulation of Aire-mediated promiscuous gene expression in the thymus. CD4+3− cells are closely associated with mTECs in adult thymus, and in fetal thymus their appearance is temporally linked with the appearance of Aire+ mTECs. We show that RANKL signals from this cell promote the maturation of RANK-expressing CD80−Aire− mTEC progenitors into CD80+Aire+ mTECs, and that transplantation of RANK-deficient thymic stroma into immunodeficient hosts induces autoimmunity. Collectively, our data reveal cellular and molecular mechanisms leading to the generation of Aire+ mTECs and highlight a previously unrecognized role for CD4+3−RANKL+ inducer cells in intrathymic self-tolerance.","title":"RANK signals from CD4+3− inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla"},{"docid":"39559521","text":"The negative selection of self-reactive thymocytes depends on the expression of tissue-specific antigens by medullary thymic epithelial cells. The autoimmune regulator (Aire) protein plays an important role in turning on these antigens, and the absence of even one Aire-induced tissue-specific antigen in the thymus can lead to autoimmunity in the antigen-expressing target organ. Recently, Aire protein has been detected in peripheral lymphoid organs, suggesting that peripheral Aire plays a complementary role here. In these peripheral sites, Aire was found to regulate the expression of a group of tissue-specific antigens that is distinct from those expressed in the thymus. Furthermore, transgenic antigen expression in extrathymic Aire-expressing cells (eTACs) can mediate deletional tolerance, but the immunological relevance of Aire-dependent, endogenous tissue-specific antigens remains to be determined.","title":"Control of central and peripheral tolerance by Aire."},{"docid":"19332616","text":"Coronary atherosclerosis is by far the most frequent cause of ischemic heart disease, and plaque disruption with superimposed thrombosis is the main cause of the acute coronary syndromes of unstable angina, myocardial infarction, and sudden death.1 2 3 4 5 Therefore, for event-free survival, the vital question is not why atherosclerosis develops but rather why, after years of indolent growth, it suddenly becomes complicated by life-threatening thrombosis. The composition and vulnerability of plaque rather than its volume or the consequent severity of stenosis produced have emerged as being the most important determinants for the development of the thrombus-mediated acute coronary syndromes; lipid-rich and soft plaques are more dangerous than collagen-rich and hard plaques because they are more unstable and rupture-prone and highly thrombogenic after disruption.6 This review will explore potential mechanisms responsible for the sudden conversion of a stable atherosclerotic plaque to an unstable and life-threatening atherothrombotic lesion—an event known as plaque fissuring, rupture, or disruption.7 8 Atherosclerosis is the result of a complex interaction between blood elements, disturbed flow, and vessel wall abnormality, involving several pathological processes: inflammation, with increased endothelial permeability, endothelial activation, and monocyte recruitment9 10 11 12 13 14 ; growth, with smooth muscle cell (SMC) proliferation, migration, and matrix synthesis15 16 ; degeneration, with lipid accumulation17 18 ; necrosis, possibly related to the cytotoxic effect of oxidized lipid19 ; calcification/ossification, which may represent an active rather than a dystrophic process20 21 ; and thrombosis, with platelet recruitment and fibrin formation.1 22 23 Thrombotic factors may play a role early during atherogenesis, but a flow-limiting thrombus does not develop until mature plaques are present, which is why thrombosis often is classified as a complication rather than a genuine component of atherosclerosis. ### Mature Plaques: Atherosis and Sclerosis As the name atherosclerosis implies, mature …","title":"Coronary plaque disruption."},{"docid":"2389574","text":"PURPOSE Overexpression of the oncogen Stathmin has been linked to aggressive endometrial carcinoma and a potential for PI3Kinase inhibitors in this disease. We wanted to validate the prognostic value of Stathmin expression in a large prospective multicenter setting. As lymph node sampling is part of current surgical staging, we also aimed to test if Stathmin expression in endometrial curettage specimens could predict lymph node metastasis. EXPERIMENTAL DESIGN A total of 1,076 endometrial cancer patients have been recruited from 10 centers to investigate the biological tumor marker Stathmin in relation to clinicopathologic variables, including lymph node status and survival. Stathmin immunohistochemical staining was carried out in 477 hysterectomy and 818 curettage specimens. RESULTS Seventy-one percent of the patients (n = 763) were subjected to lymph node sampling, of which 12% had metastatic nodes (n = 94). Overexpression of Stathmin was detected in 37% (302 of 818) of the curettage and in 18% (84 of 477) of the hysterectomy specimens investigated. Stathmin overexpression in curettage and hysterectomy specimens were highly correlated and significantly associated with nonendometrioid histology, high grade, and aneuploidy. Stathmin analysis in preoperative curettage samples significantly correlated with, and was an independent predictor of, lymph node metastases. High Stathmin expression was associated with poor disease-specific survival (P ≤ 0.002) both in curettage and hysterectomy specimens. CONCLUSIONS Stathmin immunohistochemical staining identifies endometrial carcinomas with lymph node metastases and poor survival. The value, as a predictive marker for response to PI3Kinase inhibition and as a tool to stratify patients for lymph node sampling in endometrial carcinomas, remains to be determined.","title":"Stathmin overexpression identifies high-risk patients and lymph node metastasis in endometrial cancer."},{"docid":"16839245","text":"The basic biology of the cell division cycle and its control by protein kinases was originally studied through genetic and biochemical studies in yeast and other model organisms. The major regulatory mechanisms identified in this pioneer work are conserved in mammals. However, recent studies in different cell types or genetic models are now providing a new perspective on the function of these major cell cycle regulators in different tissues. Here, we review the physiological relevance of mammalian cell cycle kinases such as cyclin-dependent kinases (Cdks), Aurora and Polo-like kinases, and mitotic checkpoint regulators (Bub1, BubR1, and Mps1) as well as other less-studied enzymes such as Cdc7, Nek proteins, or Mastl and their implications in development, tissue homeostasis, and human disease. Among these functions, the control of self-renewal or asymmetric cell division in stem/progenitor cells and the ability to regenerate injured tissues is a central issue in current research. In addition, many of these proteins play previously unexpected roles in metabolism, cardiovascular function, or neuron biology. The modulation of their enzymatic activity may therefore have multiple therapeutic benefits in human disease.","title":"Physiological relevance of cell cycle kinases."},{"docid":"9550981","text":"The adult Drosophila hindgut was recently reported to contain active, tissue-replenishing stem cells, like those of the midgut, but located within an anterior ring so as to comprise a single giant crypt. In contrast to this view, we observed no active stem cells and little cell turnover in adult hindgut tissue based on clonal marking and BrdU incorporation studies. Again contradicting the previous proposal, we showed that the adult hindgut is not generated by anterior stem cells during larval/pupal development. However, severe tissue damage within the hindgut elicits cell proliferation within a ring of putative quiescent stem cells at the anterior of the pylorus. Thus, the hindgut does not provide a model of tissue maintenance by constitutively active stem cells, but has great potential to illuminate mechanisms of stress-induced tissue repair.","title":"The Drosophila hindgut lacks constitutively active adult stem cells but proliferates in response to tissue damage."},{"docid":"3514072","text":"Gene expression is controlled by the complex interaction of transcription factors binding to promoters and other regulatory DNA elements. One common characteristic of the genomic regions associated with regulatory proteins is a pronounced sensitivity to DNase I digestion. We generated genome-wide high-resolution maps of DNase I hypersensitive (DH) sites from both seedling and callus tissues of rice (Oryza sativa). Approximately 25% of the DH sites from both tissues were found in putative promoters, indicating that the vast majority of the gene regulatory elements in rice are not located in promoter regions. We found 58% more DH sites in the callus than in the seedling. For DH sites detected in both the seedling and callus, 31% displayed significantly different levels of DNase I sensitivity within the two tissues. Genes that are differentially expressed in the seedling and callus were frequently associated with DH sites in both tissues. The DNA sequences contained within the DH sites were hypomethylated, consistent with what is known about active gene regulatory elements. Interestingly, tissue-specific DH sites located in the promoters showed a higher level of DNA methylation than the average DNA methylation level of all the DH sites located in the promoters. A distinct elevation of H3K27me3 was associated with intergenic DH sites. These results suggest that epigenetic modifications play a role in the dynamic changes of the numbers and DNase I sensitivity of DH sites during development.","title":"High-resolution mapping of open chromatin in the rice genome."}],"string":"[\n {\n \"docid\": \"1780819\",\n \"text\": \"BACKGROUND Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development. METHODS AND FINDINGS Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64) and control samples (n = 23) revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma) is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A). Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to develop precancerous endometrial lesions with increasing age, and these lesions also demonstrated a lack of PTEN expression. CONCLUSIONS HAND2 methylation is a common and crucial molecular alteration in endometrial cancer that could potentially be employed as a biomarker for early detection of endometrial cancer and as a predictor of treatment response. The true clinical utility of HAND2 DNA methylation, however, requires further validation in prospective studies. Please see later in the article for the Editors' Summary.\",\n \"title\": \"Role of DNA Methylation and Epigenetic Silencing of HAND2 in Endometrial Cancer Development\"\n },\n {\n \"docid\": \"6121668\",\n \"text\": \"OBJECTIVES To investigate the expressions of survivin and Cyclooxygenase-2 (COX-2), and their possible correlations in the development of endometrial adenocarcinoma (EC). We also looked at their association with classical prognostic factors in EC. To our knowledge, this is the first time survivin expression is investigated in terms of its relation to COX-2 in the developmental pathway of EC. METHODS Archived tissue samples of 50 EC, 30 endometrial hyperplasia and 20 proliferative endometrium were selected and immunohistochemically analyzed for survivin and COX-2 expression. RESULTS Both survivin and COX-2 were overexpressed in hyperplasia and endometrial adenocarcinoma cases compared to proliferative endometrium, which was statistically significant (p=0.01, p=0.02, respectively). Among EC cases, survivin and COX-2 were strongly positive in 38 (76%) and 30 (60%) patients, respectively. Furthermore, we found survivin and COX-2 to be positively correlated, which was also statistically significant (p=0.0001, r=0.46). Neither survivin nor COX-2 expression was correlated with classical prognostic factors of endometrial carcinoma such as myometrial invasion, grade or lymph node metastasis (p>0.05). Neither COX-2 nor survivin had an impact on overall survival (p>0.05). CONCLUSIONS Both survivin and COX-2 are overexpressed, and they seem to be early events in the occurrence of EC. Moreover, protein products of these two genes are positively correlated. COX-2 and survivin might share a common molecular pathway or enhance each other's actions in the developmental pathway of EC. Molecular basis of such a relationship should be further investigated in endometrial carcinogenesis.\",\n \"title\": \"COX-2 and survivin are overexpressed and positively correlated in endometrial carcinoma.\"\n },\n {\n \"docid\": \"30369606\",\n \"text\": \"Obtaining primary human endometrial stromal cells (HESCs) for in vitro studies is limited by the scarcity of adequate human material and the inability to passage these cells in culture for long periods. Immortalization of these cells would greatly facilitate studies; however, the process of immortalization often results in abnormal karyotypes and aberrant functional characteristics. To meet this need, we have introduced telomerase into cultured HESCs to prevent the normal shortening of telomeres observed in adult somatic cells during mitosis. We have now developed and analyzed a newly immortalized HESC line that contains no clonal chromosomal structural or numerical abnormalities. In addition, when compared with the primary unpassaged parent cells, the new cell line displayed similar biochemical endpoints after treatment with ovarian steroids. Classical decidualization response to estradiol plus medroxyprogesterone acetate were seen in both morphologically, and progestin was seen to induce or regulate the expression of IGF binding protein-1, fibronectin, prolactin, tissue factor, plasminogen activator inhibitor-1, and Fas/Fas ligand. In summary, an immortalized HESC line has been developed that is karyotypically, morphologically, and phenotypically similar to the primary parent cells, and it is a powerful and consistent resource for in vitro work.\",\n \"title\": \"A novel immortalized human endometrial stromal cell line with normal progestational response.\"\n },\n {\n \"docid\": \"24707550\",\n \"text\": \"Macrophages play a pivotal role in innate and acquired immune responses to Schistosoma mansoni. Classical (M1) or alternative (M2) activation states of these cells further delineate their roles in tissue damage through innate immunity or fibrotic remodeling, respectively. In the present study, we addressed the following question: Does systemic Th2-type cytokine polarization evoked by S. mansoni affect macrophage differentiation and activation? To this end, we analyzed bone marrow-derived macrophages from mice with S. mansoni egg-induced pulmonary granulomas and unchallenged (or naïve) mice to determine their activation state and their response to specific TLR agonists, including S. mansoni egg antigens. Unlike naïve macrophages, macrophages from Th2-polarized mice constitutively expressed significantly higher \\\"found in inflammatory zone-1\\\" (FIZZ1) and ST2 (M2 markers) and significantly lower NO synthase 2, CCL3, MIP-2, TNF-alpha, and IL-12 (M1 markers). Also, compared with naïve macrophages, Th2-polarized macrophages exhibited enhanced responses to the presence of specific TLR agonists, which consistently induced significantly higher levels of gene and protein levels for M2 and M1 markers in these cells. Together, these data show that signals received by bone marrow precursors during S. mansoni egg-induced granuloma responses dynamically alter the development of macrophages and enhance the TLR responsiveness of these cells, which may ultimately have a significant effect on the pulmonary granulomatous response.\",\n \"title\": \"A systemic granulomatous response to Schistosoma mansoni eggs alters responsiveness of bone-marrow-derived macrophages to Toll-like receptor agonists.\"\n },\n {\n \"docid\": \"8771704\",\n \"text\": \"Acute skeletal muscle injury triggers an expansion of fibro/adipogenic progenitors (FAPs) and a transient stage of fibrogenesis characterized by extracellular matrix deposition. While the perpetuation of such phase can lead to permanent tissue scarring, the consequences of its suppression remain to be studied. Using a model of acute muscle damage we were able to determine that pharmacological inhibition of FAP expansion by Nilotinib, a tyrosine kinase inhibitor with potent antifibrotic activity, exerts a detrimental effect on myogenesis during regeneration. We found that Nilotinib inhibits the damage-induced expansion of satellite cells in vivo, but it does not affect in vitro proliferation, suggesting a non cell-autonomous effect. Nilotinib impairs regenerative fibrogenesis by preventing the injury-triggered expansion and differentiation of resident CD45(-):CD31(-):α7integrin(-):Sca1(+) mesenchymal FAPs. Our data support the notion that the expansion of FAPs and transient fibrogenesis observed during regeneration play an important trophic role toward tissue-specific stem cells.\",\n \"title\": \"Pharmacological blockage of fibro/adipogenic progenitor expansion and suppression of regenerative fibrogenesis is associated with impaired skeletal muscle regeneration.\"\n },\n {\n \"docid\": \"45015767\",\n \"text\": \"BACKGROUND Adenocarcinoma of the endometrium is the most common gynecologic malignancy in the United States, accounting for approximately 36,000 diagnoses of invasive carcinoma annually. The most common histologic type, endometrioid adenocarcinoma (EC), accounts for 75-80% of patients. The objective of this work was to estimate the prevalence of concurrent carcinoma in women with a biopsy diagnosis of the precursor lesion, atypical endometrial hyperplasia (AEH). METHODS This prospective cohort study included women who had a community diagnosis of AEH. Diagnostic biopsy specimens were reviewed independently by three gynecologic pathologists who used International Society of Gynecologic Pathologists/World Health Organization criteria. Study participants underwent hysterectomy within 12 weeks of entry onto protocol without interval treatment. The hysterectomy slides also were reviewed by the study pathologists, and their findings were used in the subsequent analyses. RESULTS Between November 1998 and June 2003, 306 women were enrolled on the study. Of these, 17 women were not included in the analysis: Two patients had unreadable slides because of poor processing or insufficient tissue, 2 patients had only slides that were not endometrial, the slides for 5 patients were not available for review, and 8 of the hysterectomy specimens were excluded because they showed evidence of interval intervention, either progestin effect or ablation. In total, 289 patients were included in the current analysis. The study panel review of the AEH biopsy specimens was interpreted as follows: 74 of 289 specimens (25.6%) were diagnosed as less than AEH, 115 of 289 specimens (39.8%) were diagnosed as AEH, and 84 of 289 specimens (29.1%) were diagnosed as endometrial carcinoma. In 5.5% (16 of 289 specimens), there was no consensus on the biopsy diagnosis. The rate of concurrent endometrial carcinoma for analyzed specimens was 42.6% (123 of 289 specimens). Of these, 30.9% (38 of 123 specimens) were myoinvasive, and 10.6% (13 of 123 specimens) involved the outer 50% of the myometrium. Among the women who had hysterectomy specimens with carcinoma, 14 of 74 women (18.9%) had a study panel biopsy consensus diagnosis of less than AEH, 45 of 115 women (39.1%) had a study panel biopsy consensus diagnosis of AEH, and 54 of 84 women (64.3%) had a study panel diagnosis of carcinoma. Among women who had no consensus in their biopsy diagnosis, 10 of 16 women (62.5%) had carcinoma in their hysterectomy specimens. CONCLUSIONS The prevalence of endometrial carcinoma in patients who had a community hospital biopsy diagnosis of AEH was high (42.6%). When considering management strategies for women who have a biopsy diagnosis of AEH, clinicians and patients should take into account the considerable rate of concurrent carcinoma.\",\n \"title\": \"Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study.\"\n },\n {\n \"docid\": \"10889845\",\n \"text\": \"Obesity and insulin resistance, the key features of metabolic syndrome, are closely associated with a state of chronic, low-grade inflammation characterized by abnormal macrophage infiltration into adipose tissues. Although it has been reported that chemokines promote leukocyte migration by activating class IB phosphoinositide-3 kinase (PI3Kγ) in inflammatory states, little is known about the role of PI3Kγ in obesity-induced macrophage infiltration into tissues, systemic inflammation, and the development of insulin resistance. In the present study, we used murine models of both diet-induced and genetically induced obesity to examine the role of PI3Kγ in the accumulation of tissue macrophages and the development of obesity-induced insulin resistance. Mice lacking p110γ (Pik3cg(-/-)), the catalytic subunit of PI3Kγ, exhibited improved systemic insulin sensitivity with enhanced insulin signaling in the tissues of obese animals. In adipose tissues and livers of obese Pik3cg(-/-) mice, the numbers of infiltrated proinflammatory macrophages were markedly reduced, leading to suppression of inflammatory reactions in these tissues. Furthermore, bone marrow-specific deletion and pharmacological blockade of PI3Kγ also ameliorated obesity-induced macrophage infiltration and insulin resistance. These data suggest that PI3Kγ plays a crucial role in the development of both obesity-induced inflammation and systemic insulin resistance and that PI3Kγ can be a therapeutic target for type 2 diabetes.\",\n \"title\": \"Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance.\"\n },\n {\n \"docid\": \"15836115\",\n \"text\": \"Mitochondrial morphological and ultrastructural changes occur during apoptosis and autophagy, but whether they are relevant in vivo for tissue response to damage is unclear. Here we investigate the role of the optic atrophy 1 (OPA1)-dependent cristae remodeling pathway in vivo and provide evidence that it regulates the response of multiple tissues to apoptotic, necrotic, and atrophic stimuli. Genetic inhibition of the cristae remodeling pathway in vivo does not affect development, but protects mice from denervation-induced muscular atrophy, ischemic heart and brain damage, as well as hepatocellular apoptosis. Mechanistically, OPA1-dependent mitochondrial cristae stabilization increases mitochondrial respiratory efficiency and blunts mitochondrial dysfunction, cytochrome c release, and reactive oxygen species production. Our results indicate that the OPA1-dependent cristae remodeling pathway is a fundamental, targetable determinant of tissue damage in vivo.\",\n \"title\": \"The Opa1-Dependent Mitochondrial Cristae Remodeling Pathway Controls Atrophic, Apoptotic, and Ischemic Tissue Damage\"\n },\n {\n \"docid\": \"3210545\",\n \"text\": \"BACKGROUND Three quarter of endometrial carcinomas are treated at early stage. Still, 15 to 20% of these patients experience recurrence, with little effect from systemic therapies. Homo sapiens v-Ki-ras2 Kirsten rat sarcoma viral oncogenes homologue (KRAS) mutations have been reported to have an important role in tumorigenesis for human cancers, but there is limited knowledge regarding clinical relevance of KRAS status in endometrial carcinomas. METHODS We have performed a comprehensive and integrated characterisation of genome-wide expression related to KRAS mutations and copy-number alterations in primary- and metastatic endometrial carcinoma lesions in relation to clinical and histopathological data. A primary investigation set and clinical validation set was applied, consisting of 414 primary tumours and 61 metastatic lesions totally. RESULTS Amplification and gain of KRAS present in 3% of the primary lesions and 18% of metastatic lesions correlated significantly with poor outcome, high International Federation of Gynaecology and Obstetrics stage, non-endometrioid subtype, high grade, aneuploidy, receptor loss and high KRAS mRNA levels, also found to be associated with aggressive phenotype. In contrast, KRAS mutations were present in 14.7% of primary lesions with no increase in metastatic lesions, and did not influence outcome, but was significantly associated with endometrioid subtype, low grade and obesity. CONCLUSION These results support that KRAS amplification and KRAS mRNA expression, both increasing from primary to metastatic lesions, are relevant for endometrial carcinoma disease progression.\",\n \"title\": \"KRAS gene amplification and overexpression but not mutation associates with aggressive and metastatic endometrial cancer\"\n },\n {\n \"docid\": \"19485649\",\n \"text\": \"Transmembrane cadherins are calcium-dependent intercellular adhesion molecules. Recently, they have also been shown to be sites of actin assembly during adhesive contact formation. However, the roles of actin assembly on transmembrane cadherins during development are not fully understood. We show here, using the developing ectoderm of the Xenopus embryo as a model, that F-actin assembly is a primary function of both N-cadherin in the neural ectoderm and E-cadherin in the non-neural (epidermal) ectoderm, and that each cadherin is essential for the characteristic morphogenetic movements of these two tissues. However, depletion of N-cadherin and E-cadherin did not cause dissociation in these tissues at the neurula stage, probably owing to the expression of C-cadherin in each tissue. Depletion of each of these cadherins is not rescued by the other, nor by the expression of C-cadherin, which is expressed in both tissues. One possible reason for this is that each cadherin is expressed in a different domain of the cell membrane. These data indicate the combinatorial nature of cadherin function, the fact that N- and E-cadherin play primary roles in F-actin assembly in addition to roles in cell adhesion, and that this function is specific to individual cadherins. They also show how cell adhesion and motility can be combined in morphogenetic tissue movements that generate the form and shape of the embryonic organs.\",\n \"title\": \"N- and E-cadherins in Xenopus are specifically required in the neural and non-neural ectoderm, respectively, for F-actin assembly and morphogenetic movements.\"\n },\n {\n \"docid\": \"29148743\",\n \"text\": \"To determine the relative contributions of endothelial-derived nitric oxide (NO) vs. intravascular nitrogen oxide species in the regulation of human blood flow, we simultaneously measured forearm blood flow and arterial and venous levels of plasma nitrite, LMW-SNOs and HMW-SNOs, and red cell S-nitrosohemoglobin (SNO-Hb). Measurements were made at rest and during regional inhibition of NO synthesis, followed by forearm exercise. Surprisingly, we found significant circulating arterial-venous plasma nitrite gradients, providing a novel delivery source for intravascular NO. Further supporting the notion that circulating nitrite is bioactive, the consumption of nitrite increased significantly with exercise during the inhibition of regional endothelial synthesis of NO. The role of circulating S-nitrosothiols and SNO-Hb in the regulation of basal vascular tone is less certain. We found that low-molecular-weight S-nitrosothiols were undetectable and S-nitroso-albumin levels were two logs lower than previously reported. In fact, S-nitroso-albumin primarily formed in the venous circulation, even during NO synthase inhibition. Whereas SNO-Hb was measurable in the human circulation (brachial artery levels of 170 nM in whole blood), arterial-venous gradients were not significant, and delivery of NO from SNO-Hb was minimal. In conclusion, we present data that suggest (i) circulating nitrite is bioactive and provides a delivery gradient of intravascular NO, (ii) S-nitroso-albumin does not deliver NO from the lungs to the tissue but forms in the peripheral circulation, and (iii) SNO-Hb and S-nitrosothiols play a minimal role in the regulation of basal vascular tone, even during exercise stress.\",\n \"title\": \"Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans.\"\n },\n {\n \"docid\": \"20960682\",\n \"text\": \"BACKGROUND & AIMS GS-9620, an oral agonist of toll-like receptor 7 (TLR7), is in clinical development for the treatment of chronic hepatitis B (CHB). GS-9620 was previously shown to induce prolonged suppression of serum viral DNA and antigens in the woodchuck and chimpanzee models of CHB. Herein, we investigated the molecular mechanisms that contribute to the antiviral response to GS-9620 using in vitro models of hepatitis B virus (HBV) infection. METHODS Cryopreserved primary human hepatocytes (PHH) and differentiated HepaRG (dHepaRG) cells were infected with HBV and treated with GS-9620, conditioned media from human peripheral blood mononuclear cells treated with GS-9620 (GS-9620 conditioned media [GS-9620-CM]), or other innate immune stimuli. The antiviral and transcriptional response to these agents was determined. RESULTS GS-9620 had no antiviral activity in HBV-infected PHH, consistent with low level TLR7 mRNA expression in human hepatocytes. In contrast, GS-9620-CM induced prolonged reduction of HBV DNA, RNA, and antigen levels in PHH and dHepaRG cells via a type I interferon (IFN)-dependent mechanism. GS-9620-CM did not reduce covalently closed circular DNA (cccDNA) levels in either cell type. Transcriptional profiling demonstrated that GS-9620-CM strongly induced various HBV restriction factors - although not APOBEC3A or the Smc5/6 complex - and indicated that established HBV infection does not modulate innate immune sensing or signaling in cryopreserved PHH. GS-9620-CM also induced expression of immunoproteasome subunits and enhanced presentation of an immunodominant viral peptide in HBV-infected PHH. CONCLUSIONS Type I IFN induced by GS-9620 durably suppressed HBV in human hepatocytes without reducing cccDNA levels. Moreover, HBV antigen presentation was enhanced, suggesting additional components of the TLR7-induced immune response played a role in the antiviral response to GS-9620 in animal models of CHB. LAY SUMMARY GS-9620 is a drug currently being tested in clinical trials for the treatment of chronic hepatitis B virus (HBV) infection. GS-9620 has previously been shown to suppress HBV in various animal models, but the underlying antiviral mechanisms were not completely understood. In this study, we determined that GS-9620 does not directly activate antiviral pathways in human liver cells, but can induce prolonged suppression of HBV via induction of an antiviral cytokine called interferon. However, interferon did not destroy the HBV genome, suggesting that other parts of the immune response (e.g. activation of immune cells that kill infected cells) also play an important role in the antiviral response to GS-9620.\",\n \"title\": \"Toll-like receptor 7 agonist GS-9620 induces prolonged inhibition of HBV via a type I interferon-dependent mechanism.\"\n },\n {\n \"docid\": \"18450716\",\n \"text\": \"Adipose tissue dysfunction plays a pivotal role in the development of insulin resistance in obese individuals. Cell culture studies and gain-of-function mouse models suggest that canonical Wnt proteins modulate adipose tissue expansion. However, no genetic evidence supports a role for endogenous Wnt proteins in adipose tissue dysfunction, and the role of noncanonical Wnt signaling remains largely unexplored. Here we provide evidence from human, mouse, and cell culture studies showing that Wnt5a-mediated, noncanonical Wnt signaling contributes to obesity-associated metabolic dysfunction by increasing adipose tissue inflammation. Wnt5a expression is significantly upregulated in human visceral fat compared with subcutaneous fat in obese individuals. In obese mice, Wnt5a ablation ameliorates insulin resistance, in parallel with reductions in adipose tissue inflammation. Conversely, Wnt5a overexpression in myeloid cells augments adipose tissue inflammation and leads to greater impairments in glucose homeostasis. Wnt5a ablation or overexpression did not affect fat mass or adipocyte size. Mechanistically, Wnt5a promotes the expression of proinflammatory cytokines by macrophages in a Jun NH2-terminal kinase-dependent manner, leading to defective insulin signaling in adipocytes. Exogenous interleukin-6 administration restores insulin resistance in obese Wnt5a-deficient mice, suggesting a central role for this cytokine in Wnt5a-mediated metabolic dysfunction. Taken together, these results demonstrate that noncanonical Wnt signaling contributes to obesity-induced insulin resistance independent of adipose tissue expansion.\",\n \"title\": \"Noncanonical Wnt Signaling Promotes Obesity-Induced Adipose Tissue Inflammation and Metabolic Dysfunction Independent of Adipose Tissue Expansion\"\n },\n {\n \"docid\": \"25263942\",\n \"text\": \"Endometrial polyps are very common benign endometrial lesions, but their pathogenesis is poorly understood, except for a few studies indicating the possibility of benign stromal neoplasm. Although the histopathological diagnosis of endometrial polyp on a surgical specimen is straightforward, it is often difficult to differentiate endometrial polyp from endometrial hyperplasia on a biopsy or curettage specimen. Presently, there is no immunohistochemical marker helpful in this differential diagnosis. In this study, we examined p16 expression in 35 endometrial polyps and 33 cases of endometrial hyperplasia that included 16 simple hyperplasias, 14 complex atypical hyperplasias, and 3 complex hyperplasias without atypia. Stromal p16 expression differed significantly between the two groups; it was seen in 31 (89 %) endometrial polyps, but in only 1 (3 %) endometrial hyperplasia. The percentage of p16-positive stromal cells ranged from 10 to 90 % (mean, 47 %) and the positive cells tended to be distributed around glands. Six cases of endometrial hyperplasia within an endometrial polyp were also examined and all cases showed stromal p16 expression. There was no difference in glandular p16 expression between endometrial polyps 33 (94 %) and hyperplasia 27 (82 %). The p16-immunoreactivity was mostly confined to metaplastic epithelial cells in both groups. Stromal p16 expression might be a peculiar characteristic of endometrial polyp and constitute a useful marker for the diagnosis, especially in fragmented specimens from biopsy or curettage. Stromal p16 expression might be a reflection of p16-induced cellular senescence, which has been documented in several benign mesenchymal neoplasms.\",\n \"title\": \"Stromal p16 expression differentiates endometrial polyp from endometrial hyperplasia\"\n },\n {\n \"docid\": \"14116046\",\n \"text\": \"Retinoic acid-related orphan receptors RORα and RORγ play a regulatory role in lipid/glucose homeostasis and various immune functions, and have been implicated in metabolic syndrome and several inflammatory diseases. RORα-deficient mice are protected against age- and diet-induced obesity, hepatosteatosis, and insulin resistance. The resistance to hepatosteatosis in RORα-deficient mice is related to the reduced expression of several genes regulating lipid synthesis, transport, and storage. Adipose tissue-associated inflammation, which plays a critical role in the development of insulin resistance, is considerably diminished in RORα-deficient mice as indicated by the reduced infiltration of M1 macrophages and decreased expression of many proinflammatory genes. Deficiency in RORγ also protects against diet-induced insulin resistance by a mechanism that appears different from that in RORα deficiency. Recent studies indicated that RORs provide an important link between the circadian clock machinery and its regulation of metabolic genes and metabolic syndrome. As ligand-dependent transcription factors, RORs may provide novel therapeutic targets in the management of obesity and associated metabolic diseases, including hepatosteatosis, adipose tissue-associated inflammation, and insulin resistance.\",\n \"title\": \"Retinoic acid-related orphan receptors α and γ: key regulators of lipid/glucose metabolism, inflammation, and insulin sensitivity\"\n },\n {\n \"docid\": \"22705234\",\n \"text\": \"The African green monkey (AGM) is one of many African species endemically infected with simian immunodeficiency virus (SIV). Like the other natural hosts, AGMs do not succumb to AIDS and understanding the basis for this resistance to disease progression would be of enormous theoretical and practical importance. Early efforts by our group that concentrated on identifying immune mechanisms presumed to keep the virus under control failed to find any obvious candidates. The presumption of virus control was invalidated by the finding that SIVagm replicates in AGMs with the same vigor as HIV-1 does in humans. Focus therefore shifted to identifying possible immunopathologic features present in disease susceptible hosts but absent in the AGM natural host. The apparent immunologic tolerance of AGMs to the SIVagm core protein led to the development of a hypothesis implicating anti-Gag antibodies in the formation of immune complexes, virus trapping in the lymph nodes and immune dysfunction. The idea proved difficult to test in vivo and present work focuses on the possibility that Gag tolerance at the T-cell level plays an important role in preventing the catastrophic demise of the immune system characteristic of immunodeficiency virus infection of the heterologous primate host.\",\n \"title\": \"The role of the immune response during SIVagm infection of the African green monkey natural host.\"\n },\n {\n \"docid\": \"8538916\",\n \"text\": \"The molecular chaperone CCT/TRiC plays a central role in maintaining cellular proteostasis as it mediates the folding of the major cytoskeletal proteins tubulins and actins. CCT/TRiC is also involved in the oncoprotein cyclin E, the Von Hippel-Lindau tumour suppressor protein, cyclin B and p21(ras) folding which strongly suggests that it is involved in cell proliferation and tumor genesis. To assess the involvement of CCT/TRiC in tumor genesis, we quantified its expression levels and activity in 18 cancer, one non-cancer human cell lines and a non-cancer human liver. We show that the expression levels of CCT/TRiC in cancer cell lines are higher than that in normal cells. However, CCT/TRiC activity does not always correlate with its expression levels. We therefore documented the expression levels of CCT/TRiC modulators and partners PhLP3, Hop/P60, prefoldin and Hsc/Hsp70. Our analysis reveals a functional interplay between molecular chaperones that might account for a precise modulation of CCT/TRiC activity in cell proliferation through changes in the cellular levels of prefoldin and/or Hsc/p70 and CCT/TRiC client protein availability. Our observation and approaches bring novel insights in the role of CCT/TRiC-mediated protein folding machinery in cancer cell development.\",\n \"title\": \"The Cytosolic Chaperonin CCT/TRiC and Cancer Cell Proliferation\"\n },\n {\n \"docid\": \"16346504\",\n \"text\": \"BACKGROUND Growth arrest-specific 5 (GAS5) was reported to be implicated and aberrantly express in multiple cancers. However, the expression and mechanism of action of GAS5 were largely poor understood in endometrial carcinoma. RESULTS According to the result of real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and flow cytometry analysis, we identified that GAS5 was down-regulated in endometrial cancer cells and stimulated the apoptosis of endometrial cancer cells. To investigate the expression of GAS5, PTEN and miR-103, RT-PCR was performed. And we found that the expression of PTEN was up-regulated when endometrial cancer cells overexpressed GAS5. The prediction of bioinformatics online revealed that GAS5 could bind to miR-103, which was further found to be regulated by GAS5. Finally, we found that miR-103 mimic could decrease the mRNA and protein levels of PTEN through luciferase reporter assay and western blotting, and GAS5 plasmid may reverse this regulation effect in endometrial cancer cells. CONCLUSION In summary, we demonstrate that GAS5 acts as an tumor suppressor lncRNA in endometrial cancer. Through inhibiting the expression of miR-103, GAS5 significantly enhanced the expression of PTEN to promote cancer cell apoptosis, and, thus, could be an important mediator in the pathogenesis of endometrial cancer.\",\n \"title\": \"LncRNA-GAS5 induces PTEN expression through inhibiting miR-103 in endometrial cancer cells\"\n },\n {\n \"docid\": \"20456030\",\n \"text\": \"Mitochondria play a pivotal role in energy metabolism, programmed cell death and oxidative stress. Mutated mitochondrial DNA in diseased cells compromises the structure of key enzyme complexes and, therefore, mitochondrial function, which leads to a myriad of health-related conditions such as cancer, neurodegenerative diseases, diabetes and aging. Early detection of mitochondrial and metabolic anomalies is an essential step towards effective diagnoses and therapeutic intervention. Reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) play important roles in a wide range of cellular oxidation-reduction reactions. Importantly, NADH and FAD are naturally fluorescent, which allows noninvasive imaging of metabolic activities of living cells and tissues. Furthermore, NADH and FAD autofluorescence, which can be excited using distinct wavelengths for complementary imaging methods and is sensitive to protein binding and local environment. This article highlights recent developments concerning intracellular NADH and FAD as potential biomarkers for metabolic and mitochondrial activities.\",\n \"title\": \"Intracellular coenzymes as natural biomarkers for metabolic activities and mitochondrial anomalies.\"\n },\n {\n \"docid\": \"23577867\",\n \"text\": \"Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer.\",\n \"title\": \"Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer.\"\n },\n {\n \"docid\": \"1386103\",\n \"text\": \"Tuberculosis, a major health problem in developing countries, has reemerged in recent years in many industrialized countries. The increased susceptibility of immunocompromised individuals to tuberculosis, and many experimental studies indicate that T cell-mediated immunity plays an important role in resistance. The lymphokine interferon gamma (IFN-gamma) is thought to be a principal mediator of macrophage activation and resistance to intracellular pathogens. Mice have been developed which fail to produce IFN-gamma (gko), because of a targeted disruption of the gene for IFN-gamma. Upon infection with Mycobacterium tuberculosis, although they develop granulomas, gko mice fail to produce reactive nitrogen intermediates and are unable to restrict the growth of the bacilli. In contrast to control mice, gko mice exhibit heightened tissue necrosis and succumb to a rapid and fatal course of tuberculosis that could be delayed, but not prevented, by treatment with exogenous recombinant IFN-gamma.\",\n \"title\": \"An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection\"\n },\n {\n \"docid\": \"9239963\",\n \"text\": \"Excessive exposure to estradiol represents the main risk factor for endometrial cancer. The abnormally high estradiol levels in the endometrium of women with endometrial cancer are most likely due to overproduction by the tumour itself. Endometrial cancer cells express the genes encoding the steroidogenic enzymes involved in estradiol synthesis. Here we used RT-PCR and Western blot to show that the nuclear receptors SF1 and LRH1, two well-known regulators of steroidogenic gene expression in gonadal and adrenal cells, are also expressed in endometrial cancer cell lines. By transient transfections, we found that SF1 and LRH1, but not the related nuclear receptor NUR77, can activate the promoters of three human steroidogenic genes: STAR, HSD3B2, and CYP19A1 PII. Similarly, forskolin but not PMA, could activate all three promoters. In addition, we found that both SF1 and LRH1 can transcriptionally cooperate with the AP-1 family members c-JUN and c-FOS, known to be associated with enhanced proliferation of endometrial carcinoma cells, to further enhance activation of the STAR, HSD3B2, and CYP19A1 PII promoters. All together, our data provide novel insights into the mechanisms of steroidogenic gene expression in endometrial cancer cells and thus in the regulation of estradiol biosynthesis by tumour cells.\",\n \"title\": \"The nuclear receptors SF1 and LRH1 are expressed in endometrial cancer cells and regulate steroidogenic gene transcription by cooperating with AP-1 factors.\"\n },\n {\n \"docid\": \"1428840\",\n \"text\": \"BACKGROUND It has been suggested that identified risk factors for endometrial cancer operate through a single etiologic pathway, i.e., exposure to relatively high levels of unopposed estrogen (estrogen in the absence of progestins). Only a few studies, however, have addressed this issue directly. PURPOSE We assessed the risk of developing endometrial cancer among both premenopausal and postmenopausal women in relation to the circulating levels of steroid hormones and sex hormone-binding globulin (SHBG). The independent effect of hormones was assessed after adjustment for other known risk factors. METHODS The data used in the analysis are from a case-control study conducted in five geographic regions in the United States. Incident cases were newly diagnosed during the period from June 1, 1987, through May 15, 1990. The case patients, aged 20-74 years, were matched to control subjects by age, race, and geographic region. The community control subjects were obtained by random-digit-dialing procedures (for subjects 20-64 years old) and from files of the Health Care Financing Administration (for subjects > or = 65 years old). Additional control subjects who were having a hysterectomy performed for benign conditions were obtained from the participating centers. Women reporting use of exogenous estrogens or oral contraceptives within 6 months of interview were excluded, resulting in 68 case patients and 107 control subjects among premenopausal women and 208 case patients and 209 control subjects among postmenopausal women. The hormone analyses were performed on blood samples obtained from case patients or from hysterectomy control subjects before surgery. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of an unconditional logistic regression analysis after we controlled for matching variables and potential confounders. All P values were two-sided. RESULTS High circulating levels of androstenedione were associated with 3.6-fold and 2.8-fold increased risks among premenopausal and postmenopausal women, respectively, after adjustment for other factors (P for trend = .01 and < .001, respectively). Risks related to other hormone fractions varied by menopausal status. Among postmenopausal women, a reduced risk was associated with high SHBG levels and persisted after adjustment was made for obesity and other factors (OR = 0.51; 95% CI = 0.27-0.95). High estrone levels were associated with increased risk (OR = 3.8; 95% CI = 2.2-6.6), although adjustment for other risk factors (particularly body mass index) diminished the effect (OR = 2.2; 95% CI = 1.2-4.4). Albumin-bound estradiol (E2), a marker of the bioavailable fraction, also remained an important risk factor after adjustment was made for other factors (OR = 2.0; 95% CI = 1.0-3.9). In contrast, high concentrations of total, free, and albumin-bound E2 were unrelated to increased risk in premenopausal women. In both premenopausal and postmenopausal groups, risks associated with obesity and fat distribution were not affected by adjustment for hormones. CONCLUSION High endogenous levels of unopposed estrogen are related to increased risk of endometrial cancer, but their independence from other risk factors is inconsistent with being a common underlying biologic pathway through which all risk factors for endometrial cancer operate. IMPLICATIONS Further research should focus on alternative endocrinologic mechanisms for risk associated with obesity and body fat distribution and for the biologic relevance of the increased risk associated with androstenedione in both premenopausal and postmenopausal disease.\",\n \"title\": \"Case-control study of endogenous steroid hormones and endometrial cancer.\"\n },\n {\n \"docid\": \"3952288\",\n \"text\": \"Aire-expressing medullary thymic epithelial cells (mTECs) play a key role in preventing autoimmunity by expressing tissue-restricted antigens to help purge the emerging T cell receptor repertoire of self-reactive specificities. Here we demonstrate a novel role for a CD4+3− inducer cell population, previously linked to development of organized secondary lymphoid structures and maintenance of T cell memory in the functional regulation of Aire-mediated promiscuous gene expression in the thymus. CD4+3− cells are closely associated with mTECs in adult thymus, and in fetal thymus their appearance is temporally linked with the appearance of Aire+ mTECs. We show that RANKL signals from this cell promote the maturation of RANK-expressing CD80−Aire− mTEC progenitors into CD80+Aire+ mTECs, and that transplantation of RANK-deficient thymic stroma into immunodeficient hosts induces autoimmunity. Collectively, our data reveal cellular and molecular mechanisms leading to the generation of Aire+ mTECs and highlight a previously unrecognized role for CD4+3−RANKL+ inducer cells in intrathymic self-tolerance.\",\n \"title\": \"RANK signals from CD4+3− inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla\"\n },\n {\n \"docid\": \"39559521\",\n \"text\": \"The negative selection of self-reactive thymocytes depends on the expression of tissue-specific antigens by medullary thymic epithelial cells. The autoimmune regulator (Aire) protein plays an important role in turning on these antigens, and the absence of even one Aire-induced tissue-specific antigen in the thymus can lead to autoimmunity in the antigen-expressing target organ. Recently, Aire protein has been detected in peripheral lymphoid organs, suggesting that peripheral Aire plays a complementary role here. In these peripheral sites, Aire was found to regulate the expression of a group of tissue-specific antigens that is distinct from those expressed in the thymus. Furthermore, transgenic antigen expression in extrathymic Aire-expressing cells (eTACs) can mediate deletional tolerance, but the immunological relevance of Aire-dependent, endogenous tissue-specific antigens remains to be determined.\",\n \"title\": \"Control of central and peripheral tolerance by Aire.\"\n },\n {\n \"docid\": \"19332616\",\n \"text\": \"Coronary atherosclerosis is by far the most frequent cause of ischemic heart disease, and plaque disruption with superimposed thrombosis is the main cause of the acute coronary syndromes of unstable angina, myocardial infarction, and sudden death.1 2 3 4 5 Therefore, for event-free survival, the vital question is not why atherosclerosis develops but rather why, after years of indolent growth, it suddenly becomes complicated by life-threatening thrombosis. The composition and vulnerability of plaque rather than its volume or the consequent severity of stenosis produced have emerged as being the most important determinants for the development of the thrombus-mediated acute coronary syndromes; lipid-rich and soft plaques are more dangerous than collagen-rich and hard plaques because they are more unstable and rupture-prone and highly thrombogenic after disruption.6 This review will explore potential mechanisms responsible for the sudden conversion of a stable atherosclerotic plaque to an unstable and life-threatening atherothrombotic lesion—an event known as plaque fissuring, rupture, or disruption.7 8 Atherosclerosis is the result of a complex interaction between blood elements, disturbed flow, and vessel wall abnormality, involving several pathological processes: inflammation, with increased endothelial permeability, endothelial activation, and monocyte recruitment9 10 11 12 13 14 ; growth, with smooth muscle cell (SMC) proliferation, migration, and matrix synthesis15 16 ; degeneration, with lipid accumulation17 18 ; necrosis, possibly related to the cytotoxic effect of oxidized lipid19 ; calcification/ossification, which may represent an active rather than a dystrophic process20 21 ; and thrombosis, with platelet recruitment and fibrin formation.1 22 23 Thrombotic factors may play a role early during atherogenesis, but a flow-limiting thrombus does not develop until mature plaques are present, which is why thrombosis often is classified as a complication rather than a genuine component of atherosclerosis. ### Mature Plaques: Atherosis and Sclerosis As the name atherosclerosis implies, mature …\",\n \"title\": \"Coronary plaque disruption.\"\n },\n {\n \"docid\": \"2389574\",\n \"text\": \"PURPOSE Overexpression of the oncogen Stathmin has been linked to aggressive endometrial carcinoma and a potential for PI3Kinase inhibitors in this disease. We wanted to validate the prognostic value of Stathmin expression in a large prospective multicenter setting. As lymph node sampling is part of current surgical staging, we also aimed to test if Stathmin expression in endometrial curettage specimens could predict lymph node metastasis. EXPERIMENTAL DESIGN A total of 1,076 endometrial cancer patients have been recruited from 10 centers to investigate the biological tumor marker Stathmin in relation to clinicopathologic variables, including lymph node status and survival. Stathmin immunohistochemical staining was carried out in 477 hysterectomy and 818 curettage specimens. RESULTS Seventy-one percent of the patients (n = 763) were subjected to lymph node sampling, of which 12% had metastatic nodes (n = 94). Overexpression of Stathmin was detected in 37% (302 of 818) of the curettage and in 18% (84 of 477) of the hysterectomy specimens investigated. Stathmin overexpression in curettage and hysterectomy specimens were highly correlated and significantly associated with nonendometrioid histology, high grade, and aneuploidy. Stathmin analysis in preoperative curettage samples significantly correlated with, and was an independent predictor of, lymph node metastases. High Stathmin expression was associated with poor disease-specific survival (P ≤ 0.002) both in curettage and hysterectomy specimens. CONCLUSIONS Stathmin immunohistochemical staining identifies endometrial carcinomas with lymph node metastases and poor survival. The value, as a predictive marker for response to PI3Kinase inhibition and as a tool to stratify patients for lymph node sampling in endometrial carcinomas, remains to be determined.\",\n \"title\": \"Stathmin overexpression identifies high-risk patients and lymph node metastasis in endometrial cancer.\"\n },\n {\n \"docid\": \"16839245\",\n \"text\": \"The basic biology of the cell division cycle and its control by protein kinases was originally studied through genetic and biochemical studies in yeast and other model organisms. The major regulatory mechanisms identified in this pioneer work are conserved in mammals. However, recent studies in different cell types or genetic models are now providing a new perspective on the function of these major cell cycle regulators in different tissues. Here, we review the physiological relevance of mammalian cell cycle kinases such as cyclin-dependent kinases (Cdks), Aurora and Polo-like kinases, and mitotic checkpoint regulators (Bub1, BubR1, and Mps1) as well as other less-studied enzymes such as Cdc7, Nek proteins, or Mastl and their implications in development, tissue homeostasis, and human disease. Among these functions, the control of self-renewal or asymmetric cell division in stem/progenitor cells and the ability to regenerate injured tissues is a central issue in current research. In addition, many of these proteins play previously unexpected roles in metabolism, cardiovascular function, or neuron biology. The modulation of their enzymatic activity may therefore have multiple therapeutic benefits in human disease.\",\n \"title\": \"Physiological relevance of cell cycle kinases.\"\n },\n {\n \"docid\": \"9550981\",\n \"text\": \"The adult Drosophila hindgut was recently reported to contain active, tissue-replenishing stem cells, like those of the midgut, but located within an anterior ring so as to comprise a single giant crypt. In contrast to this view, we observed no active stem cells and little cell turnover in adult hindgut tissue based on clonal marking and BrdU incorporation studies. Again contradicting the previous proposal, we showed that the adult hindgut is not generated by anterior stem cells during larval/pupal development. However, severe tissue damage within the hindgut elicits cell proliferation within a ring of putative quiescent stem cells at the anterior of the pylorus. Thus, the hindgut does not provide a model of tissue maintenance by constitutively active stem cells, but has great potential to illuminate mechanisms of stress-induced tissue repair.\",\n \"title\": \"The Drosophila hindgut lacks constitutively active adult stem cells but proliferates in response to tissue damage.\"\n },\n {\n \"docid\": \"3514072\",\n \"text\": \"Gene expression is controlled by the complex interaction of transcription factors binding to promoters and other regulatory DNA elements. One common characteristic of the genomic regions associated with regulatory proteins is a pronounced sensitivity to DNase I digestion. We generated genome-wide high-resolution maps of DNase I hypersensitive (DH) sites from both seedling and callus tissues of rice (Oryza sativa). Approximately 25% of the DH sites from both tissues were found in putative promoters, indicating that the vast majority of the gene regulatory elements in rice are not located in promoter regions. We found 58% more DH sites in the callus than in the seedling. For DH sites detected in both the seedling and callus, 31% displayed significantly different levels of DNase I sensitivity within the two tissues. Genes that are differentially expressed in the seedling and callus were frequently associated with DH sites in both tissues. The DNA sequences contained within the DH sites were hypomethylated, consistent with what is known about active gene regulatory elements. Interestingly, tissue-specific DH sites located in the promoters showed a higher level of DNA methylation than the average DNA methylation level of all the DH sites located in the promoters. A distinct elevation of H3K27me3 was associated with intergenic DH sites. These results suggest that epigenetic modifications play a role in the dynamic changes of the numbers and DNase I sensitivity of DH sites during development.\",\n \"title\": \"High-resolution mapping of open chromatin in the rice genome.\"\n }\n]"}}},{"rowIdx":2590,"cells":{"query_id":{"kind":"string","value":"1119"},"query":{"kind":"string","value":"Sympathetic nerve activity is elevated throughout normal pregnancy."},"positive_passages":{"kind":"list like","value":[{"docid":"13907928","text":"Baseline neurovascular transduction is reduced in normotensive pregnancy; however, little is known about changes to neurovascular transduction during periods of heightened sympathetic activation. We tested the hypothesis that, despite an exacerbated muscle sympathetic nerve activity (microneurography) response to cold pressor stimulation, the blunting of neurovascular transduction in normotensive pregnant women would result in similar changes in vascular resistance and mean arterial pressure (Finometer) relative to nonpregnant controls. Baseline neurovascular transduction was reduced in pregnant women relative to controls when expressed as the quotient of both total resistance and mean arterial pressure and sympathetic burst frequency (0.32±0.07 versus 0.58±0.16 mm Hg/L/min/bursts/min, P<0.001 and 2.4±0.7 versus 3.6±0.8 mm Hg/bursts/min, P=0.001). Sympathetic activation was greater across all 3 minutes of cold pressor stimulation in the pregnant women relative to the nonpregnant controls. Peak sympathoexcitation was also greater in pregnant than in nonpregnant women, whether expressed as sympathetic burst frequency (+17±13 versus +7±8 bursts/min, P=0.049), burst incidence (+17±9 versus +6±11 bursts/100 hb, P=0.03), or total activity (+950±660 versus +363±414 arbitrary units, P=0.04). However, neurovascular transduction during peak cold pressor-induced sympathoexcitation remained blunted in pregnant women (0.25±0.11 versus 0.45±0.08 mm Hg/L/min/bursts/min, P<0.001 and 1.9±1.0 versus 3.2±0.9 mm Hg/bursts/min, P=0.006). Therefore, mean arterial pressure (93±21 versus 99±6 mm Hg, P=0.4) and total peripheral resistance (12±3 versus 14±3 mm Hg/L/min) were not different between pregnant and nonpregnant women during peak sympathoexcitation. These data indicate that the third trimester of normotensive pregnancy is associated with reductions in neurovascular transduction, which result in the dissociation of sympathetic outflow from hemodynamic outcomes, even during cold pressor-induced sympathoexcitation.","title":"Regulation of sympathetic nerve activity during the cold pressor test in normotensive pregnant and nonpregnant women."},{"docid":"5323845","text":"BACKGROUND Direct recordings from peripheral sympathetic nerves have shown an increased sympathetic drive in pregnancy-induced hypertension (PIH) and preeclampsia (PE). It is unknown whether sympathetic drive is altered in normal pregnancy, when arterial blood pressure can be normal or relatively low. The aim of this study was to measure and compare peripheral sympathetic discharge, its vasoconstrictor effect and its baroreceptor control, during pregnancy and postpartum in women with normal pregnancy (NP) and PIH and in normotensive nonpregnant (NN) women. METHODS AND RESULTS Twenty-one women with NP, 18 women with PIH, and 21 NN women had muscle sympathetic nerve activity assessed from multiunit discharges (MSNA) and from single units with defined vasoconstrictor properties (s-MSNA). The s-MSNA in NP (38+/-6.6 impulses/100 beats) was greater (P<0.05) than in NN women (19+/-1.8 impulses/100 beats) despite similar age and body weight but less than in PIH women (P<0.001) (146+/-23.5 impulses/100 beats). MSNA followed a similar trend. Cardiac baroreceptor reflex sensitivity (BRS) was impaired in NP and PIH women relative to NN. After delivery, sympathetic activity decreased to values similar to those obtained in NN, and there was an increase in BRS. In women with NP, the decrease in sympathetic output occurred despite an insignificant change in blood pressure. CONCLUSIONS Central sympathetic output was increased in women with normal pregnancy and was even greater in the hypertensive pregnant group. The findings suggest that the moderate sympathetic hyperactivity during the latter months of normal pregnancy may help to return the arterial pressure to nonpregnant levels, although when the increase in activity is excessive, hypertension may ensue.","title":"Sympathetic neural mechanisms in normal and hypertensive pregnancy in humans."},{"docid":"18997216","text":"Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting. We hypothesized spontaneous sympathetic baroreflex gain would be reduced in normotensive pregnant women relative to nonpregnant matched controls. Integrated muscle sympathetic burst incidence and total sympathetic activity (microneurography), blood pressure (Finometer), and R-R interval (ECG) were assessed at rest in 11 pregnant women (33 ± 1 wk gestation, 31 ± 1 yr, prepregnancy BMI: 23.5 ± 0.9 kg/m(2)) and 11 nonpregnant controls (29 ± 1 yr; BMI: 25.2 ± 1.7 kg/m(2)). Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P < 0.01) relative to controls. Both mean (88 ± 3 vs. 91 ± 2 mmHg, P = 0.4) and diastolic (DBP) (72 ± 3 vs. 73 ± 2 mmHg, P = 0.7) pressures were similar between pregnant and nonpregnant women, respectively, indicating an upward resetting of the baroreflex set point with pregnancy. Baroreflex gain, calculated as the linear relationship between sympathetic burst incidence and DBP, was reduced in pregnant women relative to controls (-3.7 ± 0.5 vs. -5.4 ± 0.5 bursts·100 heart beats(-1)·mmHg(-1), P = 0.03), as was baroreflex gain calculated with total sympathetic activity (-294 ± 24 vs. -210 ± 24 au·100 heart beats(-1)·mmHg(-1); P = 0.03). Cardiovagal baroreflex gain (sequence method) was not different between nonpregnant controls and pregnant women (49 ± 8 vs. 36 ± 8 ms/mmHg; P = 0.2). However, sympathetic (burst incidence) and cardiovagal gains were negatively correlated in pregnant women (R = -0.7; P = 0.02). Together, these data indicate that the influence of the sympathetic nervous system over arterial blood pressure is reduced in normotensive pregnancy, in terms of both long-term and beat-to-beat regulation of arterial pressure, likely through a baroreceptor-dependent mechanism.","title":"Sympathetic baroreflex gain in normotensive pregnant women."}],"string":"[\n {\n \"docid\": \"13907928\",\n \"text\": \"Baseline neurovascular transduction is reduced in normotensive pregnancy; however, little is known about changes to neurovascular transduction during periods of heightened sympathetic activation. We tested the hypothesis that, despite an exacerbated muscle sympathetic nerve activity (microneurography) response to cold pressor stimulation, the blunting of neurovascular transduction in normotensive pregnant women would result in similar changes in vascular resistance and mean arterial pressure (Finometer) relative to nonpregnant controls. Baseline neurovascular transduction was reduced in pregnant women relative to controls when expressed as the quotient of both total resistance and mean arterial pressure and sympathetic burst frequency (0.32±0.07 versus 0.58±0.16 mm Hg/L/min/bursts/min, P<0.001 and 2.4±0.7 versus 3.6±0.8 mm Hg/bursts/min, P=0.001). Sympathetic activation was greater across all 3 minutes of cold pressor stimulation in the pregnant women relative to the nonpregnant controls. Peak sympathoexcitation was also greater in pregnant than in nonpregnant women, whether expressed as sympathetic burst frequency (+17±13 versus +7±8 bursts/min, P=0.049), burst incidence (+17±9 versus +6±11 bursts/100 hb, P=0.03), or total activity (+950±660 versus +363±414 arbitrary units, P=0.04). However, neurovascular transduction during peak cold pressor-induced sympathoexcitation remained blunted in pregnant women (0.25±0.11 versus 0.45±0.08 mm Hg/L/min/bursts/min, P<0.001 and 1.9±1.0 versus 3.2±0.9 mm Hg/bursts/min, P=0.006). Therefore, mean arterial pressure (93±21 versus 99±6 mm Hg, P=0.4) and total peripheral resistance (12±3 versus 14±3 mm Hg/L/min) were not different between pregnant and nonpregnant women during peak sympathoexcitation. These data indicate that the third trimester of normotensive pregnancy is associated with reductions in neurovascular transduction, which result in the dissociation of sympathetic outflow from hemodynamic outcomes, even during cold pressor-induced sympathoexcitation.\",\n \"title\": \"Regulation of sympathetic nerve activity during the cold pressor test in normotensive pregnant and nonpregnant women.\"\n },\n {\n \"docid\": \"5323845\",\n \"text\": \"BACKGROUND Direct recordings from peripheral sympathetic nerves have shown an increased sympathetic drive in pregnancy-induced hypertension (PIH) and preeclampsia (PE). It is unknown whether sympathetic drive is altered in normal pregnancy, when arterial blood pressure can be normal or relatively low. The aim of this study was to measure and compare peripheral sympathetic discharge, its vasoconstrictor effect and its baroreceptor control, during pregnancy and postpartum in women with normal pregnancy (NP) and PIH and in normotensive nonpregnant (NN) women. METHODS AND RESULTS Twenty-one women with NP, 18 women with PIH, and 21 NN women had muscle sympathetic nerve activity assessed from multiunit discharges (MSNA) and from single units with defined vasoconstrictor properties (s-MSNA). The s-MSNA in NP (38+/-6.6 impulses/100 beats) was greater (P<0.05) than in NN women (19+/-1.8 impulses/100 beats) despite similar age and body weight but less than in PIH women (P<0.001) (146+/-23.5 impulses/100 beats). MSNA followed a similar trend. Cardiac baroreceptor reflex sensitivity (BRS) was impaired in NP and PIH women relative to NN. After delivery, sympathetic activity decreased to values similar to those obtained in NN, and there was an increase in BRS. In women with NP, the decrease in sympathetic output occurred despite an insignificant change in blood pressure. CONCLUSIONS Central sympathetic output was increased in women with normal pregnancy and was even greater in the hypertensive pregnant group. The findings suggest that the moderate sympathetic hyperactivity during the latter months of normal pregnancy may help to return the arterial pressure to nonpregnant levels, although when the increase in activity is excessive, hypertension may ensue.\",\n \"title\": \"Sympathetic neural mechanisms in normal and hypertensive pregnancy in humans.\"\n },\n {\n \"docid\": \"18997216\",\n \"text\": \"Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting. We hypothesized spontaneous sympathetic baroreflex gain would be reduced in normotensive pregnant women relative to nonpregnant matched controls. Integrated muscle sympathetic burst incidence and total sympathetic activity (microneurography), blood pressure (Finometer), and R-R interval (ECG) were assessed at rest in 11 pregnant women (33 ± 1 wk gestation, 31 ± 1 yr, prepregnancy BMI: 23.5 ± 0.9 kg/m(2)) and 11 nonpregnant controls (29 ± 1 yr; BMI: 25.2 ± 1.7 kg/m(2)). Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P < 0.01) relative to controls. Both mean (88 ± 3 vs. 91 ± 2 mmHg, P = 0.4) and diastolic (DBP) (72 ± 3 vs. 73 ± 2 mmHg, P = 0.7) pressures were similar between pregnant and nonpregnant women, respectively, indicating an upward resetting of the baroreflex set point with pregnancy. Baroreflex gain, calculated as the linear relationship between sympathetic burst incidence and DBP, was reduced in pregnant women relative to controls (-3.7 ± 0.5 vs. -5.4 ± 0.5 bursts·100 heart beats(-1)·mmHg(-1), P = 0.03), as was baroreflex gain calculated with total sympathetic activity (-294 ± 24 vs. -210 ± 24 au·100 heart beats(-1)·mmHg(-1); P = 0.03). Cardiovagal baroreflex gain (sequence method) was not different between nonpregnant controls and pregnant women (49 ± 8 vs. 36 ± 8 ms/mmHg; P = 0.2). However, sympathetic (burst incidence) and cardiovagal gains were negatively correlated in pregnant women (R = -0.7; P = 0.02). Together, these data indicate that the influence of the sympathetic nervous system over arterial blood pressure is reduced in normotensive pregnancy, in terms of both long-term and beat-to-beat regulation of arterial pressure, likely through a baroreceptor-dependent mechanism.\",\n \"title\": \"Sympathetic baroreflex gain in normotensive pregnant women.\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"26710772","text":"Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min(-1), 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min(-1); main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm(-5); P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.(-1) min(-1); P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml(-1), P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml(-1), P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications.","title":"Sympathetic activation during early pregnancy in humans."},{"docid":"8596837","text":"Women with a history of hypertensive pregnancy are at greater risk for future cardiovascular events; however, the mechanisms for this increased risk are unknown. Evidence suggests that an exercise stimulus unmasks latent hypertensive tendencies, identifying individuals at the greatest risk for developing cardiovascular disease. The current study examined the hypothesis that women with a hypertensive pregnancy history exhibit an augmented exercise pressor response. Normotensive women with a history of healthy pregnancy (CON; n = 9) and hypertensive pregnancy (HP+; n = 12) were studied during the mid-luteal phase of the menstrual cycle. Heart rate (HR), systolic and diastolic blood pressure (SBP, DBP), and muscle sympathetic nerve activity (MSNA) were measured during a cold pressor test (CPT), and, following a sufficient period of recovery, during static handgrip to fatigue (SHG) and post-exercise circulatory arrest (PECA). The BP, HR, and MSNA responses to the CPT were similar between groups. The SBP response to SHG and PECA was similar between groups, but DBP and HR were significantly greater in HP+ women (both p < 0.05). MSNA burst frequency, but not burst incidence or total activity, tended to be elevated in HP+ women during the stressor (peak Δ from baseline 31 ± 13 vs. 23 ± 13 bursts/min; p for group = 0.06). Despite no clinical signs of cardiovascular disease or hypertension, women with a history of hypertensive pregnancy display an enhanced cardiovascular reactivity to an exercise stimulus compared to women with a healthy pregnancy history. This response may be indicative of impaired cardiovascular control that precedes the clinical manifestation of hypertension or cardiovascular events.","title":"Sympathetic neural and cardiovascular responses during static handgrip exercise in women with a history of hypertensive pregnancy"},{"docid":"58006489","text":"Whether sensory nerve can sense bone density or metabolic activity to control bone homeostasis is unknown. Here we found prostaglandin E2 (PGE2) secreted by osteoblastic cells activates PGE2 receptor 4 (EP4) in sensory nerves to regulate bone formation by inhibiting sympathetic activity through the central nervous system. PGE2 secreted by osteoblasts increases when bone density decreases as demonstrated in osteoporotic animal models. Ablation of sensory nerves erodes the skeletal integrity. Specifically, knockout of the EP4 gene in the sensory nerves or cyclooxygenase-2 (COX2) in the osteoblastic cells significantly reduces bone volume in adult mice. Sympathetic tone is increased in sensory denervation models, and propranolol, a β2-adrenergic antagonist, rescues bone loss. Furthermore, injection of SW033291, a small molecule to increase PGE2 level locally, significantly boostes bone formation, whereas the effect is obstructed in EP4 knockout mice. Thus, we show that PGE2 mediates sensory nerve to control bone homeostasis and promote regeneration.","title":"Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis"},{"docid":"5107861","text":"Exposure to psychosocial stress is a risk factor for many diseases, including atherosclerosis. Although incompletely understood, interaction between the psyche and the immune system provides one potential mechanism linking stress and disease inception and progression. Known cross-talk between the brain and immune system includes the hypothalamic-pituitary-adrenal axis, which centrally drives glucocorticoid production in the adrenal cortex, and the sympathetic-adrenal-medullary axis, which controls stress-induced catecholamine release in support of the fight-or-flight reflex. It remains unknown, however, whether chronic stress changes hematopoietic stem cell activity. Here we show that stress increases proliferation of these most primitive hematopoietic progenitors, giving rise to higher levels of disease-promoting inflammatory leukocytes. We found that chronic stress induced monocytosis and neutrophilia in humans. While investigating the source of leukocytosis in mice, we discovered that stress activates upstream hematopoietic stem cells. Under conditions of chronic variable stress in mice, sympathetic nerve fibers released surplus noradrenaline, which signaled bone marrow niche cells to decrease CXCL12 levels through the β3-adrenergic receptor. Consequently, hematopoietic stem cell proliferation was elevated, leading to an increased output of neutrophils and inflammatory monocytes. When atherosclerosis-prone Apoe(-/-) mice were subjected to chronic stress, accelerated hematopoiesis promoted plaque features associated with vulnerable lesions that cause myocardial infarction and stroke in humans.","title":"Chronic variable stress activates hematopoietic stem cells"},{"docid":"9197786","text":"Nerve growth factor (NGF) is a potent survival and axon growth factor for neuronal populations in the peripheral nervous system. Although the mechanisms by which target-derived NGF influences survival of innervating neurons have been extensively investigated, its regulation of axonal growth and target innervation are just being elucidated. Here, we identify Wnt5a, a member of the Wnt family of secreted growth factors, as a key downstream effector of NGF in mediating axonal branching and growth in developing sympathetic neurons. Wnt5a is robustly expressed in sympathetic neurons when their axons are innervating NGF-expressing targets. NGF:TrkA signaling enhances neuronal expression of Wnt5a. Wnt5a rapidly induces axon branching while it has a long-term effect on promoting axon extension. Loss of Wnt5a function revealed that it is necessary for NGF-dependent axonal branching and growth, but not survival, in vitro. Furthermore, Wnt5a(-/-) mice display reduced innervation of NGF-expressing target tissues, and a subsequent increase in neuronal apoptosis, in vivo. Wnt5a functions in developing sympathetic neurons by locally activating protein kinase C in axons. Together, our findings define a novel regulatory pathway in which Wnt5a, expressed in sympathetic neurons in response to target-derived NGF, regulates innervation of peripheral targets.","title":"Wnt5a mediates nerve growth factor-dependent axonal branching and growth in developing sympathetic neurons."},{"docid":"1701063","text":"Semaphorin 3A (Sema3A) is a diffusible axonal chemorepellent that has an important role in axon guidance. Previous studies have demonstrated that Sema3a−/− mice have multiple developmental defects due to abnormal neuronal innervations. Here we show in mice that Sema3A is abundantly expressed in bone, and cell-based assays showed that Sema3A affected osteoblast differentiation in a cell-autonomous fashion. Accordingly, Sema3a−/− mice had a low bone mass due to decreased bone formation. However, osteoblast-specific Sema3A-deficient mice (Sema3acol1−/− and Sema3aosx−/− mice) had normal bone mass, even though the expression of Sema3A in bone was substantially decreased. In contrast, mice lacking Sema3A in neurons (Sema3asynapsin−/− and Sema3anestin−/− mice) had low bone mass, similar to Sema3a−/− mice, indicating that neuron-derived Sema3A is responsible for the observed bone abnormalities independent of the local effect of Sema3A in bone. Indeed, the number of sensory innervations of trabecular bone was significantly decreased in Sema3asynapsin−/− mice, whereas sympathetic innervations of trabecular bone were unchanged. Moreover, ablating sensory nerves decreased bone mass in wild-type mice, whereas it did not reduce the low bone mass in Sema3anestin−/− mice further, supporting the essential role of the sensory nervous system in normal bone homeostasis. Finally, neuronal abnormalities in Sema3a−/− mice, such as olfactory development, were identified in Sema3asynasin−/− mice, demonstrating that neuron-derived Sema3A contributes to the abnormal neural development seen in Sema3a−/− mice, and indicating that Sema3A produced in neurons regulates neural development in an autocrine manner. This study demonstrates that Sema3A regulates bone remodelling indirectly by modulating sensory nerve development, but not directly by acting on osteoblasts.","title":"Sema3A regulates bone-mass accrual through sensory innervations"},{"docid":"34582256","text":"The object of this study was to assess the role of brown adipose tissue (BAT) and the sympathetic nervous system in the rise in heat production associated with endotoxin-induced fever. Oxygen consumption (VO2) was found to be significantly increased (28%) over a 4-h period after two doses of endotoxin (Escherichia coli lipopolysaccharide, 0.3 mg/100 g body wt) given 24 h apart. Injection of a mixed beta-adrenoceptor antagonist (propranolol) reduced VO2 by 14% in endotoxin-treated rats, whereas the selective beta 1- (atenolol) or beta 2- (ICI 118551) antagonists suppressed VO2 by 10%. These drugs did not affect VO2 in control animals. BAT thermogenic activity assessed from measurements of in vitro mitochondrial guanosine 5'-diphosphate (GDP) binding was elevated by 54% in interscapular BAT and by 171% in other BAT depots. Surgical denervation of one lobe of the interscapular depot prevented these responses. Endotoxin failed to stimulate GDP binding in rats fed protein-deficient diets. This may have been because BAT thermogenic activity was already elevated in control rats fed these diets or because endotoxin caused a marked suppression of food intake in the protein-deficient animals. The results indicate that sympathetic activation of BAT is involved in the thermogenic responses to endotoxin and that these can be modified by dietary manipulation.","title":"Involvement of sympathetic nervous system and brown fat in endotoxin-induced fever in rats."},{"docid":"20544428","text":"Recent studies have highlighted the involvement of the peripheral immune system in delayed cellular degeneration after stroke. In the permanent middle cerebral artery occlusion (MCAO) model of stroke, the spleen decreases in size. This reduction occurs through the release of splenic immune cells. Systemic treatment with human umbilical cord blood cells (HUCBC) 24 h post-stroke blocks the reduction in spleen size while significantly reducing infarct volume. Splenectomy 2 weeks prior to MCAO also reduces infarct volume, further demonstrating the detrimental role of this organ in stroke-induced neurodegeneration. Activation of the sympathetic nervous system after MCAO results in elevated catecholamine levels both at the level of the spleen, through direct splenic innervation, and throughout the systemic circulation upon release from the adrenal medulla. These catecholamines bind to splenic alpha and beta adrenoreceptors. This study examines whether catecholamines regulate the splenic response to stroke. Male Sprague-Dawley rats either underwent splenic denervation 2 weeks prior to MCAO or received injections of carvedilol, a pan adrenergic receptor blocker, prazosin, an alpha1 receptor blocker, or propranolol, a beta receptor blocker. Denervation was confirmed by reduced splenic expression of tyrosine hydroxylase. Denervation prior to MCAO did not alter infarct volume or spleen size. Propranolol treatment also had no effects on these outcomes. Treatment with either prazosin or carvedilol prevented the reduction in spleen size, yet only carvedilol significantly reduced infarct volume (p < 0.05). These results demonstrate that circulating blood borne catecholamines regulate the splenic response to stroke through the activation of both alpha and beta adrenergic receptors.","title":"Blockade of adrenoreceptors inhibits the splenic response to stroke."},{"docid":"12337611","text":"LIN28B regulates developmental processes by modulating microRNAs (miRNAs) of the let-7 family. A role for LIN28B in cancer has been proposed but has not been established in vivo. Here, we report that LIN28B showed genomic aberrations and extensive overexpression in high-risk neuroblastoma compared to several other tumor entities and normal tissues. High LIN28B expression was an independent risk factor for adverse outcome in neuroblastoma. LIN28B signaled through repression of the let-7 miRNAs and consequently resulted in elevated MYCN protein expression in neuroblastoma cells. LIN28B–let-7–MYCN signaling blocked differentiation of normal neuroblasts and neuroblastoma cells. These findings were fully recapitulated in a mouse model in which LIN28B expression in the sympathetic adrenergic lineage induced development of neuroblastomas marked by low let-7 miRNA levels and high MYCN protein expression. Interference with this pathway might offer therapeutic perspectives.","title":"LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression"},{"docid":"13448422","text":"This review discusses some of the mechanisms inherent in diabetes that predispose patients to increased cardiac morbidity and mortality. Single photon emission computerized tomography or photon emission tomography with radioactive labeled analogues of norepinephrine have shown that cardiac sympathetic dysfunction and incompetence are early and also late abnormalities in patients with Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus. Furthermore, myocardial blood flow assessment with photon emission tomography has shown that in patients without myocardial perfusion deficits, endothelial-dependent vasodilatation is severely reduced in relation to cardiac sympathetic dysfunction. In addition, signs of endothelial activation have also been found early in patients with Type I and Type II diabetes in whom vascular disease has not been clinically detected. This activation in conjunction with glycaemic control is important in determining macrovascular mortality. Cardiac sympathetic dysfunction is partially restored to normal with near normalisation of glycaemia. Interpretations. Recently unrecognized “subtle” changes predispose the heart to failure, after ischaemia-induced remodelling, and arteriosclerotic plaques to instability and rupture. These changes act in conjunction with effects, driven by hyperglycaemia and diabetes, on the endothelium of large blood vessels, e. g. on nitric oxide release or on protein kinase-C β activation. Meticulous glucose control early on and rapid recompensation of hyperglycaemia in patients with acute coronary syndrome are part of a successful intensive multifactorial approach to prevent the heart in diabetes converting from ailing to failing. [Diabetologia (2000) 43: 1455–1469]","title":"A new look at the heart in diabetes mellitus: from ailing to failing"},{"docid":"41131087","text":"Human placental lactogen and unconjugated estriol concentrations in maternal serum were evaluated in 100 uneventful twin pregnancies, and these values were compared with those observed in 16 twin pregnancies associated with intrauterine growth retardation or single intrauterine fetal death. In pregnancies associated with intrauterine growth retardation (n = 8), human placental lactogen levels were at the lower limit of normal range for singleton pregnancies, whereas estriol levels were normal in most cases. When one of the fetuses had died before week 33 of pregnancy (n = 5), both human placental lactogen and estriol levels were low and they were almost at the levels in singleton pregnancy. When intrauterine fetal death occurred after week 36 of pregnancy (n = 3), both hormone levels remained normal until term. Thus human placental lactogen rather than estriol is a good indicator of intrauterine growth retardation in twin pregnancy. Both human placental lactogen and estriol are useful for the monitoring of the surviving fetus in the case of single intrauterine fetal death.","title":"Human placental lactogen and unconjugated estriol concentrations in twin pregnancy: monitoring of fetal development in intrauterine growth retardation and single intrauterine fetal death."},{"docid":"4409524","text":"In pregnancy, trophoblast invasion and uterine spiral artery remodelling are important for lowering maternal vascular resistance and increasing uteroplacental blood flow. Impaired spiral artery remodelling has been implicated in pre-eclampsia, a major complication of pregnancy, for a long time but the underlying mechanisms remain unclear. Corin (also known as atrial natriuretic peptide-converting enzyme) is a cardiac protease that activates atrial natriuretic peptide (ANP), a cardiac hormone that is important in regulating blood pressure. Unexpectedly, corin expression was detected in the pregnant uterus. Here we identify a new function of corin and ANP in promoting trophoblast invasion and spiral artery remodelling. We show that pregnant corin- or ANP-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice, trophoblast invasion and uterine spiral artery remodelling were markedly impaired. Consistent with this, the ANP potently stimulated human trophoblasts in invading Matrigels. In patients with pre-eclampsia, uterine Corin messenger RNA and protein levels were significantly lower than that in normal pregnancies. Moreover, we have identified Corin gene mutations in pre-eclamptic patients, which decreased corin activity in processing pro-ANP. These results indicate that corin and ANP are essential for physiological changes at the maternal–fetal interface, suggesting that defects in corin and ANP function may contribute to pre-eclampsia.","title":"Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy"},{"docid":"6123521","text":"The brain interprets experiences and translates them into behavioral and physiological responses. Stressful events are those which are threatening or, at the very least, unexpected and surprising, and the physiological and behavioral responses are intended to promote adaptation via a process called \"allostasis. \" Chemical mediators of allostasis include cortisol and adrenalin from the adrenal glands, other hormones, and neurotransmitters, the parasympathetic and sympathetic nervous systems, and cytokines and chemokines from the immune system. Two brain structures, the amygdala and hippocampus, play key roles in interpreting what is stressful and determining appropriate responses. The hippocampus, a key structure for memories of events and contexts, expresses receptors that enable it to respond to glucocorticoid hormones in the blood, it undergoes atrophy in a number of psychiatric disorders; it also responds to stressors with changes in excitability, decreased dendritic branching, and reduction in number of neurons in the dentate gyrus. The amygdala, which is important for \"emotional memories, \" becomes hyperactive in posttraumatic stress disorder and depressive illness, in animal models of stress, there is evidence for growth and hypertrophy of nerve cells in the amygdala. Changes in the brain after acute and chronic stressors mirror the pattern seen in the metabolic, cardiovascular, and immune systems, that is, short-term adaptation (allostasis) followed by long-term damage (allostatic load), eg, atherosclerosis, fat deposition obesity, bone demineralization, and impaired immune function. Allostatic load of this kind is seen in major depressive illness and may also be expressed in other chronic anxiety and mood disorders.","title":"Structural plasticity of the adult brain: how animal models help us understand brain changes in depression and systemic disorders related to depression"},{"docid":"30983338","text":"AIMS/HYPOTHESIS We assessed the association between congenital malformations and maternal hyperglycemia in pregnant women with pregestational (type 1 or type 2) diabetes and investigated if the rate of congenital malformations was similar in women with near-normal glycemic control compared to the background population. We also assessed the association between congenital malformations and maternal hyperglycemia in pregnant women with pregestational diabetes with special focus on women with near-normal HbA1c in early pregnancy. MATERIALS AND METHODS This is a literature review based on an electronic literature search of the databases PubMed, Cochrane, Embase and Web of Science conducted in July 2017 using the search terms diabetes, pregnancy, HbA1c or glycemic control and congenital anomaly or congenital anomaly. We included original papers in English published after 1997 with data on congenital malformations and HbA1c in at least 250 women with pregestational diabetes. RESULTS Nine papers with in total 6225 women with type 1 diabetes and 2334 women with type 2 diabetes were included. The prevalence of congenital malformations was 6.4% in women with type 1 diabetes and 4.3% in women with type 2 diabetes and for the combined group of women with pregestational diabetes, the relative risk compared to the background population was 3.2. In women with HbA1c < 53 mmol/mol (7.0%) in early pregnancy or HbA1c 53-64 mmol/mol (7.0-8.0%) the prevalence of congenital malformations was 4.3 and 3.7%, respectively, with a relative risk of 2.2 and 1.9, respectively. CONCLUSIONS In pregnant women with pregestational diabetes the prevalence of congenital abnormalities was threefold higher in women with pregestational diabetes compared to the background population. However, HbA1c below 53 mmol/mol (7.0%) in early pregnancy was also associated with a two times increased risk of congenital malformations compared to the background population.","title":"The prevalence of congenital malformations is still higher in pregnant women with pregestational diabetes despite near-normal HbA1c: a literature review."},{"docid":"25182647","text":"Acute fatty liver of pregnancy (AFLP) and the syndrome of hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) are rare but major disorders of the third trimester of pregnancy. Over a 10-year period, 46 women (median age, 30 years; range, 17-41 years) developed hepatic dysfunction severe enough to require transfer to our Liver Failure Unit. Three quarters of the women were nulliparous, and 5 had twin pregnancies; the median gestational age was 35 weeks (range, 24-40 weeks). At admission, 32 patients (70%) were preeclamptic and 21 (46%) were encephalopathic and/or ventilated. Thirty-two patients (70%) had clinical features and laboratory values consistent with AFLP, and 7 (15%) had HELLP syndrome. One patient had preeclamptic liver rupture requiring liver transplantation. In 6 other patients, causes of severe liver dysfunction unrelated to pregnancy were found. Infectious complications occurred in 17 of the patients with AFLP (53%) and in 2 of those with HELLP syndrome (29%). Major intra-abdominal bleeding occurred in 12 women (10 with AFLP), 9 of whom required laparotomies for clot evacuation. Four patients with AFLP (12.5%) had a fatal outcome, with a corresponding perinatal mortality rate of 9%. There were no maternal or perinatal deaths associated with HELLP syndrome. In contrast to results of many previous studies, the results of this large series suggest a relatively favorable maternal and perinatal outcome in severe AFLP and HELLP syndrome. Further improvements in outcome are likely to be achieved through the prevention of the bleeding and infectious complications associated with these disorders.","title":"Maternal and perinatal outcome in severe pregnancy-related liver disease."},{"docid":"5572127","text":"The role of ataxia telangiectasia mutated (ATM), a DNA double-strand break recognition and response protein, in inflammation and inflammatory diseases is unclear. We have previously shown that high levels of systemic DNA damage are induced by intestinal inflammation in wild-type mice. To determine the effect of Atm deficiency in inflammation, we induced experimental colitis in Atm(-/-), Atm(+/-), and wild-type mice via dextran sulfate sodium (DSS) administration. Atm(-/-) mice had higher disease activity indices and rates of mortality compared with heterozygous and wild-type mice. Systemic DNA damage and immune response were characterized in peripheral blood throughout and after three cycles of treatment. Atm(-/-) mice showed increased sensitivity to levels of DNA strand breaks in peripheral leukocytes, as well as micronucleus formation in erythroblasts, compared with heterozygous and wild-type mice, especially during remission periods and after the end of treatment. Markers of reactive oxygen and nitrogen species-mediated damage, including 8-oxoguanine and nitrotyrosine, were present both in the distal colon and in peripheral leukocytes, with Atm(-/-) mice manifesting more 8-oxoguanine formation than wild-type mice. Atm(-/-) mice showed greater upregulation of inflammatory cytokines and significantly higher percentages of activated CD69+ and CD44+ T cells in the peripheral blood throughout treatment. ATM, therefore, may be a critical immunoregulatory factor dampening the deleterious effects of chronic DSS-induced inflammation, necessary for systemic genomic stability and homeostasis of the gut epithelial barrier.","title":"Atm-deficient mice exhibit increased sensitivity to dextran sulfate sodium-induced colitis characterized by elevated DNA damage and persistent immune activation."},{"docid":"68317730","text":"Objectives Corin, an atrial natriuretic peptide-converting enzyme, has been found to promote trophoblast invasion and spiral artery remodeling. Reduced maternal plasma atrial natriuretic peptide (ANP) levels and elevated corin levels have been reported in pregnancies complicated by PE. The aim of this study was to investigate longitudinal changes in maternal plasma levels of corin and midregional proatrial natriuretic peptide (MR-PANP) in pregnancies that develop preeclampsia (PE) and gestational hypertension (GH). Methods Nested case control study drawn from a larger prospective longitudinal study in singleton pregnancies identified by screening at 11 + 0 − 13 + 6 weeks’ gestation as being at high risk for PE. Blood samples were taken every four weeks until delivery. Values were compared in pregnancies that developed preterm-PE (requiring delivery before 37 weeks), term-PE, GH, and those that remained normotensive. The distribution of maternal plasma corin and PANP were made Gaussian after log 10 transformation. Analysis of repeated measures with multilevel mixed-effects linear model (fixed effects and random effects) was performed. The multilevel model was compared to one-level model by the likelihood radio (LR) test. Results A total of 471 samples were analyzed from 122 women, including 85 that remained normotensive, 12 that developed GH, 13 term-PE and 12 preterm-PE. In the normotensive group, log10corin levels were associated with gestational age ( p p = 0.001). In the GH and term-PE groups, corin did not differ significantly from the normotensive group ( p = 0.64 and p = 0.16, respectively). Compared to the normotensive group, MR-PANP levels were significantly higher in the pregnancies that developed preterm-PE and GH ( p = 0.046 and p = 0.019, respectively), but not term-PE ( p = 0.47). Conclusions Maternal plasma corin and MR-PANP could potentially be useful biomarkers for the prediction of preterm-PE. Disclosures A. Khalil: Research Support Recipient; Commercial Interests: USCOM, Roche, Alere, NICOM, Q-fFN; Speaker: Roche.","title":"Longitudinal changes in maternal corin and mid-regional proatrial natriuretic peptide in women at risk of pre-eclampsia"},{"docid":"36838958","text":"Uncoupling protein 1 (Ucp1), which is localized in the mitochondrial inner membrane of mammalian brown adipose tissue (BAT), generates heat by uncoupling oxidative phosphorylation. Upon cold exposure or nutritional abundance, sympathetic neurons stimulate BAT to express Ucp1 to induce energy dissipation and thermogenesis. Accordingly, increased Ucp1 expression reduces obesity in mice and is correlated with leanness in humans. Despite this significance, there is currently a limited understanding of how Ucp1 expression is physiologically regulated at the molecular level. Here, we describe the involvement of Sestrin2 and reactive oxygen species (ROS) in regulation of Ucp1 expression. Transgenic overexpression of Sestrin2 in adipose tissues inhibited both basal and cold-induced Ucp1 expression in interscapular BAT, culminating in decreased thermogenesis and increased fat accumulation. Endogenous Sestrin2 is also important for suppressing Ucp1 expression because BAT from Sestrin2(-/-) mice exhibited a highly elevated level of Ucp1 expression. The redox-inactive mutant of Sestrin2 was incapable of regulating Ucp1 expression, suggesting that Sestrin2 inhibits Ucp1 expression primarily through reducing ROS accumulation. Consistently, ROS-suppressing antioxidant chemicals, such as butylated hydroxyanisole and N-acetylcysteine, inhibited cold- or cAMP-induced Ucp1 expression as well. p38 MAPK, a signaling mediator required for cAMP-induced Ucp1 expression, was inhibited by either Sestrin2 overexpression or antioxidant treatments. Taken together, these results suggest that Sestrin2 and antioxidants inhibit Ucp1 expression through suppressing ROS-mediated p38 MAPK activation, implying a critical role of ROS in proper BAT metabolism.","title":"Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species."},{"docid":"25789730","text":"Both axon and myelin degeneration have significant impact on the long-term disability of patients with white matter disorder. However, the clinical manifestations of the neurological dysfunction caused by white matter disorders are not sufficient to determine the origin of neurological deficits. A noninvasive biological marker capable of detecting and differentiating axon and myelin degeneration would be a significant addition to currently available tools. Directional diffusivities derived from diffusion tensor imaging (DTI) have been previously proposed by this group as potential biological markers to detect and differentiate axon and myelin degeneration. To further test the hypothesis that axial (lambdaparallel) and radial (lambdaperpendicular) diffusivities reflect axon and myelin pathologies, respectively, the optic nerve was examined serially using DTI in a mouse model of retinal ischemia. A significant decrease of lambdaparallel, the putative DTI axonal marker, was observed 3 days after ischemia without concurrently detectable changes in lambdaperpendicular, the putative myelin marker. This result is consistent with histological findings of significant axonal degeneration with no detectable demyelination at 3 days after ischemia. The elevation of lambdaperpendicular observed 5 days after ischemia is consistent with histological findings of myelin degeneration at this time. These results support the hypothesis that lambdaparallel and lambdaperpendicular hold promise as specific markers of axonal and myelin injury, respectively, and, further, that the coexistence of axonal and myelin degeneration does not confound this utility.","title":"Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia."},{"docid":"21297708","text":"1. Nitric oxide (NO) has been suggested as a gastrointestinal neurotransmitter, mediating the gastric receptive relaxation and the relaxation in the peristaltic reflex. The aim of the present study was to measure nerve-induced NO formation in vivo in the gastrointestinal tract. 2. Formation of the nitric oxide oxidation products nitrite and nitrate during vagal nerve stimulation were measured in the anaesthetized rabbit. Microdialysis probes were inserted into the wall of the stomach and proximal colon, and nitrite and nitrate in dialysate measured by capillary electrophoresis. 3. During bilateral vagal nerve stimulation there was an increase in nitrite and nitrate formation at the level of the stomach and in nitrite formation at the level of the colon. This increase was inhibited by intravenous administration of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME 30 mg kg-1). Furthermore, L-NAME significantly increased nerve-induced gastric and colonic contractions, as well as spontaneous colonic contractions. 4. In summary, we present a new methodological procedure for quantification of small changes in nitric oxide formation in vivo. This study provides evidence that nitric oxide is released in the stomach and colonic wall during vagal nerve activity, at concentrations able to cause inhibition of smooth muscle contractions in vivo.","title":"Nerve-induced release of nitric oxide in the rabbit gastrointestinal tract as measured by in vivo microdialysis."},{"docid":"19843244","text":"BACKGROUND AND PURPOSE The PAR(2) receptors are involved in chronic arthritis by mechanisms that are as yet unclear. Here, we examined PAR(2) activation in the rat knee joint. EXPERIMENTAL APPROACH PAR(2) in rat knee joint dorsal root ganglia (DRG) cells at L3-L5, retrogradely labelled with Fluoro-gold (FG) were demonstrated immunohistochemically. Electrophysiological recordings from knee joint nerve fibres in urethane anaesthetized Wistar rats assessed the effects of stimulating joint PAR(2) with its activating peptide, 2-furoyl-LIGRLO-NH(2) (1-100 nmol·100 μL(-1) , via close intra-arterial injection). Fibre firing rate was recorded during joint rotations before and 15 min after administration of PAR(2) activating peptide or control peptide. Leukocyte kinetics in the synovial vasculature upon PAR(2) activation were followed by intravital microscopy for 60 min after perfusion of 2-furoyl-LIGRLO-NH(2) or control peptide. Roles for transient receptor potential vanilloid-1 (TRPV1) or neurokinin-1 (NK(1) ) receptors in the PAR(2) responses were assessed using the selective antagonists, SB366791 and RP67580 respectively. KEY RESULTS PAR(2) were expressed in 59 ± 5% of FG-positive DRG cells; 100 nmol 2-furoyl-LIGRLO-NH(2) increased joint fibre firing rate during normal and noxious rotation, maximal at 3 min (normal; 110 ± 43%, noxious; 90 ± 31%). 2-Furoyl-LIGRLO-NH(2) also significantly increased leukocyte rolling and adhesion over 60 min. All these effects were blocked by pre-treatment with SB366791 and RP67580 (P < 0.05 compared with 2-furoyl-LIGRLO-NH(2) alone). CONCLUSIONS AND IMPLICATIONS PAR(2) receptors play an acute inflammatory role in the knee joint via TRPV1- and NK(1) -dependent mechanisms involving both PAR(2) -mediated neuronal sensitization and leukocyte trafficking.","title":"Activation of PAR(2) receptors sensitizes primary afferents and causes leukocyte rolling and adherence in the rat knee joint."},{"docid":"25687558","text":"The genetically obese (ob/ob) mouse exhibits defective thermoregulatory responses to cold exposure. Pathophysiological explanations for this phenomenon have focused on abnormalities in intracellular metabolism or insensitivity of peripheral tissues to the thermogenic effects of catecholamines. Because the sympathetic nervous system (SNS) is subject to feedback regulation, a peripheral impairment in thermogenesis should be associated with a compensatory increase in SNS activity. To examine SNS activity in the ob/ob mouse, norepinephrine (NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of ob/ob and lean mice. The results from studies utilizing radiolabeled NE or inhibition of NE biosynthesis with alpha-methyl-p-tyrosine to measure NE turnover demonstrated reductions in SNS activity of 33-56% in heart and of 45-73% in IBAT in ob/ob mice at ambient temperature (22 degrees C) compared with measurements in lean controls. During cold exposure (4 degrees C) NE turnover increased in heart and IBAT to a similar extent in both ob/ob and lean mice, but NE turnover rates in heart, and probably in IBAT as well, remained lower in the obese mice than in the lean despite the gradual development of hypothermia in the ob/ob mice during this period. Administration of naltrexone, a long-acting opiate antagonist, failed to reverse the suppression of SNS activity observed in the ob/ob mice. These data indicate that diminished SNS activity in ob/ob mice may be an additional factor contributing to the defective thermogenesis characteristic of these animals.","title":"Diminished sympathetic nervous system activity in genetically obese (ob/ob) mouse."},{"docid":"39776978","text":"The maintenance of adequate bone mass is dependent upon the controlled and timely removal of old, damaged bone. This complex process is performed by the highly specialized, multinucleated osteoclast. Over the past 15 years, a detailed picture has emerged describing the origins, differentiation pathways and activation stages that contribute to normal osteoclast function. This information has primarily been obtained by the development and skeletal analysis of genetically modified mouse models. Mice harboring mutations in specific genetic loci exhibit bone defects as a direct result of aberrations in normal osteoclast recruitment, formation or function. These findings include the identification of the RANK–RANKL–OPG system as a primary mediator of osteoclastogenesis, the characterization of ion transport and cellular attachment mechanisms and the recognition that matrix-degrading enzymes are essential components of resorptive activity. This Review focuses on the principal observations in osteoclast biology derived from genetic mouse models, and highlights emerging concepts that describe how the osteoclast is thought to contribute to the maintenance of adequate bone mass and integrity throughout life.","title":"Advances in osteoclast biology: old findings and new insights from mouse models"},{"docid":"21185923","text":"CD25+CD4+ regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance. We show here that glucocorticoid-induced tumor necrosis factor receptor family–related gene (GITR, also known as TNFRSF18)—a member of the tumor necrosis factor–nerve growth factor (TNF-NGF) receptor gene superfamily—is predominantly expressed on CD25+CD4+ T cells and on CD25+CD4+CD8− thymocytes in normal naïve mice. We found that stimulation of GITR abrogated CD25+CD4+ T cell–mediated suppression. In addition, removal of GITR-expressing T cells or administration of a monoclonal antibody to GITR produced organ-specific autoimmune disease in otherwise normal mice. Thus, GITR plays a key role in dominant immunological self-tolerance maintained by CD25+CD4+ regulatory T cells and could be a suitable molecular target for preventing or treating autoimmune disease.","title":"Stimulation of CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance"},{"docid":"14419116","text":"Whole cell patch-clamp recordings were made from sympathetic preganglionic neurons (SPNs) in the intermediolateral cell column of thoracolumbar spinal cord slices of 12- to 16-day-old rats, and the effects of pituitary adenylate cyclase activating polypeptide (PACAP)-38 on N-methyl-D-aspartate (NMDA)- and kainate (KA)-induced inward currents were examined. PACAP, in concentrations (10-30 nM) that caused no significant change of holding currents, reversibly increased NMDA-induced currents but not KA-induced currents. At higher concentrations (>30 nM), the peptide produced a sustained inward current. The potentiating effect of PACAP was nullified by prior incubation of the slices with the adenylate cyclase inhibitor MDL-12,330A (25 microM). Further, superfusing the slices with the membrane-permeable cyclic AMP analogue N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (100-300 microM) in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (700 microM) increased the NMDA currents. This result suggests that PACAP selectively increases NMDA-receptor-mediated responses in the rat SPNs, probably via a cyclic-AMP-dependent mechanism, providing evidence that the peptide may be involved in synaptic plasticity.","title":"Potentiation of NMDA currents by pituitary adenylate cyclase activating polypeptide in neonatal rat sympathetic preganglionic neurons."},{"docid":"25293721","text":"Placental oxidative stress plays a key role in the pathophysiology of placenta-related disorders, most notably preeclampsia (PE) and intrauterine growth restriction (IUGR). Oxidative stress occurs when accumulation of reactive oxygen species (ROS) damages DNA, proteins and lipids, an outcome that is limited by antioxidant enzymes; mitochondrial uncoupling protein 2 (UCP2) may also limit oxidative stress by reducing ROS production. Here we characterized placental antioxidant defenses during normal gestation and following glucocorticoid-induced IUGR. Placentas were collected on Days 16 and 22 of normal rat pregnancy (term = Day 23) and at Day 22 after dexamethasone treatment from Day 13. Expression of several genes encoding antioxidant enzymes (Sod1, Sod2, Sod3, Cat, Gpx3, Txn1, Txnrd1, Txnrd2, and Txnrd3) and Ucp2 was measured by quantitative RT-PCR in the labyrinth (LZ) and junctional zones (JZ) of the placenta. Expression of Sod1 and Ucp2 mRNAs and the activity of xanthine oxidase, a source of ROS, all increased from Days 16 to 22 in both placental zones, whereas Sod2 and Gpx3 increased only in the rapidly growing LZ. In contrast, Sod3 and Txnrd1 expression fell in the LZ over this period, whereas total superoxide dismutase activity remained stable. Dexamethasone treatment reduced fetal-placental growth and LZ expression of Ucp2 but increased JZ expression of Txn1. Indices of placental oxidative damage (TBARS, F2-isoprostanes, and 8-OHdG) did not change with gestational age or dexamethasone, indicative of adequate antioxidant protection. Overall, our data suggest that the rat placenta is protected from oxidative stress by the dynamic zone- and stage-dependent expression of antioxidant defense genes.","title":"Antioxidant Defenses in the Rat Placenta in Late Gestation: Increased Labyrinthine Expression of Superoxide Dismutases, Glutathione Peroxidase 3, and Uncoupling Protein 21"},{"docid":"22820637","text":"The placental leucine aminopeptidase (P-LAP), adipocyte-derived leucine aminopeptidase (A-LAP) and leukocyte-derived aminopeptidase (L-RAP) belong to one distinct group of the M1 family of amimopeptidases, which we term the \"Oxytocinase subfamily\". They share HEXXH(X)18E Zn-binding and GAMEN motifs essential for the enzymatic activities. Intracellular localization is the characteristic feature of the subfamily members. While P-LAP is translocated from intracellular vesicles to plasma membrane in a stimulus-dependent manner, both A-LAP and L-RAP are retained in the endoplasmic reticulum. They contain sequences necessary for the specific localization in the cell. It is getting evident that the subfamily members play important roles in the maintenance of homeostasis including maintenance of normal pregnancy, memory retention, blood pressure regulation and antigen presentation. In this review, current situation of this newly identified subfamily is summarized.","title":"The oxytocinase subfamily of M1 aminopeptidases."},{"docid":"16488405","text":"Physical activity induces a subclinical inflammatory response, mediated in part by leukocytes, and manifested by elevated concentrations of circulating proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). However, the source of the cytokines that appear during exercise remains unknown. In this study, we examined exercise-induced changes in plasma cytokine concentrations and their corresponding mRNA expression in peripheral blood mononuclear cells. Ten healthy [peak oxygen uptake = 48.8 ± 6.5 (SD) ml · kg−1 · min−1] but untrained men [age = 25 ± 5 (SD) yr] undertook 3 h of exercise (cycling and inclined walking) at 60–65% peak oxygen uptake. Circulating leukocyte subset counts were elevated during and 2 h postexercise but returned to normal within 24 h. Plasma concentrations of IL-1β, IL-6, and TNF-α peaked at the end of exercise and remained elevated at 2 h (IL-6) and up to 24 h (IL-1β and TNF-α) postexercise. Cytokine gene expression in circulating mononucl...","title":"Downloaded from"},{"docid":"1686881","text":"BACKGROUND Patients with familial amyloid polyneuropathy, a rare hereditary form of amyloidosis, have progressive autonomic neuropathy. The disease usually does not induce heart failure but is associated with sudden death, conduction disturbances, and an increased risk of complications during anesthesia. Although cardiac sympathetic denervation has been clearly demonstrated, the postsynaptic status of the cardiac autonomic nervous system remains unelucidated. METHODS AND RESULTS Twenty-one patients were studied (age, 39+/-11 years; normal coronary arteries; left ventricular ejection fraction 68+/-9%). To evaluate the density and affinity constants of myocardial muscarinic receptors, PET with (11)C-MQNB (methylquinuclidinyl benzilate), a specific hydrophilic antagonist, was used. Cardiac beta-receptor functional efficiency was studied by the heart rate (HR) response to intravenous infusion of isoproterenol (5 minutes after 2 mg of atropine, 5, 10, and 15 ng/kg per minute during 5 minutes per step). The mean muscarinic receptor density was higher in patients than in control subjects (B'(max), 35.5+/-8.9 versus 26.1+/-6.7 pmol/mL, P=0.003), without change in receptor affinity. The increase in HR after injection of atropine as well as of MQNB was lower in patients compared with control subjects despite a similar basal HR (DeltaHR after atropine, 11+/-21% versus 62+/-17%; P<0.001), consistent with parasympathetic denervation. Incremental infusion of isoproterenol induced a similar increase in HR in patients and control subjects. CONCLUSIONS Cardiac autonomic denervation in familial amyloid polyneuropathy results in an upregulation of myocardial muscarinic receptors but without change in cardiac beta-receptor responsiveness to catecholamines.","title":"Myocardial muscarinic receptor upregulation and normal response to isoproterenol in denervated hearts by familial amyloid polyneuropathy."},{"docid":"12631697","text":"Limited neural input results in muscle weakness in neuromuscular disease because of a reduction in the density of muscle innervation, the rate of neuromuscular junction activation or the efficiency of synaptic transmission. We developed a small-molecule fast-skeletal-troponin activator, CK-2017357, as a means to increase muscle strength by amplifying the response of muscle when neural input is otherwise diminished secondary to neuromuscular disease. Binding selectively to the fast-skeletal-troponin complex, CK-2017357 slows the rate of calcium release from troponin C and sensitizes muscle to calcium. As a consequence, the force-calcium relationship of muscle fibers shifts leftwards, as does the force-frequency relationship of a nerve-muscle pair, so that CK-2017357 increases the production of muscle force in situ at sub-maximal nerve stimulation rates. Notably, we show that sensitization of the fast-skeletal-troponin complex to calcium improves muscle force and grip strength immediately after administration of single doses of CK-2017357 in a model of the neuromuscular disease myasthenia gravis. Troponin activation may provide a new therapeutic approach to improve physical activity in diseases where neuromuscular function is compromised.","title":"Activation of fast skeletal muscle troponin as a potential therapeutic approach for treating neuromuscular diseases"}],"string":"[\n {\n \"docid\": \"26710772\",\n \"text\": \"Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min(-1), 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min(-1); main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm(-5); P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.(-1) min(-1); P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml(-1), P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml(-1), P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications.\",\n \"title\": \"Sympathetic activation during early pregnancy in humans.\"\n },\n {\n \"docid\": \"8596837\",\n \"text\": \"Women with a history of hypertensive pregnancy are at greater risk for future cardiovascular events; however, the mechanisms for this increased risk are unknown. Evidence suggests that an exercise stimulus unmasks latent hypertensive tendencies, identifying individuals at the greatest risk for developing cardiovascular disease. The current study examined the hypothesis that women with a hypertensive pregnancy history exhibit an augmented exercise pressor response. Normotensive women with a history of healthy pregnancy (CON; n = 9) and hypertensive pregnancy (HP+; n = 12) were studied during the mid-luteal phase of the menstrual cycle. Heart rate (HR), systolic and diastolic blood pressure (SBP, DBP), and muscle sympathetic nerve activity (MSNA) were measured during a cold pressor test (CPT), and, following a sufficient period of recovery, during static handgrip to fatigue (SHG) and post-exercise circulatory arrest (PECA). The BP, HR, and MSNA responses to the CPT were similar between groups. The SBP response to SHG and PECA was similar between groups, but DBP and HR were significantly greater in HP+ women (both p < 0.05). MSNA burst frequency, but not burst incidence or total activity, tended to be elevated in HP+ women during the stressor (peak Δ from baseline 31 ± 13 vs. 23 ± 13 bursts/min; p for group = 0.06). Despite no clinical signs of cardiovascular disease or hypertension, women with a history of hypertensive pregnancy display an enhanced cardiovascular reactivity to an exercise stimulus compared to women with a healthy pregnancy history. This response may be indicative of impaired cardiovascular control that precedes the clinical manifestation of hypertension or cardiovascular events.\",\n \"title\": \"Sympathetic neural and cardiovascular responses during static handgrip exercise in women with a history of hypertensive pregnancy\"\n },\n {\n \"docid\": \"58006489\",\n \"text\": \"Whether sensory nerve can sense bone density or metabolic activity to control bone homeostasis is unknown. Here we found prostaglandin E2 (PGE2) secreted by osteoblastic cells activates PGE2 receptor 4 (EP4) in sensory nerves to regulate bone formation by inhibiting sympathetic activity through the central nervous system. PGE2 secreted by osteoblasts increases when bone density decreases as demonstrated in osteoporotic animal models. Ablation of sensory nerves erodes the skeletal integrity. Specifically, knockout of the EP4 gene in the sensory nerves or cyclooxygenase-2 (COX2) in the osteoblastic cells significantly reduces bone volume in adult mice. Sympathetic tone is increased in sensory denervation models, and propranolol, a β2-adrenergic antagonist, rescues bone loss. Furthermore, injection of SW033291, a small molecule to increase PGE2 level locally, significantly boostes bone formation, whereas the effect is obstructed in EP4 knockout mice. Thus, we show that PGE2 mediates sensory nerve to control bone homeostasis and promote regeneration.\",\n \"title\": \"Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis\"\n },\n {\n \"docid\": \"5107861\",\n \"text\": \"Exposure to psychosocial stress is a risk factor for many diseases, including atherosclerosis. Although incompletely understood, interaction between the psyche and the immune system provides one potential mechanism linking stress and disease inception and progression. Known cross-talk between the brain and immune system includes the hypothalamic-pituitary-adrenal axis, which centrally drives glucocorticoid production in the adrenal cortex, and the sympathetic-adrenal-medullary axis, which controls stress-induced catecholamine release in support of the fight-or-flight reflex. It remains unknown, however, whether chronic stress changes hematopoietic stem cell activity. Here we show that stress increases proliferation of these most primitive hematopoietic progenitors, giving rise to higher levels of disease-promoting inflammatory leukocytes. We found that chronic stress induced monocytosis and neutrophilia in humans. While investigating the source of leukocytosis in mice, we discovered that stress activates upstream hematopoietic stem cells. Under conditions of chronic variable stress in mice, sympathetic nerve fibers released surplus noradrenaline, which signaled bone marrow niche cells to decrease CXCL12 levels through the β3-adrenergic receptor. Consequently, hematopoietic stem cell proliferation was elevated, leading to an increased output of neutrophils and inflammatory monocytes. When atherosclerosis-prone Apoe(-/-) mice were subjected to chronic stress, accelerated hematopoiesis promoted plaque features associated with vulnerable lesions that cause myocardial infarction and stroke in humans.\",\n \"title\": \"Chronic variable stress activates hematopoietic stem cells\"\n },\n {\n \"docid\": \"9197786\",\n \"text\": \"Nerve growth factor (NGF) is a potent survival and axon growth factor for neuronal populations in the peripheral nervous system. Although the mechanisms by which target-derived NGF influences survival of innervating neurons have been extensively investigated, its regulation of axonal growth and target innervation are just being elucidated. Here, we identify Wnt5a, a member of the Wnt family of secreted growth factors, as a key downstream effector of NGF in mediating axonal branching and growth in developing sympathetic neurons. Wnt5a is robustly expressed in sympathetic neurons when their axons are innervating NGF-expressing targets. NGF:TrkA signaling enhances neuronal expression of Wnt5a. Wnt5a rapidly induces axon branching while it has a long-term effect on promoting axon extension. Loss of Wnt5a function revealed that it is necessary for NGF-dependent axonal branching and growth, but not survival, in vitro. Furthermore, Wnt5a(-/-) mice display reduced innervation of NGF-expressing target tissues, and a subsequent increase in neuronal apoptosis, in vivo. Wnt5a functions in developing sympathetic neurons by locally activating protein kinase C in axons. Together, our findings define a novel regulatory pathway in which Wnt5a, expressed in sympathetic neurons in response to target-derived NGF, regulates innervation of peripheral targets.\",\n \"title\": \"Wnt5a mediates nerve growth factor-dependent axonal branching and growth in developing sympathetic neurons.\"\n },\n {\n \"docid\": \"1701063\",\n \"text\": \"Semaphorin 3A (Sema3A) is a diffusible axonal chemorepellent that has an important role in axon guidance. Previous studies have demonstrated that Sema3a−/− mice have multiple developmental defects due to abnormal neuronal innervations. Here we show in mice that Sema3A is abundantly expressed in bone, and cell-based assays showed that Sema3A affected osteoblast differentiation in a cell-autonomous fashion. Accordingly, Sema3a−/− mice had a low bone mass due to decreased bone formation. However, osteoblast-specific Sema3A-deficient mice (Sema3acol1−/− and Sema3aosx−/− mice) had normal bone mass, even though the expression of Sema3A in bone was substantially decreased. In contrast, mice lacking Sema3A in neurons (Sema3asynapsin−/− and Sema3anestin−/− mice) had low bone mass, similar to Sema3a−/− mice, indicating that neuron-derived Sema3A is responsible for the observed bone abnormalities independent of the local effect of Sema3A in bone. Indeed, the number of sensory innervations of trabecular bone was significantly decreased in Sema3asynapsin−/− mice, whereas sympathetic innervations of trabecular bone were unchanged. Moreover, ablating sensory nerves decreased bone mass in wild-type mice, whereas it did not reduce the low bone mass in Sema3anestin−/− mice further, supporting the essential role of the sensory nervous system in normal bone homeostasis. Finally, neuronal abnormalities in Sema3a−/− mice, such as olfactory development, were identified in Sema3asynasin−/− mice, demonstrating that neuron-derived Sema3A contributes to the abnormal neural development seen in Sema3a−/− mice, and indicating that Sema3A produced in neurons regulates neural development in an autocrine manner. This study demonstrates that Sema3A regulates bone remodelling indirectly by modulating sensory nerve development, but not directly by acting on osteoblasts.\",\n \"title\": \"Sema3A regulates bone-mass accrual through sensory innervations\"\n },\n {\n \"docid\": \"34582256\",\n \"text\": \"The object of this study was to assess the role of brown adipose tissue (BAT) and the sympathetic nervous system in the rise in heat production associated with endotoxin-induced fever. Oxygen consumption (VO2) was found to be significantly increased (28%) over a 4-h period after two doses of endotoxin (Escherichia coli lipopolysaccharide, 0.3 mg/100 g body wt) given 24 h apart. Injection of a mixed beta-adrenoceptor antagonist (propranolol) reduced VO2 by 14% in endotoxin-treated rats, whereas the selective beta 1- (atenolol) or beta 2- (ICI 118551) antagonists suppressed VO2 by 10%. These drugs did not affect VO2 in control animals. BAT thermogenic activity assessed from measurements of in vitro mitochondrial guanosine 5'-diphosphate (GDP) binding was elevated by 54% in interscapular BAT and by 171% in other BAT depots. Surgical denervation of one lobe of the interscapular depot prevented these responses. Endotoxin failed to stimulate GDP binding in rats fed protein-deficient diets. This may have been because BAT thermogenic activity was already elevated in control rats fed these diets or because endotoxin caused a marked suppression of food intake in the protein-deficient animals. The results indicate that sympathetic activation of BAT is involved in the thermogenic responses to endotoxin and that these can be modified by dietary manipulation.\",\n \"title\": \"Involvement of sympathetic nervous system and brown fat in endotoxin-induced fever in rats.\"\n },\n {\n \"docid\": \"20544428\",\n \"text\": \"Recent studies have highlighted the involvement of the peripheral immune system in delayed cellular degeneration after stroke. In the permanent middle cerebral artery occlusion (MCAO) model of stroke, the spleen decreases in size. This reduction occurs through the release of splenic immune cells. Systemic treatment with human umbilical cord blood cells (HUCBC) 24 h post-stroke blocks the reduction in spleen size while significantly reducing infarct volume. Splenectomy 2 weeks prior to MCAO also reduces infarct volume, further demonstrating the detrimental role of this organ in stroke-induced neurodegeneration. Activation of the sympathetic nervous system after MCAO results in elevated catecholamine levels both at the level of the spleen, through direct splenic innervation, and throughout the systemic circulation upon release from the adrenal medulla. These catecholamines bind to splenic alpha and beta adrenoreceptors. This study examines whether catecholamines regulate the splenic response to stroke. Male Sprague-Dawley rats either underwent splenic denervation 2 weeks prior to MCAO or received injections of carvedilol, a pan adrenergic receptor blocker, prazosin, an alpha1 receptor blocker, or propranolol, a beta receptor blocker. Denervation was confirmed by reduced splenic expression of tyrosine hydroxylase. Denervation prior to MCAO did not alter infarct volume or spleen size. Propranolol treatment also had no effects on these outcomes. Treatment with either prazosin or carvedilol prevented the reduction in spleen size, yet only carvedilol significantly reduced infarct volume (p < 0.05). These results demonstrate that circulating blood borne catecholamines regulate the splenic response to stroke through the activation of both alpha and beta adrenergic receptors.\",\n \"title\": \"Blockade of adrenoreceptors inhibits the splenic response to stroke.\"\n },\n {\n \"docid\": \"12337611\",\n \"text\": \"LIN28B regulates developmental processes by modulating microRNAs (miRNAs) of the let-7 family. A role for LIN28B in cancer has been proposed but has not been established in vivo. Here, we report that LIN28B showed genomic aberrations and extensive overexpression in high-risk neuroblastoma compared to several other tumor entities and normal tissues. High LIN28B expression was an independent risk factor for adverse outcome in neuroblastoma. LIN28B signaled through repression of the let-7 miRNAs and consequently resulted in elevated MYCN protein expression in neuroblastoma cells. LIN28B–let-7–MYCN signaling blocked differentiation of normal neuroblasts and neuroblastoma cells. These findings were fully recapitulated in a mouse model in which LIN28B expression in the sympathetic adrenergic lineage induced development of neuroblastomas marked by low let-7 miRNA levels and high MYCN protein expression. Interference with this pathway might offer therapeutic perspectives.\",\n \"title\": \"LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression\"\n },\n {\n \"docid\": \"13448422\",\n \"text\": \"This review discusses some of the mechanisms inherent in diabetes that predispose patients to increased cardiac morbidity and mortality. Single photon emission computerized tomography or photon emission tomography with radioactive labeled analogues of norepinephrine have shown that cardiac sympathetic dysfunction and incompetence are early and also late abnormalities in patients with Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus. Furthermore, myocardial blood flow assessment with photon emission tomography has shown that in patients without myocardial perfusion deficits, endothelial-dependent vasodilatation is severely reduced in relation to cardiac sympathetic dysfunction. In addition, signs of endothelial activation have also been found early in patients with Type I and Type II diabetes in whom vascular disease has not been clinically detected. This activation in conjunction with glycaemic control is important in determining macrovascular mortality. Cardiac sympathetic dysfunction is partially restored to normal with near normalisation of glycaemia. Interpretations. Recently unrecognized “subtle” changes predispose the heart to failure, after ischaemia-induced remodelling, and arteriosclerotic plaques to instability and rupture. These changes act in conjunction with effects, driven by hyperglycaemia and diabetes, on the endothelium of large blood vessels, e. g. on nitric oxide release or on protein kinase-C β activation. Meticulous glucose control early on and rapid recompensation of hyperglycaemia in patients with acute coronary syndrome are part of a successful intensive multifactorial approach to prevent the heart in diabetes converting from ailing to failing. [Diabetologia (2000) 43: 1455–1469]\",\n \"title\": \"A new look at the heart in diabetes mellitus: from ailing to failing\"\n },\n {\n \"docid\": \"41131087\",\n \"text\": \"Human placental lactogen and unconjugated estriol concentrations in maternal serum were evaluated in 100 uneventful twin pregnancies, and these values were compared with those observed in 16 twin pregnancies associated with intrauterine growth retardation or single intrauterine fetal death. In pregnancies associated with intrauterine growth retardation (n = 8), human placental lactogen levels were at the lower limit of normal range for singleton pregnancies, whereas estriol levels were normal in most cases. When one of the fetuses had died before week 33 of pregnancy (n = 5), both human placental lactogen and estriol levels were low and they were almost at the levels in singleton pregnancy. When intrauterine fetal death occurred after week 36 of pregnancy (n = 3), both hormone levels remained normal until term. Thus human placental lactogen rather than estriol is a good indicator of intrauterine growth retardation in twin pregnancy. Both human placental lactogen and estriol are useful for the monitoring of the surviving fetus in the case of single intrauterine fetal death.\",\n \"title\": \"Human placental lactogen and unconjugated estriol concentrations in twin pregnancy: monitoring of fetal development in intrauterine growth retardation and single intrauterine fetal death.\"\n },\n {\n \"docid\": \"4409524\",\n \"text\": \"In pregnancy, trophoblast invasion and uterine spiral artery remodelling are important for lowering maternal vascular resistance and increasing uteroplacental blood flow. Impaired spiral artery remodelling has been implicated in pre-eclampsia, a major complication of pregnancy, for a long time but the underlying mechanisms remain unclear. Corin (also known as atrial natriuretic peptide-converting enzyme) is a cardiac protease that activates atrial natriuretic peptide (ANP), a cardiac hormone that is important in regulating blood pressure. Unexpectedly, corin expression was detected in the pregnant uterus. Here we identify a new function of corin and ANP in promoting trophoblast invasion and spiral artery remodelling. We show that pregnant corin- or ANP-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice, trophoblast invasion and uterine spiral artery remodelling were markedly impaired. Consistent with this, the ANP potently stimulated human trophoblasts in invading Matrigels. In patients with pre-eclampsia, uterine Corin messenger RNA and protein levels were significantly lower than that in normal pregnancies. Moreover, we have identified Corin gene mutations in pre-eclamptic patients, which decreased corin activity in processing pro-ANP. These results indicate that corin and ANP are essential for physiological changes at the maternal–fetal interface, suggesting that defects in corin and ANP function may contribute to pre-eclampsia.\",\n \"title\": \"Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy\"\n },\n {\n \"docid\": \"6123521\",\n \"text\": \"The brain interprets experiences and translates them into behavioral and physiological responses. Stressful events are those which are threatening or, at the very least, unexpected and surprising, and the physiological and behavioral responses are intended to promote adaptation via a process called \\\"allostasis. \\\" Chemical mediators of allostasis include cortisol and adrenalin from the adrenal glands, other hormones, and neurotransmitters, the parasympathetic and sympathetic nervous systems, and cytokines and chemokines from the immune system. Two brain structures, the amygdala and hippocampus, play key roles in interpreting what is stressful and determining appropriate responses. The hippocampus, a key structure for memories of events and contexts, expresses receptors that enable it to respond to glucocorticoid hormones in the blood, it undergoes atrophy in a number of psychiatric disorders; it also responds to stressors with changes in excitability, decreased dendritic branching, and reduction in number of neurons in the dentate gyrus. The amygdala, which is important for \\\"emotional memories, \\\" becomes hyperactive in posttraumatic stress disorder and depressive illness, in animal models of stress, there is evidence for growth and hypertrophy of nerve cells in the amygdala. Changes in the brain after acute and chronic stressors mirror the pattern seen in the metabolic, cardiovascular, and immune systems, that is, short-term adaptation (allostasis) followed by long-term damage (allostatic load), eg, atherosclerosis, fat deposition obesity, bone demineralization, and impaired immune function. Allostatic load of this kind is seen in major depressive illness and may also be expressed in other chronic anxiety and mood disorders.\",\n \"title\": \"Structural plasticity of the adult brain: how animal models help us understand brain changes in depression and systemic disorders related to depression\"\n },\n {\n \"docid\": \"30983338\",\n \"text\": \"AIMS/HYPOTHESIS We assessed the association between congenital malformations and maternal hyperglycemia in pregnant women with pregestational (type 1 or type 2) diabetes and investigated if the rate of congenital malformations was similar in women with near-normal glycemic control compared to the background population. We also assessed the association between congenital malformations and maternal hyperglycemia in pregnant women with pregestational diabetes with special focus on women with near-normal HbA1c in early pregnancy. MATERIALS AND METHODS This is a literature review based on an electronic literature search of the databases PubMed, Cochrane, Embase and Web of Science conducted in July 2017 using the search terms diabetes, pregnancy, HbA1c or glycemic control and congenital anomaly or congenital anomaly. We included original papers in English published after 1997 with data on congenital malformations and HbA1c in at least 250 women with pregestational diabetes. RESULTS Nine papers with in total 6225 women with type 1 diabetes and 2334 women with type 2 diabetes were included. The prevalence of congenital malformations was 6.4% in women with type 1 diabetes and 4.3% in women with type 2 diabetes and for the combined group of women with pregestational diabetes, the relative risk compared to the background population was 3.2. In women with HbA1c < 53 mmol/mol (7.0%) in early pregnancy or HbA1c 53-64 mmol/mol (7.0-8.0%) the prevalence of congenital malformations was 4.3 and 3.7%, respectively, with a relative risk of 2.2 and 1.9, respectively. CONCLUSIONS In pregnant women with pregestational diabetes the prevalence of congenital abnormalities was threefold higher in women with pregestational diabetes compared to the background population. However, HbA1c below 53 mmol/mol (7.0%) in early pregnancy was also associated with a two times increased risk of congenital malformations compared to the background population.\",\n \"title\": \"The prevalence of congenital malformations is still higher in pregnant women with pregestational diabetes despite near-normal HbA1c: a literature review.\"\n },\n {\n \"docid\": \"25182647\",\n \"text\": \"Acute fatty liver of pregnancy (AFLP) and the syndrome of hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) are rare but major disorders of the third trimester of pregnancy. Over a 10-year period, 46 women (median age, 30 years; range, 17-41 years) developed hepatic dysfunction severe enough to require transfer to our Liver Failure Unit. Three quarters of the women were nulliparous, and 5 had twin pregnancies; the median gestational age was 35 weeks (range, 24-40 weeks). At admission, 32 patients (70%) were preeclamptic and 21 (46%) were encephalopathic and/or ventilated. Thirty-two patients (70%) had clinical features and laboratory values consistent with AFLP, and 7 (15%) had HELLP syndrome. One patient had preeclamptic liver rupture requiring liver transplantation. In 6 other patients, causes of severe liver dysfunction unrelated to pregnancy were found. Infectious complications occurred in 17 of the patients with AFLP (53%) and in 2 of those with HELLP syndrome (29%). Major intra-abdominal bleeding occurred in 12 women (10 with AFLP), 9 of whom required laparotomies for clot evacuation. Four patients with AFLP (12.5%) had a fatal outcome, with a corresponding perinatal mortality rate of 9%. There were no maternal or perinatal deaths associated with HELLP syndrome. In contrast to results of many previous studies, the results of this large series suggest a relatively favorable maternal and perinatal outcome in severe AFLP and HELLP syndrome. Further improvements in outcome are likely to be achieved through the prevention of the bleeding and infectious complications associated with these disorders.\",\n \"title\": \"Maternal and perinatal outcome in severe pregnancy-related liver disease.\"\n },\n {\n \"docid\": \"5572127\",\n \"text\": \"The role of ataxia telangiectasia mutated (ATM), a DNA double-strand break recognition and response protein, in inflammation and inflammatory diseases is unclear. We have previously shown that high levels of systemic DNA damage are induced by intestinal inflammation in wild-type mice. To determine the effect of Atm deficiency in inflammation, we induced experimental colitis in Atm(-/-), Atm(+/-), and wild-type mice via dextran sulfate sodium (DSS) administration. Atm(-/-) mice had higher disease activity indices and rates of mortality compared with heterozygous and wild-type mice. Systemic DNA damage and immune response were characterized in peripheral blood throughout and after three cycles of treatment. Atm(-/-) mice showed increased sensitivity to levels of DNA strand breaks in peripheral leukocytes, as well as micronucleus formation in erythroblasts, compared with heterozygous and wild-type mice, especially during remission periods and after the end of treatment. Markers of reactive oxygen and nitrogen species-mediated damage, including 8-oxoguanine and nitrotyrosine, were present both in the distal colon and in peripheral leukocytes, with Atm(-/-) mice manifesting more 8-oxoguanine formation than wild-type mice. Atm(-/-) mice showed greater upregulation of inflammatory cytokines and significantly higher percentages of activated CD69+ and CD44+ T cells in the peripheral blood throughout treatment. ATM, therefore, may be a critical immunoregulatory factor dampening the deleterious effects of chronic DSS-induced inflammation, necessary for systemic genomic stability and homeostasis of the gut epithelial barrier.\",\n \"title\": \"Atm-deficient mice exhibit increased sensitivity to dextran sulfate sodium-induced colitis characterized by elevated DNA damage and persistent immune activation.\"\n },\n {\n \"docid\": \"68317730\",\n \"text\": \"Objectives Corin, an atrial natriuretic peptide-converting enzyme, has been found to promote trophoblast invasion and spiral artery remodeling. Reduced maternal plasma atrial natriuretic peptide (ANP) levels and elevated corin levels have been reported in pregnancies complicated by PE. The aim of this study was to investigate longitudinal changes in maternal plasma levels of corin and midregional proatrial natriuretic peptide (MR-PANP) in pregnancies that develop preeclampsia (PE) and gestational hypertension (GH). Methods Nested case control study drawn from a larger prospective longitudinal study in singleton pregnancies identified by screening at 11 + 0 − 13 + 6 weeks’ gestation as being at high risk for PE. Blood samples were taken every four weeks until delivery. Values were compared in pregnancies that developed preterm-PE (requiring delivery before 37 weeks), term-PE, GH, and those that remained normotensive. The distribution of maternal plasma corin and PANP were made Gaussian after log 10 transformation. Analysis of repeated measures with multilevel mixed-effects linear model (fixed effects and random effects) was performed. The multilevel model was compared to one-level model by the likelihood radio (LR) test. Results A total of 471 samples were analyzed from 122 women, including 85 that remained normotensive, 12 that developed GH, 13 term-PE and 12 preterm-PE. In the normotensive group, log10corin levels were associated with gestational age ( p p = 0.001). In the GH and term-PE groups, corin did not differ significantly from the normotensive group ( p = 0.64 and p = 0.16, respectively). Compared to the normotensive group, MR-PANP levels were significantly higher in the pregnancies that developed preterm-PE and GH ( p = 0.046 and p = 0.019, respectively), but not term-PE ( p = 0.47). Conclusions Maternal plasma corin and MR-PANP could potentially be useful biomarkers for the prediction of preterm-PE. Disclosures A. Khalil: Research Support Recipient; Commercial Interests: USCOM, Roche, Alere, NICOM, Q-fFN; Speaker: Roche.\",\n \"title\": \"Longitudinal changes in maternal corin and mid-regional proatrial natriuretic peptide in women at risk of pre-eclampsia\"\n },\n {\n \"docid\": \"36838958\",\n \"text\": \"Uncoupling protein 1 (Ucp1), which is localized in the mitochondrial inner membrane of mammalian brown adipose tissue (BAT), generates heat by uncoupling oxidative phosphorylation. Upon cold exposure or nutritional abundance, sympathetic neurons stimulate BAT to express Ucp1 to induce energy dissipation and thermogenesis. Accordingly, increased Ucp1 expression reduces obesity in mice and is correlated with leanness in humans. Despite this significance, there is currently a limited understanding of how Ucp1 expression is physiologically regulated at the molecular level. Here, we describe the involvement of Sestrin2 and reactive oxygen species (ROS) in regulation of Ucp1 expression. Transgenic overexpression of Sestrin2 in adipose tissues inhibited both basal and cold-induced Ucp1 expression in interscapular BAT, culminating in decreased thermogenesis and increased fat accumulation. Endogenous Sestrin2 is also important for suppressing Ucp1 expression because BAT from Sestrin2(-/-) mice exhibited a highly elevated level of Ucp1 expression. The redox-inactive mutant of Sestrin2 was incapable of regulating Ucp1 expression, suggesting that Sestrin2 inhibits Ucp1 expression primarily through reducing ROS accumulation. Consistently, ROS-suppressing antioxidant chemicals, such as butylated hydroxyanisole and N-acetylcysteine, inhibited cold- or cAMP-induced Ucp1 expression as well. p38 MAPK, a signaling mediator required for cAMP-induced Ucp1 expression, was inhibited by either Sestrin2 overexpression or antioxidant treatments. Taken together, these results suggest that Sestrin2 and antioxidants inhibit Ucp1 expression through suppressing ROS-mediated p38 MAPK activation, implying a critical role of ROS in proper BAT metabolism.\",\n \"title\": \"Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species.\"\n },\n {\n \"docid\": \"25789730\",\n \"text\": \"Both axon and myelin degeneration have significant impact on the long-term disability of patients with white matter disorder. However, the clinical manifestations of the neurological dysfunction caused by white matter disorders are not sufficient to determine the origin of neurological deficits. A noninvasive biological marker capable of detecting and differentiating axon and myelin degeneration would be a significant addition to currently available tools. Directional diffusivities derived from diffusion tensor imaging (DTI) have been previously proposed by this group as potential biological markers to detect and differentiate axon and myelin degeneration. To further test the hypothesis that axial (lambdaparallel) and radial (lambdaperpendicular) diffusivities reflect axon and myelin pathologies, respectively, the optic nerve was examined serially using DTI in a mouse model of retinal ischemia. A significant decrease of lambdaparallel, the putative DTI axonal marker, was observed 3 days after ischemia without concurrently detectable changes in lambdaperpendicular, the putative myelin marker. This result is consistent with histological findings of significant axonal degeneration with no detectable demyelination at 3 days after ischemia. The elevation of lambdaperpendicular observed 5 days after ischemia is consistent with histological findings of myelin degeneration at this time. These results support the hypothesis that lambdaparallel and lambdaperpendicular hold promise as specific markers of axonal and myelin injury, respectively, and, further, that the coexistence of axonal and myelin degeneration does not confound this utility.\",\n \"title\": \"Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia.\"\n },\n {\n \"docid\": \"21297708\",\n \"text\": \"1. Nitric oxide (NO) has been suggested as a gastrointestinal neurotransmitter, mediating the gastric receptive relaxation and the relaxation in the peristaltic reflex. The aim of the present study was to measure nerve-induced NO formation in vivo in the gastrointestinal tract. 2. Formation of the nitric oxide oxidation products nitrite and nitrate during vagal nerve stimulation were measured in the anaesthetized rabbit. Microdialysis probes were inserted into the wall of the stomach and proximal colon, and nitrite and nitrate in dialysate measured by capillary electrophoresis. 3. During bilateral vagal nerve stimulation there was an increase in nitrite and nitrate formation at the level of the stomach and in nitrite formation at the level of the colon. This increase was inhibited by intravenous administration of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME 30 mg kg-1). Furthermore, L-NAME significantly increased nerve-induced gastric and colonic contractions, as well as spontaneous colonic contractions. 4. In summary, we present a new methodological procedure for quantification of small changes in nitric oxide formation in vivo. This study provides evidence that nitric oxide is released in the stomach and colonic wall during vagal nerve activity, at concentrations able to cause inhibition of smooth muscle contractions in vivo.\",\n \"title\": \"Nerve-induced release of nitric oxide in the rabbit gastrointestinal tract as measured by in vivo microdialysis.\"\n },\n {\n \"docid\": \"19843244\",\n \"text\": \"BACKGROUND AND PURPOSE The PAR(2) receptors are involved in chronic arthritis by mechanisms that are as yet unclear. Here, we examined PAR(2) activation in the rat knee joint. EXPERIMENTAL APPROACH PAR(2) in rat knee joint dorsal root ganglia (DRG) cells at L3-L5, retrogradely labelled with Fluoro-gold (FG) were demonstrated immunohistochemically. Electrophysiological recordings from knee joint nerve fibres in urethane anaesthetized Wistar rats assessed the effects of stimulating joint PAR(2) with its activating peptide, 2-furoyl-LIGRLO-NH(2) (1-100 nmol·100 μL(-1) , via close intra-arterial injection). Fibre firing rate was recorded during joint rotations before and 15 min after administration of PAR(2) activating peptide or control peptide. Leukocyte kinetics in the synovial vasculature upon PAR(2) activation were followed by intravital microscopy for 60 min after perfusion of 2-furoyl-LIGRLO-NH(2) or control peptide. Roles for transient receptor potential vanilloid-1 (TRPV1) or neurokinin-1 (NK(1) ) receptors in the PAR(2) responses were assessed using the selective antagonists, SB366791 and RP67580 respectively. KEY RESULTS PAR(2) were expressed in 59 ± 5% of FG-positive DRG cells; 100 nmol 2-furoyl-LIGRLO-NH(2) increased joint fibre firing rate during normal and noxious rotation, maximal at 3 min (normal; 110 ± 43%, noxious; 90 ± 31%). 2-Furoyl-LIGRLO-NH(2) also significantly increased leukocyte rolling and adhesion over 60 min. All these effects were blocked by pre-treatment with SB366791 and RP67580 (P < 0.05 compared with 2-furoyl-LIGRLO-NH(2) alone). CONCLUSIONS AND IMPLICATIONS PAR(2) receptors play an acute inflammatory role in the knee joint via TRPV1- and NK(1) -dependent mechanisms involving both PAR(2) -mediated neuronal sensitization and leukocyte trafficking.\",\n \"title\": \"Activation of PAR(2) receptors sensitizes primary afferents and causes leukocyte rolling and adherence in the rat knee joint.\"\n },\n {\n \"docid\": \"25687558\",\n \"text\": \"The genetically obese (ob/ob) mouse exhibits defective thermoregulatory responses to cold exposure. Pathophysiological explanations for this phenomenon have focused on abnormalities in intracellular metabolism or insensitivity of peripheral tissues to the thermogenic effects of catecholamines. Because the sympathetic nervous system (SNS) is subject to feedback regulation, a peripheral impairment in thermogenesis should be associated with a compensatory increase in SNS activity. To examine SNS activity in the ob/ob mouse, norepinephrine (NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of ob/ob and lean mice. The results from studies utilizing radiolabeled NE or inhibition of NE biosynthesis with alpha-methyl-p-tyrosine to measure NE turnover demonstrated reductions in SNS activity of 33-56% in heart and of 45-73% in IBAT in ob/ob mice at ambient temperature (22 degrees C) compared with measurements in lean controls. During cold exposure (4 degrees C) NE turnover increased in heart and IBAT to a similar extent in both ob/ob and lean mice, but NE turnover rates in heart, and probably in IBAT as well, remained lower in the obese mice than in the lean despite the gradual development of hypothermia in the ob/ob mice during this period. Administration of naltrexone, a long-acting opiate antagonist, failed to reverse the suppression of SNS activity observed in the ob/ob mice. These data indicate that diminished SNS activity in ob/ob mice may be an additional factor contributing to the defective thermogenesis characteristic of these animals.\",\n \"title\": \"Diminished sympathetic nervous system activity in genetically obese (ob/ob) mouse.\"\n },\n {\n \"docid\": \"39776978\",\n \"text\": \"The maintenance of adequate bone mass is dependent upon the controlled and timely removal of old, damaged bone. This complex process is performed by the highly specialized, multinucleated osteoclast. Over the past 15 years, a detailed picture has emerged describing the origins, differentiation pathways and activation stages that contribute to normal osteoclast function. This information has primarily been obtained by the development and skeletal analysis of genetically modified mouse models. Mice harboring mutations in specific genetic loci exhibit bone defects as a direct result of aberrations in normal osteoclast recruitment, formation or function. These findings include the identification of the RANK–RANKL–OPG system as a primary mediator of osteoclastogenesis, the characterization of ion transport and cellular attachment mechanisms and the recognition that matrix-degrading enzymes are essential components of resorptive activity. This Review focuses on the principal observations in osteoclast biology derived from genetic mouse models, and highlights emerging concepts that describe how the osteoclast is thought to contribute to the maintenance of adequate bone mass and integrity throughout life.\",\n \"title\": \"Advances in osteoclast biology: old findings and new insights from mouse models\"\n },\n {\n \"docid\": \"21185923\",\n \"text\": \"CD25+CD4+ regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance. We show here that glucocorticoid-induced tumor necrosis factor receptor family–related gene (GITR, also known as TNFRSF18)—a member of the tumor necrosis factor–nerve growth factor (TNF-NGF) receptor gene superfamily—is predominantly expressed on CD25+CD4+ T cells and on CD25+CD4+CD8− thymocytes in normal naïve mice. We found that stimulation of GITR abrogated CD25+CD4+ T cell–mediated suppression. In addition, removal of GITR-expressing T cells or administration of a monoclonal antibody to GITR produced organ-specific autoimmune disease in otherwise normal mice. Thus, GITR plays a key role in dominant immunological self-tolerance maintained by CD25+CD4+ regulatory T cells and could be a suitable molecular target for preventing or treating autoimmune disease.\",\n \"title\": \"Stimulation of CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance\"\n },\n {\n \"docid\": \"14419116\",\n \"text\": \"Whole cell patch-clamp recordings were made from sympathetic preganglionic neurons (SPNs) in the intermediolateral cell column of thoracolumbar spinal cord slices of 12- to 16-day-old rats, and the effects of pituitary adenylate cyclase activating polypeptide (PACAP)-38 on N-methyl-D-aspartate (NMDA)- and kainate (KA)-induced inward currents were examined. PACAP, in concentrations (10-30 nM) that caused no significant change of holding currents, reversibly increased NMDA-induced currents but not KA-induced currents. At higher concentrations (>30 nM), the peptide produced a sustained inward current. The potentiating effect of PACAP was nullified by prior incubation of the slices with the adenylate cyclase inhibitor MDL-12,330A (25 microM). Further, superfusing the slices with the membrane-permeable cyclic AMP analogue N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (100-300 microM) in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (700 microM) increased the NMDA currents. This result suggests that PACAP selectively increases NMDA-receptor-mediated responses in the rat SPNs, probably via a cyclic-AMP-dependent mechanism, providing evidence that the peptide may be involved in synaptic plasticity.\",\n \"title\": \"Potentiation of NMDA currents by pituitary adenylate cyclase activating polypeptide in neonatal rat sympathetic preganglionic neurons.\"\n },\n {\n \"docid\": \"25293721\",\n \"text\": \"Placental oxidative stress plays a key role in the pathophysiology of placenta-related disorders, most notably preeclampsia (PE) and intrauterine growth restriction (IUGR). Oxidative stress occurs when accumulation of reactive oxygen species (ROS) damages DNA, proteins and lipids, an outcome that is limited by antioxidant enzymes; mitochondrial uncoupling protein 2 (UCP2) may also limit oxidative stress by reducing ROS production. Here we characterized placental antioxidant defenses during normal gestation and following glucocorticoid-induced IUGR. Placentas were collected on Days 16 and 22 of normal rat pregnancy (term = Day 23) and at Day 22 after dexamethasone treatment from Day 13. Expression of several genes encoding antioxidant enzymes (Sod1, Sod2, Sod3, Cat, Gpx3, Txn1, Txnrd1, Txnrd2, and Txnrd3) and Ucp2 was measured by quantitative RT-PCR in the labyrinth (LZ) and junctional zones (JZ) of the placenta. Expression of Sod1 and Ucp2 mRNAs and the activity of xanthine oxidase, a source of ROS, all increased from Days 16 to 22 in both placental zones, whereas Sod2 and Gpx3 increased only in the rapidly growing LZ. In contrast, Sod3 and Txnrd1 expression fell in the LZ over this period, whereas total superoxide dismutase activity remained stable. Dexamethasone treatment reduced fetal-placental growth and LZ expression of Ucp2 but increased JZ expression of Txn1. Indices of placental oxidative damage (TBARS, F2-isoprostanes, and 8-OHdG) did not change with gestational age or dexamethasone, indicative of adequate antioxidant protection. Overall, our data suggest that the rat placenta is protected from oxidative stress by the dynamic zone- and stage-dependent expression of antioxidant defense genes.\",\n \"title\": \"Antioxidant Defenses in the Rat Placenta in Late Gestation: Increased Labyrinthine Expression of Superoxide Dismutases, Glutathione Peroxidase 3, and Uncoupling Protein 21\"\n },\n {\n \"docid\": \"22820637\",\n \"text\": \"The placental leucine aminopeptidase (P-LAP), adipocyte-derived leucine aminopeptidase (A-LAP) and leukocyte-derived aminopeptidase (L-RAP) belong to one distinct group of the M1 family of amimopeptidases, which we term the \\\"Oxytocinase subfamily\\\". They share HEXXH(X)18E Zn-binding and GAMEN motifs essential for the enzymatic activities. Intracellular localization is the characteristic feature of the subfamily members. While P-LAP is translocated from intracellular vesicles to plasma membrane in a stimulus-dependent manner, both A-LAP and L-RAP are retained in the endoplasmic reticulum. They contain sequences necessary for the specific localization in the cell. It is getting evident that the subfamily members play important roles in the maintenance of homeostasis including maintenance of normal pregnancy, memory retention, blood pressure regulation and antigen presentation. In this review, current situation of this newly identified subfamily is summarized.\",\n \"title\": \"The oxytocinase subfamily of M1 aminopeptidases.\"\n },\n {\n \"docid\": \"16488405\",\n \"text\": \"Physical activity induces a subclinical inflammatory response, mediated in part by leukocytes, and manifested by elevated concentrations of circulating proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). However, the source of the cytokines that appear during exercise remains unknown. In this study, we examined exercise-induced changes in plasma cytokine concentrations and their corresponding mRNA expression in peripheral blood mononuclear cells. Ten healthy [peak oxygen uptake = 48.8 ± 6.5 (SD) ml · kg−1 · min−1] but untrained men [age = 25 ± 5 (SD) yr] undertook 3 h of exercise (cycling and inclined walking) at 60–65% peak oxygen uptake. Circulating leukocyte subset counts were elevated during and 2 h postexercise but returned to normal within 24 h. Plasma concentrations of IL-1β, IL-6, and TNF-α peaked at the end of exercise and remained elevated at 2 h (IL-6) and up to 24 h (IL-1β and TNF-α) postexercise. Cytokine gene expression in circulating mononucl...\",\n \"title\": \"Downloaded from\"\n },\n {\n \"docid\": \"1686881\",\n \"text\": \"BACKGROUND Patients with familial amyloid polyneuropathy, a rare hereditary form of amyloidosis, have progressive autonomic neuropathy. The disease usually does not induce heart failure but is associated with sudden death, conduction disturbances, and an increased risk of complications during anesthesia. Although cardiac sympathetic denervation has been clearly demonstrated, the postsynaptic status of the cardiac autonomic nervous system remains unelucidated. METHODS AND RESULTS Twenty-one patients were studied (age, 39+/-11 years; normal coronary arteries; left ventricular ejection fraction 68+/-9%). To evaluate the density and affinity constants of myocardial muscarinic receptors, PET with (11)C-MQNB (methylquinuclidinyl benzilate), a specific hydrophilic antagonist, was used. Cardiac beta-receptor functional efficiency was studied by the heart rate (HR) response to intravenous infusion of isoproterenol (5 minutes after 2 mg of atropine, 5, 10, and 15 ng/kg per minute during 5 minutes per step). The mean muscarinic receptor density was higher in patients than in control subjects (B'(max), 35.5+/-8.9 versus 26.1+/-6.7 pmol/mL, P=0.003), without change in receptor affinity. The increase in HR after injection of atropine as well as of MQNB was lower in patients compared with control subjects despite a similar basal HR (DeltaHR after atropine, 11+/-21% versus 62+/-17%; P<0.001), consistent with parasympathetic denervation. Incremental infusion of isoproterenol induced a similar increase in HR in patients and control subjects. CONCLUSIONS Cardiac autonomic denervation in familial amyloid polyneuropathy results in an upregulation of myocardial muscarinic receptors but without change in cardiac beta-receptor responsiveness to catecholamines.\",\n \"title\": \"Myocardial muscarinic receptor upregulation and normal response to isoproterenol in denervated hearts by familial amyloid polyneuropathy.\"\n },\n {\n \"docid\": \"12631697\",\n \"text\": \"Limited neural input results in muscle weakness in neuromuscular disease because of a reduction in the density of muscle innervation, the rate of neuromuscular junction activation or the efficiency of synaptic transmission. We developed a small-molecule fast-skeletal-troponin activator, CK-2017357, as a means to increase muscle strength by amplifying the response of muscle when neural input is otherwise diminished secondary to neuromuscular disease. Binding selectively to the fast-skeletal-troponin complex, CK-2017357 slows the rate of calcium release from troponin C and sensitizes muscle to calcium. As a consequence, the force-calcium relationship of muscle fibers shifts leftwards, as does the force-frequency relationship of a nerve-muscle pair, so that CK-2017357 increases the production of muscle force in situ at sub-maximal nerve stimulation rates. Notably, we show that sensitization of the fast-skeletal-troponin complex to calcium improves muscle force and grip strength immediately after administration of single doses of CK-2017357 in a model of the neuromuscular disease myasthenia gravis. Troponin activation may provide a new therapeutic approach to improve physical activity in diseases where neuromuscular function is compromised.\",\n \"title\": \"Activation of fast skeletal muscle troponin as a potential therapeutic approach for treating neuromuscular diseases\"\n }\n]"}}},{"rowIdx":2591,"cells":{"query_id":{"kind":"string","value":"365"},"query":{"kind":"string","value":"ER-localized phosphatase Sac1 processes PI4P through coordination with OSBP and the endosome-localized protein sorting nexin 2."},"positive_passages":{"kind":"list like","value":[{"docid":"600437","text":"VAP (VAPA and VAPB) is an evolutionarily conserved endoplasmic reticulum (ER)-anchored protein that helps generate tethers between the ER and other membranes through which lipids are exchanged across adjacent bilayers. Here, we report that by regulating PI4P levels on endosomes, VAP affects WASH-dependent actin nucleation on these organelles and the function of the retromer, a protein coat responsible for endosome-to-Golgi traffic. VAP is recruited to retromer budding sites on endosomes via an interaction with the retromer SNX2 subunit. Cells lacking VAP accumulate high levels of PI4P, actin comets, and trans-Golgi proteins on endosomes. Such defects are mimicked by downregulation of OSBP, a VAP interactor and PI4P transporter that participates in VAP-dependent ER-endosomes tethers. These results reveal a role of PI4P in retromer-/WASH-dependent budding from endosomes. Collectively, our data show how the ER can control budding dynamics and association with the cytoskeleton of another membrane by direct contacts leading to bilayer lipid modifications.","title":"Endosome-ER Contacts Control Actin Nucleation and Retromer Function through VAP-Dependent Regulation of PI4P"}],"string":"[\n {\n \"docid\": \"600437\",\n \"text\": \"VAP (VAPA and VAPB) is an evolutionarily conserved endoplasmic reticulum (ER)-anchored protein that helps generate tethers between the ER and other membranes through which lipids are exchanged across adjacent bilayers. Here, we report that by regulating PI4P levels on endosomes, VAP affects WASH-dependent actin nucleation on these organelles and the function of the retromer, a protein coat responsible for endosome-to-Golgi traffic. VAP is recruited to retromer budding sites on endosomes via an interaction with the retromer SNX2 subunit. Cells lacking VAP accumulate high levels of PI4P, actin comets, and trans-Golgi proteins on endosomes. Such defects are mimicked by downregulation of OSBP, a VAP interactor and PI4P transporter that participates in VAP-dependent ER-endosomes tethers. These results reveal a role of PI4P in retromer-/WASH-dependent budding from endosomes. Collectively, our data show how the ER can control budding dynamics and association with the cytoskeleton of another membrane by direct contacts leading to bilayer lipid modifications.\",\n \"title\": \"Endosome-ER Contacts Control Actin Nucleation and Retromer Function through VAP-Dependent Regulation of PI4P\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"11250124","text":"Synaptic vesicle recycling involves AP-2/clathrin-mediated endocytosis, but it is not known whether the endosomal pathway is also required. Mice deficient in the tissue-specific AP-1-sigma1B complex have impaired synaptic vesicle recycling in hippocampal synapses. The ubiquitously expressed AP-1-sigma1A complex mediates protein sorting between the trans-Golgi network and early endosomes. Vertebrates express three sigma1 subunit isoforms: A, B and C. The expressions of sigma1A and sigma1B are highest in the brain. Synaptic vesicle reformation in cultured neurons from sigma1B-deficient mice is reduced upon stimulation, and large endosomal intermediates accumulate. The sigma1B-deficient mice have reduced motor coordination and severely impaired long-term spatial memory. These data reveal a molecular mechanism for a severe human X-chromosome-linked mental retardation.","title":"AP-1/sigma1B-adaptin mediates endosomal synaptic vesicle recycling, learning and memory."},{"docid":"9680193","text":"The ubiquitin-binding protein Hrs and endosomal sorting complex required for transport (ESCRT)-I and ESCRT-III are involved in sorting endocytosed and ubiquitinated receptors to lysosomes for degradation and efficient termination of signaling. In this study, we have investigated the role of the ESCRT-II subunit Vps22/EAP30 in degradative protein sorting of ubiquitinated receptors. Vps22 transiently expressed in HeLa cells was detected in endosomes containing endocytosed epidermal growth factor receptors (EGFRs) as well as Hrs and ESCRT-I and ESCRT-III. Depletion of Vps22 by small interfering RNA, which was accompanied by decreased levels of other ESCRT-II subunits, greatly reduced degradation of EGFR and its ligand EGF as well as the chemokine receptor CXCR4. EGFR accumulated on the limiting membranes of early endosomes and aberrantly small multivesicular bodies in Vps22-depleted cells. Phosphorylation and nuclear translocation of extracellular-signal-regulated kinase1/2 downstream of the EGF-activated receptor were sustained by depletion of Hrs or the ESCRT-I subunit Tsg101. In contrast, this was not the case when Vps22 was depleted. These results indicate an important role for Vps22 in ligand-induced EGFR and CXCR4 turnover and suggest that termination of EGF signaling occurs prior to ESCRT-II engagement.","title":"Vps22/EAP30 in ESCRT-II mediates endosomal sorting of growth factor and chemokine receptors destined for lysosomal degradation."},{"docid":"4429388","text":"The ESCRT (endosomal sorting complex required for transport) pathway is required for terminal membrane fission events in several important biological processes, including endosomal intraluminal vesicle formation, HIV budding and cytokinesis. VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly, possibly in conjunction with membrane fission. Here we show that the microtubule interacting and transport (MIT) domains of human VPS4A and VPS4B bind conserved sequence motifs located at the carboxy termini of the CHMP1–3 class of ESCRT-III proteins. Structures of VPS4A MIT–CHMP1A and VPS4B MIT–CHMP2B complexes reveal that the C-terminal CHMP motif forms an amphipathic helix that binds in a groove between the last two helices of the tetratricopeptide-like repeat (TPR) of the VPS4 MIT domain, but in the opposite orientation to that of a canonical TPR interaction. Distinct pockets in the MIT domain bind three conserved leucine residues of the CHMP motif, and mutations that inhibit these interactions block VPS4 recruitment, impair endosomal protein sorting and relieve dominant-negative VPS4 inhibition of HIV budding. Thus, our studies reveal how the VPS4 ATPases recognize their CHMP substrates to facilitate the membrane fission events required for the release of viruses, endosomal vesicles and daughter cells.","title":"ESCRT-III recognition by VPS4 ATPases"},{"docid":"11289247","text":"The regulation and coordination of mitochondrial metabolism with hematopoietic stem cell (HSC) self-renewal and differentiation is not fully understood. Here we report that depletion of PTPMT1, a PTEN-like mitochondrial phosphatase, in inducible or hematopoietic-cell-specific knockout mice resulted in hematopoietic failure due to changes in the cell cycle and a block in the differentiation of HSCs. Surprisingly, the HSC pool was increased by ∼40-fold in PTPMT1 knockout mice. Reintroduction of wild-type PTPMT1, but not catalytically deficient PTPMT1 or truncated PTPMT1 lacking mitochondrial localization, restored differentiation capabilities of PTPMT1 knockout HSCs. Further analyses demonstrated that PTPMT1 deficiency altered mitochondrial metabolism and that phosphatidylinositol phosphate substrates of PTPMT1 directly enhanced fatty-acid-induced activation of mitochondrial uncoupling protein 2. Intriguingly, depletion of PTPMT1 from myeloid, T lymphoid, or B lymphoid progenitors did not cause any defects in lineage-specific knockout mice. This study establishes a crucial role of PTPMT1 in the metabolic regulation of HSC function.","title":"Metabolic regulation by the mitochondrial phosphatase PTPMT1 is required for hematopoietic stem cell differentiation."},{"docid":"17017465","text":"The small GTPases, Rab5 and Rac, are essential for endocytosis and actin remodeling, respectively. Coordination of these processes is critical to achieve spatial restriction of intracellular signaling, which is essential for a variety of polarized functions. Here, we show that clathrin- and Rab5-mediated endocytosis are required for the activation of Rac induced by motogenic stimuli. Rac activation occurs on early endosomes, where the RacGEF Tiam1 is also recruited. Subsequent recycling of Rac to the plasma membrane ensures localized signaling, leading to the formation of actin-based migratory protrusions. Thus, membrane trafficking of Rac is required for the spatial resolution of Rac-dependent motogenic signals. We further demonstrate that a Rab5-to-Rac circuitry controls the morphology of motile mammalian tumor cells and primordial germinal cells during zebrafish development, suggesting that this circuitry is relevant for the regulation of migratory programs in various cells, in both in vitro settings and whole organisms.","title":"Endocytic Trafficking of Rac Is Required for the Spatial Restriction of Signaling in Cell Migration"},{"docid":"19561411","text":"Orai1 and stromal interaction molecule 1 (STIM1) mediate store-operated Ca(2+) entry (SOCE) in immune cells. STIM1, an endoplasmic reticulum (ER) Ca(2+) sensor, detects store depletion and interacts with plasma membrane (PM)-resident Orai1 channels at the ER-PM junctions. However, the molecular composition of these junctions in T cells remains poorly understood. Here, we show that junctophilin-4 (JP4), a member of junctional proteins in excitable cells, is expressed in T cells and localized at the ER-PM junctions to regulate Ca(2+) signaling. Silencing or genetic manipulation of JP4 decreased ER Ca(2+) content and SOCE in T cells, impaired activation of the nuclear factor of activated T cells (NFAT) and extracellular signaling-related kinase (ERK) signaling pathways, and diminished expression of activation markers and cytokines. Mechanistically, JP4 directly interacted with STIM1 via its cytoplasmic domain and facilitated its recruitment into the junctions. Accordingly, expression of this cytoplasmic fragment of JP4 inhibited SOCE. Furthermore, JP4 also formed a complex with junctate, a Ca(2+)-sensing ER-resident protein, previously shown to mediate STIM1 recruitment into the junctions. We propose that the junctate-JP4 complex located at the junctions cooperatively interacts with STIM1 to maintain ER Ca(2+) homeostasis and mediate SOCE in T cells.","title":"Junctophilin-4, a component of the endoplasmic reticulum-plasma membrane junctions, regulates Ca2+ dynamics in T cells."},{"docid":"18264714","text":"All cells perceive and respond to environmental stresses through elaborate stress-sensing networks. Yeast cells sense stress through diverse signaling pathways that converge on the transcription factors Msn2 and Msn4, which respond by initiating rapid, idiosyncratic cycles into and out of the nucleus. To understand the role of Msn2/4 nuclear localization dynamics, we combined time-lapse studies of Msn2-GFP localization in living cells with computational modeling of stress-sensing signaling networks. We find that several signaling pathways, including Ras/protein kinase A, AMP-activated kinase, the high-osmolarity response mitogen-activated protein kinase pathway, and protein phosphatase 1, regulate activation of Msn2 in distinct ways in response to different stresses. Moreover, we find that bursts of nuclear localization elicit a more robust transcriptional response than does sustained nuclear localization. Using stochastic modeling, we reproduce in silico the responses of Msn2 to different stresses, and demonstrate that bursts of localization arise from noise in the signaling pathways amplified by the small number of Msn2 molecules in the cell. This noise imparts diverse behaviors to genetically identical cells, allowing cell populations to \"hedge their bets\" in responding to an uncertain future, and to balance growth and survival in an unpredictable environment.","title":"Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses"},{"docid":"4388082","text":"In a Drosophila follicle the oocyte always occupies a posterior position among a group of sixteen germline cells. Although the importance of this cell arrangement for the subsequent formation of the anterior-posterior axis of the embryo is well documented, the molecular mechanism responsible for the posterior localization of the oocyte was unknown. Here we show that the homophilic adhesion molecule DE-cadherin mediates oocyte positioning. During follicle biogenesis, DE-cadherin is expressed in germline (including oocyte) and surrounding follicle cells, with the highest concentration of DE-cadherin being found at the interface between oocyte and posterior follicle cells. Mosaic analysis shows that DE-cadherin is required in both germline and follicle cells for correct oocyte localization, indicating that germline-soma interactions may be involved in this process. By analysing the behaviour of the oocyte in follicles with a chimaeric follicular epithelium, we find that the position of the oocyte is determined by the position of DE-cadherin-expressing follicle cells, to which the oocyte attaches itself selectively. Among the DE-cadherin positive follicle cells, the oocyte preferentially contacts those cells that express higher levels of DE-cadherin. On the basis of these data, we propose that in wild-type follicles the oocyte competes successfully with its sister germline cells for contact to the posterior follicle cells, a sorting process driven by different concentrations of DE-cadherin. This is, to our knowledge, the first in vivo example of a cell-sorting process that depends on differential adhesion mediated by a cadherin.","title":"Drosophila oocyte localization is mediated by differential cadherin-based adhesion."},{"docid":"2593298","text":"Receptor endocytosis is a fundamental step in controlling the magnitude, duration, and nature of cell signaling events. Confluent endothelial cells are contact inhibited in their growth and respond poorly to the proliferative signals of vascular endothelial growth factor (VEGF). In a previous study, we found that the association of vascular endothelial cadherin (VEC) with VEGF receptor (VEGFR) type 2 contributes to density-dependent growth inhibition (Lampugnani, G.M., A. Zanetti, M. Corada, T. Takahashi, G. Balconi, F. Breviario, F. Orsenigo, A. Cattelino, R. Kemler, T.O. Daniel, and E. Dejana. 2003. J. Cell Biol. 161:793–804). In the present study, we describe the mechanism through which VEC reduces VEGFR-2 signaling. We found that VEGF induces the clathrin-dependent internalization of VEGFR-2. When VEC is absent or not engaged at junctions, VEGFR-2 is internalized more rapidly and remains in endosomal compartments for a longer time. Internalization does not terminate its signaling; instead, the internalized receptor is phosphorylated, codistributes with active phospholipase C–γ, and activates p44/42 mitogen-activated protein kinase phosphorylation and cell proliferation. Inhibition of VEGFR-2 internalization reestablishes the contact inhibition of cell growth, whereas silencing the junction-associated density-enhanced phosphatase-1/CD148 phosphatase restores VEGFR-2 internalization and signaling. Thus, VEC limits cell proliferation by retaining VEGFR-2 at the membrane and preventing its internalization into signaling compartments.","title":"Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from intracellular compartments"},{"docid":"12871002","text":"We have studied the function of a conserved germline-specific nucleotidyltransferase protein, CDE-1, in RNAi and chromosome segregation in C. elegans. CDE-1 localizes specifically to mitotic chromosomes in embryos. This localization requires the RdRP EGO-1, which physically interacts with CDE-1, and the Argonaute protein CSR-1. We found that CDE-1 is required for the uridylation of CSR-1 bound siRNAs, and that in the absence of CDE-1 these siRNAs accumulate to inappropriate levels, accompanied by defects in both meiotic and mitotic chromosome segregation. Elevated siRNA levels are associated with erroneous gene silencing, most likely through the inappropriate loading of CSR-1 siRNAs into other Argonaute proteins. We propose a model in which CDE-1 restricts specific EGO-1-generated siRNAs to the CSR-1 mediated, chromosome associated RNAi pathway, thus separating it from other endogenous RNAi pathways. The conserved nature of CDE-1 suggests that similar sorting mechanisms may operate in other animals, including mammals.","title":"CDE-1 Affects Chromosome Segregation through Uridylation of CSR-1-Bound siRNAs"},{"docid":"15600979","text":"EMSY links the BRCA2 pathway to sporadic breast/ovarian cancer. It encodes a nuclear protein that binds to the BRCA2 N-terminal domain implicated in chromatin/transcription regulation, but when sporadically amplified/overexpressed, increased EMSY level represses BRCA2 transactivation potential and induces chromosomal instability, mimicking the activity of BRCA2 mutations in the development of hereditary breast/ovarian cancer. In addition to chromatin/transcription regulation, EMSY may also play a role in the DNA-damage response, suggested by its ability to localize at chromatin sites of DNA damage/repair. This implies that EMSY overexpression may also repress BRCA2 in DNA-damage replication/checkpoint and recombination/repair, coordinated processes that also require its interacting proteins: PALB2, the partner and localizer of BRCA2; RPA, replication/checkpoint protein A; and RAD51, the inseparable recombination/repair enzyme. Here, using a well-characterized recombination/repair assay system, we demonstrate that a slight increase in EMSY level can indeed repress these two processes independently of transcriptional interference/repression. Since EMSY, RPA and PALB2 all bind to the same BRCA2 region, these findings further support a scenario wherein: (a) EMSY amplification may mimic BRCA2 deficiency, at least by overriding RPA and PALB2, crippling the BRCA2/RAD51 complex at DNA-damage and replication/transcription sites; and (b) BRCA2/RAD51 may coordinate these processes by employing at least EMSY, PALB2 and RPA. We extensively discuss the molecular details of how this can happen to ascertain its implications for a novel recombination mechanism apparently conceived as checkpoint rather than a DNA repair system for cell division, survival, death, and human diseases, including the tissue specificity of cancer predisposition, which may renew our thinking about targeted therapy and prevention.","title":"EMSY overexpression disrupts the BRCA2/RAD51 pathway in the DNA-damage response: implications for chromosomal instability/recombination syndromes as checkpoint diseases"},{"docid":"31851367","text":"Estrogens are key regulators of growth, differentiation, and the physiological functions of a wide range of target tissues, including the male and female reproductive tracts, breast, and skeletal, nervous, cardiovascular, digestive and immune systems. The majority of these biological activities of estrogens are mediated through two genetically distinct receptors, ERalpha and ERbeta, which function as hormone-inducible transcription factors. Over the past decade, it has become increasingly clear that the recruitment of coregulatory proteins to ERs is required for ER-mediated transcriptional and biological activities. These \"coactivator\" complexes enable the ERs to respond appropriately: 1) to hormones or pharmacological ligands, 2) interpret extra- and intra-cellular signals, 3) catalyze the process of chromatin condensation and 4) to communicate with the general transcription apparatus at target gene promoters. In addition to activating proteins, the existence of corepressors, proteins that function as negative regulators of ER activity in either physiological or pharmacological contexts, provides an additional level of complexity in ER action. This review also describes current efforts aimed at developing pharmaceutical agents that target ER-cofactor interactions as therapeutics for estrogen-associated pathologies.","title":"Coregulators in nuclear estrogen receptor action: from concept to therapeutic targeting."},{"docid":"12800122","text":"Subdividing proliferating tissues into compartments is an evolutionarily conserved strategy of animal development [1-6]. Signals across boundaries between compartments can result in local expression of secreted proteins organizing growth and patterning of tissues [1-6]. Sharp and straight interfaces between compartments are crucial for stabilizing the position of such organizers and therefore for precise implementation of body plans. Maintaining boundaries in proliferating tissues requires mechanisms to counteract cell rearrangements caused by cell division; however, the nature of such mechanisms remains unclear. Here we quantitatively analyzed cell morphology and the response to the laser ablation of cell bonds in the vicinity of the anteroposterior compartment boundary in developing Drosophila wings. We found that mechanical tension is approximately 2.5-fold increased on cell bonds along this compartment boundary as compared to the remaining tissue. Cell bond tension is decreased in the presence of Y-27632 [7], an inhibitor of Rho-kinase whose main effector is Myosin II [8]. Simulations using a vertex model [9] demonstrate that a 2.5-fold increase in local cell bond tension suffices to guide the rearrangement of cells after cell division to maintain compartment boundaries. Our results provide a physical mechanism in which the local increase in Myosin II-dependent cell bond tension directs cell sorting at compartment boundaries.","title":"Increased Cell Bond Tension Governs Cell Sorting at the Drosophila Anteroposterior Compartment Boundary"},{"docid":"6492658","text":"Weeble mutant mice have severe locomotor instability and significant neuronal loss in the cerebellum and in the hippocampal CA1 field. Genetic mapping was used to localize the mutation to the gene encoding inositol polyphosphate 4-phosphatase type I (Inpp4a), where a single nucleotide deletion results in a likely null allele. The substrates of INPP4A are intermediates in a pathway affecting intracellular Ca(2+) release but are also involved in cell cycle regulation through binding the Akt protooncogene; dysfunction in either may account for the neuronal loss of weeble mice. Although other mutations in phosphoinositide enzymes are associated with synaptic defects without neuronal loss, weeble shows that Inpp4a is critical for the survival of a subset of neurons during postnatal development in mice.","title":"A Null Mutation in Inositol Polyphosphate 4-Phosphatase Type I Causes Selective Neuronal Loss in Weeble Mutant Mice"},{"docid":"6333347","text":"An emerging family of kinases related to the Drosophila Aurora and budding yeast Ipl1 proteins has been implicated in chromosome segregation and mitotic spindle formation in a number of organisms. Unlike other Aurora/Ipl1-related kinases, the Caenorhabditis elegans orthologue, AIR-2, is associated with meiotic and mitotic chromosomes. AIR-2 is initially localized to the chromosomes of the most mature prophase I–arrested oocyte residing next to the spermatheca. This localization is dependent on the presence of sperm in the spermatheca. After fertilization, AIR-2 remains associated with chromosomes during each meiotic division. However, during both meiotic anaphases, AIR-2 is present between the separating chromosomes. AIR-2 also remains associated with both extruded polar bodies. In the embryo, AIR-2 is found on metaphase chromosomes, moves to midbody microtubules at anaphase, and then persists at the cytokinesis remnant. Disruption of AIR-2 expression by RNA- mediated interference produces entire broods of one-cell embryos that have executed multiple cell cycles in the complete absence of cytokinesis. The embryos accumulate large amounts of DNA and microtubule asters. Polar bodies are not extruded, but remain in the embryo where they continue to replicate. The cytokinesis defect appears to be late in the cell cycle because transient cleavage furrows initiate at the proper location, but regress before the division is complete. Additionally, staining with a marker of midbody microtubules revealed that at least some of the components of the midbody are not well localized in the absence of AIR-2 activity. Our results suggest that during each meiotic and mitotic division, AIR-2 may coordinate the congression of metaphase chromosomes with the subsequent events of polar body extrusion and cytokinesis.","title":"AIR-2: An Aurora/Ipl1-related Protein Kinase Associated with Chromosomes and Midbody Microtubules Is Required for Polar Body Extrusion and Cytokinesis in Caenorhabditis elegans Embryos "},{"docid":"4324278","text":"The rapamycin-sensitive TOR signalling pathway in Saccharomyces cerevisiae activates a cell-growth program in response to nutrients such as nitrogen and carbon. The TOR1 and TOR2 kinases (TOR) control cytoplasmic protein synthesis and degradation through the conserved TAP42 protein. Upon phosphorylation by TOR, TAP42 binds and possibly inhibits type 2A and type-2A-related phosphatases; however, the mechanism by which TOR controls nuclear events such as global repression of starvation-specific transcription is unknown. Here we show that TOR prevents transcription of genes expressed upon nitrogen limitation by promoting the association of the GATA transcription factor GLN3 with the cytoplasmic protein URE2. The binding of GLN3 to URE2 requires TOR-dependent phosphorylation of GLN3. Phosphorylation and cytoplasmic retention of GLN3 are also dependent on the TOR effector TAP42, and are antagonized by the type-2A-related phosphatase SIT4. TOR inhibits expression of carbon-source-regulated genes by stimulating the binding of the transcriptional activators MSN2 and MSN4 to the cytoplasmic 14-3-3 protein BMH2. Thus, the TOR signalling pathway broadly controls nutrient metabolism by sequestering several transcription factors in the cytoplasm.","title":"The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors."},{"docid":"24555417","text":"In many species, oocyte meiosis is carried out in the absence of centrioles. As a result, microtubule organization, spindle assembly, and chromosome segregation proceed by unique mechanisms. Here, we report insights into the principles underlying this specialized form of cell division, through studies of C. elegans KLP-15 and KLP-16, two highly homologous members of the kinesin-14 family of minus-end-directed kinesins. These proteins localize to the acentriolar oocyte spindle and promote microtubule bundling during spindle assembly; following KLP-15/16 depletion, microtubule bundles form but then collapse into a disorganized array. Surprisingly, despite this defect we found that during anaphase, microtubules are able to reorganize into a bundled array that facilitates chromosome segregation. This phenotype therefore enabled us to identify factors promoting microtubule organization during anaphase, whose contributions are normally undetectable in wild-type worms; we found that SPD-1 (PRC1) bundles microtubules and KLP-18 (kinesin-12) likely sorts those bundles into a functional orientation capable of mediating chromosome segregation. Therefore, our studies have revealed an interplay between distinct mechanisms that together promote spindle formation and chromosome segregation in the absence of structural cues such as centrioles.","title":"Interplay between microtubule bundling and sorting factors ensures acentriolar spindle stability during C. elegans oocyte meiosis"},{"docid":"24558930","text":"Although assembly of acentrosomal meiotic spindles has been extensively studied, little is known about the segregation of chromosomes on these spindles. Here, we show in Caenorhabditis elegans oocytes that the kinetochore protein, KNL-1, directs assembly of meiotic kinetochores that orient chromosomes. However, in contrast to mitosis, chromosome separation during meiotic anaphase is kinetochore-independent. Before anaphase, meiotic kinetochores and spindle poles disassemble along with the microtubules on the poleward side of chromosomes. During anaphase, microtubules then form between the separating chromosomes. Functional analysis implicated a set of proteins that localize to a ring-shaped domain between kinetochores during pre-anaphase spindle assembly and anaphase separation. These proteins are localized by the chromosomal passenger complex, which regulates the loss of meiotic chromosome cohesion. Thus, meiotic segregation in C. elegans is a two-stage process, where kinetochores orient chromosomes, but are then dispensable for their separation. We suggest that separation is controlled by a meiosis-specific chromosomal domain to coordinate cohesin removal and chromosome segregation.","title":"A kinetochore-independent mechanism drives anaphase chromosome separation during acentrosomal meiosis"},{"docid":"25510546","text":"Increased lipid supply causes beta cell death, which may contribute to reduced beta cell mass in type 2 diabetes. We investigated whether endoplasmic reticulum (ER) stress is necessary for lipid-induced apoptosis in beta cells and also whether ER stress is present in islets of an animal model of diabetes and of humans with type 2 diabetes. Expression of genes involved in ER stress was evaluated in insulin-secreting MIN6 cells exposed to elevated lipids, in islets isolated from db/db mice and in pancreas sections of humans with type 2 diabetes. Overproduction of the ER chaperone heat shock 70 kDa protein 5 (HSPA5, previously known as immunoglobulin heavy chain binding protein [BIP]) was performed to assess whether attenuation of ER stress affected lipid-induced apoptosis. We demonstrated that the pro-apoptotic fatty acid palmitate triggers a comprehensive ER stress response in MIN6 cells, which was virtually absent using non-apoptotic fatty acid oleate. Time-dependent increases in mRNA levels for activating transcription factor 4 (Atf4), DNA-damage inducible transcript 3 (Ddit3, previously known as C/EBP homologous protein [Chop]) and DnaJ homologue (HSP40) C3 (Dnajc3, previously known as p58) correlated with increased apoptosis in palmitate- but not in oleate-treated MIN6 cells. Attenuation of ER stress by overproduction of HSPA5 in MIN6 cells significantly protected against lipid-induced apoptosis. In islets of db/db mice, a variety of marker genes of ER stress were also upregulated. Increased processing (activation) of X-box binding protein 1 (Xbp1) mRNA was also observed, confirming the existence of ER stress. Finally, we observed increased islet protein production of HSPA5, DDIT3, DNAJC3 and BCL2-associated X protein in human pancreas sections of type 2 diabetes subjects. Our results provide evidence that ER stress occurs in type 2 diabetes and is required for aspects of the underlying beta cell failure.","title":"Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes"},{"docid":"42855554","text":"To clarify the fate of glycosylphosphatidylinositol (GPI) in mammals, we developed GPI-anchored enhanced green fluorescent protein (EGFP-GPI) and transgenic mice carrying this fusion construct. When it was introduced to culture cells, the EGFP-GPI protein was correctly sorted to plasma membranes and microsomes depending on GPI biosynthesis. Transgenic mice carrying EGFP-GPI were found to show a broad transgene expression. Histologically, a prominent polarized localization of EGFP-GPI protein was observed in various epithelia, the nervous system and liver and secreted from some exocrine glands, as well as non-polarized presence in non-epithelial tissues, demonstrating a tissue-inherent manner of GPI sorting.","title":"Tissue-inherent fate of GPI revealed by GPI-anchored GFP transgenesis."},{"docid":"20460020","text":"Efficient local monocyte/macrophage recruitment is critical for tissue repair. Recruited macrophages are polarized toward classical (proinflammatory) or alternative (prohealing) activation in response to cytokines, with tight temporal regulation crucial for efficient wound repair. Estrogen acts as a potent anti-inflammatory regulator of cutaneous healing. However, an understanding of estrogen/estrogen receptor (ER) contribution to macrophage polarization and subsequent local effects on wound healing is lacking. Here we identify, to our knowledge previously unreported, a role whereby estrogen receptor α (ERα) signaling preferentially polarizes macrophages from a range of sources to an alternative phenotype. Cell-specific ER ablation studies confirm an in vivo role for inflammatory cell ERα, but not ERβ, in poor healing associated with an altered cytokine profile and fewer alternatively activated macrophages. Furthermore, we reveal intrinsic changes in ERα-deficient macrophages, which are unable to respond to alternative activation signals in vitro. Collectively, our data reveal that inflammatory cell-expressed ERα promotes alternative macrophage polarization, which is beneficial for timely healing. Given the diverse physiological roles of ERs, these findings will likely be of relevance to many pathologies involving excessive inflammation.","title":"Estrogen receptor-alpha promotes alternative macrophage activation during cutaneous repair."},{"docid":"35231675","text":"CLIP-170 is a \"cytoplasmic linker protein\" implicated in endosome-microtubule interactions and in control of microtubule dynamics. CLIP-170 localizes dynamically to growing microtubule plus ends, colocalizing with the dynein activator dynactin and the APC-binding protein EB1. This shared \"plus-end tracking\" behavior suggests that CLIP-170 might interact with dynactin and/or EB1. We have used site-specific mutagenesis of CLIP-170 and a transfection/colocalization assay to address this question in mammalian tissue culture cells. Our results indicate that CLIP-170 interacts, directly or indirectly, with both dynactin and EB1. We find that the CLIP-170/dynactin interaction is mediated by the second metal binding motif of the CLIP-170 tail. In contrast, the CLIP-170/EB1 interaction requires neither metal binding motif. In addition, our experiments suggest that the CLIP-170/dynactin interaction occurs via the shoulder/sidearm subcomplex of dynactin and can occur in the cytosol (i.e., it does not require microtubule binding). These results have implications for the targeting of both dynactin and EB1 to microtubule plus ends. Our data suggest that the CLIP-170/dynactin interaction can target dynactin complex to microtubule plus ends, although dynactin likely also targets MT plus ends directly via the microtubule binding motif of the p150(Glued) subunit. We find that CLIP-170 mutants alter p150(Glued) localization without affecting EB1, indicating that EB1 can target microtubule plus ends independently of dynactin.","title":"CLIP-170 interacts with dynactin complex and the APC-binding protein EB1 by different mechanisms."},{"docid":"37964706","text":"Ca2+ entry through store-operated Ca2+ channels drives the production of the pro-inflammatory molecule leukotriene C4 (LTC4) from mast cells through a pathway involving Ca2+-dependent protein kinase C, mitogen-activated protein kinases ERK1/2, phospholipase A2, and 5-lipoxygenase. Here we examine whether local Ca2+ influx through store-operated Ca2+ release-activated Ca2+ (CRAC) channels in the plasma membrane stimulates this signaling pathway. Manipulating the amplitude and spatial extent of Ca2+ entry by altering chemical and electrical gradients for Ca2+ influx or changing the Ca2+ buffering of the cytoplasm all impacted on protein kinase C and ERK activation, generation of arachidonic acid and LTC4 secretion, with little change in the bulk cytoplasmic Ca2+ rise. Similar bulk cytoplasmic Ca2+ concentrations were achieved when CRAC channels were activated in 0.25 mm external Ca2+ versus 2 mm Ca2+ and 100 nm La3+, an inhibitor of CRAC channels. However, despite similar bulk cytoplasmic Ca2+, protein kinase C activation and LTC4 secretion were larger in 2 mm Ca2+ and La3+ than in 0.25 mm Ca2+, consistent with the central involvement of a subplasmalemmal Ca2+ rise. The nonreceptor tyrosine kinase Syk coupled CRAC channel opening to protein kinase C and ERK activation. Recombinant TRPC3 channels also activated protein kinase C, suggesting that subplasmalemmal Ca2+ rather than a microdomain exclusive to CRAC channels is the trigger. Hence a subplasmalemmal Ca2+ increase in mast cells is highly versatile in that it triggers cytoplasmic responses through generation of intracellular messengers as well as long distance changes through increased secretion of paracrine signals.","title":"Local Ca2+ influx through Ca2+ release-activated Ca2+ (CRAC) channels stimulates production of an intracellular messenger and an intercellular pro-inflammatory signal."},{"docid":"17194716","text":"In this study, the mechanisms of actin-bundling in filopodia were examined. Analysis of cellular localization of known actin cross-linking proteins in mouse melanoma B16F1 cells revealed that fascin was specifically localized along the entire length of all filopodia, whereas other actin cross-linkers were not. RNA interference of fascin reduced the number of filopodia, and remaining filopodia had abnormal morphology with wavy and loosely bundled actin organization. Dephosphorylation of serine 39 likely determined cellular filopodia frequency. The constitutively active fascin mutant S39A increased the number and length of filopodia, whereas the inactive fascin mutant S39E reduced filopodia frequency. Fluorescence recovery after photobleaching of GFP-tagged wild-type and S39A fascin showed that dephosphorylated fascin underwent rapid cycles of association to and dissociation from actin filaments in filopodia, with t1/2 < 10 s. We propose that fascin is a key specific actin cross-linker, providing stiffness for filopodial bundles, and that its dynamic behavior allows for efficient coordination between elongation and bundling of filopodial actin filaments.","title":"Role of fascin in filopodial protrusion"},{"docid":"25623469","text":"A newly emerging family of phosphatases that are members of the haloacid dehalogenase superfamily contains the catalytic motif DXDX(T/V). A member of this DXDX(T/V) phosphatase family known as Dullard was recently shown to be a potential regulator of neural tube development in Xenopus [Satow R, Chan TC, Asashima M (2002) Biochem Biophys Res Commun 295:85-91]. Herein, we demonstrate that human Dullard and the yeast protein Nem1p perform similar functions in mammalian cells and yeast cells, respectively. In addition to similarity in primary sequence, Dullard and Nem1p possess similar domains and show similar substrate preferences, and both localize to the nuclear envelope. Additionally, we show that human Dullard can rescue the aberrant nuclear envelope morphology of nem1Delta yeast cells, functionally replacing Nem1p. Finally, Nem1p, has been shown to deposphorylate the yeast phosphatidic acid phosphatase Smp2p [Santos-Rosa H, Leung J, Grimsey N, Peak-Chew S, Siniossoglou S (2005) EMBO J 24:1931-1941], and we show that Dullard dephosphorylates the mammalian phospatidic acid phosphatase, lipin. Therefore, we propose that Dullard participates in a unique phosphatase cascade regulating nuclear membrane biogenesis, and that this cascade is conserved from yeast to mammals.","title":"A conserved phosphatase cascade that regulates nuclear membrane biogenesis."},{"docid":"1991105","text":"Mitochondrial division is important for mitochondrial distribution and function. Recent data have demonstrated that ER-mitochondria contacts mark mitochondrial division sites, but the molecular basis and functions of these contacts are not understood. Here we show that in yeast, the ER-mitochondria tethering complex, ERMES, and the highly conserved Miro GTPase, Gem1, are spatially and functionally linked to ER-associated mitochondrial division. Gem1 acts as a negative regulator of ER-mitochondria contacts, an activity required for the spatial resolution and distribution of newly generated mitochondrial tips following division. Previous data have demonstrated that ERMES localizes with a subset of actively replicating mitochondrial nucleoids. We show that mitochondrial division is spatially linked to nucleoids and that a majority of these nucleoids segregate prior to division, resulting in their distribution into newly generated tips in the mitochondrial network. Thus, we postulate that ER-associated division serves to link the distribution of mitochondria and mitochondrial nucleoids in cells. DOI:http://dx.doi.org/10.7554/eLife.00422.001.","title":"ER-associated mitochondrial division links the distribution of mitochondria and mitochondrial DNA in yeast"},{"docid":"13936152","text":"Partitioning tissues into compartments that do not intermix is essential for the correct morphogenesis of animal embryos and organs. Several hypotheses have been proposed to explain compartmental cell sorting, mainly differential adhesion, but also regulation of the cytoskeleton or of cell proliferation. Nevertheless, the molecular and cellular mechanisms that keep cells apart at boundaries remain unclear. Here we demonstrate, in early Drosophila melanogaster embryos, that actomyosin-based barriers stop cells from invading neighbouring compartments. Our analysis shows that cells can transiently invade neighbouring compartments, especially when they divide, but are then pushed back into their compartment of origin. Actomyosin cytoskeletal components are enriched at compartmental boundaries, forming cable-like structures when the epidermis is mitotically active. When MyoII (non-muscle myosin II) function is inhibited, including locally at the cable by chromophore-assisted laser inactivation (CALI), in live embryos, dividing cells are no longer pushed back, leading to compartmental cell mixing. We propose that local regulation of actomyosin contractibility, rather than differential adhesion, is the primary mechanism sorting cells at compartmental boundaries.","title":"An actomyosin-based barrier inhibits cell mixing at compartmental boundaries in Drosophila embryos"},{"docid":"16557565","text":"Plants, compared to animals, exhibit an amazing adaptability and plasticity in their development. This is largely dependent on the ability of plants to form new organs, such as lateral roots, leaves, and flowers during postembryonic development. Organ primordia develop from founder cell populations into organs by coordinated cell division and differentiation. Here, we show that organ formation in Arabidopsis involves dynamic gradients of the signaling molecule auxin with maxima at the primordia tips. These gradients are mediated by cellular efflux requiring asymmetrically localized PIN proteins, which represent a functionally redundant network for auxin distribution in both aerial and underground organs. PIN1 polar localization undergoes a dynamic rearrangement, which correlates with establishment of auxin gradients and primordium development. Our results suggest that PIN-dependent, local auxin gradients represent a common module for formation of all plant organs, regardless of their mature morphology or developmental origin.","title":"Local, Efflux-Dependent Auxin Gradients as a Common Module for Plant Organ Formation"},{"docid":"935538","text":"RNA-binding proteins are at the heart of posttranscriptional gene regulation, coordinating the processing, storage, and handling of cellular RNAs. We show here that GRSF1, previously implicated in the binding and selective translation of influenza mRNAs, is targeted to mitochondria where it forms granules that colocalize with foci of newly synthesized mtRNA next to mitochondrial nucleoids. GRSF1 preferentially binds RNAs transcribed from three contiguous genes on the light strand of mtDNA, the ND6 mRNA, and the long noncoding RNAs for cytb and ND5, each of which contains multiple consensus binding sequences. RNAi-mediated knockdown of GRSF1 leads to alterations in mitochondrial RNA stability, abnormal loading of mRNAs and lncRNAs on the mitochondrial ribosome, and impaired ribosome assembly. This results in a specific protein synthesis defect and a failure to assemble normal amounts of the oxidative phosphorylation complexes. These data implicate GRSF1 as a key regulator of posttranscriptional mitochondrial gene expression.","title":"The mitochondrial RNA-binding protein GRSF1 localizes to RNA granules and is required for posttranscriptional mitochondrial gene expression."},{"docid":"3155374","text":"Binding interactions between the plasma membrane and the cytoskeleton define cell functions such as cell shape, formation of cell processes, cell movement, and endocytosis. Here we use optical tweezers tether force measurements and show that plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2) acts as a second messenger that regulates the adhesion energy between the cytoskeleton and the plasma membrane. Receptor stimuli that hydrolyze PIP2 lowered adhesion energy, a process that could be mimicked by expressing PH domains that sequester PIP2 or by targeting a 5'-PIP2-phosphatase to the plasma membrane to selectively lower plasma membrane PIP2 concentration. Our study suggests that plasma membrane PIP2 controls dynamic membrane functions and cell shape by locally increasing and decreasing the adhesion between the actin-based cortical cytoskeleton and the plasma membrane.","title":"Phosphatidylinositol 4,5-Bisphosphate Functions as a Second Messenger that Regulates Cytoskeleton–Plasma Membrane Adhesion"}],"string":"[\n {\n \"docid\": \"11250124\",\n \"text\": \"Synaptic vesicle recycling involves AP-2/clathrin-mediated endocytosis, but it is not known whether the endosomal pathway is also required. Mice deficient in the tissue-specific AP-1-sigma1B complex have impaired synaptic vesicle recycling in hippocampal synapses. The ubiquitously expressed AP-1-sigma1A complex mediates protein sorting between the trans-Golgi network and early endosomes. Vertebrates express three sigma1 subunit isoforms: A, B and C. The expressions of sigma1A and sigma1B are highest in the brain. Synaptic vesicle reformation in cultured neurons from sigma1B-deficient mice is reduced upon stimulation, and large endosomal intermediates accumulate. The sigma1B-deficient mice have reduced motor coordination and severely impaired long-term spatial memory. These data reveal a molecular mechanism for a severe human X-chromosome-linked mental retardation.\",\n \"title\": \"AP-1/sigma1B-adaptin mediates endosomal synaptic vesicle recycling, learning and memory.\"\n },\n {\n \"docid\": \"9680193\",\n \"text\": \"The ubiquitin-binding protein Hrs and endosomal sorting complex required for transport (ESCRT)-I and ESCRT-III are involved in sorting endocytosed and ubiquitinated receptors to lysosomes for degradation and efficient termination of signaling. In this study, we have investigated the role of the ESCRT-II subunit Vps22/EAP30 in degradative protein sorting of ubiquitinated receptors. Vps22 transiently expressed in HeLa cells was detected in endosomes containing endocytosed epidermal growth factor receptors (EGFRs) as well as Hrs and ESCRT-I and ESCRT-III. Depletion of Vps22 by small interfering RNA, which was accompanied by decreased levels of other ESCRT-II subunits, greatly reduced degradation of EGFR and its ligand EGF as well as the chemokine receptor CXCR4. EGFR accumulated on the limiting membranes of early endosomes and aberrantly small multivesicular bodies in Vps22-depleted cells. Phosphorylation and nuclear translocation of extracellular-signal-regulated kinase1/2 downstream of the EGF-activated receptor were sustained by depletion of Hrs or the ESCRT-I subunit Tsg101. In contrast, this was not the case when Vps22 was depleted. These results indicate an important role for Vps22 in ligand-induced EGFR and CXCR4 turnover and suggest that termination of EGF signaling occurs prior to ESCRT-II engagement.\",\n \"title\": \"Vps22/EAP30 in ESCRT-II mediates endosomal sorting of growth factor and chemokine receptors destined for lysosomal degradation.\"\n },\n {\n \"docid\": \"4429388\",\n \"text\": \"The ESCRT (endosomal sorting complex required for transport) pathway is required for terminal membrane fission events in several important biological processes, including endosomal intraluminal vesicle formation, HIV budding and cytokinesis. VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly, possibly in conjunction with membrane fission. Here we show that the microtubule interacting and transport (MIT) domains of human VPS4A and VPS4B bind conserved sequence motifs located at the carboxy termini of the CHMP1–3 class of ESCRT-III proteins. Structures of VPS4A MIT–CHMP1A and VPS4B MIT–CHMP2B complexes reveal that the C-terminal CHMP motif forms an amphipathic helix that binds in a groove between the last two helices of the tetratricopeptide-like repeat (TPR) of the VPS4 MIT domain, but in the opposite orientation to that of a canonical TPR interaction. Distinct pockets in the MIT domain bind three conserved leucine residues of the CHMP motif, and mutations that inhibit these interactions block VPS4 recruitment, impair endosomal protein sorting and relieve dominant-negative VPS4 inhibition of HIV budding. Thus, our studies reveal how the VPS4 ATPases recognize their CHMP substrates to facilitate the membrane fission events required for the release of viruses, endosomal vesicles and daughter cells.\",\n \"title\": \"ESCRT-III recognition by VPS4 ATPases\"\n },\n {\n \"docid\": \"11289247\",\n \"text\": \"The regulation and coordination of mitochondrial metabolism with hematopoietic stem cell (HSC) self-renewal and differentiation is not fully understood. Here we report that depletion of PTPMT1, a PTEN-like mitochondrial phosphatase, in inducible or hematopoietic-cell-specific knockout mice resulted in hematopoietic failure due to changes in the cell cycle and a block in the differentiation of HSCs. Surprisingly, the HSC pool was increased by ∼40-fold in PTPMT1 knockout mice. Reintroduction of wild-type PTPMT1, but not catalytically deficient PTPMT1 or truncated PTPMT1 lacking mitochondrial localization, restored differentiation capabilities of PTPMT1 knockout HSCs. Further analyses demonstrated that PTPMT1 deficiency altered mitochondrial metabolism and that phosphatidylinositol phosphate substrates of PTPMT1 directly enhanced fatty-acid-induced activation of mitochondrial uncoupling protein 2. Intriguingly, depletion of PTPMT1 from myeloid, T lymphoid, or B lymphoid progenitors did not cause any defects in lineage-specific knockout mice. This study establishes a crucial role of PTPMT1 in the metabolic regulation of HSC function.\",\n \"title\": \"Metabolic regulation by the mitochondrial phosphatase PTPMT1 is required for hematopoietic stem cell differentiation.\"\n },\n {\n \"docid\": \"17017465\",\n \"text\": \"The small GTPases, Rab5 and Rac, are essential for endocytosis and actin remodeling, respectively. Coordination of these processes is critical to achieve spatial restriction of intracellular signaling, which is essential for a variety of polarized functions. Here, we show that clathrin- and Rab5-mediated endocytosis are required for the activation of Rac induced by motogenic stimuli. Rac activation occurs on early endosomes, where the RacGEF Tiam1 is also recruited. Subsequent recycling of Rac to the plasma membrane ensures localized signaling, leading to the formation of actin-based migratory protrusions. Thus, membrane trafficking of Rac is required for the spatial resolution of Rac-dependent motogenic signals. We further demonstrate that a Rab5-to-Rac circuitry controls the morphology of motile mammalian tumor cells and primordial germinal cells during zebrafish development, suggesting that this circuitry is relevant for the regulation of migratory programs in various cells, in both in vitro settings and whole organisms.\",\n \"title\": \"Endocytic Trafficking of Rac Is Required for the Spatial Restriction of Signaling in Cell Migration\"\n },\n {\n \"docid\": \"19561411\",\n \"text\": \"Orai1 and stromal interaction molecule 1 (STIM1) mediate store-operated Ca(2+) entry (SOCE) in immune cells. STIM1, an endoplasmic reticulum (ER) Ca(2+) sensor, detects store depletion and interacts with plasma membrane (PM)-resident Orai1 channels at the ER-PM junctions. However, the molecular composition of these junctions in T cells remains poorly understood. Here, we show that junctophilin-4 (JP4), a member of junctional proteins in excitable cells, is expressed in T cells and localized at the ER-PM junctions to regulate Ca(2+) signaling. Silencing or genetic manipulation of JP4 decreased ER Ca(2+) content and SOCE in T cells, impaired activation of the nuclear factor of activated T cells (NFAT) and extracellular signaling-related kinase (ERK) signaling pathways, and diminished expression of activation markers and cytokines. Mechanistically, JP4 directly interacted with STIM1 via its cytoplasmic domain and facilitated its recruitment into the junctions. Accordingly, expression of this cytoplasmic fragment of JP4 inhibited SOCE. Furthermore, JP4 also formed a complex with junctate, a Ca(2+)-sensing ER-resident protein, previously shown to mediate STIM1 recruitment into the junctions. We propose that the junctate-JP4 complex located at the junctions cooperatively interacts with STIM1 to maintain ER Ca(2+) homeostasis and mediate SOCE in T cells.\",\n \"title\": \"Junctophilin-4, a component of the endoplasmic reticulum-plasma membrane junctions, regulates Ca2+ dynamics in T cells.\"\n },\n {\n \"docid\": \"18264714\",\n \"text\": \"All cells perceive and respond to environmental stresses through elaborate stress-sensing networks. Yeast cells sense stress through diverse signaling pathways that converge on the transcription factors Msn2 and Msn4, which respond by initiating rapid, idiosyncratic cycles into and out of the nucleus. To understand the role of Msn2/4 nuclear localization dynamics, we combined time-lapse studies of Msn2-GFP localization in living cells with computational modeling of stress-sensing signaling networks. We find that several signaling pathways, including Ras/protein kinase A, AMP-activated kinase, the high-osmolarity response mitogen-activated protein kinase pathway, and protein phosphatase 1, regulate activation of Msn2 in distinct ways in response to different stresses. Moreover, we find that bursts of nuclear localization elicit a more robust transcriptional response than does sustained nuclear localization. Using stochastic modeling, we reproduce in silico the responses of Msn2 to different stresses, and demonstrate that bursts of localization arise from noise in the signaling pathways amplified by the small number of Msn2 molecules in the cell. This noise imparts diverse behaviors to genetically identical cells, allowing cell populations to \\\"hedge their bets\\\" in responding to an uncertain future, and to balance growth and survival in an unpredictable environment.\",\n \"title\": \"Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses\"\n },\n {\n \"docid\": \"4388082\",\n \"text\": \"In a Drosophila follicle the oocyte always occupies a posterior position among a group of sixteen germline cells. Although the importance of this cell arrangement for the subsequent formation of the anterior-posterior axis of the embryo is well documented, the molecular mechanism responsible for the posterior localization of the oocyte was unknown. Here we show that the homophilic adhesion molecule DE-cadherin mediates oocyte positioning. During follicle biogenesis, DE-cadherin is expressed in germline (including oocyte) and surrounding follicle cells, with the highest concentration of DE-cadherin being found at the interface between oocyte and posterior follicle cells. Mosaic analysis shows that DE-cadherin is required in both germline and follicle cells for correct oocyte localization, indicating that germline-soma interactions may be involved in this process. By analysing the behaviour of the oocyte in follicles with a chimaeric follicular epithelium, we find that the position of the oocyte is determined by the position of DE-cadherin-expressing follicle cells, to which the oocyte attaches itself selectively. Among the DE-cadherin positive follicle cells, the oocyte preferentially contacts those cells that express higher levels of DE-cadherin. On the basis of these data, we propose that in wild-type follicles the oocyte competes successfully with its sister germline cells for contact to the posterior follicle cells, a sorting process driven by different concentrations of DE-cadherin. This is, to our knowledge, the first in vivo example of a cell-sorting process that depends on differential adhesion mediated by a cadherin.\",\n \"title\": \"Drosophila oocyte localization is mediated by differential cadherin-based adhesion.\"\n },\n {\n \"docid\": \"2593298\",\n \"text\": \"Receptor endocytosis is a fundamental step in controlling the magnitude, duration, and nature of cell signaling events. Confluent endothelial cells are contact inhibited in their growth and respond poorly to the proliferative signals of vascular endothelial growth factor (VEGF). In a previous study, we found that the association of vascular endothelial cadherin (VEC) with VEGF receptor (VEGFR) type 2 contributes to density-dependent growth inhibition (Lampugnani, G.M., A. Zanetti, M. Corada, T. Takahashi, G. Balconi, F. Breviario, F. Orsenigo, A. Cattelino, R. Kemler, T.O. Daniel, and E. Dejana. 2003. J. Cell Biol. 161:793–804). In the present study, we describe the mechanism through which VEC reduces VEGFR-2 signaling. We found that VEGF induces the clathrin-dependent internalization of VEGFR-2. When VEC is absent or not engaged at junctions, VEGFR-2 is internalized more rapidly and remains in endosomal compartments for a longer time. Internalization does not terminate its signaling; instead, the internalized receptor is phosphorylated, codistributes with active phospholipase C–γ, and activates p44/42 mitogen-activated protein kinase phosphorylation and cell proliferation. Inhibition of VEGFR-2 internalization reestablishes the contact inhibition of cell growth, whereas silencing the junction-associated density-enhanced phosphatase-1/CD148 phosphatase restores VEGFR-2 internalization and signaling. Thus, VEC limits cell proliferation by retaining VEGFR-2 at the membrane and preventing its internalization into signaling compartments.\",\n \"title\": \"Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from intracellular compartments\"\n },\n {\n \"docid\": \"12871002\",\n \"text\": \"We have studied the function of a conserved germline-specific nucleotidyltransferase protein, CDE-1, in RNAi and chromosome segregation in C. elegans. CDE-1 localizes specifically to mitotic chromosomes in embryos. This localization requires the RdRP EGO-1, which physically interacts with CDE-1, and the Argonaute protein CSR-1. We found that CDE-1 is required for the uridylation of CSR-1 bound siRNAs, and that in the absence of CDE-1 these siRNAs accumulate to inappropriate levels, accompanied by defects in both meiotic and mitotic chromosome segregation. Elevated siRNA levels are associated with erroneous gene silencing, most likely through the inappropriate loading of CSR-1 siRNAs into other Argonaute proteins. We propose a model in which CDE-1 restricts specific EGO-1-generated siRNAs to the CSR-1 mediated, chromosome associated RNAi pathway, thus separating it from other endogenous RNAi pathways. The conserved nature of CDE-1 suggests that similar sorting mechanisms may operate in other animals, including mammals.\",\n \"title\": \"CDE-1 Affects Chromosome Segregation through Uridylation of CSR-1-Bound siRNAs\"\n },\n {\n \"docid\": \"15600979\",\n \"text\": \"EMSY links the BRCA2 pathway to sporadic breast/ovarian cancer. It encodes a nuclear protein that binds to the BRCA2 N-terminal domain implicated in chromatin/transcription regulation, but when sporadically amplified/overexpressed, increased EMSY level represses BRCA2 transactivation potential and induces chromosomal instability, mimicking the activity of BRCA2 mutations in the development of hereditary breast/ovarian cancer. In addition to chromatin/transcription regulation, EMSY may also play a role in the DNA-damage response, suggested by its ability to localize at chromatin sites of DNA damage/repair. This implies that EMSY overexpression may also repress BRCA2 in DNA-damage replication/checkpoint and recombination/repair, coordinated processes that also require its interacting proteins: PALB2, the partner and localizer of BRCA2; RPA, replication/checkpoint protein A; and RAD51, the inseparable recombination/repair enzyme. Here, using a well-characterized recombination/repair assay system, we demonstrate that a slight increase in EMSY level can indeed repress these two processes independently of transcriptional interference/repression. Since EMSY, RPA and PALB2 all bind to the same BRCA2 region, these findings further support a scenario wherein: (a) EMSY amplification may mimic BRCA2 deficiency, at least by overriding RPA and PALB2, crippling the BRCA2/RAD51 complex at DNA-damage and replication/transcription sites; and (b) BRCA2/RAD51 may coordinate these processes by employing at least EMSY, PALB2 and RPA. We extensively discuss the molecular details of how this can happen to ascertain its implications for a novel recombination mechanism apparently conceived as checkpoint rather than a DNA repair system for cell division, survival, death, and human diseases, including the tissue specificity of cancer predisposition, which may renew our thinking about targeted therapy and prevention.\",\n \"title\": \"EMSY overexpression disrupts the BRCA2/RAD51 pathway in the DNA-damage response: implications for chromosomal instability/recombination syndromes as checkpoint diseases\"\n },\n {\n \"docid\": \"31851367\",\n \"text\": \"Estrogens are key regulators of growth, differentiation, and the physiological functions of a wide range of target tissues, including the male and female reproductive tracts, breast, and skeletal, nervous, cardiovascular, digestive and immune systems. The majority of these biological activities of estrogens are mediated through two genetically distinct receptors, ERalpha and ERbeta, which function as hormone-inducible transcription factors. Over the past decade, it has become increasingly clear that the recruitment of coregulatory proteins to ERs is required for ER-mediated transcriptional and biological activities. These \\\"coactivator\\\" complexes enable the ERs to respond appropriately: 1) to hormones or pharmacological ligands, 2) interpret extra- and intra-cellular signals, 3) catalyze the process of chromatin condensation and 4) to communicate with the general transcription apparatus at target gene promoters. In addition to activating proteins, the existence of corepressors, proteins that function as negative regulators of ER activity in either physiological or pharmacological contexts, provides an additional level of complexity in ER action. This review also describes current efforts aimed at developing pharmaceutical agents that target ER-cofactor interactions as therapeutics for estrogen-associated pathologies.\",\n \"title\": \"Coregulators in nuclear estrogen receptor action: from concept to therapeutic targeting.\"\n },\n {\n \"docid\": \"12800122\",\n \"text\": \"Subdividing proliferating tissues into compartments is an evolutionarily conserved strategy of animal development [1-6]. Signals across boundaries between compartments can result in local expression of secreted proteins organizing growth and patterning of tissues [1-6]. Sharp and straight interfaces between compartments are crucial for stabilizing the position of such organizers and therefore for precise implementation of body plans. Maintaining boundaries in proliferating tissues requires mechanisms to counteract cell rearrangements caused by cell division; however, the nature of such mechanisms remains unclear. Here we quantitatively analyzed cell morphology and the response to the laser ablation of cell bonds in the vicinity of the anteroposterior compartment boundary in developing Drosophila wings. We found that mechanical tension is approximately 2.5-fold increased on cell bonds along this compartment boundary as compared to the remaining tissue. Cell bond tension is decreased in the presence of Y-27632 [7], an inhibitor of Rho-kinase whose main effector is Myosin II [8]. Simulations using a vertex model [9] demonstrate that a 2.5-fold increase in local cell bond tension suffices to guide the rearrangement of cells after cell division to maintain compartment boundaries. Our results provide a physical mechanism in which the local increase in Myosin II-dependent cell bond tension directs cell sorting at compartment boundaries.\",\n \"title\": \"Increased Cell Bond Tension Governs Cell Sorting at the Drosophila Anteroposterior Compartment Boundary\"\n },\n {\n \"docid\": \"6492658\",\n \"text\": \"Weeble mutant mice have severe locomotor instability and significant neuronal loss in the cerebellum and in the hippocampal CA1 field. Genetic mapping was used to localize the mutation to the gene encoding inositol polyphosphate 4-phosphatase type I (Inpp4a), where a single nucleotide deletion results in a likely null allele. The substrates of INPP4A are intermediates in a pathway affecting intracellular Ca(2+) release but are also involved in cell cycle regulation through binding the Akt protooncogene; dysfunction in either may account for the neuronal loss of weeble mice. Although other mutations in phosphoinositide enzymes are associated with synaptic defects without neuronal loss, weeble shows that Inpp4a is critical for the survival of a subset of neurons during postnatal development in mice.\",\n \"title\": \"A Null Mutation in Inositol Polyphosphate 4-Phosphatase Type I Causes Selective Neuronal Loss in Weeble Mutant Mice\"\n },\n {\n \"docid\": \"6333347\",\n \"text\": \"An emerging family of kinases related to the Drosophila Aurora and budding yeast Ipl1 proteins has been implicated in chromosome segregation and mitotic spindle formation in a number of organisms. Unlike other Aurora/Ipl1-related kinases, the Caenorhabditis elegans orthologue, AIR-2, is associated with meiotic and mitotic chromosomes. AIR-2 is initially localized to the chromosomes of the most mature prophase I–arrested oocyte residing next to the spermatheca. This localization is dependent on the presence of sperm in the spermatheca. After fertilization, AIR-2 remains associated with chromosomes during each meiotic division. However, during both meiotic anaphases, AIR-2 is present between the separating chromosomes. AIR-2 also remains associated with both extruded polar bodies. In the embryo, AIR-2 is found on metaphase chromosomes, moves to midbody microtubules at anaphase, and then persists at the cytokinesis remnant. Disruption of AIR-2 expression by RNA- mediated interference produces entire broods of one-cell embryos that have executed multiple cell cycles in the complete absence of cytokinesis. The embryos accumulate large amounts of DNA and microtubule asters. Polar bodies are not extruded, but remain in the embryo where they continue to replicate. The cytokinesis defect appears to be late in the cell cycle because transient cleavage furrows initiate at the proper location, but regress before the division is complete. Additionally, staining with a marker of midbody microtubules revealed that at least some of the components of the midbody are not well localized in the absence of AIR-2 activity. Our results suggest that during each meiotic and mitotic division, AIR-2 may coordinate the congression of metaphase chromosomes with the subsequent events of polar body extrusion and cytokinesis.\",\n \"title\": \"AIR-2: An Aurora/Ipl1-related Protein Kinase Associated with Chromosomes and Midbody Microtubules Is Required for Polar Body Extrusion and Cytokinesis in Caenorhabditis elegans Embryos \"\n },\n {\n \"docid\": \"4324278\",\n \"text\": \"The rapamycin-sensitive TOR signalling pathway in Saccharomyces cerevisiae activates a cell-growth program in response to nutrients such as nitrogen and carbon. The TOR1 and TOR2 kinases (TOR) control cytoplasmic protein synthesis and degradation through the conserved TAP42 protein. Upon phosphorylation by TOR, TAP42 binds and possibly inhibits type 2A and type-2A-related phosphatases; however, the mechanism by which TOR controls nuclear events such as global repression of starvation-specific transcription is unknown. Here we show that TOR prevents transcription of genes expressed upon nitrogen limitation by promoting the association of the GATA transcription factor GLN3 with the cytoplasmic protein URE2. The binding of GLN3 to URE2 requires TOR-dependent phosphorylation of GLN3. Phosphorylation and cytoplasmic retention of GLN3 are also dependent on the TOR effector TAP42, and are antagonized by the type-2A-related phosphatase SIT4. TOR inhibits expression of carbon-source-regulated genes by stimulating the binding of the transcriptional activators MSN2 and MSN4 to the cytoplasmic 14-3-3 protein BMH2. Thus, the TOR signalling pathway broadly controls nutrient metabolism by sequestering several transcription factors in the cytoplasm.\",\n \"title\": \"The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors.\"\n },\n {\n \"docid\": \"24555417\",\n \"text\": \"In many species, oocyte meiosis is carried out in the absence of centrioles. As a result, microtubule organization, spindle assembly, and chromosome segregation proceed by unique mechanisms. Here, we report insights into the principles underlying this specialized form of cell division, through studies of C. elegans KLP-15 and KLP-16, two highly homologous members of the kinesin-14 family of minus-end-directed kinesins. These proteins localize to the acentriolar oocyte spindle and promote microtubule bundling during spindle assembly; following KLP-15/16 depletion, microtubule bundles form but then collapse into a disorganized array. Surprisingly, despite this defect we found that during anaphase, microtubules are able to reorganize into a bundled array that facilitates chromosome segregation. This phenotype therefore enabled us to identify factors promoting microtubule organization during anaphase, whose contributions are normally undetectable in wild-type worms; we found that SPD-1 (PRC1) bundles microtubules and KLP-18 (kinesin-12) likely sorts those bundles into a functional orientation capable of mediating chromosome segregation. Therefore, our studies have revealed an interplay between distinct mechanisms that together promote spindle formation and chromosome segregation in the absence of structural cues such as centrioles.\",\n \"title\": \"Interplay between microtubule bundling and sorting factors ensures acentriolar spindle stability during C. elegans oocyte meiosis\"\n },\n {\n \"docid\": \"24558930\",\n \"text\": \"Although assembly of acentrosomal meiotic spindles has been extensively studied, little is known about the segregation of chromosomes on these spindles. Here, we show in Caenorhabditis elegans oocytes that the kinetochore protein, KNL-1, directs assembly of meiotic kinetochores that orient chromosomes. However, in contrast to mitosis, chromosome separation during meiotic anaphase is kinetochore-independent. Before anaphase, meiotic kinetochores and spindle poles disassemble along with the microtubules on the poleward side of chromosomes. During anaphase, microtubules then form between the separating chromosomes. Functional analysis implicated a set of proteins that localize to a ring-shaped domain between kinetochores during pre-anaphase spindle assembly and anaphase separation. These proteins are localized by the chromosomal passenger complex, which regulates the loss of meiotic chromosome cohesion. Thus, meiotic segregation in C. elegans is a two-stage process, where kinetochores orient chromosomes, but are then dispensable for their separation. We suggest that separation is controlled by a meiosis-specific chromosomal domain to coordinate cohesin removal and chromosome segregation.\",\n \"title\": \"A kinetochore-independent mechanism drives anaphase chromosome separation during acentrosomal meiosis\"\n },\n {\n \"docid\": \"25510546\",\n \"text\": \"Increased lipid supply causes beta cell death, which may contribute to reduced beta cell mass in type 2 diabetes. We investigated whether endoplasmic reticulum (ER) stress is necessary for lipid-induced apoptosis in beta cells and also whether ER stress is present in islets of an animal model of diabetes and of humans with type 2 diabetes. Expression of genes involved in ER stress was evaluated in insulin-secreting MIN6 cells exposed to elevated lipids, in islets isolated from db/db mice and in pancreas sections of humans with type 2 diabetes. Overproduction of the ER chaperone heat shock 70 kDa protein 5 (HSPA5, previously known as immunoglobulin heavy chain binding protein [BIP]) was performed to assess whether attenuation of ER stress affected lipid-induced apoptosis. We demonstrated that the pro-apoptotic fatty acid palmitate triggers a comprehensive ER stress response in MIN6 cells, which was virtually absent using non-apoptotic fatty acid oleate. Time-dependent increases in mRNA levels for activating transcription factor 4 (Atf4), DNA-damage inducible transcript 3 (Ddit3, previously known as C/EBP homologous protein [Chop]) and DnaJ homologue (HSP40) C3 (Dnajc3, previously known as p58) correlated with increased apoptosis in palmitate- but not in oleate-treated MIN6 cells. Attenuation of ER stress by overproduction of HSPA5 in MIN6 cells significantly protected against lipid-induced apoptosis. In islets of db/db mice, a variety of marker genes of ER stress were also upregulated. Increased processing (activation) of X-box binding protein 1 (Xbp1) mRNA was also observed, confirming the existence of ER stress. Finally, we observed increased islet protein production of HSPA5, DDIT3, DNAJC3 and BCL2-associated X protein in human pancreas sections of type 2 diabetes subjects. Our results provide evidence that ER stress occurs in type 2 diabetes and is required for aspects of the underlying beta cell failure.\",\n \"title\": \"Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes\"\n },\n {\n \"docid\": \"42855554\",\n \"text\": \"To clarify the fate of glycosylphosphatidylinositol (GPI) in mammals, we developed GPI-anchored enhanced green fluorescent protein (EGFP-GPI) and transgenic mice carrying this fusion construct. When it was introduced to culture cells, the EGFP-GPI protein was correctly sorted to plasma membranes and microsomes depending on GPI biosynthesis. Transgenic mice carrying EGFP-GPI were found to show a broad transgene expression. Histologically, a prominent polarized localization of EGFP-GPI protein was observed in various epithelia, the nervous system and liver and secreted from some exocrine glands, as well as non-polarized presence in non-epithelial tissues, demonstrating a tissue-inherent manner of GPI sorting.\",\n \"title\": \"Tissue-inherent fate of GPI revealed by GPI-anchored GFP transgenesis.\"\n },\n {\n \"docid\": \"20460020\",\n \"text\": \"Efficient local monocyte/macrophage recruitment is critical for tissue repair. Recruited macrophages are polarized toward classical (proinflammatory) or alternative (prohealing) activation in response to cytokines, with tight temporal regulation crucial for efficient wound repair. Estrogen acts as a potent anti-inflammatory regulator of cutaneous healing. However, an understanding of estrogen/estrogen receptor (ER) contribution to macrophage polarization and subsequent local effects on wound healing is lacking. Here we identify, to our knowledge previously unreported, a role whereby estrogen receptor α (ERα) signaling preferentially polarizes macrophages from a range of sources to an alternative phenotype. Cell-specific ER ablation studies confirm an in vivo role for inflammatory cell ERα, but not ERβ, in poor healing associated with an altered cytokine profile and fewer alternatively activated macrophages. Furthermore, we reveal intrinsic changes in ERα-deficient macrophages, which are unable to respond to alternative activation signals in vitro. Collectively, our data reveal that inflammatory cell-expressed ERα promotes alternative macrophage polarization, which is beneficial for timely healing. Given the diverse physiological roles of ERs, these findings will likely be of relevance to many pathologies involving excessive inflammation.\",\n \"title\": \"Estrogen receptor-alpha promotes alternative macrophage activation during cutaneous repair.\"\n },\n {\n \"docid\": \"35231675\",\n \"text\": \"CLIP-170 is a \\\"cytoplasmic linker protein\\\" implicated in endosome-microtubule interactions and in control of microtubule dynamics. CLIP-170 localizes dynamically to growing microtubule plus ends, colocalizing with the dynein activator dynactin and the APC-binding protein EB1. This shared \\\"plus-end tracking\\\" behavior suggests that CLIP-170 might interact with dynactin and/or EB1. We have used site-specific mutagenesis of CLIP-170 and a transfection/colocalization assay to address this question in mammalian tissue culture cells. Our results indicate that CLIP-170 interacts, directly or indirectly, with both dynactin and EB1. We find that the CLIP-170/dynactin interaction is mediated by the second metal binding motif of the CLIP-170 tail. In contrast, the CLIP-170/EB1 interaction requires neither metal binding motif. In addition, our experiments suggest that the CLIP-170/dynactin interaction occurs via the shoulder/sidearm subcomplex of dynactin and can occur in the cytosol (i.e., it does not require microtubule binding). These results have implications for the targeting of both dynactin and EB1 to microtubule plus ends. Our data suggest that the CLIP-170/dynactin interaction can target dynactin complex to microtubule plus ends, although dynactin likely also targets MT plus ends directly via the microtubule binding motif of the p150(Glued) subunit. We find that CLIP-170 mutants alter p150(Glued) localization without affecting EB1, indicating that EB1 can target microtubule plus ends independently of dynactin.\",\n \"title\": \"CLIP-170 interacts with dynactin complex and the APC-binding protein EB1 by different mechanisms.\"\n },\n {\n \"docid\": \"37964706\",\n \"text\": \"Ca2+ entry through store-operated Ca2+ channels drives the production of the pro-inflammatory molecule leukotriene C4 (LTC4) from mast cells through a pathway involving Ca2+-dependent protein kinase C, mitogen-activated protein kinases ERK1/2, phospholipase A2, and 5-lipoxygenase. Here we examine whether local Ca2+ influx through store-operated Ca2+ release-activated Ca2+ (CRAC) channels in the plasma membrane stimulates this signaling pathway. Manipulating the amplitude and spatial extent of Ca2+ entry by altering chemical and electrical gradients for Ca2+ influx or changing the Ca2+ buffering of the cytoplasm all impacted on protein kinase C and ERK activation, generation of arachidonic acid and LTC4 secretion, with little change in the bulk cytoplasmic Ca2+ rise. Similar bulk cytoplasmic Ca2+ concentrations were achieved when CRAC channels were activated in 0.25 mm external Ca2+ versus 2 mm Ca2+ and 100 nm La3+, an inhibitor of CRAC channels. However, despite similar bulk cytoplasmic Ca2+, protein kinase C activation and LTC4 secretion were larger in 2 mm Ca2+ and La3+ than in 0.25 mm Ca2+, consistent with the central involvement of a subplasmalemmal Ca2+ rise. The nonreceptor tyrosine kinase Syk coupled CRAC channel opening to protein kinase C and ERK activation. Recombinant TRPC3 channels also activated protein kinase C, suggesting that subplasmalemmal Ca2+ rather than a microdomain exclusive to CRAC channels is the trigger. Hence a subplasmalemmal Ca2+ increase in mast cells is highly versatile in that it triggers cytoplasmic responses through generation of intracellular messengers as well as long distance changes through increased secretion of paracrine signals.\",\n \"title\": \"Local Ca2+ influx through Ca2+ release-activated Ca2+ (CRAC) channels stimulates production of an intracellular messenger and an intercellular pro-inflammatory signal.\"\n },\n {\n \"docid\": \"17194716\",\n \"text\": \"In this study, the mechanisms of actin-bundling in filopodia were examined. Analysis of cellular localization of known actin cross-linking proteins in mouse melanoma B16F1 cells revealed that fascin was specifically localized along the entire length of all filopodia, whereas other actin cross-linkers were not. RNA interference of fascin reduced the number of filopodia, and remaining filopodia had abnormal morphology with wavy and loosely bundled actin organization. Dephosphorylation of serine 39 likely determined cellular filopodia frequency. The constitutively active fascin mutant S39A increased the number and length of filopodia, whereas the inactive fascin mutant S39E reduced filopodia frequency. Fluorescence recovery after photobleaching of GFP-tagged wild-type and S39A fascin showed that dephosphorylated fascin underwent rapid cycles of association to and dissociation from actin filaments in filopodia, with t1/2 < 10 s. We propose that fascin is a key specific actin cross-linker, providing stiffness for filopodial bundles, and that its dynamic behavior allows for efficient coordination between elongation and bundling of filopodial actin filaments.\",\n \"title\": \"Role of fascin in filopodial protrusion\"\n },\n {\n \"docid\": \"25623469\",\n \"text\": \"A newly emerging family of phosphatases that are members of the haloacid dehalogenase superfamily contains the catalytic motif DXDX(T/V). A member of this DXDX(T/V) phosphatase family known as Dullard was recently shown to be a potential regulator of neural tube development in Xenopus [Satow R, Chan TC, Asashima M (2002) Biochem Biophys Res Commun 295:85-91]. Herein, we demonstrate that human Dullard and the yeast protein Nem1p perform similar functions in mammalian cells and yeast cells, respectively. In addition to similarity in primary sequence, Dullard and Nem1p possess similar domains and show similar substrate preferences, and both localize to the nuclear envelope. Additionally, we show that human Dullard can rescue the aberrant nuclear envelope morphology of nem1Delta yeast cells, functionally replacing Nem1p. Finally, Nem1p, has been shown to deposphorylate the yeast phosphatidic acid phosphatase Smp2p [Santos-Rosa H, Leung J, Grimsey N, Peak-Chew S, Siniossoglou S (2005) EMBO J 24:1931-1941], and we show that Dullard dephosphorylates the mammalian phospatidic acid phosphatase, lipin. Therefore, we propose that Dullard participates in a unique phosphatase cascade regulating nuclear membrane biogenesis, and that this cascade is conserved from yeast to mammals.\",\n \"title\": \"A conserved phosphatase cascade that regulates nuclear membrane biogenesis.\"\n },\n {\n \"docid\": \"1991105\",\n \"text\": \"Mitochondrial division is important for mitochondrial distribution and function. Recent data have demonstrated that ER-mitochondria contacts mark mitochondrial division sites, but the molecular basis and functions of these contacts are not understood. Here we show that in yeast, the ER-mitochondria tethering complex, ERMES, and the highly conserved Miro GTPase, Gem1, are spatially and functionally linked to ER-associated mitochondrial division. Gem1 acts as a negative regulator of ER-mitochondria contacts, an activity required for the spatial resolution and distribution of newly generated mitochondrial tips following division. Previous data have demonstrated that ERMES localizes with a subset of actively replicating mitochondrial nucleoids. We show that mitochondrial division is spatially linked to nucleoids and that a majority of these nucleoids segregate prior to division, resulting in their distribution into newly generated tips in the mitochondrial network. Thus, we postulate that ER-associated division serves to link the distribution of mitochondria and mitochondrial nucleoids in cells. DOI:http://dx.doi.org/10.7554/eLife.00422.001.\",\n \"title\": \"ER-associated mitochondrial division links the distribution of mitochondria and mitochondrial DNA in yeast\"\n },\n {\n \"docid\": \"13936152\",\n \"text\": \"Partitioning tissues into compartments that do not intermix is essential for the correct morphogenesis of animal embryos and organs. Several hypotheses have been proposed to explain compartmental cell sorting, mainly differential adhesion, but also regulation of the cytoskeleton or of cell proliferation. Nevertheless, the molecular and cellular mechanisms that keep cells apart at boundaries remain unclear. Here we demonstrate, in early Drosophila melanogaster embryos, that actomyosin-based barriers stop cells from invading neighbouring compartments. Our analysis shows that cells can transiently invade neighbouring compartments, especially when they divide, but are then pushed back into their compartment of origin. Actomyosin cytoskeletal components are enriched at compartmental boundaries, forming cable-like structures when the epidermis is mitotically active. When MyoII (non-muscle myosin II) function is inhibited, including locally at the cable by chromophore-assisted laser inactivation (CALI), in live embryos, dividing cells are no longer pushed back, leading to compartmental cell mixing. We propose that local regulation of actomyosin contractibility, rather than differential adhesion, is the primary mechanism sorting cells at compartmental boundaries.\",\n \"title\": \"An actomyosin-based barrier inhibits cell mixing at compartmental boundaries in Drosophila embryos\"\n },\n {\n \"docid\": \"16557565\",\n \"text\": \"Plants, compared to animals, exhibit an amazing adaptability and plasticity in their development. This is largely dependent on the ability of plants to form new organs, such as lateral roots, leaves, and flowers during postembryonic development. Organ primordia develop from founder cell populations into organs by coordinated cell division and differentiation. Here, we show that organ formation in Arabidopsis involves dynamic gradients of the signaling molecule auxin with maxima at the primordia tips. These gradients are mediated by cellular efflux requiring asymmetrically localized PIN proteins, which represent a functionally redundant network for auxin distribution in both aerial and underground organs. PIN1 polar localization undergoes a dynamic rearrangement, which correlates with establishment of auxin gradients and primordium development. Our results suggest that PIN-dependent, local auxin gradients represent a common module for formation of all plant organs, regardless of their mature morphology or developmental origin.\",\n \"title\": \"Local, Efflux-Dependent Auxin Gradients as a Common Module for Plant Organ Formation\"\n },\n {\n \"docid\": \"935538\",\n \"text\": \"RNA-binding proteins are at the heart of posttranscriptional gene regulation, coordinating the processing, storage, and handling of cellular RNAs. We show here that GRSF1, previously implicated in the binding and selective translation of influenza mRNAs, is targeted to mitochondria where it forms granules that colocalize with foci of newly synthesized mtRNA next to mitochondrial nucleoids. GRSF1 preferentially binds RNAs transcribed from three contiguous genes on the light strand of mtDNA, the ND6 mRNA, and the long noncoding RNAs for cytb and ND5, each of which contains multiple consensus binding sequences. RNAi-mediated knockdown of GRSF1 leads to alterations in mitochondrial RNA stability, abnormal loading of mRNAs and lncRNAs on the mitochondrial ribosome, and impaired ribosome assembly. This results in a specific protein synthesis defect and a failure to assemble normal amounts of the oxidative phosphorylation complexes. These data implicate GRSF1 as a key regulator of posttranscriptional mitochondrial gene expression.\",\n \"title\": \"The mitochondrial RNA-binding protein GRSF1 localizes to RNA granules and is required for posttranscriptional mitochondrial gene expression.\"\n },\n {\n \"docid\": \"3155374\",\n \"text\": \"Binding interactions between the plasma membrane and the cytoskeleton define cell functions such as cell shape, formation of cell processes, cell movement, and endocytosis. Here we use optical tweezers tether force measurements and show that plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2) acts as a second messenger that regulates the adhesion energy between the cytoskeleton and the plasma membrane. Receptor stimuli that hydrolyze PIP2 lowered adhesion energy, a process that could be mimicked by expressing PH domains that sequester PIP2 or by targeting a 5'-PIP2-phosphatase to the plasma membrane to selectively lower plasma membrane PIP2 concentration. Our study suggests that plasma membrane PIP2 controls dynamic membrane functions and cell shape by locally increasing and decreasing the adhesion between the actin-based cortical cytoskeleton and the plasma membrane.\",\n \"title\": \"Phosphatidylinositol 4,5-Bisphosphate Functions as a Second Messenger that Regulates Cytoskeleton–Plasma Membrane Adhesion\"\n }\n]"}}}],"truncated":false,"partial":false},"paginationData":{"pageIndex":25,"numItemsPerPage":100,"numTotalItems":2592,"offset":2500,"length":100}},"jwt":"eyJhbGciOiJFZERTQSJ9.eyJyZWFkIjp0cnVlLCJwZXJtaXNzaW9ucyI6eyJyZXBvLmNvbnRlbnQucmVhZCI6dHJ1ZX0sImlhdCI6MTc1NzU4NTc2Mywic3ViIjoiL2RhdGFzZXRzL3Nza3RvcmEvbmZjb3JwdXMtc2NpZmFjdC1maXFhLWZldmVyLWNvbWJpbmUtNjQ4IiwiZXhwIjoxNzU3NTg5MzYzLCJpc3MiOiJodHRwczovL2h1Z2dpbmdmYWNlLmNvIn0.5MmDgJ1mMc1b8T9XAeOX_HOgnrR0K4n4CppL_Ykt5xdBDP6sN2OU9mqk7H0OvcFN4AoHY39ZZ0BN3fDaNj-ICg","displayUrls":true},"discussionsStats":{"closed":0,"open":0,"total":0},"fullWidth":true,"hasGatedAccess":true,"hasFullAccess":true,"isEmbedded":false,"savedQueries":{"community":[],"user":[]}}">
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{
"docid": "MED-4791",
"text": "Dietary consumption of fish is widely recommended because of the beneficial effects of omega-3 polyunsaturated fatty acids on the risks of cardiovascular and Alzheimer's diseases. The American Heart Association currently recommends eating at least two servings of fish per week. We are concerned that consumption of farmed fish may provide a means of transmission of infectious prions from cows with bovine spongiform encephalopathy to humans, causing variant Creutzfeldt Jakob disease.",
"title": "Bovine spongiform encephalopathy and aquaculture."
},
{
"docid": "MED-4792",
"text": "In transmissible spongiform encephalopathies (TSEs), a group of fatal neurodegenerative disorders affecting many species, the key event in disease pathogenesis is the accumulation of an abnormal conformational isoform (PrPSc) of the host-encoded cellular prion protein (PrPC). While the precise mechanism of the PrPC to PrPSc conversion is not understood, it is clear that host PrPC expression is a prerequisite for effective infectious prion propagation. Although there have been many studies on TSEs in mammalian species, little is known about TSE pathogenesis in fish. Here we show that while gilthead sea bream (Sparus aurata) orally challenged with brain homogenates prepared either from a BSE infected cow or from scrapie infected sheep developed no clinical prion disease, the brains of TSE-fed fish sampled two years after challenge did show signs of neurodegeneration and accumulation of deposits that reacted positively with antibodies raised against sea bream PrP. The control groups, fed with brains from uninfected animals, showed no such signs. Remarkably, the deposits developed much more rapidly and extensively in fish inoculated with BSE-infected material than in the ones challenged with the scrapie-infected brain homogenate, with numerous deposits being proteinase K-resistant. These plaque-like aggregates exhibited congophilia and birefringence in polarized light, consistent with an amyloid-like component. The neurodegeneration and abnormal deposition in the brains of fish challenged with prion, especially BSE, raises concerns about the potential risk to public health. As fish aquaculture is an economically important industry providing high protein nutrition for humans and other mammalian species, the prospect of farmed fish being contaminated with infectious mammalian PrPSc, or of a prion disease developing in farmed fish is alarming and requires further evaluation.",
"title": "Evaluation of the Possible Transmission of BSE and Scrapie to Gilthead Sea Bream (Sparus aurata)"
}
] |
[
{
"docid": "MED-728",
"text": "In a 1995 pivotal study, Kushner described the attitudes, practice behaviors, and barriers to the delivery of nutrition counseling by primary care physicians. This article recognized nutrition and dietary counseling as key components in the delivery of preventive services by primary care physicians. Kushner called for a multifaceted approach to change physicians' counseling practices. The prevailing belief today is that little has changed. Healthy People 2010 and the U.S. Preventive Task Force identify the need for physicians to address nutrition with patients. The 2010 objective was to increase to 75% the proportion of office visits that included ordering or providing diet counseling for patients with a diagnosis of cardiovascular disease, diabetes, or hypertension. At the midcourse review, the proportion actually declined from 42% to 40%. Primary care physicians continue to believe that providing nutrition counseling is within their realm of responsibility. Yet the gap remains between the proportion of patients who physicians believe would benefit from nutrition counseling and those who receive it from their primary care physician or are referred to dietitians and other healthcare professionals. The barriers cited in recent years continue to be those listed by Kushner: lack of time and compensation and, to a lesser extent, lack of knowledge and resources. The 2010 Surgeon General's Vision for a Healthy and Fit Nation and First Lady Obama's \"Let's Move Campaign\" spotlight the need for counseling adults and children on diet and physical activity.",
"title": "Barriers to providing nutrition counseling cited by physicians: a survey of primary care practitioners."
},
{
"docid": "MED-5124",
"text": "Background Reduction in dietary cholesterol is recommended to prevent cardiovascular disease (CVD). Although eggs are important sources of cholesterol and other nutrients, limited and inconsistent data are available on the effects of egg consumption on the risk of CVD and mortality. Objectives To examine the association between egg consumption and the risk of CVD and mortality. Design Prospective cohort study of 21,327 participants from the Physicians' Health Study I. Egg consumption was assessed using a simple abbreviated food questionnaire. We used Cox regression to estimate relative risks. Results After an average follow up of 20 years, a total of 1,550 new myocardial infarction (MI), 1,342 incident strokes, and 5,169 deaths occurred in this cohort. Egg consumption was not associated with incident MI or stroke in a multivariable Cox regression. In contrast, adjusted hazard ratios (95% CI) for mortality were 1.0 (reference), 0.94 (0.87-1.02), 1.03 (0.95-1.11), 1.05 (0.93-1.19), and 1.23 (1.11-1.36) for egg consumption of <1, 1, 2-4, 5-6, and 7+ per week, respectively, (p for trend <0.0001). This association was stronger among diabetic subjects with a 2-fold increased risk of death comparing the highest to the lowest category of egg consumption than non-diabetic subjects (HR: 1.22 (1.09-1.35) (p for interaction 0.09). Conclusions Our data suggest that infrequent egg consumption does not influence the risk of CVD and only confers a modest increased risk for total mortality in male physicians. In addition, egg consumption was positively related to mortality and such relation was stronger among diabetic subjects in this selective population.",
"title": "Egg Consumption and Cardiovascular Disease and Mortality The Physicians' Health Study"
},
{
"docid": "MED-965",
"text": "Since the discovery in the 1980s that nitric oxide (NO) is in fact the elusive endothelium-derived relaxing factor, it has become evident that NO is not only a major cardiovascular signalling molecule, but that changes in its bioavailability are crucial in determining whether atherosclerosis will develop or not. Sustained high levels of harmful circulating stimuli associated with cardiovascular risk factors such as diabetes mellitus elicit responses in endothelial cells that appear sequentially, namely endothelial cell activation and endothelial dysfunction (ED). ED, characterised by reduced NO bioavailability, is now recognised by many as an early, reversible precursor of atherosclerosis. The pathogenesis of ED is multifactorial; however, oxidative stress appears to be the common underlying cellular mechanism in the ensuing loss of vaso-active, inflammatory, haemostatic and redox homeostasis in the body’s vascular system. The role of ED as a pathophysiological link between early endothelial cell changes associated with cardiovascular risk factors and the development of ischaemic heart disease is of importance to basic scientists and clinicians alike.",
"title": "Endothelial dysfunction: the early predictor of atherosclerosis"
},
{
"docid": "MED-1467",
"text": "Human adiposity has long been associated with insulin resistance and increased cardiovascular risk, and abdominal adiposity is considered particularly adverse. Intra-abdominal fat is associated with insulin resistance, possibly mediated by greater lipolytic activity, lower adiponectin levels, resistance to leptin, and increased inflammatory cytokines, although the latter contribution is less clear. Liver lipid is also closely associated with, and likely to be an important contributor to, insulin resistance, but it may also be in part the consequence of the lipogenic pathway of insulin action being up-regulated by hyperinsulinemia and unimpaired signaling. Again, intramyocellular triglyceride is associated with muscle insulin resistance, but anomalies include higher intramyocellular triglyceride in insulin-sensitive athletes and women (vs men). Such issues could be explained if the \"culprits\" were active lipid moieties such as diacylglycerol and ceramide species, dependent more on lipid metabolism and partitioning than triglyceride amount. Subcutaneous fat, especially gluteofemoral, appears metabolically protective, illustrated by insulin resistance and dyslipidemia in patients with lipodystrophy. However, some studies suggest that deep sc abdominal fat may have adverse properties. Pericardial and perivascular fat relate to atheromatous disease, but not clearly to insulin resistance. There has been recent interest in recognizable brown adipose tissue in adult humans and its possible augmentation by a hormone, irisin, from exercising muscle. Brown adipose tissue is metabolically active, oxidizes fatty acids, and generates heat but, because of its small and variable quantities, its metabolic importance in humans under usual living conditions is still unclear. Further understanding of specific roles of different lipid depots may help new approaches to control obesity and its metabolic sequelae.",
"title": "Adiposity and insulin resistance in humans: the role of the different tissue and cellular lipid depots."
},
{
"docid": "MED-1190",
"text": "The serum concentration of high-density lipoprotein cholesterol and the proportion it constitutes of total serum cholesterol are high in children and low in sufferers from coronary heart disease (CHD). Studies in elderly black Africans in Western Transvaal showed them to be free of CHD. HDL concentrations measured at birth and in groups of 10- to 12-year-olds, 16- to 18-year olds, and 60- to 69-year-olds showed mean values of 0.96, 1.71, 1.58, and 1.94 mmol/l (36, 66, 61, and 65 mg/100 ml) respectively; these concentrations constitued about 56%, 54%, and 45%, and 47%, of total cholesterol. Values thus did not fall from youth to age as they did in whites. Rural South African blacks live on a diet high in fibre and low in animal protein and fat; children are active; and adults remain active even when old. These high values of HDL may well be representative for a population that is active, used to a frugal traditional diet, and free from CHD.",
"title": "High high-density-lipoprotein cholesterol in African children and adults in a population free of coronary heart diseae."
},
{
"docid": "MED-5197",
"text": "BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) are carcinogens formed in or on the surface of well-done meat, cooked at high temperature. METHODS: We estimated breast cancer risk in relation to intake of cooked meat in a population-based, case-control study (1508 cases and 1556 controls) conducted in Long Island, NY from 1996 to 1997. Lifetime intakes of grilled or barbecued and smoked meats were derived from the interviewer-administered questionnaire data. Dietary intakes of PAH and HCA were derived from the self-administered modified Block food frequency questionnaire of intake 1 year before reference date. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Modest increased risk was observed among postmenopausal, but not premenopausal, women consuming the most grilled or barbecued and smoked meats over the life course (OR = 1.47; CI = 1.12-1.92 for highest vs. lowest tertile of intake). Postmenopausal women with low fruit and vegetable intake, but high lifetime intake of grilled or barbecued and smoked meats, had a higher OR of 1.74 (CI = 1.20-2.50). No associations were observed with the food frequency questionnaire-derived intake measures of PAHs and HCAs, with the possible exception of benzo(alpha)pyrene from meat among postmenopausal women whose tumors were positive for both estrogen receptors and progesterone receptors (OR = 1.47; CI = 0.99-2.19). CONCLUSIONS: These results support the accumulating evidence that consumption of meats cooked by methods that promote carcinogen formation may increase risk of postmenopausal breast cancer.",
"title": "Cooked meat and risk of breast cancer--lifetime versus recent dietary intake."
},
{
"docid": "MED-4162",
"text": "Large numbers of US women stopped taking hormone therapies (HT), especially estrogen/progestin (EP) formulations, after the Women's Health Initiative trial detected elevated risks of breast cancer in EP users and was halted in July 2002. Recent reports have indicated substantial and significant declines in population-based breast cancer incidence, particularly hormone-sensitive forms, for 2003 and 2004. Are these events linked? This commentary considers the available evidence linking the mass cessation of HT in 2002 to the breast cancer incidence declines of 2003/2004 and quantifies the potential impact of the cessation on the overall burden of breast cancer in the US.",
"title": "Declines in breast cancer after the WHI: apparent impact of hormone therapy."
},
{
"docid": "MED-5052",
"text": "OBJECTIVE: Habitual green tea consumption has long been associated with health benefits including chemoprevention and cardiovascular protection. This non-systematic literature review presents the clinical evidence to date. METHOD: A literature review of peer-reviewed articles on observational and interventional studies was conducted to include green tea, its extract or its purified polyphenol (-)-epigallocatechin-3-gallate (EGCG). Electronic databases searched included PubMed (1966-2009) and the Cochrane Library (Issue 4, 2008). RESULTS: Observational studies are inconclusive on the benefits of habitual consumption of green tea in the prevention of most cancers. However, there are trends towards prevention in breast and prostate cancers. Interventional studies have demonstrated reduction in relapses following surgical resection in colorectal adenomas and increased survival rates in epithelial ovarian cancer. Observational studies indicate that green tea may provide protection against hypertension and reduce the risk for stroke, and interventional studies are providing biochemical and physiological evidence. CONCLUSION: Although the overall clinical evidence is inconclusive, habitual green tea consumption may be providing some level of chemoprevention in prostate and breast cancer. Green tea may also attenuate the risk factors association with the development of atherosclerosis thus reducing the incidence of cardiovascular events and stoke.",
"title": "Can green tea do that? A literature review of the clinical evidence."
},
{
"docid": "MED-1637",
"text": "Epidemiologic studies suggest that tea consumption decreases the risk for cardiovascular events. However, there has been no clinical report examining the effects of tea consumption on coronary circulation. The purpose of this study was to evaluate the effects of black tea on coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). This was a double-blind crossover study of 10 healthy male volunteers conducted to compare the effects of black tea and caffeine on coronary circulation. The coronary flow velocity of the left anterior descending coronary artery was measured at baseline and at hyperemia during adenosine triphosphate infusion by TTDE to determine CFVR. The CFVR ratio was defined as the ratio of CFVR after beverage consumption to CFVR before beverage consumption. All data were divided into 2 groups according to beverage type: group T (black tea) and group C (caffeine). Two-way analysis of variance showed a significant group effect and interaction in CFVR before and after beverage consumption (p = 0.001). CFVR significantly increased after tea consumption in group T (4.5 +/- 0.9 vs 5.2 +/- 0.9, p <0.0001). The CFVR ratio of group T was larger than that of group C (1.18 +/- 0.07 vs 1.04 +/- 0.08, p = 0.002). Acute black tea consumption improves coronary vessel function, as determined by CFVR.",
"title": "Black tea increases coronary flow velocity reserve in healthy male subjects."
},
{
"docid": "MED-2180",
"text": "Objectives To compare the energy and macronutrient content of main meals created by television chefs with ready meals sold by supermarkets, and to compare both with nutritional guidelines published by the World Health Organization and UK Food Standards Agency. Design Cross sectional study. Setting Three supermarkets with the largest share of the grocery market in the United Kingdom, 2010. Samples 100 main meal recipes from five bestselling cookery books by UK television chefs and 100 own brand ready meals from the three leading UK supermarkets. Main outcome measures Number of meals for which the nutritional content complied with WHO recommendations, and the proportion of nutrients classified as red, amber, or green using the UK FSA’s “traffic light” system for labelling food. Results No recipe or ready meal fully complied with the WHO recommendations. The ready meals were more likely to comply with the recommended proportions of energy derived from carbohydrate (18% v 6%, P=0.01) and sugars (83% v 81%, P=0.05) and fibre density (56% v 14% P<0.01). The recipes were more likely to comply with the recommended sodium density (36% v 4%, P<0.01), although salt used for seasoning was not assessed. The distributions of traffic light colours under the FSA’s food labelling recommendations differed: the modal traffic light was red for the recipes (47%) and green for ready meals (42%). Overall, the recipes contained significantly more energy (2530 kJ v 2067 kJ), protein (37.5 g v 27.9 g), fat (27.1 g v 17.2 g), and saturated fat (9.2 g v 6.8 g; P<0.01 for all) and significantly less fibre (3.3 g v 6.5 g, P<0.01) per portion than the ready meals. Conclusions Neither recipes created by television chefs nor ready meals sold by three of the leading UK supermarkets complied with WHO recommendations. Recipes were less healthy than ready meals, containing significantly more energy, protein, fat, and saturated fat, and less fibre per portion than the ready meals.",
"title": "Christmas 2012: Research: Nutritional content of supermarket ready meals and recipes by television chefs in the United Kingdom: cross sectional study"
},
{
"docid": "MED-3695",
"text": "BACKGROUND: Antibiotics alter the microbial balance within the gastrointestinal tract. Probiotics may prevent antibiotic-associated diarrhea (AAD) via restoration of the gut microflora. Antibiotics are prescribed frequently in children and AAD is common in this population. OBJECTIVES: To assess the efficacy and adverse effects of probiotics (any specified strain or dose) for the prevention of antibiotic-associated diarrhea in children. To assess adverse events associated with the use of probiotics when co-administered with antibiotics in children. SEARCH STRATEGY: MEDLINE, EMBASE, CENTRAL, CINAHL , AMED, and the Web of Science (inception to August 2006) were searched along with specialized registers including the Cochrane IBD/FBD Review Group, CISCOM, Chalmers PedCAM Research Register and trial registries from inception to 2005. Letters were sent to authors of included trials, nutra/pharmaceutical companies, and experts in the field requesting additional information on ongoing or unpublished trials. Conference proceedings, dissertation abstracts, and reference lists from included and relevant articles were hand searched. SELECTION CRITERIA: Randomized, parallel, controlled (placebo, active, or no treatment) trials comparing co-administered probiotics with antibiotics for the prevention of diarrhea secondary to antibiotic use in children (0 to 18 years). DATA COLLECTION AND ANALYSIS: Methodological quality assessment and data extraction were conducted independently by two authors (BCJ, AS). Dichotomous data (incidence of diarrhea, adverse events) were combined using pooled relative risks, and continuous data (mean duration of diarrhea, mean daily stool frequency) as weighted mean differences, along with their corresponding 95% confidence intervals. Adverse events were summarized using risk difference. For overall pooled results on the incidence of diarrhea, a priori sensitivity analyses included per protocol versus intention to treat, random versus fixed effects, and methodological quality criterion. Subgroup analysis were conducted on probiotic strain, dose, definition of antibiotic-associated diarrhea, and antibiotic agent. MAIN RESULTS: Ten studies met the inclusion criteria. Trials included treatment with either Lactobacilli spp., Bifidobacterium spp., Streptococcus spp., or Saccharomyces boulardii alone or in combination. Six studies used a single strain probiotic agent and four combined two probiotic strains. The per protocol analysis for 9/10 trials reporting on the incidence of diarrhea show statistically significant results favouring probiotics over active/non active controls (RR 0.49; 95% CI 0.32 to 0.74). However, intention to treat analysis showed non-significant results overall (RR 0.90; 95% CI 0.50 to 1.63). Five of ten trials monitored for adverse events (n = 647); none reported a serious adverse event. AUTHORS' CONCLUSIONS: Probiotics show promise for the prevention of pediatric AAD. While per protocol analysis yields treatment effect estimates that are both statistically and clinically significant, as does analysis of high quality studies, the estimate from the intention to treat analysis was not statistically significant. Future studies should involve probiotic strains and doses with the most promising evidence (e.g., Lactobacillus GG, Lactobacillus sporogenes, Saccharomyces boulardii at 5 to 40 billion colony forming units/day). Research done to date does not permit determination of the effect of age (e.g., infant versus older children) or antibiotic duration (e.g., 5 days versus 10 days). Future trials would benefit from a validated primary outcome measure for antibiotic-associated diarrhea that is sensitive to change and reflects what treatment effect clinicians, parents, and children consider important. The current data are promising, but it is premature to routinely recommend probiotics for the prevention of pediatric AAD.",
"title": "Probiotics for the prevention of pediatric antibiotic-associated diarrhea."
},
{
"docid": "MED-1172",
"text": "Background The widespread use of organophosphorus (OP) pesticides has led to frequent exposure in adults and children. Because such exposure may cause adverse health effects, particularly in children, the sources and patterns of exposure need to be studied further. Objectives We assessed young urban/suburban children’s longitudinal exposure to OP pesticides in the Children’s Pesticide Exposure Study (CPES) conducted in the greater Seattle, Washington, area, and used a novel study design that allowed us to determine the contribution of dietary intake to the overall OP pesticide exposure. Methods Twenty-three children 3–11 years of age who consumed only conventional diets were recruited for this 1-year study conducted in 2003–2004. Children switched to organic diets for 5 consecutive days in the summer and fall sampling seasons. We measured specific urinary metabolites for malathion, chlorpyrifos, and other OP pesticides in urine samples collected twice daily for a period of 7, 12, or 15 consecutive days during each of the four seasons. Results By substituting organic fresh fruits and vegetables for corresponding conventional food items, the median urinary metabolite concentrations were reduced to nondetected or close to non-detected levels for malathion and chlorpyrifos at the end of the 5-day organic diet intervention period in both summer and fall seasons. We also observed a seasonal effect on the OP urinary metabolite concentrations, and this seasonality corresponds to the consumption of fresh produce throughout the year. Conclusions The findings from this study demonstrate that dietary intake of OP pesticides represents the major source of exposure in young children.",
"title": "Dietary Intake and Its Contribution to Longitudinal Organophosphorus Pesticide Exposure in Urban/Suburban Children"
},
{
"docid": "MED-3465",
"text": "Blueberries are rich in antioxidants known as anthocyanins, which may exhibit significant health benefits. Strenous exercise is known to acutely generate oxidative stress and an inflammatory state, and serves as an on-demand model to test antioxidant and anti-inflammatory compounds. The purpose of this study was to examine whether 250 g of blueberries per day for 6 weeks and 375 g given 1 h prior to 2.5 h of running at ∼72% maximal oxygen consumption counters oxidative stress, inflammation, and immune changes. Twenty-five well-trained subjects were recruited and randomized into blueberry (BB) (N = 13) or control (CON) (N = 12) groups. Blood, muscle, and urine samples were obtained pre-exercise and immediately postexercise, and blood and urine 1 h postexercise. Blood was examined for F₂-isoprostanes for oxidative stress, cortisol, cytokines, homocysteine, leukocytes, T-cell function, natural killer (NK), and lymphocyte cell counts for inflammation and immune system activation, and ferric reducing ability of plasma for antioxidant capacity. Muscle biopsies were examined for glycogen and NFkB expression to evaluate stress and inflammation. Urine was tested for modification of DNA (8-OHDG) and RNA (5-OHMU) as markers of nucleic acid oxidation. A 2 (treatment) × 3 (time) repeated measures ANOVA was used for statistical analysis. Increases in F₂-isoprostanes and 5-OHMU were significantly less in BB and plasma IL-10 and NK cell counts were significantly greater in BB vs. CON. Changes in all other markers did not differ. This study indicates that daily blueberry consumption for 6 weeks increases NK cell counts, and acute ingestion reduces oxidative stress and increases anti-inflammatory cytokines.",
"title": "Effect of blueberry ingestion on natural killer cell counts, oxidative stress, and inflammation prior to and after 2.5 h of running."
},
{
"docid": "MED-4639",
"text": "Low fecal weight and slow bowel transit time are thought to be associated with bowel cancer risk, but few published data defining bowel habits in different communities exist. Therefore, data on stool weight were collected from 20 populations in 12 countries to define this risk more accurately, and the relationship between stool weight and dietary intake of nonstarch polysaccharides (NSP) (dietary fiber) was quantified. In 220 healthy U.K. adults undertaking careful fecal collections, median daily stool weight was 106 g/day (men, 104 g/day; women, 99 g/day; P = 0.02) and whole-gut transit time was 60 hours (men, 55 hours; women, 72 hours; P = 0.05); 17% of women, but only 1% of men, passed < 50 g stool/day. Data from other populations of the world show average stool weight to vary from 72 to 470 g/day and to be inversely related to colon cancer risk (r = -0.78). Meta-analysis of 11 studies in which daily fecal weight was measured accurately in 26 groups of people (n = 206) on controlled diets of known NSP content shows a significant correlation between fiber intake and mean daily stool weight (r = 0.84). Stool weight in many Westernized populations is low (80-120 g/day), and this is associated with increased colon cancer risk. Fecal output is increased by dietary NSP. Diets characterized by high NSP intake (approximately 18 g/day) are associated with stool weights of 150 g/day and should reduce the risk of bowel cancer.",
"title": "Fecal weight, colon cancer risk, and dietary intake of nonstarch polysaccharides (dietary fiber)"
},
{
"docid": "MED-2714",
"text": "Aromatherapy is becoming increasingly popular; however there are few clear indications for its use. To systematically review the literature on aromatherapy in order to discover whether any clinical indication may be recommended for its use, computerised literature searches were performed to retrieve all randomised controlled trials of aromatherapy from the following databases: MEDLINE, EMBASE, British Nursing Index, CISCOM, and AMED. The methodological quality of the trials was assessed using the Jadad score. All trials were evaluated independently by both authors and data were extracted in a pre-defined, standardised fashion. Twelve trials were located: six of them had no independent replication; six related to the relaxing effects of aromatherapy combined with massage. These studies suggest that aromatherapy massage has a mild, transient anxiolytic effect. Based on a critical assessment of the six studies relating to relaxation, the effects of aromatherapy are probably not strong enough for it to be considered for the treatment of anxiety. The hypothesis that it is effective for any other indication is not supported by the findings of rigorous clinical trials.",
"title": "Aromatherapy: a systematic review."
},
{
"docid": "MED-1785",
"text": "We tested the hypothesis that 75 g of whole-shelled walnuts/day added to the Western-style diet of healthy young men would beneficially affect semen quality. A randomized, parallel two-group dietary intervention trial with single-blind masking of outcome assessors was conducted with 117 healthy men, age 21-35 yr old, who routinely consumed a Western-style diet. The primary outcome was improvement in conventional semen parameters and sperm aneuploidy from baseline to 12 wk. Secondary endpoints included blood serum and sperm fatty acid (FA) profiles, sex hormones, and serum folate. The group consuming walnuts (n = 59) experienced improvement in sperm vitality, motility, and morphology, but no change was seen in the group continuing their usual diet but avoiding tree nuts (n = 58). Comparing differences between the groups from baseline, significance was found for vitality (P = 0.003), motility (P = 0.009), and morphology (normal forms; P = 0.04). Serum FA profiles improved in the walnut group with increases in omega-6 (P = 0.0004) and omega-3 (P = 0.0007) but not in the control group. The plant source of omega-3, alpha-linolenic acid (ALA) increased (P = 0.0001). Sperm aneuploidy was inversely correlated with sperm ALA, particularly sex chromosome nullisomy (Spearman correlation, -0.41, P = 0.002). Findings demonstrated that walnuts added to a Western-style diet improved sperm vitality, motility, and morphology.",
"title": "Walnuts improve semen quality in men consuming a Western-style diet: randomized control dietary intervention trial."
},
{
"docid": "MED-4837",
"text": "BACKGROUND: Gallstone disease known as cholelithiasis is the most common digestive surgical disorder and account for an important part of health care expenditure. Attempt was made to analyse the gallstone for typing depending upon the composition. AIMS & OBJECTIVES: The main objective of this study was to see the prevalence of different types of gallstone in Nepal and to correlate them with the clinical findings. MATERIALS & METHODS: Gallstones of 80 different patients who underwent cholecystectomy for cholelithiasis were collected from 20th January 2005 to 16th May 2006 in Department of Pathology, Kathmandu Medical College Teaching Hospital. Detailed history was taken. Stones were analyzed with chemical and enzymatic methods using clinical spectrophotometer. RESULTS & CONCLUSION: The most commonly involved age group for cholelithiasis (32.5%) is found to be 30-39 years with a female predominance (M: F=1:3.2). Cholelithiasis was found more commonly among non-vegetarian with the vegetarian: non-vegetarian ratio 1:9. Mixed type stone was found to be the most common type of stone comprising 78.75%, followed by cholesterol stone 12.5%, Brown pigment stone 7.5% and Black pigment stone 1.25%.",
"title": "Prevalence of different types of gallstone in the patients with cholelithiasis at Kathmandu Medical College, Nepal."
},
{
"docid": "MED-5074",
"text": "Cooking as a domestic processing method has a great impact on food nutrients. Most Brassica (Brassicaceae, Cruciferae) vegetables are mainly consumed after being cooked, and cooking considerably affects their health-promoting compounds (specifically, glucosinolates, phenolic compunds, minerals, and vitamin C studied here). The microwave cooking process presents controversial results in the literature due to the different conditions that are employed (time, power, and added water). Therefore, the aim of this work was to study the influence of these conditions during microwave cooking on the human bioactive compounds of broccoli. The results show a general decrease in the levels of all the studied compounds except for mineral nutrients which were stable under all cooking conditions. Vitamin C showed the greatest losses mainly because of degradation and leaching, whereas losses for phenolic compounds and glucosinolates were mainly due to leaching into water. In general, the longest microwave cooking time and the higher volume of cooking water should be avoided to minimize losses of nutrients.",
"title": "Effects of microwave cooking conditions on bioactive compounds present in broccoli inflorescences."
},
{
"docid": "MED-3012",
"text": "The fish ingredient N3-docosahexaenoic acid 22:6 n-3 (DHA) stimulates brain development. On the other hand methylmercury (MeHg) in fish disturbs the developing central nervous system. In this Context the IQ score in children is considered as an aggregate measure of in utero brain development. To determine the effect of DHA exposure on prenatal neurodevelopment the maternal DHA intake during pregnancy was compared with its epidemiologically observed effect on the IQ score of children. For MeHg the maternal intake was converted into its accumulation in the maternal body. The maternal body burden then was compared with its epidemiologically observed relationship with the IQ score. Taking the MeHg and DHA content of 33 fish species the net effect of these compounds on the IQ score was quantified. For most fish species the adverse effect of MeHg on the IQ score exceeded the beneficial effect of DHA. In the case of long-living predators a negative effect up to 10 points on the IQ score was found. The results of this study indicate that food interventions aiming at the beneficial effects of fish consumption should focus on fish species with a high DHA content, while avoiding fish species with a high MeHg content. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Fish consumption during child bearing age: a quantitative risk-benefit analysis on neurodevelopment."
},
{
"docid": "MED-5250",
"text": "Several prospective studies considered the relation between coffee consumption and mortality. Most studies, however, were underpowered to detect an association, since they included relatively few deaths. To obtain quantitative overall estimates, we combined all published data from prospective studies on the relation of coffee with mortality for all causes, all cancers, cardiovascular disease (CVD), coronary/ischemic heart disease (CHD/IHD) and stroke. A bibliography search, updated to January 2013, was carried out in PubMed and Embase to identify prospective observational studies providing quantitative estimates on mortality from all causes, cancer, CVD, CHD/IHD or stroke in relation to coffee consumption. A systematic review and meta-analysis was conducted to estimate overall relative risks (RR) and 95 % confidence intervals (CI) using random-effects models. The pooled RRs of all cause mortality for the study-specific highest versus low (≤1 cup/day) coffee drinking categories were 0.88 (95 % CI 0.84-0.93) based on all the 23 studies, and 0.87 (95 % CI 0.82-0.93) for the 19 smoking adjusting studies. The combined RRs for CVD mortality were 0.89 (95 % CI 0.77-1.02, 17 smoking adjusting studies) for the highest versus low drinking and 0.98 (95 % CI 0.95-1.00, 16 studies) for the increment of 1 cup/day. Compared with low drinking, the RRs for the highest consumption of coffee were 0.95 (95 % CI 0.78-1.15, 12 smoking adjusting studies) for CHD/IHD, 0.95 (95 % CI 0.70-1.29, 6 studies) for stroke, and 1.03 (95 % CI 0.97-1.10, 10 studies) for all cancers. This meta-analysis provides quantitative evidence that coffee intake is inversely related to all cause and, probably, CVD mortality.",
"title": "A meta-analysis of prospective studies of coffee consumption and mortality for all causes, cancers and cardiovascular diseases."
},
{
"docid": "MED-2436",
"text": "The content of low density lipoprotein (LDL) receptors in tissue from primary breast cancers was determined and its prognostic information compared with that of variables of established prognostic importance. Frozen tumour specimens were selected, and tissue from 72 patients (32 of whom had died) were studied. The LDL receptor content showed an inverse correlation with the survival time. Analysis by a multivariate statistical method showed that the presence of axillary metastasis, content of receptors for oestrogen and LDL, diameter of the tumour, and DNA pattern were all of prognostic value with regard to patient survival. Improved methods of predicting survival time in patients with breast cancer may be of value in the choice of treatment for individual patients.",
"title": "Content of low density lipoprotein receptors in breast cancer tissue related to survival of patients."
},
{
"docid": "MED-3619",
"text": "Diagnostic imaging is an indispensable part of contemporary medical and dental practice. Over the last few decades there has been a dramatic increase in the use of ionizing radiation for diagnostic imaging. The carcinogenic effects of high-dose exposure are well known. Does diagnostic radiation rarely cause cancer? We don't know but we should act as if it does. Accordingly, dentists should select patients wisely - only make radiographs when there is patient-specific reason to believe there is a reasonable expectation the radiograph will offer unique information influencing diagnosis or treatment. Low-dose examinations should be made: intraoral imaging - use fast film or digital sensors, thyroid collars, rectangular collimation; panoramic and lateral cephalometric imaging - use digital systems or rare-earth film screen combinations; and cone beam computed tomography - use low-dose machines, restrict field size to region of interest, reduce mA and length of exposure arc as appropriate. © 2012 Australian Dental Association.",
"title": "Update on the biological effects of ionizing radiation, relative dose factors and radiation hygiene."
},
{
"docid": "MED-3100",
"text": "Dioxins invade the body mainly through the diet, and produce toxicity through the transformation of aryl hydrocarbon receptor (AhR). An inhibitor of the transformation should therefore protect against the toxicity and ideally be part of the diet. We examined flavonoids ubiquitously expressed in plant foods as one of the best candidates, and found that the subclasses flavones and flavonols suppressed antagonistically the transformation of AhR induced by 1 nM of 2,3,7,8-tetrachlorodibenzo-p-dioxin, without exhibiting agonistic effects that transform AhR. The antagonistic IC(50) values ranged from 0.14 to 10 microM, close to the physiological levels in human.",
"title": "Flavones and flavonols at dietary levels inhibit a transformation of aryl hydrocarbon receptor induced by dioxin."
},
{
"docid": "MED-4560",
"text": "The good news about coronary atherosclerosis is that it takes an awful lot of plaque before symptoms of myocardial ischemia occur. The bad news is that despite the need for large quantities of plaque for symptoms to occur, nevertheless nearly half of us in the United States eventually have the necessary quantity. Atherosclerosis is infrequently hereditary in origin. Most of us get atherosclerosis because we consume too much fat, cholesterol, and calories. The consequence is an elevated ( > 150 mg/dl) serum total cholesterol level, and the higher the number is above 150, the greater is the quantity of plaque deposited in our arteries. If the serum total cholesterol level can be prevented from rising to more than 150 mg/dl, plaques are not laid down; if elevated levels are lowered to 150 mg/dl, further plaque does not form, and parts of those present may vanish. A fruit-vegetarian-starch diet is necessary as a rule to achieve the 150 mg/dl level in most adults. Lipid-lowering drugs are required in the patients with familial hypercholesterolemia and in most patients with atherosclerotic events. The best news about atherosclerosis is that it can be prevented in those without the hereditary form, and it can be arrested by lowering elevated serum total (and LDL) cholesterol to the 150 mg/dl level.",
"title": "Preventing and arresting coronary atherosclerosis."
},
{
"docid": "MED-5171",
"text": "The objective of this study was to determine the prevalence of enterohemorrhagic Escherichia coli (EHEC), E. coli O157, Salmonella, and Listeria monocytogenes in retail food samples from Seattle, Wash. A total of 2,050 samples of ground beef (1,750 samples), mushrooms (100 samples), and sprouts (200 samples) were collected over a 12-month period and analyzed for the presence of these pathogens. PCR assays, followed by culture confirmation were used to determine the presence or absence of each organism. Of the 1,750 ground beef samples analyzed, 61 (3.5%) were positive for EHEC, and 20 (1.1%) of these were positive for E. coli O157. Salmonella was present in 67 (3.8%) of the 1,750 ground beef samples. Of 512 ground beef samples analyzed, 18 (3.5%) were positive for L. monocytogenes. EHEC was found in 12 (6.0%) of the 200 sprout samples, and 3 (1.5%) of these yielded E. coli O157. Of the 200 total sprout samples, 14 (7.0%) were positive for Salmonella and none were positive for L. monocytogenes. Among the 100 mushroom samples, 4 (4.0%) were positive for EHEC but none of these 4 samples were positive for E. coli O157. Salmonella was detected in 5 (5.0%) of the mushroom samples, and L. monocytogenes was found in 1 (1.0%) of the samples.",
"title": "Incidence of enterohemorrhagic Escherichia coli, Escherichia coli O157, Salmonella, and Listeria monocytogenes in retail fresh ground beef, sprouts..."
},
{
"docid": "MED-3734",
"text": "Cranberry products and especially cranberry juice (CJ) have been consumed for health reasons primarily due to their effect on urinary tract infections. We investigated the quantity of both free and total (after hydrolysis) phenolic antioxidants in cranberry products using the Folin assay. The order of amount of total polyphenols in cranberry foods on a fresh weight basis was as follows: dried > frozen > sauce > jellied sauce. On a serving size basis for all cranberry products, the order was as follows: frozen > 100% juice > dried > 27% juice > sauce > jellied sauce. High fructose corn syrup (HFCS) is a major source of sugar consumption in the U.S. and contains both glucose and fructose, potential mediators of oxidative stress. We investigated the effect of the consumption of HFCS and ascorbate with CJ antioxidants or without CJ (control) given to 10 normal individuals after an overnight fast. Plasma antioxidant capacity, glucose, triglycerides, and ascorbate were measured 6 times over 7 h after the consumption of a single 240 mL serving of the two different beverages. The control HFCS caused a slight decrease in plasma antioxidant capacity at all time points and thus an oxidative stress in spite of the presence of ascorbate. CJ produced an increase in plasma antioxidant capacity that was significantly greater than control HFCS at all time points. Postprandial triglycerides, due to fructose in the beverages, were mainly responsible for the oxidative stress and were significantly correlated with the oxidative stress as measured by the antioxidant capacity. Cranberries are an excellent source of high quality antioxidants and should be examined in human supplementation studies.",
"title": "Cranberries and cranberry products: powerful in vitro, ex vivo, and in vivo sources of antioxidants."
},
{
"docid": "MED-1037",
"text": "Ancient Egypt was one of the greatest civilizations to have arisen, becoming the cradle of scientific enquiry and social development over 3 millennia; undoubtedly its knowledge of medicine has been vastly underestimated. Few artefacts survive which describe the medical organization, but from the extent of the diseases afflicting that ancient populus there would have been much to study. Evidence from papyri, tomb bas reliefs and the writings of historians of antiquity tell of an intense interest in the sciences, humanities and medicine born of an educated society which had overcome the superstitions of its nomadic ancestors.",
"title": "A brief journey into medical care and disease in ancient Egypt."
},
{
"docid": "MED-3102",
"text": "BACKGROUND: Halogenated aromatic hydrocarbons including dioxins and non-halogenated polycyclic aromatic hydrocarbons are ligands of an aryl hydrocarbon receptor (AhR) and stimulate its transformation. Exposure to these environmental contaminants occurs mainly through diet. Recent articles demonstrated that certain food factors regulate the AhR transformation and expression of downstream drug-metabolizing enzymes. OBJECTIVE: To explain the actions of these food factors on the AhR transformation, as the mechanisms underlying are not fully understood. METHODS: This review introduces recent articles that have demonstrated the molecular mechanisms by which food factors regulate the AhR transformation and downstream drug-metabolizing enzymes. RESULTS/CONCLUSION: The role of classical ligands including dioxins as agonists of the receptor is well documented. As to the food factors, they act as antagonists because they basically suppress the AhR transformation by different mechanisms. Moreover, the fate and metabolism of food factors are important to understand their mechanisms.",
"title": "An update on the dietary ligands of the AhR."
},
{
"docid": "MED-1345",
"text": "This article explores the reaction when an article challenging received wisdom is published and covered extensively by the media (1). The article in question was a meta-analysis of antidepressant clinical trials indicating that for most patients, difference between drug and placebo was not clinically significant. Reactions ranged from denial that the effects of antidepressants are so small to criticisms of the clinical trials that were analyzed. Each of these reactions is explored and countered.",
"title": "Challenging Received Wisdom: Antidepressants and the Placebo Effect"
},
{
"docid": "MED-2819",
"text": "OBJECTIVES: Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. We highlight both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA). We also explore the recent literature on the molecular mechanisms of curcumin mediated alterations in gene expression mediated via activator protein 1 (AP-1)/nuclear factor-kappa B (NF-kappaB) signalling in chondrocytes, osteoblasts and synovial fibroblasts. METHODS: A computer-aided search of the PubMed/Medline database aided by a text-mining tool to interrogate the ResNet Mammalian database 6.0. RESULTS: Recent work has shown that curcumin protects human chondrocytes from the catabolic actions of interleukin-1 beta (IL-1beta) including matrix metalloproteinase (MMP)-3 up-regulation, inhibition of collagen type II and down-regulation of beta1-integrin expression. Curcumin blocks IL-1beta-induced proteoglycan degradation, AP-1/NF-kappaB signalling, chondrocyte apoptosis and activation of caspase-3. CONCLUSIONS: The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. Nevertheless, before initiating extensive clinical trials, more basic research is required to improve its solubility, absorption and bioavailability and gain additional information about its safety and efficacy in different species. Once these obstacles have been overcome, curcumin and structurally related biochemicals may become safer and more suitable nutraceutical alternatives to the non-steroidal anti-inflammatory drugs that are currently used for the treatment of OA. Copyright 2009 Osteoarthritis Research Society International. All rights reserved.",
"title": "Biological actions of curcumin on articular chondrocytes."
}
] |
7956
|
Some stock's prices don't fluctuate widely - Is it an advantages?
|
[
{
"docid": "293027",
"text": "What is your investment goal? Many investors buy for the long haul, not short-term gain. If you're looking for long-term gain then daily fluctuations should be of no concern to you. If you want to day-trade and time the market (buy low and sell high with a short holding period) then yes less volatile stock can be less profitable, but they also carry less risk. In that case, though, transaction fees have more of an impact, and you usually have to trade in larger quantities to reduce the impact of transaction fees.",
"title": ""
},
{
"docid": "483765",
"text": "Oracle specifically is paying a dividend with a current yield of about 1.4% annually and has appreciated nearly 50% over the last 5 years. Granted, the past doesn't guarantee the future but the company has paid a pretty steady dividend since 2009. If you're buying as part of an employee program you would presumably be holding the shares for a long time and the daily and even monthly movements aren't terribly relevant to a long term holding period. Additionally, you may be able to buy the shares at a discount to the market price as part of your employee program. You probably also won't pay any transaction fee.",
"title": ""
},
{
"docid": "127702",
"text": "I don't think you are reading the stock chart right. ORCL has a beta of 1.12 which means it has more volatility than the market as a whole. See image below for a fairly wild stock chart for a year. I would not truly consider ESPP participation investing, unless you intend to buy and hold the stock. If you intend to sell the stock soon after you are able, it is more speculation. ESPP's are okay based upon the terms. If the stock was a constant price, and you could sell right away, then an ESPP plan would be easy money. Often, employees are often given a 15% discount to purchase the stock. If you can sell it before any price drop, then you are guaranteed to make 15% on the money invested minus any commissions. Some employers make ESPP participants hold the stock for a year. This makes such a plan less of a value. The reasons are the stock can drop in price during that time, you could need the money, or (in the best case) your money is tied up longer making the ROI less. The reasons people invest in stock are varied and is far to much to discuss in a single post. Some of your colleagues are using the ESPP solely to earn the discount in their money.",
"title": ""
},
{
"docid": "598295",
"text": "Apart from making money from the price difference, some stocks also give dividends, or bonus issues. For long term investors whom are looking for steady income, they may be more interested with the dividend pay-out instead of the capital-appreciation.",
"title": ""
}
] |
[
{
"docid": "127689",
"text": "\"I think this is a good question with no single right answer. For a conservative investor, possible responses to low rates would be: Probably the best response is somewhere in the middle: consider riskier investments for a part of your portfolio, but still hold on to some cash, and in any case do not expect great results in a bad economy. For a more detailed analysis, let's consider the three main asset classes of cash, bonds, and stocks, and how they might preform in a low-interest-rate environment. (By \"\"stocks\"\" I really mean mutual funds that invest in a diversified mixture of stocks, rather than individual stocks, which would be even riskier. You can use mutual funds for bonds too, although diversification is not important for government bonds.) Cash. Advantages: Safe in the short term. Available on short notice for emergencies. Disadvantages: Low returns, and possibly inflation (although you retain the flexibility to move to other investments if inflation increases.) Bonds. Advantages: Somewhat higher returns than cash. Disadvantages: Returns are still rather low, and more vulnerable to inflation. Also the market price will drop temporarily if rates rise. Stocks. Advantages: Better at preserving your purchasing power against inflation in the long term (20 years or more, say.) Returns are likely to be higher than stocks or bonds on average. Disadvantages: Price can fluctuate a lot in the short-to-medium term. Also, expected returns are still less than they would be in better economic times. Although the low rates may change the question a little, the most important thing for an investor is still to be familiar with these basic asset classes. Note that the best risk-adjusted reward might be attained by some mixture of the three.\"",
"title": ""
},
{
"docid": "329527",
"text": "The problem with predicting with accuracy what a stock price will do in any given situation is that there are two main factors that affect a stocks price. The first factor is based somewhat in math as it takes into account numbers such as supply and demand, earnings per share, expected earnings, book value, debt ratio and a wide variety of other numbers. You can compile all those numbers into a variety of formulas and come up with a rational estimate of what the stock should sell for. This is all well and good and if the market were entirely rational it would rarely make news because it would be predictable and boring. This is where our second factor throws a wrench in the works. The second factor affecting stock price is emotional. There are many examples of people's emotions affecting stock price but if you would like a good example look up the price fluctuations of Apple (AAPL) after their last couple earnings reports. Numerically their company looks good, their earnings were healthy, their EPS is below average yet their price fell following the report. Why is that? There really isn't a rational reason for it, it is driven by the emotions behind unmet expectations. In a more general sense sometimes price goes down and people get scared and sell causing further decline, sometimes people get excited and see it as opportunity to buy in and the price stabilizes. It is much more difficult to anticipate the reaction the market will have to people's emotional whims which is why predicting stock price with accuracy is near impossible. As a thought along the same line ask yourself this question; if the stock market were entirely rational and price could be predicted with accuracy why is there such a wide range of available strike prices available in the options market? It seems that if stock price could be predicted with anything remotely reassembling accuracy the options market need a much smaller selection of available strike prices.",
"title": ""
},
{
"docid": "446629",
"text": "Algorithmic trading essentially banks on the fact that a price will fluctuate in tiny amounts over short periods of time, meaning the volatility is high in that given time frame. As the time frame increases the efficiency of algorithmic trading decreases and proper investment strategies such as due diligence, stock screening, and technical analysis become the more efficient methods. Algorithms become less effective as the time frame increases due to the smoothing effect of volatility over time. Writing an algorithm that could predict future long-term prices would be an impossible feat because as the time frame is scaled up there are far less price fluctuations and trends (volatility smooths out) and so there is little to no benchmark for the formulas. An algorithm simply wouldn't make sense for a long-term position. A computer can't predict, say, the next quarter, an ousted CEO, a buyout, or anything else that could effect the price of the security, never mind the psychology behind it all. Vice versa, researching a company's fundamentals just to bank on a 0.25% daily swing would not be efficient. Tax advantages or not, it is the most efficient methods that are preferred for a given time-scale of trading.",
"title": ""
},
{
"docid": "433516",
"text": "The time horizon is usually very short for a home down payment. I would use Certificates of Deposit (CDs) with a short maturity (in the horizon of your intended use) or Money Market accounts. Depending on what the interests rates are where you are looking. You don't want the money in the market 100% (i.e. stocks) as the fluctuations might be too wide around the time you intend to pull the money out (and that will be soon).",
"title": ""
},
{
"docid": "197047",
"text": "Ok you're looking at this in a very confusing way. First, as said by CapitalNumb3rs, the dividend yield is the dividends paid in the year as a percent of the stock price. Given this fact then if the stock price moves down and the dividend stays the same then the yield increases. Company's don't usually pay out on a yield basis, that's mostly just a calculation to measure how strong a dividend is. This could mean either A. The stock is underpriced and will rise which will lower the yield to a more normal level or B. the company is not doing as well and eventually the dividends will decrease to a point where the yield again looks more normal. Second off let's look at it in a more realistic way that still takes into account your assumptions: **YEAR 1** 1. Instead of assuming buying 35% let's put this into a share amount. Let's say there are 1,000,000 shares so you just bought 350k shares for $700k. You paid a price of $2/share. Let's assume the market decides that's a fair price and it stays that way through the end of year 1. This gives us a market capitalization of $2 million. 2. The dividend paid out at year 1 is $60k so you could calculate on a per share basis which would be a dividend of $60k / 1 million shares or a $0.06 dividend per share. Our stock price is still at $2.00 so our yield comes out to $0.06 / $2.00 or 3.0% **YEAR 2** Assuming no additional shares issued there are still a total of 1 million shares outstanding. You owned 350k and now want to purchase another 50k (5% of outstanding share float). The market price you are able to purchase the 50k shares at has now changed which means that share price is now valued at $1.50 / share. We have a dividend paid out at $100k, which comes out to a dividend per share of $0.10. We have a share value of $1.50 and the $0.10 dividend per share giving us a new yield of 6.66%. **CONCLUSION:** There are many factors that can cause a company's stock price to fluctuate, some of it is hype based but some of it is a result of material changes. In your case the stock went down 25%. In most scenarios where a stock would have that much decline it would likely either not have been paying a dividend in the first place or would maybe not be paying one for much longer. Most companies that pay dividends are larger and more mature companies with a steady, healthy and predictable cash flow. Also most companies that are that size would not trade a stock under $3.00, I know this is just an example but the scenario is definitely a bit extreme in terms of the price drop and dividend increase. Again the yield is just a calculation that depends on the dividend that is usually planned in advance and the stock price that can fluctuate for many reasons. I hope this made everything more clear and let me know if you have any other questions.",
"title": ""
},
{
"docid": "519390",
"text": "\"Wouldn't this be part of your investing strategy to know what price is considered a \"\"good\"\" price for the stock? If you are going to invest in company ABC, shouldn't you have some idea of whether the stock price of $30, $60, or $100 is the bargain price you want? I'd consider this part of the due diligence if you are picking individual stocks. Mutual funds can be a bit different in automatically doing fractional shares and not quite as easy to analyze as a company's financials in a sense. I'm more concerned with the fact that you don't seem to have a good idea of what the price is that you are willing to buy the stock so that you take advantage of the volatility of the market. ETFs would be similar to mutual funds in some ways though I'd probably consider the question that may be worth considering here is how much do you want to optimize the price you pay versus adding $x to your position each time. I'd probably consider estimating a ballpark and then setting the limit price somewhere within that. I wouldn't necessarily set it to the maximum price you'd be willing to pay unless you are trying to ride a \"\"hot\"\" ETF using some kind of momentum strategy. The downside of a momentum strategy is that it can take a while to work out the kinks and I don't use one though I do remember a columnist from MSN Money that did that kind of trading regularly.\"",
"title": ""
},
{
"docid": "184077",
"text": "\"Your employer sends the money that you choose to contribute, plus employer match if any, to the administrator of the 401k plan who invests the money as you have directed, choosing between the alternatives offered by the administrator. Typically, the alternatives are several different mutual funds with different investment styles, e.g. a S&P 500 index fund, a bond fund, a money-market fund, etc. Now, a statement such as \"\"I see my 401k is up 10%\"\" is meaningless unless you tell us how you are making the comparison. For example, if you have just started employment and $200 goes into your 401k each month and is invested in a money-market fund (these are paying close to 0% interest these days), then your 11th contribution increases your 401k from $2000 to $2200 and your 401k is \"\"up 10%\"\". More generally, suppose for simplicity that all the 401k investment is in just one (stock) mutual fund and that you own 100 shares of the fund as of right now. Suppose also that your next contribution will not occur for three weeks when you get your next paycheck, at which time additional shares of the mutual fund will be purchased Now, the value of the mutual fund shares (often referred to as net asset value or NAV) fluctuates as stock prices rise and fall, and so the 401k balance = number of shares times NAV changes in accordance with these fluctuations. So, if the NAV increases by 10% in the next two weeks, your 401k balance will have increased by 10%. But you still own only 100 shares of the mutual fund. You cannot use the 10% increase in value to buy more shares in the mutual fund because there is no money to pay for the additional shares you wish to purchase. Notice that there is no point selling some of the shares (at the 10% higher NAV) to get cash because you will be purchasing shares at the higher NAV too. You could, of course, sell shares of the stock mutual fund at the higher NAV and buy shares of some other fund available to you in the 401k plan. One advantage of doing this inside the 401k plan is that you don't have to pay taxes (now) on the 10% gain that you have made on the sale. Outside tax-deferred plans such as 401k and IRA plans, such gains would be taxable in the year of the sale. But note that selling the shares of the stock fund and buying something else indicates that you believe that the NAV of your stock mutual fund is unlikely to increase any further in the near future. A third possibility for your 401k being up by 10% is that the mutual fund paid a dividend or made a capital gains distribution in the two week period that we are discussing. The NAV falls when such events occur, but if you have chosen to reinvest the dividends and capital gains, then the number of shares that you own goes up. With the same example as before, the NAV goes up 10% in two weeks at which time a capital gains distribution occurs, and so the NAV falls back to where it was before. So, before the capital gains distribution, you owned 100 shares at $10 NAV which went up to $11 NAV (10% increase in NAV) for a net increase in 401k balance from $1000 to $1100. The mutual fund distributes capital gains in the amount of $1 per share sending the NAV back to $10, but you take the $100 distribution and plow it back into the mutual fund, purchasing 10 shares at the new $10 NAV. So now you own 110 shares at $10 NAV (no net change in price in two weeks) but your 401k balance is $1100, same as it was before the capital gains distribution and you are up 10%. Or, you could have chosen to invest the distributions into, say, a bond fund available in your 401k plan and still be up 10%, with no change in your stock fund holding, but a new investment of $100 in a bond fund. So, being up 10% can mean different things and does not necessarily mean that the \"\"return\"\" can be used to buy more shares.\"",
"title": ""
},
{
"docid": "30774",
"text": "The biggest challenge with owning any individual stock is price fluctuation, which is called risk. The scenarios you describe assume that the stock behaves exactly as you predict (price/portfolio doubles) and you need to consider risk. One way to measure risk in a stock or in a portfolio is Sharpe Ratio (risk adjusted return), or the related Sortino ratio. One piece of advice that is often offered to individual investors is to diversify, and the stated reason for diversification is to reduce risk. But that is not telling the whole story. When you are able to identify stocks that are not price correlated, you can construct a portfolio that reduces risk. You are trying to avoid 10% tax on the stock grant (25%-15%), but need to accept significant risk to avoid the 10% differential tax ($1000). An alternative to a single stock is to invest in an ETF (much lower risk), which you can buy and hold for a long time, and the price/growth of an ETF (ex. SPY) can be charted versus your stock to visualize the difference in growth/fluctuation. Look up the beta (volatility) of your stock compared to SPY (for example, IBM). Compare the beta of IBM and TSLA and note that you may accept higher volatility when you invest in a stock like Tesla over IBM. What is the beta of your stock? And how willing are you to accept that risk? When you can identify stocks that move in opposite directions, and mix your portfolio (look up beta balanced portolio), you can smooth out the variability (reduce the risk), although you may reduce your absolute return. This cannot be done with a single stock, but if you have more money to invest you could compose the rest of your portfolio to balance the risk for this stock grant, keep the grant shares, and still effectively manage risk. Some years ago I had accumulated over 10,000 shares (grants, options) in a company where I worked. During the time I worked there, their price varied between $30/share and < $1/share. I was able to liquidate at $3/share.",
"title": ""
},
{
"docid": "508764",
"text": "Mutual funds don't work like stocks in that way. The price of a mutual fund is set at the end of each day and doesn't fluctuate during the day. So no matter when you put in your order, it will be filled at the end of the day at whatever the closing price is for that day. Here is some good information on that There is no continuous pricing of fund shares throughout the trading day. When an investor places an order to buy or sell a fund's shares, the order is executed based on the NAV calculated at the end of that trading day, regardless of what time during the day the order was placed. On the other hand, if the investor were to check the price of his or her fund shares halfway through the business day, the price quoted would be the previous day's NAV because that was the last time the fund calculated and reported the value. -http://www.finweb.com/investing/how-mutual-funds-are-priced.html",
"title": ""
},
{
"docid": "473658",
"text": "ETFs offer the flexibility of stocks while retaining many of the benefits of mutual funds. Since an ETF is an actual fund, it has the diversification of its potentially many underlying securities. You can find ETFs with stocks at various market caps and style categories. You can have bond or mixed ETFs. You can even get ETFs with equal or fundamental weighting. In short, all the variety benefits of mutual funds. ETFs are typically much less expensive than mutual funds both in terms of management fees (expense ratio) and taxable gains. Most of them are not actively managed; instead they follow an index and therefore have a low turnover. A mutual fund may actively trade and, if not balanced with a loss, will generate capital gains that you pay taxes on. An ETF will produce gains only when shifting to keep inline with the index or you yourself sell. As a reminder: while expense ratio always matters, capital gains and dividends don't matter if the ETF or mutual fund is in a tax-advantaged account. ETFs have no load fees. Instead, because you trade it like a stock, you will pay a commission. Commissions are straight, up-front and perfectly clear. Much easier to understand than the various ways funds might charge you. There are no account minimums to entry with ETFs, but you will need to buy complete shares. Only a few places allow partial shares. It is generally harder to dollar-cost average into an ETF with regular automated investments. Also, like trading stocks, you can do those fancy things like selling short, buying on margin, options, etc. And you can pay attention to the price fluctuations throughout the day if you really want to. Things to make you pause: if you buy (no-load) mutual funds through the parent company, you'll get them at no commission. Many brokerages have No Transaction Fee (NTF) agreements with companies so that you can buy many funds for free. Still look out for that expense ratio though (which is probably paying for that NTF advantage). As sort of a middle ground: index funds can have very low expense ratios, track the same index as an ETF, can be tax-efficient or tax-managed, free to purchase, easy to dollar-cost average and easier to automate/understand. Further reading:",
"title": ""
},
{
"docid": "16292",
"text": "I asked a friend and he gave me a good explanation, so I'm just gonna paste it here for others: There is a simple and a complex answer depending on how much you want to understand the pricing dynamic of options. LEAPs don't react 1:1 with a stock move because the probability of your option being in the money at expiry is still very much up in the air so you basically don't get full credit for a move in the stock this far out from expiry. The more complex answer involves a discussion of option 'greeks'. Delta, Gamma, Theta, Vega, and Rho are variables that affect the pricing of all options. The key greek in this case is Delta because it describes mathematically the expected move of an option as a ratio vs changes in stock price. For put options the ratio is -1 to 0 where -1 is direct correlation between stock price and option price and 0 is no correlation. The Delta increases as an option gets deeper in the money and also as it gets closer to expiry and reflects the probability of the option expiring in the money. For your option contract the current Delta is -0.5673 so -3.38 * -0.5673 = 1.9 which is close. Also keep in mind that that strike price had a last trade at 12:03 when the stock was at 13.3 and the current ask price is 22.30 so the last price isn't a true reflection of the market value. As for the other greeks, Gamma is a reflection of volatility in the sense that it affects the rate of change of Delta as price and time changes. Theta is the value of the time component of the option and is expressed as the expected time decay per day. The problem is that the time premium is really some arbitrary number that the market maker seems to be able to change at will without justification and it can fluctuate wildly over short periods of time and I think this may explain some of the discrepancy. If you bought the options when AAPL was $118.68 a couple weeks ago (option price of $18.85) and now AAPL is at $112.34 and the Delta over that time averaged at -0.55 then your expected option price would be $22.34 (($118.68 - $112.34) * 0.55 + 18.85 = $22.34) so you lost around $0.24 in time premium or 'Theta burn' over the last 2 weeks assuming it opens trading around 22.1 on Monday. Your broker should have information about the option contract greeks somewhere. For my platform I have to put the cursor over top of the option contract for it to show me the greeks. If your broker doesn't have this then you can get it from nasdaq.com. This is another reason that I only invest in deep in the money LEAPs because the time premium is much much lower than near the money and also because delta is much higher so if I want to trade out of it early I don't feel like I'm getting ripped off not getting paid for a stock price move. For example look at the Jan 17 175 put. The Delta is -0.9 and the time premium is only $0-1 depending if you are looking at the bid or ask. The only downside is expected returns are lower for deep in the money contracts and they are expensive to buy.",
"title": ""
},
{
"docid": "100546",
"text": "\"A company doesn't offer up 100% of its shares to the market. There's a float amount of varying significance, maybe 30% of the shares are put up for public offer. Generally some amount of current shareholders will pledge some or all of their shares for offer to the public. This may be how the venture capital, private equity or other current investors cash out their initial investment. The company may issue new shares in order to raise money for some initiative. It may be a combination of existing shares and new. Additionally, a company may hold some \"\"treasury shares\"\" on its balance sheet. In this instance fluctuations in the share price directly affect the health of the balance sheet. As far as incentive goes, stock options to management and C-Suite employees keep everyone interested in an increasing stock price.\"",
"title": ""
},
{
"docid": "191677",
"text": "10-Q is the quarterly report, and accordingly is filed quarterly. Similarly, 10-K is the annual report. 8-K is a general form for notification of material events. It is filed every time a material event is required to be reported to the shareholders. It may accompany the periodical reports, but doesn't have to. It can be filed on its own. If you're only interested in the financial statements, then you should be looking for the 10K/10Q forms. SEC will tell you when the forms were filed (dates), but it won't tell you what's more material and what's less. So you can plot a stock price graph on these dates, and see what was deemed more material by the investors based on the price fluctuations, but be prepared to find fluctuations that have no correlation to filings - because the market as a whole can drag the stock up or down. Also, some events may not be required to be reported to SEC, but may be deemed material by the investors. For example, a Cupertino town hall meeting discussing the zoning for the new AAPL HQ building may be deemed material by the investors, based on the sentiments, even if no decision was made to be reported to SEC.",
"title": ""
},
{
"docid": "583378",
"text": "There's a lot of hype about HFT. It involves computers doing things that people don't really understand and making a bunch of rich guys a bunch of money, and there was a crisis and so we hate rich wall street guys this year, and so it's a hot-button issue. Meh. There's some reason for concern about the safety of the markets, but I think there's also a lot more of people trying to sell you a newspaper. Remember that while HFT may mean there are a lot of trades, the buying and the selling add up to the same thing. Meanwhile, people who buy stock to hold on to it for significant periods of time will still affect the quantity of stock out there on the market, applying pressure to the price, buying and selling at the prices that they think the security is worth. As a result, it's unlikely that high-frequency trading moves the stock price very far from the price that the rest of the market would determine for very long; if it did, the lower-frequency traders could take advantage of it, buying if it's too low and selling if it's too high. How long do you plan to hold a stock? If you're trying to do day-trading, you might have some trouble; these people are competing with you to do the same thing, and have significant resources at their disposal. If you're holding onto your stock for years on end (like you probably should be doing with most stock) then a trivial premium or discount on the price probably isn't going to be a big deal for you.",
"title": ""
},
{
"docid": "5572",
"text": "\"It's not necessarily bad but it can cause the stock price to become a lot more volatile. Depends on which side of the bet you're on ;) Suppose a hedge fund manager thinks a company is poorly run. He may buy a ton of shares so that he can get rid of the current CEO and replace it with his/her own. For the hedge fund and others long on the stock, this is good. Those who are trading options or using some short-term strategies could get screwed because of the sudden volatility. My next point is related to the above. What is the intrinsic value of a stock? The current price of a stock is the equilibrium of all investor's perception of the stock's value. Professionals make up a value for a stock using models such as DCF. Once they do so they trade based on what they believe the value of the stock is. You might calculate a stock is worth 70 and I believe it's 80 so the stock price is going to fluctuate a bit but it should keep within that range (assuming we're the only investors). Then comes a hedge fund manager, say Carl Icahn, and discloses a stake in our stock. \"\"Wow, the stock must be really valuable!\"\" Everyone starts buying this stock so up it goes to 90, simply because the guy who seems to know what he's doing bought it. The point here is that now it's not trading based on intrinsic value, now it's purely psychological. Ie. it's now a momentum stock, which you have no idea when it'll crash. Look at Tesla, Netflix, or just google momentum stocks. All the big crashes in stock prices happen when these big funds unload their stocks. A surge in supply will cut the price. The problem is you can't predict when some fund manager will decide to sell some stake of his. Tying everything together is liquidity. The more liquid a stock is, the easier it is to obtain and the less volatile it is. The more people playing the game, with not too big shares of stock, the faster the price will converge to some equilibrium and with less volatility. Institutional investors take away liquidity.\"",
"title": ""
},
{
"docid": "288403",
"text": "Earnings per share is the company profit (or loss), divided by the number of outstanding shares. The number should always be compared to the share price, so for instance if the EPS is $1 and the share price is $10, the EPS is 10% of the share price. This means that if the company keeps up this earning you should expect to make 10% yearly on your investment, long term. The stock price may fluctuate, but if the company keeps on making money you will eventually do so too as investor. If the EPS is low it means that the market expects the earnings to rise in the future, either because the company has a low profit margin that can be vastly improved, or because the business is expected to grow. Especially the last case may be a risky investment as you will lose money if the company doesn't grow fast enough, even if it does make a healthy profit. Note that the listed EPS, like most key figures, is based on the last financial statement. Recent developments could mean that better or worse is generally expected. Also note that the earnings of some companies will fluctuate wildly, for instance companies that produce movies or video games will tend to have a huge income for a quarter or two following a new release, but may be in the negative in some periods. This is fine as long as they turn a profit long term, but you will have to look at data for a longer period in order to determine this.",
"title": ""
},
{
"docid": "329662",
"text": "\"As the other answer said, the person who owns the lent stock does not benefit directly. They may benefit indirectly in that brokers can use the short lending profits to reduce their fees or in that they have the option to short other stocks at the same terms. Follow-up question: what prevents the broker lending the shares for a very short time (less than a day), pocketing the interest and returning the lenders their shares without much change in share price (because borrowing period was very short). What prevents them from doing that many times a day ? Lack of market. Short selling for short periods of time isn't so common as to allow for \"\"many\"\" times a day. Some day traders may do it occasionally, but I don't know that it would be a reliable business model to supply them. If there are enough people interested in shorting the stock, they will probably want to hold onto it long enough for the anticipated movement to happen. There are transaction costs here. Both fees for trading at all and the extra charges for short sale borrowing and interest. Most stocks do not move down by large enough amounts \"\"many\"\" times a day. Their fluctuations are smaller. If the stock doesn't move enough to cover the transaction fees, then that seller lost money overall. Over time, sellers like that will stop trading, as they will lose all their money. All that said, there are no legal blocks to loaning the stock out many times, just practical ones. If a stock was varying wildly for some bizarre reason, it could happen.\"",
"title": ""
},
{
"docid": "415281",
"text": "I agree that high volatility just means the underlying stock price fluctuates more, and it does not imply if the stock is going up or down. But a high volatility in the price of an underlying also means that there is a higher chance that the underlying price could reach extreme prices (albeit in either direction). However, if you purchased a call option then if the underlying price reached an extremely high value, then you will be richly rewarded. But if the underlying price reached an extremely low value, you won't lose any more than the initial premium that you paid. There is no additional risk on your side, it's capped to the premium that you paid for the call option. It's this asymmetric outcome (Heads - I win, Tails - I don't lose) combined with high volatility that means that call options will increase in value when the underlying price becomes more volatile. If the optionality wasn't there then the price wouldn't be related to the volatility of the underlying. But that would be called a Future or a Forward :-)",
"title": ""
},
{
"docid": "466711",
"text": "Because buying at discount provides a considerable safety of margin -- it increases the likelihood of profiting. The margin serves to cushion future adverse price movement. Why is so much effort made to get a small percentage off an investment, if one is then willing to let the investment drop another 20% or more with the reason of being in it for the long term? Nobody can predict the stock price. Now if a long term investor happens to buy some stocks and the market crashes the next day, he could afford to wait for the stock prices to bounce back. Why should he sells immediately to incur a definite loss, should he has confidence in the underlying companies to recover eventually? One can choose to buy wisely, but the market fluctuation is out of his/her control. Wouldn't you agree that he/she should spend much efforts on something that can be controlled?",
"title": ""
},
{
"docid": "374225",
"text": "\"First of all, it's great you're now taking full advantage of your employer match – i.e. free money. Next, on the question of the use of a life cycle / target date fund as a \"\"hedge\"\": Life cycle funds were introduced for hands-off, one-stop-shopping investors who don't like a hassle or don't understand. Such funds are gaining in popularity: employers can use them as a default choice for automatic enrollment, which results in more participation in retirement savings plans than if employees had to opt-in. I think life cycle funds are a good innovation for that reason. But, the added service and convenience typically comes with higher fees. If you are going to be hands-off, make sure you're cost-conscious: Fees can devastate a portfolio's performance. In your case, it sounds like you are willing to do some work for your portfolio. If you are confident that you've chosen a good equity glide path – that is, the initial and final stock/bond allocations and the rebalancing plan to get from one to the other – then you're not going to benefit much by having a life cycle fund in your portfolio duplicating your own effort with inferior components. (I assume you are selecting great low-cost, liquid index funds for your own strategy!) Life cycle are neat, but replicating them isn't rocket science. However, I see a few cases in which life cycle funds may still be useful even if one has made a decision to be more involved in portfolio construction: Similar to your case: You have a company savings plan that you're taking advantage of because of a matching contribution. Chances are your company plan doesn't offer a wide variety of funds. Since a life cycle fund is available, it can be a good choice for that account. But make sure fees aren't out of hand. If much lower-cost equity and bond funds are available, consider them instead. Let's say you had another smaller account that you were unable to consolidate into your main account. (e.g. a Traditional IRA vs. your Roth, and you didn't necessarily want to convert it.) Even if that account had access to a wide variety of funds, it still might not be worth the added hassle or trading costs of owning and rebalancing multiple funds inside the smaller account. There, perhaps, the life cycle fund can help you out, while you use your own strategy in your main account. Finally, let's assume you had a single main account and you buy partially into the idea of a life cycle fund and you find a great one with low fees. Except: you want a bit of something else in your portfolio not provided by the life cycle fund, e.g. some more emerging markets, international, or commodity stock exposure. (Is this one reason you're doing it yourself?) In that case, where the life cycle fund doesn't quite have everything you want, you could still use it for the bulk of the portfolio (e.g. 85-95%) and then select one or two specific additional ETFs to complement it. Just make sure you factor in those additional components into the overall equity weighting and adjust your life cycle fund choice accordingly (e.g. perhaps go more conservative in the life cycle, to compensate.) I hope that helps! Additional References:\"",
"title": ""
},
{
"docid": "60001",
"text": "Yes, from the point-of-view to the end speculator/investor in stocks, it is ludicrous to take on liabilities when you don't have to. That's why single-stock options are far more liquid than single-stock futures. However, if you are a farmer with a huge mortgage depending upon the chaos of agricultural markets which are extremely volatile, a different structure might appeal to you. You could long your inputs while shorting your outputs, locking in a profit. That profit is probably lower than what one could expect over the long run without hedging, but it will surely be less volatile. Here's where the advantage of futures come in for that kind of structure: the margin on the longs and shorts can offset each other, forcing the farmer to have to put up much less of one's own money to hedge. With options, this is not the case. Also, the gross margin between the inputs rarely fluctuate to an unmanageable degree, so if your shorts rise faster than your longs, you'll only have to post margin in the amount of the change in the net of the longs and shorts. This is why while options on commodities exist to satisfy speculators, futures are the most liquid.",
"title": ""
},
{
"docid": "20079",
"text": "The basic idea behind a derivative is very simple actually. It is a contract where the final value depends on (is derived from) the value of something else. Stock, for instance, is not a derivative because the contract itself is actually ownership of part of a company. Whereas car insurance is a derivative because the payout depends on the value of something else namely your (and other peoples') cars. The problem with such a simple definition is that it covers such a broad class. It covers simple contracts like Futures where the end value just depends on the price of something on a future date. But it extends to contracts complicated enough that people in finance call them Exotics. Derivatives are broadly used for two things reducing risk (sometimes called insurance) and speculation. A farmer can use derivatives to make sure she gets paid a certain amount for her corn. A banker can group a bunch of loans together and sell slices to reduce the pain of a particular loan failing. At the same time people can use the same instruments to speculate on the price of (for example) that corn or those loans and the main advantage is that they don't have to buy the corn or loans directly. Any farmer will tell you corn can be very expensive to store. Derivatives generally cause problems both individually and sometimes world wide when people don't properly understand the risks involved. The most famous example being Mortgage-backed Securities and the recent Great Recession. You can start understand the instruments and their risks by this wonderful Wikipedia article and later perhaps a used collection of CFA books which cover derivatives in great detail. Edit: Michael Grünewald mentioned Hull's text on derivatives a wonderful middle ground between Wikipedia and the CFA books that I can't believe I didn't think about myself.",
"title": ""
},
{
"docid": "115134",
"text": "How I understand it is: supply/demand affect price of stock negatively/positively, respectively. Correct. Volume is the amount of buying/selling activity in these stocks (more volume = more fluctuation, right?). Sort of. Higher volume means higher liquidity. That is, a stock that is traded more is easier to trade. It doesn't necessarily mean more fluctuation and in the real world, it often means that these are well-understood stocks with a high amount of analyst coverage. This tends towards these stocks not being as volatile as smaller stocks with less liquidity. Company revenue (and profit) will help an investor predict company growth. That is one factor in a stock price. There are certain stocks that you would buy without them making a profit because their future revenue looks potentially explosive. However, these stocks are very risky and are bubble-prone. If you're starting out in the share market, it's generally a good idea to invest in index funds (I am not a broker, my advice should not be taken as financial advice). These funds aggregate risk by holding a lot of different companies. Also, statistics have shown that over time, buying and holding index funds long term tends to dramatically outperform other investment strategies, particularly for people with low amounts of capital.",
"title": ""
},
{
"docid": "520216",
"text": "\"It's interesting that after reading this article you would make an assumption about where the stock market is headed. This article specifically says that the only way to know that is to know where interest rates are going, and for that we can guarantee no one knows. The takeaway is this: \"\"The key to investing is not assessing how much an industry is going to affect society, or how much it will grow, but rather determining the competitive advantage of any given company and, above all, the durability of that advantage. The products or services that have wide, sustainable moats around them are the ones that deliver rewards to investors.\"\" Intelligent investors should have no concern about what \"\"the market\"\" is doing. Analyze businesses, not the stock market.\"",
"title": ""
},
{
"docid": "344175",
"text": "The benefit of a dividend reinvestment program is you, generally, don't pay transaction costs or commissions and you don't have to remember to do it. Whether or not you may be able to eek out a little more by managing this yourself is a crapshoot and the equivalent of timing the market. If you're so good at timing the market you shouldn't even be holding the stock, you should be buying and selling as the price fluctuates.",
"title": ""
},
{
"docid": "91032",
"text": "Don't go for the 'fast buck'. There's no such thing. There are two types of people that make money on the stock market: Investors and Speculators. Investors are people that pick a stock that's relatively low, relatively secure, and buy the stock for the long run, 5, 10 years or more. Warren Buffet said his ideal period for investing is forever. Basically, a well run company should always be a good investment. Speculators go for the fluctuations in stock prices. Day traders, Options, etc. It's risky business and you'll be able to lose a lot of money in a short term. There's always a risk when you invest your money, so go with MrChrister's advise to start with a simulator. Have fun.",
"title": ""
},
{
"docid": "117082",
"text": "\"Someone who buys a stock is fundamentally buying a share of all future dividends, plus the future liquidation value of the company in the event that it is liquidated. While some investors may buy stocks in the hope that they will be able to find other people willing to pay more for the stock than they did, that's a zero sum game. The only way investors can make money in the aggregate is if either stocks pay dividends or if the money paid for company assets at liquidation exceeds total net price for which the company sold shares. One advantage of dividends from a market-rationality perspective is that dividend payments are easy to evaluate than company value. Ideally, the share price of a company should match the present per-share cash value of all future dividends and liquidation, but it's generally impossible to know in advance what that value will be. Stock prices may sometimes rise because of factors which increase the expected per-share cash value of future dividends and liquidations. In a sane market, rising prices on an item will reduce people's eagerness to buy and increase people's eagerness to sell. Unfortunately, in a marketplace where steady price appreciation is expected the feedback mechanisms responsible for stability get reversed. Rapidly rising prices act as a red flag to buyers--unfortunately, bulls don't see red flags as signal to stop, but rather as a signal to charge ahead. For a variety of reasons including the disparate treatment of dividends and capital gains, it's often not practical for a company to try to stabilize stock prices through dividends and stock sales. Nonetheless, dividends are in a sense far more \"\"real\"\" than stock price appreciation, since paying dividends generally requires that companies actually have sources of revenues and profits. By contrast, it's possible for stock prices to go through the roof for companies which have relatively few assets of value and no real expectation of becoming profitable businesses, simply because investors see rising stock prices as a \"\"buy\"\" signal independent of any real worth.\"",
"title": ""
},
{
"docid": "116675",
"text": "Dividend yield is a tough thing to track because it's a moving target. Dividends are paid periodically the yield is calculated based on the stock price when the dividend is declared (usually, though some services may update this more frequently). I like to calculate my own dividend by annualizing the dividend payment divided by my cost basis per share. As an example, say you have shares in X, Co. X issues a quarterly dividend of $1 per share and the share price is $100; coincidentally this is the price at which you purchased your shares. But a few years goes by and now X issues it's quarterly dividend of $1.50 per share, and the share price is $160. However your shares only cost you $100. Your annual yield on X is 6%, not the published 3.75%. All of this is to say that looking back on dividend yields is somewhat similar to nailing jello to the wall. Do you look at actual dividends paid through the year divided by share price? Do you look at the annualized dividend at the time of issue then average those? The stock price will fluctuate, that will change the yield; depending on where you bought your stock, your actual yield will vary from the published amount as well.",
"title": ""
},
{
"docid": "173052",
"text": "\"Probably the best way to investigate this is to look at an example. First, as the commenters above have already said, the log-return from one period is log(price at time t/price at time t-1) which is approximately equal to the percentage change in the price from time t-1 to time t, provided that this percentage change is not big compared to the size of the price. (Note that you have to use the natural log, ie. log to the base e -- ln button on a calculator -- here.) The main use of the log-return is that is a proxy for the percentage change in the price, which turns out to be mathematically convenient, for various reasons which have mostly already been mentioned in the comments. But you already know this; your actual question is about the average log-return over a period of time. What does this indicate about the stock? The answer is: if the stock price is not changing very much, then the average log-return is about equal to the average percentage change in the price, and is very easy and quick to calculate. But if the stock price is very volatile, then the average log-return can be wildly different to the average percentage change in the price. Here is an example: the closing prices for Pitchfork Oil from last week's trading are: 10, 5, 12, 5, 10, 2, 15. The percentage changes are: -0.5, 1.4, -0.58, 1, -0.8, 6.5 (where -0.5 means -50%, etc.) The average percentage change is 1.17, or 117%. On the other hand, the log-returns for the same period are -0.69, 0.88, -0.88, 0.69, -1.6, 2, and the average log-return is about 0.068. If we used this as a proxy for the average percentage change in the price over the whole seven days, we would get 6.8% instead of 117%, which is wildly wrong. The reason why it is wrong is because the price fluctuated so much. On the other hand, the closing prices for United Marshmallow over the same period are 10, 11, 12, 11, 12, 13, 15. The average percentage change from day to day is 0.073, and the average log-return is 0.068, so in this case the log-return is very close to the percentage change. And it has the advantage of being computable from just the first and last prices, because the properties of logarithms imply that it simplifies to (log(15)-log(10))/6. Notice that this is exactly the same as for Pitchfork Oil. So one reason why you might be interested in the average log-return is that it gives a very quick way to estimate the average return, if the stock price is not changing very much. Another, more subtle reason, is that it actually behaves better than the percentage return. When the price of Pitchfork jumps from 5 to 12 and then crashes back to 5 again, the percentage changes are +140% and -58%, for an average of +82%. That sounds good, but if you had bought it at 5, and then sold it at 5, you would actually have made 0% on your money. The log-returns for the same period do not have this disturbing property, because they do add up to 0%. What's the real difference in this example? Well, if you had bought $1 worth of Pitchfork on Tuesday, when it was 5, and sold it on Wednesday, when it was 12, you would have made a profit of $1.40. If you had then bought another $1 on Wednesday and sold it on Thursday, you would have made a loss of $0.58. Overall, your profit would have been $0.82. This is what the average percentage return is calculating. On the other hand, if you had been a long-term investor who had bought on Tuesday and hung on until Thursday, then quoting an \"\"average return\"\" of 82% is highly misleading, because it in no way corresponds to the return of 0% which you actually got! The moral is that it may be better to look at the log-returns if you are a buy-and-hold type of investor, because log-returns cancel out when prices fluctuate, whereas percentage changes in price do not. But the flip-side of this is that your average log-return over a period of time does not give you much information about what the prices have been doing, since it is just (log(final price) - log(initial price))/number of periods. Since it is so easy to calculate from the initial and final prices themselves, you commonly won't see it in the financial pages, as far as I know. Finally, to answer your question: \"\"Does knowing this single piece of information indicate something about the stock?\"\", I would say: not really. From the point of view of this one indicator, Pitchfork Oil and United Marshmallow look like identical investments, when they are clearly not. Knowing the average log-return is exactly the same as knowing the ratio between the final and initial prices.\"",
"title": ""
},
{
"docid": "484778",
"text": "\"There are a few reason why the stock price decreases after a dividend is paid: What's the point of paying a dividend if the stock price automatically decreases? Don't the shareholders just break even? Companies have to do something with their profits. They beholden to their shareholders to make them money either by increasing the share value or paying dividends. So they have the choice between reinvesting their profits into the company to grow the business or just handing the profits directly to the owners of the business (the shareholders). Some companies are as big as they want to be and investing their profits into more capital offers them diminishing returns. These companies are more likely to pay dividends to their shareholders. I assume the price of the stock \"\"naturally\"\" increases over the year to reflect the amount of the dividend payment. This is kind of a vague question but then doesn't it make it difficult to evaluate the fluctuations in stock price (in the way that you would a company that doesn't pay a dividend)? It depends on the company. The price may recover the dividend drop... could take a few days to a week. And that dependings on the company's performance and the overall market performance. With respect to options, I assume nothing special happens? So say I bought $9 call options yesterday that were in the money, all of a sudden they're just not? Is this typically priced into the option price? Is there anything else I need to know about buying options in companies that pay dividends? What if I had an in-the-money option, and all of a sudden out of nowhere a company decides to pay a dividend for the first time. Am I just screwed? One key is that dividends are announced in advance (typically at least, if not always; not sure if it's required by law but I wouldn't be surprised). This is one reason people will sometimes exercise a call option early, because they want to get the actual stock in order to earn the dividend. For \"\"out of the ordinary\"\" large cash dividends (over 10% is the guideline), stock splits, or other situations an option can be adjusted: http://www.888options.com/help/faq/splits.jsp#3 If you have an options account, they probably sent you a \"\"Characteristics and Risks of Standardized Options\"\" booklet. It has a section discussing this topic and the details of what kinds of situations trigger an adjustment. A regular pre-announced <10% dividend does not, while a special large dividend would, is what I roughly get from it. That \"\"Characteristics and Risks of Standardized Options\"\" is worth reading by the way; it's long and complicated, but well, options are complicated. Finally, do all companies reduce their stock price when they pay a dividend? Are they required to? I'm just shocked I've never heard of this before. The company doesn't directly control the stock price, but I do believe this is automatic. I think the market does this automatically because if they didn't, there would be enough people trying to do dividend capture arbitrage that it would ultimately drive down the price.\"",
"title": ""
}
] |
PLAIN-1237
|
gallbladder disease
|
[
{
"docid": "MED-2205",
"text": "AIM: To investigate the effects of proteins purified from sweet potato storage roots on human colorectal cancer cell lines. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst 33258 nuclear staining and Boyden transwell chamber methods were used to determine whether purified sweet potato protein (SPP) from fresh sweet potato roots affected proliferation, migration and invasion, respectively, of human colorectal cancer SW480 cells in vitro. The inhibitory effects of SPP on growth of human colorectal cancer HCT-8 cells intraperitoneally xenografted in nude mice and spontaneous lung metastasis of murine Lewis lung carcinoma 3LL cells subcutaneously transplanted in C57 BL/6 mice were also investigated in vivo. RESULTS: SPP inhibited the proliferation of SW480 cells in a dose-dependent manner, with an IC50 value of 38.732 μmol/L (r2 = 0.980, P = 0.003) in the MTT assay. Hoechst 33258 nuclear staining further revealed inhibition of cell viability and induction of apoptosis by SPP. The transwell assay disclosed significant reduction in migrated cells/field by 8 μmol/L SPP (8.4 ± 2.6 vs 23.3 ± 5.4, P = 0.031) and invaded cells/field through the ECMatrix by 0.8 μmol/L SPP, compared with the control (25.2 ± 5.2 vs 34.8 ± 6.1, P = 0.038). Both intraperitoneal (ip) and intragastric (ig) administration of SPP led to significant suppression of growth of intraperitoneally inoculated HCT-8 cells in nude mice to 58.0% ± 5.9% (P = 0.037) and 43.5% ± 7.1% (P = 0.004) of the controls, respectively, after 9 d treatment. Bloody ascites additionally disappeared after ip injection of trypsin inhibitor. Notably, ig and ip administration of SPP induced a significant decrease in spontaneous pulmonary metastatic nodule formation in C57 BL/6 mice (21.0 ± 12.3 and 27.3 ± 12.7 nodules/lung vs 42.5 ± 4.5 nodules/lung in controls, respectively, P < 0.05) after 25 d treatment. Moreover, the average weight of primary tumor nodules in the hind leg of mice decreased from 8.2 ± 1.3 g/mice in the control to 6.1 ± 1.4 g/mice in the ip group (P = 0.035). CONCLUSION: SPP exerts significant antiproliferative and antimetastatic effects on human colorectal cancer cell lines, both in vitro and in vivo.",
"title": "Anticancer effects of sweet potato protein on human colorectal cancer cells"
},
{
"docid": "MED-2781",
"text": "Our previous study demonstrated that curcumin, an active compound of Curcuma xanthorrhiza and C. domestica, produces a positive cholekinetic effect. A 20 mg amount of curcumin is capable of contracting the gall bladder by up to 29% within an observation time of 2 h. The aim of the current study was to define the dosage of curcumin capable of producing a 50% contraction of the gall bladder, and to determine if there is a linear relationship between doubling the curcumin dosage and the doubling of gall bladder contraction. A randomised, single-blind, three-phase, crossover-designed examination was carried out on 12 healthy volunteers. Ultrasonography was carried out serially to measure the gall bladder volume. The data obtained was analysed by analysis of variance (ANOVA). The fasting volumes of gall bladders were similar (P > 0.50), with 17.28 +/- 5.47 mL for 20 mg curcumin, 18.34 +/- 3.75 mL for 40 mg and 18.24 +/- 3.72 mL for 80 mg. The percentage decrease in gall bladder volume 2 h after administration of 20, 40 and 80 mg was 34.10 +/- 10.16, 51.15 +/- 8.08 and 72.25 +/- 8.22, respectively, which was significantly different (P < 0.01). On the basis of the present findings, it appears that the dosage of cucumin capable of producing a 50% contraction of the bladder was 40 mg. This study did not show any linear relationship between doubling curcumin dosage and the doubling of gall bladder contraction.",
"title": "Effect of different curcumin dosages on human gall bladder."
},
{
"docid": "MED-2788",
"text": "Turmeric root has been used medicinally in China and India for thousands of years. The active components are thought to be the curcuminoids, primarily curcumin, which is commonly available worldwide as a standardized extract. This article reviews the pharmacology of curcuminoids, their use and efficacy, potential adverse effects, and dosage and standardization. Preclinical studies point to mechanisms of action that are predominantly anti-inflammatory and antineoplastic, while early human clinical trials suggest beneficial effects for dyspepsia, peptic ulcer, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, uveitis, orbital pseudotumor, and pancreatic cancer. Curcumin is well-tolerated; the most common side effects are nausea and diarrhea. Theoretical interactions exist due to purported effects on metabolic enzymes and transport proteins, but clinical reports do not support any meaningful interactions. Nonetheless, caution, especially with chemotherapy agents, is advised. Late-phase clinical trials are still needed to confirm most beneficial effects.",
"title": "Clinical utility of curcumin extract."
},
{
"docid": "MED-2210",
"text": "We investigated the effects of sporamin, the major soluble protein with a kunitz-type trypsin inhibitory activity in the root tuber of the sweet potato, on cell proliferation, apoptosis, Akt/GSK-3 signaling and its related genes to provide more insights in the mechanism behind the inhibitory effects of sporamin in a human tongue cancer line Tca8113. In this study, sporamin inhibited cell proliferation and induced apoptosis in Tca8113 cells in a concentration-dependent and time-dependent manner. Consistently, Bax was up-regulated and Bcl-2 was down-regulated in sporamin-treated cells. Furthermore, Akt/GSK-3 signaling was down-regulated in sporamin-treated cells. Consistently, the phosphorylated Bad was significantly declined in sporamin-treated Tca8113 cells. These results suggest the antiproliferative effects of sporamin in Tca8113 cells might result partly from induction of apoptosis by down-regulating Akt/GSK-3 pathway. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.",
"title": "Sporamin induce apoptosis in human tongue carcinoma cells by down-regulating Akt/GSK-3 signaling."
},
{
"docid": "MED-2206",
"text": "Sweet potato is one of the crops selected for NASA's Advanced Life Support Program for potential long-duration lunar/Mars missions. This article presents recipes of products made from sweet potato and determines the consumer acceptability of products containing from 6% to 20% sweet potato on a dry weight basis. These products were developed for use in nutritious and palatable meals for future space explorers. Sensory evaluation (appearance/color, aroma, texture, flavor/taste, and overall acceptability) studies were conducted to determine the consumer acceptability of vegetarian products made with sweet potato using panelists at NASA/Johnson Space Center in Houston, TX. None of these products including the controls, contained any ingredient of animal origin with the exception of sweet potato pie. A 9-point hedonic scale (9 being like extremely and 1 being dislike extremely) was used to evaluate 10 products and compare them to similar commercially available products used as controls. The products tested were pancakes, waffles, tortillas, bread, pie, pound cake, pasta, vegetable patties, doughnuts, and pretzels. All of the products were either liked moderately or liked slightly with the exception of the sweet potato vegetable patties, which were neither liked nor disliked. Mean comparisons of sensory scores of sweet potato recipes and their controls were accomplished by using the Student t-test. Because of their nutritional adequacy and consumer acceptability, these products are being recommended to NASA's Advanced Life Support Program for inclusion in a vegetarian menu plan designed for lunar/Mars space missions.",
"title": "Consumer acceptance of vegetarian sweet potato products intended for space missions."
},
{
"docid": "MED-2787",
"text": "BACKGROUND: The extract of medicinal plants containing curcumin is traditionally believed to have a positive contraction effect on the human gall-bladder. AIMS: To compare the effect of 20 mg curcumin or placebo on the gall-bladder volume of healthy volunteers. METHODS: A randomized, double blind and crossover design study was carried out in 12 healthy volunteers (seven males and five females). Ultrasonography examination was carried out serially to measure the gall-bladder volume. The data obtained was analysed by paired Student's t-test. RESULTS: The fasting gall-bladder volumes of 15.74 +/- 4.29 mL on curcumin and 15.98 +/- 4.08 mL on placebo were similar (P > 0.20). The gall-bladder volume was reduced within the period after curcumin administration. The percentage of gall-bladder volume reduction at 0.5, 1.0, 1.5 and 2.0 h after 20 mg curcumin administration were 11.8 +/- 6.9, 16.8 +/- 7.4, 22.0 +/- 8.5 and 29. 3 +/- 8.3%, respectively, which was statistically significant compared to placebo. CONCLUSION: On the basis of the present findings, it appears that curcumin induces contraction of the human gall-bladder.",
"title": "The effect of curcumin and placebo on human gall-bladder function: an ultrasound study."
},
{
"docid": "MED-2777",
"text": "BACKGROUND: Gout, an inflammatory arthritis, reportedly afflicts more than 2 million men and women in the United States. Previous reports have suggested an association between gout and kidney stone disease; however, these studies did not adjust for such important potential confounders as obesity and the presence of hypertension. To our knowledge, no published study has examined the independent association between gout and kidney stone disease. METHODS: We used a national probability sample of the US population to determine the independent association between reported gout and history of kidney stone disease. RESULTS: Among men and women 20 years and older, 5.6% (10 million) reported the previous passage of a kidney stone and 2.7% (5.1 million) reported a diagnosis of gout by a physician. Moreover, 8.6% of individuals who reported the passage of a kidney stone on two or more occasions had a history of gout. Conversely, the prevalence of previous kidney stones in subjects with reported gout was 13.9%. In the age-adjusted model, gout was associated with an increased odds ratio (OR) for previous kidney stones (OR, 1.97; 95% confidence interval [CI], 1.37 to 2.83). After further adjustment for sex, race, body mass index, and presence of hypertension, the OR for previous kidney stones in individuals with gout decreased to 1.49 (95% CI, 1.04 to 2.14). CONCLUSION: Showing an independent association between kidney stone disease and gout strongly suggests that they share common underlying pathophysiological mechanisms. Identification of these mechanisms may lead to improved preventive strategies for both conditions. Copyright 2002 by the National Kidney Foundation, Inc.",
"title": "The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988-1994."
},
{
"docid": "MED-2201",
"text": "Measuring food prices per gram, rather than per calorie, is one way to make healthful vegetables appear less expensive. However, a better measure of affordability would take the nutrient content of vegetables into account. This study, based on analyses of US Department of Agriculture datasets, aimed to identify which vegetables, including juices and soups, provided the most nutrients per unit cost. Nutrient density was measured using the Nutrient Rich Foods (NRF) index, based on nine nutrients to encourage: protein; fiber; vitamins A, C, and E; calcium; iron; magnesium; and potassium; and on three nutrients to limit: saturated fat, added sugar, and sodium. Food cost in dollars was calculated per 100 g, per 100 kcal, per serving, and per nutrient content. One-way analyses of variance with post hoc tests were used to determine statistical significance. Results showed that tomato juices and tomato soups, dark green leafy and nonleafy vegetables, and deep yellow vegetables, including sweet potatoes, had the highest NRF scores overall. Highest NRF scores per dollar were obtained for sweet potatoes, white potatoes, tomato juices and tomato soups, carrots, and broccoli. Tomato sauces, raw tomatoes, and potato chips were eaten more frequently than were many other vegetables that were both more affordable and more nutrient-rich. These new measures of affordable nutrition can help foodservice and health professionals identify those vegetables that provide the highest nutrient density per unit cost. Processed vegetables, including soups and juices, can contribute to the quality and the affordability of the diet. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.",
"title": "New metrics of affordable nutrition: which vegetables provide most nutrients for least cost?"
},
{
"docid": "MED-2810",
"text": "Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be \"Curecumin\".",
"title": "Curcumin as \"Curecumin\": from kitchen to clinic."
},
{
"docid": "MED-2204",
"text": "The initial investigation of the nature of the proteins in the tuber of sweet potato (Ipomoea batatas Lam.) revealed a globulin-designated \"ipomoein,\" which was reported by Jones and Gersdorff, (1931). Later, \"ipomoein\" was renamed \"sporamin\" and was found to be a major storage protein that accounted for over 80% of the total protein in the tuberous root. To date, sporamin has been studied by a series of biochemical and molecular approaches. The first purification of sporamin into two major fractions, A and B, was successfully completed in 1985. Several characteristics of the protein, such as the diversification of the nucleotide sequences in the gene family, the protein structure, the biological functions of storage, defense, inhibitory activity and ROS scavenging, were identified. In the past decade, sporamin was classified as a Kunitz-type trypsin inhibitor, and its insect-resistance capability has been examined in transgenic tobacco and cauliflower plants, indicating the multiple functions of this protein has evolved to facilitate the growth and development of sweet potato. Sporamin is constitutively expressed in the tuberous root and is not normally expressed in the stem or leaves. However, this protein is expressed systemically in response to wounding and other abiotic stresses. These dual expression patterns at the transcriptional level revealed that the complex regulatory mechanism of sporamin was modulated by environmental stresses. The versatile functions of sporamin make this storage protein a good research model to study molecular evolution, regulatory mechanisms and physiological functions in plants. This review summarizes and discusses recent approaches and future perspectives in agricultural biotechnology. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Multiple biological functions of sporamin related to stress tolerance in sweet potato (Ipomoea batatas Lam)."
},
{
"docid": "MED-2818",
"text": "Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. Apart from curcumin's potent antioxidant capacity at neutral and acidic pH, its mechanisms of action include inhibition of several cell signalling pathways at multiple levels, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno-modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. Although curcumin's low systemic bioavailability following oral dosing may limit access of sufficient concentrations for pharmacological effect in certain tissues, the attainment of biologically active levels in the gastrointestinal tract has been demonstrated in animals and humans. Sufficient data currently exist to advocate phase II clinical evaluation of oral curcumin in patients with invasive malignancy or pre-invasive lesions of the gastrointestinal tract, particularly the colon and rectum.",
"title": "Curcumin: the story so far."
},
{
"docid": "MED-2208",
"text": "BACKGROUND: Bikunin, a Kunitz-type protease inhibitor, specifically inhibits tumor invasion and metastasis. METHODS: The authors initially evaluated the therapeutic efficacy of once-daily oral administration of different doses of bikunin against human ovarian carcinoma HRA cells growing in the peritonea of nude mice. For the in vivo studies, female 7-week-old nude mice were randomized to 1 of 4 groups: bikunin-treated groups (n = 9 in each group) received 3, 10, or 30 microg/g body weight per day bikunin for 7 days via gastrointestinal gavage, and a control group (n = 9) received the vehicle solution (phosphate-buffered saline) via gastrointestinal gavage. On Day 9, the abdominal cavity was examined by two observers who were blinded to treatment. RESULTS: After oral administration, intact bikunin was detectable in mouse serum specimens at 3 and 6 hours. This was followed by a decline at 12 hours. The mice given bikunin at the highest dose level had a 40% decrease in tumor load. The highest uptake in the tumor was obtained with [125I]bikunin 12 hours postadministration. No effect on either food intake or body weight was observed in the treated versus sham groups. The current study was the first to report the potent activity of once-daily oral administration of bikunin against ovarian carcinoma. Next, the authors performed a Phase I trial to determine the maximum-tolerated dose (MTD) and safety of a once-daily oral administration schedule. The indication was locally advanced uterine cervical carcinoma after definitive treatment. An escalating dose (3, 10, and 30 mg/kg per day) of bikunin was administered orally to nine patients for 7 days. There were no dose-limiting toxicities and the MTD of the bikunin schedule was not defined. The authors also obtained preliminary data on its effect on urokinase-type plasminogen activator expression at the highest dose level. CONCLUSIONS: Once-daily oral administration of bikunin was found to be safe in humans and exhibited signs of biologic activity. Copyright 2004 American Cancer Society.",
"title": "Therapeutic efficacy of once-daily oral administration of a Kunitz-type protease inhibitor, bikunin, in a mouse model and in human cancer."
},
{
"docid": "MED-2780",
"text": "Spices, such as cinnamon, cloves, cardamom, garlic, ginger, cumin, coriander and turmeric are used all over the world as flavouring and colouring ingredients in Indian foods. Previous studies have shown that spices contain variable amounts of total oxalates but there are few reports of soluble oxalate contents. In this study, the total, soluble and insoluble oxalate contents of ten different spices commonly used in Indian cuisine were measured. Total oxalate content ranged from 194 (nutmeg) to 4,014 (green cardamom) mg/100 g DM, while the soluble oxalate contents ranged from 41 (nutmeg) to 3,977 (green cardamom) mg/100 g DM. Overall, the percentage of soluble oxalate content of the spices ranged from 4.7 to 99.1% of the total oxalate content which suggests that some spices present no risk to people liable to kidney stone formation, while other spices can supply significant amounts of soluble oxalates and therefore should be used in moderation.",
"title": "Total and soluble oxalate content of some Indian spices."
},
{
"docid": "MED-2816",
"text": "Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.",
"title": "Plant-derived health: the effects of turmeric and curcuminoids."
},
{
"docid": "MED-2815",
"text": "Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin, a component of turmeric: from farm to pharmacy."
},
{
"docid": "MED-2202",
"text": "The overall objective of this chapter is to review the past, present, and future role of the sweet potato (Ipomoea batatas [L.] Lam) in human nutrition. Specifically, the chapter describes the role of the sweet potato in human diets; outlines the biochemical and nutritional composition of the sweet potato with emphasis on its beta-carotene and anthocyanin contents; highlights sweet potato utilization, and its potential as value-added products in human food systems; and demonstrates the potential of the sweet potato in the African context. Early records have indicated that the sweet potato is a staple food source for many indigenous populations in Central and South Americas, Ryukyu Island, Africa, the Caribbean, the Maori people, Hawaiians, and Papua New Guineans. Protein contents of sweet potato leaves and roots range from 4.0% to 27.0% and 1.0% to 9.0%, respectively. The sweet potato could be considered as an excellent novel source of natural health-promoting compounds, such as beta-carotene and anthocyanins, for the functional food market. Also, the high concentration of anthocyanin and beta-carotene in sweet potato, combined with the high stability of the color extract make it a promising and healthier alternative to synthetic coloring agents in food systems. Starch and flour processing from sweet potato can create new economic and employment activities for farmers and rural households, and can add nutritional value to food systems. Repositioning sweet potato production and its potential for value-added products will contribute substantially to utilizing its benefits and many uses in human food systems. Multidisciplinary, integrated research and development activities aimed at improving production, storage, postharvest and processing technologies, and quality of the sweet potato and its potential value-added products are critical issues, which should be addressed globally.",
"title": "Sweet potato: a review of its past, present, and future role in human nutrition."
},
{
"docid": "MED-2209",
"text": "This study investigated the effect of different traditional cooking methods on glycemic index (GI) and glycemic response of ten Sweet potato (Ipomoea batatas) cultivars commonly eaten in Jamaica. Matured tubers were cooked by roasting, baking, frying, or boiling then immediately consumed by the ten nondiabetic test subjects (5 males and 5 females; mean age of 27 ± 2 years). The GI varied between 41 ± 5–93 ± 5 for the tubers studied. Samples prepared by boiling had the lowest GI (41 ± 5–50 ± 3), while those processed by baking (82 ± 3–94 ± 3) and roasting (79 ± 4–93 ± 2) had the highest GI values. The study indicates that the glycemic index of Jamaican sweet potatoes varies significantly with the method of preparation and to a lesser extent on intravarietal differences. Consumption of boiled sweet potatoes could minimize postprandial blood glucose spikes and therefore, may prove to be more efficacious in the management of type 2 diabetes mellitus.",
"title": "Relationship between Processing Method and the Glycemic Indices of Ten Sweet Potato (Ipomoea batatas) Cultivars Commonly Consumed in Jamaica"
},
{
"docid": "MED-2782",
"text": "BACKGROUND & AIMS: Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). METHODS: Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. RESULTS: Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed. CONCLUSIONS: Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.",
"title": "Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial."
},
{
"docid": "MED-2200",
"text": "Cancer of the gallbladder is rare but fatal, and has an unusual geographic and demographic distribution. Gallstones and obesity have been suggested as possible risk factors. As diet is known to influence both these factors, we carried out the present study to evaluate the possible role of diet in gallbladder carcinogenesis. A case-control study involving 64 newly diagnosed cases of gallbladder cancer and 101 cases of gallstones was carried out. The dietary evaluation was carried out by the dietary recall method based on a preset questionnaire developed specifically for the present study, keeping in mind the common dietary habits prevailing in this part of the world. Odds ratios (OR) and 95% confidence interval (CI) were calculated for various dietary items. A significant reduction in odds ratio was seen with the consumption of radish (OR 0.4; 95% CI 0.17-0.94), green chilli (OR 0.45; 95% CI 0.21-0.94) and sweet potato (OR 0.33; 95% CI 0.13-0.83) among vegetables, and mango (OR 0.4; 95% CI 0.16-0.99), orange (OR; 0.45; 95% CI 0.22-0.93), melon (OR 0.3; 95% CI 0.14-0.64) and papaya (OR 0.44; 95% 0.2-0.64) among fruits. A reduction in odds was also seen with the consumption of cruciferous vegetables, beans, onion and turnip, however the difference was not statistically significant. On the other hand, an increase in the odds was observed with consumption of capsicum (OR 2.2), beef (OR 2.58), tea (OR 1.98), red chilli (OR 1.29) and mutton (OR 1.2), however the difference was statistically not significant. In conclusion, the results of the present study show a protective effect of vegetables and fruits on gallbladder carcinogenesis, but red meat (beef and mutton) was found to be associated with increased risk of gallbladder cancer.",
"title": "Diet and gallbladder cancer: a case-control study."
},
{
"docid": "MED-2783",
"text": "Although much has been published about curcumin, which is obtained from turmeric, comparatively little is known about turmeric itself. Turmeric, a golden spice obtained from the rhizome of the plant Curcuma longa, has been used to give color and taste to food preparations since ancient times. Traditionally, this spice has been used in Ayurveda and folk medicine for the treatment of such ailments as gynecological problems, gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of turmeric against such disorders. Various chemical constituents have been isolated from this spice, including polyphenols, sesquiterpenes, diterpenes, triterpenoids, sterols, and alkaloids. Curcumin, which constitutes 2-5% of turmeric, is perhaps the most-studied component. Although some of the activities of turmeric can be mimicked by curcumin, other activities are curcumin-independent. Cell-based studies have demonstrated the potential of turmeric as an antimicrobial, insecticidal, larvicidal, antimutagenic, radioprotector, and anticancer agent. Numerous animal studies have shown the potential of this spice against proinflammatory diseases, cancer, neurodegenerative diseases, depression, diabetes, obesity, and atherosclerosis. At the molecular level, this spice has been shown to modulate numerous cell-signaling pathways. In clinical trials, turmeric has shown efficacy against numerous human ailments including lupus nephritis, cancer, diabetes, irritable bowel syndrome, acne, and fibrosis. Thus, a spice originally common in the kitchen is now exhibiting activities in the clinic. In this review, we discuss the chemical constituents of turmeric, its biological activities, its molecular targets, and its potential in the clinic. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Multitargeting by turmeric, the golden spice: From kitchen to clinic."
},
{
"docid": "MED-2207",
"text": "The objective of this study was to investigate the antiproliferative effect and the mechanism of trypsin inhibitor (TI) from sweet potato [Ipomoea batatas (L.) Lam. 'Tainong 57'] storage roots on NB4 promyelocytic leukemia cells. The results showed that TI inhibited cellular growth of NB4 promyelocytic leukemia cells in a time-dependent and dose-dependent manner, and treatment for 72 h induced a marked inhibition of cellular growth, showing an IC50 of 57.1 +/- 8.26 microg/mL. TI caused cell cycle arrest at the G1 phase as determined by flow cytometric analysis and apoptosis as shown by DNA laddering. TI-induced cell apoptosis involved p53, Bcl-2, Bax, and cytochrome c protein in NB4 cells. P53 and Bax proteins were accumulated, and antiapoptotic molecule Bcl-2 was decreased in the tested cells in a time-dependent manner during TI treatment. TI also induced a substantial release of cytochrome c from the mitochondria into the cytosol. Hence, TI induced apoptosis in NB4 cells through a mitochondria-dependent pathway, which was associated with the activation of caspase-3 and -8. These results demonstrated that TI induces NB4 cell apoptosis through the inhibition of cell growth and the activation of the pathway of caspase-3 and -8 cascades.",
"title": "Growth inhibition and induction of apoptosis in NB4 promyelocytic leukemia cells by trypsin inhibitor from sweet potato storage roots."
},
{
"docid": "MED-2785",
"text": "Curcumin is extensively used as a spice and pigment and has anticarcinogenic effects that could be linked to its antioxidant properties. However, some studies suggest that this natural compound possesses both pro- and antioxidative effects. In this study, we found that curcumin induced DNA damage to both the mitochondrial and nuclear genomes in human hepatoma G2 cells. Using quantitative polymerase chain reaction and immunocytochemistry staining of 8-hydroxydeoxyguanosine, we demonstrated that curcumin induced dose-dependent damage in both the mitochondrial and nuclear genomes and that the mitochondrial damage was more extensive. Nuclear DNA fragments were also evident in comet assays. The mechanism underlies the elevated level of reactive oxygen species and lipid peroxidation generated by curcumin. The lack of DNA damage at low doses suggested that low levels of curcumin does not induce DNA damage and may play an antioxidant role in carcinogenesis. But at high doses, we found that curcumin imposed oxidative stress and damaged DNA. These data reinforce the hypothesis that curcumin plays a conflicting dual role in carcinogenesis. Also, the extensive mitochondrial DNA damage might be an initial event triggering curcumin-induced cell death.",
"title": "Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 cells."
},
{
"docid": "MED-2786",
"text": "Alzheimer's disease (AD) is the most common form of dementia. There is limited choice in modern therapeutics, and drugs available have limited success with multiple side effects in addition to high cost. Hence, newer and alternate treatment options are being explored for effective and safer therapeutic targets to address AD. Turmeric possesses multiple medicinal uses including treatment for AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric. It is generally believed that curcumin is the most important constituent of the curcuminoid mixture that contributes to the pharmacological profile of parent curcuminoid mixture or turmeric. A careful literature study reveals that the other two constituents of the curcuminoid mixture also contribute significantly to the effectiveness of curcuminoids in AD. Therefore, it is emphasized in this review that each component of the curcuminoid mixture plays a distinct role in making curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents turmeric in its medicinal value better than curcumin alone. The progress in understanding the disease etiology demands a multiple-site-targeted therapy, and the curcuminoid mixture of all components, each with different merits, makes this mixture more promising in combating the challenging disease. Copyright © 2013 John Wiley & Sons, Ltd.",
"title": "Therapeutic potential of turmeric in Alzheimer's disease: curcumin or curcuminoids?"
},
{
"docid": "MED-2203",
"text": "Constipation is a common health problem that adversely affects quality of life and the prognosis of hospitalized patients with acute coronary syndromes (ACS). The purpose of this study was to develop and test the sweet potato/footbath/acupressure massage (SFA) intervention as a safe treatment for prevention of constipation and to increase satisfaction with bowel emptying in hospitalized patients with ACS. The study was a prospective, randomized controlled trial with a sample of 93 patients (SFA group, n = 44; usual care group, n = 49). Patients in the SFA group received SFA intervention combined with usual care. The results showed that there were statistical differences between the two groups in terms of (1) the incidence of constipation; (2) the use of laxatives and enemas; (3) patients' subjective satisfaction with their bowel emptying during hospitalization; and (4) sensation of incomplete evacuation and anorectal obstruction/blockade. The SFA intervention was more effective, economical, and practical than usual care alone in managing constipation and satisfaction with defecation in patients hospitalized with ACS.",
"title": "The effect of a sweet potato, footbath, and acupressure intervention in preventing constipation in hospitalized patients with acute coronary syndro..."
}
] |
[
{
"docid": "MED-4838",
"text": "With a prevalence of 10-15% in adults in Europe and the USA, gallstones are the most common digestive disease needing admission to hospital in the West. The interplay between interprandial and postprandial physiological responses to endogenous and dietary lipids underscores the importance of coordinated hepatobiliary and gastrointestinal functions to prevent crystallisation and precipitation of excess biliary cholesterol. Indeed, identifying the metabolic and transcriptional pathways that drive the regulation of biliary lipid secretion has been a major achievement in the field. We highlight scientific advances in protein and gene regulation of cholesterol absorption, synthesis, and catabolism, and biliary lipid secretion with respect to the pathogenesis of cholesterol gallstone disease. We discuss the physical-chemical mechanisms of gallstone formation in bile and the active role of the gallbladder and the intestine. We also discuss gaps in our knowledge of the pathogenesis of gallstone formation and the potential for gene targeting in therapy.",
"title": "Cholesterol gallstone disease."
},
{
"docid": "MED-4640",
"text": "BACKGROUND: The gut and immune system form a complex integrated structure that has evolved to provide effective digestion and defence against ingested toxins and pathogenic bacteria. However, great variation exists in what is considered normal healthy gut and immune function. Thus, whilst it is possible to measure many aspects of digestion and immunity, it is more difficult to interpret the benefits to individuals of variation within what is considered to be a normal range. Nevertheless, it is important to set standards for optimal function for use both by the consumer, industry and those concerned with the public health. The digestive tract is most frequently the object of functional and health claims and a large market already exists for gut-functional foods worldwide. AIM: To define normal function of the gut and immune system and describe available methods of measuring it. RESULTS: We have defined normal bowel habit and transit time, identified their role as risk factors for disease and how they may be measured. Similarly, we have tried to define what is a healthy gut flora in terms of the dominant genera and their metabolism and listed the many, varied and novel methods for determining these parameters. It has proved less easy to provide boundaries for what constitutes optimal or improved gastric emptying, gut motility, nutrient and water absorption and the function of organs such as the liver, gallbladder and pancreas. The many tests of these functions are described. We have discussed gastrointestinal well being. Sensations arising from the gut can be both pleasant and unpleasant. However, the characteristics of well being are ill defined and merge imperceptibly from acceptable to unacceptable, a state that is subjective. Nevertheless, we feel this is an important area for future work and method development. The immune system is even more difficult to make quantitative judgements about. When it is defective, then clinical problems ensure, but this is an uncommon state. The innate and adaptive immune systems work synergistically together and comprise many cellular and humoral factors. The adaptive system is extremely sophisticated and between the two arms of immunity there is great redundancy, which provides robust defences. New aspects of immune function are discovered regularly. It is not clear whether immune function can be \"improved\". Measuring aspects of immune function is possible but there is no one test that will define either the status or functional capacity of the immune system. Human studies are often limited by the ability to sample only blood or secretions such as saliva but it should be remembered that only 2% of lymphocytes circulate at any given time, which limits interpretation of data. We recommend assessing the functional capacity of the immune system by: measuring specific cell functions ex vivo. measuring in vivo responses to challenge, e. g. change in antibody in blood or response to antigens. determining the incidence and severity of infection in target populations during naturally occurring episodes or in response to attenuated pathogens.",
"title": "PASSCLAIM--gut health and immunity."
},
{
"docid": "MED-1717",
"text": "BACKGROUND: Excess bodyweight, expressed as increased body-mass index (BMI), is associated with the risk of some common adult cancers. We did a systematic review and meta-analysis to assess the strength of associations between BMI and different sites of cancer and to investigate differences in these associations between sex and ethnic groups. METHODS: We did electronic searches on Medline and Embase (1966 to November 2007), and searched reports to identify prospective studies of incident cases of 20 cancer types. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 5 kg/m2 increase in BMI. FINDINGS: We analysed 221 datasets (141 articles), including 282,137 incident cases. In men, a 5 kg/m2 increase in BMI was strongly associated with oesophageal adenocarcinoma (RR 1.52, p<0.0001) and with thyroid (1.33, p=0.02), colon (1.24, p<0.0001), and renal (1.24, p <0.0001) cancers. In women, we recorded strong associations between a 5 kg/m2 increase in BMI and endometrial (1.59, p<0.0001), gallbladder (1.59, p=0.04), oesophageal adenocarcinoma (1.51, p<0.0001), and renal (1.34, p<0.0001) cancers. We noted weaker positive associations (RR <1.20) between increased BMI and rectal cancer and malignant melanoma in men; postmenopausal breast, pancreatic, thyroid, and colon cancers in women; and leukaemia, multiple myeloma, and non-Hodgkin lymphoma in both sexes. Associations were stronger in men than in women for colon (p<0.0001) cancer. Associations were generally similar in studies from North America, Europe and Australia, and the Asia-Pacific region, but we recorded stronger associations in Asia-Pacific populations between increased BMI and premenopausal (p=0.009) and postmenopausal (p=0.06) breast cancers. INTERPRETATION: Increased BMI is associated with increased risk of common and less common malignancies. For some cancer types, associations differ between sexes and populations of different ethnic origins. These epidemiological observations should inform the exploration of biological mechanisms that link obesity with cancer.",
"title": "Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies."
},
{
"docid": "MED-2162",
"text": "BACKGROUND: The influence of excess body weight on the risk of death from cancer has not been fully characterized. METHODS: In a prospectively studied population of more than 900,000 U.S. adults (404,576 men and 495,477 women) who were free of cancer at enrollment in 1982, there were 57,145 deaths from cancer during 16 years of follow-up. We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites, while controlling for other risk factors in multivariate proportional-hazards models. We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population. RESULTS: The heaviest members of this cohort (those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of at least 40) had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. For men, the relative risk of death was 1.52 (95 percent confidence interval, 1.13 to 2.05); for women, the relative risk was 1.62 (95 percent confidence interval, 1.40 to 1.87). In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin's lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. On the basis of associations observed in this study, we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women. CONCLUSIONS: Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites. Copyright 2003 Massachusetts Medical Society",
"title": "Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults."
},
{
"docid": "MED-983",
"text": "BACKGROUND: Our goal was to forecast the global burden of Alzheimer's disease and evaluate the potential impact of interventions that delay disease onset or progression. METHODS: A stochastic, multistate model was used in conjunction with United Nations worldwide population forecasts and data from epidemiological studies of the risks of Alzheimer's disease. RESULTS: In 2006, the worldwide prevalence of Alzheimer's disease was 26.6 million. By 2050, the prevalence will quadruple, by which time 1 in 85 persons worldwide will be living with the disease. We estimate about 43% of prevalent cases need a high level of care, equivalent to that of a nursing home. If interventions could delay both disease onset and progression by a modest 1 year, there would be nearly 9.2 million fewer cases of the disease in 2050, with nearly the entire decline attributable to decreases in persons needing a high level of care. CONCLUSIONS: We face a looming global epidemic of Alzheimer's disease as the world's population ages. Modest advances in therapeutic and preventive strategies that lead to even small delays in the onset and progression of Alzheimer's disease can significantly reduce the global burden of this disease.",
"title": "Forecasting the global burden of Alzheimer's disease."
},
{
"docid": "MED-4431",
"text": "BACKGROUND: Workers in poultry plants have high exposure to a variety of transmissible agents present in poultry and their products. Subjects in the general population are also exposed. It is not known whether many of these agents cause disease in humans. If they do, we reason this would be readily evident in a highly exposed group such as poultry workers. We report here on mortality from non-malignant diseases in a cohort of poultry workers. METHODS: Mortality was compared with that of the US general population, and with that of a comparison group from the same union. Risk was estimated by standardized mortality ratio, proportional mortality ratio, and directly standardized risk ratio. RESULTS: Poultry workers as a group had an overall excess of deaths from diabetes, anterior horn disease, and hypertensive disease, and a deficit of deaths from intracerebral hemorrhage. Deaths from zoonotic bacterial diseases, helminthiasis, myasthenia gravis, schizophrenia, other diseases of the spinal cord, diseases of the esophagus and peritonitis were non-significantly elevated overall by all analyses, and significantly so in particular race/sex subgroups. CONCLUSIONS: Poultry workers may have excess occurrence of disease affecting several organs and systems, probably originating from widespread infection with a variety of microorganisms. The results for neurologic diseases could well represent important clues to the etiology of these diseases in humans. The small numbers of deaths involved in some cases limit interpretation.",
"title": "Mortality in the Baltimore union poultry cohort: non-malignant diseases."
},
{
"docid": "MED-5030",
"text": "Study Objectives: To examine sex-specific associations between sleep duration and mortality from cardiovascular disease and other causes. Design: Cohort study. Setting: Community-based study. Participants: A total of 98,634 subjects (41,489 men and 57,145 women) aged 40 to 79 years from 1988 to 1990 and were followed until 2003. Interventions: N/A. Measurements and Results: During a median follow-up of 14.3 years, there were 1964 deaths (men and women: 1038 and 926) from stroke, 881 (508 and 373) from coronary heart disease, 4287 (2297 and 1990) from cardiovascular disease, 5465 (3432 and 2033) from cancer, and 14,540 (8548 and 5992) from all causes. Compared with a sleep duration of 7 hours, sleep duration of 4 hours or less was associated with increased mortality from coronary heart disease for women and noncardiovascular disease/noncancer and all causes in both sexes. The respective multivariable hazard ratios were 2.32 (1.19–4.50) for coronary heart disease in women, 1.49 (1.02–2.18) and 1.47 (1.01–2.15) for noncardiovascular disease/noncancer, and 1.29 (1.02–1.64) and 1.28 (1.03–1.60) for all causes in men and women, respectively. Long sleep duration of 10 hours or longer was associated with 1.5- to 2-fold increased mortality from total and ischemic stroke, total cardiovascular disease, noncardiovascular disease/noncancer, and all causes for men and women, compared with 7 hours of sleep in both sexes. There was no association between sleep duration and cancer mortality in either sex. Conclusions: Both short and long sleep duration were associated with increased mortality from cardiovascular disease, noncardiovascular disease/noncancer, and all causes for both sexes, yielding a U-shaped relationship with total mortality with a nadir at 7 hours of sleep. Citation: Ikehara S; Iso H; Date C; Kikuchi S; Watanabe Y; Wada Y; Inaba Y; Tamakoshi A. Association of sleep duration with mortality from cardiovascular disease and other causes for Japanese men and women: the JACC study. SLEEP 2009;32(3):259–301.",
"title": "Association of Sleep Duration with Mortality from Cardiovascular Disease and Other Causes for Japanese Men and Women: the JACC Study"
},
{
"docid": "MED-975",
"text": "Diverticular disease of the colon is a new disease that appeared at the beginning of this century. It is now the commonest disease of the colon in the Western world, being found in 1 in 3 people of over 60 years of age. The pathogenesis of the disease involves excessive segmentation, but this does not explain its aetiology. The historical appearance of the disease on the clinical scene and its geographical distribution suggest that it is due to the removal of fibre from carbohydrates. The author treated 70 patients with symptomatic diverticular disease with a high-fibre diet. The results of this and the effects of bran are discussed.",
"title": "Diverticular disease of the colon. The first of the Western diseases shown to be due to a deficiency of dietary fibre."
},
{
"docid": "MED-3480",
"text": "Studies on the association between plant foods and cerebrovascular diseases have given contradictory results suggesting the existence of some effect-modifying factors. The present study determines whether the consumption of plant foods (i.e. fruits and berries, vegetables, and cereals) predicts a decreased cerebrovascular disease incidence in a population with low fruit and vegetable and high wholegrain intake. This cohort study on 3932 men and women was based on data from the Finnish Mobile Clinic Health Examination Survey, conducted in 1968-72. The participants were 40-74 years of age and free of cardiovascular diseases at baseline. Data on the plant food consumption were derived from a 1-year dietary history interview. During a 24-year follow-up 625 cases of cerebrovascular diseases occurred, leading to either hospitalisation or death. An inverse association was found between fruit consumption and the incidence of cerebrovascular diseases, ischaemic stroke and intracerebral haemorrhage. The adjusted relative risks (RR) between the highest and lowest quartiles of intake of any cerebrovascular disease, ischaemic stroke and intracerebral haemorrhage were 0.75 (95 % CI 0.59, 0.94), 0.73 (95 % CI 0.54, 1.00) and 0.47 (95 % CI 0.24, 0.92), respectively. These associations were primarily due to the consumption of citrus fruits and occurred only in men. Total consumption of vegetables or cereals was not associated with the cerebrovascular disease incidence. The consumption of cruciferous vegetables, however, predicted a reduced risk of cerebrovascular diseases (RR 0.79; 95 % CI 0.63, 0.99), ischaemic stroke (RR 0.67; 95 % CI 0.49, 0.92) and intracerebral haemorrhage (RR 0.49; 95 % CI 0.25, 0.98). In conclusion, the consumption of fruits, especially citrus, and cruciferous vegetables may protect against cerebrovascular diseases.",
"title": "Plant foods and the risk of cerebrovascular diseases: a potential protection of fruit consumption."
},
{
"docid": "MED-5281",
"text": "Alterations of endothelial cells and the vasculature play a central role in the pathogenesis of a broad spectrum of the most dreadful of human diseases, as endothelial cells have the key function of participating in the maintenance of patent and functional capillaries. The endothelium is directly involved in peripheral vascular disease, stroke, heart disease, diabetes, insulin resistance, chronic kidney failure, tumor growth, metastasis, venous thrombosis, and severe viral infectious diseases. Dysfunction of the vascular endothelium is thus a hallmark of human diseases. In this review the main endothelial abnormalities found in various human diseases such as cancer, diabetes mellitus, atherosclerosis, and viral infections are addressed.",
"title": "The Vascular Endothelium and Human Diseases"
},
{
"docid": "MED-3706",
"text": "Autoimmune diseases are complex diseases resulting of the interaction between both genetics and environmental factors over time. Different phases in the development of autoimmune diseases are characterized by the detection of serum autoantibodies several months or years before the onset of clinical manifestations and subsequent diagnosis. In addition to serum antibodies, genetic susceptibility factors may predict the future development of the disease. Currently, prediction in type 1 diabetes is the most accurate, with the analysis of genetic susceptibility factors in first-degree relatives of patients and several autoantibody tests. In the future, multiple antibodies test, in combination with the analysis of genetics, epigenetics and immunological anomalies in fine models may allow the precise prediction in autoimmune diseases. Prevention measures might thus be introduced as an attempt to avoid or delay the disease. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Are autoimmune diseases predictable?"
},
{
"docid": "MED-4345",
"text": "BACKGROUND: n-3 (omega-3) Polyunsaturated fatty acids (PUFAs), fish, and nuts can regulate inflammatory processes and responses. OBJECTIVE: We investigated whether dietary intakes of PUFAs [n-3, n-6 (omega-6), and α-linolenic acid], fish, and nuts were associated with 15-y mortality attributed to noncardiovascular, noncancer inflammatory diseases. DESIGN: The analyses involved 2514 participants aged ≥49 y at baseline. Dietary data were collected by using a semiquantitative food-frequency questionnaire, and PUFA, fish, and nut intakes were calculated. Inflammatory disease mortality was confirmed from the Australian National Death Index. RESULTS: Over 15 y, 214 subjects died of inflammatory diseases. Women in the highest tertiles of total n-3 PUFA intake, compared with those in the lowest tertile of intake at baseline, had a 44% reduced risk of inflammatory disease mortality (P for trend = 0.03). This association was not observed in men. In both men and women, each 1-SD increase in energy-adjusted intake of α-linolenic acid was inversely associated with inflammatory mortality (hazard ratio: 0.83; 95% CI: 0.71, 0.98). Subjects in the second and third tertiles of nut consumption had a 51% and 32% reduced risk of inflammatory disease mortality, respectively, compared with those in the first tertile (reference). Dietary intakes of long-chain n-3 and n-6 PUFAs and fish were not associated with inflammatory disease mortality. CONCLUSIONS: We report on a novel link between dietary intake of total n-3 PUFA and risk of inflammatory disease mortality in older women. Furthermore, our data indicate a protective role of nuts, but not fish, against inflammatory disease mortality.",
"title": "Consumption of polyunsaturated fatty acids, fish, and nuts and risk of inflammatory disease mortality."
},
{
"docid": "MED-1167",
"text": "Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies, autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "Pesticides and human chronic diseases: evidences, mechanisms, and perspectives."
},
{
"docid": "MED-4013",
"text": "OBJECTIVE: The purpose of this study was to determine whether periodontal disease is associated with endothelial dysfunction and systemic inflammation. Epidemiological studies suggest that severe periodontal disease is associated with increased cardiovascular disease risk, but the mechanisms remain unknown. METHODS AND RESULTS: We assessed flow-mediated dilation and nitroglycerin-mediated dilation of the brachial artery using vascular ultrasound in 26 subjects with advanced periodontal disease and 29 control subjects. The groups were matched for age and sex, and patients with hypercholesterolemia, diabetes mellitus, hypertension, and history of cigarette smoking were excluded. We also examined serum levels of C-reactive protein using an established high-sensitivity method. Subjects with advanced periodontal disease had lower flow-mediated dilation compared with control patients (7.8+/-4.6% versus 11.7+/-5.3%, P=0.005). Nitroglycerin-mediated dilation was equivalent in the two groups. Subjects with advanced periodontitis exhibited higher serum levels of high-sensitivity C-reactive protein compared with healthy controls patients (2.3+/-2.3 versus 1.0+/-1.0 mg/L, P=0.03). CONCLUSIONS: Subjects with advanced periodontal disease exhibit endothelial dysfunction and evidence of systemic inflammation, possibly placing them at increased risk for cardiovascular disease.",
"title": "Periodontal disease is associated with brachial artery endothelial dysfunction and systemic inflammation."
},
{
"docid": "MED-4496",
"text": "BACKGROUND: Many constituents of fruits and vegetables may reduce the risk for coronary heart disease, but data on the relationship between fruit and vegetable consumption and risk for coronary heart disease are sparse. OBJECTIVE: To evaluate the association of fruit and vegetable consumption with risk for coronary heart disease. DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study and the Health Professionals' Follow-Up Study. PARTICIPANTS: 84 251 women 34 to 59 years of age who were followed for 14 years and 42 148 men 40 to 75 years who were followed for 8 years. All were free of diagnosed cardiovascular disease, cancer, and diabetes at baseline. MEASUREMENTS: The main outcome measure was incidence of nonfatal myocardial infarction or fatal coronary heart disease (1127 cases in women and 1063 cases in men). Diet was assessed by using food-frequency questionnaires. RESULTS: After adjustment for standard cardiovascular risk factors, persons in the highest quintile of fruit and vegetable intake had a relative risk for coronary heart disease of 0.80 (95% CI, 0.69 to 0.93) compared with those in the lowest quintile of intake. Each 1-serving/d increase in intake of fruits or vegetables was associated with a 4% lower risk for coronary heart disease (relative risk, 0.96 [CI, 0.94 to 0.99]; P = 0.01, test for trend). Green leafy vegetables (relative risk with 1-serving/d increase, 0.77 [CI, 0.64 to 0.93]), and vitamin C-rich fruits and vegetables (relative risk with 1-serving/d increase, 0.94 [CI, 0.88 to 0.99]) contributed most to the apparent protective effect of total fruit and vegetable intake. CONCLUSIONS: Consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C-rich fruits and vegetables, appears to have a protective effect against coronary heart disease.",
"title": "The effect of fruit and vegetable intake on risk for coronary heart disease."
},
{
"docid": "MED-4173",
"text": "OBJECTIVE: To assess the public health significance of premature weaning of infants from breast milk on later-life risk of chronic illness. DESIGN: A review and summary of recent meta-analyses of studies linking premature weaning from breast milk with later-life chronic disease risk is presented followed by an estimation of the approximate exposure in a developed Western country, based on historical breast-feeding prevalence data for Australia since 1927. The population-attributable proportion of chronic disease associated with current patterns of artificial feeding in infancy is estimated. RESULTS: After adjustment for major confounding variables, current research suggests that the risks of chronic disease are 30-200 % higher in those who were not breast-fed compared to those who were breast-fed in infancy. Exposure to premature weaning ranges from 20 % to 90 % in post-World War II age cohorts. Overall, the attributable proportion of chronic disease in the population is estimated at 6-24 % for a 30 % exposure to premature weaning. CONCLUSIONS: Breast-feeding is of public health significance in preventing chronic disease. There is a small but consistent effect of premature weaning from breast milk in increasing later-life chronic disease risk. Risk exposure in the Australian population is substantial. Approximately 90 % of current 35-45-year-olds were weaned from breast-feeding by 6 months of age. Encouraging greater duration and exclusivity of breast-feeding is a potential avenue for reducing future chronic disease burden and health system costs.",
"title": "Chronic disease and infant nutrition: is it significant to public health?"
},
{
"docid": "MED-3938",
"text": "Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson’s disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson’s disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson’s disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson’s disease patients. When stratified by sex, the female Parkinson’s disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson’s disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson’s disease-related pathology. Furthermore, these data support epidemiological and laboratory studies reporting a link between PCB exposure and an increased risk for Parkinson’s disease, including greater susceptibility of females.",
"title": "Association between polychlorinated biphenyls and Parkinson’s disease neuropathology"
},
{
"docid": "MED-970",
"text": "Objective To examine the associations of a vegetarian diet and dietary fibre intake with risk of diverticular disease. Design Prospective cohort study. Setting The EPIC-Oxford study, a cohort of mainly health conscious participants recruited from around the United Kingdom. Participants 47 033 men and women living in England or Scotland of whom 15 459 (33%) reported consuming a vegetarian diet. Main outcome measures Diet group was assessed at baseline; intake of dietary fibre was estimated from a 130 item validated food frequency questionnaire. Cases of diverticular disease were identified through linkage with hospital records and death certificates. Hazard ratios and 95% confidence intervals for the risk of diverticular disease by diet group and fifths of intake of dietary fibre were estimated with multivariate Cox proportional hazards regression models. Results After a mean follow-up time of 11.6 years, there were 812 cases of diverticular disease (806 admissions to hospital and six deaths). After adjustment for confounding variables, vegetarians had a 31% lower risk (relative risk 0.69, 95% confidence interval 0.55 to 0.86) of diverticular disease compared with meat eaters. The cumulative probability of admission to hospital or death from diverticular disease between the ages of 50 and 70 for meat eaters was 4.4% compared with 3.0% for vegetarians. There was also an inverse association with dietary fibre intake; participants in the highest fifth (≥25.5 g/day for women and ≥26.1 g/day for men) had a 41% lower risk (0.59, 0.46 to 0.78; P<0.001 trend) compared with those in the lowest fifth (<14 g/day for both women and men). After mutual adjustment, both a vegetarian diet and a higher intake of fibre were significantly associated with a lower risk of diverticular disease. Conclusions Consuming a vegetarian diet and a high intake of dietary fibre were both associated with a lower risk of admission to hospital or death from diverticular disease.",
"title": "Diet and risk of diverticular disease in Oxford cohort of European Prospective Investigation into Cancer and Nutrition (EPIC): prospective study of British vegetarians and non-vegetarians"
},
{
"docid": "MED-5293",
"text": "Summary Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. Methods We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. Findings In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2–7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5–7·0]), and alcohol use (5·5% [5·0–5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8–9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6–8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4–6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2–10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water we and sanitation accounting for 0·9% (0·4–1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. Interpretation Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. Funding Bill & Melinda Gates Foundation.",
"title": "A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010"
},
{
"docid": "MED-2385",
"text": "The purpose of this investigation was to estimate the total hair mercury of diseased people (not including patients of mercury poisoning such as Minamata disease). Hair samples were collected from 133 diseased volunteers in Tokyo and the surrounding areas from Oct. 1992 to June 1993. The total mercury concentrations in the hair of ordinary diseased people (atopic dermatitis, asthma, dementia, cerebral infarct, osteoporosis, hypertension and diabetes) were from 2.08 ppm to 36.5 ppm. Those values were considerably higher than that of healthy people of the same age groups. However, the uptake routes and the metabolic mechanism of high hair mercury concentrations in diseased people are not clear.",
"title": "Concentration of mercury in hair of diseased people in Japan."
},
{
"docid": "MED-5303",
"text": "IMPORTANCE: Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy. OBJECTIVES: To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries. DESIGN: We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages. RESULTS: US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th. CONCLUSIONS AND RELEVANCE: From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.",
"title": "The state of US health, 1990-2010: burden of diseases, injuries, and risk factors."
},
{
"docid": "MED-1948",
"text": "Over the last ten years curcumin has been reported to be effective against a wide variety of diseases and is characterized as having anti-carcinogenic, hepatoprotective, thrombosuppressive, cardioprotective, anti-arthritic, and anti-infectious properties. Recent studies performed in both vertebrate and invertebrate models have been conducted to determine whether curcumin was also neuroprotective. The efficacy of curcumin in several pre-clinical trials for neurodegenerative diseases has created considerable excitement mainly due to its lack of toxicity and low cost. This suggests that curcumin could be a worthy candidate for nutraceutical intervention. Since aging is a common risk factor for neurodegenerative diseases, it is possible that some compounds that target aging mechanisms could also prevent these kinds of diseases. One potential mechanism to explain several of the general health benefits associated with curcumin is that it may prevent aging-associated changes in cellular proteins that lead to protein insolubility and aggregation. This loss in protein homeostasis is associated with several age-related diseases. Recently, curcumin has been found to help maintain protein homeostasis and extend lifespan in the model invertebrate Caenorhabditis elegans. Here, we review the evidence from several animal models that curcumin improves healthspan by preventing or delaying the onset of various neurodegenerative diseases.",
"title": "Curcumin and neurodegenerative diseases"
},
{
"docid": "MED-2082",
"text": "BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease S..."
},
{
"docid": "MED-2590",
"text": "Nineteen people without prior history of documented heart disease were studied for 8 months to determine the effect of treatment based on an immunologic unified theory of vascular disease. Subjects underwent myocardial perfusion imaging to quantify the extent and severity of coronary artery disease, along with assessment of wall motion abnormalities and ejection fraction by both nuclear and echocardiographic methods. These tests were repeated at the end of the study. Treatment consisted of dietary changes, treatment of cholesterol, triglycerides, homocysteine, lipoprotein (a), fibrinogen, C-reactive protein, and infection. Patients who followed the dietary recommendations demonstrated statistically reduced disease in all three major coronary arteries, whereas those individuals who followed high-protein diets demonstrated statistically greater levels of disease.",
"title": "Reversing heart disease in the new millennium--the Fleming unified theory."
},
{
"docid": "MED-4919",
"text": "OBJECTIVE: Mass screening for celiac disease is controversial. The objective of this study was to determine whether detection of childhood celiac disease by mass screening improves long-term health status and health-related quality of life. METHODS: We conducted a prospective 10-year follow-up study of 32 children who were aged 2 to 4 years, had celiac disease identified by mass screening, and had a gluten-free diet (19) or a normal gluten-containing diet (13). The follow-up included assessments of general health status, celiac disease-associated symptoms, celiac disease-associated serum antibodies, and health-related quality of life. RESULTS: Ten years after mass screening, 81% of the children were adhering to a gluten-free diet. The health status improved in 66% of the treated children: in 41% by early treatment and in 25% by prevention of the gluten-dependent symptoms that they developed after diagnosis. For 19% of the children, treatment after screening would not have improved their health status, because they had no symptoms at screening and have remained symptom-free while consuming gluten. The health-related quality of life of the children with symptoms improved significantly after 1 year of gluten-free diet. Ten years after screening, the health-related quality of life of the children with celiac disease was similar to that of the reference population. CONCLUSION: Identification by mass screening led 10 years later to health improvement in 66% of children without deterioration of generic health-related quality of life. There is a good compliance after mass screening. In a research setting, delaying treatment for children without symptoms seems to be an option after a positive screening test. Long-term follow-up studies are needed to assess possible long-term complications in untreated, nonsymptomatic celiac disease.",
"title": "Long-term health and quality-of-life consequences of mass screening for childhood celiac disease: a 10-year follow-up study."
},
{
"docid": "MED-2658",
"text": "The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.",
"title": "Alkylphenols--potential modulators of the allergic response."
},
{
"docid": "MED-2924",
"text": "Recent advances have been made in our scientific understanding of how berries promote human health and prevent chronic illnesses such as some cancers, heart disease, and neurodegenerative diseases. Cancer is rapidly overtaking heart disease as the number one killer disease in developed countries, and this phenomenon is coupled with a growing aging population and concomitant age-related diseases. Therefore, it is not surprising that consumers are turning toward foods with medicinal properties as promising dietary interventions for disease prevention and health maintenance. Among fruits, berries of all colors have emerged as champions with substantial research data supporting their abilities to positively affect multiple disease states. Apart from several essential dietary components found in berries, such as vitamins, minerals, and fiber, berries also contain numerous bioactives that provide health benefits that extend beyond basic nutrition. Berry bioactives encompass a wide diversity of phytochemicals (phytonutrients) ranging from fat-soluble/lipophilic to water-soluble/hydrophilic compounds. Recent research from laboratories across the globe has provided useful insights into the biological effects and underlying mechanisms of actions resulting from eating berries. The cluster of papers included here represents a cross section of topics discussed at the 2009 International Berry Health Benefits Symposium. Together, these papers provide valuable insight into recent research trends and advances made into evaluating the various health benefits that may result from the consumption of berries and their derived products.",
"title": "Recent trends and advances in berry health benefits research."
},
{
"docid": "MED-3966",
"text": "Crohn's disease is a modern Western disease characterised by transmural inflammation of the gastrointestinal tract. It is of unknown aetiology, but evidence suggests that it results from a combination of genetic predisposition and environmental factors. Bacterial-sized microparticles (0.1-1.0 microm) are potent adjuvants in model antigen-mediated immune responses and are increasingly associated with disease. Microparticles of TiO2 and aluminosilicate accumulate in macrophages of human gut-associated lymphoid tissue where the earliest signs of lesions in Crohn's disease are observed. Dietary microparticles are of endogenous or exogenous origin. Endogenous microparticles dominate and are calcium phosphate (most probably hydroxyapatite), which precipitates in the lumen of the mid-distal gastrointestinal tract due to secretion of Ca and phosphate in the succus entericus. Exogenous dietary microparticles are contaminants (soil and/or dust) and food additives. TiO2, for example, is a food colourant, and aluminosilicates are anti-caking agents, although some aluminosilicates occur as natural contaminants. Food additives alone account for ingestion of approximately 10(12) particles/person per d. Possible mechanisms for the role of exogenous and endogenous dietary microparticles in promoting toleragenic or immune responses of gastrointestinal mucosal phagocytosis are discussed. In a double-blind randomised pilot study we have shown that a diet low in Ca and exogenous microparticles appears to alleviate the symptoms of ileal Crohn's disease, with a significant (P= 0.002) improvement in the Crohn's disease activity index. A multi-centre trial and further mechanistic studies at the cellular level are underway.",
"title": "Fine and ultrafine particles of the diet: influence on the mucosal immune response and association with Crohn's disease."
},
{
"docid": "MED-5018",
"text": "Purpose of review This article reviews the AAP’s statement on early nutritional interventions on the development of atopic disease in infants and children. Recent findings Recent findings suggest that restriction of maternal diet during pregnancy and lactation does not play a major role in the development of allergic disease. In high risk infants exclusive breastfeeding for at least 4 months prevents or delays atopic dermatitis, cow milk allergy, and wheezing early in life. There is evidence that supplementing breastfeeding with a hydrolyzed formula protects against atopic disease, especially atopic dermatitis in at risk infants. Finally there is little evidence that delaying the introduction of complimentary foods beyond 4 to 6 months of age has any protective effect against allergy. There is insufficient data that any dietary intervention beyond 4 to 6 months of age has any protective effect against developing atopic disease. Summary In high risk infants there is evidence for exclusive breastfeeding for at least 4 months and delaying of complimentary foods until 4 to 6 months prevents the development of allergy. There is some evidence that supplementing hydrolyzed formulas in high risk infants may delay or prevent allergic disease. There is no convincing evidence that maternal manipulation of diet during pregnancy or lactation, use of soy products, or infant dietary restrictions beyond 4 to 6 months has any effect on the development of atopic disease.",
"title": "American Academy of Pediatrics recommendations on the Effects of Early Nutritional Interventions on the Development of Atopic Disease"
},
{
"docid": "MED-3387",
"text": "Respiratory exposure to diacetyl and diacetyl-containing flavorings used in butter-flavored microwave popcorn (BFMP) causes lung disease, including bronchiolitis obliterans (BO), in flavorings and popcorn manufacturing workers. However, there are no published reports of lung disease among BFMP consumers. We present a case series of three BFMP consumers with biopsy-confirmed BO. We review data relating to consumer exposures, estimate case exposures, and compare them to diacetyl-containing flavoring-exposed manufacturing workers with lung disease. These consumer cases' exposure levels are comparable to those that caused disease in workers. We were unable to identify any other exposures or diseases known or suspected to cause BO in these cases. BFMP poses a significant respiratory risk to consumers. Some manufacturers have substituted diacetyl with other alpha-diketones that are likely to pose a similar risk. Simple consumer practices such as cooling the popcorn bag would eliminate the risk of severe lung disease.",
"title": "Bronchiolitis obliterans and consumer exposure to butter-flavored microwave popcorn: a case series."
}
] |
4707
|
Legal Financing
|
[
{
"docid": "521967",
"text": "Find a lawyer or law firm who wants to represent you and talk to them.",
"title": ""
}
] |
[
{
"docid": "13718",
"text": "There are two Questions: Financial institutions do not care about your nationality, only your ability to pay over time. For long term debt the lender will want assurances that the borrower has the ability and means to pay the debt over time. A legal resident in the US should have no more difficulty obtaining financing than a citizen under similar life circumstances. The Lender is also under legal obligation to confirm that the borrower is who they say they are, will have the ability to pay over time AND have no malicious intent in the purchase. Persons who do not have legal status in the US, AND who do not have the means to pay for property outright will have difficulty obtaining financing as they will have trouble establishing the requirements of the Lender. This is simple math, a lender will be reluctant to lend to any person who is more likely to have difficulty paying the obligation than another. In your case Your father would be an unlikely candidate for a mortgage because he cannot establish his legal status nor can he guarantee that he will have the legal right to earn a means to pay the loan back. This puts the lender at risk both of losing the money lent AND losing the right to repossess the property if the borrower doesn't pay. Despite all of the obstacles I have indicated above, it is still possible for your father to purchase property legally, but the risk and the cost go way up for him as a borrower. There may be sellers willing to finance property over time, but your father's status puts him at a disadvantage if the seller is not honest. There may be community coalitions which can help you work through the challenges of property ownership. Please see these related articles",
"title": ""
},
{
"docid": "291526",
"text": "As long as you don't finance and the payment is upfront, its up to you and your customer how to pay. If you provide the product before the payment is being made or finance in any way (i.e.: there's debt), then the Canadian dollar, being legal tender in Canada, must be accepted. Considering the large amount, you would probably not be accepting cash anyway, so the point is moot. How they pay their credit cards is not your problem. However, do take into the account the currency exchange rates and fees that add costs to purchasing your product. If you don't have any physical presence (i.e.: online store only, no physical location on Canadian soil), then it goes by the rules of the jurisdiction where you've incorporated. Check with the local legal professional to be sure.",
"title": ""
},
{
"docid": "597229",
"text": "While r/finance has some great advice and posters who are well versed in their fields, this appears to be a legal question and if you're really concerned about the legality, I would strongly advise you to check in with a lawyer, not an online internet commenter. While there is a lot of good content on this site, you do see comments where the person is completely talking out of their ass. It would suck for you to raise concerns at your job, based on faulty 'legal' advice.",
"title": ""
},
{
"docid": "485195",
"text": "Since your credit score is much better than hers, you should apply for the credit card yourself alone to get the best chance of approval for your card of choice. Once you have the card, you can add her as an authorized user, which will get her a card of her own, tied to your account. Most banks will begin reporting to both of your credit reports, which should help her credit score over time. Keep in mind that you are solely legally responsible for the debt; your girlfriend will be able to make charges and will have no legal responsibility for the debt. Make sure you are comfortable with that. For what it is worth, in general, I recommend against combining your finances with someone who you are not married to, but it seems that you have already done that, so adding a shared credit card to your finances shouldn't be any worse than what you are already doing.",
"title": ""
},
{
"docid": "294621",
"text": "This is correct. The most rapidly expanding areas in finance resemble computer science more than they resemble traditional finance. The compliance and legal side of things, however, is only getting more and more complicated. At my firm, the compliance personnel outnumber the traders three to one.",
"title": ""
},
{
"docid": "227910",
"text": "For providing financing assistance to the clients, Invoice Finance and Factoring Services are provided by some recognized professional financial services providers in London. They can help in improving cash flows and credit control. Before applying for loans, a business has to undergo the lengthy processes and legal formalities. To simplify these procedures, Forfaiting Financial Services in London are provided to many organizations.",
"title": ""
},
{
"docid": "453263",
"text": "Is your name on the title at all? You may have (slightly) more leverage in that case, but co-signing any loans is not a good idea, even for a friend or relative. As this article notes: Generally, co-signing refers to financing, not ownership. If the primary accountholder fails to make payments on the loan or the retail installment sales contract (a type of auto financing dealers sell), the co-signer is responsible for those payments, or their credit will suffer. Even if the co-signer makes the payments, they’re still not the owner if their name isn’t on the title. The Consumer Finance Protection Bureau (CFPB) notes: If you co-sign a loan, you are legally obligated to repay the loan in full. Co-signing a loan does not mean serving as a character reference for someone else. When you co-sign, you promise to pay the loan yourself. It means that you risk having to repay any missed payments immediately. If the borrower defaults on the loan, the creditor can use the same collection methods against you that can be used against the borrower such as demanding that you repay the entire loan yourself, suing you, and garnishing your wages or bank accounts after a judgment. Your credit score(s) may be impacted by any late payments or defaults. Co-signing an auto loan does not mean you have any right to the vehicle, it just means that you have agreed to become obligated to repay the amount of the loan. So make sure you can afford to pay this debt if the borrower cannot. Per this article and this loan.com article, options to remove your name from co-signing include: If you're name isn't on the title, you'll have to convince your ex-boyfriend and the bank to have you removed as the co-signer, but from your brief description above, it doesn't seem that your ex is going to be cooperative. Unfortunately, as the co-signer and guarantor of the loan, you're legally responsible for making the payments if he doesn't. Not making the payments could ruin your credit as well. One final option to consider is bankruptcy. Bankruptcy is a drastic option, and you'll have to weigh whether the disruption to your credit and financial life will be worth it versus repaying the balance of that auto loan. Per this post: Another not so pretty option is bankruptcy. This is an extreme route, and in some instances may not even guarantee a name-removal from the loan. Your best bet is to contact a lawyer or other source of legal help to review your options on how to proceed with this issue.",
"title": ""
},
{
"docid": "208051",
"text": "Shanghai can not be the international financial center of China, or China's inbound/outbound trade, as long as it does not have rule of law. Even Chinese corporates go to Hong Kong to sign contracts because the commercial legal system is efficient, fair, and predictable. Shanghai is a city (and a great one, no doubt!) doing business in a restricted, capital-controlled currency, under a legal system which is corrupt and arbitrary. You wouldn't want to get into a dispute there with, say, Bank of China. When there is a trusted legal system in China then finance will follow. Meanwhile, show me anyone who wants to sign an ISDA agreement under Chinese law, subject an international bond indenture to Chinese law (rather than New York or English law), or do a securitization using Chinese law or counterparties. HK's biggest problem may be that the Mainland is imperiling rule of law in the SAR. If that is lost, the city has no reason to exist.",
"title": ""
},
{
"docid": "327544",
"text": "Until they're old enough to be legally responsible for their own credit, the only thing you can really do is show them by example how to manage money and credit in your own finances. Teach them budgeting, immerse them in understanding how credit and financing work, and teach them smart ways to make their money work for them. When they're teenagers, you could potentially approach small banks or credit unions about ways to perhaps co-sign loans for them and let them make payments to learn good habits for managing their responsibilities, but that's not always easy either. It won't do anything for their credit, but having the responsibility of coming in to make payments might instill good habits and help their self-esteem at the same time. You have great intentions, but as has been pointed out here already, from a legal standpoint there's not much you can do. All you can do is prepare them for the day when they are on their own and can enter into credit agreements. Kids going to college get into real trouble with credit because cards are handed out like candy to them by the banks, so teaching them money management skills is invaluable and something you can do now.",
"title": ""
},
{
"docid": "547932",
"text": "\"To supplement @littleadv's answer, I discovered that our friends at both Skeptics Stack Exchange and Politics Stack Exchange have also addressed this question — at least a few times that I could find. Please refer to: Skeptics SE: Was the 16th Amendment (income tax) improperly ratified? ... with an accepted answer posted by Money's own @DJClayworth. Skeptics SE: Has income tax been found unconstitutional by a court? ... which also mentions the useful IRS page The Truth About Frivolous Tax Arguments. I also highlight the mention to this valuable FAQ mentioned by @Paul, who also participates here at Money, in a comment on the accepted answer: For more information on bad legal arguments, see Tax Protester Legal FAQ – Paul Jan 7 '14 at 6:29 Politics SE: Constitutionality of the Income Tax. I'll add that Money SE is best suited for practical questions relating to an individual's personal finances. While \"\"find ways to [...], minimize taxes, [...]\"\" is specifically mentioned as on-topic, a key word there is \"\"minimize\"\", not \"\"evade\"\". While questions here can overlap with legal or political issues, the focus at Money SE remains on the practical.\"",
"title": ""
},
{
"docid": "195372",
"text": "\"Someone asked this over in /r/darknetmarkets , they were asking how to profit off NV specifically, but here's what I wrote there, I'd be curious what you guys think: > Go back in time about 6 mo, case the medical scene for movers and shakers, write some proposals to help them expand. Traditional banks won't touch financing these guys with a 10ft stick right now, the Fed has told them straight up they will lose FDIC membership if they touch \"\"drug money\"\" (cough cough tobacco and alcohol don't count? cough cough). If you don't have a time machine, either come up with a way to be a bank to these guys without going to a Fed lockup, or go finance expansion in the next state which legalizes. It's gonna be a while until these guys get integrated with the regular money system to the point they have stocks and such. Or maybe the Fed freezing them out as they make a fortune will just push forward crypto currency and hasten the collapse of the current money oligarchy, who knows. There was also some comments about shipping from NV to home states, which is probably a bad idea for many reasons. I did however feel I can offer some insight on a legal president for this kind of behavior, but exactly how legal reshipping to avoid direct shipping of a purchase to a state is (I mean, once it's your proper legal property and you're just shipping it to yourself that does seem legal, right?) or if it would get the same blind eye when done with pot are huge unknowns: >I'm sure the Feds will not see a problem with sending drugs to yourself across state lines! Actually funny enough I live in the wine region of CA and there is a whole business here of wine \"\"storage and shipping\"\" places. It's up to the states to decide how or if they allow alcohol to be shipped into their state from others, and a bunch of state have very complex rules or just don't allow it. So if you come out here for tourism, drink some wine at a winery, like it, and ask if you can have some shipped home, the answer is about 50/50 to be 'no'. And if you're a average income pleb, that's your answer. If you're some rich dude however, you can say \"\"ah gotcha, pesky laws... well here's the address of my storage and shipping place, send the 2 cases there then\"\", nobody bats an eye, and off the cases go. Guy goes home, calls up the shipping place, and says \"\"hey pull those cases, my personal property, and ship them to me\"\" and, somehow, magically, this is now legal. I have no idea who's taking on the liability here, if the shipping place has them sign off \"\"we will ship wherever you ask, it's not our job to verify the legality of your request\"\" then I guess it's on the consumer, but if you have an entire business built around circumventing state law it would seem to me that this should be a legal problem. But, wine is a high-end commodity, rich people make their own rules, and if CA turns a blind eye to this practice they get to collect the sales tax as it's sold in CA and shipped to a location in CA, whereas fighting it would hurt their tourism and also send the tax income to the states being shipped to. C.R.E.A.M. baby! Re-reading this now I'm not even sure if there IS a liability here. They bought the property in CA, paid tax in CA, and had it sent to a mailing address in CA. What they do after that with their personal property is not the states business, right? I'd imagine this would be drastically different if shipping for resale. Similarly, I think this all only works if you complete the transaction while physically in the state. So at most this might turn on some weed tourism. The big difference in all of this is that the Fed is fine with alcohol, but not weed, so, while I suspect someone will form such a weed storage and shipping place at some point, I don't really want to be first in line to see how this flys and if it lands you in trouble with the Fed.\"",
"title": ""
},
{
"docid": "109025",
"text": "\"It sounds like you are describing \"\"seller-financed\"\" mortgages (also sometimes called \"\"self-financed\"\", where \"\"self\"\" is the seller). In essence the buyer and seller enter into a legal contract (a promissory note) that specifies the payment schedule, interest rate, etc. The nature of the agreement is similar to the kind of mortgage agreement you'd get from the bank, but no bank is involved; it's just an agreeement directly between the buyer and seller. If you search for \"\"seller-financed mortgage\"\" or \"\"self-financed mortgage\"\" you can find a good deal more info about this kind of arrangement. Here is a useful article from Investopedia, here is one from Forbes, and here is one from Nolo. Broadly speaking, the advantages and disadvantages of seller financing are two sides of the same coin: by doing the agreement yourself without bank involvement, you can cut out procedural red tape, delays, and requirements that a bank might insist on --- but in so doing you may expose yourself to risks that those procedures are designed to shield you from. Most obviously, as the seller, you receive only the down payment up front (not the entire purchase price, as you would if the buyer got a bank loan), and if the buyer doesn't follow through on the agreement, you're on your own as far as starting foreclosure, etc. You can read up on some of the linked pages for more details about the pros and cons. In general, as those pages note, seller-financed mortgages are relatively rare. A home is a big purchase, and if you don't know what you're doing it's easy to screw up in a way that could cost you a large amount of money if things go wrong.\"",
"title": ""
},
{
"docid": "566382",
"text": "Most states do have a cooling-off period where the buyer can rescind the purchase as well as a legally allowed limit to how long the dealer has to secure financing when they buyer has opted for dealer-financing. If the dealer did inform you during the allowed window, they will refund your down payment minus mileage fees at a state set cost per mile that you used the car. If the dealer did not inform you during the allowed window, depending on the state, they may have to refund the entire down payment. In any case, the problem is that the bank does not want to offer you the loan, you can try to negotiate and have the dealer use what leverage they have to coerce the bank, but there is probably no way for you to force the loan through. Alternatively you can seek your own financing from your own bank or credit union, which will likely allow the sale to go through. UPDATE - Colorado laws allow the dealer 10 days to inform you that they cannot obtain financing on the terms agreed upon in the original contract. That contract contained wording related to the mileage fees. You can find that info on page 8 of the linked PDF under the heading D. USAGE FEE AND MILEAGE CHARGE",
"title": ""
},
{
"docid": "319749",
"text": "Again I don't know how well this applies to all finance professions but in my field a lot of what we do is effectively communicate finance and valuation information to clients. Essentially we are contracted to perform analysis, then we write a report conveying the meaning of that analysis to the client. A good amount of the work we do often has legal implications as well so our writing has to stand up to litigation and cross examination. Perhaps being a good writer won't be crucial for your position but in my opinion writing is mostly about how to effectively communicate an idea. In that context writing is very useful in teaching you how to get your message across. I hope that makes sense.",
"title": ""
},
{
"docid": "233479",
"text": "The sales manager and/or finance manager applied a rebate that did not apply. It's their fault. They have internal accounts to handle these situations as they do come up from time to time. The deal is done. They have no legal ground.",
"title": ""
},
{
"docid": "391370",
"text": "This is not a finance issue, it is a legal one. You need to talk to a lawyer. To save your credit you can pay off the bank now and fight out the details with your ex later. The bank is still owed their money.",
"title": ""
},
{
"docid": "126814",
"text": "I'd be a bit concerned about someone who wanted to transact that large of a transaction in cash. Also consider what you are going to do with the funds, if you deposit it, you will need to tell the bank where it comes from. Why does the bank want to know, because most legal businesses don't transact business with large sums of currency.. What does that tell you about the likelihood the person you are about to do business with is a criminal or involved in criminal affairs? The lower bill of sale price might be more than just to dodge taxes, it could be part of money laundering.. If they can turn right around and 'sell' the boat for $10K, or trade it in on a bigger boat for the same amount, and have a bill than says $4K, then they have just come up with a legal explanation for how they made 6 grand. and you could potentially be considered an accomplice if someone is checking up on their finances. Really, is it worth the risk.",
"title": ""
},
{
"docid": "291680",
"text": "**Absolutely do not ever use one of these loans**. These loans will lead you down a long road of huge interest and credit trouble. They are nothing more then legal loan sharks. But I'm sure I don't have to tell the people of /r/finance this. Do I?",
"title": ""
},
{
"docid": "133623",
"text": "Mr. Raphael Lilla has been operating as the Executive Director of SBC Group AG Bouchs (Switzerland) since July, 2016. With a professional experience of over 20 years in the legal and finance industries, Mr. Lilla takes pride in his association with the International Society of Business Leaders.",
"title": ""
},
{
"docid": "513367",
"text": "This is more legal and less personal finance question. You should immediately lodge a police complaint mentioning that some persons are using your PAN card details for activities not authorized by you. In the meantime also engage the services of a CA and reply back to income tax authorities. Do not ignore the notice.",
"title": ""
},
{
"docid": "486367",
"text": "As you point out, the main benefits of a pension/retirement account over a traditional cash/taxable account are the legal and tax benefits. Most Western countries establish a specific legal definition for an account which is often taxed less or not at all relative to taxable accounts and which contains some protection for the owner in case of a bankruptcy. The typical drawbacks for investing within such structures are limited investment choice, limited withdrawal rights (either in terms of age or rate of withdrawal), and maximum contributions. The benefits are usually very clear, and your decision whether or not to open a pension/retirement account should depend on a careful weighing of the benefits and drawbacks. As to whether you may end up with less than you started, that depends on what you invest in. As with all of finance, you must take more risk to get more return. Although the choices inside a pension/retirement account may be worded somewhat differently, they are usually fundamentally no different than some of the most popular investments available for ordinary taxable accounts.",
"title": ""
},
{
"docid": "327428",
"text": "\"There are 2 and 3 family houses that have an \"\"owner occupied\"\" clause for certain financing. Of course, one would rent out the extra apartments without question. The key thing is that owner-occupied means just that, occupancy for tax purposes. Just using a small area like an office won't satisfy the requirement, so no, this isn't legal.\"",
"title": ""
},
{
"docid": "300391",
"text": "Here is a pretty exhaustive article on that question. Long story short, it is an insurance policy against the possibility that the person selling the property to you doesn't legally own it. If there was some mistake or fraud along the way the proper owner could theoretically repossess the property without you getting your money back. If you are financing the property, it is almost a certainty that the lender will require you to buy it whether you want it or not.",
"title": ""
},
{
"docid": "357280",
"text": "I've been an F&I Manager at a new car dealership for over ten years, and I can tell you this with absolute certainty, your deal is final. There is no legal obligation for you whatsoever. I see this post is a few weeks old so I am sure by now you already know this to be true, but for future reference in case someone in a similar situation comes across this thread, they too will know. This is a completely different situation to the ones referenced earlier in the comments on being called by the dealer to return the vehicle due to the bank not buying the loan. That only pertains to customers who finance, the dealer is protected there because on isolated occasions, which the dealer hates as much as the customer, trust me, you are approved on contingency that the financing bank will approve your loan. That is an educated guess the finance manager makes based on credit history and past experience with the bank, which he is usually correct on. However there are times, especially late afternoon on Fridays when banks are preparing to close for the weekend the loan officer may not be able to approve you before closing time, in which case the dealer allows you to take the vehicle home until business is back up and running the following Monday. He does this mostly to give you sense of ownership, so you don't go down the street to the next dealership and go home in one of their vehicles. However, there are those few instances for whatever reason the bank decides your credit just isn't strong enough for the rate agreed upon, so the dealer will try everything he can to either change to a different lender, or sell the loan at a higher rate which he has to get you to agree upon. If neither of those two things work, he will request that you return the car. Between the time you sign and the moment a lender agrees to purchase your contract the dealer is the lien holder, and has legal rights to repossession, in all 50 states. Not to mention you will sign a contingency contract before leaving that states you are not yet the owner of the car, probably not in so many simple words though, but it will certainly be in there before they let you take a car before the finalizing contract is signed. Now as far as the situation of the OP, you purchased your car for cash, all documents signed, the car is yours, plain and simple. It doesn't matter what state you are in, if he's cashed the check, whatever. The buyer and seller both signed all documents stating a free and clear transaction. Your business is done in the eyes of the law. Most likely the salesman or finance manager who signed paperwork with you, noticed the error and was hoping to recoup the losses from a young novice buyer. Regardless of the situation, it is extremely unprofessional, and clearly shows that this person is very inexperienced and reflects poorly on management as well for not doing a better job of training their employees. When I started out, I found myself in somewhat similar situations, both times I offered to pay the difference of my mistake, or deduct it from my part of the sale. The General Manager didn't take me up on my offer. He just told me we all make mistakes and to just learn from it. Had I been so unprofessional to call the customer and try to renegotiate terms, I would have without a doubt been fired on the spot.",
"title": ""
},
{
"docid": "498350",
"text": "\"I get it, but I'm just saying it's not as simple as saying \"\"if you can't settle down for a few weeks, you don't really want the job\"\". A person who uses marijuana for medical purposes is *not* legally protected from these drug tests (the courts have ruled on this), but it may not be reasonable for them to stop taking their medicine for six to twelve weeks. Finance companies sometimes do hair tests, although it's less common.\"",
"title": ""
},
{
"docid": "276466",
"text": "Dumb Coder has already given you a link to a website that explains your rights. The only thing that remains is how to execute the return without getting more grief from the dealer. Though the legal aspects are different, I believe the principle is the same. I had a case where I had to rescind the sale of a vehicle in the US. I was within my legal rights to do so, but I knew that when I returned to the dealership they would not be pleased with my decision. I executed my plan by writing a letter announcing my intention to return the vehicle siting the relevant laws involved with a space at the bottom of the letter for the sales person to acknowledge receipt of the letter and indicate that there was no visible damage to the car when the vehicle was returned. I printed two copies of the letter, one for them to keep, and one for me to keep with the signed acknowledgement of receipt. As expected, they asked me to meet with the finance manager who told me that I wouldn't be able to return the car. I thanked him for meeting with me and told him that I would be happy to meet in court if I didn't receive a check within 7 days. (That was his obligation under the local laws that applied.)",
"title": ""
},
{
"docid": "92938",
"text": "gnasher729's answer is fundamentally correct and deserves the checkmark, but I'd like to give an economic explanation for how this economically functions. The key point from gnasher729's answer's that the interest rate is 49.9% for one company. While this may be much higher than the equilibrium rate, the true market interest rate, it is not completely unreasonable because of the risk. For credit to be continually produced, default risk must be compensated because this is a cost to the lender. Most are not in business to lose money, so making loans to borrowers that default 40% of the time would make this interest rate reasonable. For UK citizens, this would not be such a problem because the lender can usually pursue the borrower for the balance, but if the borrower can disavow the loan and leave the legal reach of the UK creditors, the collection rate is 0%. The guarantee by the foreign persons not present in the UK is incidental and probably more of a regulatory requirement since the inability to collect from them is just as unlikely. One should always look for the lowest price with at least minimum quality when shopping for anything, but you are right to be apprehensive legally. Read every line and be sure that you yourself understand every clause before signing. If alternative cheaper financing is available, it is probably superior.",
"title": ""
},
{
"docid": "14219",
"text": "\"Consumer facing finance is heavily regulated. You are liable for the recommendations you make; if they are based on a black box you risk problems when sued. It is difficult to explain in a court of law why a neural network came to a particular conclusion. It is much easier to provide advice (models) in the \"\"educated counterparty\"\" market. Not only do institutional investors in general expect to pay for a quality advice (consumers in general expect to get online advice for free) but the legal implications are different.\"",
"title": ""
},
{
"docid": "547302",
"text": "\"My teacher always says the property interest the beneficiary \"\"holds\"\" or \"\"possesses\"\" is an equitable interest. I might just seem out of place here because it's a legal term and probably not commonplace outside that sphere. But the beneficiaries equitable interest is possessed or held in that regard. From this equitable interest is the income stream. If that just seems like a bunch of gibberish to you than don't mind me, just trying to learn the ins and outs of trusts not the world of finance generally.\"",
"title": ""
},
{
"docid": "228992",
"text": "Its participating preferred with a 1x liquidation preference. Very unfriendly for the company owner. Most startups these days are seeded with convertible notes because there's less thinking about the valuation of the company; that question is booted to the series A. its also easier to draw up the legal docs; pretty much a standard loan agreement. Finally, it can be far friendlier for the owner depending on if the note is an uncapped note. This is expensive financing and your friend can definitely find cheaper money if he looks for it.",
"title": ""
}
] |
897
|
Overexpressing Cnp1 N-tail variants rescues the temperature-sensitive growth defect of scm3-139.
|
[
{
"docid": "14338915",
"text": "The mechanisms ensuring specific incorporation of CENP-A at centromeres are poorly understood. Mis16 and Mis18 are required for CENP-A localization at centromeres and form a complex that is conserved from fission yeast to human. Fission yeast sim1 mutants that alleviate kinetochore domain silencing are defective in Scm3(Sp), the ortholog of budding yeast Scm3(Sc). Scm3(Sp) depends on Mis16/18 for its centromere localization and like them is recruited to centromeres in late anaphase. Importantly, Scm3(Sp) coaffinity purifies with CENP-A(Cnp1) and associates with CENP-A(Cnp1) in vitro, yet localizes independently of intact CENP-A(Cnp1) chromatin and is differentially released from chromatin. While Scm3(Sc) has been proposed to form a unique hexameric nucleosome with CENP-A(Cse4) and histone H4 at budding yeast point centromeres, we favor a model in which Scm3(Sp) acts as a CENP-A(Cnp1) receptor/assembly factor, cooperating with Mis16 and Mis18 to receive CENP-A(Cnp1) from the Sim3 escort and mediate assembly of CENP-A(Cnp1) into subkinetochore chromatin.",
"title": "Fission Yeast Scm3: A CENP-A Receptor Required for Integrity of Subkinetochore Chromatin"
}
] |
[
{
"docid": "10189634",
"text": "CENP-A chromatin forms the foundation for kinetochore assembly. Replication-independent incorporation of CENP-A at centromeres depends on its chaperone HJURP(Scm3), and Mis18 in vertebrates and fission yeast. The recruitment of Mis18 and HJURP(Scm3) to centromeres is cell cycle regulated. Vertebrate Mis18 associates with Mis18BP1(KNL2), which is critical for the recruitment of Mis18 and HJURP(Scm3). We identify two novel fission yeast Mis18-interacting proteins (Eic1 and Eic2), components of the Mis18 complex. Eic1 is essential to maintain Cnp1(CENP-A) at centromeres and is crucial for kinetochore integrity; Eic2 is dispensable. Eic1 also associates with Fta7(CENP-Q/Okp1), Cnl2(Nkp2) and Mal2(CENP-O/Mcm21), components of the constitutive CCAN/Mis6/Ctf19 complex. No Mis18BP1(KNL2) orthologue has been identified in fission yeast, consequently it remains unknown how the key Cnp1(CENP-A) loading factor Mis18 is recruited. Our findings suggest that Eic1 serves a function analogous to that of Mis18BP1(KNL2), thus representing the functional counterpart of Mis18BP1(KNL2) in fission yeast that connects with a module within the CCAN/Mis6/Ctf19 complex to allow the temporally regulated recruitment of the Mis18/Scm3(HJURP) Cnp1(CENP-A) loading factors. The novel interactions identified between CENP-A loading factors and the CCAN/Mis6/Ctf19 complex are likely to also contribute to CENP-A maintenance in other organisms.",
"title": "Eic1 links Mis18 with the CCAN/Mis6/Ctf19 complex to promote CENP-A assembly"
},
{
"docid": "16686383",
"text": "The centromeric histone H3 variant (CenH3) is essential for chromosome segregation in eukaryotes. We identify posttranslational modifications of Saccharomyces cerevisiae CenH3, Cse4. Functional characterization of cse4 phosphorylation mutants shows growth and chromosome segregation defects when combined with kinetochore mutants okp1 and ame1. Using a phosphoserine-specific antibody, we show that the association of phosphorylated Cse4 with centromeres increases in response to defective microtubule attachment or reduced cohesion. We determine that evolutionarily conserved Ipl1/Aurora B contributes to phosphorylation of Cse4, as levels of phosphorylated Cse4 are reduced at centromeres in ipl1 strains in vivo, and in vitro assays show phosphorylation of Cse4 by Ipl1. Consistent with these results, we observe that a phosphomimetic cse4-4SD mutant suppresses the temperature-sensitive growth of ipl1-2 and Ipl1 substrate mutants dam1 spc34 and ndc80, which are defective for chromosome biorientation. Furthermore, cell biology approaches using a green fluorescent protein-labeled chromosome show that cse4-4SD suppresses chromosome segregation defects in dam1 spc34 strains. On the basis of these results, we propose that phosphorylation of Cse4 destabilizes defective kinetochores to promote biorientation and ensure faithful chromosome segregation. Taken together, our results provide a detailed analysis, in vivo and in vitro, of Cse4 phosphorylation and its role in promoting faithful chromosome segregation.",
"title": "Phosphorylation of centromeric histone H3 variant regulates chromosome segregation in Saccharomyces cerevisiae"
},
{
"docid": "21425864",
"text": "Glycosyl phosphatidylinositols (GPIs) anchor many proteins to the surface of eukaryotic cells and may also serve as sorting signals on proteins and participate in signal transduction. We have isolated a Saccharomyces cerevisiae GPI anchoring mutant, gpi1, using a colony screen for cells blocked in [3H]inositol incorporation into protein. The gpi1 mutant is defective in vitro in the synthesis of N-acetylglucosaminyl phosphatidylinositol, the first intermediate in GPI synthesis, and is also temperature-sensitive for growth. Completion of the first step in GPI assembly is therefore required for growth of the unicellular eukaryote S. cerevisiae. GPI synthesis could therefore be exploited as a target for antifungal or antiparasitic agents.",
"title": "A conditionally lethal yeast mutant blocked at the first step in glycosyl phosphatidylinositol anchor synthesis."
},
{
"docid": "26117607",
"text": "Down syndrome cell adhesion molecule (Dscam) seems likely to play a key role in the \"alternative adaptive immunity\" that has been reported in invertebrates. Dscam consists of a cytoplasmic tail that is involved in signal transduction and a hypervariable extracellular region that might use a pathogen recognition mechanism similar to that used by the vertebrate antibodies. In our previous paper, we isolated a unique tail-less form of Dscam from Litopenaeus vannamei. In this study, we report the first membrane-bound form of shrimp Dscam: PmDscam was isolated from Penaeus monodon, and it occurred in both membrane-bound and tail-less forms. Phylogenetic analysis showed that while the crustacean Dscams from shrimp and water flea did not share a single subclade, they were distinct from the invertebrate Dscam-like molecules and from the insecta Dscams. In the extracellular region, the variable regions of PmDscam were located in N-terminal Ig2, N-terminal Ig3 and the entire Ig7 domain. The PmDscam extracellular variants and transmembrane domain variants were produced by mutually exclusive alternative splicing events. The cytoplasmic tail variants were produced by exon inclusion/exclusion. Based on the genomic organization of Daphnia Dscam's cytoplasmic tail, we propose a model of how the shrimp Dscam genomic locus might use Type III polyadenylation to generate both the tail-less and membrane-bound forms.",
"title": "Penaeus monodon Dscam (PmDscam) has a highly diverse cytoplasmic tail and is the first membrane-bound shrimp Dscam to be reported."
},
{
"docid": "18676539",
"text": "FANCM is a component of the Fanconi anemia (FA) core complex and one FA patient (EUFA867) with biallelic mutations in FANCM has been described. Strikingly, we found that EUFA867 also carries biallelic mutations in FANCA. After correcting the FANCA defect in EUFA867 lymphoblasts, a \"clean\" FA-M cell line was generated. These cells were hypersensitive to mitomycin C, but unlike cells defective in other core complex members, FANCM(-/-) cells were proficient in monoubiquitinating FANCD2 and were sensitive to the topoisomerase inhibitor camptothecin, a feature shared only with the FA subtype D1 and N. In addition, FANCM(-/-) cells were sensitive to UV light. FANCM and a C-terminal deletion mutant rescued the cross-linker sensitivity of FANCM(-/-) cells, whereas a FANCM ATPase mutant did not. Because both mutants restored the formation of FANCD2 foci, we conclude that FANCM functions in an FA core complex-dependent and -independent manner.",
"title": "Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M."
},
{
"docid": "57574395",
"text": "Defective brain hormonal signaling has been associated with Alzheimer's disease (AD), a disorder characterized by synapse and memory failure. Irisin is an exercise-induced myokine released on cleavage of the membrane-bound precursor protein fibronectin type III domain-containing protein 5 (FNDC5), also expressed in the hippocampus. Here we show that FNDC5/irisin levels are reduced in AD hippocampi and cerebrospinal fluid, and in experimental AD models. Knockdown of brain FNDC5/irisin impairs long-term potentiation and novel object recognition memory in mice. Conversely, boosting brain levels of FNDC5/irisin rescues synaptic plasticity and memory in AD mouse models. Peripheral overexpression of FNDC5/irisin rescues memory impairment, whereas blockade of either peripheral or brain FNDC5/irisin attenuates the neuroprotective actions of physical exercise on synaptic plasticity and memory in AD mice. By showing that FNDC5/irisin is an important mediator of the beneficial effects of exercise in AD models, our findings place FNDC5/irisin as a novel agent capable of opposing synapse failure and memory impairment in AD.",
"title": "Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models"
},
{
"docid": "17671145",
"text": "The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptor-related orphan receptor γ (ROR-γ) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-γ drives AR expression in the tumors. ROR-γ recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an AR-ROR response element (RORE) to stimulate AR gene transcription. ROR-γ antagonists suppress the expression of both AR and its variant AR-V7 in prostate cancer (PCa) cell lines and tumors. ROR-γ antagonists also markedly diminish genome-wide AR binding, H3K27ac abundance and expression of the AR target gene network. Finally, ROR-γ antagonists suppressed tumor growth in multiple AR-expressing, but not AR-negative, xenograft PCa models, and they effectively sensitized CRPC tumors to enzalutamide, without overt toxicity, in mice. Taken together, these results establish ROR-γ as a key player in CRPC by acting upstream of AR and as a potential therapeutic target for advanced PCa.",
"title": "ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer"
},
{
"docid": "4312169",
"text": "Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (α-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.",
"title": "Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma"
},
{
"docid": "13293033",
"text": "Down syndrome (DS) is the most frequent cause of human congenital mental retardation. Cognitive deficits in DS result from perturbations of normal cellular processes both during development and in adult tissues, but the mechanisms underlying DS etiology remain poorly understood. To assess the ability of induced pluripotent stem cells (iPSCs) to model DS phenotypes, as a prototypical complex human disease, we generated bona fide DS and wild-type (WT) nonviral iPSCs by episomal reprogramming. DS iPSCs selectively overexpressed chromosome 21 genes, consistent with gene dosage, which was associated with deregulation of thousands of genes throughout the genome. DS and WT iPSCs were neurally converted at >95% efficiency and had remarkably similar lineage potency, differentiation kinetics, proliferation, and axon extension at early time points. However, at later time points DS cultures showed a twofold bias toward glial lineages. Moreover, DS neural cultures were up to two times more sensitive to oxidative stress-induced apoptosis, and this could be prevented by the antioxidant N-acetylcysteine. Our results reveal a striking complexity in the genetic alterations caused by trisomy 21 that are likely to underlie DS developmental phenotypes, and indicate a central role for defective early glial development in establishing developmental defects in DS brains. Furthermore, oxidative stress sensitivity is likely to contribute to the accelerated neurodegeneration seen in DS, and we provide proof of concept for screening corrective therapeutics using DS iPSCs and their derivatives. Nonviral DS iPSCs can therefore model features of complex human disease in vitro and provide a renewable and ethically unencumbered discovery platform.",
"title": "Integration-free induced pluripotent stem cells model genetic and neural developmental features of down syndrome etiology."
},
{
"docid": "30675656",
"text": "Frizzled family proteins have been described as receptors of Wnt signaling molecules. In Drosophila, the two known Frizzled proteins are associated with distinct developmental processes. Genesis of epithelial planar polarity requires Frizzled, whereas Dfz2 affects morphogenesis by wingless-mediated signaling. Dishevelled is required in both signaling pathways. Here, we use genetic and overexpression assays to show that Dishevelled activates JNK cascades. Rescue analysis reveals different protein domain requirements in Dishevelled for the two pathways; the C-terminal DEP domain is essential to rescue planar polarity defects and induce JNK signaling. Furthermore, the planar polarity-specific dsh1 allele is mutated in the DEP domain. Our results indicate that different Wnt/Fz signals activate distinct intracellular pathways, and Dishevelled discriminates among them by distinct domain interactions.",
"title": "Dishevelled Activates JNK and Discriminates between JNK Pathways in Planar Polarity and wingless Signaling"
},
{
"docid": "2356950",
"text": "Methyl-CpG binding protein 1 (MBD1) regulates gene expression via a DNA methylation-mediated epigenetic mechanism. We have previously demonstrated that MBD1 deficiency impairs adult neural stem/progenitor cell (aNSC) differentiation and neurogenesis, but the underlying mechanism was unclear. Here, we show that MBD1 regulates the expression of several microRNAs in aNSCs and, specifically, that miR-184 is directly repressed by MBD1. High levels of miR-184 promoted proliferation but inhibited differentiation of aNSCs, whereas inhibition of miR-184 rescued the phenotypes associated with MBD1 deficiency. We further found that miR-184 regulates the expression of Numblike (Numbl), a known regulator of brain development, by binding to the 3'-UTR of Numbl mRNA and affecting its translation. Expression of exogenous Numbl could rescue the aNSC defects that result from either miR-184 overexpression or MBD1 deficiency. Therefore, MBD1, miR-184, and Numbl form a regulatory network that helps control the balance between proliferation and differentiation of aNSCs.",
"title": "Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation."
},
{
"docid": "23160444",
"text": "Neuronal growth cones move forward by dynamically connecting actin-based motility to substrate adhesion, but the mechanisms at the individual molecular level remain unclear. We cultured primary neurons on N-cadherin-coated micropatterned substrates, and imaged adhesion and cytoskeletal proteins at the ventral surface of growth cones using single particle tracking combined to photoactivated localization microscopy (sptPALM). We demonstrate transient interactions in the second time scale between flowing actin filaments and immobilized N-cadherin/catenin complexes, translating into a local reduction of the actin retrograde flow. Normal actin flow on micropatterns was rescued by expression of a dominant negative N-cadherin construct competing for the coupling between actin and endogenous N-cadherin. Fluorescence recovery after photobleaching (FRAP) experiments confirmed the differential kinetics of actin and N-cadherin, and further revealed a 20% actin population confined at N-cadherin micropatterns, contributing to local actin accumulation. Computer simulations with relevant kinetic parameters modeled N-cadherin and actin turnover well, validating this mechanism. Such a combination of short- and long-lived interactions between the motile actin network and spatially restricted adhesive complexes represents a two-tiered clutch mechanism likely to sustain dynamic environment sensing and provide the force necessary for growth cone migration.",
"title": "Two-tiered coupling between flowing actin and immobilized N-cadherin/catenin complexes in neuronal growth cones."
},
{
"docid": "7717468",
"text": "Microbial survival in a host is usually dependent on the ability of a pathogen to undergo changes that promote escape from host defense mechanisms. The human-pathogenic fungus Cryptococcus neoformans undergoes phenotypic switching in vivo that promotes persistence in tissue. By microarray and real-time PCR analyses, the allergen 1 gene (ALL1) was found to be downregulated in the hypervirulent mucoid switch variant, both during logarithmic growth and during intracellular growth in macrophages. The ALL1 gene encodes a small cytoplasmic protein that is involved in capsule formation. Growth of an all1Delta gene deletion mutant was normal. Similar to cells of the mucoid switch variant, all1Delta cells produced a larger polysaccharide capsule than cells of the smooth parent and the complemented strain produced, and the enlarged capsule inhibited macrophage phagocytosis. The mutant exhibited a modest defect in capsule induction compared to all of the other variants. In animal models the phenotype of the all1Delta mutant mimicked the hypervirulent phenotype of the mucoid switch variant, which is characterized by decreased host survival and elevated intracranial pressure. Decreased survival is likely the result of both an ineffective cell-mediated immune response and impaired phagocytosis by macrophages. Consequently, we concluded that, unlike loss of most virulence-associated genes, where loss of gene function results in attenuated virulence, loss of the ALL1 gene enhances virulence by altering the host-pathogen interaction and thereby impairing clearance. Our data identified the first cryptococcal gene associated with elevated intracranial pressure and support the hypothesis that an environmental opportunistic pathogen has modified its virulence in vivo by epigenetic downregulation of gene function.",
"title": "Loss of allergen 1 confers a hypervirulent phenotype that resembles mucoid switch variants of Cryptococcus neoformans."
},
{
"docid": "14471161",
"text": "Circadian disruption accelerates cancer progression, whereas circadian reinforcement could halt it. Mice with P03 pancreatic adenocarcinoma (n = 77) were synchronized and fed ad libitum (AL) or with meal timing (MT) from Zeitgeber time (ZT) 2 to ZT6 with normal or fat diet. Tumor gene expression profiling was determined with DNA microarrays at endogenous circadian time (CT) 4 and CT16. Circadian mRNA expression patterns were determined for clock genes Rev-erbalpha, Per2, and Bmal1, cellular stress genes Hspa8 and Cirbp, and cyclin A2 gene Ccna2 in liver and tumor. The 24-hour patterns in telemetered rest-activity and body temperature and plasma corticosterone and insulin-like growth factor-I (IGF-I) were assessed. We showed that MT inhibited cancer growth by approximately 40% as compared with AL (P = 0.011) irrespective of calorie intake. Clock gene transcription remained arrhythmic in tumors irrespective of feeding schedule or diet. Yet, MT upregulated or downregulated the expression of 423 tumor genes, according to CT. Moreover, 36 genes involved in cellular stress, cell cycle, and metabolism were upregulated at one CT and downregulated 12 h apart. MT induced >10-fold circadian expression of Hspa8, Cirbp, and Ccna2 in tumors. Corticosterone or IGF-I patterns played no role in tumor growth inhibition. In contrast, MT consistently doubled the circadian amplitude of body temperature. Peak and trough respectively corresponded to peak expressions of Hspa8 and Cirbp in tumors. The reinforcement of the host circadian timing system with MT induced 24-hour rhythmic expression of critical genes in clock-deficient tumors, which translated into cancer growth inhibition. Targeting circadian clocks represents a novel potential challenge for cancer therapeutics.",
"title": "Cancer inhibition through circadian reprogramming of tumor transcriptome with meal timing."
},
{
"docid": "23117928",
"text": "Infection of Sulfolobus islandicus REY15A with mixtures of different Sulfolobus viruses, including STSV2, did not induce spacer acquisition by the host CRISPR immune system. However, coinfection with the tailed fusiform viruses SMV1 and STSV2 generated hyperactive spacer acquisition in both CRISPR loci, exclusively from STSV2, with the resultant loss of STSV2 but not SMV1. SMV1 was shown to activate adaptation while itself being resistant to CRISPR-mediated adaptation and DNA interference. Exceptionally, a single clone S-1 isolated from an SMV1 + STSV2-infected culture, that carried STSV2-specific spacers and had lost STSV2 but not SMV1, acquired spacers from SMV1. This effect was also reproducible on reinfecting wild-type host cells with a variant SMV1 isolated from the S-1 culture. The SMV1 variant lacked a virion protein ORF114 that was shown to bind DNA. This study also provided evidence for: (i) limits on the maximum sizes of CRISPR loci; (ii) spacer uptake strongly retarding growth of infected cultures; (iii) protospacer selection being essentially random and non-directional, and (iv) the reversible uptake of spacers from STSV2 and SMV1. A hypothesis is presented to explain the interactive conflicts between SMV1 and the host CRISPR immune system.",
"title": "Inter-viral conflicts that exploit host CRISPR immune systems of Sulfolobus."
},
{
"docid": "26625002",
"text": "The outer membrane channel TolC is a key component of multidrug efflux and type I secretion transporters in Escherichia coli. Mutational inactivation of TolC renders cells highly susceptible to antibiotics and leads to defects in secretion of protein toxins. Despite impairment of various transport functions, no growth defects were reported in cells lacking TolC. Unexpectedly, we found that the loss of TolC notably impairs cell division and growth in minimal glucose medium. The TolC-dependent phenotype was further exacerbated by the loss of ygiB and ygiC genes expressed in the same operon as tolC and their homologues yjfM and yjfC located elsewhere on the chromosome. Our results show that this growth deficiency is caused by depletion of the critical metabolite NAD(+) and high NADH/NAD(+) ratios. The increased amounts of PspA and decreased rates of NADH oxidation in Delta tolC membranes indicated stress on the membrane and dissipation of a proton motive force. We conclude that inactivation of TolC triggers metabolic shutdown in E. coli cells grown in minimal glucose medium. The Delta tolC phenotype is partially rescued by YgiBC and YjfMC, which have parallel functions independent from TolC.",
"title": "Metabolic shutdown in Escherichia coli cells lacking the outer membrane channel TolC."
},
{
"docid": "24725136",
"text": "BACKGROUND The combination of ataxia and hypogonadism was first described more than a century ago, but its genetic basis has remained elusive. METHODS We performed whole-exome sequencing in a patient with ataxia and hypogonadotropic hypogonadism, followed by targeted sequencing of candidate genes in similarly affected patients. Neurologic and reproductive endocrine phenotypes were characterized in detail. The effects of sequence variants and the presence of an epistatic interaction were tested in a zebrafish model. RESULTS Digenic homozygous mutations in RNF216 and OTUD4, which encode a ubiquitin E3 ligase and a deubiquitinase, respectively, were found in three affected siblings in a consanguineous family. Additional screening identified compound heterozygous truncating mutations in RNF216 in an unrelated patient and single heterozygous deleterious mutations in four other patients. Knockdown of rnf216 or otud4 in zebrafish embryos induced defects in the eye, optic tectum, and cerebellum; combinatorial suppression of both genes exacerbated these phenotypes, which were rescued by nonmutant, but not mutant, human RNF216 or OTUD4 messenger RNA. All patients had progressive ataxia and dementia. Neuronal loss was observed in cerebellar pathways and the hippocampus; surviving hippocampal neurons contained ubiquitin-immunoreactive intranuclear inclusions. Defects were detected at the hypothalamic and pituitary levels of the reproductive endocrine axis. CONCLUSIONS The syndrome of hypogonadotropic hypogonadism, ataxia, and dementia can be caused by inactivating mutations in RNF216 or by the combination of mutations in RNF216 and OTUD4. These findings link disordered ubiquitination to neurodegeneration and reproductive dysfunction and highlight the power of whole-exome sequencing in combination with functional studies to unveil genetic interactions that cause disease. (Funded by the National Institutes of Health and others.).",
"title": "Ataxia, dementia, and hypogonadotropism caused by disordered ubiquitination."
},
{
"docid": "6766459",
"text": "Fever is commonly used to diagnose disease and is consistently associated with increased mortality in critically ill patients. However, the molecular controls of elevated body temperature are poorly understood. We discovered that the expression of RNA-binding motif protein 3 (RBM3), known to respond to cold stress and to modulate microRNA (miRNA) expression, was reduced in 30 patients with fever, and in THP-1-derived macrophages maintained at a fever-like temperature (40 °C). Notably, RBM3 expression is reduced during fever whether or not infection is demonstrable. Reduced RBM3 expression resulted in increased expression of RBM3-targeted temperature-sensitive miRNAs, we termed thermomiRs. ThermomiRs such as miR-142-5p and miR-143 in turn target endogenous pyrogens including IL-6, IL6ST, TLR2, PGE2 and TNF to complete a negative feedback mechanism, which may be crucial to prevent pathological hyperthermia. Using normal PBMCs that were exogenously exposed to fever-like temperature (40 °C), we further demonstrate the trend by which decreased levels of RBM3 were associated with increased levels of miR-142-5p and miR-143 and vice versa over a 24 h time course. Collectively, our results indicate the existence of a negative feedback loop that regulates fever via reduced RBM3 levels and increased expression of miR-142-5p and miR-143.",
"title": "RBM3 regulates temperature sensitive miR-142–5p and miR-143 (thermomiRs), which target immune genes and control fever"
},
{
"docid": "26596106",
"text": "In the yeast S. cerevisiae, ribosome assembly is linked to environmental conditions by the coordinate transcriptional regulation of genes required for ribosome biogenesis. In this study we show that two nonessential stress-responsive genes, YAR1 and LTV1, function in 40S subunit production. We provide genetic and biochemical evidence that Yar1, a small ankyrin-repeat protein, physically interacts with RpS3, a component of the 40S subunit, and with Ltv1, a protein recently identified as a substoichiometric component of a 43S preribosomal particle. We demonstrate that cells lacking YAR1 or LTV1 are hypersensitive to particular protein synthesis inhibitors and exhibit aberrant polysome profiles, with a reduced absolute number of 40S subunits and an excess of free 60S subunits. Surprisingly, both mutants are also hypersensitive to a variety of environmental stress conditions. Overexpression of RPS3 suppresses both the stress sensitivity and the ribosome biogenesis defect of Deltayar1 mutants, but does not suppress either defect in Deltaltv1 mutants. We propose that YAR1 and LTV1 play distinct, nonessential roles in 40S subunit production. The stress-sensitive phenotypes of strains lacking these genes reveal a hitherto unknown link between ribosome biogenesis factors and environmental stress sensitivity.",
"title": "Genetic and biochemical interactions among Yar1, Ltv1 and Rps3 define novel links between environmental stress and ribosome biogenesis in Saccharomyces cerevisiae."
},
{
"docid": "34016944",
"text": "PURPOSE Tyrosine kinase (TK) inhibitors are emerging as a promising new approach to the treatment of HER overexpressing tumors, however optimal use of these agents awaits further definition of the downstream signaling pathways that mediate their effects. We reported previously that both EGFR- and Her2-overexpressing tumors are sensitive to the new EGFR-selective TK inhibitor gefitinib (ZD1839, \"Iressa\"), and sensitivity to this agent correlated with its ability to down-regulate Akt. However, EGFR-overexpressing MDA-468 cells, which lack PTEN function, are resistant to ZD1839, and ZD1839 is unable to down-regulate Akt activity in these cells. EXPERIMENTAL DESIGN To study the role of PTEN function, we generated MDA468 cells with tet-inducible PTEN expression. RESULTS We show here that the resistance of MDA-468 cells to ZD1839 is attributable to EGFR-independent constitutive Akt activation caused by loss of PTEN function in these cells. Reconstitution of PTEN function through tet-inducible expression restores ZD1839 sensitivity to these cells and reestablishes EGFR-stimulated Akt signaling. Although restoration of PTEN function to tumors is difficult to implement clinically, much of the effects of PTEN loss are attributable to overactive PI3K/Akt pathway signaling, and this overactivity can be modulated by pharmacologic approaches. We show here that pharmacologic down-regulation of constitutive PI3K/Akt pathway signaling using the PI3K inhibitor LY294002 similarly restores EGFR-stimulated Akt signaling and sensitizes MDA-468 cells to ZD1839. CONCLUSIONS Sensitivity to ZD1839 requires intact growth factor receptor-stimulated Akt signaling activity. PTEN loss leads to uncoupling of this signaling pathway and results in ZD1839 resistance, which can be reversed with reintroduction of PTEN or pharmacologic down-regulation of constitutive PI3K/Akt pathway activity. These data have important predictive and therapeutic clinical implications.",
"title": "Resistance to gefitinib in PTEN-null HER-overexpressing tumor cells can be overcome through restoration of PTEN function or pharmacologic modulation of constitutive phosphatidylinositol 3'-kinase/Akt pathway signaling."
},
{
"docid": "22362025",
"text": "Small regulatory RNAs are key regulators of gene expression. One class of small regulatory RNAs, termed the endogenous small interfering RNAs (endo siRNAs), is thought to negatively regulate cellular transcripts via an RNA interference (RNAi)-like mechanism termed endogenous RNAi (endo RNAi). A complex of proteins composed of ERI-1/3/5, RRF-3, and DICER (the ERI/DICER complex) mediates endo RNAi processes in Caenorhabditis elegans. We conducted a genetic screen to identify additional components of the endo RNAi machinery. Our screen recovered alleles of eri-9, which encodes a novel DICER-interacting protein, and a missense mutation within the helicase domain of DICER [DCR-1(G492R)]. ERI-9(-) and DCR-1(G492) animals exhibit defects in endo siRNA expression and a concomitant failure to regulate mRNAs that exhibit sequence homology to these endo siRNAs, indicating that ERI-9 and the DCR-1 helicase domain function in the C. elegans endo RNAi pathway. We define a subset of Eri mutant animals (including eri-1, rrf-3, eri-3, and dcr-1, but not eri-9 or ergo-1) that exhibit temperature-sensitive, sperm-specific sterility and defects in X chromosome segregation. Among these mutants we find multiple aberrations in sperm development beginning with cytokinesis and extending through terminal differentiation. These results identify novel components of the endo RNAi machinery, demonstrate differential requirements for the Eri factors in the sperm-producing germline, and begin to delineate the functional requirement for the ERI/DICER complex in sperm development.",
"title": "Requirement for the ERI/DICER complex in endogenous RNA interference and sperm development in Caenorhabditis elegans."
},
{
"docid": "10169908",
"text": "PURPOSE We have previously identified solute-linked carrier family A1 member 5 (SLC1A5) as an overexpressed protein in a shotgun proteomic analysis of stage I non-small cell lung cancer (NSCLC) when compared with matched controls. We hypothesized that overexpression of SLC1A5 occurs to meet the metabolic demand for lung cancer cell growth and survival. EXPERIMENTAL DESIGN To test our hypothesis, we first analyzed the protein expression of SLC1A5 in archival lung cancer tissues by immunohistochemistry and immunoblotting (N = 98) and in cell lines (N = 36). To examine SLC1A5 involvement in amino acid transportation, we conducted kinetic analysis of l-glutamine (Gln) uptake in lung cancer cell lines in the presence and absence of a pharmacologic inhibitor of SLC1A5, gamma-l-Glutamyl-p-Nitroanilide (GPNA). Finally, we examined the effect of Gln deprivation and uptake inhibition on cell growth, cell-cycle progression, and growth signaling pathways of five lung cancer cell lines. RESULTS Our results show that (i) SLC1A5 protein is expressed in 95% of squamous cell carcinomas (SCC), 74% of adenocarcinomas (ADC), and 50% of neuroendocrine tumors; (ii) SLC1A5 is located at the cytoplasmic membrane and is significantly associated with SCC histology and male gender; (iii) 68% of Gln is transported in a Na(+)-dependent manner, 50% of which is attributed to SLC1A5 activity; and (iv) pharmacologic and genetic targeting of SLC1A5 decreased cell growth and viability in lung cancer cells, an effect mediated in part by mTOR signaling. CONCLUSIONS These results suggest that SLC1A5 plays a key role in Gln transport controlling lung cancer cells' metabolism, growth, and survival.",
"title": "SLC1A5 mediates glutamine transport required for lung cancer cell growth and survival."
},
{
"docid": "12948892",
"text": "Evidence has been accumulated that glioblastoma cells release and exploit glutamate for proliferation and migration by autocrine or paracrine loops through Ca2+-permeable AMPA-type glutamate receptors. Here, we show that Ca2+ signaling mediated by AMPA receptor regulates the growth and motility of glioblastoma cells via activation of Akt. Ca2+ supplied through Ca2+-permeable AMPA receptor phosphorylated Akt at Ser-473, thereby facilitating proliferation and mobility. A dominant-negative form of Akt inhibited cell proliferation and migration accelerated by overexpression of Ca2+-permeable AMPA receptor. In contrast, introduction of a constitutively active form of Akt rescued tumor cells from apoptosis induced by the conversion of Ca2+-permeable AMPA receptor to Ca2+-impermeable receptors by the delivery of GluR2 cDNA. Therefore, Akt functions as downstream effectors for Ca2+-signaling mediated by AMPA receptor in glioblastoma cells. The activation of the glutamate-AMPA receptor-Akt pathway may contribute to the high degree of anaplasia and invasive growth of human glioblastoma. This novel pathway might give an alternative therapeutic target.",
"title": "Ca2+-permeable AMPA receptors regulate growth of human glioblastoma via Akt activation."
},
{
"docid": "22522432",
"text": "The stable contact of ISW2 with nucleosomal DNA approximately 20 bp from the dyad was shown by DNA footprinting and photoaffinity labeling using recombinant histone octamers to require the histone H4 N-terminal tail. Efficient ISW2 remodeling also required the H4 N-terminal tail, although the lack of the H4 tail can be mostly compensated for by increasing the incubation time or concentration of ISW2. Similarly, the length of extranucleosomal DNA affected the stable contact of ISW2 with this same internal nucleosomal site, with the optimal length being 70 to 85 bp. These data indicate the histone H4 tail, in concert with a favorable length of extranucleosomal DNA, recruits and properly orients ISW2 onto the nucleosome for efficient nucleosome remodeling. One consequence of this property of ISW2 is likely its previously observed nucleosome spacing activity.",
"title": "Regulation of ISW2 by concerted action of histone H4 tail and extranucleosomal DNA."
},
{
"docid": "12225214",
"text": "Ubiquitination controls a broad range of cellular functions. The last step of the ubiquitination pathway is regulated by enzyme type 3 (E3) ubiquitin ligases. E3 enzymes are responsible for substrate specificity and catalyze the formation of an isopeptide bond between a lysine residue of the substrate (or the N terminus of the substrate) and ubiquitin. MIR1 and MIR2 are two E3 ubiquitin ligases encoded by Kaposi's sarcoma-associated herpesvirus that mediate the ubiquitination of major histocompatibility complex class I (MHC I) molecules and subsequent internalization. Here, we found that MIR1, but not MIR2, promoted down-regulation of MHC I molecules lacking lysine residues in their intracytoplasmic domain. In the presence of MIR1, these MHC I molecules were ubiquitinated, and their association with ubiquitin was sensitive to beta2-mercaptoethanol, unlike lysine-ubiquitin bonds. This form of ubiquitination required a cysteine residue in the intracytoplasmic tail of MHC I molecules. An MHC I molecule containing a single cysteine residue in an artificial glycine and alanine intracytoplasmic domain was endocytosed and degraded in the presence of MIR1. Thus, ubiquitination can occur on proteins lacking accessible lysines or an accessible N terminus.",
"title": "Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase."
},
{
"docid": "3127341",
"text": "The glucagon-like peptide-1 receptor (GLP-1R) is a key physiological regulator of insulin secretion and a major therapeutic target for the treatment of type II diabetes. However, regulation of GLP-1R function is complex with multiple endogenous peptides that interact with the receptor, including full-length (1-37) and truncated (7-37) forms of GLP-1 that can exist in an amidated form (GLP-1(1-36)NH₂ and GLP-1(7-36)NH₂) and the related peptide oxyntomodulin. In addition, the GLP-1R possesses exogenous agonists, including exendin-4, and the allosteric modulator, compound 2 (6,7-dichloro-2-methylsulfonyl-3-tert-butylaminoquinoxaline). The complexity of this ligand-receptor system is further increased by the presence of several single nucleotide polymorphisms (SNPs) that are distributed across the receptor. We have investigated 10 GLP-1R SNPs, which were characterized in three physiologically relevant signaling pathways (cAMP accumulation, extracellular signal-regulated kinase 1/2 phosphorylation, and intracellular Ca²⁺ mobilization); ligand binding and cell surface receptor expression were also determined. We demonstrate both ligand- and pathway-specific effects for multiple SNPs, with the most dramatic effect observed for the Met¹⁴⁹ receptor variant. At the Met¹⁴⁹ variant, there was selective loss of peptide-induced responses across all pathways examined, but preservation of response to the small molecule compound 2. In contrast, at the Cys³³³ variant, peptide responses were preserved but there was attenuated response to compound 2. Strikingly, the loss of peptide function at the Met¹⁴⁹ receptor variant could be allosterically rescued by compound 2, providing proof-of-principle evidence that allosteric drugs could be used to treat patients with this loss of function variant.",
"title": "Polymorphism and ligand dependent changes in human glucagon-like peptide-1 receptor (GLP-1R) function: allosteric rescue of loss of function mutation."
},
{
"docid": "33076846",
"text": "Polyploidization can precede the development of aneuploidy in cancer. Polyploidization in megakaryocytes (Mks), in contrast, is a highly controlled developmental process critical for efficient platelet production via unknown mechanisms. Using primary cells, we demonstrate that the guanine exchange factors GEF-H1 and ECT2, which are often overexpressed in cancer and are essential for RhoA activation during cytokinesis, must be downregulated for Mk polyploidization. The first (2N-4N) endomitotic cycle requires GEF-H1 downregulation, whereas subsequent cycles (>4N) require ECT2 downregulation. Exogenous expression of both GEF-H1 and ECT2 prevents endomitosis, resulting in proliferation of 2N Mks. Furthermore, we have shown that the mechanism by which polyploidization is prevented in Mks lacking Mkl1, which is mutated in megakaryocytic leukemia, is via elevated GEF-H1 expression; shRNA-mediated GEF-H1 knockdown alone rescues this ploidy defect. These mechanistic insights enhance our understanding of normal versus malignant megakaryocytopoiesis, as well as aberrant mitosis in aneuploid cancers.",
"title": "Role of RhoA-specific guanine exchange factors in regulation of endomitosis in megakaryocytes."
},
{
"docid": "435529",
"text": "HEN1-mediated 2'-O-methylation has been shown to be a key mechanism to protect plant microRNAs (miRNAs) and small interfering RNAs (siRNAs) as well as animal piwi-interacting RNAs (piRNAs) from degradation and 3' terminal uridylation [1-8]. However, enzymes uridylating unmethylated miRNAs, siRNAs, or piRNAs in hen1 are unknown. In this study, a genetic screen identified a second-site mutation hen1 suppressor1-2 (heso1-2) that partially suppresses the morphological phenotypes of the hypomorphic hen1-2 allele and the null hen1-1 allele in Arabidopsis. HESO1 encodes a terminal nucleotidyl transferase that prefers to add untemplated uridine to the 3' end of RNA, which is completely abolished by 2'-O-methylation. heso1-2 affects the profile of u-tailed miRNAs and siRNAs and increases the abundance of truncated and/or normal sized ones in hen1, which often results in increased total amount of miRNAs and siRNAs in hen1. In contrast, overexpressing HESO1 in hen1-2 causes more severe morphological defects and less accumulation of miRNAs. These results demonstrate that HESO1 is an enzyme uridylating unmethylated miRNAs and siRNAs in hen1. These observations also suggest that uridylation may destabilize unmethylated miRNAs through an unknown mechanism and compete with 3'-to-5' exoribonuclease activities in hen1. This study shall have implications on piRNA uridylation in hen1 in animals.",
"title": "Uridylation of miRNAs by HEN1 SUPPRESSOR1 in Arabidopsis"
},
{
"docid": "4455466",
"text": "Recognition of modified histones by ‘reader’ proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific ‘Ser 31’ residue in a composite pocket formed by the tandem bromo–PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.",
"title": "ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression"
},
{
"docid": "519974",
"text": "Mammals detect temperature with specialized neurons in the peripheral nervous system. Four TRPV-class channels have been implicated in sensing heat, and one TRPM-class channel in sensing cold. The combined range of temperatures that activate these channels covers a majority of the relevant physiological spectrum sensed by most mammals, with a significant gap in the noxious cold range. Here, we describe the characterization of ANKTM1, a cold-activated channel with a lower activation temperature compared to the cold and menthol receptor, TRPM8. ANKTM1 is a distant family member of TRP channels with very little amino acid similarity to TRPM8. It is found in a subset of nociceptive sensory neurons where it is coexpressed with TRPV1/VR1 (the capsaicin/heat receptor) but not TRPM8. Consistent with the expression of ANKTM1, we identify noxious cold-sensitive sensory neurons that also respond to capsaicin but not to menthol.",
"title": "ANKTM1, a TRP-like Channel Expressed in Nociceptive Neurons, Is Activated by Cold Temperatures"
}
] |
5765
|
When does it make sense for the money paid for equity to go to the corporation?
|
[
{
"docid": "289656",
"text": "If Jack owns all of the one million founding shares (which I assume you meant), and wants to transfer 250,000 shares to Venturo, then he is just personally selling shares to Venturo and the corporation gains nothing. If Jack does not own all of the founding shares, and the corporation had retained some, then the corporate shares could be sold to raise cash for the corporation. Usually in situations like this, the corporation will create more shares, diluting existing shareholders, and then sell the new shares on the open market to raise cash.",
"title": ""
},
{
"docid": "2205",
"text": "If the check is written as a check to BigCo, it is less clear how Jack can compensate himself for the equity sale. It is as if the equity was owned by the corporation, not by Jack. This is correct. If the check is written to BigCo, then it is BigCo issuing new shares. Jack doesn't compensate himself for the equity sale, as he didn't sell anything. The company traded shares for money which it uses for expansion. In the long term, the capital gain from expansion may exceed the value of a $200,000 no-interest loan to the company. If the value of the company before investing $250,000 is $1 million, then the value after investing is $1.25 million. So $250,000 is 20% of the value of the company. BigCo should not give the buyer 25% of BigCo but only 20% in that example. If it does give 25%, the buyer is getting a $312,500 stake for only $250,000. With the other example, Jack sells 25% of the company for $250,000 from his personal shares. This doesn't change the assessed value of the company, just Jack's stake. Jack then loans the company $200,000. This also doesn't change the assessed value of the company (at least in theory). It gains $200,000 but has an offsetting debt of $200,000. In net, that's no change. Assets and liabilities balance the same. So if you know that the assessed value of the company is $1 million and that the buyer is paying $250,000 for a 25% stake at that same valuation, then you know that the check is being written to Jack. If the check is written to BigCo, then one or more of those numbers is incorrect. The buyer could be getting a 20% stake. The new value of the company after the investment is $1.25 million. Or paying $333,333.33. The new value of the company after the investment is $1,333,333.33. Or BigCo could only be worth $750,000 before the investment. The new value of the company after the investment is $1 million. Or Jack is getting screwed, selling $312,500 in stock (25%) for only $250,000. Jack's shares drop from being worth $1 million to only $937,500. The value of the company is $1.25 million. Or some combination of smaller changes that balances.",
"title": ""
},
{
"docid": "303810",
"text": "The check is written to BigCo. Jack is being diluted, corporation issues more shares. There's no gain, no change in Jack's equity value. Jack didn't lose or win anything. BigCo was worth $1M before the additional money, it is worth $1.25M after the additional money, with Jack owning the same $1M, but the cake is now bigger (obviously the numbers are wrong in your example, but you get the point).",
"title": ""
},
{
"docid": "121622",
"text": "\"BigCo is selling new shares and receives the money from Venturo. If Venturo is offering $250k for 25% of the company, then the valuation that they are agreeing on is a value of $1m for the company after the new investment is made. If Jack is the sole owner of one million shares before the new investment, then BigCo sells 333,333 shares to Venturo for $250k. The new total number of shares of BigCo is 1,333,333; Venturo holds 25%, and Jack holds 75%. The amount that Jack originally invested in the company is irrelevant. At the moment of the sale, the Venturo and Jack agree that Jack's stake is worth $750k. The value of Jack's stake may have gone up, but he owes no capital gains tax, because he hasn't realized any of his gains yet. Jack hasn't sold any of his stake. You might think that he has, because he used to hold 100% and now he holds 75%. However, the difference is that the company is worth more than was before the sale. So the value of his stake was unchanged immediately before and after the sale. Jack agrees to this because the company needs this additional capital in order to meet its potential. (See \"\"Why is stock dilution legal?\"\") For further explanation and another example of this, see the question \"\"If a startup receives investment money, does the startup founder/owner actually gain anything?\"\" Your other scenario, where Venturo purchases existing shares directly from Jack, is not practical in this situation. If Jack sells his existing shares, you are correct that the company does not gain any additional capital. An investor would not want to invest in the company this way, because the company is struggling and needs new capital.\"",
"title": ""
}
] |
[
{
"docid": "115814",
"text": "Does it make sense for stocks to earn a premium indefinitely? Yes. There is good reason to think that the stock market will make money indefinitely: the stock market is the primary mechanism through which investors bear market risk, which requires compensation. If you think of all the owners of firms (stockholders and bondholders, generally) the risk premium that stocks earn stocks is the way bondholders pay equityholders to bear the risk that they do not wish to. Will stock prices always go up in the long run? As long as companies pay out less in dividends than their profit, prices will go up. That could change if we were to change our corporate culture and/or tax practices so that firms paid out more in dividends. However, for the purposes of your question, I think it doesn't matter much whether the investor makes money as dividends or capital gains. Does the 5-7% guess apply only to the US market? I didn't write (nor read) the books in question, but most likely that is a global number. The US dominates the global equity market, so it's often a good proxy. However, international returns taken together have no less risk and earn no less over long horizons in general. The particular examples you have pointed out are special cases that only apply to a part of the global economy and a particular time period. There are plenty of examples of stock markets and time periods that did much better than the US market to offset your examples. Is 5-7% a reasonable long-term estimate of equity returns? Equity will always earn more in expectation than risk-free securities will. How much more depends on major economic factors. 5-7% has been a good estimate for the market risk premium for many, many decades (stocks should earn this plus whatever the risk-free rate is). However, that is just an empirical observation, not a rule. It can change. Some day technological progress could slow down or stop, we could run out of important resources in a way that we can't compensate for, our population permanently could stop growing, aliens could invade, etc. Down the road it is certainly possible for expected equity returns to go down and never go back up again. This would result from a permanent, global, economic shift that I think would be pretty obvious. That is, you wouldn't have to look at stock prices to know it was happening.",
"title": ""
},
{
"docid": "235484",
"text": "\"Is all interest on a first time home deductible on taxes? What does that even mean? If I pay $14,000 in taxes will My taxes be $14,000 less. Will my taxable income by that much less? If you use the standard deduction in the US (assuming United States), you will have 0 benefit from a mortgage. If you itemize deductions, then your interest paid (not principal) and your property tax paid is deductible and reduces your income for tax purposes. If your marginal tax rate is 25% and you pay $10000 in interest and property tax, then when you file your taxes, you'll owe (or get a refund) of $2500 (marginal tax rate * (amount of interest + property tax)). I have heard the term \"\"The equity on your home is like a bank\"\". What does that mean? I suppose I could borrow using the equity in my home as collateral? If you pay an extra $500 to your mortgage, then your equity in your house goes up by $500 as well. When you pay down the principal by $500 on a car loan (depreciating asset) you end up with less than $500 in value in the car because the car's value is going down. When you do the same in an appreciating asset, you still have that money available to you though you either need to sell or get a loan to use that money. Are there any other general benefits that would drive me from paying $800 in rent, to owning a house? There are several other benefits. These are a few of the positives, but know that there are many negatives to home ownership and the cost of real estate transactions usually dictate that buying doesn't make sense until you want to stay put for 5-7 years. A shorter duration than that usually are better served by renting. The amount of maintenance on a house you own is almost always under estimated by new home owners.\"",
"title": ""
},
{
"docid": "538490",
"text": "An equity tax does seem to make some sense. It would probably help to stave off deflation as well because it would encourage growth and investment where people would otherwise choose to sit on their money or worse. An equity tax on currency or liquid investments of even .5% APR would have a huge effect on the behavior of corporations. Sadly the largest of them would have the resources to avoid the tax by keeping all of their money out of the country.",
"title": ""
},
{
"docid": "42625",
"text": "\"This question drives at what value a shareholder actually provides to a corporation, and by extent, to the economy. If you subscribe for new shares (like in an Initial Public Offering), it is very straightforward to say \"\"I have provided capital to the corporation, which it is using to advance its business.\"\" If you buy shares that already exist (like in a typical share purchase on a public exchange), your money doesn't go to the company. Instead, it goes to someone who paid someone who paid someone who paid someone (etc.) who originally contributed money to the corporation. In theory, the value of a share price does not directly impact the operation of the company itself, apart from what @DanielCarson aptly noted (employee stock options are affected by share price, impacting morale, etc.). This is because in theory, the true value of a company (and thus, the value of a share) is the present value of all future cashflows (dividends + final liquidation). This means that in a technical sense, a company's share price should result from the company's value. The company's true value does not result from the share price. But what you are doing as a shareholder is impacting the liquidity available to other potential investors (also as mentioned by @DanielCarson, in reference to the desirability for future financing). The more people who invest their money in the stock market, the more liquid those stocks become. This is the true value you add to the economy by investing in stocks - you add liquidity to the market, decreasing the risk of capital investment generally. The fewer people there are who are willing to invest in a particular company, the harder it is for an investor to buy or sell shares at will. If it is difficult to sell shares in a company, the risk of holding shares in that company is higher, because you can't \"\"cash out\"\" as easily. This increased risk then does change the value of the shares - because even though the corporation's internal value is the same, the projected cashflows of the shares themselves now has a question mark around the ability to sell when desired. Whether this actually has an impact on anything depends on how many people join you in your declaration of ethical investing. Like many other forms of social activism, success relies on joint effort. This goes beyond the direct and indirect impacts mentioned above; if 'ethical investing' becomes more pronounced, it may begin to stigmatize the target companies (fewer people wanting to work for 'blacklist' corporations, fewer people buying their products, etc.).\"",
"title": ""
},
{
"docid": "345681",
"text": "\"Equity does not represent production divisions in a company (i.e. chocolate, strawberry, and vanilla does not make sense). In Sole proprietorship, equity represents 1 owner. In Partnership, equity has at least two sub-accounts, namely Partner 1 and Partner 2. In Corporations, equity may have Common Stockholders and Preferred Stockholders, or even different class of shares for insiders and angel investors. As you can see, equity represents who owns the company. It is not what the company does or manufactures. First and foremost, define the boundary of the firm. Are your books titled \"\"The books of the family of Doe\"\", \"\"The books of Mr & Mrs Doe\"\", or \"\"The books of Mr & Mrs Doe & Sons\"\". Ask yourself, who \"\"owns\"\" this family. If you believe that a marriage is perpetual until further notice then it does not make any sense to constantly calculate which parent owns the family more. In partnership, firm profits are attributed to partner's accounts using previously agreed ratio. For example, (60%/40% because Partner 1 is more hard working and valuable to the firm. Does your child own this family? Does he/she have any rights to use the assets, to earn income from the assets, to transfer the assets to others, or to enforce private property rights? If they don't have a part of these rights, they are certainly NOT part of Equity. So what happens to the expenses of children if you follow the \"\"partnership\"\" model? There are two ways. The first way is to attribute the Loss to the parents/family since you do not expect the children to repay. It is an unrecoverable loss written off. The second way is to create a Debtor(Asset) account to aggregate all child expense, then create a separate book called \"\"The books Children 1\"\", and classify the expense in that separate book. I advise using \"\"The family of Doe\"\" as the firm's boundary, and having 1 Equity account to simplify everything. It is ultimately up to you to decide the boundaries.\"",
"title": ""
},
{
"docid": "3750",
"text": "\"The implication is market irrationality is stronger than market rationality. Aka nothing makes sense when TSLA climbs to $400 or when CMG rises to $750. I wouldn't say there is a systematic flaw in valuation. I think there is just a lot of ignorance. Markets are more open to household investors than ever before. You used to go to your broker and ask him what's up and he'd give you the inside scoop since you pay them money. Now you go onto marketwatch and get some random nobody's opinion on everything and make stock selections based on that. But eventually the chickens come home to roost and things will correct itself. Big players will jump ship and cause signals to other traders to jump ship. The public can pump stocks up pretty high but it doesn't just go to infinity. Eventually someone will stop and say, \"\"wtf is going on\"\" and start selling. Stocks are sold on a basis of a limit order book so it's real prices that people are paying. People don't care about prices currently because most don't have any finance knowledge but want to invest their own money. They just hear about Tesla doing something amazing (from some clickbait article or news outlet) and can't stop thinking about buying Tesla. They go to Chipotle and think \"\"wow this place is so good and hip, they must be a great investment\"\". The markets have been filled with more subjective analysis than ever before especially with so much low quality information at your fingertips. Equally ignorant people startin blogs about investment and personal finance being shepherds for other ignorant people. In the end they all lose. People who exclaim \"\"this stock is going up to $250 easily\"\" with literally zero quantitative analysis or even a baseline reference point to back it up are prime examples of this. Ignorance of markets and cheap money almost always lead to market runs that end catastrophically. Dot com bubble, 1929 market crash, 2008, it's always the same. People who have no business taking loans out or buying on margin or leveraging positions with debt only to get fucked over once things are brought back down to Earth. After 2 runs of QE, we now have cheap money and with everyone being a crier for their personal investment strategy, we now also have rampant ignorance. I don't expect things to last but no one can call the bottom or the top, or else you'd be very very rich. Have a safe portfolio, don't try to time the markets. Have a strategy that hedges against unexpected change, don't try to gamble on this change. Because it's ultimately impossible to predict the movement of every single person on this earth that invests their money into markets. So don't try. Just be prepared. ---- To expand further into valuation theory: at the end of the day, people invest their money to make more money. It's as simple as that. If your money doesn't grow in an investment vehicle, it's ultimately a shit investment. But no one values intrinsic value of a company's equity before they decide whether or not $380 for TSLA is a good/bad deal. As a result, stocks can be pumped up way higher and people still see the gains on their stocks through capital gains fueled by other optimistic investors. Non-zero sum goes both ways. People can make shitloads of money on stock without an equitable loser--people can also lose shitloads on stock without any real winner emerging from the rubble. When this bubble bursts, lots and lots of people will lose money on TSLA when people's expectations become rational and they stop paying $300 a share for a negative or 70 PE ratio. It's insane what multipliers people will pay for these companies without even realizing the implication--if you buy a share of a company with a PE ratio of 70, you just paid 70 times their earnings for a share. In an ideal world where they released every single penny of earnings as dividends, it would take you 70 periods to reclaim your money on that share. This obviously doesn't take into account capital gains, but capital gains aren't supposed to be this irrational to where a stock can be pumped up into 70x PE ratio in the first place. It's a whole messed up web of confusion and irrationality and eventually something will catalyze a reaction. Imagine a market where everyone just agreed to pump up a single stock to infinity and everyone just rakes in shitloads of money. Would this work? Of course not. It's literally a pyramid scheme that relies on future generations to constantly inject capital--no real value is being created by this scheme. It requires constantly more future generations to continue adding money into the scheme and will crash once people stop pumping money into it. The same thing will happen here. Everyone \"\"agreed\"\" to pump up TSLA (in a sense) but eventually people will realize this is stupid as shit and the pyramid will come tumbling down because there is nothing they receive from this scheme other than the money from other people. It's essentially moving money around, making 0 use of it, until people stop pumping money into the system and everyone realizes that nothing of real value had been produced through the use of this money. Ultimately the only thing that creates real value is the money that is returned to shareholders from an outside party--the company you're invested in. Real value is not created when people exchange stock and money. So why do these transactions create higher values in equity? The basis of equity valuation states that dividends are the only way for companies to raise the price of their stock, going off the traditional Dividend Discount Model. And theoretically, that's the only logical explanation. Buying and trading stock does nothing for the company, minus T Stock they might own. Ultimately the only party creating real value is the underlying company. If they aren't creating real value, then their stock should not be increasing, period. The way they create value is by efficiently utilizing assets to generate returns on investment which can be returned to investors through dividends. Dividends can only be increased (while maintaining an equitable payout ratio) by generating more net income that can increase the actual pool of money that can be allocated back to investors. TSLA does not do this. TSLA regularly loses money and overpromises. There is no logical explanation for any of this except that everyone is irrational. Obviously theory is not the same as in practice but the theory is important here because it's really the basis for any investment at all. At the end of the day, a share of stock is the right to a share of the company's equity. People own equity in companies because companies generate money that it returns back to its owners. That's what a company does. That's what an owner does. If you own shares of a company, you're an owner. And if your company does not return more money back to you YoY, then why are you invested in them? Ultimately, you're riding a capital gains wave that will eventually subside once market irrationality succumbs to rationality. And it always does because the real value always catches up to the fake value that is caused by pumping and dumping stocks.\"",
"title": ""
},
{
"docid": "149493",
"text": "\"For this to work, those who control the dilution must also control their salaries because the only way for them to be paid off when it's the corporation itself selling is to gain access to the proceeds. When a corporation sells newly issued equity, the corporation itself owns the money. To at least have the appearance of propriety, the scammers must be paid those proceeds. Both actions imply that the board is captured by the scammers. There are many corporations that seem to do this even with persistently large market capitalizations. The key difference between this and pump-and-dump is that its a fraudulent group of investors selling in this case instead of the corporation itself. A detailed simple example Corporations are mandated by law to be little oligarchies; although, \"\"republic\"\" is now becoming more appropriate with all of the new shareholder rights. A corporation is controlled at root by the board of directors who are elected by the shareholders. The board has no direct operational control, as that is left to the \"\"king\"\", the CEO; however, the board does control what everyone wants access to: the money. Board members have all sorts of legal qualitative mandates on how to behave, and they've functioned fairly decently efficiently over the long run, but there are definitely some bad apples. Boards are somewhat intransigent since it's difficult to hold board elections, and usually only specific board members are put up for election by a shareholder vote, so a bad one has the potential to really get stuck in there. Once a bad one is in there, they don't care because they know it will be tough to get them out, so they run roughshod over the company's purse. Only the board can take action on major funding such as the CEO's operating budget, board compensation, financing, investment, etc, some with shareholder approval, some without. The corporation itself owns all of those assets, but the board controls them. In this example, they scheme with most likely the top executive, but a rubber stamp top executive could allow a lower rung to scheme with the board, but the board is always constant until the law is changed. Because there's no honor amongst thieves, the board votes which can require some combination of executive and shareholder approval are taken very close together: sell shares, increase salaries to key executive schemers, increase board compensation. The trusting shareholders believe this is in the best interests of the company at large so go along. So the money flows from existing & new shareholders to the corporation now controlled by a malicious board and then finally to the necessary malicious executive and the vital malicious board.\"",
"title": ""
},
{
"docid": "512429",
"text": "\"So some background here - when corporations, large ones have to deal with tax, they generally try to avoid as much tax as possible. Since there are places that are \"\"tax havens\"\" where there is less to even no tax on profit, a lot of money gets routed there to avoid taxes in other places (US or other unfavorable countries). The problem with this from an IRS/government view is that they keep losing millions/billions of dollars in money because of this. I think the corporate federal tax rate is around 35% and that is without state taxes. Unfortunately when you have less and less money at home - less investment at home happens. Corporations stop doing business at home because they have more money somewhere else - and it makes sense to move more of the company to where the money is or to more favorable tax locations. Even worse - the corporation might just \"\"save\"\" its money somewhere else and kill all reinvestment - thus the money is effectively dead to the rest of the economy. There is a lot of talk about a 'one-time' repatriation tax to allow companies that have dodged their tax burdens to have their money come back to the US (and thus can be used locally) at 10% instead of 35% since there is theroretically a vast amount of cash that would be injected into the US economy. The government is hoping this stimulation will help GDP grow, taxes grow, and help the economy as a whole. In reality, it will reward corporations that broke the law (even though everyone does it), and probably just go into savings accounts here in the US - and not be the \"\"silver bullet\"\" to the economy on verge of collapse again.\"",
"title": ""
},
{
"docid": "399191",
"text": "\"what does negative Total Equity means in McDonald's balance sheet? It means that their liabilities exceed their total assets. Usually is means that a company has accumulated losses over time, but that's just one explanation. But, isn't McDonald a very healthy company, and never lost money? Just because a company has \"\"always\"\" money does not mean it's a healthy company. It may have borrowed a lot of money in order to operate, and now the growth is not able to keep up with the debt load. In McDonald's case, the major driver in the equity change is the fact that they have bought back over $20 Billion in stock over the past few years, which reduces assets and equity. If they had instead paid off debt, their equity would not be negative, but their debt may be so cheap (in terms of interest rate) that it made more financial sense to buy back stock instead of paying off debt. There are too many variables to assess that in this forum.\"",
"title": ""
},
{
"docid": "333755",
"text": "\"There are many different methods for a corporation to get money, but they mostly fall into three categories: earnings, debt and equity. Earnings would be just the corporation's accumulation of cash due to the operation of its business. Perhaps if cash was needed for a particular reason immediately, a business may consider selling a division or group of assets to another party, and using the proceeds for a different part of the business. Debt is money that (to put it simply) the corporation legally must repay to the lender, likely with periodic interest payments. Apart from the interest payments (if any) and the principal (original amount leant), the lender has no additional rights to the value of the company. There are, basically, 2 types of corporate debt: bank debt, and bonds. Bank debt is just the corporation taking on a loan from a bank. Bonds are offered to the public - ie: you could potentially buy a \"\"Tesla Bond\"\", where you give Tesla $1k, and they give you a stated interest rate over time, and principal repayments according to a schedule. Which type of debt a corporation uses will depend mostly on the high cost of offering a public bond, the relationships with current banks, and the interest rates the corporation thinks it can get from either method. Equity [or, shares] is money that the corporation (to put it simply) likely does not have a legal obligation to repay, until the corporation is liquidated (sold at the end of its life) and all debt has already been repaid. But when the corporation is liquidated, the shareholders have a legal right to the entire value of the company, after those debts have been paid. So equity holders have higher risk than debt holders, but they also can share in higher reward. That is why stock prices are so volatile - the value of each share fluctuates based on the perceived value of the entire company. Some equity may be offered with specific rules about dividend payments - maybe they are required [a 'preferred' share likely has a stated dividend rate almost like a bond, but also likely has a limited value it can ever receive back from the corporation], maybe they are at the discretion of the board of directors, maybe they will never happen. There are 2 broad ways for a corporation to get money from equity: a private offering, or a public offering. A private offering could be a small mom and pop store asking their neighbors to invest 5k so they can repair their business's roof, or it could be an 'Angel Investor' [think Shark Tank] contributing significant value and maybe even taking control of the company. Perhaps shares would be offered to all current shareholders first. A public offering would be one where shares would be offered up to the public on the stock exchange, so that anyone could subscribe to them. Why a corporation would use any of these different methods depends on the price it feels it could get from them, and also perhaps whether there are benefits to having different shareholders involved in the business [ie: an Angel investor would likely be involved in the business to protect his/her investment, and that leadership may be what the corporation actually needs, as much or more than money]. Whether a corporation chooses to gain cash from earnings, debt, or equity depends on many factors, including but not limited to: (1) what assets / earnings potential it currently has; (2) the cost of acquiring the cash [ie: the high cost of undergoing a public offering vs the lower cost of increasing a bank loan]; and (3) the ongoing costs of that cash to both the corporation and ultimately the other shareholders - ie: a 3% interest rate on debt vs a 6% dividend rate on preferred shares vs a 5% dividend rate on common shares [which would also share in the net value of the company with the other current shareholders]. In summary: Earnings would be generally preferred, but if the company needs cash immediately, that may not be suitable. Debt is generally cheap to acquire and interest rates are generally lower than required dividend rates. Equity is often expensive to acquire and maintain [either through dividend payments or by reduction of net value attributable to other current shareholders], but may be required if a new venture is risky. ie: a bank/bondholder may not want to lend money for a new tech idea because it is too risky to just get interest from - they want access to the potential earnings as well, through equity.\"",
"title": ""
},
{
"docid": "108770",
"text": "\"A bit strange but okay. The way I would think about this is again that you need to determine for what purpose you're computing this, in much the same way you would if you were to build out the model. The IPO valuation is not going to be relevant to the accretion/dilution analysis unless you're trying to determine whether the transaction was net accretive at exit. But that's a weird analysis to do. For longer holding periods like that you're more likely to look at IRR, not EPS. EPS is something investors look at over the short to medium term to get a sense of whether the company is making good acquisition decisions. And to do that short-to-medium term analysis, they look at earnings. Damodaran would say this is a shitty way of looking at things and that you should probably be looking at some measure of ROIC instead, and I tend to agree, but I don't get paid to think like an investor, I get paid to sell shit to them (if only in indirect fashion). The short answer to your question is that no, you should not incorporate what you are calling liquidation value when determining accretion/dilution, but only because the market typically computes accretion/dilution on a 3-year basis tops. I've never put together a book or seen a press release in my admittedly short time in finance that says \"\"the transaction is estimated to be X% accretive within 4 years\"\" - that just seems like an absurd timeline. Final point is just that from an accounting perspective, a gain on a sale of an asset is not going to get booked in either EBITDA or OCF, so just mechanically there's no way for the IPO value to flow into your accretion/dilution analysis there, even if you are looking at EBITDA/shares. You could figure the gain on sale into some kind of adjusted EBITDA/shares version of EPS, but this is neither something I've ever seen nor something that really makes sense in the context of using EPS as a standardized metric across the market. Typically we take OUT non-recurring shit in EPS, we don't add it in. Adding something like this in would be much more appropriate to measuring the success of an acquisition/investing vehicle like a private equity fund, not a standalone operating company that reports operational earnings in addition to cash flow from investing. And as I suggest above, that's an analysis for which the IRR metric is more ideally situated. And just a semantic thing - we typically wouldn't call the exit value a \"\"liquidation value\"\". That term is usually reserved for dissolution of a corporate entity and selling off its physical or intangible assets in piecemeal fashion (i.e. not accounting for operational synergies across the business). IPO value is actually just going to be a measure of market value of equity.\"",
"title": ""
},
{
"docid": "79411",
"text": "\"This is not an end-all answer but it'll get you started I have been through accounting courses in college as well as worked as a contractor (files as sole proprietor) for a few years but IANAA (I am not an accountant). Following @MasonWheeler's answer, if you're making that much money you should hire a bean counter to at least overlook your bookkeeping. What type of business? First, if you're the sole owner of the business you will most likely file as a sole proprietorship. If you don't have an official business entity, you should get it registered officially asap, and file under that name. The problem with sole proprietorships is liability. If you get sued, not only are your business' assets vulnerable but they can go after your personal assets too (including house/cars/etc). Legally, you and your business are considered one and the same. To avoid liability issues, you could setup a S corporation. Basically, the business is considered it's own entity and legal matters can only take as much as the business owns. You gain more protection but if you don't explicitly keep your business finances separate from your personal finances, you can get into a lot of trouble. Also, corporations generally pay out more in taxes. Technically, since the business is it's own entity you'll need to pay yourself a 'reasonable salary'. If you skip the salary and pay yourself the profits directly (ie evade being taxed on income/salary) the IRS will shut you down (that's one of the leading causes of corporations being shut down). You can also pay distribute bonuses on top of that but it would be wise to burn the words 'within reason' into your memory first. The tax man gets mad if you short him on payroll taxes. S corporations are complicated, if you go that route definitely seek help from an accountant. Bookkeeping If you're not willing to pay a full time accountant you'll need to do a lot of studying about how this works. Generally, even if you have a sole proprietorship it's best to have a separate bank account for all of your business transactions. Every source/drain of money will fall into one of 3 categories... Assets - What your business owns: Assets can be categorized by liquidity. Meaning how fast you can transform them directly into cash. Just because a company is worth a lot doesn't necessarily mean it has a lot of cash. Some assets depreciate (lose value over time) whereas some are very hard to transform back into cash based on the value and/or market fluctuations (like property). Liabilities - What you owe others and what others owe you: Everything you owe and everything that is owed to you gets tracked. Just like credit cards, it's completely possible to owe more than you own as long as you can pay the interest to maintain the loans. Equity - the net worth of the company: The approach they commonly teach in schools is called double-entry bookkeeping where they use the equation: In practice I prefer the following because it makes more sense: Basically, if you account for everything correctly both sides of the equation should match up. If you choose to go the sole proprietorship route, it's smart to track everything I've mentioned above but you can choose to keep things simple by just looking at your Equity. Equity, the heart of your business... Basically, every transaction you make having to do with your business can be simplified down to debits (money/value) increasing and credits (money/value) decreasing. For a very simple company you can assess this by looking at net profits. Which can be calculated with: Revenues, are made up of money earned by services performed and goods sold. Expenses are made up of operating costs, materials, payroll, consumables, interest on liabilities, etc. Basically, if you brought in 250K but it cost you 100K to make that happen, you've made 150K for the year in profit. So, for your taxes you can count up all the money you've made (Revenues), subtract all of the money you've paid out (Expenses) and you'll know how much profit you've made. The profit is what you pay taxes on. The kicker is, there are gray areas when it comes to deducting expenses. For instance, you can deduct the expense of using your car for business but you need to keep a log and can only expense the miles you traveled explicitly for business. Same goes for deducting dedicated workspaces in your house. Basically, do the research if you're not 100% sure about a deduction. If you don't keep detailed books and try to expense stuff without proof, you can get in trouble if the IRS comes knocking. There are always mythical stories about 'that one guy' who wrote off his boat on his taxes but in reality, you can go to jail for tax fraud if you do that. It comes down to this. At the end of the year, if your business took in a ton of money you'll owe a lot in taxes. The better you can justify your expenses, the more you can reduce that debt. One last thing. You'll also have to pay your personal federal/state taxes (including self-employment tax). That means medicare/social security, etc. If this is your first foray into self-employment you're probably not familiar with the fact that 1099 employers pick up 1/2 of the 15% medicare/social security bill. Typically, if you have an idea of what you make annually, you should be paying this out throughout the year. My pay as a contractor was always erratic so I usually paid it out once/twice a year. It's better to pay too much than too little because the gov't will give you back the money you overpaid. At the end of the day, paying taxed sucks more if you're self-employed but it balances out because you can make a lot more money. If as you said, you've broken six figures, hire a damn accountant/adviser to help you out and start reading. When people say, \"\"a business degree will help you advance in any field,\"\" it's subjects like accounting are core requirements to become a business undergrad. If you don't have time for more school and don't want to pay somebody else to take care of it, there's plenty of written material to learn it on your own. It's not rocket surgery, just basic arithmetic and a lot of business jargon (ie almost as much as technology).\"",
"title": ""
},
{
"docid": "410874",
"text": "\"all the other answers are spot on, but look at it this way. really all you mean when you say \"\"building equity\"\" is \"\"accumulating wealth\"\". if that is the goal, then having her invest the money in a brokerage (e.g. ira) account makes a lot more sense. if you can't afford the apartment without her, then you can't afford to pay out her portion of the equity in the future. which means she is not building equity, you are just borrowing money from her. the safest and simplest thing for you to do is to agree on a number that does not include \"\"equity\"\". to be really safe, you might want to both sign something in writing that says she will never have an equity stake unless you agree to it in writing. it doesn't have to be anything fancy. in fact, the shorter the better. i am thinking about 3 sentences should do the trick. if you feel you absolutely have to borrow money from her on a monthly basis to afford your mortgage, then i recommend you make it an unsecured loan. just be sure to specify the interest rate (even if it is zero), and the repayment terms (and ideally, late payment penalties). again, nothing fancy, 10 sentences maybe. e.g. \"\"john doe will borrow x$ per month, until jane doe vacates the apartment. after such time, john doe will begin repaying the loan at y$ per month....\"\" that said, borrowing money from friends and family almost never turns out well. at the very least, you need to save up a few months of rent so that if you do break up, you have time to find another roommate. disclaimer: i do not have any state-issued professional licenses.\"",
"title": ""
},
{
"docid": "159590",
"text": "Is she entitled to more of the equity because she made more? No. Equity should be determined by how much each paid. But she is entitled to more of the equity if she paid more. And that may be what she is saying. That she contributed more to the household's finances than you did. If you always paid the mortgage out of the joint account, you could presumably go back and look at the account to find out how much each of you contributed to it. That would give you a reasonable split for the remainder of the equity after your initial investment. If you both put your entire paychecks into the joint account every time, then it will be the same as the ratio of what you each made. That would also make sense for splitting up whatever remains in that account. While you're doing that, you may want to ask for more for your original $65,000. By my calculation, if your mortgage was 3.5%, that $65,000 saved the household more than $12,000 in interest that became equity instead. So you could reasonably bump your return on the initial investment up to $77,000 while making the concession on the rest of the equity. This is just a suggestion for a framework for splitting the equity. If you can agree on a split, it will almost certainly be easier than going to a mediator or court.",
"title": ""
},
{
"docid": "306149",
"text": "Fully Paid up Partly Paid up: A company may issue stock to you which is only partly paid up, for example, a company may issue a stock of face value 10 to you and ask you to pay 5 now and other 5 will be adjusted later by some other mechanism. This stock shall be partly paid up. Usually, these stocks are issued in different circumstances, for example as part payment for debentures, preference shares or other capital structuring. On the other hand for a fully paid up share no more money needs to be paid by you or no other adjustments need to be made. So, above, the company is issuing you with stocks for which you will need to pay no further money, they are fully paid for. Authorized Capital: Authorized capital of a company is the amount of money a company can raise by selling stock (not debt, equity). This number is registered when the company is incorporated, subsequently, this number can be revised upward by applying to the registrar of companies. Now, this means that at max. the company is authorized to raise this much capital and no more. However, a company may raise less than this, which is called Issued Capital. In your case, the company is raising its authorized capital by applying to the registrar of companies, though in this case they are looking at their full authorized capital to be issued capital, it was not necessary to do so. Increase of Authorized capital: The main benefit is that the company can get more money in form of equity and utilize the same, perhaps, for expansion of business etc., that is the primary benefit. Bonus Share: Usually, companies keep some surplus as reserve, this money comes out of the profit the company makes and is essentially money of the shareholders. This reserve surplus is maintained for situations, when the money may be required for exigencies. However, this surplus grows over a few years and the company usually the company plans for an expansion of business. However, this money cannot be just taken, as it belongs to the shareholder, so shareholders are issued extra equity in proportion to their current holding and this surplus is capitalized i.e. used as part of the company's equity capital. Bonus declaration does not add t o the value of the company and the share prices fall in proportion (but not quite) to the bonus.",
"title": ""
},
{
"docid": "314056",
"text": "This question is indeed rather complicated. Let's simplify it a little bit. Paying down your mortgage makes sense if your expected return in the rest of your portfolio is less than the cost of the mortgage. In many cases, people may also decide to pay down their mortgage because they are risk-averse and do not like carrying debt. There's no tax benefit to doing so, though; Canada doesn't generally allow you to write off mortgage interest, unlike the U.S. As to keeping money in the corporation or not, I'm not going to address that. I don't have a firm enough understanding of corporate taxation. Canadian Couch Potato advises treating all of your investment assets as one large portfolio. That is what you are trying to do here. However, let's consider a different approach. If you do not have enough money to max out your RRSP or TFSA, you may choose to keep your TFSA for an emergency fund, where the money is kept highly liquid. Keep your cash in an interest-bearing TFSA, or perhaps invest it in the money market, inside your TFSA. Then, use your RRSP for the rest of your investment money, split according to your investment goals. This is not the most tax-efficient approach, but it is nice and simple. But you are looking for the most tax-efficient approach. So, let's assume you have enough to more than max out your TFSA and RRSP contributions, and all of your investments are going toward your retirement, which is at least a decade away. Because you are not taxed on your investment income from RRSPs (until you withdraw the money) or TFSA, it makes sense to hold the least tax-efficient investments there. Tax-advantaged investments such as Canadian equities should be held in your investment accounts outside of TFSA and RRSPs. Again, the Canadian Couch Potato has a great article on where to put your investment assets. That article covers interest, dividends, foreign dividends, and capital gains, as well as RRSPs, RESPs, and TFSAs. That article recommends holding Canadian equities in a taxable account, REITs in a tax-sheltered account (TFSA or RRSP), bonds, GICs, and money-market funds in a tax-sheltered account (as these count as interest). The article goes into rather more detail than this, and is worth checking out. It mentions the 15% withholding tax on US-listed ETFs, for example. In addition to that website, I recommend the following three books: The above three resources strongly advocate passive indexed investments, which I like but not everyone agrees with. All three specifically discuss tax implications, which is why I include them here.",
"title": ""
},
{
"docid": "80913",
"text": "\"It should be pretty obvious that without knowing what sort of assets the company owns, and what sort of net earnings are being generated it's impossible to say what a $20k equity investment should get you in terms of ownership percentage. With that said, you want to look at a few to several years of books, look for trends. Some things to understand that might be subtle red flags: It's extremely common for early stage investors to essentially make loans rather than strictly buying shares. In the worst case scenario creditors get to participate in liquidation proceedings before shareholders do. You may be better off investing in this business via a loan that's convertible to equity at your discretion. Single owner service companies are difficult because all of the net earnings go to the proprietor and that person maintains all of the relationships. So taking something like 5 years of net earnings as the value of the company doesn't make much sense because you (or someone else) couldn't just step in and replace the owner. Granted, you aren't contemplating taking over the business, but it negates using an X years of net earnings valuation method. When you read about valuation there is a sort of overriding assumption that no single person could topple the operation which couldn't be farther from the truth in single employee service companies. Additionally, understand that your investment in a single owner company hinges completely on one person's ability and willingness to work. It's really vital to understand the purpose of the funds. Someone will be hired? $20,000 couldn't be even six months of wages... Put things in to perspective with a pad, pen and calculator. Don't invest in the pipe dream of a friend of yours, and DEFINITELY don't hand this person the downpayment for their new house. The first rule of investing is \"\"don't lose money,\"\" this isn't emotional, this is a dollars and cents pragmatic process. Why does the business need this money? How will you be paid back? Personally, I think it would be more gratifying to put $20k in a blender and watch it blend, this is probably a horrible investment. The risk should just be left to credit card companies.\"",
"title": ""
},
{
"docid": "117509",
"text": "What kind of financial analysis would make you comfortable about this decision? The HELOC and ARM are the biggest red flags to me in your current situation. While I don't expect interest rates to skyrocket in the near future, they introduce an interest rate risk that is easy to get rid of. Getting rid of the HELOC and converting to a fixed mortgage would be my first priority. If you also want to upgrade to a new home at the same time (meaning buy a new home contingent on the sale of your first, paying off the HELOC and mortgage), that's fine, but make sure that you can comfortably afford the payment on a fixed-rate mortgage with at least 20% down. I would not take additional cash out of your equity just to save it. You're going to pay more in interest that you're going to get in savings. From there things get trickier. While many people would keep the first property on a mortgage and rent it out, I am not willing to be a landlord for a part-time job, especially when the interest on the mortgage gouges my return on the rent. PLus leverage increases the risks as well - all it takes is to go one or two months without rent and you can find yourself unable to make a mortgage payment, wrecking your credit and possibly risking foreclosure. So my options in order of precedence would be: At what point does it make sense to become a landlord? The complicated answer is when the benefits (rent, appreciation) relative to the costs (maintenance, interest, taxes, etc.) and risks (lost rent, bad renters, home value variance) give you a better return that you could find in investments of similar risk. The simple answer is when you can pay cash for it. That takes interest and lost rent out of the equation. Again, some are willing to take those risks and pay 20% down on rental property. Some are able to make it work. Some of those go broke or lose their properties. when calculating the 20% down of a new property, does that need to be liquid funds, or can that be based on the value of the home you are selling You can make the purchase of the new home contingent on the sale of the first if you need to get the equity out of it to make the 20%. Do NOT refinance the first just to pull out the equity to make a down payment. It's not worth the fees of a refinance.",
"title": ""
},
{
"docid": "48569",
"text": "Most businesses want to grow, and there are a variety of ways to raise the money needed to hire new employees and otherwise invest in the business to increase the rate of that growth. You as a stock holder should hope that management is choosing the least expensive option for growth. Some of the options are debt, selling equity to venture capitalists, or selling equity on the open market (going public). If they choose debt, they pay interest on that debt. If they choose to sell equity to venture capitalists, then your shares get diluted, but hopefully the growth makes up for some of that dilution. If they choose to go public, dilution is still a concern, but the terms are usually a little more favorable for the company selling because the market is so liquid. In the US, current regulations for publicly traded companies cost somewhere in the neighborhood of $1M/year, so that's the rule of thumb for considering whether going public makes sense when calculating the cost of fundraising, but as mentioned, regulations make it less advantageous for executives who choose to sell their shares after the company goes public. (They can't sell when good spot prices appear.) Going public is often considered the next step for a company that has grown past the initial venture funding phase, but if cash-flow is good, plenty of companies decide to just reinvest profits and skip the equity markets altogether.",
"title": ""
},
{
"docid": "538518",
"text": "\"I am not familiar with this broker, but I believe this is what is going on: When entering combination orders (in this case the purchase of stocks and the writing of a call), it does not make sense to set a limit price on the two \"\"legs\"\" of the order separately. In that case it may be possible that one order gets executed, but the other not, for example. Instead you can specify the total amount you are willing to pay (net debit) or receive (net credit) per item. For this particular choice of a \"\"buy and write\"\" strategy, a net credit does not make sense as JoeTaxpayer has explained. Hence if you would choose this option, the order would never get executed. For some combinations of options it does make sense however. It is perhaps also good to see where the max gain numbers come from. In the first case, the gain would be maximal if the stock rises to the strike of the call or higher. In that case you would be payed out $2,50 * 100 = $250, but you have paid $1,41*100 for the combination, hence this leaves a profit of $109 (disregarding transaction fees). In the other case you would have been paid $1,41 for the position. Hence in that case the total profit would be ($1,41+$2,50)*100 = $391. But as said, such an order would not be executed. By the way, note that in your screenshot the bid is at 0, so writing a call would not earn you anything at all.\"",
"title": ""
},
{
"docid": "177528",
"text": "Founder makes available 100% equity, but uses a reasonable amount of the proceeds to pay him/herself a salary (or wage) and from that salary invests in the same initial offering to acquire shares for him/herself. I see several problems. What is a reasonable salary? Also, this leaves the door open to the following scam: Founders say that they are going to follow this plan. However, instead of buying shares, they simply quit after being paid the salary. They use knowledge gained from this business to start a competitor. Investors are left holding an empty company. Tax consequences. The founder would pay income tax on the salary. By contrast, if the founder instead sells shares, that would be capital gains tax, which is lower in many countries (e.g. the United States). Why would I want to invest in a business where the founders don't believe in it enough to take a significant equity stake? Consider the Amazon.com example. Jeff Bezos makes a minimal salary, around $80,000 a year, less than many of his employees. But he has a substantial ownership position. If the company doesn't make money, he won't. Would investors really value the stocks with a P/E of 232.10 in 2016 if they didn't trust him to make the right long term decisions? It's also worth noting that most initial public offerings (IPOs) are not made when the founder is the only employee. A single employee company instead looks for private investors, often called angel investors. Companies generally don't go public until they are established in some way, often making money. Negotiating with angel investors is different from negotiating with the public. They can personally review the books and once invested tend to have input on how the money is spent. In other words, this is mostly solving the wrong problem if you talk about IPOs. This might make more sense with a crowdfunded venture, as that replaces a few angel investors with many individuals. But most crowdfunded ventures tend to approach things from the opposite direction. Instead of looking for investors, they look for customers. If they offer a useful product, they will get customers. If not, they never get the money. Beyond all this, if a founder is only going to get a fair salary some of the time, then why put in any sweat equity? This works fine if the company looks valuable after a year. What if it doesn't? The founder is out a year of sweat equity and has nothing in return. That happens now too, but the possibility of the big return offsets it. You're taking out the big return. I don't think that this is good for either founders or investors. The founder trades a potentially good or even great return for a mediocre return. The investors trade a situation where both they and the founder benefit from a successful company to one where they benefit a lot more than the founder. That's not good for either side.",
"title": ""
},
{
"docid": "288701",
"text": "Yes, there are times when co-signing is the right choice. One is when you know more about the person than the loan issuer does. Consider a young person who has just started working in a volatile field, the kind of job where you can be told on Friday that you only get one shift next week but things might pick up the week after, and who makes maybe $12 an hour in that job. You've done the math and with 40 hour weeks they can easily afford the loan. Furthermore, you know this person well and you know that after a few weeks of not enough shifts, they've got the gumption to go out and find a second job or a different job that will give them 40 hours or more a week. And you know that they have some savings they could use to ensure that no payments will be missed even on low-wage weeks. You can cosign for this person, say for a car loan to get them a car they can drive to that job, knowing that they aren't going to walk away and just stop making the payments. The loan issuer doesn't know any of that. Or consider a young person with poor credit but good income who has recently decided to get smart about money, has written out a budget and a plan to rehabilitate their credit, and who you know will work passionately to make every payment and get the credit score up to a place where they can buy a house or whatever their goal is. Again, you can cosign for this person to make that happen, because you know something the lender doesn't. Or consider a middle aged person who's had some very hard knocks: laid off in a plant closing perhaps, marriage failure, lost all their house equity when the market collapsed, that sort of thing. They have a chance to start over again somewhere else and you have a chance to help. Again you know this isn't someone who is going to mismanage their money and walk away from the payments and leave you holding the bag. If you would give the person the money anyway (say, a car for your newly graduated child) then cosigning instead gives them more of a sense of accomplishment, since they paid for it, and gives them a great credit rating too. If you would not give the person the entire loan amount, but would make their payments for many months or even a year (say, your brother's mortgage for the house where he lives with a sick wife and 3 small children), then cosigning is only making official what you would have done anyway. Arrange with the borrower that if they can't make their payments any more, you will backstop them AND the item (car, house, whatever) is going up for sale to cover your losses. If you don't think you could enforce that just from the strength of the relationship, reconsider co-signing. Then sign what you need to sign and step away from it. It's their loan, not yours. You want them to pay it and to manage it and to leave you out of it until it's all paid off and they thank you for your help. If things go south, you will have to pay, and it may take a while for you to sell the item or otherwise stop the paying, so you do need to be very confident that the borrower is going to make every single payment on time. My point is just that you can have that confidence, based on personal knowledge of character, employment situation, savings and other resources, in a way that a lender really cannot.",
"title": ""
},
{
"docid": "273187",
"text": "why does it make sense financially to buy property and become a landlord? Because then your investment generates cash instead of just sitting idle. All taxes, fees and repairs aside it would take almost 21 years before I start making profits. No - your profit will be the rents that you collect (minus expenses). You still have an asset that is worth roughly what you paid for it (and might go up in value), so you don't need to recoup the entire cost of the property before making a profit. Compared to investing the same 150k in an ETF portfolio with conservative 4% in annual returns I would have made around 140k € after taxes in the same 21 years i.e. almost doubled the money. If you charge 600 € / month (and never miss a month of rental income), after 21 years you have made 151k € in rents plus you still have a property. That property is most likely going to be worth more than you paid for it, so you should have at least 300k € in assets. Having said all that, it does NOT always make sense to invest in rental property. Being a landlord can be a hard job, and there are many risks involved that are different that risks in financial investments.",
"title": ""
},
{
"docid": "446652",
"text": "I think I understand what I am doing wrong. To provide some clarity, I am trying to determine what the value of a project is to a firm. To do this I am taking FCF, not including interest or principal payments, and discounting back to get an NPV enterprise value. I then back off net debt to get to equity value. I believe what I am doing wrong is that I show that initial $50M as a cash outflow in period 0 and then back it off again when I go from enterprise value to equity value. Does this make any sense? Thanks for your help.",
"title": ""
},
{
"docid": "392741",
"text": "\"Someone's (or, a bank's) \"\"exposure to equities\"\" refers to the amount of value which has a risk that fluctuates with the equities market (ie: the stock market). In very broad terms, I think it might make sense to say that exposure to equities could mean, for example, owning many rental properties, if the rental market was \"\"highly correlated\"\" with the equities market. That is - if house prices go down when the equities market goes down, and if that relationship is very strong, then owning a house means you are exposed to the equities market. However, in the sense it is used there, it seems to mean direct exposure to equities - ie: owning stocks and stock-based funds.\"",
"title": ""
},
{
"docid": "569490",
"text": "> K-12 teachers never make six figure sums. In the U.S. that seems true. I found [this from 2012](http://money.usnews.com/careers/best-jobs/high-school-teacher/salary) that puts the median high-school teacher's salary at $55,050, with the top ten percent making about $85k. (By the way, this [OECD chart from 2013](http://educationbythenumbers.org/content/us-teachers-6th-highest-paid-world_982/) shows that the U.S. ranks 6th in the world in pay for primary-school teachers. I was surprised when I found this out.) > Professors in universities sometimes do, but for every professor that makes a lot of money there are probably dozens of untenured faculty who are barely making enough to feed themselves and put gas in their cars. You may be interested in [this chart from 2011](http://chronicle.com/article/Average-Faculty-Salaries-by/126586/) that gives salaries for professors, associate professors, assistant professors, new assistant professors, and instructors--all broken down by field. The data are only for four-year colleges and universities, though; that excludes community colleges, but I'm not sure whether it includes business schools, medical schools, or other graduate institutions. Not surprisingly, law and engineering are the most lucrative fields. > The real reason the big corporate interests want to privatize US education is to use all those jobs as bargaining chips in globalization. Interesting. Can you explain how this is intended to work? And if it would make sense for American corporations to do this, would it make sense for corporations from other countries to do it too? Are they doing it? I don't know anything about GATS or TiSA. Edit: grammar",
"title": ""
},
{
"docid": "104485",
"text": "If you have a new company and you want to attract investors, such as venture capitalists and private equity, incorporating in Delaware LLC probably makes sense. There are actually many investors who will only invest in a Delaware Online incorporation, so starting off by creating a Delaware corporation from the beginning may save a lot of money and stress down the road. You can also choose to form an LLC in Delaware, to begin with, then convert it to a C corporation later.",
"title": ""
},
{
"docid": "23569",
"text": "Does this make sense? Some corporate behemoth was making tons of money by selling disgusting sludge which I would not feed to a fucking dog, and because the true nature of this shit came to light, they lost a lot of business. They only had the business in the first place because people were unaware of what they were doing, and when the people learned, they were disgusted and tended to avoid it.",
"title": ""
},
{
"docid": "65040",
"text": "As the owner of the S-corp, it is far easier for you to move money in/out of the company as contributions and distributions rather than making loans to the company. Loans require interest payments, 1099-INT forms, and have tax consequences, whereas the distributions don't need to be reported because you pay taxes on net profits regardless of whether the money was distributed. If you were paid interest, disregard this answer. I don't know if or how you could re-categorize the loan once there's a 1099-INT involved. If no interest was ever paid, you just need to account for it properly: If the company didn't pay you any interest and never issued you a 1099-INT form (i.e. you wrote a check to the company, no promissory note, no tax forms, no payments, no interest, etc.) then you can categorize that money as a capital contribution. You can likewise take that money back out of the company as a capital distribution and neither of these events are taxable nor do they need to be reported to the IRS. In Quickbooks, create the following Equity accounts -- one for each shareholder making capital contributions and distributions: When putting money into the company, deposit into your corporate bank account and use the Capital Contribution equity account. When taking money out of the company, write yourself a check and use the Distributions account. At the end of every tax year, you can close out your Contributions and Distributions to Retained Earnings by making a general journal entry. For example, debit retained earnings and credit distributions on Dec 31 every year to zero-out the distributions account. For contributions, do the reverse and credit retained earnings. There are other ways of recording these transactions -- for example I think some people just use a Member Capital equity account instead of separate accounts for contributions and distributions -- and QB might warn you about posting journal entries to the special Retained Earnings account at the end of the year. In any case, this is how my CPA set up my books and it's been working well enough for many years. Still, never a bad idea to get a second opinion from your CPA. Be sure to pay yourself a reasonable salary, you can't get out of payroll taxes and just distribute profits -- that's a big red flag that can trigger an audit. If you're simply distributing back the money you already put into the company, that should be fine.",
"title": ""
},
{
"docid": "475560",
"text": "\"Recently, I asked about what the company valuation is and how many shares does my 4% represent.CFO told me that there is no point to talk about \"\"shares\"\" or \"\"stock\"\" since the company is not public. Is it right? No, it is wrong. Shares and stocks exist regardless of how they can be traded. Once a company is formed, there are stocks that belong to the owners in the proportion of the ownership. They may not exist physically, but they do exist on paper. As an owner of 5% of the company, you own 5% of the company stocks. I asked if my investor portion equity will be subjected under a vesting schedule, CFO said yes. That doesn't make sense to me, because I bought those 4%? Aren't those supposed to be fully vested? I agree to my employee equity to be vested. Doesn't make sense to me either, since your money is already in their pocket. But I'm not sure if its illegal. If that's what is written in the signed contract - then may be its possible to have that situation. But it doesn't make much sense, because these shares are granted to you in return to your money, not some potential future work (as the 1% employee's portion). You already gave the money, so why wouldn't they be vested? Best to read the contract upon which you gave them your money, I really hope you have at least that and not just gave them a check....\"",
"title": ""
}
] |
200124
|
The Weeknd is a singer.
|
[
{
"docid": "The_Weeknd",
"text": "The Weeknd ( born Abel Makkonen Tesfaye ; February 16 , 1990 ) is a Canadian singer , songwriter , and record producer . The Weeknd initially gained recognition after anonymously uploading several songs to YouTube in late 2010 . This allowed him to release of his debut mixtape , House of Balloons , in early 2011 . He released two further independent projects later that year , Thursday and Echoes of Silence , before signing to Republic Records in September 2012 . The three mixtapes received widespread critical acclaim upon release , and proceeded the release of the compilation album Trilogy . In 2013 , he released his debut studio album Kiss Land , which debuted at number two on the Billboard 200 . It was later confirmed to have sold over 273,000 copies in the United States . The Weeknd released his second album , Beauty Behind the Madness , in 2015 , breaking chart records in the process . It saw him become the first ever artist to have simultaneously held the top three spots on the Billboard Hot R&B Songs chart , with `` Earned It '' , `` The Hills '' , and `` Ca n't Feel My Face '' . It also became his first number one album on the US Billboard 200 , and saw triple platinum certification by the Recording Industry Association of America ( RIAA ) . The album additionally oversaw his first Grammy Award win for Best Urban Contemporary Album , as well as `` Earned It '' winning Best R&B Performance . He won both awards at the 58th Annual Grammy Awards ceremony in 2016 . He released his third studio album , Starboy , in 2016 to generally positive critical reception . The album 's title track topped the chart in several countries , including the U.S. , the UK and Canada , and became The Weeknd 's third number-one single . It gave him his second consecutive number one album , which also later saw platinum certification . Alongside his Grammy Award wins , The Weeknd has won nine Juno Awards and two American Music Awards . He has also founded the record label XO , and is a producer under both his given and stage names .",
"title": ""
}
] |
[
{
"docid": "Prisoner_(The_Weeknd_song)",
"text": "`` Prisoner '' is a song by Canadian singer The Weeknd , featuring American singer Lana Del Rey for his second studio album Beauty Behind the Madness ( 2015 ) . The artists co-wrote the song with Illangelo , who co-produced it with The Weeknd .",
"title": ""
},
{
"docid": "Starboy_(song)",
"text": "`` Starboy '' is a song recorded by Canadian singer The Weeknd for his third studio album of the same name . It features French electronic duo Daft Punk and was written by the trio alongside Doc McKinney , Henry Walter and Jason Quenneville , being produced by Daft Punk and co-produced by The Weeknd , McKinney and Cirkut . It was released as the first single from the album on September 22 , 2016 , by XO and Republic Records . It is an R&B and electropop song with lyrics that contain themes of extravagance of a celebrity life . `` Starboy '' topped the charts in countries such as Canada , France , Netherlands , New Zealand and Sweden , as well as the US Billboard Hot 100 , where it became The Weeknd 's third chart-topper , and Daft Punk 's first chart-topper . The music video for the song was directed by frequent collaborator Grant Singer , who directed The Weeknd 's previous music videos for `` Ca n't Feel My Face '' and `` The Hills '' . In the music video , The Weeknd is shown trying to destroy evidence of his previous self , including his own awards from his past album , Beauty Behind the Madness . The video has been described as The Weeknd 's attempt to murder his former persona .",
"title": ""
},
{
"docid": "Low_Life_(song)",
"text": "`` Low Life '' is a song by American hip hop recording artist Future , featuring Canadian singer The Weeknd . It was released on March 1 , 2016 , as the lead single from Future 's fourth studio album , EVOL ( 2016 ) . The song was written by Future , Metro Boomin , The Weeknd and DaHeala . The song was produced by Metro Boomin , DaHeala and Ben Billions with co-production by The Weeknd .",
"title": ""
},
{
"docid": "Secrets_(The_Weeknd_song)",
"text": "`` Secrets '' is a song by Canadian singer The Weeknd , from his third studio album Starboy ( 2016 ) . The song was written by Tesfaye , Doc McKinney , Walter Wiggins , Roland Orzabal , Coz Canler , Jimmy Marinos , Wally Palamarchuk , Mike Skill and Peter Solley , being produced by McKinney , Cirkut and The Weeknd . The song samples `` Pale Shelter '' , a song by the band Tears for Fears as well as `` Talking in Your Sleep '' by The Romantics .",
"title": ""
},
{
"docid": "False_Alarm_(The_Weeknd_song)",
"text": "`` False Alarm '' is a song by Canadian singer and songwriter The Weeknd , released as a promotional single from his third album Starboy on September 29 , 2016 .",
"title": ""
},
{
"docid": "In_the_Night_(The_Weeknd_song)",
"text": "`` In the Night '' is a song by Canadian singer The Weeknd from his second studio album Beauty Behind the Madness ( 2015 ) . The song was released as the album 's third single ( fourth overall ) on November 17 , 2015 .",
"title": ""
},
{
"docid": "Trilogy_(The_Weeknd_album)",
"text": "Trilogy is a compilation album by Canadian singer The Weeknd , released on 13 November 2012 , by XO and Republic Records . It is composed of re-mixed and remastered versions of his 2011 mixtapes House of Balloons , Thursday , and Echoes of Silence , and three previously-unreleased songs . Trilogy received generally positive reviews from critics , who reinforced the previous acclaim of the mixtapes , although some found it indulgent . It was promoted with three singles and The Weeknd 's concert tour during September to November 2012 . The album charted at number five and number four in Canada and the United States , respectively .",
"title": ""
},
{
"docid": "Lust_for_Life_(Lana_Del_Rey_song)",
"text": "`` Lust for Life '' is a song by American singer Lana Del Rey featuring Canadian singer The Weeknd . It was released on April 19 , 2017 , through Polydor Records and Interscope Records , as the second single from her upcoming fifth studio album of the same name ( 2017 ) . The song was written and produced by Del Rey and Rick Nowels , with additional writing from The Weeknd and Max Martin and additional production from Dean Reid and Kieron Menzies . It is her first song to feature another artist .",
"title": ""
},
{
"docid": "Rockin'_(song)",
"text": "`` Rockin '' is a song by Canadian singer The Weeknd from his third studio album , Starboy . The song was released to top 40 radio in Europe on May 9 , 2017 , as the album 's fourth international single . The song was written by The Weeknd , Max Martin , Ali Payami , Canadian rapper Belly , Peter Svensson , and Savan Kotecha , and produced by Payami and Martin , with The Weeknd serving as a co-producer . Like the rest of the tracks from Starboy , `` Rockin ' '' charted on the Billboard Hot 100 , reaching number 44 . It reached the top twenty on both the R&B Songs chart and Hot R&B / Hip-Hop Songs chart . The song charted at number 25 on the Canadian Hot 100 .",
"title": ""
},
{
"docid": "Crew_Love",
"text": "`` Crew Love '' is a song by Canadian rapper Drake from his second studio album Take Care . The song features guest vocals from fellow Canadian singer The Weeknd . Production was provided by The Weeknd , Noah `` 40 '' Shebib and Illangelo . `` Crew Love '' was released as the album 's seventh single in the United Kingdom on July 30 , 2012 .",
"title": ""
},
{
"docid": "Tell_Your_Friends_(song)",
"text": "`` Tell Your Friends '' is a song by Canadian singer The Weeknd , from his second studio album Beauty Behind the Madness ( 2015 ) . The song was written by Abel Tesfaye , Kanye West , Christopher Pope , Carlo Montagnese , Carl Marshall and Robert Holmes . It was produced by Che Pope , Kanye West , Omar Riad , Illangelo , Mike Dean , Noah Goldstein and The Weeknd .",
"title": ""
},
{
"docid": "The_Weeknd_discography",
"text": "Canadian singer and songwriter The Weeknd has released three studio albums , three mixtapes , and one compilation album , Trilogy ( 2012 ) , which is the compilation of all three of his mixtapes : House of Balloons , Thursday , and Echoes of Silence . Kiss Land ( 2013 ) , Beauty Behind the Madness ( 2015 ) , and Starboy , which was released in 2016 . Twenty-six singles ( including ten as a featured artist ) .",
"title": ""
},
{
"docid": "Wanderlust_(The_Weeknd_song)",
"text": "`` Wanderlust '' is a song by Canadian singer The Weeknd from his debut studio album Kiss Land ( 2013 ) . The song is heavily sampled with `` Precious Little Diamond '' by Dutch disco group Fox the Fox , and was released as the sixth single from the album on March 31 , 2014 . A remix of `` Wanderlust '' by Pharrell Williams also appears as a bonus track on the iTunes edition of Kiss Land .",
"title": ""
},
{
"docid": "Ali_Payami",
"text": "Ali Payami is an Swedish music composer , producer , writer , and singer . He has collaborated in the production of music with numerous popular artists including Adam Lambert , Ariana Grande , Ellie Goulding , Katy Perry , Taylor Swift , The Weeknd and Tove Lo . Payami 's first number one hit on the Billboard Hot 100 was The Weeknd 's single Ca n't Feel My Face .",
"title": ""
},
{
"docid": "Wicked_Games",
"text": "`` Wicked Games '' is the debut single by Canadian singer The Weeknd . It was recorded at Site Sound Studios and mixed at Liberty Studios in Toronto . Producers Doc McKinney and Illangelo co-wrote the song and performed all instrumentation . Originally recorded for The Weeknd 's 2011 mixtape House of Balloons , the song was remastered and released as the lead single for his 2012 album Trilogy . It was released as a digital single on October 22 , 2012 , by XO and Republic Records . Upon release , the single received widespread acclaim from music critics . On May 9 , 2013 , `` Wicked Games '' was certified double platinum by the Recording Industry Association of America ( RIAA ) , for shipments of 1,000,000 units in the United States . This song is also featured on the soundtrack for the movie Southpaw , the soundtrack 's executive producer being American rapper Eminem who went on to produce a remix with The Weeknd on his later song `` The Hills '' .",
"title": ""
},
{
"docid": "Might_Not",
"text": "`` Might Not '' is a song by Canadian rapper Belly . The song was released on December 18 , 2015 by Roc Nation and XO as a single from his mixtape Up For Days . The track was produced by Ben Billions , DaHeala and Merlin Watts . The song features Canadian singer The Weeknd . It reached number 68 on the US Billboard Hot 100 . The official remix features The Weeknd , along with 2 Chainz and Yo Gotti . It is a hip hop and trap song in the key of C minor .",
"title": ""
},
{
"docid": "Twenty_Eight_(song)",
"text": "`` Twenty Eight '' is a song by Canadian singer The Weeknd . It was recorded at Site Sound Studios and mixed at Liberty Studios in Toronto . Producer Doc McKinney and Illangelo co-wrote the song and performed all instrumentation . The song was one of three bonus tracks included at the end of each of the compilation 's discs from The Weeknd 's 2012 album Trilogy . The song was released as the second single for the album , released as a digital single on December 10 , 2012 , by XO and Republic Records .",
"title": ""
},
{
"docid": "Earned_It",
"text": "`` Earned It '' , alternatively titled `` Earned It ( Fifty Shades of Grey ) '' , is a song by Canadian singer The Weeknd . The song was released as the lead single from the soundtrack to the 2015 film Fifty Shades of Grey and was included on The Weeknd 's second studio album Beauty Behind the Madness . `` Earned It '' peaked at number three on the Billboard Hot 100 , becoming The Weeknd 's first top five single . The song 's popularity made Fifty Shades of Grey the latest soundtrack to generate concurrent top-ten singles with Ellie Goulding 's `` Love Me like You Do '' , which also peaked at number three . Its music video was directed by the film 's director Sam Taylor-Johnson , features the film 's lead actress Dakota Johnson , and it features clips of the film and the same BDSM theme . The song was nominated for Best Original Song at the 88th Academy Awards and won the Grammy Award for Best R&B Performance at the 58th Annual Grammy Awards .",
"title": ""
},
{
"docid": "House_of_Balloons",
"text": "House of Balloons is the debut mixtape by Canadian singer The Weeknd . It was released as a free download on March 21 , 2011 , by XO . The mixtape was also released on his official website . Its music incorporates electronic and urban genres , including R&B and soul , along with trip hop , indie rock and dream pop tones . The contributions to the mixtape 's production came from Canadian record producers such as Doc McKinney , Zodiac and Illangelo , among others . In September 2013 , The Weeknd revealed that the House of Balloons is a real place , located at 65 Spencer Ave in Toronto .",
"title": ""
},
{
"docid": "Starboy",
"text": "Starboy or Star Boy may refer to : Star boy , or star-boy at Christmas Star Boy , comics , a member of the Legion of Super-Heroes Star Boy , Jr. , Mexican wrestler , son of Star Boy InterPlane Starboy , proposed Czech homebuilt aircraft designed by InterPlane Aircraft of Zbraslavice Starboy Award , Oulu International Children 's and Youth Film Festival Starboy , game from list of Amstrad CPC games Starboy Nathan , English R&B singer Starboy Entertainment , a record label founded by Nigerian singer Wizkid Matt `` Starboy '' Bowden , rock musician and activist from New Zealand Starboy ( album ) , 2016 album by The Weeknd `` Starboy '' ( song ) , 2016 song by The Weeknd featuring Daft Punk `` Star Boy '' , song by Buffy Sainte Marie from Buffy `` Starboy '' , song by Guided by Voices from Same Place the Fly Got Smashed",
"title": ""
},
{
"docid": "List_of_awards_and_nominations_received_by_The_Weeknd",
"text": "Abel Tesfaye , known by his stage name The Weeknd , is a Canadian singer , songwriter and record producer . He rose to prominence following the release of his critically acclaimed mixtape House of Balloons , which was nominated for The Canadian Polaris Prize . After signing with the Republic Records in 2012 , he released his debut studio album , Kiss Land the following year to positive reviews . In 2015 , he won the Grammy Award for Best Urban Contemporary Album and Best R&B Performance for his second album , Beauty Behind the Madness . He has received a total of 75 awards out of 192 nominations .",
"title": ""
},
{
"docid": "Echoes_of_Silence",
"text": "Echoes of Silence is the third mixtape by Canadian singer The Weeknd , released December 21 , 2011 , by his official website . The release follows his Polaris Music Prize-nominated debut release House of Balloons and his second mixtape Thursday , both released earlier the same year . The project is the final installment in the trilogy of free albums released by The Weeknd in 2011 . The album was preceded by the release of the single , `` Initiation '' . Long-time collaborator Carlo `` Illangelo '' Montagnese returned to produce the bulk of the project , with other production contributions coming from Clams Casino and DropxLife of the XO crew . Rapper Juicy J contributes a short spoken-word interlude at the end of `` Same Old Song '' .",
"title": ""
},
{
"docid": "I_Feel_It_Coming",
"text": "`` I Feel It Coming '' is a song by Canadian singer The Weeknd featuring French electronic duo Daft Punk , from his third studio album , Starboy ( 2016 ) . It was written by the trio alongside Doc McKinney , Cirkut and Eric Chedeville , being produced by Daft Punk , with The Weeknd , McKinney and Cirkut serving as co-producers . The song was released for digital download on November 18 , 2016 , alongside `` Party Monster '' , as promotional singles . It was first sent to British contemporary hit radio on November 24 , 2016 , and it was released to US rhythmic contemporary radio on December 6 , 2016 through XO and Republic Records , serving as the album 's second single , following their previous collaboration `` Starboy '' .",
"title": ""
},
{
"docid": "Kiss_Land",
"text": "Kiss Land is the debut studio album by Canadian singer The Weeknd . It was released on September 10 , 2013 , by XO and Republic Records . The album was supported by six singles : `` Kiss Land '' , `` Belong to the World '' , `` Love in the Sky '' , `` Live For '' , `` Pretty '' and `` Wanderlust '' . The album 's sole guest appearance comes from frequent collaborator Drake . The album 's production was primarily handled by DannyBoyStyles , The Weeknd himself and Jason `` DaHeala '' Quenneville . Kiss Land received generally positive reviews from critics . The album debuted at number two on the Billboard 200 , selling 95,000 copies in its first week . As of August 2015 , the album had sold 273,000 copies in the United States .",
"title": ""
},
{
"docid": "Illangelo",
"text": "Carlo Montagnese ( born July 29 , 1987 ) , better known as Illangelo , is a Grammy Award-winning Canadian producer , songwriter , musician and mixing engineer from Calgary , Alberta , who came to attention as long-time collaborator of The Weeknd . His work includes executive production of The Weeknd 's 2011 mixtapes , the 2012 compilation album from The Weeknd titled Trilogy along with singles from rappers Wiz Khalifa 's `` Remember You '' , Drake 's `` Crew Love '' , Ricky Hil 's `` Nomads '' , all those featuring The Weeknd , and remixes such as Lady Gaga `` Marry The Night ( The Weeknd & Illangelo Remix ) '' and Florence and the Machine 's `` Shake It Out ( The Weeknd Remix ) '' . He released his debut concept album History of Man on August 20 , 2013 under his label Hear the Art Inc. & Bromance Records .",
"title": ""
},
{
"docid": "Thursday_(album)",
"text": "Thursday is the second mixtape by Canadian singer The Weeknd , independently released on August 19 , 2011 . It follows his critically acclaimed , Polaris Music Prize-nominated debut mixtape House of Balloons ( 2011 ) . Its music incorporates downtempo , dubstep , dream pop , hip hop , rock and reggae styles . As with his previous works , Canadian record producers Doc McKinney and Illangelo were responsible for production of the mixtape . Young Money artist Drake contributes guest vocals to the track `` The Zone '' . Thursday received generally positive reviews from critics , who drew comparisons to House of Balloons . `` Rolling Stone '' and `` The Birds Part 1 '' were released as buzz singles to precede the mixtape 's release . Thursday was later remastered and packaged with The Weeknd 's compilation album Trilogy ( 2012 ) .",
"title": ""
},
{
"docid": "Pray_For_Love",
"text": "`` Pray for Love '' is a rap song by American rapper Travis Scott featuring Canadian singer The Weeknd , and it was one of the songs from his debut album Rodeo .",
"title": ""
},
{
"docid": "Often",
"text": "`` Often '' is a song by Canadian singer The Weeknd . The track was released on July 31 , 2014 as the first single from his second studio album , Beauty Behind the Madness ( 2015 ) . The song reached number 59 on the Billboard Hot 100 and number 69 on the Canadian Hot 100 . The song samples the song `` Ben Sana Vurgunum '' sung by the Turkish singer Nükhet Duru .",
"title": ""
},
{
"docid": "Love_Me_Harder",
"text": "`` Love Me Harder '' is a song recorded by American singer Ariana Grande and Canadian singer The Weeknd from Grande 's second studio album , My Everything ( 2014 ) . It was written by Max Martin , Savan Kotecha , Peter Svensson , Ali Payami , Abel Tesfaye and Ahmad Balshe . The song was produced by Payami and Peter Carlsson , with Svensson serving as a vocal producer . It was released by Republic Records on September 30 , 2014 as the fourth single from the album . `` Love Me Harder '' is a synthpop and R&B track , with `` throbbing ' , electro-heavy chorus '' , guitar riff and `` big vacuum-esque synths zip '' . Lyrically , the song focuses on a deeper understanding of love as an emotional and physical state , having double entendres about rough sex . In the United States , the song peaked at number seven on the Billboard Hot 100 , becoming Grande 's fourth consecutive top-ten single off the album and making her the artist with the most top-ten singles in 2014 . The Hannah Lux Davis-directed video finds Grande and The Weeknd in an abandoned house in the desert filled with sand . As of March 2016 , the song has sold 1.2 million copies in the United States .",
"title": ""
},
{
"docid": "Derek_Wise",
"text": "Derek Bissue ( born December 11 , 1992 ) , better known by his stage name Derek Wise , is a Canadian hip hop recording artist from Toronto , Ontario . He is known to be affiliated with XO , the label and collective founded by singer The Weeknd .",
"title": ""
}
] |
883
|
Omnivores produce more trimethylamine N-oxide from dietary I-carnitine than vegans.
|
[
{
"docid": "14803797",
"text": "Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk.",
"title": "Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis"
}
] |
[
{
"docid": "6327940",
"text": "Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.",
"title": "Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity."
},
{
"docid": "33684572",
"text": "Recent studies indicate both clinical and mechanistic links between atherosclerotic heart disease and intestinal microbial metabolism of certain dietary nutrients producing trimethylamine N-oxide (TMAO). Here we test the hypothesis that gut microbial transplantation can transmit choline diet-induced TMAO production and atherosclerosis susceptibility. First, a strong association was noted between atherosclerotic plaque and plasma TMAO levels in a mouse diversity panel (n = 22 strains, r = 0.38; p = 0.0001). An atherosclerosis-prone and high TMAO-producing strain, C57BL/6J, and an atherosclerosis-resistant and low TMAO-producing strain, NZW/LacJ, were selected as donors for cecal microbial transplantation into apolipoprotein e null mice in which resident intestinal microbes were first suppressed with antibiotics. Trimethylamine (TMA) and TMAO levels were initially higher in recipients on choline diet that received cecal microbes from C57BL/6J inbred mice; however, durability of choline diet-dependent differences in TMA/TMAO levels was not maintained to the end of the study. Mice receiving C57BL/6J cecal microbes demonstrated choline diet-dependent enhancement in atherosclerotic plaque burden as compared with recipients of NZW/LacJ microbes. Microbial DNA analyses in feces and cecum revealed transplantation of donor microbial community features into recipients with differences in taxa proportions between donor strains that were transmissible to recipients and that tended to show coincident proportions with TMAO levels. Proportions of specific taxa were also identified that correlated with plasma TMAO levels in donors and recipients and with atherosclerotic lesion area in recipients. Atherosclerosis susceptibility may be transmitted via transplantation of gut microbiota. Gut microbes may thus represent a novel therapeutic target for modulating atherosclerosis susceptibility.",
"title": "Transmission of atherosclerosis susceptibility with gut microbial transplantation."
},
{
"docid": "12709184",
"text": "IMPORTANCE Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality, but the relationship is not well established. OBJECTIVE To evaluate the association between vegetarian dietary patterns and mortality. DESIGN Prospective cohort study; mortality analysis by Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. SETTING Adventist Health Study 2 (AHS-2), a large North American cohort. PARTICIPANTS A total of 96,469 Seventh-day Adventist men and women recruited between 2002 and 2007, from which an analytic sample of 73,308 participants remained after exclusions. EXPOSURES Diet was assessed at baseline by a quantitative food frequency questionnaire and categorized into 5 dietary patterns: nonvegetarian, semi-vegetarian, pesco-vegetarian, lacto-ovo-vegetarian, and vegan. MAIN OUTCOME AND MEASURE The relationship between vegetarian dietary patterns and all-cause and cause-specific mortality; deaths through 2009 were identified from the National Death Index. RESULTS There were 2570 deaths among 73,308 participants during a mean follow-up time of 5.79 years. The mortality rate was 6.05 (95% CI, 5.82-6.29) deaths per 1000 person-years. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs nonvegetarians was 0.88 (95% CI, 0.80-0.97). The adjusted HR for all-cause mortality in vegans was 0.85 (95% CI, 0.73-1.01); in lacto-ovo-vegetarians, 0.91 (95% CI, 0.82-1.00); in pesco-vegetarians, 0.81 (95% CI, 0.69-0.94); and in semi-vegetarians, 0.92 (95% CI, 0.75-1.13) compared with nonvegetarians. Significant associations with vegetarian diets were detected for cardiovascular mortality, noncardiovascular noncancer mortality, renal mortality, and endocrine mortality. Associations in men were larger and more often significant than were those in women. CONCLUSIONS AND RELEVANCE Vegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality. Results appeared to be more robust in males. These favorable associations should be considered carefully by those offering dietary guidance.",
"title": "Vegetarian dietary patterns and mortality in Adventist Health Study 2."
},
{
"docid": "39187170",
"text": "Adipose tissue exerts important endocrine and metabolic functions in health and disease. Yet the bioenergetics of this tissue is not characterized in humans and possible regional differences are not elucidated. Using high resolution respirometry, mitochondrial respiration was quantified in human abdominal subcutaneous and intra-abdominal visceral (omentum majus) adipose tissue from biopsies obtained in 20 obese patients undergoing bariatric surgery. Mitochondrial DNA (mtDNA) and genomic DNA (gDNA) were determined by the PCR technique for estimation of mitochondrial density. Adipose tissue samples were permeabilized and respirometric measurements were performed in duplicate at 37 degrees C. Substrates (glutamate (G) + malate (M) + octanoyl carnitine (O) + succinate (S)) were added sequentially to provide electrons to complex I + II. ADP ((D)) for state 3 respiration was added after GM. Uncoupled respiration was measured after addition of FCCP. Visceral fat contained more mitochondria per milligram of tissue than subcutaneous fat, but the cells were smaller. Robust, stable oxygen fluxes were found in both tissues, and coupled state 3 (GMOS(D)) and uncoupled respiration were significantly (P < 0.05) higher in visceral (0.95 +/- 0.05 and 1.15 +/- 0.06 pmol O(2) s(1) mg(1), respectively) compared with subcutaneous (0.76 +/- 0.04 and 0.98 +/- 0.05 pmol O(2) s(1) mg(1), respectively) adipose tissue. Expressed per mtDNA, visceral adipose tissue had significantly (P < 0.05) lower mitochondrial respiration. Substrate control ratios were higher and uncoupling control ratio lower (P < 0.05) in visceral compared with subcutaneous adipose tissue. We conclude that visceral fat is bioenergetically more active and more sensitive to mitochondrial substrate supply than subcutaneous fat. Oxidative phosphorylation has a higher relative activity in visceral compared with subcutaneous adipose tissue.",
"title": "Mitochondrial respiration in subcutaneous and visceral adipose tissue from patients with morbid obesity."
},
{
"docid": "6793674",
"text": "Circulating trimethylamine N-oxide (TMAO), a canonical metabolite from gut flora, has been related to the risk of cardiovascular disorders. However, the association between circulating TMAO and the risk of cardiovascular events has not been quantitatively evaluated. We performed a systematic review and meta-analysis of all available cohort studies regarding the association between baseline circulating TMAO and subsequent cardiovascular events. Embase and PubMed databases were searched for relevant cohort studies. The overall hazard ratios for the developing of cardiovascular events (CVEs) and mortality were extracted. Heterogeneity among the included studies was evaluated with Cochran's Q Test and I2 statistics. A random-effect model or a fixed-effect model was applied depending on the heterogeneity. Subgroup analysis and meta-regression were used to evaluate the source of heterogeneity. Among the 11 eligible studies, three reported both CVE and mortality outcome, one reported only CVEs and the other seven provided mortality data only. Higher circulating TMAO was associated with a 23% higher risk of CVEs (HR = 1.23, 95% CI: 1.07-1.42, I2 = 31.4%) and a 55% higher risk of all-cause mortality (HR = 1.55, 95% CI: 1.19-2.02, I2 = 80.8%). Notably, the latter association may be blunted by potential publication bias, although sensitivity analysis by omitting one study at a time did not significantly change the results. Further subgroup analysis and meta-regression did not support that the location of the study, follow-up duration, publication year, population characteristics or the samples of TMAO affect the results significantly. Higher circulating TMAO may independently predict the risk of subsequent cardiovascular events and mortality.",
"title": "Circulating trimethylamine N‐oxide and the risk of cardiovascular diseases: a systematic review and meta‐analysis of 11 prospective cohort studies"
},
{
"docid": "11181416",
"text": "Because arginase hydrolyzes arginine to produce ornithine and urea, it has the potential to regulate nitric oxide (NO) and polyamine synthesis. We tested whether expression of the cytosolic isoform of arginase (arginase I) was limiting for NO or polyamine production by activated RAW 264.7 macrophage cells. RAW 264.7 cells, stably transfected to overexpress arginase I or beta-galactosidase, were treated with interferon-gamma to induce type 2 NO synthase or with lipopolysaccharide or 8-bromo-cAMP (8-BrcAMP) to induce ornithine decarboxylase. Overexpression of arginase I had no effect on NO synthesis. In contrast, cells overexpressing arginase I produced twice as much putrescine after activation than did cells expressing beta-galactosidase. Cells overexpressing arginase I also produced more spermidine after treatment with 8-BrcAMP than did cells expressing beta-galactosidase. Thus endogenous levels of arginase I are limiting for polyamine synthesis, but not for NO synthesis, by activated macrophage cells. This study also demonstrates that it is possible to alter arginase I levels sufficiently to affect polyamine synthesis without affecting induced NO synthesis.",
"title": "Arginase I: a limiting factor for nitric oxide and polyamine synthesis by activated macrophages?"
},
{
"docid": "35962023",
"text": "Recent studies suggest a close relationship between cell metabolism and apoptosis. We have evaluated changes in lipid metabolism on permeabilized hepatocytes treated with truncated Bid (tBid) in the presence of caspase inhibitors and exogenous cytochrome c. The measurement of β-oxidation flux by labeled palmitate demonstrates that tBid inhibits β-oxidation, thereby resulting in the accumulation of palmitoyl-coenzyme A (CoA) and depletion of acetyl-carnitine and acylcarnitines, which is pathognomonic for inhibition of carnitine palmitoyltransferase-1 (CPT-1). We also show that tBid decreases CPT-1 activity by a mechanism independent of both malonyl-CoA, the key inhibitory molecule of CPT-1, and Bak and/or Bax, but dependent on cardiolipin decrease. Overexpression of Bcl-2, which is able to interact with CPT-1, counteracts the effects exerted by tBid on β-oxidation. The unexpected role of tBid in the regulation of lipid β-oxidation suggests a model in which tBid-induced metabolic decline leads to the accumulation of toxic lipid metabolites such as palmitoyl-CoA, which might become participants in the apoptotic pathway.",
"title": "tBid induces alterations of mitochondrial fatty acid oxidation flux by malonyl-CoA-independent inhibition of carnitine palmitoyltransferase-1"
},
{
"docid": "44693226",
"text": "Many studies have shown that caloric restriction (40%) decreases mitochondrial reactive oxygen species (ROS) generation in rodents. Moreover, we have recently found that 7 weeks of 40% protein restriction without strong caloric restriction also decreases ROS production in rat liver. This is interesting since it has been reported that protein restriction can also extend longevity in rodents. In the present study we have investigated the possible role of dietary lipids in the effects of caloric restriction on mitochondrial oxidative stress. Using semipurified diets, the ingestion of lipids in male Wistar rats was decreased by 40% below controls, while the other dietary components were ingested at exactly the same level as in animals fed ad libitum. After 7 weeks of treatment the liver mitochondria of lipid-restricted animals showed significant increases in oxygen consumption with complex I-linked substrates (pyruvate/malate and glutamate/malate). Neither mitochondrial H(2)O(2) production nor oxidative damage to mitochondrial or nuclear DNA was modified in lipid-restricted animals. Oxidative damage to mitochondrial DNA was one order of magnitude higher than that of nuclear DNA in both dietary groups. These results deny a role for lipids and reinforce the possible role of dietary proteins as being responsible for the decrease in mitochondrial ROS production and DNA damage in caloric restriction.",
"title": "Effect of lipid restriction on mitochondrial free radical production and oxidative DNA damage."
},
{
"docid": "22995164",
"text": "Nitrosoglutathione [(GSNO), 500 nmol/l] relaxed the norepinephrine precontracted rat aortic rings. The relaxation effect was pronouncedly enhanced by H2S- and HS−-donor NaHS (30 μmol/l) at 7.5 pH but not at 6.3 pH. To study molecular mechanism of this effect, we investigated whether NaHS can release NO from NO donors. Using an electron paramagnetic resonance spectroscopy method of spin trap and by measuring the NO oxidation product, which is nitrite, by the Griess reaction, we report that NaHS released NO from nitrosothiols, namely from GSNO, S-nitroso-N-acetyl-dl-penicillamine (SNAP), from metal nitrosyl complex nitroprusside (SNP) and from rat brain homogenate and murine L1210 leukaemia cells. From the observation that the releasing effect was more pronounced at 8.0 pH than 6.0 pH, we suppose that HS−, rather than H2S, is responsible for the NO-releasing effect. Since in mammals, H2S and HS− are produced endogenously, we assume that their effect to release NO from nitrosothiols and from metal nitrosyl complexes are responsible for some of their biological activities and that this mechanism may be involved in S-nitrosothiol-signalling reactions.",
"title": "H2S and HS− donor NaHS releases nitric oxide from nitrosothiols, metal nitrosyl complex, brain homogenate and murine L1210 leukaemia cells"
},
{
"docid": "13380011",
"text": "Partial inhibition of mitochondrial respiratory complex I by rotenone reproduces aspects of Parkinson's disease in rodents. The hypothesis that rotenone enhancement of neuronal cell death is attributable to oxidative stress was tested in an acute glutamate excitotoxicity model using primary cultures of rat cerebellar granule neurons. As little as 5 nM rotenone increased mitochondrial superoxide (O2*-) levels and potentiated glutamate-induced cytoplasmic Ca2+ deregulation, the first irreversible stage of necrotic cell death. However, the potent cell-permeant O2*- trap manganese tetrakis (N-ethylpyridinium-2yl) porphyrin failed to prevent the effects of the inhibitor. The bioenergetic consequences of rotenone addition were quantified by monitoring cell respiration. Glutamate activation of NMDA receptors used the full respiratory capacity of the in situ mitochondria, and >80% of the glutamate-stimulated respiration was attributable to increased cellular ATP demand. Rotenone at 20 nM inhibited basal and carbonyl cyanide p-trifluoromethoxyphenylhydrazone-stimulated cell respiration and caused respiratory failure in the presence of glutamate. ATP synthase inhibition by oligomycin was also toxic in the presence of glutamate. We conclude that the cell vulnerability in the rotenone model of partial complex I deficiency under these specific conditions is primarily determined by spare respiratory capacity rather than oxidative stress.",
"title": "Spare respiratory capacity rather than oxidative stress regulates glutamate excitotoxicity after partial respiratory inhibition of mitochondrial complex I with rotenone."
},
{
"docid": "24349992",
"text": "Loss of stromal fibroblast caveolin-1 (Cav-1) is a powerful single independent predictor of poor prognosis in human breast cancer patients, and is associated with early tumor recurrence, lymph node metastasis and tamoxifen-resistance. We developed a novel co-culture system to understand the mechanism(s) by which a loss of stromal fibroblast Cav-1 induces a \"lethal tumor micro-environment. \" Here, we propose a new paradigm to explain the powerful prognostic value of stromal Cav-1. In this model, cancer cells induce oxidative stress in cancer-associated fibroblasts, which then acts as a \"metabolic\" and \"mutagenic\" motor to drive tumor-stroma co-evolution, DNA damage and aneuploidy in cancer cells. More specifically, we show that an acute loss of Cav-1 expression leads to mitochondrial dysfunction, oxidative stress and aerobic glycolysis in cancer associated fibroblasts. Also, we propose that defective mitochondria are removed from cancer-associated fibroblasts by autophagy/mitophagy that is induced by oxidative stress. As a consequence, cancer associated fibroblasts provide nutrients (such as lactate) to stimulate mitochondrial biogenesis and oxidative metabolism in adjacent cancer cells (the \"Reverse Warburg Effect\"). We provide evidence that oxidative stress in cancer-associated fibroblasts is sufficient to induce genomic instability in adjacent cancer cells, via a bystander effect, potentially increasing their aggressive behavior. Finally, we directly demonstrate that nitric oxide (NO) over-production, secondary to Cav-1 loss, is the root cause for mitochondrial dysfunction in cancer associated fibroblasts. In support of this notion, treatment with anti-oxidants (such as N-acetyl-cysteine, metformin and quercetin) or NO inhibitors (L-NAME) was sufficient to reverse many of the cancer-associated fibroblast phenotypes that we describe. Thus, cancer cells use \"oxidative stress\" in adjacent fibroblasts (i) as an \"engine\" to fuel their own survival via the stromal production of nutrients and (ii) to drive their own mutagenic evolution towards a more aggressive phenotype, by promoting genomic instability. We also present evidence that the \"field effect\" in cancer biology could also be related to the stromal production of ROS and NO species. eNOS-expressing fibroblasts have the ability to downregulate Cav-1 and induce mitochondrial dysfunction in adjacent fibroblasts that do not express eNOS. As such, the effects of stromal oxidative stress can be laterally propagated, amplified and are effectively \"contagious\"--spread from cell-to-cell like a virus--creating an \"oncogenic/mutagenic\" field promoting widespread DNA damage.",
"title": "Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells."
},
{
"docid": "15615957",
"text": "UNLABELLED Fruit and vegetable consumption has been inversely associated with the risk of chronic diseases including cancer and cardiovascular disease, with the beneficial effects attributed to a variety of protective antioxidants, carotenoids and phytonutrients. The objective of the present study was to determine the effect of supplementation with dehydrated concentrates from mixed fruit and vegetable juices (Juice Plus+R) on serum antioxidant and folate status, plasma homocysteine levels and markers for oxidative stress and DNA damage. Japanese subjects (n=60; age 27.8 yrs; BMI 22.1) were recruited to participate in a double-blind placebo controlled study and were randomized into 2 groups of 30, matched for sex, age, BMI and smoking status (39 males, 22 smokers; 21 females, 13 smokers). Subjects were given encapsulated supplements containing mixed fruit and vegetable juice concentrates or a matching placebo for 28 days, with blood and urine samples collected at baseline, day 14 and day 28 for analytical testing. Compared with the placebo, 28 day supplementation significantly increased the concentration of serum beta-carotene 528% (p<0.0001), lycopene 80.2% (p<0.0005), and alpha tocopherol 39.5% (p<0.0001). Serum folate increased 174.3% (p<0.0001) and correlated with a decrease in plasma homocysteine of -19.9% (p<0.03). Compared with baseline, measures of oxidative stress decreased with serum lipid peroxides declining -10.5% (p<0.02) and urine 8OHdG decreasing -21.1% (p<0.02). Evaluation of data from smokers only (n=17) after 28 days of active supplementation showed comparable changes. CONCLUSION In the absence of dietary modification, supplementation with the fruit and vegetable juice concentrate capsules proved to be a highly bioavailable source of phytonutrients. Important antioxidants were elevated to desirable levels associated with decreased risk of disease while markers of oxidative stress were reduced, and folate status improved with a concomitant decrease in homocysteine, and these benefits occurred to a similar extent in smokers when compared to non-smokers.",
"title": "Original Article"
},
{
"docid": "35828148",
"text": "Apocynin has been reported to require dimerization by myeloperoxidase (MPO) to inhibit leukocyte NADPH oxidase. (-)-Epicatechin, a dietary flavan-3-ol, has been identified as a 'prodrug' of apocynin-like metabolites that inhibit endothelial NADPH oxidase activity and elevate the cellular level of nitric oxide. Since (-)-epicatechin has tentatively been identified as substrate of MPO, we studied the one-electron oxidation of (-)-epicatechin by MPO. By using multi-mixing stopped-flow technique, we demonstrate that (-)-epicatechin is one of the most efficient electron donors for heme peroxidases investigated so far. Second order rate constants for the (-)-epicatechin-mediated conversion of MPO-compound I to compound II and compound II to resting enzyme were estimated to be 1.9 x 10(7) and 4.5 x 10(6) M(-1)s(-1), respectively (pH 7, 25 degrees C). The data indicate that (-)-epicatechin is capable of undergoing fast MPO-mediated one-electron oxidation.",
"title": "Kinetic evidence for rapid oxidation of (-)-epicatechin by human myeloperoxidase."
},
{
"docid": "25974070",
"text": "The amount and type of dietary fat have long been associated with the risk of CVD. Arterial stiffness and endothelial dysfunction are important risk factors in the aetiology of CHD. A range of methods exists to assess vascular function that may be used in nutritional science, including clinic and ambulatory blood pressure monitoring, pulse wave analysis, pulse wave velocity, flow-mediated dilatation and venous occlusion plethysmography. The present review focuses on the quantity and type of dietary fat and effects on blood pressure, arterial compliance and endothelial function. Concerning fat quantity, the amount of dietary fat consumed habitually appears to have little influence on vascular function independent of fatty acid composition, although single high-fat meals postprandially impair endothelial function compared with low-fat meals. The mechanism is related to increased circulating lipoproteins and NEFA which may induce pro-inflammatory pathways and increase oxidative stress. Regarding the type of fat, cross-sectional data suggest that saturated fat adversely affects vascular function whereas polyunsaturated fat (mainly linoleic acid (18 : 2n-6) and n-3 PUFA) are beneficial. EPA (20 : 5n-3) and DHA (22 : 6n-3) can reduce blood pressure, improve arterial compliance in type 2 diabetics and dyslipidaemics, and augment endothelium-dependent vasodilation. The mechanisms for this vascular protection, and the nature of the separate physiological effects induced by EPA and DHA, are priorities for future research. Since good-quality observational or interventional data on dietary fatty acid composition and vascular function are scarce, no further recommendations can be suggested in addition to current guidelines at the present time.",
"title": "Dietary saturated and unsaturated fats as determinants of blood pressure and vascular function."
},
{
"docid": "5687200",
"text": "AIMS The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. METHODS A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. RESULTS Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [-6.2 kg (95% CI -6.6 to -5.3) vs. -3.2 kg (95% CI -3.7 to -2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5-39) vs. 20% (95% CI 14-25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. CONCLUSIONS A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.",
"title": "Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes"
},
{
"docid": "6191684",
"text": "CONTEXT Chronic tension-type headaches are characterized by near-daily headaches and often are difficult to manage in primary practice. Behavioral and pharmacological therapies each appear modestly effective, but data are lacking on their separate and combined effects. OBJECTIVE To evaluate the clinical efficacy of behavioral and pharmacological therapies, singly and combined, for chronic tension-type headaches. DESIGN AND SETTING Randomized placebo-controlled trial conducted from August 1995 to January 1998 at 2 outpatient sites in Ohio. PARTICIPANTS Two hundred three adults (mean age, 37 years; 76% women) with diagnosis of chronic tension-type headaches (mean, 26 headache d/mo). INTERVENTIONS Participants were randomly assigned to receive tricyclic antidepressant (amitriptyline hydrochloride, up to 100 mg/d, or nortriptyline hydrochloride, up to 75 mg/d) medication (n = 53), placebo (n = 48), stress management (eg, relaxation, cognitive coping) therapy (3 sessions and 2 telephone contacts) plus placebo (n = 49), or stress management therapy plus antidepressant medication (n = 53). MAIN OUTCOME MEASURES Monthly headache index scores calculated as the mean of pain ratings (0-10 scale) recorded by participants in a daily diary 4 times per day; number of days per month with at least moderate pain (pain rating >/=5), analgesic medication use, and Headache Disability Inventory scores, compared by intervention group. RESULTS Tricyclic antidepressant medication and stress management therapy each produced larger reductions in headache activity, analgesic medication use, and headache-related disability than placebo, but antidepressant medication yielded more rapid improvements in headache activity. Combined therapy was more likely to produce clinically significant (>/=50%) reductions in headache index scores (64% of participants) than antidepressant medication (38% of participants; P =.006), stress management therapy (35%; P =.003), or placebo (29%; P =.001). On other measures the combined therapy and its 2 component therapies produced similar outcomes. CONCLUSIONS Our results indicate that antidepressant medication and stress management therapy are each modestly effective in treating chronic tension-type headaches. Combined therapy may improve outcome relative to monotherapy.",
"title": "Management of chronic tension-type headache with tricyclic antidepressant medication, stress management therapy, and their combination: a randomized controlled trial."
},
{
"docid": "28644298",
"text": "Epstein-Barr virus (EBV) latency III infection converts B lymphocytes into lymphoblastoid cell lines (LCLs) by expressing EBV nuclear and membrane proteins, EBNAs, and latent membrane proteins (LMPs), which regulate transcription through Notch and tumor necrosis factor receptor pathways. The role of NF-kappa B in LMP1 and overall EBV latency III transcriptional effects was investigated by treating LCLs with BAY11-7082 (BAY11). BAY11 rapidly and irreversibly inhibited NF-kappa B, decreased mitochondrial membrane potential, induced apoptosis, and altered LCL gene expression. BAY11 effects were similar to those of an NF-kappa B inhibitor, Delta N-I kappa B alpha, in effecting decreased JNK1 expression and in microarray analyses. More than 80% of array elements that decreased with Delta N-I kappa B alpha expression decreased with BAY11 treatment. Newly identified NF-kappa B-induced, LMP1-induced, and EBV-induced genes included pleckstrin, Jun-B, c-FLIP, CIP4, and I kappa B epsilon. Of 776 significantly changed array elements, 134 were fourfold upregulated in EBV latency III, and 74 were fourfold upregulated with LMP1 expression alone, whereas only 28 were more than fourfold downregulated by EBV latency III. EBV latency III-regulated gene products mediate cell migration (EBI2, CCR7, RGS1, RANTES, MIP1 alpha, MIP1 beta, CXCR5, and RGS13), antigen presentation (major histocompatibility complex proteins and JAW1), mitogen-activated protein kinase pathway (DUSP5 and p62Dok), and interferon (IFN) signaling (IFN-gamma R alpha, IRF-4, and STAT1). Comparison of EBV latency III LCL gene expression to immunoglobulin M (IgM)-stimulated B cells, germinal-center B cells, and germinal-center-derived lymphomas clustered LCLs with IgM-stimulated B cells separately from germinal-center cells or germinal-center lymphoma cells. Expression of IRF-2, AIM1, ASK1, SNF2L2, and components of IFN signaling pathways further distinguished EBV latency III-infected B cells from IgM-stimulated or germinal-center B cells.",
"title": "Role of NF-kappa B in cell survival and transcription of latent membrane protein 1-expressing or Epstein-Barr virus latency III-infected cells."
},
{
"docid": "24594624",
"text": "Maternal diabetes mellitus is a significant risk factor for structural birth defects, including congenital heart defects and neural tube defects. With the rising prevalence of type 2 diabetes mellitus and obesity in women of childbearing age, diabetes mellitus-induced birth defects have become an increasingly significant public health problem. Maternal diabetes mellitus in vivo and high glucose in vitro induce yolk sac injuries by damaging the morphologic condition of cells and altering the dynamics of organelles. The yolk sac vascular system is the first system to develop during embryogenesis; therefore, it is the most sensitive to hyperglycemia. The consequences of yolk sac injuries include impairment of nutrient transportation because of vasculopathy. Although the functional relationship between yolk sac vasculopathy and structural birth defects has not yet been established, a recent study reveals that the quality of yolk sac vasculature is related inversely to embryonic malformation rates. Studies in animal models have uncovered key molecular intermediates of diabetic yolk sac vasculopathy, which include hypoxia-inducible factor-1α, apoptosis signal-regulating kinase 1, and its inhibitor thioredoxin-1, c-Jun-N-terminal kinases, nitric oxide, and nitric oxide synthase. Yolk sac vasculopathy is also associated with abnormalities in arachidonic acid and myo-inositol. Dietary supplementation with fatty acids that restore lipid levels in the yolk sac lead to a reduction in diabetes mellitus-induced malformations. Although the role of the human yolk in embryogenesis is less extensive than in rodents, nevertheless, human embryonic vasculogenesis is affected negatively by maternal diabetes mellitus. Mechanistic studies have identified potential therapeutic targets for future intervention against yolk sac vasculopathy, birth defects, and other complications associated with diabetic pregnancies.",
"title": "New development of the yolk sac theory in diabetic embryopathy: molecular mechanism and link to structural birth defects."
},
{
"docid": "19327364",
"text": "Sera from 526 Old-World monkeys and apes, representing 50 species and 20 genera and living in US zoos and vivaria, were screened for antibodies to HTLV-I, HTLV-III/LAV, and simian-AIDS retrovirus, type I (SRV-I). Sera were screened initially by ELISA, and ELISA-positive sera, as well as ELISA-negative sera from cage contacts, were further tested by Western blotting. A large number of false-positive and a small number of false-negative ELISA sera were identified. Although most true positive reactions were directed to a single retrovirus, a number of individuals from 4 species were positive for more than one retrovirus. Specific seroreactivity to HTLV-I was found in 39/526 (7%) animals of 15 species. True positive reactions to SRV-I were found in 21/516 (4%) animals, including talapoins and 2 species of macaques. Specific serologic reactions to HTLV-III/LAV were detected in 23/526 (4%) monkeys. Many of the HTLV-III/LAV seropositive animals were from one mixed-species zoo exhibit, containing sooty mangabeys, mandrills, Kolb's guenons, and talapoins. A type D virus was isolated from the blood of 3/10 SRV-I antibody-positive Tonkeana macaques, but from none of 11 seropositive talapoins. A lentivirus was isolated from the blood of 4/7 HTLV-III/LAV seropositive sooty mangabeys, but not from seropositive talapoins in the same exhibit or from 2 seropositive colobus from another zoo. The sooty mangabey lentivirus produced generalized lymphadenopathy, leukopenia, and decreased levels of T4 lymphocytes in 2 experimentally infected rhesus macaques.",
"title": "Seroepidemiologic survey of captive Old-World primates for antibodies to human and simian retroviruses, and isolation of a lentivirus from sooty mangabeys (Cercocebus atys)."
},
{
"docid": "23245050",
"text": "Dietary status was evaluated in eight highly trained female cyclists. Each cyclist kept a 3-day weighed food record. Diets were analyzed for nutrient content using a computerized software package. Blood was also obtained and evaluated for hemoglobin, hematocrit, and albumin. For an athletic group, the cyclists' diets were found to be low in energy (85% RDA) and carbohydrate (4.4 gm/kg body weight per day). Mean daily dietary intakes were well below the RDAs for folacin (76% RDA), magnesium (81%), iron (59%), and zinc (48%). In addition, more than one-third of the cyclists failed to consume 67% of the RDA for the following micronutrients: pyridoxine, folacin, cobalamin, vitamin E, magnesium, iron, and zinc. Hemoglobin (135 gm/L), hematocrit (0.39), and albumin (45 gm/L) values were all normal, although most hemoglobin values were in the lower 50% of normal range. Foods such as meats, poultry, fish, beans, peas, and nuts were low or absent from the diets of most athletes. Dietary quality in this group of female cyclists could have been greatly improved with the addition of more of those foods. These athletes could benefit from nutrition education and diet counseling.",
"title": "Dietary status of trained female cyclists."
},
{
"docid": "25135304",
"text": "The purpose of this study was to examine the relation of leptin to metabolic and dietary factors in college-age adults. Young adult women and men (n = 32) were recruited and underwent testing for measurement of body mass index, body composition, peak oxygen consumption (VO2peak), dietary intake, and plasma levels of leptin and insulin. Ln leptin was significantly greater for women than for men (2.1 versus 1.2 ng/mL, respectively). This difference remained significant even after adjusting ln leptin for fat mass and fat-free mass as covariates in separate analyses. VO2peak was higher for men than for women and this remained significant after adjustment for differences in fat-free mass and total body mass. Significant correlations were found between ln leptin and indicators of fat mass in women and men, with higher correlations for similar variables observed in men (r = 0.548, 0.674, and 0.732 for body mass index, percentage of body fat, and fat mass [kg] for women, respectively, and r = 0.740, 0.888, 0.858 for body mass index, percentage of body fat, and fat mass [kg] for men, respectively). Ln leptin showed a significant inverse relationship with VO2peak (r = -0.751) in men only. After adjusting ln leptin for body fat mass using partial correlations, ln leptin was not significantly associated with any of the measured variables. Alternatively, after normalization of ln leptin using fat mass as the divisor, a less adequate statistical analysis method, men showed statistical significant correlations between ln leptin and dietary intake and VO2peak. Although plasma leptin values were higher in women, stronger associations were evident for men than for women between leptin and metabolic and dietary factors.",
"title": "Relation of plasma leptin concentrations to sex, body fat, dietary intake, and peak oxygen uptake in young adult women and men."
},
{
"docid": "20672596",
"text": "Maximum activities of some key enzymes of metabolism were studied in elicited (inflammatory) macrophages of the mouse and lymph-node lymphocytes of the rat. The activity of hexokinase in the macrophage is very high, as high as that in any other major tissue of the body, and higher than that of phosphorylase or 6-phosphofructokinase, suggesting that glucose is a more important fuel than glycogen and that the pentose phosphate pathway is also important in these cells. The latter suggestion is supported by the high activities of both glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. However, the rate of glucose utilization by 'resting' macrophages incubated in vitro is less than the 10% of the activity of 6-phosphofructokinase: this suggests that the rate of glycolysis is increased dramatically during phagocytosis or increased secretory activity. The macrophages possess higher activities of citrate synthase and oxoglutarate dehydrogenase than do lymphocytes, suggesting that the tricarboxylic acid cycle may be important in energy generation in these cells. The activity of 3-oxoacid CoA-transferase is higher in the macrophage, but that of 3-hydroxybutyrate dehydrogenase is very much lower than those in the lymphocytes. The activity of carnitine palmitoyltransferase is higher in macrophages, suggesting that fatty acids as well as acetoacetate could provide acetyl-CoA as substrate for the tricarboxylic acid cycle. No detectable rate of acetoacetate or 3-hydroxybutyrate utilization was observed during incubation of resting macrophages, but that of oleate was 1.0 nmol/h per mg of protein or about 2.2% of the activity of palmitoyltransferase. The activity of glutaminase is about 4-fold higher in macrophages than in lymphocytes, which suggests that the rate of glutamine utilization could be very high. The rate of utilization of glutamine by resting incubated macrophages was similar to that reported for rat lymphocytes, but was considerably lower than the activity of glutaminase.",
"title": "Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by murine macrophages."
},
{
"docid": "2659805",
"text": "A number of methods have been developed to assist subjects in providing an estimate of portion size but their application in improving portion size estimation by children has not been investigated systematically. The aim was to develop portion size assessment tools for use with children and to assess the accuracy of children's estimates of portion size using the tools. The tools were food photographs, food models and an interactive portion size assessment system (IPSAS). Children (n 201), aged 4-16 years, were supplied with known quantities of food to eat, in school. Food leftovers were weighed. Children estimated the amount of each food using each tool, 24 h after consuming the food. The age-specific portion sizes represented were based on portion sizes consumed by children in a national survey. Significant differences were found between the accuracy of estimates using the three tools. Children of all ages performed well using the IPSAS and food photographs. The accuracy and precision of estimates made using the food models were poor. For all tools, estimates of the amount of food served were more accurate than estimates of the amount consumed. Issues relating to reporting of foods left over which impact on estimates of the amounts of foods actually consumed require further study. The IPSAS has shown potential for assessment of dietary intake with children. Before practical application in assessment of dietary intake of children the tool would need to be expanded to cover a wider range of foods and to be validated in a 'real-life' situation.",
"title": "Children's estimates of food portion size: the development and evaluation of three portion size assessment tools for use with children."
},
{
"docid": "22889972",
"text": "Inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) have been implicated in atherogenesis. However, the precise role of TNF-alpha in atherogenesis is still unclear. To examine the effect of TNF-alpha on atherogenesis, we generated compound-deficient mice in apolipoprotein E (apoE) and TNF-alpha (apoE-/-/TNF-alpha-/-) and compared them with apoE-/- mice. Although serum total cholesterol levels were markedly elevated in both apoE-/-/TNF-alpha-/- and apoE-/- mice compared to wild-type mice, no differences were observed between apoE-/-/TNF-alpha-/- and apoE-/- mice. The atherosclerotic plaque area in the aortic luminal surface of apoE-/-/TNF-alpha-/- mice (n=8, 3.1+/-0.4%) was significantly smaller than that of apoE-/- mice (n=7, 4.7+/-0.4%, p<0.001) despite the lack of difference in serum cholesterol levels. The atherosclerotic lesion size in the aortic sinus of apoE-/-/TNF-alpha-/- mice (n=10, 5.1+/-0.3 x 10(5)microm(2)) was also significantly smaller than that of apoE-/- mice (n=11, 7.0+/-0.3 x 10(5)microm(2), p<0.0001). RT-PCR analysis indicated that the expression levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) were significantly higher in apoE-/- than apoE-/-/TNF-alpha-/- mice. Macrophages from apoE(-/-) mice showed higher uptake level of oxidized LDL and increased expression level of scavenger receptor class A (SRA) compared to those from apoE-/-/TNF-alpha-/- mice. These results indicate that TNF-alpha plays an atherogenic role by upregulating the expressions of ICAM-1, VCAM-1 and MCP-1 in the vascular wall, and by inducing SRA expression and oxidized LDL uptake in macrophages.",
"title": "Disruption of tumor necrosis factor-alpha gene diminishes the development of atherosclerosis in ApoE-deficient mice."
},
{
"docid": "43048059",
"text": "AIMS The present study aims to investigate the interaction between nitric oxide (NO) and hydrogen sulfide (H(2)S), the two important gaseous mediators in rat hearts. METHODS AND RESULTS Intracellular calcium in isolated cardiomyocytes was measured with a spectrofluorometric method using Fura-2. Myocyte contractility was measured with a video edge system. NaHS (50 µM, an H(2)S donor) had no significant effect on the resting calcium level, electrically induced (EI) calcium transients, and cell contractility in ventricular myocytes. Stimulating endogenous NO production with l-arginine or exogenous application of NO donors [sodium nitroprusside (SNP) and 2-(N,N-diethylamino)-diazenolate-2-oxide] decreased myocyte twitch amplitudes accompanied by slower velocities of both cell contraction and relaxation. Surprisingly, NaHS reversed the negative inotropic and lusitropic effects of the above three NO-increasing agents. In addition, the mixture of SNP + NaHS increased, whereas SNP alone decreased, the resting calcium level and the amplitudes of EI calcium transients. Angeli's salt, a nitroxyl anion (HNO) donor, mimicked the effect of SNP + NaHS on calcium handling and myocyte contractility. Three thiols, N-acetyl-cysteine, l-cysteine, and glutathione, abolished the effects of HNO and SNP + NaHS on myocyte contraction. Neither Rp-cAMP [a protein kinase A (PKA) inhibitor] nor Rp-cGMP [a protein kinase G (PKG) inhibitor] affected the effects of SNP + NaHS, suggesting a cAMP/PKA- or cGMP/PKG-independent mechanism. CONCLUSION H(2)S may interact with NO to form a thiol sensitive molecule (probably HNO) which produces positive inotropic and lusitropic effects. Our findings may shed light on the interaction of NO and H(2)S and provide new clues to treat cardiovascular diseases.",
"title": "Hydrogen sulfide interacts with nitric oxide in the heart: possible involvement of nitroxyl."
},
{
"docid": "41310252",
"text": "The epidemiological evidence that a high-fat diet promotes the development of obesity is considered suggestive but not definitive. The purpose of this paper is to provide a review of various epidemiological methods that have been used to address this issue as well as an updated summary of the existing evidence. Ecological studies describing dietary fat intake and obesity at the population level provide mixed results and are likely to be biased by both confounding and unknown data quality factors that differ systematically across the populations studied. Cross-sectional studies are generally in agreement that the concentration of fat in the diet is positively associated with relative weight. Prospective studies of diet in relation to subsequent weight change give inconsistent results. This may be due to behavioural factors such as dieting in response to weight gain; in addition, this type of study rarely takes into account the possible interaction between genetic predisposition and dietary fat in promoting weight gain. Finally, intervention studies in free-living subjects are considered, providing evidence of a consistent but short-lived period of active weight loss on low-fat diets. The experimental evidence on this relationship is more conclusive than the epidemiological evidence, although biological mechanisms remain controversial. Some areas for future epidemiological research involve: longitudinal studies of dietary fat intake as a predictor of growth in children; observational studies relating total dietary fat and specific types of fat to overall as well as regional adiposity; and randomized intervention studies of the effect of low-fat diets with particular emphasis on and familial predisposition to obesity and other possible modifying factors.",
"title": "Dietary fat and obesity: evidence from epidemiology."
},
{
"docid": "2139357",
"text": "BACKGROUND The role of the diffusible messenger nitric oxide (NO) in the regulation of pain transmission is still a debate of matter, pro-nociceptive and/or anti-nociceptive. S-Nitrosylation, the reversible post-translational modification of selective cysteine residues in proteins, has emerged as an important mechanism by which NO acts as a signaling molecule. The occurrence of S-nitrosylation in the spinal cord and its targets that may modulate pain transmission remain unclarified. The \"biotin-switch\" method and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were employed for identifying S-nitrosylated proteins. RESULTS Here we show that actin was a major protein S-nitrosylated in the spinal cord by the NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP). Interestingly, actin was S-nitrosylated, more in the S2 fraction than in the P2 fraction of the spinal homogenate. Treatment of PC12 cells with SNAP caused rapid S-nitrosylation of actin and inhibited dopamine release from the cells. Just like cytochalasin B, which depolymerizes actin, SNAP decreased the amount of filamentous actin cytoskeleton just beneath the membrane. The inhibition of dopamine release was not attenuated by inhibitors of soluble guanylyl cyclase and cGMP-dependent protein kinase. CONCLUSION The present study demonstrates that actin is a major S-nitrosylated protein in the spinal cord and suggests that NO directly regulates neurotransmitter release by S-nitrosylation in addition to the well-known phosphorylation by cGMP-dependent protein kinase.",
"title": "Involvement of S-nitrosylation of actin in inhibition of neurotransmitter release by nitric oxide"
},
{
"docid": "13714201",
"text": "Aims The gut microbiome influences metabolic syndrome (MetS) and inflammation and is therapeutically modifiable. Arterial stiffness is poorly correlated with most traditional risk factors. Our aim was to examine whether gut microbial composition is associated with arterial stiffness. Methods and results We assessed the correlation between carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, and gut microbiome composition in 617 middle-aged women from the TwinsUK cohort with concurrent serum metabolomics data. Pulse wave velocity was negatively correlated with gut microbiome alpha diversity (Shannon index, Beta(SE)= -0.25(0.07), P = 1 × 10-4) after adjustment for covariates. We identified seven operational taxonomic units associated with PWV after adjusting for covariates and multiple testing-two belonging to the Ruminococcaceae family. Associations between microbe abundances, microbe diversity, and PWV remained significant after adjustment for levels of gut-derived metabolites (indolepropionate, trimethylamine oxide, and phenylacetylglutamine). We linearly combined the PWV-associated gut microbiome-derived variables and found that microbiome factors explained 8.3% (95% confidence interval 4.3-12.4%) of the variance in PWV. A formal mediation analysis revealed that only a small proportion (5.51%) of the total effect of the gut microbiome on PWV was mediated by insulin resistance and visceral fat, c-reactive protein, and cardiovascular risk factors after adjusting for age, body mass index, and mean arterial pressure. Conclusions Gut microbiome diversity is inversely associated with arterial stiffness in women. The effect of gut microbiome composition on PWV is only minimally mediated by MetS. This first human observation linking the gut microbiome to arterial stiffness suggests that targeting the microbiome may be a way to treat arterial ageing.",
"title": "Gut microbial diversity is associated with lower arterial stiffness in women"
},
{
"docid": "16252863",
"text": "The list of preventable and reversible risk factors for atherosclerotic cardiovascular disease continues to grow. Cigarette smoking, high blood pressure, physical inactivity, elevated cholesterol, underlying lipoprotein abnormalities, lipoprotein(a), diabetes, overweight, male gender, and age are well-established risk factors. During the 1990s, there have been many reports associating elevated plasma homocysteine levels with arteriosclerotic cardiovascular disease and consistent evidence that dietary and supplemental folic acid can reduce homocysteine levels.1 2 The article by Robinson and colleagues3 in this issue of Circulation presents further evidence of the importance of homocysteine and suggestive evidence that plasma folate and plasma pyrixodal-l-phosphate (vitamin B6) are protective factors. Their study is part of the European Concerted Action Project,4 which examined 750 patients younger than age 60 with diagnoses within the previous 12 months of coronary, cerebrovascular, or peripheral vascular disease and 800 healthy control subjects. The patient groups were young (47 years for cases and 44 years for control subjects) and heterogeneous, with nonfatal clinical events or symptoms of arteriosclerotic cardiovascular disease supported by ECG, angiographic, or Doppler evidence; the study involved 19 centers in nine European countries. Men in the highest quintile for fasting total homocysteine (tHcy), compared with the remainder of the population, had an estimated relative risk of 2.2 (95% confidence interval [CI], 1.6 to 2.9), with a striking dose-response relationship and a more-than-multiplicative interaction with cigarette smoking and high blood pressure on vascular disease risk4 ; the corresponding estimated relative risk for coronary heart disease was similar (2.0; 95% CI 1.6 to 2.8). (tHcy is the sum of homocysteine and homocysteinyl moieties of oxidized disulfides, homocystine, and cysteine- homocysteine. ) Robinson and colleagues3 examined three B vitamins in detail to determine their effects on fasting and post–methionine-loading tHcy levels and any independent effects on cardiovascular disease …",
"title": "Preventing coronary heart disease: B vitamins and homocysteine."
},
{
"docid": "37336085",
"text": "PURPOSE We assessed the nephroprotective effects of montelukast sodium and N-acetylcysteine on secondary renal damage due to unilateral ureteral obstruction in a rat model. MATERIALS AND METHODS In this study 30 Wistar albino male rats were randomized into 3 groups, including placebo, N-acetylcysteine and montelukast sodium. Three rats served as the control group. The left ureter of the rats was sutured with 4-zero polyglactin sutures. Medications were given 3 days before obstruction and continued for 15 days. Dimercaptosuccinic acid renal scintigraphy was performed before obstruction and on day 15. Rats were sacrificed on day 15 and histopathological examinations were done. We biochemically assessed oxidative stress markers (myeloperoxidase and malondialdehyde), sulfhydryl and total nitrite for lipid peroxidation, oxidative protein damage and antioxidant levels, respectively. RESULTS On pathological examination inflammation and tubular epithelial damage in the N-acetylcysteine and montelukast sodium groups were less than in the placebo group (p <0.05). No difference was seen in normal kidneys. Myeloperoxidase, malondialdehyde and total nitrite levels in the N-acetylcysteine group, and myeloperoxidase and malondialdehyde levels in the montelukast sodium group were lower than in the placebo group (p <0.05). No statistical difference was seen in sulfhydryl levels (p >0.05) or among the N-acetylcysteine, montelukast sodium and placebo groups on scintigraphy (p >0.05). No pathological, chemical and scintigraphic differences were seen among the N-acetylcysteine, montelukast sodium and sham treated groups (p >0.05). CONCLUSIONS N-acetylcysteine and montelukast sodium have a protective effect against obstructive damage of the kidney. However, further investigations are needed.",
"title": "Do Montelukast Sodium and N-Acetylcysteine Have a Nephroprotective Effect on Unilateral Ureteral Obstruction? A Placebo Controlled Trial in a Rat Model."
}
] |
7760
|
What is the best strategy for after hours trading?
|
[
{
"docid": "16806",
"text": "I would never trade after hours and I have 30 years of trading experience. It is a very volatile emotion driven market without a lot of the big players that arbitrage wrong pricing. If I were you I would simply use limit orders you input while the market is closed. If you want to get kute you can put in low-ball offers (and vice versa) to see if they get filled in the volatility at market open. Then check in (when?) when you wake up (or before you go to bed, etc) and revise the limit if not filled. In other words don't 'trade'. Know what your company is worth and put in orders that reflect that.",
"title": ""
},
{
"docid": "240744",
"text": "First you will need a plan stating three main points: You will have to decide what criteria you will use to answer these points. You might use Fundamental Analysis to find what to buy and Technical Analysis to decide when to buy and when to sell (your buy and sell triggers). Once you have a Trading Plan in place you would need to find a broker with conditional orders. You can place conditional buy orders to get in a trade (for example if the price moves above or below a target price). You can place conditional stop loss orders if your trade goes against you, and you can also place conditional profit target stops to automatically get out if rises to your desired profit target. You can place one, two or many conditional orders after hours which will enable you to trade without being in front of your screen all day long.",
"title": ""
}
] |
[
{
"docid": "396657",
"text": "The study of technical analysis is generally used (sometimes successfully) to time the markets. There are many aspects to technical analysis, but the simplest form is to look for uptrends and downtrends in the charts. Generally higher highs and higher lows is considered an uptrend. And lower lows and lower highs is considered a downtrend. A trend follower would go with the trend, for example see a dip to the trend-line and buy on the rebound. A simple strategy for this is shown in the chart below: I would be buying this stock when the price hits or gets very close to the trendline and then it bounces back above it. I would then have sold this stock once it has broken through below the trendline. This may also be an appropriate time if you were looking to short this stock. Other indicators could also be used in combination for additional confirmation of what is happening to the price. Another type of trader is called a bottom fisher. A bottom fisher would wait until a break above the downtrend line (second chart) and buy after confirmation of a higher high and possibly a higher low (as this could be the start of a new uptrend). There are many more strategies dealing with the study of technical analysis, and if you are interested you would need to find and learn about ones that suit your investment styles, whether you prefer short term trading or longer term investing, and your appetite for risk. You can develop strategies using various indicators and then paper trade or backtest these strategies. You can also manually backtest a strategy in most charting packages. You can go back in time on the chart so that the right side of the chart shows a date in the past (say one year ago or 10 years ago), then you can click forward one day at a time (or one week at a time if using weekly charts). With your indicators on the chart you can do virtual trades to buy or sell whenever a signal is given as you move forward in time. This way you may be able to check years of data in a day to see if your strategy works. Whatever you do, you need to document your strategies in writing in a written trading or investment plan together with a risk management strategy. You should always follow the rules in your written plan to avoid you making decisions based on emotions. By backtesting or paper trading your strategies it will give you confidence that they will work over the long term. There is a lot of work involved at the start, but once you have developed a documented strategy that has been thoroughly backtested, it will take you minimal time to successfully manage your investments. In my shorter term trading (positions held from a couple of days to a few weeks) I spend about half an hour per night to manage my trades and am up about 50% over the last 7 months. For my longer term investing (positions held from months to years) I spend about an hour per week and have been averaging over 25% over the last 4 years. Technical Analysis does work for those who have a documented plan, have approached it in a systematic way and use risk management to protect their existing and future capital. Most people who say that is doesn't work either have not used it themselves or have used it ad-hock without putting in the initial time and work to develop a documented and systematic approach to their trading or investing.",
"title": ""
},
{
"docid": "220110",
"text": "Very common question. There is no any rule of thumb. This solely depends on your trading strategy. I will share my own experience. My day starts with the daily chart, if I have a signal, either I open my position or I check 30 minute chart to make sure that it won't go too much against my trade. and I open my position. If I am waiting for the signal the minimum timeframe is 4 hours for me. I use 30 minutes to find the best time to enter the market. So, this is totally something special for my trading strategy, that is why those things can change based on the different strategies. I also check weekly and monthly charts to confirm trend. I have been busy with forex since 2007 and I am a verified investor on etoro At the end, I never use 1,5,15,60 minute charts as they are against my strategy.",
"title": ""
},
{
"docid": "118712",
"text": "In general a stock can open at absolutely any price with no regard for the closing price or after hours price the previous day. The opening price will be determined by the best bid and offer made by people who decide to trade the next day. Some of the those people may have put orders in on a prior day that are still on the books and matter, but there's a lot of time overnight for people to cancel orders and enter new ones, which is especially likely to happen if there was substantive news overnight. As for what you can do in your case, you have the same options that you always had: Sell or hold. If you're selling, you can sell after hours, in the pre-open hours, or during the trading day. There's nothing we can say about this case that's really any different than we can say about any other stock on any other day.",
"title": ""
},
{
"docid": "361163",
"text": "The sentiment is because between closing and opening a lot can happen, and between opening and the time your order actually goes through, even more can happen. An after-hours trade has an extra amount of short-term risk attached; the price of a stock at the opening bell is technically the same as its price as of the closing the previous trading day, but within a tenth of a second, which is forever in a computerized exchange, that price may move drastically one way or the other, based on news and on other markets. The sentiment, therefore, is simple; if you're trading after-hours, you're trading risky. You're not trading based on what the market's actually doing, you're trading based on what you think the market will do in the morning, and there's still more math going on every second in the privately-held supercomputers in rented cubes in the NYSE basement than you could do all night, digesting this news and projecting what it's going to do to the stocks. Now, if you've done your homework and the stock looks like a good long-term buy, with or without any after-hours news, then place the order at 3 in the morning; who cares what the stock's gonna do at the opening bell. You're gonna hold that stock for the next ten years, maybe; what it does in 5 seconds of opening turmoil is relatively minor compared to the monthly trends that you should be worrying about.",
"title": ""
},
{
"docid": "532599",
"text": "The two answers so far are right, but there's a third factor - for many stocks, there's after hours trading. So the official 4PM close is not what the stock's last trade was when they open again. Regardless, even that after hour price is not the starting point as Muro points out.",
"title": ""
},
{
"docid": "255396",
"text": "Unless you have a lot of money to get rid of you should spend at least a year trading with a dummy account. It takes a long time to work out what is gong on and your training will get very expensive if you start using real money. Don't start trading with real money until you : Have a strategy. Never trade on a whim. Only trade if your strategy says it is time to trade. Are able to stick to that strategy. It is amazing how easy it is to stray from your strategy just because you feel it is right or you have to try to make up some losses. You will lose money doing this. You are making significant profits for at least 6 months using 1. and 2. with your dummy account. Even after all this, you will probably still lose money. Make sure you only trade with money you can afford to lose. ie. Never trade with this months rent money.",
"title": ""
},
{
"docid": "467463",
"text": "Typically the settlement price for a financial instrument (such as AAPL stock) underlying a derivative contract is determined from the average price of trading in that instrument during some short time window specified by the exchange offering the derivative. (Read the fine print on your contract to learn the exact date and time of that settlement period.) Because it's in an exchange's best interest to appear as fair as possible, the exchange will in general pick a high-volume period of time -- such as the close of trading on the expiry date -- in which to determine the settlement price. Now, the expiry date/time may be different from the last time at which the option can be traded, which may be different from the underlying settlement time. For example, most US equity options currently expire on the Saturday following the third Friday of the month, whereas they can last be traded at end-of-day on the third Friday of the month, and the settlement period may be at a slightly different time on the third Friday of the month. (Again, read the contract to know for sure.) Moreover, your broker may demand to know whether you plan to exercise the option at an even earlier date/time. So, to answer your question: After-hours trading can only affect the settlement price of an underlying instrument if the exchange in question decides that the settlement period should happen during after-hours trading. But since no exchange that wants to stay in business would possibly do that, the answer is no. Contract expiry time, contract exercise time, final contract trading time, and underlying settlement time may all fall at different dates/times. The important one for your question is settlement time.",
"title": ""
},
{
"docid": "131117",
"text": "Disclaimer: I don't work in the finance industry, and simply took a few classes in corporate finance and management during my undergrad. It depends on what type of investing you're talking about. If you're talking about building a portfolio of securities, then CAPM is the basis for most valuation models. Generally, CAPM will have you discount based on your best available risk-free rate (usually t-bills or some other fixed income source with a reliable backer). Even after your valuation, the basic theory of risk management for an investment portfolio is still to maintain a diverse basket of poorly correlated products. If you're talking about corporate finance where a firm is considering an investment such as a new project, then a determining a WACC and using it as a discount rate for your cash flow is a basic strategy. This is a basic strategy, but there are better ones depending on the specifics of the investment. This is where evaluating exposures is important. To hedge counterparty risk, you might discount by the estimated probability of non-payment or buy trade insurance. To hedge currency risk, you might buy forwards, options, or look into a money market hedge. To hedge political risks like repatriation or changes in tax laws or regulation you might buy political risk insurance. To hedge exposure to a particular commodity price, you can trade futures.",
"title": ""
},
{
"docid": "576632",
"text": "\"If I really understood it, you bet that a quote/currency/stock market/anything will rise or fall within a period of time. So, what is the relationship with trading ? I see no trading at all since I don't buy or sell quotes. You are not betting as in \"\"betting on the outcome of an horse race\"\" where the money of the participants is redistributed to the winners of the bet. You are betting on the price movement of a security. To do that you have to buy/sell the option that will give you the profit or the loss. In your case, you would be buying or selling an option, which is a financial contract. That's trading. Then, since anyone should have the same technic (call when a currency rises and put when it falls)[...] How can you know what will be the future rate of exchange of currencies? It's not because the price went up for the last minutes/hours/days/months/years that it will continue like that. Because of that everyone won't have the same strategy. Also, not everyone is using currencies to speculate, there are firms with real needs that affect the market too, like importers and exporters, they will use financial products to protect themselves from Forex rates, not to make profits from them. [...] how the brokers (websites) can make money ? The broker (or bank) will either: I'm really afraid to bet because I think that they can bankrupt at any time! Are my fears correct ? There is always a probability that a company can go bankrupt. But that's can be very low probability. Brokers are usually not taking risks and are just being intermediaries in financial transactions (but sometime their computer systems have troubles.....), thanks to that, they are not likely to go bankrupt you after you buy your option. Also, they are regulated to insure that they are solid. Last thing, if you fear losing money, don't trade. If you do trade, only play with money you can afford to lose as you are likely to lose some (maybe all) money in the process.\"",
"title": ""
},
{
"docid": "241059",
"text": "\"NASDAQ has Pre and After market : NASDAQ Trading Schedule Regular Trading Session Schedule The NASDAQ Stock Market Trading Sessions (Eastern Time) Pre-Market Trading Hours from 4:00 a.m. to 9:30 a.m. Market Hours from 9:30 a.m. to 4:00 p.m. After-Market Hours from 4:00 p.m. to 8:00 p.m. Quote and order-entry from 4:00 a.m. to 8:00 p.m. Quotes are open and firm from 4:00 a.m. to 8:00 p.m. You can trade in Pre/After Market but liquidity is very low. If an \"\"unexpected world events\"\" occurs, the volume/liquidity will most certainly increase. Another example is the Forex Market that's open 24/7 around the world. As one major forex market closes, another one opens. According to GMT, for instance, forex trading hours move around the world like this: available in New York between 01:00 pm – 10:00 pm GMT; at 10:00 pm GMT Sydney comes online; Tokyo opens at 00:00 am and closes at 9:00 am GMT; and to complete the loop, London opens at 8:00 am and closes at 05:00 pm GMT. This enables traders and brokers worldwide, together with the participation of the central banks from all continents, to trade online 24 hours a day. src\"",
"title": ""
},
{
"docid": "106817",
"text": "1. It is difficult. There is no formal process outside of undergrad and MBA programs to easily gain access to interviews. At your level, its mostly about connections. If willing to start near bottom, go to your business school and start applying to bank associate programs. Sounds like you would like sales and trading more than M&A, so focus there. 2. If you got in at associate level, you would do 1-3 months of training and then get assigned a desk. Finance going through a tough time right now, so trajectory isn't what it used to be. Expect to be a VP after 2-4 years, then its all dependent on luck and skill. 3. If you land a job at a top 15 bank, you should be making total comp of 150k or more after the first year. Salaries not quite at 150k, but most VPS make over 150k salary, not to mention bigger bonus's. 4. If you did M&A you would be working very serious hours. If you go into Sales and Trading your hours will be anywhere from 40 to 60 hours a week depending on the desk. Trading hours tend to be the shortest. 5. Boston isn't a hot bed for i-banking finance. NYC, London, Sing, Hong Kong tend to be the places to be. I know nobody in Boston that could help.",
"title": ""
},
{
"docid": "360059",
"text": "\"There are people (well, companies) who make money doing roughly what you describe, but not exactly. They're called \"\"market makers\"\". Their value for X% is somewhere on the scale of 1% (that is to say: a scale at which almost everything is \"\"volatile\"\"), but they use leverage, shorting and hedging to complicate things to the point where it's nothing like a simple as making a 1% profit every time they trade. Their actions tend to reduce volatility and increase liquidity. The reason you can't do this is that you don't have enough capital to do what market makers do, and you don't receive any advantages that the exchange might offer to official market makers in return for them contracting to always make both buy bids and sell offers (at different prices, hence the \"\"bid-offer spread\"\"). They have to be able to cover large short-term losses on individual stocks, but when the stock doesn't move too much they do make profits from the spread. The reason you can't just buy a lot of volatile stocks \"\"assuming I don't make too many poor choices\"\", is that the reason the stocks are volatile is that nobody knows which ones are the good choices and which ones are the poor choices. So if you buy volatile stocks then you will buy a bunch of losers, so what's your strategy for ensuring there aren't \"\"too many\"\"? Supposing that you're going to hold 10 stocks, with 10% of your money in each, what do you do the first time all 10 of them fall the day after you bought them? Or maybe not all 10, but suppose 75% of your holdings give no impression that they're going to hit your target any time soon. Do you just sit tight and stop trading until one of them hits your X% target (in which case you start to look a little bit more like a long-term investor after all), or are you tempted to change your strategy as the months and years roll by? If you will eventually sell things at a loss to make cash available for new trades, then you cannot assess your strategy \"\"as if\"\" you always make an X% gain, since that isn't true. If you don't ever sell at a loss, then you'll inevitably sometimes have no cash to trade with through picking losers. The big practical question then is when that state of affairs persists, for how long, and whether it's in force when you want to spend the money on something other than investing. So sure, if you used a short-term time machine to know in advance which volatile stocks are the good ones today, then it would be more profitable to day-trade those than it would be to invest for the long term. Investing on the assumption that you'll only pick short-term winners is basically the same as assuming you have that time machine ;-) There are various strategies for analysing the market and trying to find ways to more modestly do what market makers do, which is to take profit from the inherent volatility of the market. The simple strategy you describe isn't complete and cannot be assessed since you don't say how to decide what to buy, but the selling strategy \"\"sell as soon as I've made X% but not otherwise\"\" can certainly be improved. If you're keen you can test a give strategy for yourself using historical share price data (or current share price data: run an imaginary account and see how you're doing in 12 months). When using historical data you have to be realistic about how you'd choose what stocks to buy each day, or else you're just cheating at solitaire. When using current data you have to beware that there might not be a major market slump in the next 12 months, in which case you won't know how your strategy performs under conditions that it inevitably will meet eventually if you run it for real. You also have to be sure in either case to factor in the transaction costs you'd be paying, and the fact that you're buying at the offer price and selling at the bid price, you can't trade at the headline mid-market price. Finally, you have to consider that to do pure technical analysis as an individual, you are in effect competing against a bank that's camped on top of the exchange to get fastest possible access to trade, it has a supercomputer and a team of whizz-kids, and it's trying to find and extract the same opportunities you are. This is not to say the plucky underdog can't do well, but there are systematic reasons not to just assume you will. So folks investing for their retirement generally prefer a low-risk strategy that plays the averages and settles for taking long-term trends.\"",
"title": ""
},
{
"docid": "251300",
"text": "The answer is to your question is somewhat complicated. You will be unable to compete with the firms traditionally associated with High Frequency Trading in any of their strategies. Most of these strategies which involve marketing making, latency arbitrage, and rebate collection. The amount of engineering required to build the infrastructure required to run this at scale makes it something which can only be undertaken by a team of highly skilled engineers. Indeed, the advantage of firms competing in this space such as TradeBot, TradeWorx, and Getco comes from this infrastructure as most of the strategies that are developed are necessarily simple due to the latency requirements. Now if you expand the definition of HFT to include all computerized automated trading you most certainly can build strategies that are profitable. It is not something that you probably want to tackle on your own but I know of a couple of people that did go it alone successfully for a couple of years before joining an established firm to run a book for them. In order to be successful you will most likely need to develop a unique strategies. The good news is because that you are trying to deploy a very tiny amount of capital you can engage in trades that larger firms would not because the strategies cannot hold enough capital relative to the firms capital base. I am the co-founder of a small trading firm that successfully trades the US Equities and Equity Derivatives markets. A couple of things to note is that if you want to do this you should consider building a real business. Having some more smart brains around you will help. You don't need exchange colocation for all strategies. Many firms, including ours, colocate in a data center that simply has proximity to the exchanges data centers. You will need to keep things simple to be effective. Don't except all the group think that this is impossible. It is possible although as a single individual it will be more difficult. It will require long, long hours as you climb the algorithmic trading learning curve. Good luck.",
"title": ""
},
{
"docid": "414036",
"text": "\"During market hours, there are a lot of dealers offering to buy and sell all exchange traded stocks. Dealers don't actually care about the company's fundamentals and they set their prices purely based on order flow. If more people start to buy than sell, the dealer notices his inventory going down and starts upping the price (both his bid and ask). There are also traders who may not be \"\"dealers\"\", but are willing to sell if the price goes high enough or buy if the price goes low enough. This keeps the prices humming along smoothly. During normal trading hours, if you buy something and turn around and sell it two minutes later, you'll probably be losing a couple cents per share. Outside normal market hours, the dealers who continue to have a bid and ask listed know that they don't have access to good price information -- there isn't a liquid market of continuous buying and selling for the dealer to set prices he considers safe. So what does he do? He widens the spread. He doesn't know what the market will open tomorrow at and doesn't know if he'll be able to react quickly to news. So instead of bidding $34.48 and offering at $34.52, he'll move that out to $33 and $36. The dealer still makes money sometimes off this because maybe some trader realized that he has options expiring tomorrow, or a short position that he's going to get a margin call on, or some kind of event that pretty much forces him to trade. Or maybe he's just panicking and overreacting to some news. So why not trade after hours? Because there's no liquidity, and trading when there's no liquidity costs you a lot.\"",
"title": ""
},
{
"docid": "177424",
"text": "\"No, a jump in market capitalization does not equal the amount that has been invested. Market cap is simply the stock price times the total number of shares. This represents a theoretical value of the company. I say \"\"theoretical\"\" because the company might not be able to be sold for that at all. The quoted stock price is simply what the last buyer and seller of stock agreed upon for the price of their trade. They really only represent themselves; other investors may decide that the stock is worth more or less than that. The stock price can move on very little volume. In this case, Amazon had released a very good earnings report after the bell yesterday, and the price jumped in after hours trading. The stock price is up, but that simply means that the few shares traded overnight sold for much higher than the closing price yesterday. After the market opens today and many more shares are traded, we'll get a better idea what large numbers of investors feel about the price. But no matter what the price does, the change in market cap does not equal the amount of new money being invested in the company. Market cap is the price of the most recent trades extrapolated out across all the shares.\"",
"title": ""
},
{
"docid": "481298",
"text": "Stop orders and stop limit orders typically do not execute during extended hours after the general market session has closed. Stop orders are market orders and market orders especially are not executed during extended hours. Although there are exceptions because a broker can say one thing and do another thing with the way order types are presented to customers vs what their programming actually does. The regulatory burden is a slap on the wrist, so you need to ask the broker what their practices are. Orders created during normal market hours do not execute in extended sessions, different orders would have to be made during the extended session. Your stop order should execute if the normal market hour price stays below your stop price. So a stop limit would actually be worse here, because a stop limit will create a limit order which may never get hit (since it is above the best bid best ask)",
"title": ""
},
{
"docid": "498014",
"text": "It looks like GOOG did not have a pre-market trade until 7:14 am ET, so Google Finance was still reporting the last trade it had, which was in the after-hours session yesterday. FB, on the other hand, was trading like crazy after-hours yesterday and pre-market today as it had an earnings report yesterday.",
"title": ""
},
{
"docid": "355548",
"text": "As a futures trader, I can tell you that the highs and lows for the ES futures diverge simply because they trade around the clock, from 6PM ET to 5PM ET the next day. The SPX is only open during market hours, as is the SPY, but the SPY also trades in the extended hours sessions for about 3.5 hours before and after the regular hours of 930 AM ET to 4PM ET ET. So bottom line, while they pretty much track each other, the difference in their trading hours results in the highs and lows being different.",
"title": ""
},
{
"docid": "265365",
"text": "There are several reasons it is not recommended to trade stocks pre- or post-market, meaning outside of RTH (regular trading hours). Since your question is not very detailed I have to assume you trade with a time horizon of at least more than a day, meaning you do not trade intra-day. If this is true, all of the above points are a non-issue for you and a different set of points becomes important. As a general rule, using (3) is the safest regardless of what and how you trade because you get price guarantee in trade for execution guarantee. In the case of mid to longer term trading (1 week+) any of those points is viable, depending on how you want to do things, what your style is and what is the most comfortable for you. A few remarks though: (2) are market orders, so if the open is quite the ride and you are in the back of the execution queue, you can get significant slippage. (1) may require (live) data of the post-market session, which is often not easy to come by for the entire US stock universe. Depending on your physical execution method (phone, fax, online), you may lack accurate information of the post-market. If you want to execute orders based on RTH and only want to do that after hours because of personal schedule constraints, this is not really important. Personally I would always recommend (3), independent of the use case because it allows you more control over your orders and their fills. TL;DR: If you are trading long-term it does not really matter. If you go down to the intra-day level of holding time, it becomes relevant.",
"title": ""
},
{
"docid": "57520",
"text": "Pre-Market trading activity is shown on the site from 4:15 - 9:30 AM (actual trading starts at 4:00 AM EST) The NASDAQ Stock Market Trading Sessions (Eastern Time) Pre-Market Trading Hours from 4:00 a.m. to 9:30 a.m. Market Hours from 9:30 a.m. to 4:00 p.m. After-Market Hours from 4:00 p.m. to 8:00 p.m. Read more: http://www.nasdaq.com/about/trading-schedule.aspx#ixzz38OtcISrq In this case GOOG did not trade in the Pre-market until that time and FB was.",
"title": ""
},
{
"docid": "378889",
"text": "\"Often these types of trades fall into two different categories. An error by broker or exchange. Exchange clearing out part of their books incorrectly is an example. Most exchanges make firms reopen their positions for after market hours. There may have been an issue doing so or exchange could incorrectly cancel positions. I was in the direct feed industry for years and this was a big issue. At the same time the broker can issue a no limit buy on accident (or has software that is prospecting and said software has a bug or written poorly). unscrupulous parties looking to feign an upswing or downswing in market. Let's say you hold 500k shares in a stock that sells for $11. You could possibly buy 100 shares for $13. Trust me you will find a seller. Then you are hoping that people see that trade as a \"\"norm\"\" and trade from there, allowing you to rake in $1M for spending an extra $200 - NOTE this is not normal and an extreme example. This was so common in the early days of NASDAQ after hours that they discontinued using the after hours trades as part of historical information that they keep like daily/yearly high or closing price. The liquidity allows for manipulation. It isn't seen as much now since this has been done a million times but it does still happen.\"",
"title": ""
},
{
"docid": "515579",
"text": "If I understand you correctly, you are noticing that a stock's price can change drastically when the time changes from pre-market trading hours to open market hours. This could occur because a much smaller pool of investors make trades during pre-market and after-market hours. When the regular market opens there is a large influx of trades, causing the prices to jump.",
"title": ""
},
{
"docid": "176883",
"text": "\"A 'Call' gives you the right, but not the obligation, to buy a stock at a particular price. The price, called the \"\"strike price\"\" is fixed when you buy the option. Let's run through an example - AAPL trades @ $259. You think it's going up over the next year, and you decide to buy the $280 Jan11 call for $12. Here are the details of this trade. Your cost is $1200 as options are traded on 100 shares each. You start to have the potential to make money only as Apple rises above $280 and the option trades \"\"in the money.\"\" It would take a move to $292 for you to break even, but after that, you are making $100 for each dollar it goes higher. At $300, your $1200 would be worth $2000, for example. A 16% move on the stock and a 67% increase on your money. On the other hand, if the stock doesn't rise enough by January 2011, you lose it all. A couple points here - American options are traded at any time. If the stock goes up next week, your $1200 may be worth $1500 and you can sell. If the option is not \"\"in the money\"\" its value is pure time value. There have been claims made that most options expire worthless. This of course is nonsense, you can see there will always be options with a strike below the price of the stock at expiration and those options are \"\"in the money.\"\" Of course, we don't know what those options were traded at. On the other end of this trade is the option seller. If he owns Apple, the sale is called a \"\"covered call\"\" and he is basically saying he's ok if the stock goes up enough that the buyer will get his shares for that price. For him, he knows that he'll get $292 (the $280, plus the option sale of $12) for a stock that is only $259 today. If the stock stays under $280, he just pocketed $12, 4.6% of the stock value, in just 3 months. This is why call writing can be a decent strategy for some investors. Especially if the market goes down, you can think of it as the investor lowering his cost by that $12. This particular strategy works best in a flat to down market. Of course in a fast rising market, the seller misses out on potentially high gains. (I'll call it quits here, just to say a Put is the mirror image, you have the right to sell a stock at a given price. It's the difference similar to shorting a stock as opposed to buying it.) If you have a follow up question - happy to help. EDIT - Apple closed on Jan 21, 2011 at $326.72, the $280 call would have been worth $46.72 vs the purchase price of $12. Nearly 4X return (A 289% gain) in just over 4 months for a stock move of 26%. This is the leverage you can have with options. Any stock could just as easily trade flat to down, and the entire option premium, lost.\"",
"title": ""
},
{
"docid": "69395",
"text": "\"Your plan already answers your own question in the best possible way: If you want to be able to make the most possible profit from a large downward move in a stock (in this case, a stock that tracks gold), with a limited, defined risk if there is an upward move, the optimal strategy is to buy a put option. There are a few Exchange Traded Funds (ETFs) that track the price of gold. think of them as stocks that behave like gold, essentially. Two good examples that have options are GLD and IAU. (When you talk about gold, you'll hear a lot about futures. Forget them, for now. They do the same essential thing for your purposes, but introduce more complexity than you need.) The way to profit from a downward move without protection against an upward move is by shorting the stock. Shorting stock is like the opposite of buying it. You make the amount of money the stock goes down by, or lose the amount it goes up by. But, since stocks can go up by an infinite amount, your possible loss is unlimited. If you want to profit on a large downward move without an unlimited loss if you're wrong and it goes up, you need something that makes money as the stock drops, but can only lose so much if it goes up. (If you want to be guaranteed to lose nothing, your best investment option is buying US Treasuries, and you're technically still exposed to the risk that US defaults on its debt, although if you're a US resident, you'll likely have bigger problems than your portfolio in that situation.) Buying a put option has the exact asymmetrical exposure you want. You pay a limited premium to buy it, and at expiration you essentially make the full amount that the stock has declined below the strike price, less what you paid for the option. That last part is important - because you pay a premium for the option, if it's down just a little, you might still lose some or all of what you paid for it, which is what you give up in exchange for it limiting your maximum loss. But wait, you might say. When I buy an option, I can lose all of my money, cant I? Yes, you can. Here's the key to understanding the way options limit risk as compared to the corresponding way to get \"\"normal\"\" exposure through getting long, or in your case, short, the stock: If you use the number of options that represent the number of shares you would have bought, you will have much, much less total money at risk. If you spend the same \"\"bag 'o cash\"\" on options as you would have spent on stock, you will have exposure to way more shares, and have the same amount of money at risk as if you bought the stock, but will be much more likely to lose it. The first way limits the total money at risk for a similar level of exposure; the second way gets you exposure to a much larger amount of the stock for the same money, increasing your risk. So the best answer to your described need is already in the question: Buy a put. I'd probably look at GLD to buy it on, simply because it's generally a little more liquid than IAU. And if you're new to options, consider the following: \"\"Paper trade\"\" first. Either just keep track of fake buys and sells on a spreadsheet, or use one of the many online services where you can track investments - they don't know or care if they're real or not. Check out www.888options.com. They are an excellent learning resource that isn't trying to sell you anything - their only reason to exist is to promote options education. If you do put on a trade, don't forget that the most frustrating pitfall with buying options is this: You can be basically right, and still lose some or all of what you invest. This happens two ways, so think about them both before you trade: If the stock goes in the direction you think, but not enough to make back your premium, you can still lose. So you need to make sure you know how far down the stock has to be to make back your premium. At expiration, it's simple: You need it to be below the strike price by more than what you paid for the option. With options, timing is everything. If the stock goes down a ton, or even to zero - free gold! - but only after your option expires, you were essentially right, but lose all your money. So, while you don't want to buy an option that's longer than you need, since the premium is higher, if you're not sure if an expiration is long enough out, it isn't - you need the next one. EDIT to address update: (I'm not sure \"\"not long enough\"\" was the problem here, but...) If the question is just how to ensure there is a limited, defined amount you can lose (even if you want the possible loss to be much less than you can potentially make, the put strategy described already does that - if the stock you use is at $100, and you buy a put with a 100 strike for $5, you can make up to $95. (This occurs if the stock goes to zero, meaning you could buy it for nothing, and sell it for $100, netting $95 after the $5 you paid). But you can only lose $5. So the put strategy covers you. If the goal is to have no real risk of loss, there's no way to have any real gain above what's sometimes called the \"\"risk-free-rate\"\". For simplicity's sake, think of that as what you'd get from US treasuries, as mentioned above. If the goal is to make money whether the stock (or gold) goes either up or down, that's possible, but note that you still have (a fairly high) risk of loss, which occurs if it fails to move either up or down by enough. That strategy, in its most common form, is called a straddle, which basically means you buy a call and a put with the same strike price. Using the same $100 example, you could buy the 100-strike calls for $5, and the 100-strike puts for $5. Now you've spent $10 total, and you make money if the stock is up or down by more than $10 at expiration (over 110, or under 90). But if it's between 90 and 100, you lose money, as one of your options will be worthless, and the other is worth less than the $10 total you paid for them both.\"",
"title": ""
},
{
"docid": "448952",
"text": "I don't think that the trading volume would impact a broker's ability to find shares to short. You might think that a lot more people are trying to short a stock during regular trading hours than in the pre-market, and that's probably true. But what's also true is that a lot more people are covering their shorts during regular trading hours than in the pre-market. For stocks that have difficulty in finding shares to short, any time someone covers a short is an opportunity for you to enter a short. If you want to short a stock and your broker is rejecting your order because they can't find shares to short, then I would recommend that you continue placing that order throughout the day. You might get lucky and submit one of those orders right after someone else has covered their short and before anyone else can enter a short. I have had success doing this in the past.",
"title": ""
},
{
"docid": "151587",
"text": "This is dependent on the broker according to The Options Industry Council. Your broker will specify what they would do upon expiry (or hours before last trade) if you did not indicate your preference. Most likely they will conduct a probabilistic simulation to see whether exercising the contracts may result in margin deficit even after selling the delivered shares under extreme circumstances. In most cases, brokers tend to liquidate the option for you (sell to close) before expiry. I've seen people complain about certain brokers forcing liquidation at terrible bid-ask spreads even though the options are still days to expiry. It is better for you to close the position on your own beforehand. The best brokers would allow margin deficit and let you deposit the required amount of money afterward. Please consult your broker's materials. If you can't find them, use live chat or email tickets.",
"title": ""
},
{
"docid": "376179",
"text": "Coolness - It's not only a matter of staying calm when being up or down. You must keep yourself from chasing a stock that appears to be running away. Or from betting all your money that something(like say a crash) will happen tomorrow because that would be great for you. Use your head not your heart. Empathy - You need to understand what other speculators, investors, institutions and algorithms are going to do when there is a new development or technical signal. And why. For publicly traded corporations, fundamentals and technical indicators only have the value that people(and their algorithms) choose to assign to them at that particular moment. And every stock has a different population trading it. There is no rule of thumb. Patience - To trade successfully, you must avoid trading at all costs. Heh. If you can't find any good trade to do, don't open positions in order to meet your targets, buy a new smartphone, or to fight boredom. Diligence - If your strategy relies on tight stops, don't make exceptions. If your strategy relies on position sizing, don't close when you are a few points down. Luck - In the end almost every trade can turn against you very badly. You must prepare for the worst and hope for the best. You can't buy luck, or get luckier, but you can attempt to stack probabilities: diversify, buy options to insure your positions, reduce holding time, avoid known volatility events, etc.",
"title": ""
},
{
"docid": "585447",
"text": "Before you go filling your head with useless information as there is way too much stuff out there on the stock market. First ask yourself a few questions: There is going to be a balance between the three... don't kid yourself. After you answer these questions find a trading strategy to get the returns you are looking for. Remember the higher returns you expect... the more time you have to put in. Find a trading strategy you like and that works for you. Ounce you have your strategy then find the stocks or ETF that work for that strategy.... Ignore everything else, it is designed to separate you from your money. Making money in the stock market is easy, don't let the media hype and negative people tell you any different. Find something that works for you and perfect it... stick to it.",
"title": ""
},
{
"docid": "116599",
"text": "Well the article did mention that if you continually beat your bookmaker you're likely to get rejected in future which is hilarious, but personally I have actually bet on sports and I've found that it's a fairly easy game to win at if you don't go for bets with huge odds and I don't think I've ever placed a bet where after I lost and said 'what the hell just happened'. I only really bet on rugby and soccer though, so team sports may be a bit less prone to corruption from the bookmakers. I'm not saying I think this is a safe way to do business though, I don't think day trading is either. I think they are both speculation. I just think that sports betting has a lot more for a speculator to work with before they develop a strategy. For instance, I always bet on New Zealand winning a rugby game, their players line up as the top in their respective positions and their game strategy essentially has the rules of the game exploited to the maximum. All of the data on this team based on their past performance is actually applicable to their future performance, skilled players usually continue to be so up till a certain age, skilled coaches who stay in their position mean no variation in team strategy. That makes me feel confident that even though New Zealand might lose a game here or there, that they will continue to be winners, and even though the gains on their wins aren't much, consistently winning with them over time builds up to a nice bit of profit. With day trading in the stock market, so much of the variation in prices is due to non accounting fundamentals, and even though historical data can be useful we know that investor sentiment, secret information, and a myriad of other factors mean that unless you are extremely experienced or have a natural eye for reading markets that most traders will lose. I know developing strategies do work for some people, but I think I've seen it said on this sub a couple times that 'trading strategies work - until they don't.' I only speak as a uni student who has limited research beyond Bloomberg articles etc... but from what I can tell, the majority of day traders lose money eventually, and even with AI, the profits are only noteable when the capital input is extremely high. Sports events can't really be swung by the confidence of supporters, and yes corruption is rampant in sports as with every industry, but at least the data you have tells a fairly good story about where the bets will head in the future.",
"title": ""
},
{
"docid": "234892",
"text": "Yes, exactly. VaR is just a single tailed confidence interval. To go from model to strategy, you need to design some kind of indicator (i.e. when to buy and when to short or stay out). In practice, this will look like a large matrix with values ranging from -1 to 1 (corresponding to shorting and holding respectively) for each security and each day (or hour, or minute, or tick, etc.), which you then just multiply with the matrix of the stock returns. The resulting matrix will be your daily returns for each stock, you can then just row sum for daily returns of a portfolio, or calculate a cumulative product for cumulative returns. A simple example of an indicator would be something like a value of 1 when the price of the stock is below the 30 day moving average, and 0 otherwise. You can use a battery of econometric models to design these indicators, but the rest of the strategy design is essentially the same, and it's *relatively* easy to build a one-size-fits-all back-testing code. I'll try to edit this post later and link a blog that goes through some of the code. Edit: [Here](http://www.signalplot.com/simple-machine-learning-model-trade-spy/) is a post that discusses implementing a simple ML strategy. You can ignore most of the content but if you go through the github, you'll see how the ML model is implemented as a strategy. An even easier example can be found from [the github connected to this post](http://www.signalplot.com/how-to-measure-the-performance-of-a-trading-strategy/), where the author is just using a totally arbitrary signal. As you can see, deriving a signal can be a ton of work, but once you have, actually simulating the strategy can be done in just a few lines of code. Hopefully the author won't mind me linking his page here, but I find his coding style to be very clean and good for educational purposes.",
"title": ""
}
] |
PLAIN-1671
|
mushrooms
|
[
{
"docid": "MED-3302",
"text": "In November 2007 a novel neuropathy, immune-mediated polyradiculoneuropathy (IP), was identified among workers at a Minnesota swine abattoir where a unique compressed air technique was used to remove porcine brains. An epidemiologic investigation at another abattoir in Indiana that also uses this process was launched to evaluate workers self-reporting neurologic illness compatible with IP. A nested case-control study was performed to identify cases and risk factors. Six confirmed, one probable, and three possible IP cases were detected. IP cases were 28-52 years old, of Latino origin, and 62.5% female. Onset dates ranged from April 2005-December 2007; 60% were hospitalized. IP cases at this plant were similar in clinical presentation and exposure risks to those detected in Minnesota. Swine abattoirs using similar brain extraction methods should discontinue this process.",
"title": "A clustering of immune-mediated polyradiculoneuropathy among swine abattoir workers exposed to aerosolized porcine brains, Indiana, United States."
},
{
"docid": "MED-3308",
"text": "An occupational health survey conducted in a workshop in which asbestos cement was used showed initial atmospheric asbestos levels ranging from 1.9 to 27.5 fibres per millilitre of air. Radiological changes suggestive of asbestos-related pleural disease were found in 2 workers (2.5%), while 3 (3.8%) had borderline features of asbestosis. The survey confirmed that uncontrolled and hazardous use of asbestos continues in industry despite public awareness of its dangers and the Asbestos Regulations of 1987.",
"title": "Third wave of asbestos-related disease from secondary use of asbestos. A case report from industry."
},
{
"docid": "MED-3294",
"text": "In the past two decades or so, a number of viruses have emerged in the global swine population. Some, such as porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2), cause economically important diseases in pigs, whereas others such as porcine torque teno virus (TTV), now known as Torque teno sus virus (TTSuV), porcine bocavirus (PBoV) and related novel parvoviruses, porcine kobuvirus, porcine toroviruses (PToV) and porcine lymphotropic herpesviruses (PLHV), are mostly subclinical in swine herds. Although some emerging swine viruses such as swine hepatitis E virus (swine HEV), porcine endogenous retrovirus (PERV) and porcine sapovirus (porcine SaV) may have a limited clinical implication in swine health, they do pose a potential public health concern in humans due to zoonotic (swine HEV) or potential zoonotic (porcine SaV) and xenozoonotic (PERV, PLHV) risks. Other emerging viruses such as Nipah virus, Bungowannah virus and Menangle virus not only cause diseases in pigs but some also pose important zoonotic threat to humans. This article focuses on emerging and re-emerging swine viruses that have a limited or uncertain clinical and economic impact on pig health. The transmission, epidemiology and pathogenic potential of these viruses are discussed. In addition, the two economically important emerging viruses, PRRSV and PCV2, are also briefly discussed to identify important knowledge gaps. © 2012 Blackwell Verlag GmbH.",
"title": "Emerging and re-emerging swine viruses."
},
{
"docid": "MED-3704",
"text": "The most relevant cause of morbidity and mortality in cystic fibrosis (CF) patients is the lung pathology characterized by chronic infection and inflammation sustained mainly by Pseudomonas aeruginosa (P. aeruginosa). Innovative pharmacological approaches to control the excessive inflammatory process in the lung of CF patients are thought to be beneficial to reduce the extensive airway tissue damage. Medicinal plants from the so-called traditional Asian medicine are attracting a growing interest because of their potential efficacy and safety. Due to the presence of different active compounds in each plant extract, understanding the effect of each component is important to pursue selective and reproducible applications. Extracts from Emblica officinalis (EO) were tested in IB3-1 CF bronchial epithelial cells exposed to the P. aeruginosa laboratory strain PAO1. EO strongly inhibited the PAO1-dependent expression of the neutrophil chemokines IL-8, GRO-alpha, GRO-gamma, of the adhesion molecule ICAM-1 and of the pro-inflammatory cytokine IL-6. Pyrogallol, one of the compounds extracted from EO, inhibited the P. aeruginosa-dependent expression of these pro-inflammatory genes similarly to the whole EO extract, whereas a second compound purified from EO, namely 5-hydroxy-isoquinoline, had no effect. These results identify Pyrogallol as an active compound responsible for the anti-inflammatory effect of EO and suggest to extend the investigation in pre-clinical studies in airway animal models in vivo, to test the efficacy and safety of this molecule in CF chronic lung inflammatory disease.",
"title": "Pyrogallol, an active compound from the medicinal plant Emblica officinalis, regulates expression of pro-inflammatory genes in bronchial epithelial..."
},
{
"docid": "MED-3288",
"text": "In the fall of 2007, the Minnesota Department of Health was notified of 11 cases of an unexplained neurological illness, all linked to a pork processing plant, Quality Pork Processors, Inc., in Austin, MN. The cluster of workers had been experiencing similar symptoms, including fatigue, pain, numbness, and tingling in their extremities as well as weakness. The symptoms were described as more sensory than motor, and all patients had evidence of polyradiculoneuropathy with signs of nerve root irritation. An epidemiological investigation revealed that the only commonality between cases was their exposure to a pork brain extraction procedure involving compressed air. As relatives of the cases remained asymptomatic and all cultures for known pathogens were negative, the etiology of the syndrome seemed not to be infectious. Clinically, the syndrome was most akin to chronic inflammatory demyelinating polyneuropathy. Laboratory tests corroborated the clinical findings, revealing inflammation of peripheral nerves and nerve roots; however, these cases also had features clinically distinct from chronic inflammatory demyelinating polyneuropathy as well as laboratory testing revealing a novel immunoglobulin G immunostaining pattern. This suggested that the observed inflammation was the result of 1 or more unidentified antigens. This syndrome was ultimately dubbed progressive inflammatory neuropathy and was theorized to be an autoimmune reaction to aerosolized porcine neural tissue. Since the investigation's outset, 18 cases of progressive inflammatory neuropathy have been identified at the Minnesota pork processing plant, with 5 similar cases at an Indiana plant and 1 case at a Nebraskan plant. The plants in which cases have been identified have since stopped the use of compressed air in removing pork brains. All cases have stabilized or improved, with some requiring immunosuppressive and analgesic treatment. The study of progressive inflammatory neuropathy is ongoing, and the details of this investigation highlight the value of epidemiological principles in the identification and containment of outbreaks while researchers attempt to uncover the unique pathophysiology and potential etiology of the illness. Mt Sinai J Med 76:442-447, 2009. (c) 2009 Mount Sinai School of Medicine.",
"title": "Outbreak of progressive inflammatory neuropathy following exposure to aerosolized porcine neural tissue."
},
{
"docid": "MED-2364",
"text": "We have recently demonstrated that both antibodies to Gal alpha(1,3)Gal, and the Gal alpha(1,3)Gal binding lectin (IB4), bind a synthetic peptide (DAHWESWL), there being a similar recognition of carbohydrate and peptide structures. We now report that the anti-Gal alpha(1,3)Gal antibodies and IB4 lectin also react with peptides encoded by mucin genes (MUC 1, 3, 4)-sequences known to be rich in serine, threonine and proline. This activity was demonstrated (1) by the ability of mucin derived peptides to block the reaction of anti-Gal alpha(1,3)Gal antibodies and IB4 lectin with a Gal alpha(1,3)Gal+ pig endothelial cell line; the reactions were specific and did not occur with a random peptide containing the same sequences or with other mucin peptides; (2) by the fact that anti-mucin1 antibodies could react with the Gal alpha(1,3)Gal expressed after transfection of COS cells (Gal alpha(1,3)Gal-,Muc1-) with cDNA encoding the pig alpha, 3galactosyltransferase; and (3) that the IB4 lectin and anti-Gal alpha(1,3)Gal antibodies could react with mucin 1 found on the surface of human breast cancer cells. Thus natural occurring anti-Gal alpha(1,3)Gal antibodies found in all human serum can react with self (Muc1) peptides expressed in large amounts on the surface of tumour cells but not on normal cells. The findings are of interest and serve to explain the previously reported findings that human cells can, at times, express Gal alpha(1,3)Gal; such expression is an artefact, the reaction is due to the phenomenon described herein, i.e. that anti-Gal alpha(1,3)Gal antibodies react with mucin peptides.",
"title": "Natural human anti-Gal alpha(1,3)Gal antibodies react with human mucin peptides."
},
{
"docid": "MED-4582",
"text": "Objective: Diet may be associated with risk of dementia and Alzheimer's disease (AD). We examined the association between fruit and vegetable consumption in midlife and risk for all types of dementia and AD. Methods: Participants were 3,779 members of the Swedish Twin Registry who completed a diet questionnaire approximately 30 years prior to cognitive screening and full clinical evaluation for dementia as part of the HARMONY study. Among the participants, 355 twins were diagnosed with dementia. Among these, 81 twin pairs were discordant for dementia (50 discordant for AD). Data were analyzed with logistic regression for the entire sample using generalized estimating equations to adjust for relatedness of twins, and with conditional logistic regression for the co-twin control design. Results: In fully-adjusted models, a medium or great proportion of fruits and vegetables in the diet, compared to no or small, was associated with a decreased risk of dementia and AD. This effect was observed among women and those with angina. Similar, but non-significant, odds ratios were found in the co-twin control analyses. Conclusion: Our findings suggest that higher fruit and vegetable consumption may reduce the risk of dementia, especially among women and those with angina pectoris in midlife.",
"title": "Midlife Fruit and Vegetable Consumption and Risk of Dementia in Later Life in Swedish Twins"
},
{
"docid": "MED-2273",
"text": "Objective To examine and quantify the relation between purine intake and the risk of recurrent gout attacks among gout patients. Methods The authors conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for 1 year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, clinical symptoms and signs, medications (including antigout medications), and presence of potential risk factors (including daily intake of various purine-containing food items) during the 2-day period prior to the gout attack. The same exposure information was also assessed over 2-day control periods. Results This study included 633 participants with gout. Compared with the lowest quintile of total purine intake over a 2-day period, OR of recurrent gout attacks were 1.17, 1.38, 2.21 and 4.76, respectively, with each increasing quintile (p for trend <0.001). The corresponding OR were 1.42, 1.34, 1.77 and 2.41 for increasing quintiles of purine intake from animal sources (p for trend <0.001), and 1.12, 0.99, 1.32 and 1.39 from plant sources (p=0.04), respectively. The effect of purine intake persisted across subgroups by sex, use of alcohol, diuretics, allopurinol, NSAIDs and colchicine. Conclusions The study findings suggest that acute purine intake increases the risk of recurrent gout attacks by almost fivefold among gout patients. Avoiding or reducing amount of purine-rich foods intake, especially of animal origin, may help reduce the risk of gout attacks.",
"title": "Purine-rich foods intake and recurrent gout attacks"
},
{
"docid": "MED-2363",
"text": "We have previously shown that an antibody pool present in normal human serum binds cytokine receptors in vitro and may therefore interfere with assays that capture cytokines using their receptors. Here we show that this antibody pool is the same as the natural antibody termed anti-gal, that binds to the alpha-galactosyl carbohydrate epitope (alpha-gal) and which is the predominant obstacle to xenotransplantation. We report that there are high levels of IgD anti alpha-gal in most volunteers, in addition to the IgG2, IgA and IgM immunoglobulin isotypes against alpha-gal previously described. To determine if anti-gal may interfere with assays that depend on capture of cytokine with its receptor, we measured levels of several anti-carbohydrate antibodies in a cohort of patients with advanced atherosclerosis that had previously been used to measure levels of active TGF-beta using such an assay. For many isotype / carbohydrate combinations, there is a large and significant difference between the levels of anti-carbohydrate antibodies in patients with atherosclerosis and controls, after adjustment for age, sex and blood group. These results are similar to the previous data obtained for active TGF-beta, and therefore we cannot discount the possibility that anti-gal contributed to the previous data. Following further adjustment for several risk factors associated with cardiovascular disease, several anti-carbohydrate antibodies were still significantly different between patients and controls. Therefore, anti-carbohydrate antibodies may represent a new class of risk factors that may be associated with presence of advanced atherosclerosis, although larger studies will be required to confirm this hypothesis.",
"title": "A pattern of anti-carbohydrate antibody responses present in patients with advanced atherosclerosis."
},
{
"docid": "MED-4309",
"text": "Biogenic monoamines such as serotonin, tryptamine, and tyramine function as neurotransmitters and mitogenic factors in animals and are involved in flowering, morphogenesis, and protection from and adaptation to environmental changes in plants. In plants, serotonin and tyramine are conjugated to form phenolic compounds via thioester linkages during the synthesis of hydroxycinnamic acid amides, including p-coumaroylserotonin (CS), feruloylserotonin (FS), p-coumaroyltyramine (CT), and feruloyltyramine (FT). In this study, we determined the amounts of the biogenic monoamines CS, FS, CT, and FT in commonly consumed vegetables using high-performance liquid chromatography. Serotonin, tryptamine, and tyramine were detected in all vegetables tested. The serotonin levels ranged from 1.8 to 294 microg/g of dry weight, the tryptamine levels ranged from 0.8 to 372 microg/g of dry weight, and the tyramine levels ranged from 1.4 to 286 microg/g of dry weight. The highest serotonin and tryptamine contents were found in tomato and cherry tomato (140.3-222 microg/g of dry weight), while paprika and green pepper had higher tyramine contents than the other vegetables (286 and 141.5 microg/g of dry weight, respectively). Overall, the levels of CS, FS, CT, and FT ranged from 0.03 to 13.8 microg/g of dry weight, with green onion possessing the highest levels of CS (0.69 microg/g of dry weight), FT (1.99 microg/g of dry weight), and CT (13.85 microg/g of dry weight).",
"title": "HPLC analysis of serotonin, tryptamine, tyramine, and the hydroxycinnamic acid amides of serotonin and tyramine in food vegetables."
},
{
"docid": "MED-3990",
"text": "BACKGROUND: The available evidence on vitamin D and mortality is inconclusive. OBJECTIVES: To assess the beneficial and harmful effects of vitamin D for prevention of mortality in adults. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science (to January 2011). We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. SELECTION CRITERIA: We included randomised trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention. Vitamin D could have been administered as supplemental vitamin D (vitamin D(3) (cholecalciferol) or vitamin D(2) (ergocalciferol)) or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol) or 1,25-dihydroxyvitamin D (calcitriol)). DATA COLLECTION AND ANALYSIS: Six authors extracted data independently. Random-effects and fixed-effect model meta-analyses were conducted. For dichotomous outcomes, we calculated the risk ratios (RR). To account for trials with zero events, meta-analyses of dichotomous data were repeated using risk differences (RD) and empirical continuity corrections. Risk of bias was considered in order to minimise risk of systematic errors. Trial sequential analyses were conducted to minimise the risk of random errors. MAIN RESULTS: Fifty randomised trials with 94,148 participants provided data for the mortality analyses. Most trials included elderly women (older than 70 years). Vitamin D was administered for a median of two years. More than one half of the trials had a low risk of bias. Overall, vitamin D decreased mortality (RR 0.97, 95% confidence interval (CI) 0.94 to 1.00, I(2) = 0%). When the different forms of vitamin D were assessed separately, only vitamin D(3) decreased mortality significantly (RR 0.94, 95% CI 0.91 to 0.98, I(2) = 0%; 74,789 participants, 32 trials) whereas vitamin D(2), alfacalcidol, or calcitriol did not. Trial sequential analysis supported our finding regarding vitamin D(3), corresponding to 161 individuals treated to prevent one additional death. Vitamin D(3) combined with calcium increased the risk of nephrolithiasis (RR 1.17, 95% CI 1.02 to 1.34, I(2) = 0%). Alfacalcidol and calcitriol increased the risk of hypercalcaemia (RR 3.18, 95% CI 1.17 to 8.68, I(2) = 17%). Data on health-related quality of life and health economics were inconclusive. AUTHORS' CONCLUSIONS: Vitamin D in the form of vitamin D(3) seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care. Vitamin D(2), alfacalcidol, and calcitriol had no statistically significant effect on mortality. Vitamin D(3) combined with calcium significantly increased nephrolithiasis. Both alfacalcidol and calcitriol significantly increased hypercalcaemia.",
"title": "Vitamin D supplementation for prevention of mortality in adults."
},
{
"docid": "MED-3919",
"text": "The steroid hormone output of the adrenal gland is crucial in the maintenance of hormonal homeostasis, with hormonal imbalances being associated with numerous clinical conditions which include, amongst others, hypertension, metabolic syndrome, cardiovascular disease, insulin resistance and type 2 diabetes. Aspalathus linearis (Rooibos), which has been reported to aid stress-related symptoms linked to metabolic diseases, contains a wide spectrum of bioactive phenolic compounds of which aspalathin is unique. In this study the inhibitory effects of Rooibos and the dihydrochalcones, aspalathin and nothofagin, were investigated on adrenal steroidogenesis. The activities of both cytochrome P450 17α-hydroxylase/17,20 lyase and cytochrome P450 21-hydroxylase were significantly inhibited in COS-1 cells. In order to study the effect of these compounds in H295R cells, a human adrenal carcinoma cell line, a novel UPLC-MS/MS method was developed for the detection and quantification of twenty-one steroid metabolites using a single chromatographic separation. Under both basal and forskolin-stimulated conditions, the total amount of steroids produced in H295R cells significantly decreased in the presence of Rooibos, aspalathin and nothofagin. Under stimulated conditions, Rooibos decreased the total steroid output 4-fold and resulted in a significant reduction of aldosterone and cortisol precursors. Dehydroepiandrosterone-sulfate levels were unchanged, while the levels of androstenedione (A4) and 11β-hydroxyandrostenedione (11βOH-A4) were inhibited 5.5 and 2.3-fold, respectively. Quantification of 11βOH-A4 showed this metabolite to be a major product of steroidogenesis in H295R cells and we confirm, for the first time, that this steroid metabolite is the product of the hydroxylation of A4 by human cytochrome P450 11β-hydroxylase. Taken together our results demonstrate that Rooibos, aspalathin and nothofagin influence steroid hormone biosynthesis and the flux through the mineralocorticoid, glucocorticoid and androgen pathways, thus possibly contributing to the alleviation of negative effects arising from elevated glucocorticoid levels. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "The influence of Aspalathus linearis (Rooibos) and dihydrochalcones on adrenal steroidogenesis: quantification of steroid intermediates and end pro..."
},
{
"docid": "MED-3991",
"text": "Few foods contain ergocalciferol or cholecalciferol. Treatment of mushrooms with UV light increases ergocalciferol content and could provide a dietary source of vitamin D. We evaluated the impact of consuming UV-treated white button mushrooms (Agaricus bisporus) on the vitamin D status of healthy adults. Thirty-eight volunteers were randomized to 4 treatments consumed with a standard meal for 6 wk: the control (C) group received untreated mushrooms providing 0.85 μg/d ergocalciferol (n = 10); groups M1 and M2 received UV-treated mushrooms providing 8.8 (n = 10) and 17.1 μg/d (n = 9), respectively; and the supplement (S) group received purified ergocalciferol plus untreated mushrooms, providing a total of 28.2 μg/d (n = 9). Serum total 25-hydroxyvitamin D [25(OH)D] and 25-hydroxyergocalciferol [25(OH)D2] were 83 ± 38 and 2.4 ± 2.0 nmol/L, respectively, at baseline (mean ± SD). At wk 6, 25(OH)D2 had increased and was higher in all treatment groups than in the C group, whereas 25-hydroxycholecalciferol [25(OH)D3] had decreased and was lower in the M2 and S groups than in the C group. Increases in 25(OH)D2 for groups C, M1, M2, and S were 1.2 ± 5.2, 13.8 ± 7.3, 12.7 ± 3.7, and 32.8 ± 3.3 nmol/L and decreases in 25(OH)D3 were -3.9 ± 16.3, -10.4 ± 6.4, -20.6 ± 14.6, and -29.5 ± 15.9 nmol/L, respectively. Concentrations did not change in group C. In summary, ergocalciferol was absorbed and metabolized to 25(OH)D2 but did not affect vitamin D status, because 25(OH)D3 decreased proportionally.",
"title": "Ergocalciferol from mushrooms or supplements consumed with a standard meal increases 25-hydroxyergocalciferol but decreases 25-hydroxycholecalcifer..."
},
{
"docid": "MED-3707",
"text": "OBJECTIVE: Secretory immunoglobulin A (SIgA) acts as the first line of adaptive humoral immune defense at mucosal surfaces. A lack of SIgA or the inability to produce antigen-specific SIgA can lead to an increased risk of infections. Dietary intake may improve mucosal immunity by accelerating SIgA secretion. This study investigated the effect of dietary intake of Agaricus bisporus white button mushroom (WBM) on salivary IgA (sIgA) secretion in healthy subjects. METHODS: Twenty-four healthy volunteers were randomly assigned to a normal daily diet (control group) or a normal diet with WBM. The subjects in the active group (n = 12, 41.4 ± 11.3 y old) consumed 100 g of blanched WBM daily with their normal diet for 1 wk, whereas those in the control group consumed their normal diet (n = 12, 43.5 ± 12.5 y old) without WBM. Saliva was collected before and after commencement of the study and every week thereafter for 3 wk. Saliva flow rate, sIgA concentration, and osmolality were determined and the sIgA:osmolality ratio and the sIgA secretion rate were calculated. RESULTS: There was no significant difference between pre- and postdietary mushroom intakes for all indices in the control group (P > 0.05). In contrast, the mean sIgA secretion rate increased significantly at weeks 1 and 2 by 53% and 56%, respectively, compared with that at week 0 (P < 0.0005) in the WBM intake group and then returned to a baseline level at week 3. Changes in sIgA secretion rate over the intervention period were greater in the WBM group than in the control group without WBM. In both groups, no significant changes in osmolality and saliva IgG were noted. There was, however, a significant increase in the sIgA:osmolality ratio (P < 0.0012), confirming the postdietary WBM-induced sIgA increase. CONCLUSION: The dietary intake of A. bisporus WBM significantly accelerates sIgA secretion, thereby indicating its potential health benefits for improving mucosal immunity. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.",
"title": "Dietary intake of Agaricus bisporus white button mushroom accelerates salivary immunoglobulin A secretion in healthy volunteers."
},
{
"docid": "MED-3703",
"text": "OBJECTIVE: To provide an overview of what is currently known about the relationship between allergies and cancer. DATA SOURCES: Publications were selected from a systematic review of the English-language literature from established databases (eg, MEDLINE, EBSCO) and the references of materials identified through these databases. STUDY SELECTION: Publications assessing the association between asthma, hay fever, or other allergy-related diseases and cancer were included in this review. RESULTS: Individuals with any type of allergy have a decreased risk for cancer (compared with the general population), including glioma, colorectal cancer, cancer of the larynx, non-Hodgkin lymphoma, cancer of the esophagus, oral cancer, pancreatic cancer, stomach cancer, and uterine body cancer. However, an increased risk for bladder cancer, lymphoma, myeloma, and prostate cancer exists among those with allergies. Studies that involve breast cancer, leukemia, lung cancer, melanoma, and thyroid cancer have shown no association or conflicting results related to allergies. More research is needed before conclusions can be made about the relation between allergies and Kaposi sarcoma, liver cancer, and cancer of the ovaries. CONCLUSIONS: The association between allergies and cancer is site specific. Further research is needed to verify these results and to determine why such associations exist.",
"title": "The association between allergies and cancer: what is currently known?"
},
{
"docid": "MED-5048",
"text": "Despite the continuing reports supporting the hepatoprotective effects of green tea against ethanol intoxication, there remain controversies regarding the active compound(s) and molecular mechanism. These issues were addressed in the present study using cultured HepG2 cells exposed to a lethal dose of ethanol. Gamma-glutamyl transferase (GGT) was chosen as a marker of ethanol toxicity because it is widely used in clinics. When the cells were treated with ethanol at various concentrations, there was a dose-dependent increase of GGT activity in the culture media and loss of cell viability. Pretreatment of the cells with green tea extract attenuated the changes significantly. Among the green tea constituents, (-)-epigallocatechin gallate (EGCG) attenuated the ethanol cytotoxicity effectively, whereas L-theanine and caffeine had no effects. The ethanol cytotoxicity was also attenuated by alcohol dehydrogenase inhibitor 4-methyl pyrazol and GGT inhibitor acivicin as well as by thiol modulators such as S-adenosyl-L-methionine, N-acetyl-L-cysteine and glutathione. EGCG failed to prevent the intracellular glutathione loss caused by ethanol, but it appeared to be a strong GGT inhibitor. Therefore the cytoprotective effects of green tea could be attributed to the inhibition of GGT activity by EGCG. This study suggests that GGT inhibitors including EGCG may provide a novel strategy for attenuating ethanol-induced liver damage.",
"title": "Effect of green tea and (-)-epigallocatechin gallate on ethanol-induced toxicity in HepG2 cells."
},
{
"docid": "MED-3318",
"text": "Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (≥30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (≥50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (≥40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis.",
"title": "Cigarette Smoking and Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Cohort Consortium"
},
{
"docid": "MED-3317",
"text": "Twenty-four patients, all of whom were exposed to aerosolized porcine brain tissue through work-place environment (abattoir), developed a syndrome of immune-mediated polyradiculoneuropathy; three also had central nervous system manifestations (transverse myelitis, meningoencephalitis, and aseptic meningitis). Patients had characteristic electrophysiological findings of very distal and proximal conduction slowing (prolonged distal and F-wave latencies, regions where the blood-nerve barrier is the most permeable) and all patients' serum contained a novel IgG immunofluorescence pattern. Nerve pathology, when available, showed mild changes of segmental demyelination, axonal degeneration, and inflammatory changes. Patients had meaningful improvement of symptoms and electrophysiologic findings with immune therapy and with removal of exposure to aerosolized brain tissue. We postulate that this outbreak is an auto-immune polyradiculoneuropathy triggered by occupational exposure to multiple aerosolized porcine neural tissue antigens that result in neural damage where the blood-nerve barrier is the least robust. © 2011 Peripheral Nerve Society.",
"title": "Auto-immune polyradiculoneuropathy and a novel IgG biomarker in workers exposed to aerosolized porcine brain."
},
{
"docid": "MED-1298",
"text": "Obesity-induced insulin resistance has been suggested to be a systemic inflammatory condition with activation of the innate immune system. Animal studies indicate that certain dietary fibers such as (1,3)(1,6)-beta-D-glycans (BDG) have potent effects on immune activity such as increasing the antiinflammatory cytokine interleukin-10 (IL-10) and reducing the secretion of inflammatory factors. Therefore, we hypothesized that BDG consumption improves inflammatory markers and insulin sensitivity in overweight and obese subjects with moderately increased levels of C-reactive protein, indicating subclinical inflammation. We screened 180 overweight and obese subjects for moderately increased C-reactive protein levels on 2 or more occasions, in the absence of any signs of acute infection. Twelve of the subjects met all inclusion criteria and were investigated in a randomized, double-blind, placebo-controlled, crossover design for 2 x 4 weeks (washout > or =4 weeks). Subjects ingested capsules containing 3 x 0.5 g of highly purified BDG or 3 x 0.5 g of placebo (waxy maize starch) daily. Maintenance of the normal diet of the participants and the correct intake of the capsules were monitored, using 6 x 3-day food recording and counting of the provided capsules. Predefined outcome measures were BDG-induced changes in pro and antiinflammatory markers in circulating blood and gene expression in adipose tissue and peripheral insulin sensitivity expressed as M value. The BDG consumption for 4 weeks significantly increased both circulating levels and adipose tissue messenger RNA (mRNA) expression of the antiinflammatory cytokine IL-10 in overweight and obese humans. Insulin sensitivity as well as circulating levels and mRNA expression of proinflammatory cytokines were unaffected by BDG treatment. Increased IL-10 after BDG consumption might be a contributing factor to the known beneficial effects of dietary fiber intake.",
"title": "Increased interleukin-10 but unchanged insulin sensitivity after 4 weeks of (1, 3)(1, 6)-beta-glycan consumption in overweight humans."
},
{
"docid": "MED-4096",
"text": "A variety of statistics are used to quantify the burden (occurrence and outcome) of cancer generally and of breast cancer specifically. When undertaking any cancer control program, understanding these statistics, their source, and their quality is important for assessing the current situation, allocating resources to different control strategies, and evaluating progress. Two core statistics are the cancer incidence rate and the cancer mortality rate, which provide estimates of the average risk of acquiring and of dying from the disease, respectively. About 16% of the world's population is covered by registration systems that produce cancer incidence statistics, while mortality data are available for about 29%. Breast cancer incidence and mortality vary considerably by world region. In general, the incidence is high (greater than 80 per 100,000) in developed regions of the world and low (less than 30 per 100,000), though increasing, in developing regions; the range of mortality rates is much less (approximately 6-23 per 100,000) because of the more favorable survival of breast cancer in (high-incidence) developed regions. The incidence of breast cancer is increasing almost everywhere. This unfavorable trend is due in part to increases in risk factors (decreased childbearing and breast-feeding, increased exogenous hormone exposure, and detrimental dietary and lifestyle changes, including obesity and less physical activity). On the other hand, mortality is now decreasing in many high-risk countries due to a combination of intensified early detection efforts and the introduction of mammographic screening, resulting in the diagnosis of more small, early stage tumors, and advances in treatment.",
"title": "Use of statistics to assess the global burden of breast cancer."
},
{
"docid": "MED-2354",
"text": "A new natural anti-alpha-galactosyl IgG antibody (anti-Gal) was found to be present in high titer in the serum of every normal individual studied. The antibody was isolated by affinity chromatography on a melibiose-Sepharose column. The reactivity of the antibody was assessed by its interaction with alpha-galactosyl residues on rabbit erythrocytes (RabRBC). The specificity was determined by inhibition experiments with various carbohydrates. The anti-Gal interacts with alpha-galactosyl residues, possibly on glycolipids of human RBC (HuRBC), after removal of membrane proteins by treatment with pronase. In addition, the anti-Gal bind specifically to normal and pathologically senescent HuRBC, suggesting a physiological role for this natural antibody in the aging of RBC. The ubiquitous presence of anti-Gal in high titers throughout life implies a constant antigenic stimulation. In addition to the theoretical interest in the antibody, the study of the anti-Gal reactivity seems to bear immunodiagnostic significance. Decrease in the antibody titer was found to reflect humoral immunodeficiency disorders.",
"title": "A unique natural human IgG antibody with anti-alpha-galactosyl specificity"
},
{
"docid": "MED-2353",
"text": "Summary Anti-Gal is the most abundant natural antibody in humans, constituting ∼ 1% of immunoglobulins. Anti-Gal is naturally produced also in apes and Old World monkeys. The ligand of anti-Gal is a carbohydrate antigen called the ‘α-gal epitope’ with the structure Galα1-3Galβ1-4GlcNAc-R. The α-gal epitope is present as a major carbohydrate antigen in non-primate mammals, prosimians and New World monkeys. Anti-Gal can contributes to several immunological pathogeneses. Anti-Gal IgE produced in some individuals causes allergies to meat and to the therapeutic monoclonal antibody cetuximab, all presenting α-gal epitopes. Aberrant expression of the α-gal epitope or of antigens mimicking it in humans may result in autoimmune processes, as in Graves' disease. α-Gal epitopes produced by Trypanosoma cruzi interact with anti-Gal and induce ‘autoimmune like’ inflammatory reactions in Chagas' disease. Anti-Gal IgM and IgG further mediate rejection of xenografts expressing α-gal epitopes. Because of its abundance, anti-Gal may be exploited for various clinical uses. It increases immunogenicity of microbial vaccines (e.g. influenza vaccine) presenting α-gal epitopes by targeting them for effective uptake by antigen-presenting cells. Tumour lesions are converted into vaccines against autologous tumour-associated antigens by intra-tumoral injection of α-gal glycolipids, which insert into tumour cell membranes. Anti-Gal binding to α-gal epitopes on tumour cells targets them for uptake by antigen-presenting cells. Accelerated wound healing is achieved by application of α-gal nanoparticles, which bind anti-Gal, activate complement, and recruit and activate macrophages that induce tissue regeneration. This therapy may be of further significance in regeneration of internally injured tissues such as ischaemic myocardium and injured nerves.",
"title": "Anti-Gal: an abundant human natural antibody of multiple pathogeneses and clinical benefits"
},
{
"docid": "MED-1292",
"text": "There has been enormous interest in the biologic activity of mushrooms and innumerable claims have been made that mushrooms have beneficial effects on immune function with subsequent implications for inhibition of tumor growth. The majority of these observations are anecdotal and often lack standardization. However, there remains considerable data on both in vitro and in vivo effects that reflect on the potential of mushroom compounds to influence human immunity. A number of these effects are beneficial but, unfortunately, many responses are still characterized based on phenomenology and there is more speculation than substance. With respect to tumor biology, although many neoplastic lesions are immunogenic, tumor antigens frequently are self antigens and induce tolerance and many patients with cancer exhibit suppressed immune responses, including defective antigen presentation. Therefore, if and when mushroom extracts are effective, they more likely function as a result of improved antigen presentation by dendritic cells than by a direct cytopathic effect. In this review we attempt to place these data in perspective, with a particular focus on dendritic cell populations and the ability of mushroom extracts to modulate immunity. There is, at present, no scientific basis for the use of either mushrooms or mushroom extracts in the treatment of human patients but there is significant potential for rigorous research to understand the potential of mushrooms in human disease and thence to focus on appropriate clinical trials to demonstrate effectiveness and/ or potential toxicity.",
"title": "The immunobiology of mushrooms."
},
{
"docid": "MED-4581",
"text": "We prospectively examined fruit and vegetable intake in relation to cognitive function and decline among aging women. Participants were followed from in 1976 with biennial questionnaires, and food frequency questionnaires were administered in 1984, 1986, and every 4 years thereafter. From 1995 to 2001, we administered, by telephone, six cognitive tests measuring general cognition, verbal memory, category fluency, and working memory. We repeated assessments two years later for 13,388 women (>90% follow-up). We averaged dietary intakes from 1984 through the first cognitive assessment, and used linear regression to obtain multivariable-adjusted mean differences in performance and decline in performance across intake levels. Fruits were not associated with cognition or cognitive decline. However, total vegetable intake was significantly associated with less decline. Specifically, on a global score combining all tests, women in the highest quintile of cruciferous vegetables declined slower (by 0.04 unit; 95% confidence interval, 0.003, 0.07; p trend = 0.1) compared with the lowest quintile. Women consuming the most green leafy vegetables also experienced slower decline than women consuming the least amount (by 0.05 unit; 95% confidence interval, 0.02, 0.09; p trend < 0.001). These mean differences were equivalent to those observed for women about 1 to 2 years apart in age.",
"title": "Fruit and vegetable consumption and cognitive decline in aging women."
},
{
"docid": "MED-3710",
"text": "A two-step method was developed to quantitatively assess the infection rate of the entomophthoraceous fungus, Zoophthora anhuiensis (Li) Humber, on the green peach aphid, Myzus persicae (Sulzer). Firstly, a standard time-dose-mortality relationship, established by modeling data from bioassay 1 at varying conidial dosages (0.4 - 10.4 conidia/mm2) of Z. anhuiensis F97028, was used to yield an estimate of expected mortality probability at a given dosage. Secondly, bioassay 2 was conducted by simultaneously exposing six < or = 4-day-old nymphal colonies to a shower of Z. anhuiensis conidia at each of four dosages (resulting from exposures of 0.3 - 8.0 min). Subsequently, the colonies were separately immersed in a 0.1% chlorothalonil solution for 0.5 min to disinfect all surviving conidia on the host integument from 1 - 12 h after exposure under temperature treatments of 15 and 20 degrees C, respectively. The infection rate during a specific period from the end of the exposure to the immersion was then estimated as the ratio of the observed mortality over the expected mortality probability at a particular dosage. The results showed that the infection of M. persicae from Z. anhuiensis was highly rapid with little difference between aphid colonies maintained at 15 and 20 degrees C before being immersed in the fungicidal solution after exposure. The first 6-hour period after exposure was most crucial to successful infection of the fungus with the infection rate greatly depending on conidial dosages. It took < or = 1 h to infect > 50% of the aphids at a dosage of > 1.5 conida/mm2 and > 90% at > 50 conidia/mm2.",
"title": "Quantitative assessment of the infection rate of the entomophthoraceous fungus, Zoophthora anhuiensis against the green peach aphid Myzus persicae."
},
{
"docid": "MED-3989",
"text": "Vitamin D(2) (ergocalciferol) and sterols were analyzed in mushrooms sampled nationwide in the United States to update the USDA Nutrient Database for Standard Reference. Vitamin D(2) was assayed using HPLC with [(3)H]-vitamin D(3) internal standard and sterols by GC-FID mass spectrometric (MS) confirmation. Vitamin D(2) was low (0.1-0.3 μg/100 g) in Agaricus bisporus (white button, crimini, portabella) and enoki, moderate in shiitake and oyster (0.4-0.7 μg/100 g), and high in morel, chanterelle, maitake (5.2-28.1 μg/100 g) and UV-treated portabella (3.4-20.9 μg/100 g), with significant variability among composites for some types. Ergosterol (mg/100 g) was highest in maitake and shiitake (79.2, 84.9) and lowest in morel and enoki (26.3, 35.5); the range was <10 mg/100 g among white button composites but 12-50 mg/100 g among samples of other types. All mushrooms contained ergosta-5,7-dienol (22,23-dihydroergosterol) (3.53-18.0 mg/100 g) and (except morel) ergosta-7-enol. Only morel contained brassicasterol (28.6 mg/100 g) and campesterol (1.23-4.54 mg/100 g) and no ergosta-7,22-dienol. MS was critical in distinguishing campesterol from ergosta-7,22-dienol.",
"title": "Vitamin D and sterol composition of 10 types of mushrooms from retail suppliers in the United States."
},
{
"docid": "MED-2360",
"text": "Lyme-like illness (also known as southern tick-associated rash illness [STARI] or Masters disease) is vectored by the Lone Star tick (Amblyomma americanum). Lyme-like illness lesions, which are similar to the erythema migrans rash of Lyme disease, tend to have lymphocytic dermal infiltrates. With the exception of Borrelia lonestari, the possible causative agent or agents of Lyme-like illness have not been cultured. More research is needed to fully understand this newly recognized zoonosis. Clinicians are encouraged to increase their knowledge and awareness of this Lyme disease mimic.",
"title": "STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness."
},
{
"docid": "MED-3706",
"text": "Autoimmune diseases are complex diseases resulting of the interaction between both genetics and environmental factors over time. Different phases in the development of autoimmune diseases are characterized by the detection of serum autoantibodies several months or years before the onset of clinical manifestations and subsequent diagnosis. In addition to serum antibodies, genetic susceptibility factors may predict the future development of the disease. Currently, prediction in type 1 diabetes is the most accurate, with the analysis of genetic susceptibility factors in first-degree relatives of patients and several autoantibody tests. In the future, multiple antibodies test, in combination with the analysis of genetics, epigenetics and immunological anomalies in fine models may allow the precise prediction in autoimmune diseases. Prevention measures might thus be introduced as an attempt to avoid or delay the disease. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Are autoimmune diseases predictable?"
},
{
"docid": "MED-3986",
"text": "BACKGROUND/OBJECTIVES: Mushrooms contain very little or any vitamin D(2) but are abundant in ergosterol, which can be converted into vitamin D(2) by ultraviolet (UV) irradiation. Our objective was to investigate the bioavailability of vitamin D(2) from vitamin D(2)-enhanced mushrooms by UV-B in humans, and comparing it with a vitamin D(2) supplement. SUBJECTS/METHODS: Fresh mushrooms were irradiated with an UV-B dose of 1.5 J/cm(2), increasing vitamin D(2) content from <1 to 491 μg/100 g and made to an experimental soup. In this 5-week, single-blinded, randomized, placebo-controlled trial, 26 young subjects with serum 25-hydroxyvitamin D (25OHD) ≤ 50 nmol/l were randomly assigned into three groups ((a) mushroom, (b) supplement and (c) placebo). They received during winter (a) 28,000 IU (700 μg) vitamin D(2) via the experimental soup, or (b) 28,000 IU vitamin D(2) via a supplement or (c) placebo, respectively. RESULTS: After 2 weeks, serum 25OHD was significantly higher in the mushroom than in the placebo group (P=0.001). The serum 25OHD concentrations in the mushroom and supplement groups rose significantly and similarly over the study period by 3.9 nmol/l (95% confidence interval (95% CI): 2.9, 4.8) and by 4.7 nmol/l per week (95% CI: 3.8, 5.7), respectively. CONCLUSIONS: We are the first to demonstrate in humans that the bioavailability of vitamin D(2) from vitamin D(2)-enhanced button mushrooms via UV-B irradiation was effective in improving vitamin D status and not different to a vitamin D(2) supplement. This trial was registered at http://germanctr.de as DRKS00000195.",
"title": "Bioavailability of vitamin D₂ from UV-B-irradiated button mushrooms in healthy adults deficient in serum 25-hydroxyvitamin D: a randomized controll..."
},
{
"docid": "MED-4881",
"text": "The effects of microbial transglutaminase (MTGase) at different levels (0 to 0.8 units/g sample) on the properties of gels from lizardfish (Saurida undosquamis) mince set at 25 degrees C for 2 h or 40 degrees C for 30 min prior to heating at 90 degrees C for 20 min were studied. Breaking force and deformation of gels increased with increasing MTGase amount added (P<0.05). At the same MTGase level used, gels with the prior setting at 40 degrees C for 30 min showed a higher breaking force compared with those subjected to prior setting at 25 degrees C for 2 h (P<0.05). Sodium dodecyl sulfate-polyacrylamide gel electrophoretic study revealed that myosin heavy chain (MHC) underwent polymerization to a higher extent in the presence of MTGase. Regardless of setting condition, microstructure of gel added with MTGase was finer with a smaller void compared with that of gel without MTGase. Therefore, setting temperature affected the property of gels added with MTGase. Gel properties of mince obtained from lizardfish stored in ice for different times (0 to 10 d) with and without MTGase at a level 0.6 units/g were determined. Irrespective of MTGase addition, breaking force and deformation of all gels decreased as the storage time of lizardfish increased (P<0.05). The addition of MTGase was able to increase both breaking force and deformation of the resulting gel produced from lizardfish kept in ice for all storage times used. Therefore, both freshness and MTGase addition had the direct impact on gel properties of lizardfish mince.",
"title": "Improvement of gelling properties of lizardfish mince as influenced by microbial transglutaminase and fish freshness."
},
{
"docid": "MED-4882",
"text": "OBJECTIVE: To determine whether chicken-based formula can replace soy-based formula in infants with cow milk allergy. SUBJECTS AND METHODS: Thirty-eight infants with cow's milk allergy, aged between 2-24 months of age were randomized to receive either chicken-based formula or soy-based formula for 14 days. RESULTS: In the group of soy-based formula, 12 out of 18 infants had evidence of intolerance and could not continue with the formula. However, only 4 out of 20 infants in the chicken-based formula group had evidence of clinical intolerance. All other 16 infants were fed the chicken-based formula with success. The number of infants who were intolerant to chicken formula was significantly lower than the number of those fed soy-based formula (p = 0.009). CONCLUSION: Chicken-based formula can be used more effectively than soy-based formula in infants with cow milk allergy.",
"title": "Comparisons of a chicken-based formula with soy-based formula in infants with cow milk allergy."
},
{
"docid": "MED-2272",
"text": "To assess the physiologic effects of cherry consumption, we measured plasma urate, antioxidant and inflammatory markers in 10 healthy women who consumed Bing sweet cherries. The women, age 22-40 y, consumed two servings (280 g) of cherries after an overnight fast. Blood and urine samples were taken before the cherry dose, and at 1.5, 3 and 5 h postdose. Plasma urate decreased 5 h postdose, mean +/- SEM = 183 +/- 15 micro mol/L compared with predose baseline of 214 +/- 13 micro mol/L (P < 0.05). Urinary urate increased postdose, with peak excretion of 350 +/- 33 micro mol/mmol creatinine 3 h postdose compared with 202 +/- 13 at baseline (P < 0.01). Plasma C-reactive protein (CRP) and nitric oxide (NO) concentrations had decreased marginally 3 h postdose (P < 0.1), whereas plasma albumin and tumor necrosis factor-alpha were unchanged. The vitamin C content of the cherries was solely as dehydroascorbic acid, but postdose increases in plasma ascorbic acid indicated that dehydroascorbic acid in fruits is bioavailable as vitamin C. The decrease in plasma urate after cherry consumption supports the reputed anti-gout efficacy of cherries. The trend toward decreased inflammatory indices (CRP and NO) adds to the in vitro evidence that compounds in cherries may inhibit inflammatory pathways.",
"title": "Consumption of cherries lowers plasma urate in healthy women."
},
{
"docid": "MED-5047",
"text": "Our objective was to examine whether habitual green tea consumption is associated with blood glucose levels and other biomarkers of glucose metabolism. We conducted a cross-sectional study of 35 male volunteers, 23–63 years old and residing in Shizuoka Prefecture in Japan. Biochemical data were measured and we conducted a questionnaire survey on health, lifestyle, and nutrition, as well as frequency of consumption and concentrations (1%, 2%, and 3%) of green tea. Men who consumed a 3% concentration of green tea showed lower mean values of fasting blood glucose and fructosamine than those who consumed a 1% concentration. Fasting blood glucose levels were found to be significantly associated with green tea concentration (β = −0.14, p = 0.03). However, green tea consumption frequency showed no significant differences in mean levels of blood glucose, fructosamine and hemoglobin A1c. In conclusion, our findings suggest that the consumption of green tea at a high concentration has the potential to reduce blood glucose levels.",
"title": "The Association between Concentrations of Green Tea and Blood Glucose Levels"
},
{
"docid": "MED-3700",
"text": "Background An increased risk of breast cancer is associated with alcohol consumption; however, it is controversial whether red wine increases this risk. Aromatase inhibitors (AIs) prevent the conversion of androgens to estrogen and occur naturally in grapes, grape juice, and red, but not white wine. We tested whether red wine is a nutritional AI in premenopausal women. Methods In a cross-over design, 36 women (mean age [SD], 36 [8] years) were assigned to 8 ounces (237 mL) of red wine daily then white wine for 1 month each, or the reverse. Blood was collected twice during the menstrual cycle for measurement of estradiol (E2), estrone (E1), androstenedione (A), total and free testosterone (T), sex hormone binding globulin (SHBG), luteinizing hormone (LH), and follicle stimulating hormone (FSH). Results Red wine demonstrated higher free T vs. white wine (mean difference 0.64 pg/mL [0.2 SE], p=0.009) and lower SHBG (mean difference −5.0 nmol/L [1.9 SE], p=0.007). E2 levels were lower in red vs. white wine but not statistically significant. LH was significantly higher in red vs. white wine (mean difference 2.3 mIU/mL [1.3 SE], p=0.027); however, FSH was not. Conclusion Red wine is associated with significantly higher free T and lower SHBG levels, as well as a significant higher LH level vs. white wine in healthy premenopausal women. These data suggest that red wine is a nutritional AI and may explain the observation that red wine does not appear to increase breast cancer risk.",
"title": "Red Versus White Wine as a Nutritional Aromatase Inhibitor in Premenopausal Women: A Pilot Study"
},
{
"docid": "MED-3988",
"text": "Context: Two reports suggested that vitamin D2 is less effective than vitamin D3 in maintaining vitamin D status. Objective: Our objective was to determine whether vitamin D2 was less effective than vitamin D3 in maintaining serum 25-hydroxyvitamin D levels or increased the catabolism of 25-hydroxyvitamin D3. Subjects and Design: This was a randomized, placebo-controlled, double-blinded study of healthy adults ages 18–84 yr who received placebo, 1000 IU vitamin D3, 1000 IU vitamin D2, or 500 IU vitamin D2 plus 500 IU vitamin D3 daily for 11 wk at the end of the winter. Results: Sixty percent of the healthy adults were vitamin D deficient at the start of the study. The circulating levels of 25-hydroxyvitamin D (mean ± sd) increased to the same extent in the groups that received 1000 IU daily as vitamin D2 (baseline 16.9 ± 10.5 ng/ml; 11 wk 26.8 ± 9.6 ng/ml), vitamin D3 (baseline 19.6 ± 11.1 ng/ml; 11 wk 28.9 ± 11.0 ng/ml), or a combination of 500 IU vitamin D2 and 500 IU vitamin D3 (baseline 20.2 ± 10.4 ng/ml; 11 wk 28.4 ± 7.7 ng/ml). The 25-hydroxyvitamin D3 levels did not change in the group that received 1000 IU vitamin D2 daily. The 1000 IU dose of vitamin D2 or vitamin D3 did not raise 25-hydroxyvitamin D levels in vitamin D-deficient subjects above 30 ng/ml. Conclusion: A 1000 IU dose of vitamin D2 daily was as effective as 1000 IU vitamin D3 in maintaining serum 25-hydroxyvitamin D levels and did not negatively influence serum 25-hydroxyvitamin D3 levels. Therefore, vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin D status.",
"title": "Vitamin D2 Is as Effective as Vitamin D3 in Maintaining Circulating Concentrations of 25-Hydroxyvitamin D"
},
{
"docid": "MED-4312",
"text": "Eosinophilia–myalgia syndrome (EMS) is characterized by subacute onset of myalgias and peripheral eosinophilia, followed by chronic neuropathy and skin induration. An epidemic of EMS in 1989 was linked to L-tryptophan consumption originating from a single source. Following the Food and Drug Administration (FDA) ban on the sale of L-tryptophan, the incidence of EMS declined rapidly. Moreover, no new cases have been published since the FDA ban was lifted in 2005. We report the clinical, histopathological and immunogenetic features of a new case of L-tryptophan-associated EMS along with evidence of activated transforming growth factor-ß and interleukin-4 signaling in the lesional skin.",
"title": "Post-epidemic eosinophilia myalgia syndrome associated with L-Tryptophan"
},
{
"docid": "MED-3920",
"text": "Green tea is reported to have wide ranging beneficial health outcomes across epidemiological studies, which have been attributed to its flavonoid content. We investigated whether the flavonoid epigallocatechin gallate (EGCG) modulates brain activity and self-reported mood in a double-blind, placebo controlled crossover study. Participants completed baseline assessments of cognitive and cardiovascular functioning, mood and a resting state electroencephalogram (EEG) before and then 120 min following administration of 300 mg EGCG or matched placebo. EGCG administration was associated with a significant overall increase in alpha, beta and theta activity, also reflected in overall EEG activity, more dominant in midline frontal and central regions, specifically in the frontal gyrus and medial frontal gyrus. In comparison to placebo the EGCG treatment also increased self-rated calmness and reduced self rated stress. This pattern of results suggests that participants in the EGCG condition may have been in a more relaxed and attentive state after consuming EGCG. This is in keeping with the widespread consumption of green tea for its purported relaxing/refreshing properties. The modulation of brain function due to EGCG is deserving of further controlled human studies. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Acute neurocognitive effects of epigallocatechin gallate (EGCG)."
},
{
"docid": "MED-2352",
"text": "BACKGROUND: Carbohydrate-specific IgE antibodies present on nonprimate mammalian proteins were incriminated recently in delayed meat anaphylaxis. The aim of this study was to explore whether anaphylaxis to mammalian kidney is also associated with galactose-α-1,3-galactose (αGal)-specific IgE. METHODS: Fourteen patients with anaphylaxis to pork or beef kidney underwent prick tests to meat and kidney. Some patients also underwent skin tests to Erbitux(®) (cetuximab). IgE antibodies to αGal, swine urine proteins, beef and pork meat, serum albumin proteins, cat, and rFel d 1 were measured by ImmunoCAP(®). The αGal levels were estimated in meats and kidney by ELISA inhibition assay. Cross-reactivity between αGal and pork kidney was studied with the ImmunoCAP(®) inhibition assay. RESULTS: Among the 14 patients, 12 presented with anaphylactic shock. Reactions occurred within 2 h from exposure in 67% of patients. Associated risk factors were observed in 10 cases, and alcohol was the main cofactor. Three patients underwent an oral challenge to pork kidney, and anaphylaxis occurred after ingestion of small quantities (1-2 g). Prick tests to kidney were positive in 54% of patients. All tested patients showed positive skin tests to Erbitux(®). All patients tested positive for IgE to αGal, with levels ranging from 0.4 to 294 kU/l. IgE binding to αGal was inhibited by raw pork kidney extract (mean, 77%; range, 55-87%), which showed a high amount of αGal determinants. CONCLUSIONS: Pork or beef kidney anaphylaxis is related to αGal IgE. Its peculiar severity could be due to an elevated content of αGal epitopes in kidney. © 2012 John Wiley & Sons A/S.",
"title": "Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose."
},
{
"docid": "MED-2356",
"text": "Background In 2009, we reported a novel form of delayed anaphylaxis to red meat, which is related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. Objectives To investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur. Methods Serum assays were carried out using biotinylated proteins and extracts bound to a streptavidin ImmunoCAP. Results Prospective studies on IgE antibodies in three subjects following tick bites showed an increase in IgE to alpha-gal of twenty-fold or greater. Other evidence included i) a strong correlation between histories of tick bites and IgE to alpha-gal (χ2=26.8, p<0.001), ii) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and iii) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A. americanum (rs=0.75, p<0.001). Conclusion The results presented here provide evidence that tick bites are a cause, or possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.",
"title": "The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose"
},
{
"docid": "MED-3307",
"text": "OBJECTIVE: workers in slaughterhouses and processing plants that handle pigs, and pork butchers/meatcutters have been little studied for health risks associated with employment, in spite of the fact that they are potentially exposed to oncogenic and non-oncogenic transmissible agents and chemical carcinogens at work. We report here on an update of mortality in 510 workers employed in abattoirs and processing plants that almost exclusively handled pigs and pork products. METHODS: standardized mortality ratios (SMRs) were estimated for the cohort as a whole, and in subgroups defined by race and sex, using the corresponding US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time 45% of them died. RESULTS: mortality was significantly increased overall in the cohort. A statistically significant excess of deaths was observed for colon and lung cancers in the entire cohort, SMR=2.7 (95% CI, 1.2-5.1), SMR=1.8 (95% CI, 1.1-2.7), respectively. Significant SMRs in the cohort as a whole were also observed for senile and pre-senile psychotic conditions (SMR=5.1, 95% CI, 1.4-13.1), and pneumonia (SMR=2.6, 95% CI, 1.3-4.8). An observed excess of subarachnoid hemorrhage was seen mainly in whites (SMR=10.1, 95% CI, 1.2-36.3). There was a suggestion of an excess of deaths from ischemic heart disease also, but the elevated SMR was confined to men and was not statistically significant. CONCLUSION: this study confirms the excess occurrence of lung and colon cancers, and stroke previously reported in this occupational group. New findings are the excess of risk for senile and pre-senile psychotic conditions and pneumonia, which together with the excess of colon cancer appear specific for pig/pork workers, as they were not evident in much larger studies of workers in abattoirs and processing plants handling cattle and sheep. However, caution should be exercised in interpreting these findings, since some of them could have occurred by chance, resulting from our examination of a large number of causes of death in multiple study subgroups. For the moment, the significance of these findings remains unknown until they are confirmed in larger studies of adequate statistical power. Studies that will take into account possible occupational and non-occupational confounding factors are needed. Copyright © 2011. Published by Elsevier Inc.",
"title": "Mortality in workers employed in pig abattoirs and processing plants."
},
{
"docid": "MED-2365",
"text": "Twenty-five patients living in a tick-endemic region of Sydney, New South Wales developed red meat allergy after experiencing large local reactions to tick bites. This represents a potentially novel cross-reaction between an arthropod and a food protein. (MJA 2009; 190: 510-511).",
"title": "An association between tick bite reactions and red meat allergy in humans."
},
{
"docid": "MED-1293",
"text": "In the domain of nutrition, exploring the diet-health linkages is major area of research. The outcomes of such interventions led to widespread acceptance of functional and nutraceutical foods; however, augmenting immunity is a major concern of dietary regimens. Indeed, the immune system is incredible arrangement of specific organs and cells that enabled humans to carry out defense against undesired responses. Its proper functionality is essential to maintain the body homeostasis. Array of plants and their components hold immunomodulating properties. Their possible inclusion in diets could explore new therapeutic avenues to enhanced immunity against diseases. The review intended to highlight the importance of garlic (Allium sativum), green tea (Camellia sinensis), ginger (Zingiber officinale), purple coneflower (Echinacea), black cumin (Nigella sativa), licorice (Glycyrrhiza glabra), Astragalus and St. John's wort (Hypericum perforatum) as natural immune boosters. These plants are bestowed with functional ingredients that may provide protection against various menaces. Modes of their actions include boosting and functioning of immune system, activation and suppression of immune specialized cells, interfering in several pathways that eventually led to improvement in immune responses and defense system. In addition, some of these plants carry free radical scavenging and anti-inflammatory activities that are helpful against cancer insurgence. Nevertheless, interaction between drugs and herbs/botanicals should be well investigated before recommended for their safe use, and such information must be disseminated to the allied stakeholders.",
"title": "Immunity: plants as effective mediators."
},
{
"docid": "MED-4651",
"text": "BACKGROUND: Several publications reported breast cancer incidence rates continued to decrease among white women, following the decline of about 7% from 2002 to 2003. However, none of these reports exclusively examined the trend after 2003. In this paper, we examined breast cancer incidence rates among non-Hispanic (NH) white women from 2003 to 2007 to determine whether the decrease in breast cancer incidence rates indeed persisted through 2007. In addition, we present breast cancer incidence trends for NH black and Hispanic women and postmenopausal hormone use for all three racial/ethnic groups. METHODS: Breast cancer incidence rates were calculated by race/ethnicity, age and ER status using data from the Surveillance, Epidemiology, and End Results (SEER) 12 registries for 2000 to 2007. Prevalence of postmenopausal hormone use was calculated using National Health Interview Survey data from 2000, 2005, and 2008. RESULTS: From 2003 to 2007, overall breast cancer incidence rates did not change significantly among NH white women in any age group. However, rates increased (2.7% per year) for ER+ breast cancers in ages 40 to 49, and decreased for ER- breast cancers in ages 40 to 49 and 60 to 69. Similarly, overall breast cancer incidence rates did not change significantly for black and Hispanic women. Hormone use continued to decrease from 2005 to 2008 in all groups, although the decreases were smaller compared to those from 2000 to 2005. CONCLUSIONS: The sharp decline in breast cancer incidence rates that occurred from 2002 to 2003 among NH white women did not continue through 2007. IMPACT: Further studies are needed to better understand the recent breast cancer trends. ©2011 AACR.",
"title": "Breast cancer incidence rates in U.S. women are no longer declining."
},
{
"docid": "MED-1294",
"text": "Beta-glucans are a heterogeneous group of natural polysaccharides mostly investigated for their immunological effects. Due to the low systemic availability of oral preparations, it has been thought that only parenterally applied beta-glucans can modulate the immune system. However, several in vivo and in vitro investigations have revealed that orally applied beta-glucans also exert such effects. Various receptor interactions, explaining possible mode of actions, have been detected. The effects mainly depend on the source and structure of the beta-glucans. In the meantime, several human clinical trials with dietary insoluble yeast beta-glucans have been performed. The results confirm the previous findings of in vivo studies. The results of all studies taken together clearly indicate that oral intake of insoluble yeast beta-glucans is safe and has an immune strengthening effect.",
"title": "Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan"
},
{
"docid": "MED-3985",
"text": "Deficiency of vitamin D is usually caused by dietary deficiency and/or lack of exposure to sunlight in dark skinned individuals living at northern latitudes. Simple vitamin D deficiency is commonly treated by prescribing a vitamin D containing calcium supplement. This report presents a patient who rejected this approach and instead, after researching alternative treatment options independently, opted to self-treat by consuming UVB-irradiated mushrooms. The beneficial effect of this on the patient's plasma biochemical markers is shown. Further research into the beneficial effect of consuming UVB-irradiated mushrooms is required.",
"title": "Vitamin D deficiency treated by consuming UVB-irradiated mushrooms"
},
{
"docid": "MED-3702",
"text": "BACKGROUND: Increased prevalence of allergic diseases in western societies has been described as an epidemic. The precise turning point for the epidemic and the antigens responsible for it remain obscure. OBJECTIVE: To evaluate how the prevalence of atopic disease has changed in terms of detectable sensitization to aeroallergens and dietary allergens in a cross-sectional comparison of subjects from birth cohorts more than 60 years apart. METHODS: We studied four groups of 100 subjects each (at ages 7, 27, 47 and 67 years), representing those born in 1990, 1963-66, 1943-46 and in 1923-26, respectively. Serum total and specific IgE concentrations against aeroallergens and dietary allergens were determined. A questionnaire elicited information on symptoms, allergic diseases and medication. RESULTS: The proportion of subjects with detectable IgE antibodies against aeroallergens increased consistently from the oldest to the youngest birth cohorts; chi2 trend=56.809, P<0.0001. Similar progression was not seen in sensitization to dietary allergens. The proportion of those with diagnosed asthma differed significantly (chi2=13.45, P=0.004) across the birth cohorts. The lowest prevalence of asthma and sensitization to dietary allergens was detected in those born in 1943-46, i.e. during or immediately after World War II. CONCLUSION: Prevalence of sensitization to airborne allergens, unlike that to dietary allergens, has increased over a long period of time. Our results support the concept of the immune function being programmed by external factors early in life. They also call for caution when interpretations of the pace and possible causes of the allergy epidemic are made on the basis of short-term studies.",
"title": "The allergy epidemic extends beyond the past few decades."
},
{
"docid": "MED-3464",
"text": "The purpose of this study was to determine the effects of consuming sweet cherries on plasma lipids and markers of inflammation in healthy humans. Healthy men and women (n = 18) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. After a 12-h fast, blood samples were taken before the start of cherry consumption (study d 0 and 7), 14 and 28 d after the start of cherry supplementation (study d 21 and 35), and 28 d after the discontinuation (study d 64) of cherry consumption. After cherries were consumed for 28 d, circulating concentrations of C-reactive protein (CRP), regulated upon activation, normal T-cell expressed, and secreted (RANTES), and NO decreased by 25 (P < 0.05), 21 (P < 0.05), and 18% (P = 0.07) respectively. After the discontinuation of cherry consumption for 28 d (d 64), concentrations of RANTES continued to decrease (P = 0.001), whereas those of CRP and NO did not differ from either d 7 (pre-cherries) or d 35 (post-cherries). Plasma concentrations of IL-6 and its soluble receptor, intercellular adhesion molecule-1, and tissue inhibitor of metalloproteinases-2 did not change during the study. Cherry consumption did not affect the plasma concentrations of total-, HDL-, LDL-, and VLDL- cholesterol, triglycerides, subfractions of HDL, LDL, VLDL, and their particle sizes and numbers. It also did not affect fasting blood glucose or insulin concentrations or a number of other chemical and hematological variables. Results of the present study suggest a selective modulatory effect of sweet cherries on CRP, NO, and RANTES. Such anti-inflammatory effects may be beneficial for the management and prevention of inflammatory diseases.",
"title": "Consumption of Bing sweet cherries lowers circulating concentrations of inflammation markers in healthy men and women."
},
{
"docid": "MED-2362",
"text": "The study of the expression of Gal alpha 1----3Gal beta 1----4GlcNAc residues on mammalian glycoconjugates is of particular interest since as many as 1% of circulating IgG antibodies in man (the natural anti-Gal antibody) interact specifically with this carbohydrate residue. In recent studies, we have found that Gal alpha 1----3Gal beta 1----4GlcNAc residues are abundant on red cells and nucleated cells of nonprimate mammals, prosimians, and New World monkeys, but their expression is diminished in Old World monkeys, apes, and humans. In the present work, we have analyzed the expression of these residues on secreted mammalian glycoproteins. For this purpose, we have developed a radioimmunoassay (RIA) which enables the quantification of Gal alpha 1----3Gal beta 1----4GlcNAc residues on the secreted glycoproteins. Purified biotinylated anti-Gal was used as the antibody in the RIA, and bovine thyroglobulin enriched for Gal alpha 1----3Gal beta 1----4GlcNAc residues served as a solid-phase antigen. In this study, it is reported for the first time that the evolutionary pattern of Gal alpha 1----3Gal beta 1----4GlcNAc residue distribution in in vivo secreted glycoproteins is similar to that observed in membranes of cell lines and of red cells. Thyroglobulin, fibrinogen, or IgG molecules from nonprimate mammals and from New World monkeys express varying amounts of Gal alpha 1----3Gal beta 1----4GlcNAc residues ranging between 0.01 and 11 residues per molecule, whereas no such residues are present on any of these glycoproteins of human or Old World monkey origin.(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Distribution of Gal alpha 1----3Gal beta 1----4GlcNAc residues on secreted mammalian glycoproteins (thyroglobulin, fibrinogen, and immunoglobulin G..."
},
{
"docid": "MED-1291",
"text": "There is significant interest in the use of mushrooms and/or mushroom extracts as dietary supplements based on theories that they enhance immune function and promote health. To some extent, select mushrooms have been shown to have stimulatory action on immune responsiveness, particularly when studied in vitro. However, despite their widespread use for potential health benefits, there is a surprising paucity of epidemiologic and experimental studies that address the biologic activities of mushrooms after oral administration to animals or humans. There have been a number of studies that have addressed the ability of mushrooms to modulate mononuclear cell activation and the phenotypic expression of cytokines and their cognate receptors. There have also been a number of attempts to determine antitumor activities of mushrooms. Such studies are important because many of the components of mushrooms do potentially have significant biologic activity. All data, however, should be tempered by the possibility that there are toxic levels of metals, including arsenic, lead, cadmium, and mercury as well as the presence of radioactive contamination with 137Cs. In this review, we will present the comparative biology with respect to both immunological and antitumor activities of mushroom extracts and also highlight the need for further evidence-based research.",
"title": "Mushrooms, tumors, and immunity: an update."
},
{
"docid": "MED-3923",
"text": "OBJECTIVE: Inadvertent exposure to the ubiquitous weed, Urtica dioica, called \"stinging nettles\" produces an immediate stinging and burning sensation on the skin. This investigation evaluates the structural effect that stinging nettle spicules may have on the clinical manifestation of these symptoms. This hypothesis was investigated by exposing murine skin to stinging nettles and then evaluating the skin using electron microscopy. It was hypothesized that the mechanism of action of stinging nettles is both biochemical and mechanical, which may have clinical significance regarding treatment for acute exposure. METHODS: Fresh post-mortem dermis samples from the carcasses of genetically modified hairless mice were brushed under the stem and leaf of a stinging nettle plant, mimicking the clinical method of exposure a patient might experience. Another set of mouse skin samples was obtained but not exposed to the nettles. Both sets of skin samples were imaged with scanning electron microscopy. RESULTS: The skin samples that were not exposed to nettle leaves were uniform, with occasional striated hairs on the skin surface and no nettle spicules. The skin samples exposed to nettle leaves showed many smooth nettle spicules piercing the skin surface. A few spicules retained their bases, which appear empty of any liquid contents. CONCLUSIONS: The mechanism of action of stinging nettles dermatitis appears to be both biochemical and mechanical. Impalement of spicules into the skin likely accounts for the mechanical irritation in addition to the known adverse chemical effects of stinging nettles. Further investigation of treatment modalities is warranted. Copyright © 2011 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.",
"title": "Mechanism of action of stinging nettles."
},
{
"docid": "MED-5171",
"text": "The objective of this study was to determine the prevalence of enterohemorrhagic Escherichia coli (EHEC), E. coli O157, Salmonella, and Listeria monocytogenes in retail food samples from Seattle, Wash. A total of 2,050 samples of ground beef (1,750 samples), mushrooms (100 samples), and sprouts (200 samples) were collected over a 12-month period and analyzed for the presence of these pathogens. PCR assays, followed by culture confirmation were used to determine the presence or absence of each organism. Of the 1,750 ground beef samples analyzed, 61 (3.5%) were positive for EHEC, and 20 (1.1%) of these were positive for E. coli O157. Salmonella was present in 67 (3.8%) of the 1,750 ground beef samples. Of 512 ground beef samples analyzed, 18 (3.5%) were positive for L. monocytogenes. EHEC was found in 12 (6.0%) of the 200 sprout samples, and 3 (1.5%) of these yielded E. coli O157. Of the 200 total sprout samples, 14 (7.0%) were positive for Salmonella and none were positive for L. monocytogenes. Among the 100 mushroom samples, 4 (4.0%) were positive for EHEC but none of these 4 samples were positive for E. coli O157. Salmonella was detected in 5 (5.0%) of the mushroom samples, and L. monocytogenes was found in 1 (1.0%) of the samples.",
"title": "Incidence of enterohemorrhagic Escherichia coli, Escherichia coli O157, Salmonella, and Listeria monocytogenes in retail fresh ground beef, sprouts..."
},
{
"docid": "MED-1299",
"text": "OBJECTIVE: Several studies have shown a baker's yeast beta-1,3/1,6-d-glucan, extracted from Saccharomyces cerevisiae, is effective in reducing the incidence of cold and flu symptoms. This study evaluated the effect of a specific beta-glucan supplement (Wellmune) on upper respiratory tract symptoms and psychological well-being in women with moderate levels of psychological stress. METHODS: Healthy women (38 ± 12 years old) prescreened for moderate levels of psychological stress, self-administered a placebo (n = 38) or 250 mg of Wellmune (n = 39) daily for 12 weeks. We used the Profile of Mood States (POMS) psychological survey to assess changes in mental/physical energy levels (vigor) and overall well-being (global mood state). A quantitative health perception log was used to track upper respiratory symptoms. RESULTS: Subjects in the Wellmune group reported fewer upper respiratory symptoms compared to placebo (10% vs 29%), better overall well-being (global mood state: 99 ± 19 vs 108 ± 23, p < 0.05), and superior mental/physical energy levels (vigor: 19.9 ± 4.7 vs 15.8 ± 6.3, p < 0.05). CONCLUSIONS: These data show that daily dietary supplementation with Wellmune reduces upper respiratory symptoms and improves mood state in stressed subjects, and thus it may be a useful approach for maintaining immune protection against daily stressors.",
"title": "Baker's yeast beta-glucan supplement reduces upper respiratory symptoms and improves mood state in stressed women."
},
{
"docid": "MED-4884",
"text": "In this study, magnetic resonance imaging (MRI) was applied to study the structural aspects of the tomato fruit. The main study was performed on tomatoes (cv. Tradiro) using a 0.2-T electromagnet scanner. Spin-echo images were acquired to visualize the tomato macrostructure. The air bubble content in tissues was evaluated by exploiting susceptibility effects using multiple gradient echo images. The microstructure was further studied by measuring spin-spin (T(2)) and spin-lattice (T(1)) relaxation time distributions. Nuclear magnetic resonance relaxometry, macro vision imaging and chemical analysis were used as complementary and independent experimental methods in order to emphasize the MRI results. MRI images showed that the air bubble content varied between tissues. The presence of gas was attested by macro vision images. Quantitative imaging showed that T(2) and T(1) maps obtained by MRI reflected the structural differences between tomato tissues and made it possible to distinguish between them. The results indicated that cell size and chemical composition contribute to the relaxation mechanism.",
"title": "An investigation of the structural aspects of the tomato fruit by means of quantitative nuclear magnetic resonance imaging."
},
{
"docid": "MED-2278",
"text": "OBJECTIVES: To investigate the anti-inflammatory and anti-oxidative effects of anthocyanins from cherries on Freund's adjuvant-induced arthritis (AIA) in rats. METHODS: Arthritis was induced intradermally by injection with 0.1 mL of complete Freund's adjuvant (CFA) into the right hind footpad of male Sprague Dawley (SD) rats. Anthocyanins at 40, 20 and 10 mg/kg (body weight) were administered orally to the treated rats for 28 days after the injection. Tumour necrosis factor-alpha (TNFalpha) in serum and prostaglandin E2 (PGE2) in paws were assayed by radioimmunoassay (RIA), and anti-oxidative effects was assayed by measuring total anti-oxidative capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum. RESULTS: Anthocyanins at 40 mg/kg significantly decreased the levels of TNFalpha in serum and PGE2 in paws, simultaneously improving the anti-oxidative status of AIA. We found that at this dosage T-AOC was potentized, the activity of SOD increased and the level of MDA in serum decreased. However, anthocyanins at 20 and 10 mg/kg had less effect on the inflammatory factors and anti-oxidative capacity of AIA. CONCLUSIONS: Anthocyanins have potential anti-inflammatory and anti-oxidative effects on AIA.",
"title": "Anti-inflammatory and anti-oxidative effects of cherries on Freund's adjuvant-induced arthritis in rats."
},
{
"docid": "MED-4098",
"text": "To investigate effects of dietary mushrooms and joint effects of mushrooms and green tea on breast cancer, a case-control study was conducted in southeast China in 2004-2005. The incident cases were 1,009 female patients aged 20-87 years with histologically confirmed breast cancer. The 1,009 age-matched controls were healthy women randomly recruited from outpatient breast clinics. Information on frequency and quantity of dietary intake of mushrooms and tea consumption, usual diet, and lifestyle were collected by face-to-face interview using a validated and reliable questionnaire. Compared with nonconsumers, the Odds ratios (Ors) were 0.36 (95% CI = 0.25-0.51) and 0.53 (0.38-0.73) for daily intake of >or=10 g fresh mushrooms and >or=4 g dried mushrooms, based on multivariate logistic regression analysis adjusting for established and potential confounders. There were dose-response relationships with significant tests for trend (p < 0.001). The inverse association was found in both pre- and postmenopausal women. Compared with those who consumed neither mushrooms nor green tea, the ORs were 0.11 (0.06-0.20) and 0.18 (0.11-0.29) for daily high intake of fresh and dried mushrooms combined with consuming beverages made from >or=1.05 g dried green tea leaves per day. The corresponding linear trends were statistically significant for joint effect (p < 0.001). We conclude that higher dietary intake of mushrooms decreased breast cancer risk in pre- and postmenopausal Chinese women and an additional decreased risk of breast cancer from joint effect of mushrooms and green tea was observed. More research is warranted to examine the effects of dietary mushrooms and mechanism of joint effects of phytochemicals on breast cancer.",
"title": "Dietary intakes of mushrooms and green tea combine to reduce the risk of breast cancer in Chinese women."
},
{
"docid": "MED-3922",
"text": "The aqueous extracts of Hibiscus sabdariffa have been commonly used in folk medicine. Nevertheless, the compounds or metabolites responsible for its healthy effects have not yet been identified. The major metabolites present in rat plasma after acute ingestion of a polyphenol-enriched Hibiscus sabdariffa extract were characterized and quantified in order to study their bioavailability. The antioxidant status of the plasma samples was also measured through several complementary antioxidant techniques. High-performance liquid chromatography coupled to time-of-flight mass spectrometry (HPLC-ESI-TOF-MS) was used for the bioavailability study. The antioxidant status was measured by ferric reducing ability of plasma method, thiobarbituric acid reactive substances assay, and superoxide dismutase activity assay. Seventeen polyphenols and metabolites have been detected and quantified. Eleven of these compounds were metabolites. Although phenolic acids were found in plasma without any modification in their structures, most flavonols were found as quercetin or kaempferol glucuronide conjugates. Flavonol glucuronide conjugates, which show longer half-life elimination values, are proposed to contribute to the observed lipid peroxidation inhibitory activity in the cellular membranes. By contrast, phenolic acids appear to exert their antioxidant activity through ferric ion reduction and superoxide scavenging at shorter times. We propose that flavonol-conjugated forms (quercetin and kaempferol) may be the compounds responsible for the observed antioxidant effects and contribute to the healthy effects of H. sabdariffa polyphenolic extract. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Bioavailability study of a polyphenol-enriched extract from Hibiscus sabdariffa in rats and associated antioxidant status."
},
{
"docid": "MED-3314",
"text": "OBJECTIVES: Evidence suggests that certain occupations and related exposures may increase the risk of malignant lymphoma. Farming, printing and paper industry, wood processing, meat handling and processing, welding, shoe and leather manufacturing and teaching profession are among the categories that have been implicated in previous studies. The relationship between occupation and malignant lymphoma has been investigated in a large European prospective study. METHODS: We investigated occupational risks for lymphomas in the European Prospective Investigation into Cancer and Nutrition (EPIC). The mean follow-up time for 348,555 subjects was 9 years (SD: 2 years). The analysis was based on 866 and 48 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). These were identified in the EPIC subcohorts with occupational data. Data on 52 occupations were collected through standardised questionnaires. Cox proportional hazard models were used to explore the association between occupation and risk of malignant lymphoma. RESULTS: The following occupations were positively associated with malignant NHL after adjustment for study centre, age, sex, socioeconomic status (SES), smoking and alcohol: butchers (HR=1.53, 95% CI 1.05 to 2.48, including multiple myeloma/plasmacytoma; HR=1.30, 95% CI 1.00 to 2.66, excluding multiple myeloma/plasmacytoma) and car repair workers (HR=1.50, 95% CI 1.01 to 2.00, including multiple myeloma/plasmacytoma; HR=1.51, 95% CI 1.01 to 2.31, excluding multiple myeloma/plasmacytoma). HL was associated with gasoline station occupation (HR=4.59, 95% CI 1.08 to 19.6). CONCLUSION: The findings in this current study of a higher risk of NHL among car repair workers and butchers and a higher risk of HL among gasoline station workers suggest a possible role from occupationally related exposures, such as solvents and zoonotic viruses, as risk factors for malignant lymphoma.",
"title": "Occupation and risk of lymphoma: a multicentre prospective cohort study (EPIC)."
},
{
"docid": "MED-4720",
"text": "Tritiated naloxone, a powerful opiate antagonist, specifically binds to an opiate receptor of mammalian brain and guinea pig intestine. Competition for the opiate receptor by various opiates and their antagonists closely parallels their pharmacological potency. The opiate receptor is confined to nervous tissue.",
"title": "Opiate receptor: demonstration in nervous tissue."
},
{
"docid": "MED-3313",
"text": "INTRODUCTION: Asbestos is banned in most Western countries but related malignancies are still of clinical concern because of their long latencies. This review identifies and addresses some controversial occupational and clinical aspects of asbestos-related malignancies. METHODS: Papers published in English from 1980 to 2009 were retrieved from PubMed. A total of 307 original articles were identified and 159 were included. ASSESSMENT OF EXPOSURE: The retrospective assessment of exposure is usually performed by using questionnaires and job exposure matrices and by careful collection of medical history. In this way crucial information about manufacturing processes and specific jobs can be obtained. In addition, fibers and asbestos bodies are counted in lung tissue, broncho-alveolar lavage, and sputum, but different techniques and interlaboratory variability hamper the interpretation of reported measurements. SCREENING FOR MALIGNANCIES: The effectiveness of low-dose chest CT screening in exposed workers is debatable. Several biomarkers have also been considered to screen individuals at risk for lung cancer and mesothelioma but reliable signatures are still missing. ATTRIBUTION OF LUNG CANCER: Exposures correlating with lung cancer are high and in the same range where asbestosis occurs. However, the unresolved question is whether the presence of fibrosis is a requirement for the attribution of lung cancer to asbestos. The etiology of lung cancer is difficult to define in cases of low-level asbestos exposure and concurrent smoking habits. MESOTHELIOMA: The diagnosis of malignant mesothelioma may also be difficult, because of procedures in sampling, fixation, and processing, and uses of immunohistochemical probes. CONCLUSIONS: Assessment of exposure is crucial and requires accurate medical and occupational histories. Quantitative analysis of asbestos body burden is better performed in digested lung tissues by counting asbestos bodies by light microscopy and/or uncoated fibers by transmission electron microscopy. The benefits of screenings for asbestos-related malignancies are equivocal. The attribution of lung cancer to asbestos exposure is difficult in a clinical setting because of the need to assess asbestos body burden and the fact that virtually all these patients are also tobacco smokers or former smokers. Given the premise that asbestosis is necessary to causally link lung cancer to asbestos, it follows that the assessment of both lung fibrosis and asbestos body burden is necessary.",
"title": "Occupational toxicology of asbestos-related malignancies."
},
{
"docid": "MED-3987",
"text": "Background: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D]. Objective: The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans. Design: The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials. Results: A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation. Conclusions: This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3 could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.",
"title": "Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis"
},
{
"docid": "MED-2366",
"text": "Glycoconjugates and their antibodies are vital components of host-tumor interaction. This review concentrates on the oncological implications of research concerning the alpha gal triad; the alpha 1-->3 galactosyl epitope (alpha Gal), the enzyme responsible for its construction, alpha 1,3 galactosyl transferase (alpha 1-3GT), and its associated antibody: anti-gal. Alpha gal epitopes, previously assumed to be absent from human tissue, have been demonstrated on several human cancer cell lines, senescent red blood cells, and Graves' disease thyrocytes. Alpha-gal presence on neoplastic lines is correlated with increased metastatic formation in animal models. The mechanisms of human response to these neoantigens are complex, as natural anti-gal antibodies exist in high titers in normal sera, thus predicting immunological recognition of cells expressing alpha gal epitopes. Hypotheses vary regarding the pathogenic contributions of metastasis-associated phenomena such as de novo expression of alpha gal and its unmasking by desialylation. The means by which alpha gal is sporadically expressed in human tissue remain unknown, as the galactosyl transferase which produces this epitope in constitutively expressive animals has undergone significant mutation at the genomic level in humans. Pathological re-expression is presumed to require permissive changes at a cellular level. Detailing these alterations is a prerequisite to the comprehension of the metastatic phenotype. In this context, the possibility of therapeutic strategies affecting alpha gal expression are also discussed.",
"title": "A possible role for the alpha 1-->3 galactosyl epitope and the natural anti-gal antibody in oncogenesis."
},
{
"docid": "MED-3292",
"text": "The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.",
"title": "The Restriction of Zoonotic PERV Transmission by Human APOBEC3G"
},
{
"docid": "MED-3701",
"text": "Estrogen synthesized in situ plays a more important role in breast cancer cell proliferation than does circulating estrogen. Aromatase is the enzyme that converts androgen to estrogen and is expressed at a higher level in breast cancer tissue than in surrounding noncancer tissue. A promising route of chemoprevention against breast cancer may be through the suppression of in situ estrogen formation using aromatase inhibitors. A diet high in fruits and vegetables may reduce the incidence of breast cancer, because they contain phytochemicals that can act as aromatase inhibitors. In our previous studies, we found that grapes and wine contain potent phytochemicals that can inhibit aromatase. We show that red wine was more effective than white wine in suppressing aromatase activity. Interestingly, our results from white wine studies suggest a weak inductive effect of alcohol on aromatase activity. On the other hand, the potent effect of anti-aromatase chemicals in red wine overcomes the weak inductive effect of alcohol in wine. Several purification procedures were performed on whole red wine to separate active aromatase inhibitors from non-active compounds. These techniques included liquid-liquid extraction, silica gel chromatography, various solid phase extraction (SPE) columns, and high performance liquid chromatography. An active Pinot Noir red wine SPE C18 column fraction (20% acetonitrile:water) was more effective than complete Pinot Noir wine in suppressing aromatase assay. This red wine extract was further analyzed in a transgenic mouse model in which aromatase was over-expressed in mammary tissue. Our gavaged red wine extract completely abrogated aromatase-induced hyperplasia and other neoplastic changes in mammary tissue. These results suggest that red wine or red wine extract may be a chemopreventive diet supplement for postmenopausal women who have a high risk of breast cancer. Further research is underway to purify and characterize the active compounds in red wine that are responsible for the inhibition of aromatase.",
"title": "Anti-aromatase chemicals in red wine."
},
{
"docid": "MED-3310",
"text": "We observed five consecutive cases of Hypersensitivity Pneumonitis in subjects working in a salami factory. The workers had to clean the white mould growing on salami surface using a manual wire brush. The five patients (four female) had a mean age of 39 +/- 15 years; two were smokers. Three patients had an acute clinical presentation with fever, dyspnoea, dry cough, oxygen desaturation, and presented at the emergency department with suspected diagnosis of community acquired pneumonia. The mean latency for developing respiratory symptoms was 11.6 days. Pulmonary function test demonstrated a reduction in diffusing capacity (DLCO) in all 5 patients (60 +/- 15% of predicted value). Skin prick test was positive for Penicillium spp in 3 cases and for Cladosporium and Aspergillus spp in 2 others. Specific IgG antibodies against Penicillium spp were positive in 3 subjects; 2 were positive for Aspergillus Fumigatus. The prevailing radiological pattern was a ground glass appearance in the three patients with acute clinical onset and a centrilobular one in patients with subacute onset. All patients were advised to avoid exposure to the antigens. Follow-up visits including pulmonary function testing, and DLCO measurement were conducted at one, three and six months. HRCT was performed at six month. Four subjects had a complete radiological and clinical resolution after changing work. Only one patient was treated with oral steroids for severe dyspnoea and progressive reduction of DLCO, gaining a complete radiological and clinical stability at six months.",
"title": "A new type of Hypersensitivity Pneumonitis: salami brusher's disease."
},
{
"docid": "MED-3712",
"text": "Herein, it was reported and compared the chemical composition and nutritional value of the most consumed species as fresh cultivated mushrooms: Agaricus bisporus (white and brown mushrooms), Pleurotus ostreatus (oyster mushroom), Pleurotus eryngii (King oyster mushroom), Lentinula edodes (Shiitake) and Flammulina velutipes (Golden needle mushroom). Shiitake revealed the highest levels of macronutrients, unless proteins, as also the highest sugars, tocopherols and PUFA levels, and the lowest SFA content. White and brown mushrooms showed similar macronutrients composition, as also similar values of total sugars, MUFA, PUFA and total tocopherols. Oyster and king oyster mushrooms gave the highest MUFA contents with similar contents in PUFA, MUFA and SFA in both samples. They also revealed similar moisture, ash, carbohydrates and energy values. This study contributes to the elaboration of nutritional databases of the most consumed fungi species worldwide, allowing comparison between them. Moreover it was reported that cultivated and the wild samples of the same species have different chemical composition, including sugars, fatty acids and tocopherols profiles. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Chemical composition and nutritional value of the most widely appreciated cultivated mushrooms: an inter-species comparative study."
},
{
"docid": "MED-3921",
"text": "BACKGROUND: To evaluate health benefits attributed to Hibiscus sabdariffa L. a randomized, open-label, two-way crossover study was undertaken to compare the impact of an aqueous H. sabdariffa L. extract (HSE) on the systemic antioxidant potential (AOP; assayed by ferric reducing antioxidant power (FRAP)) with a reference treatment (water) in eight healthy volunteers. The biokinetic variables were the areas under the curve (AUC) of plasma FRAP, ascorbic acid and urate that are above the pre-dose concentration, and the amounts excreted into urine within 24 h (Ae(0-24) ) of antioxidants as assayed by FRAP, ascorbic acid, uric acid, malondialdehyde (biomarker for oxidative stress), and hippuric acid (metabolite and potential biomarker for total polyphenol intake). RESULTS: HSE caused significantly higher plasma AUC of FRAP, an increase in Ae(0-24) of FRAP, ascorbic acid and hippuric acid, whereas malondialdehyde excretion was reduced. Furthermore, the main hibiscus anthocyanins as well as one glucuronide conjugate could be quantified in the volunteers' urine (0.02% of the administered dose). CONCLUSION: The aqueous HSE investigated in this study enhanced the systemic AOP and reduced the oxidative stress in humans. Furthermore, the increased urinary hippuric acid excretion after HSE consumption indicates a high biotransformation of the ingested HSE polyphenols, most likely caused by the colonic microbiota. Copyright © 2012 Society of Chemical Industry.",
"title": "Consumption of Hibiscus sabdariffa L. aqueous extract and its impact on systemic antioxidant potential in healthy subjects."
},
{
"docid": "MED-3698",
"text": "Purpose Single-variable analyses have associated physical activity, diet, and obesity with survival after breast cancer. This report investigates interactions among these variables. Patients and Methods A prospective study was performed of 1,490 women diagnosed and treated for early-stage breast cancer between 1991 and 2000. Enrollment was an average of 2 years postdiagnosis. Only seven women were lost to follow-up through December 2005. Results In univariate analysis, reduced mortality was weakly associated with higher vegetable-fruit consumption, increased physical activity, and a body mass index that was neither low weight nor obese. In a multivariate Cox model, only the combination of consuming five or more daily servings of vegetables-fruits, and accumulating 540+ metabolic equivalent tasks-min/wk (equivalent to walking 30 minutes 6 d/wk), was associated with a significant survival advantage (hazard ratio, 0.56; 95% CI, 0.31 to 0.98). The approximate 50% reduction in risk associated with these healthy lifestyle behaviors was observed in both obese and nonobese women, although fewer obese women were physically active with a healthy dietary pattern (16% v 30%). Among those who adhered to this healthy lifestyle, there was no apparent effect of obesity on survival. The effect was stronger in women who had hormone receptor–positive cancers. Conclusion A minority of breast cancer survivors follow a healthy lifestyle that includes both recommended intakes of vegetables-fruits and moderate levels of physical activity. The strong protective effect observed suggests a need for additional investigation of the effect of the combined influence of diet and physical activity on breast cancer survival.",
"title": "Greater Survival After Breast Cancer in Physically Active Women With High Vegetable-Fruit Intake Regardless of Obesity"
},
{
"docid": "MED-2359",
"text": "INTRODUCTION: ALPHA-GAL is a glycoconjugate present on cell membranes of mammals and bacteria but not humans who display anti-Gal antibodies (AB) in high titers provoked by the commensal gut flora. In the present study, we sought to determine the longitudinal course of alpha-Gal specific AB titers of all isotypes over 8 weeks among healthy adult subjects. Furthermore, we hypothesized that inflammatory bowel disease (IBD) patients display increased anti-Gal titers. MATERIALS AND METHODS: We drew serum from healthy probands (n=20) weekly for 8 weeks and obtained plasma samples of from patients suffering from Crohn's disease (n=20) and ulcerative colitis (n=20). We measured anti-Gal ABs of all isotypes and total immunoglobulin (Ig) content using an enzyme-linked immunosorbent assay technique. For statistical evaluation of the longitudinal titers, we calculated confidence intervals for the slopes of a random intercept model, comparing variances between and within the probands. For group comparisons, we performed paired student t-tests and Pearson correlations. RESULTS: Alpha-Gal specific IgG, IgM, IgD, and IgA titers remained unvaried within a narrow range upon longitudinal observation. Most probands did not display alpha-Gal specific IgE ABs. Crohn's disease patients showed highly increased alpha-Gal-specific IgA titers compared with control subjects (P<.01). CONCLUSION: Apart from IgE, alpha-Gal-specific ABs of all isotypes remained constant over longer time periods in healthy subjects. Thus, significant titer changes actually represent increased antigen exposure and a specific anti-alpha-Gal response. Crohn's disease patients display increased anti-Gal IgA titers compared with healthy controls, which reflects a chronically impaired mucosal gut barrier in this patient cohort. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Anti-Gal titers in healthy adults and inflammatory bowel disease patients."
},
{
"docid": "MED-4583",
"text": "Fruits and vegetables are among the most nutritious and healthy of foods, and are related to the prevention of many chronic diseases. The aim of the study was to examine the relationship between intake of different plant foods and cognitive performance in elderly individuals in a cross-sectional study. Two thousand and thirty-one elderly subjects (aged 70-74 years; 55% women) recruited from the general population in Western Norway underwent extensive cognitive testing and completed a comprehensive FFQ. The cognitive test battery covered several domains (Kendrick Object Learning Test, Trail Making Test--part A, modified versions of the Digit Symbol Test, Block Design, Mini-Mental State Examination and Controlled Oral Word Association Test). A validated and self-reported FFQ was used to assess habitual food intake. Subjects with intakes of >10th percentile of fruits, vegetables, grain products and mushrooms performed significantly better in cognitive tests than those with very low or no intake. The associations were strongest between cognition and the combined intake of fruits and vegetables, with a marked dose-dependent relationship up to about 500 g/d. The dose-related increase of intakes of grain products and potatoes reached a plateau at about 100-150 g/d, levelling off or decreasing thereafter, whereas the associations were linear for mushrooms. For individual plant foods, the positive cognitive associations of carrots, cruciferous vegetables, citrus fruits and high-fibre bread were most pronounced. The only negative cognitive association was with increased intake of white bread. In the elderly, a diet rich in plant foods is associated with better performance in several cognitive abilities in a dose-dependent manner.",
"title": "Cognitive performance among the elderly in relation to the intake of plant foods. The Hordaland Health Study."
},
{
"docid": "MED-3709",
"text": "The gut immune system has the challenge of responding to pathogens while remaining relatively unresponsive to food antigens and the commensal microflora. In the developed world, this ability appears to be breaking down, with chronic inflammatory diseases of the gut commonplace in the apparent absence of overt infections. In both mouse and man, mutations in genes that control innate immune recognition, adaptive immunity, and epithelial permeability are all associated with gut inflammation. This suggests that perturbing homeostasis between gut antigens and host immunity represents a critical determinant in the development of gut inflammation and allergy.",
"title": "Immunity, inflammation, and allergy in the gut."
},
{
"docid": "MED-1300",
"text": "Purpose The effect of brewers’ yeast (1,3)-(1,6)-beta-d-glucan consumption on the number of common cold episodes in healthy subject was investigated. Methods In a placebo-controlled, double-blind, randomized, multicentric clinical trial, 162 healthy participants with recurring infections received 900 mg of either placebo (n = 81) or an insoluble yeast (1,3)-(1,6)-beta-d-glucan preparation (n = 81) per day over a course of 16 weeks. Subjects were instructed to document each occurring common cold episode in a diary and to rate ten predefined infection symptoms during an infections period, resulting in a symptom score. The subjects were examined by the investigator during the episode visit on the 5th day of each cold episode. Results In the per protocol population, supplementation with insoluble yeast (1,3)-(1,6)-beta-glucan reduced the number of symptomatic common cold infections by 25 % as compared to placebo (p = 0.041). The mean symptom score was 15 % lower in the beta-glucan as opposed to the placebo group (p = 0.125). Beta-glucan significantly reduced sleep difficulties caused by cold episode as compared to placebo (p = 0.028). Efficacy of yeast beta-glucan was rated better than the placebo both by physicians (p = 0.004) participants (p = 0.012). Conclusion The present study demonstrated that yeast beta-glucan preparation increased the body’s potential to defend against invading pathogens.",
"title": "Yeast (1,3)-(1,6)-beta-glucan helps to maintain the body’s defence against pathogens: a double-blind, randomized, placebo-controlled, multicentric study in healthy subjects"
},
{
"docid": "MED-3713",
"text": "BACKGROUND: Th17 is a subset of T-helper lymphocytes that produce proinflammatory cytokines, mainly IL-17. Serum IL-17 is increased in allergic patients and relates to clinical severity. Recently, it has been reported that CD161 is a highly upregulated gene in Th17 clones and all IL-17-producing cells are contained in CD161(+) T cells. This study aimed at comparing the frequency of peripheral CD161(+) T cells in patients with allergic rhinitis (AR) and in healthy controls and at relating CD161 expression with symptom severity. METHODS: Forty-four patients with AR and 29 healthy non-allergic subjects were evaluated. CD161 expression was evaluated on CD3(+), CD4(+) and CD8(+) cells by double immunofluorescence staining and fluorescence activated cell sorter analysis. Symptom severity was assessed by the Visual Analogue Scale. RESULTS: Allergic patients showed a significantly higher frequency of CD3(+)CD161(+), CD4(+)CD161(+) and CD8(+)CD161(+) cells than healthy non-allergic subjects (p < 0.0001). Moreover, the expression of CD161 cells was significantly related to clinical severity. CONCLUSIONS: This study provides evidence that a higher frequency of CD161(+) T cells is present in the peripheral blood of AR patients. Copyright © 2012 S. Karger AG, Basel.",
"title": "Higher frequencies of CD161+ circulating T lymphocytes in allergic rhinitis patients compared to healthy donors."
},
{
"docid": "MED-2355",
"text": "Anaphylaxis is a severe allergic reaction that can be rapidly progressing and fatal. In instances where the triggering allergen is not known, establishing the etiology of anaphylaxis is pivotal to long-term risk management. Our recent work has identified a novel IgE antibody (Ab) response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal), that has been associated with two distinct forms of anaphylaxis: (1) immediate onset anaphylaxis during first exposure to intravenous cetuximab, and (2) delayed onset anaphylaxis 3–6 h after ingestion of mammalian food products (e.g., beef and pork). The results of our studies strongly suggest that tick bites are a cause, if not the only significant cause, of IgE Ab responses to alpha-gal in the southern, eastern and central United States. Patients with IgE Ab to alpha-gal continue to emerge and, increasingly, these cases involve children. This IgE Ab response cross-reacts with cat and dog but does not appear to pose a risk for asthma; however, it may impair diagnostic testing in some situations.",
"title": "Delayed Anaphylaxis to Red Meat in Patients with IgE Specific for Galactose alpha-1,3-Galactose (alpha-gal)"
},
{
"docid": "MED-4883",
"text": "The art of the musical anus is reviewed in the light of its most prominent performers and of anorectal physiological aspects related to this specific musical performance.",
"title": "[Flatufonia--or the musical anus]."
},
{
"docid": "MED-1296",
"text": "Natural immunomodulators are getting more and more popular. The popularity, however, often brings over-optimistic claims and mediocre effects. The purpose of the present study was to directly compare eleven most commonly used immunomodulators. Through testing both cellular and humoral branches of immune reactions, we found that most of the immunomodulators tested have limited, if any, effects, with glucan being consistently the most active molecule strongly stimulating every reaction evaluated. These data were also confirmed using a Lewis lung cancer model, where only glucan and resveratrol lowered the number of metastases.",
"title": "Natural immunomodulators and their stimulation of immune reaction: true or false?"
},
{
"docid": "MED-3697",
"text": "BACKGROUND: Many studies have analyzed the effect of behavioral risk factors such as common lifestyle patterns on the risk of disease. The aim of this study was to assess the effect of a healthy lifestyle index on the risk of breast cancer. METHODS: A population-based case-control study was conducted in Mexico from 2004 to 2007. One thousand incident cases and 1,074 controls, matched to cases by 5-year age category, region, and health institution, participated in the study. A healthy lifestyle index was developed by means of principal components by using dietary pattern, physical activity, alcohol consumption, and tobacco smoking. A conditional logistic regression model was used to assess this association. RESULTS: The healthy lifestyle index was defined as the combined effect of moderate and/or vigorous-intensity physical activity, low consumption of fat, processed foods, refined cereals, complex sugars, and the avoidance of tobacco smoking and alcohol consumption. Results showed a protective effect on both pre- (OR = 0.50, 95% CI: 0.29-0.84) and postmenopausal women (OR = O.20, 95% CI: 0.11-0.37) when highest versus lowest index quintiles were compared. CONCLUSIONS: Healthy lifestyle was associated with a reduction in the odds of having breast cancer. Primary prevention of this disease should be promoted in an integrated manner. Effective strategies need to be identified to engage women in healthy lifestyles. IMPACT: This study is the first to assess a healthy lifestyle index in relation to the risk of breast cancer. ©2011 AACR.",
"title": "Healthy lifestyle on the risk of breast cancer."
},
{
"docid": "MED-2276",
"text": "A limited number of studies have demonstrated that some modulators of inflammation can be altered by the consumption of sweet cherries. We have taken a proteomics approach to determine the effects of dietary cherries on targeted gene expression. The purpose was then to determine changes caused by cherry consumption in the plasma concentrations of multiple biomarkers for several chronic inflammatory diseases in healthy humans with modestly elevated C-reactive protein (CRP; range, 1-14 mg/L; mean, 3.5 mg/L; normal, <1.0 mg/L). Eighteen men and women (45-61 y) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. Fasting blood samples were taken before the start of consuming the cherries (study d 7), 28 d after the initiation of cherry supplementation (d 35), and 28 d after the discontinuation (d 63). Of the 89 biomarkers assessed, cherry consumption for 28 d altered concentrations of 9, did not change those of 67, and the other 13 were below the detection limits. Cherry consumption decreased (P < 0.05) plasma concentrations of extracellular newly identified ligand for the receptor for advanced glycation end products (29.0%), CRP (20.1%), ferritin (20.3%), plasminogen activator inhibitor-1 (19.9%), endothelin-1 (13.7%), epidermal growth factor (13.2%), and IL-18 (8.1%) and increased that of IL-1 receptor antagonist (27.9%) compared with corresponding values on study d 7. The ferritin concentration continued to decrease between d 35 and 63 and it was significantly lower on d 63 than on d 7. Because the participants in this study were healthy, no clinical pathology end points were measured. However, results from the present study demonstrate that cherry consumption selectively reduced several biomarkers associated with inflammatory diseases.",
"title": "Sweet bing cherries lower circulating concentrations of markers for chronic inflammatory diseases in healthy humans."
},
{
"docid": "MED-4097",
"text": "The identification of modifiable lifestyle factors that could reduce the risk of breast cancer is a research priority. Despite the enormous chemo preventive potential of green tea and compelling evidence from animal studies, its role in breast cancer development in humans is still unclear. Part of the uncertainty is related to the relatively small number of epidemiological studies on green tea and breast cancer and that the overall results from case-control studies and prospective cohort studies are discordant. In addition, the mechanisms by which green tea intake may influence risk of breast cancer in humans remains not well studied. We review the human studies that have evaluated the relationship between green tea intake and four biomarkers (sex steroid hormones, mammographic density, insulin-like growth factor, adiponectin) that are believed to be important in breast cancer development. Results from these biomarker studies are also inconclusive. Limitations of human studies and areas of further investigations are discussed.",
"title": "Green Tea and Breast Cancer"
},
{
"docid": "MED-3305",
"text": "BACKGROUND AND AIM: The occurrence of malignant pleural mesothelioma (MPM) has been reported among population groups with no documented professional exposure to asbestos fibres living in different geographic areas. This paper reviews existing data related to non occupational MPM including its occurrence in the province of Catania (Sicily, Italy). METHODS: An electronic search of literature related to non occupational MPM was performed including the year 2005. RESULTS: Non occupational MPM in subjects living in areas contaminated by a variety of asbestos and non asbestos fibres has been well documented through a number of epidemiologic studies including cases series, case-control studies, and a cohort study. In addition, the observation of familial clustering of MPM, suggests that genetic factors may play a role in the pathogenesis of this malignancy. The epidemiological evidence also suggests that MPM may occur as a result of the interaction between environmental carcinogens, genetic factors, and virus infection. CONCLUSION: It is likely that genetic predisposition and non-occupational exposure to low doses of asbestos and asbestos-like fibres may concur to the development of malignant mesothelioma. However, additional epidemiological and laboratory studies are needed to further understand the relationship between environmental exposure and individual susceptibility to this malignancy.",
"title": "Non-occupational malignant pleural mesothelioma due to asbestos and non-asbestos fibres."
},
{
"docid": "MED-2368",
"text": "BACKGROUND: Microparticles (MPs) with procoagulant activity are present in human atherosclerosis, but no detailed information is available on their composition. METHODS AND RESULTS: To obtain insights into the role of MPs in atherogenesis, MP proteins were identified by tandem mass spectrometry, metabolite profiles were determined by high-resolution nuclear magnetic resonance spectroscopy, and antibody reactivity was assessed against combinatorial antigen libraries. Plaque MPs expressed surface antigens consistent with their leukocyte origin, including major histocompatibility complex classes I and II, and induced a dose-dependent stimulatory effect on T-cell proliferation. Notably, taurine, the most abundant free organic acid in human neutrophils, which scavenges myeloperoxidase-catalyzed free radicals, was highly enriched in plaque MPs. Moreover, fluorescent labeling of proteins on the MP surface suggested immunoglobulins to be trapped inside, which was confirmed by flow cytometry analysis on permeabilized and nonpermeabilized plaque MPs. Colabeling for CD14 and IgG established that more than 90% of the IgG containing MPs were CD14(+), indicating a macrophage origin. Screening against an antigen library revealed that the immunologic profiles of antibodies in MPs were similar to those found in plaques but differed profoundly from antibodies in plasma and unexpectedly, showed strong reactions with oligosaccharide antigens, in particular blood group antigen A. CONCLUSIONS: This study provides the first evidence that immunoglobulins are present within MPs derived from plaque macrophages, that the portfolio of plaque antibodies is different from circulating antibodies in plasma, and that anticarbohydrate antibodies are retained in human atherosclerotic lesions.",
"title": "Proteomics, metabolomics, and immunomics on microparticles derived from human atherosclerotic plaques."
},
{
"docid": "MED-2369",
"text": "Background Carbohydrate moieties are frequently encountered in food and can elicit IgE responses, the clinical significance of which has been unclear. Recent work, however, has shown that IgE antibodies to galactose-α-1,3-galactose (α-gal), a carbohydrate commonly expressed on nonprimate mammalian proteins, are capable of eliciting serious, even fatal, reactions. Objective We sought to determine whether IgE antibodies to α-gal are present in sera from patients who report anaphylaxis or urticaria after eating beef, pork, or lamb. Methods Detailed histories were taken from patients presenting to the University of Virginia Allergy Clinic. Skin prick tests (SPTs), intradermal skin tests, and serum IgE antibody analysis were performed for common indoor, outdoor, and food allergens. Results Twenty-four patients with IgE antibodies to α-gal were identified. These patients described a similar history of anaphylaxis or urticaria 3 to 6 hours after the ingestion of meat and reported fewer or no episodes when following an avoidance diet. SPTs to mammalian meat produced wheals of usually less than 4 mm, whereas intradermal or fresh-food SPTs provided larger and more consistent wheal responses. CAP-RAST testing revealed specific IgE antibodies to beef, pork, lamb, cow’s milk, cat, and dog but not turkey, chicken, or fish. Absorption experiments indicated that this pattern of sensitivity was explained by an IgE antibody specific for α-gal. Conclusion We report a novel and severe food allergy related to IgE antibodies to the carbohydrate epitope α-gal. These patients experience delayed symptoms of anaphylaxis, angioedema, or urticaria associated with eating beef, pork, or lamb.",
"title": "Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-α-1,3-galactose"
},
{
"docid": "MED-5049",
"text": "OBJECTIVE: To evaluate the hypolipemic and antioxidant effects of soy and green tea alone and/or in association in dyslipidemic subjects. METHODS: One hundred dyslipidemic individuals were allocated into four groups. The soy group ingested 50 g of soy (kinako) daily, and the green tea group ingested 3 g of green tea in 500 mL of water per day. A third group ingested 50 g of soy and 3 g of green tea daily, and the control group had a hypocholesterolemic diet. Evaluations were performed at baseline and after 45 and 90 d. Plasma levels of total cholesterol, high-density lipoprotein, and triacylglycerols were evaluated by automated methods. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. LDL was isolated by ultracentrifugation. Total plasma antioxidant capacity and plasma levels of total lipid hydroperoxides and those linked to LDL were evaluated by chemiluminescence. The results were expressed as median values and their 25th to 75th percentiles, with a 5% level of significance. RESULTS: No significant difference occurred in LDL, high-density lipoprotein cholesterol, and triacylglycerol levels across groups. However, a statistically significant difference in total cholesterol occurred within the soy/green tea group 45 and 90 d after intervention. No statistically significant difference occurred in plasma levels of lipid hydroperoxides or those linked to LDL in any of the groups studied. All the groups that used soy and/or green tea presented increased total plasma antioxidant potential. CONCLUSION: Soy and green tea, alone or in combination, increased the total antioxidant potential of hypercholesterolemic patients, whereas only the combination decreased total cholesterol levels.",
"title": "Association between soy and green tea (Camellia sinensis) diminishes hypercholesterolemia and increases total plasma antioxidant potential in dysli..."
},
{
"docid": "MED-3311",
"text": "OBJECTIVES: We studied mortality in two separate cohorts of workers in abattoirs (N=4996) and meat processing plants (N=3642) belonging to a meatcutters' union, because they were exposed to viruses that cause cancer in food animals, and also to chemical carcinogens at work. METHODS: Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated for each cohort as a whole and in subgroups defined by race and sex, using the US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time over 60% of them died. RESULTS: An excess of deaths from cancers of the base of the tongue, esophagus, lung, skin, bone and bladder, lymphoid leukemia, and benign tumors of the thyroid and other endocrine glands, and possibly Hodgkin's disease, was observed in abattoir and meat processing workers. Significantly lower SMRs were recorded for cancer of the thymus, mediastinum, pleura, etc., breast cancer, and non-Hodgkin's lymphoma. CONCLUSION: This study confirms the excess occurrence of cancer in workers in abattoirs and meat processing plants, butchers, and meatcutters, previously reported in this cohort and other similar cohorts worldwide. Large nested case-control studies are now needed to examine which specific occupational and non-occupational exposures are responsible for the excess. There is now sufficient evidence for steps to be taken to protect workers from carcinogenic exposures at the workplace. There are also serious implications for the general population which may also be exposed to some of these viruses. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Cancer mortality in workers employed in cattle, pigs, and sheep slaughtering and processing plants."
},
{
"docid": "MED-5050",
"text": "Tea is the most widely consumed beverage in the world after water. Tea is known to be a rich source of flavonoid antioxidants. However tea also contains a unique amino acid, L-theanine that may modulate aspects of brain function in humans. Evidence from human electroencephalograph (EEG) studies show that it has a direct effect on the brain (Juneja et al. Trends in Food Science & Tech 1999;10;199-204). L-theanine significantly increases activity in the alpha frequency band which indicates that it relaxes the mind without inducing drowsiness. However, this effect has only been established at higher doses than that typically found in a cup of black tea (approximately 20mg). The aim of the current research was to establish this effect at more realistic dietary levels. EEG was measured in healthy, young participants at baseline and 45, 60, 75, 90 and 105 minutes after ingestion of 50mg L-theanine (n=16) or placebo (n=19). Participants were resting with their eyes closed during EEG recording. There was a greater increase in alpha activity across time in the L-theanine condition (relative to placebo (p+0.05). A second study replicated this effect in participants engaged in passive activity. These data indicate that L-theanine, at realistic dietary levels, has a significant effect on the general state of mental alertness or arousal. Furthermore, alpha activity is known to play an important role in critical aspects of attention, and further research is therefore focussed on understanding the effect of L-theanine on attentional processes.",
"title": "L-theanine, a natural constituent in tea, and its effect on mental state."
},
{
"docid": "MED-2357",
"text": "Patients with cancer have circulating heterophile antibodies that agglutinate animal red cells via recognition of the mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), which was long considered an oncofetal antigen in humans. However, humans are genetically deficient in Neu5Gc production and instead metabolically accumulate Neu5Gc from dietary sources, particularly red meats and milk products. Moreover, mice with a human-like defect showed no alternate pathway for Neu5Gc synthesis and even normal humans express anti-Neu5Gc antibodies. We show here that human tumors accumulate Neu5Gc that is covalently attached to multiple classes of glycans. The paradox of human tumor Neu5Gc accumulation in the face of circulating anti-Neu5Gc antibodies was hypothesized to be due to facilitation of tumor progression by the resulting low-grade chronic inflammation. Indeed, murine tumors expressing human-like levels of Neu5Gc show accelerated growth in syngeneic mice with a human-like Neu5Gc deficiency, coincident with the induction of anti-Neu5Gc antibodies and increased infiltration of inflammatory cells. Transfer of polyclonal monospecific syngeneic mouse anti-Neu5Gc serum also enhanced growth of transplanted syngeneic tumors bearing human-like levels of Neu5Gc, with tumors showing evidence for antibody deposition, enhanced angiogenesis and chronic inflammation. These effects were suppressed by a cyclooxygenase-2 inhibitor, a drug type known to reduce human carcinoma risk. Finally, affinity-purified human anti-Neu5Gc antibodies also accelerate growth of Neu5Gc-containing tumors in Neu5Gc-deficient mice. Taken together, the data suggest that the human propensity to develop diet-related carcinomas is contributed to by local chronic inflammation, resulting from interaction of metabolically-accumulated dietary Neu5Gc with circulating anti-Neu5Gc antibodies.",
"title": "Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression"
},
{
"docid": "MED-3153",
"text": "This was a placebo-controlled, double-blind study designed to evaluate the effect of a commercially available dietary supplement on upper-respiratory tract symptoms (URTI) and mood state. Seventy-five marathon runners (35 men, 40 women) ranging in age from 18-53 years, mean age: 36 ± 9, self-administered placebo, 250 mg or 500 mg of BETA 1,3/1,6 GLUCAN (commercial name Wellmune WGP®) daily during the 4 week post-marathon trial period following the 2007 Carlsbad Marathon. Subjects filled out the profile of mood state (POMS) assessment and a questionnaire style health log measuring health status and URTI symptoms after 2- and 4-week treatment administrations. During the course of the 4-week study, subjects in the treatment groups (250 mg and 500 mg BETA-GLUCAN per day) reported significantly fewer URTI symptoms, better overall health and decreased confusion, fatigue, tension, and anger, and increased vigor based on the POMS survey compared to placebo. BETA-GLUCAN may prevent URTI symptoms, and improve overall health and mood following a competitive marathon. Key points",
"title": "Effect of BETA 1, 3/1, 6 GLUCAN on Upper Respiratory Tract Infection Symptoms and Mood State in Marathon Athletes"
},
{
"docid": "MED-3924",
"text": "PURPOSE: To determine the effects of therapy with Urtica dioica for symptomatic relief of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: A 6-month, double-blind, placebo-controlled, randomized, partial crossover, comparative trial of Urtica dioica with placebo in 620 patients was conducted. Patients were evaluated using the International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), Serum Prostatic- Specific Antigen (PSA), testosterone levels, and prostate size. At the end of 6-month trial, unblinding revealed that patients who initially received the placebo were switched to Urtica dioica. Both groups continued the medication up to 18 months. RESULTS: 558 patients (90%) completed the study (287/305, 91% in the Urtica dioica group, and 271/315, 86% in the placebo group). By intention- to-treat analysis, at the end of 6-month trial, 232 (81%) of 287 patients in the Urtica dioica group reported improved LUTS compared with 43 (16%) of 271 patients in the placebo group (P < 0.001). Both IPSS and Qmax showed greater improvement with drug than with placebo. The IPSS went from 19.8 down to 11.8 with Urtica dioica and from 19.2 to 17.7 with placebo (P = 0.002). Peak flow rates improved by 3.4 mL/s for placebo recipients and by 8.2 mL/s for treated patients (P < 0.05). In Urtica dioica group, PVR decreased from an initial value of 73 to 36 mL (P < 0.05). No appreciable change was seen in the placebo group. Serum PSA and testosterone levels were unchanged in both groups. A modest decrease in prostate size as measured by transrectal ultrasonography (TRUS) was seen in Urtica dioica group (from 40.1 cc initially to 36.3 cc; P < 0.001). There was no change in the prostate volume at the end of study with placebo. At 18-month follow-up, only patients who continued therapy, had a favorable treatment variables value. No side effects were identified in either group. CONCLUSION: In the present study, Urtica dioica have beneficial effects in the treatment of symptomatic BPH. Further clinical trials should be conducted to confirm these results before concluding that Urtica dioica is effective.",
"title": "Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study."
},
{
"docid": "MED-4433",
"text": "BACKGROUND: The role of zoonotic biological agents in human cancer occurrence has been little studied. Humans are commonly exposed to viruses that naturally infect and cause cancer in food animals such as poultry that constitute part of the biological environment. It is not known if these viruses cause cancer in humans. OBJECTIVE: To study cancer mortality in the largest cohort to date, of 20,132 workers in poultry slaughtering and processing plants, a group with the highest human exposures to these viruses. METHODS: Mortality in poultry workers was compared with that in the US general population through the estimation of standardized mortality ratios. RESULTS: Significantly increased risks were observed in the cohort as a whole or in subgroups, for several cancer sites, viz: cancers of the buccal cavity and pharynx; pancreas; trachea/bronchus/lung; brain; cervix; lymphoid leukemia; monocytic leukemia; and tumors of the hemopoietic and lymphatic systems. Elevated SMRs that were not statistically significant were observed for cancers of the liver, nasopharynx, myelofibrosis, and myeloma. New sites observed to be significantly in excess in this study were cancers of the cervix and penis. CONCLUSION: This large study provides evidence that a human group with high exposure to poultry oncogenic viruses has increased risk of dying from several cancers. Other occupational carcinogenic exposures could be of importance in explaining some of the findings, such as fumes from wrapping machines. These findings may have implications for public health amongst persons in the general population who may also be exposed to these viruses. What is needed now are epidemiologic studies that can demonstrate whether the excess of specific cancers can be attributed to specific occupational exposures while adequately controlling for other potential occupational and non-occupational carcinogenic exposures. Copyright 2010 Elsevier Inc. All rights reserved.",
"title": "Cancer mortality in poultry slaughtering/processing plant workers belonging to a union pension fund."
},
{
"docid": "MED-3535",
"text": "Cherries, and in particular sweet cherries, are a nutritionally dense food rich in anthocyanins, quercetin, hydroxycinnamates, potassium, fiber, vitamin C, carotenoids, and melatonin. UV concentration, degree of ripeness, postharvest storage conditions, and processing, each can significantly alter the amounts of nutrients and bioactive components. These constituent nutrients and bioactive food components support the potential preventive health benefits of cherry intake in relation to cancer, cardiovascular disease, diabetes, inflammatory diseases, and Alzheimer's disease. Mechanistically, cherries exhibit relatively high antioxidant activity, low glycemic response, COX 1 and 2 enzyme inhibition, and other anti-carcinogenic effects in vitro and in animal experiments. Well-designed cherry feeding studies are needed to further substantiate any health benefits in humans.",
"title": "Cherries and health: a review."
},
{
"docid": "MED-3321",
"text": "Avian leukosis/sarcoma viruses (ALSV) infect and cause cancers in chickens. Poultry workers are exposed to ALSV and other infectious agents in the workplace. This study examines if industrial hygiene assessment of antibody levels in poultry workers can identify risky job tasks at the higher exposure risk to an infectious agent, i.e., ALSV. We compared ALSV antibody levels in poultry workers and control subjects. Occupational and demographical factors were examined for an association with the exposure risk in poultry workers. We found that the antibody levels were significantly higher in poultry workers than in control subjects. Job category and age together were significantly associated with the antibody levels in workers. Certain job tasks were identified with significantly higher antibody levels as compared to others, implying that recommendations should be made to protect workers at these jobs. The findings of this study indicate that the measurement of antibody levels in workers can be useful for industrial hygiene assessment of exposure to infectious agents.",
"title": "Occupational exposure assessment using antibody levels: exposure to avian leukosis/sarcoma viruses in the poultry industry."
},
{
"docid": "MED-3295",
"text": "Background Few studies have investigated mortality in seafood workers worldwide, and no such study has been conducted in the United States. The objective of this study was to investigate mortality in American seafood workers. Methods The study population was derived from 4 states and consisted of 4116 subjects who worked mainly in seafood processing plants. They were followed up from 1966 to 2003. Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated, using the US general population for comparison. Results About 45% of the cohort was born after 1949. A total of 788 deaths were recorded; 53% of the decedents were female, and 88% were white. The SMRs for stomach cancer and disorders of the thyroid gland in the cohort as a whole were 2.1 (95% confidence interval [CI], 1.1–3.8) and 6.1 (95% CI 1.3–18.0), respectively. The SMRs for breast cancer, and occlusion/stenosis of the pre-cerebral/cerebral arteries in the cohort as a whole were 0.5 (95% CI, 0.3–0.9) and 0.5 (95% CI, 0.2–0.8), respectively. The SMR for ischemic heart disease in white females was 0.8 (95% CI, 0.6–0.9). Conclusions This cohort had excess deaths from stomach cancer and disorders of the thyroid gland, and deficit of deaths from breast cancer, stroke and ischemic heart disease. The significance of these findings is unknown, especially as less than 20% of the cohort were deceased. Nevertheless, the cohort is unique and important, and further follow-up may shed more light on mortality patterns in this occupational group.",
"title": "Cancer and Noncancer Mortality Among American Seafood Workers"
},
{
"docid": "MED-4165",
"text": "Ergothioneine is a native membrane-impermeable thiol compound that is specifically accumulated in cells via the organic cation transporter OCTN1. In humans, OCTN1 and ergothioneine have been implicated in the etiopathogenesis of autoimmune disorders. However, available evidence about dietary sources and the functional role of ergothioneine in human physiology is scarce. Here, we analyzed the ergothioneine content in common foods using liquid chromatography tandem-mass spectrometry. Additionally, we assessed the protective potency of ergothioneine against various oxidative stressors in OCTN1-expressing cells in comparison with the main intracellular thiol antioxidant glutathione by evaluating cell viability with the MTT reduction assay. Only some food contained ergothioneine with highest concentrations detected in specialty mushrooms, kidney, liver, black and red beans, and oat bran. Ergothioneine exhibited cell protection only against copper(II)-induced toxicity but was far less potent than glutathione, indicting that ergothioneine is not involved in the intracellular antioxidant thiol defense system.",
"title": "Dietary sources and antioxidant effects of ergothioneine."
},
{
"docid": "MED-4649",
"text": "Aromatase cytochrome P450 is the only enzyme in vertebrates known to catalyse the biosynthesis of all oestrogens from androgens1–3. Aromatase inhibitors therefore constitute a front-line therapy for oestrogen-dependent breast cancer3,4. In a three-step process, each step requiring 1 mol of O2, 1 mol of NADPH, and coupling with its redox partner cytochrome P450 reductase, aromatase converts androstenedione, testosterone and 16α-hydroxytestosterone to oestrone, 17β-oestradiol and 17β,16α-oestriol, respectively1–3. The first two steps are C19-methyl hydroxylation steps, and the third involves the aromatization of the steroid A-ring, unique to aromatase. Whereas most P450s are not highly substrate selective, it is the hallmark androgenic specificity that sets aromatase apart. The structure of this enzyme of the endoplasmic reticulum membrane has remained unknown for decades, hindering elucidation of the biochemical mechanism. Here we present the crystal structure of human placental aromatase, the only natural mammalian, full-length P450 and P450 in hormone biosynthetic pathways to be crystallized so far. Unlike the active sites of many microsomal P450s that metabolize drugs and xenobiotics, aromatase has an androgen-specific cleft that binds the androstenedione molecule snugly. Hydrophobic and polar residues exquisitely complement the steroid backbone. The locations of catalytically important residues shed light on the reaction mechanism. The relative juxtaposition of the hydrophobic amino-terminal region and the opening to the catalytic cleft shows why membrane anchoring is necessary for the lipophilic substrates to gain access to the active site. The molecular basis for the enzyme’s androgenic specificity and unique catalytic mechanism can be used for developing next-generation aromatase inhibitors.",
"title": "Structural basis for androgen specificity and oestrogen synthesis in human aromatase"
},
{
"docid": "MED-3708",
"text": "Asthma is a phenotypically heterogeneous disorder of multifactorial origins that affects 300 million people suffering from asthma and more than 250,000 asthma-related deaths each year. Although treatment for asthma has improved, its prevalence continues to increase, particularly in low and middle income countries, or in some ethnic groups in which prevalence was previously low. Observed spatio-temporal variations in the increased prevalence of asthma depend on exposure to environmental factors. Recently, several arguments are also in favor of the involvement of host susceptibility and stress in the observed increase of asthma prevalence. Further investigations are warranted to better understand mechanisms underlying asthma increase or stagnation. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Is the asthma epidemic still ascending?"
},
{
"docid": "MED-3306",
"text": "OBJECTIVES: Occupation as a farmer has been associated with increased risks of haematological cancers in adults. This study aimed to examine whether farm exposures in childhood contribute to these risks, by using parental occupation in farming as a proxy for growing up on a farm. METHODS: New Zealand death records (1998-2003) of persons aged 35-85 were extracted (n=114 289). For 82.3% usual occupation and the occupation of at least one of the parents could be coded (n=94 054). Unconditional logistic regression analyses included 3119 haematological cancer deaths (cases) and 90 935 deaths from other causes (controls). ORs for farming and growing up on a farm were adjusted for each other, year of birth, age at death, socio-economic status, Māori ethnicity, immigration status and sex. RESULTS: Growing up on a livestock farm was positively associated with haematological cancer (OR 1.22, 95% CI 1.05 to 1.41), particularly for poultry farms (OR 2.99, 95% CI 1.44 to 6.21), while growing up on a crop farm was not (OR 0.81, 95% CI 0.64 to 1.03). Crop farming in adulthood was associated with an increased haematological cancer risk (OR 1.49, 95% CI 1.13 to 1.96), while livestock farming was not (OR 0.80, 95% CI 0.63 to 1.00), except for beef cattle farming (OR 2.99, 95% CI 1.28 to 7.00). These results did not change appreciably when different control groups with different causes of death were used. CONCLUSIONS: These results could suggest a role for early life biological exposures in the development of haematological cancers.",
"title": "Farming, growing up on a farm, and haematological cancer mortality."
},
{
"docid": "MED-1295",
"text": "A number of polysaccharides with beta-glycosidic linkage are widespread in nature in a variety of sources. All have a common structure and the (1-->3)-beta-D-glucan backbone is essential. They have attracted attention over the years because of their bioactive and medicinal properties. In many cases their functional role is a mystery, in others it is well established. Because of their insoluble chemical nature, particulate (1-->3)-beta-D-glucans are not suitable for many medical applications. Various methods of changing or modifying the beta-D-glucan chemical structure and transforming it to a soluble form have been published. The beta-D-glucan bioactive properties can be affected positively or negatively by such modifications. This review examines beta-glucan sources in nature, health effects and structure-activity relationships. It presents the current state of beta-D-glucan solubilization methods and discusses their effectiveness and application possibilities for the future.",
"title": "Natural and modified (1-->3)-beta-D-glucans in health promotion and disease alleviation."
},
{
"docid": "MED-4880",
"text": "BACKGROUND/AIMS: The beneficial or harmful effect of the low-carbohydrate (low-carb), high-protein, high-fat diet (Atkins diet) has not been clearly demonstrated. We determined the effect of a low-carb diet and restricted feeding (70% ad libitum intake) on serum levels of cholesterol, triacylglycerol, glucose, ketone bodies and insulin in rats. METHODS: In experiment 1, each of 4 groups with 10 adult rats was assigned to a high-carb diet (AIN-93G) + ad libitum intake or restricted feeding, or a low-carb diet (53% horsemeat) + ad libitum intake or restricted feeding (2 x 2 factorial). In experiment 2, each of 3 groups with 10 adult rats was assigned to a control (AIN-93G) or low-carb diets (53% beef or horsemeat). RESULTS: Restricted feeding and the low-carb diet reduced (p<0.01) serum triacylglycerol compared with ad libitum intake and the AIN-93G diet, respectively (experiment 1). The dietary effect on serum total cholesterol, high-density or low-density lipid cholesterol appeared to be inconsistent, but restricted feeding increased the low-density lipoprotein cholesterol level. The serum ketone body level was increased by the low-carb diet compared with AIN-93G (experiment 2). CONCLUSION: Restricted feeding and a low-carb diet are beneficial for alleviating cardiovascular disease risk factors, and their effects are additive, restricted feeding being more pronounced. Copyright 2009 S. Karger AG, Basel.",
"title": "Effects of very-low-carbohydrate (horsemeat- or beef-based) diets and restricted feeding on weight gain, feed and energy efficiency, as well as ser..."
},
{
"docid": "MED-3696",
"text": "The authors assessed the association between moderate alcohol consumption and breast cancer risk in the Women's Health Study (United States, 1992-2004). During an average of 10 years of follow-up, 1,484 cases of total breast cancer (1,190 invasive and 294 in situ) were documented among 38,454 women who, at baseline, were free of cancer and cardiovascular disease and provided detailed dietary information, including alcohol consumption, for the preceding 12 months. Higher alcohol consumption was associated with a modest increase in breast cancer risk; the multivariable relative risks for > or =30 g/day of alcohol vs. none were 1.32 (95% confidence interval (CI): 0.96, 1.82) for total breast cancer and 1.43 (95% CI: 1.02, 2.02) for invasive breast cancer. An increased risk was limited to estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors; the multivariable relative risks for an increment of 10 g/day of alcohol were 1.11 (95% CI: 1.03, 1.20) for ER+PR+ tumors (804 cases), 1.00 (95% CI: 0.81, 1.24) for ER+PR- tumors (125 cases), and 0.99 (95% CI: 0.82, 1.20) for ER-PR- tumors (167 cases). The association also seemed strongest among those taking postmenopausal hormones currently, but the test for interaction was not significant. The findings from this prospective study suggest that moderate alcohol consumption increases breast cancer risk.",
"title": "Alcohol consumption and breast cancer risk in the Women's Health Study."
},
{
"docid": "MED-2351",
"text": "Anti-Gal is a natural Ab abundantly produced in humans. It interacts specifically with the carbohydrate epitope Gal alpha 1-3Gal beta 1-4GlcNAc-R (termed the alpha-galactosyl epitope). This epitope is expressed in large amounts on thyrocytes of nonprimate mammals, but not of humans. We have previously found that binding of anti-Gal to alpha-galactosyl epitopes on porcine thyrocytes results in stimulatory effects similar to those exerted by thyroid-stimulating hormone (thyrotropin). In the present study, we tested the hypothesis that anti-Gal may contribute to Graves' disease (GD) pathogenesis by stimulation of the thyrocytes of patients with this autoimmune disorder. Anti-Gal binding and stimulatory effects were assessed in primary thyrocyte cultures. Anti-Gal specifically bound to GD thyrocytes and induced an increase in cAMP synthesis, 125I uptake, and DNA synthesis in these cells. Furthermore, the stimulatory effects of autologous sera on GD thyrocytes were greatly reduced after specific depletion of anti-Gal from these sera. No binding and no stimulatory effects of anti-Gal were observed, however, with normal human thyrocytes and with thyrocytes from thyrotoxic patients who lack thyroid-stimulating Igs or thyrotropin binding inhibiting Igs. These in vitro stimulatory effects of anti-Gal on GD thyrocytes suggest that this natural Ab may contribute to the in vivo continuous stimulation of thyrocytes in GD patients. The possibility that anti-Gal may stimulate GD thyrocytes via interaction with aberrantly expressed alpha-galactosyl epitopes on the thyroid-stimulating hormone receptor is discussed.",
"title": "Specific stimulation of Graves' disease thyrocytes by the natural anti-Gal antibody from normal and autologous serum."
},
{
"docid": "MED-3315",
"text": "PURPOSE: To test the hypothesis that exposure to poultry oncogenic viruses that widely occurs occupationally in poultry workers and in the general population, may be associated with increased risks of deaths from liver and pancreatic cancers, and to identify new risk factors. METHODS: A pilot case-cohort study of both cancers within a combined cohort of 30,411 highly exposed poultry workers and 16,408 control subjects was conducted, and risk assessed by logistic regression odds ratios (OR) and proportional hazards risk ratios. RESULTS: New occupational findings were recorded respectively for pancreatic/liver cancers, for slaughtering of poultry (OR = 8.9, 95% confidence interval [CI]: 2.7-29.3)/OR = 9.1, 95% CI: 1.9-42.9); catching of live chickens (OR = 3.6, 95% CI: 1.2-10.9)/OR = 1.0, 95% CI: 0.1-8.5); killing other types of animals for food (OR = 4.8, 95% CI: 1.5-16.6)/OR = 2.0, 95% CI: 0.2-18.2), and ever worked on a pig raising farm (OR = 3.0, 95% CI: 1.0-8.2) for pancreatic cancer only. New non-occupational findings for liver cancer were for receiving immunization with yellow fever vaccine (OR = 8.7, 95% CI: 1.0-76.3); and vaccination with typhoid vaccine (OR = 6.3, 95% CI: 1.1-37.4). The study also confirmed previously reported risk factors for both diseases. CONCLUSIONS: This study provides preliminary evidence that exposure to poultry oncogenic viruses may possibly be associated with the occurrence of liver and pancreatic cancers. Case-control studies nested within occupational cohorts of highly exposed subjects of sufficient statistical power may provide an efficient and valid method of investigating/confirming these findings. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "A pilot case-cohort study of liver and pancreatic cancers in poultry workers."
},
{
"docid": "MED-3711",
"text": "The incidence of autoimmune, allergic and inflammatory disease is increasing due to as yet unidentified environmental factors related to western living conditions. Here, I propose that alterations in the gut microbiome, acting via regulatory T cells (Tregs), may be responsible for this epidemic. Tregs control the threshold for peripheral antigen recognition via tonic downregulation of dendritic cell (DC) costimulation, and are also implicated in maintaining the tolerogenic function of DCs. In this model, minor perturbations in Treg number or function are predicted to lower the activation threshold, allowing proliferation and differentiation of self-reactive CD4T cells of too low an affinity to have undergone negative selection in the thymus. Failure to maintain the tolerogenic commitment of DCs exposed to commensal microbes and allergens could result in potentially pathogenic, allergic and inflammatory responses at epithelial surfaces.",
"title": "Regulatory T-cell abnormalities and the global epidemic of immuno-inflammatory disease."
},
{
"docid": "MED-3918",
"text": "The study material consisted of five herbs: chamomile (flowers), mint (leaves), St John's wort (flowers and leaves), sage (leaves) and nettle (leaves), sourced from three producers. The calcium, magnesium, iron, zinc and copper contents were determined for both dried herb samples and prepared infusions, and the extraction rates were calculated. Mineral components were determined using atomic absorption spectrometry. Analysis showed that the contents of individual elements in herbs and infusions depended on the type of raw material, as well as on its origin. Moreover, it was found that iron penetrated the herbal infusions to the lowest degree (4.4-12.4%), while copper did so to the highest (26.7-50.7%). It is felt that in average consumption the herbal infusions are not important as calcium, magnesium, iron, zinc and copper sources in human nutrition.",
"title": "Herbal infusions as a source of calcium, magnesium, iron, zinc and copper in human nutrition."
},
{
"docid": "MED-4916",
"text": "Agaritine (N-(gamma-L(+)-glutamyl)-4-hydroxymethyl-phenylhydrazine) was identified and quantified by high-pressure liquid chromatography and used as a marker for the occurrence of phenylhydrazine derivatives in the cultivated Agaricus bitorquis and A. garicus hortensis mushrooms. Although relatively high levels of agaritine (around 700 mg kg(-1)) could be found in freshly harvested A. bitorquis from early flushes, samples from supermarkets contained less agaritine. The content of 28 samples varied between 165 and 457 mg kg(-1), on average being 272 +/- 69 mg kg(-1). The highest amounts of agaritine were found in the skin of the cap and in the gills, the lowest being in the stem. There was no significant difference in agaritine content of the two mushroom species in our study. Pronounced reduction in agaritine content was observed during storage of mushrooms in the refrigerator or freezer, as well as during drying of the mushrooms. The degree of reduction was dependent on the length and condition of storage and was usually in the region 20-75%. No reduction in agaritine content was observed during freeze-drying. Depending on the cooking procedure, household processing of cultivated Agaricus mushrooms reduced the agaritine content to various degrees. Boiling extracted around 50% of the agaritine content into the cooking broth within 5min and degraded 20-25% of the original agaritine content of the mushrooms. Prolonged boiling, as when preparing a sauce, reduced the content in the solid mushroom further (around 10% left after 2h). Dry baking of the cultivated mushroom, a process similar to pizza baking, reduced the agaritine content by approximately 25%, whereas frying in oil or butter or deep frying resulted in a more marked reduction (35-70%). Microwave processing of the cultivated mushrooms reduced the agaritine content to one-third of the original level. Thus, the exposure to agaritine was substantially less when consuming processed Agaricus mushrooms as compared with consuming the raw mushrooms. However, it is not yet known to what extent agaritine and other phenylhydrazine derivatives occurring in the cultivated mushroom are degraded into other biologically active compounds during the cooking procedure.",
"title": "Influence of storage and household processing on the agaritine content of the cultivated Agaricus mushroom."
},
{
"docid": "MED-4650",
"text": "Aromatase is a cytochrome P450 enzyme (CYP19) and is the rate limiting enzyme in the conversion of androgens to estrogens. Suppression of in situ estrogen production through aromatase inhibition is the current treatment strategy for hormone-responsive breast cancers. Drugs that inhibit aromatase have been developed and are currently utilized as adjuvant therapy for breast cancer in post-menopausal women with hormone dependent breast cancer. Natural compounds have been studied extensively for important biologic effects such as antioxidant, anti-tumor and anti-viral effects. A significant number of studies have also investigated the aromatase inhibitory properties of a variety of plant extracts and phytochemicals. The identification of natural compounds that inhibit aromatase could be useful both from a chemopreventive standpoint and in the development of new aromatase inhibitory drugs. This review will discuss whole food extracts and the common classes of phytochemicals which have been investigated for potential aromatase inhibitory activity. We will review reported aromatase inhibition, kinetic data and possible structural variations that may inhibit or enhance the interaction of phytochemicals with the aromatase enzyme.",
"title": "Phytochemicals for breast cancer prevention by targeting aromatase."
},
{
"docid": "MED-3705",
"text": "The association of inflammation with modern human diseases (e.g. obesity, cardiovascular disease, type 2 diabetes mellitus, cancer) remains an unsolved mystery of current biology and medicine. Inflammation is a protective response to noxious stimuli that unavoidably occurs at a cost to normal tissue function. This fundamental tradeoff between the cost and benefit of the inflammatory response has been optimized over evolutionary time for specific environmental conditions. Rapid change of the human environment due to niche construction outpaces genetic adaptation through natural selection, leading increasingly to a mismatch between the modern environment and selected traits. Consequently, multiple tradeoffs that affect human physiology are not optimized to the modern environment, leading to increased disease susceptibility. Here we examine the inflammatory response from an evolutionary perspective. We discuss unique aspects of the inflammatory response and its evolutionary history that can help explain the association between inflammation and modern human diseases.",
"title": "Evolution of Inflammatory Diseases"
},
{
"docid": "MED-2367",
"text": "Naturally developing xenospecific Abs are well-documented barriers to xenograft transplantation in humans, but whether analogous xenoreactive T cell immunity develops is not known. We used an enzyme-linked immunospot assay to determine the frequency and cytokine profiles of xenoreactive PBLs from a panel of human volunteers. Because naive T cells produce only IL-2 in short term culture, IFN-gamma production by this approach is a measure of a memory immune response. Stimulation of human PBLs or purified T lymphocytes with stimulator cells from inbred swine revealed a high frequency of IFN-gamma producers with 5-fold fewer IL-2 producers. In contrast, lymphocytes obtained from neonatal umbilical cord blood contained swine-specific IL-2 producers but few IFN-gamma producers, which is what one would expect to find with a naive phenotype. Moreover, PBLs from adults with a history of abstention from pork consumption responded to swine cells with a significantly lower frequency of IFN-gamma producers than PBLs from adults with unrestricted diets did, suggesting that pork consumption may result in priming of swine-specific T cell immunity. Our findings provide the first evidence for naturally occurring xenospecific T cell immunity in humans. The detected strength of this memory response suggests that it will present a formidable barrier to transplantation of swine organs.",
"title": "Naturally developing memory T cell xenoreactivity to swine antigens in human peripheral blood lymphocytes."
},
{
"docid": "MED-3316",
"text": "BACKGROUND: Between November, 2006, and May, 2008, a subacute neurological syndrome affected workers from two swine abattoirs in Minnesota and Indiana who had occupational exposure to aerosolised porcine brain. We aimed to describe the pathogenic and immunological characteristics of this illness. METHODS: All patients from two abattoirs who presented or were referred to the Mayo Clinic (Rochester, MN, USA) with neurological symptoms were included. We recorded details of exposure to aerosolised brain tissue and did comprehensive neurological, laboratory, neuroimaging, electrophysiological, pathological, and autoimmune serological assessments. Healthy controls were recruited from the community and from workers at the plant in Minnesota. FINDINGS: 24 patients were identified (21 from Minnesota, three from Indiana). The shortest duration from first exposure to symptom onset was 4 weeks. No infectious agent that could trigger disease was identified. All patients developed polyradiculoneuropathy, which was usually sensory predominant and painful. Two patients had initial CNS manifestations: transverse myelitis and meningoencephalitis. Nerve conduction studies localised abnormalities to the most proximal and distal nerve segments. Quantitative sensory and autonomic testing revealed involvement of large and small sensory fibres and sweat fibres. MRI showed prominent abnormalities of roots and ganglia. Nerve biopsies identified mild demyelination, axonal degeneration, and perivascular inflammation. Protein concentrations were high in the CSF of 18 (86%) of 21 patients. Sera from all patients and 29 (34%) of 85 unaffected workplace controls (but none of 178 community controls) had a distinctive neural-reactive IgG; 75% of patients' sera contained an IgG specific to myelin basic protein. Seropositivity correlated directly with exposure risk in patients and controls. 17 patients required immunomodulatory therapies, six improved spontaneously, and one was lost to follow-up after exposure stopped. INTERPRETATION: The neurological disorder described is autoimmune in origin and is related to occupational exposure to multiple aerosolised porcine brain tissue antigens. The pattern of nerve involvement suggests vulnerability of nerve roots and terminals where the blood-nerve barrier is most permeable. FUNDING: Mayo Clinic Foundation; Minnesota Department of Health; Centers for Disease Control and Prevention. Copyright 2010 Elsevier Ltd. All rights reserved.",
"title": "An outbreak of neurological autoimmunity with polyradiculoneuropathy in workers exposed to aerosolised porcine neural tissue: a descriptive study."
},
{
"docid": "MED-3320",
"text": "OBJECTIVES: Reticuloendotheliosis viruses (REV) are a group of retroviruses like avian leukosis/sarcoma viruses (ALSV) that naturally infect and cause cancers in chickens. We recently found that ALSV antibody levels were associated with job tasks in the poultry industry. The objectives of this study are to examine whether a similar association can be found with REV antibody levels and to examine the correlation between REV and ALSV antibody levels. METHODS: Relative risk was estimated comparing REV antibody levels of 45 poultry workers with those of 44 controls. The expected mean antibody level was predicted for the association with employment by a generalized linear model. Correlation coefficient was measured between ALSV and REV antibody levels. RESULTS: REV antibody levels were significantly higher in poultry workers than in control subjects and were associated with gender and employment conditions, especially employment duration. The relative risk was significantly higher for some job categories. A significant correlation was observed between REV and ALSV antibody levels, which was strong among poultry workers, but weak among the control subjects. CONCLUSION: Antibody levels can be validly used to identify certain job tasks associated with high risk of exposure to REV in the workplace, and the practical implication is recommendations for protection at these job tasks. Importantly, in situations where there is exposure to multiple pathogens in the workplace, the analysis of antibody levels of one pathogen may sufficiently represent exposure to the other correlated pathogens. This suggested exposure assessment may hold true for pathogens with a similar route of transmission.",
"title": "Industrial hygiene assessment of reticuloendotheliosis viruses exposure in the poultry industry."
},
{
"docid": "MED-2274",
"text": "Objective To study the relation between cherry intake and the risk of recurrent gout attacks among individuals with gout. Methods We conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for one year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, symptoms and signs, medications (including anti-gout medications), and potential risk factors (including daily intake of cherries and cherry extract) during the 2-day period prior to the gout attack. We assessed the same exposure information over 2-day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression. Results Our study included 633 individuals with gout. Cherry intake over a 2-day period was associated with a 35% lower risk of gout attacks compared with no intake (multivariate odds ratio [OR] = 0.65, 95% CI: 0.50-0.85). Cherry extract intake showed a similar inverse association (multivariate OR=0.55, 95% CI: 0.30-0.98). The effect of cherry intake persisted across subgroups by sex, obesity status, purine intake, alcohol use, diuretic use, and use of anti-gout medications. When cherry intake was combined with allopurinol use, the risk of gout attacks was 75% lower than periods without either exposure (OR=0.25, 95% CI: 0.15-0.42). Conclusions These findings suggest that cherry intake is associated with a lower risk of gout attacks.",
"title": "Cherry Consumption and the Risk of Recurrent Gout Attacks"
},
{
"docid": "MED-4719",
"text": "Among the many known health benefits of tea catechins count anti-inflammatory and neuroprotective activities, as well as effects on the regulation of food intake. Here we address cannabimimetic bioactivity of catechin derivatives occurring in tea leaves as a possible cellular effector of these functionalities. Competitive radioligand binding assays using recombinant human cannabinoid receptors expressed in Chem-1 and CHO cells identified (-)-epigallocatechin-3-O-gallate, EGCG (K(i)=33.6 microM), (-)-epigallocatechin, EGC (K(i)=35.7 microM), and (-)-epicatechin-3-O-gallate, ECG (K(i)=47.3 microM) as ligands with moderate affinity for type 1 cannabinoid receptors, CB1. Binding to CB2 was weaker with inhibition constants exceeding 50 microM for EGC and ECG. The epimers (+)-catechin and (-)-epicatechin exhibited negligible affinities for both CB1 and CB2. It can be concluded that central nervous cannabinoid receptors may be targeted by selected tea catechins but signaling via peripheral type receptors is less likely to play a major role in vivo.",
"title": "Tea catechins' affinity for human cannabinoid receptors."
},
{
"docid": "MED-3699",
"text": "BACKGROUND: In 2007 the World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) issued 8 recommendations (plus 2 special recommendations) on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. OBJECTIVE: We aimed to investigate whether concordance with the WCRF/AICR recommendations was related to cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. DESIGN: The present study included 386,355 EPIC participants from 9 European countries. At recruitment, dietary, anthropometric, and lifestyle information was collected. A score was constructed based on the WCRF/AICR recommendations on weight management, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, alcoholic drinks, and breastfeeding for women; the score range was 0-6 for men and 0-7 for women. Higher scores indicated greater concordance with WCRF/AICR recommendations. The association between the score and cancer risk was estimated by using multivariable Cox regression models. RESULTS: Concordance with the score was significantly associated with decreased risk of cancer. A 1-point increment in the score was associated with a risk reduction of 5% (95% CI: 3%, 7%) for total cancer, 12% (95% CI: 9%, 16%) for colorectal cancer, and 16% (95% CI: 9%, 22%) for stomach cancer. Significant associations were also observed for cancers of the breast, endometrium, lung, kidney, upper aerodigestive tract, liver, and esophagus but not for prostate, ovarian, pancreatic, and bladder cancers. CONCLUSION: Adherence to the WCRF/AICR recommendations for cancer prevention may lower the risk of developing most types of cancer.",
"title": "Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk o..."
},
{
"docid": "MED-3312",
"text": "BACKGROUND: Heavy alcohol consumption, viral hepatitis, and diabetes are risk factors for hepatocellular carcinoma (HCC). However, to the authors' knowledge, the information concerning their interaction effect in patients with risk of HCC is sparse. METHODS: A population-based, case-control study of HCC was conducted during 1984-2002. The study involved 295 HCC cases and 435 age-, gender-, and race-matched control subjects among Hispanic and non-Hispanic whites and blacks in Los Angeles County, California. Lifestyle risk factors were ascertained through in-person interviews. Infections with the hepatitis B and C (HCV) viruses were determined using their serologic markers. RESULTS: Fourteen HCC cases but no control subjects tested positive for the hepatitis B surface antigen. Seropositivity for antibodies to HCV was associated with an odds ratio (OR) of 125 (95% confidence interval [95% CI], 17-909) for HCC, whereas seropositivity for antibodies to the hepatitis B core antigen was related to an OR of 2.9 (95% CI, 1.7-5.0). Heavy alcohol consumption and cigarette smoking were found to be independently associated with a statistically significant two to threefold increase in risk of HCC after adjustment for hepatitis B and C serology. Subjects with a history of diabetes had an OR of 2.7 (95% CI, 1.6-4.3) for HCC compared with nondiabetic subjects. A synergistic interaction on HCC risk was observed between heavy alcohol consumption and diabetes (OR = 4.2; 95% CI, 2.6-5.8), heavy alcohol consumption and viral hepatitis (OR = 5.5; 95% CI, 3.9-7.0), or between diabetes and viral hepatitis (OR = 4.8; 95% CI, 2.7-6.9). CONCLUSIONS: Heavy alcohol consumption, diabetes, and viral hepatitis were found to exert independent and synergistic effects on risk of HCC in U.S. blacks and whites. Copyright 2004 American Cancer Society.",
"title": "Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S."
},
{
"docid": "MED-4721",
"text": "[3H]CP 55,940, a radiolabeled synthetic cannabinoid, which is 10-100 times more potent in vivo than delta 9-tetrahydrocannabinol, was used to characterize and localize a specific cannabinoid receptor in brain sections. The potencies of a series of natural and synthetic cannabinoids as competitors of [3H]CP 55,940 binding correlated closely with their relative potencies in several biological assays, suggesting that the receptor characterized in our in vitro assay is the same receptor that mediates behavioral and pharmacological effects of cannabinoids, including human subjective experience. Autoradiography of cannabinoid receptors in brain sections from several mammalian species, including human, reveals a unique and conserved distribution; binding is most dense in outflow nuclei of the basal ganglia--the substantia nigra pars reticulata and globus pallidus--and in the hippocampus and cerebellum. Generally high densities in forebrain and cerebellum implicate roles for cannabinoids in cognition and movement. Sparse densities in lower brainstem areas controlling cardiovascular and respiratory functions may explain why high doses of delta 9-tetrahydrocannabinol are not lethal.",
"title": "Cannabinoid receptor localization in brain."
},
{
"docid": "MED-2361",
"text": "The most common clinical manifestation of Lyme disease is the characteristic rash, erythema migrans (EM). In the 1980s EM-like eruptions were reported in Missouri and other southeastern states. The EM-like eruptions, which were of unknown etiology, often followed the bite of the Lone Star tick (Amblyomma americanum) and the rash is called STARI (southern tick-associated rash illness). Although the Lone Star tick is found in the Lyme disease-endemic areas of New England and Mid-Atlantic regions of the United States, STARI has been reported only once from the Northeast and Mid-Atlantic regions. We report a child from Connecticut who visited Long Island, New York, and developed a rash that was thought to be EM. Because the patient failed to respond to antibiotics used to treat Lyme disease, an investigation ensued, and the diagnosis of STARI was established.",
"title": "Southern Tick-Associated Rash Illness (STARI) in the North: STARI following a tick bite in Long Island, New York."
}
] |
[
{
"docid": "MED-864",
"text": "Hepatotoxic effect related to Ganoderma lucidum (Lingzhi) mushroom powder was first described in a patient from Hong Kong in 2004. In 2005, the authors experienced a case of fatal fulminant hepatitis associated with such a preparation. Both patients had taken other therapeutic agents and traditionally boiled Lingzhi without any toxic effect. After switching to taking Lingzhi in powder form for 1-2 months, the hepatotoxic episode occurred in both patients. The toxic role of Lingzhi powder needs close monitoring in the future, especially in combination with other drugs.",
"title": "Fatal fulminant hepatitis associated with Ganoderma lucidum (Lingzhi) mushroom powder."
},
{
"docid": "MED-1592",
"text": "The presence of natural estrogen hormones as trace concentrations in the environment has been reported by many researchers and is of growing concern due to its possible adverse effects on the ecosystem. In this study, municipal biosolids, poultry manure (PM) and cow manure (CM), and spent mushroom compost (SMC) were analyzed for the presence of seven estrogen hormones. 17α-estradiol, 17β-estradiol, 17α-dihydroequilin, and estrone were detected in the sampled biosolids and manures at concentrations ranging from 6 to 462 ng/g of dry solids. 17α-estradiol, 17β-estradiol, and estrone were also detected in SMC at concentrations ranging from 4 to 28 ng/g of dry solids. Desorption experiments were simulated in the laboratory using deionized water (milli-Q), and the aqueous phase was examined for the presence of estrogen hormones to determine their desorption potential. Very low desorption of 0.4% and 0.2% estrogen hormones was observed from municipal biosolids and SMC, respectively. An estimate of total estrogen contribution from different solid waste sources is reported. Animal manures (PM and CM) contribute to a significant load of estrogen hormones in the natural environment.",
"title": "Occurrence of estrogen hormones in biosolids, animal manure and mushroom compost."
},
{
"docid": "MED-4713",
"text": "INTRODUCTION: Kombucha \"mushroom'' tea is touted to have medicinal properties. Here, we present a case of hyperthermia, lactic acidosis, and acute renal failure within 15 hours of Kombucha tea ingestion. CASE PRESENTATION: A 22 year old male, newly diagnosed with HIV, became short of breath and febrile to 103.0F, within twelve hours of Kombucha tea ingestion. He subsequently became combative and confused, requiring sedation and intubation for airway control. Laboratories revealed a lactate of 12.9 mmol/L, and serum creatinine of 2.1 mg/dL. DISCUSSION: Kombucha tea is black tea fermented in a yeast-bacteria medium. Several case reports exist of serious, and sometimes fatal, hepatic dysfunction and lactic acidosis within close proximity to ingestion. CONCLUSION: While Kombucha tea is considered a healthy elixir, the limited evidence currently available raises considerable concern that it may pose serious health risks. Consumption of this tea should be discouraged, as it may be associated with life-threatening lactic acidosis.",
"title": "A case of Kombucha tea toxicity."
},
{
"docid": "MED-5363",
"text": "OBJECTIVE: Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. METHODS: Subjects were 521 municipal employees (309 men and 212 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D >or=16) with adjustment for potential confounding variables. RESULTS: We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62-1.59) and 0.44 (0.25-0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms. CONCLUSIONS: Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status.",
"title": "Dietary patterns and depressive symptoms among Japanese men and women."
},
{
"docid": "MED-3683",
"text": "BACKGROUND: The aim of this study was to investigate whether consumption of Lactobacillus plantarum HEAL 9 (DSM 15312) and Lactobacillus paracasei 8700:2 (DSM 13434) could affect naturally acquired common cold infections in healthy subjects. METHODS: A randomised, parallel, double-blind placebo-controlled study was performed to investigate whether intake of this probiotic mixture could reduce the risk of common cold episodes, number of days with common cold symptoms, frequency and severity of symptoms, and cellular immune response in common cold infections. A total of 272 subjects were supplemented daily with either 10(9) cfu (colony forming units) of probiotics (N = 135) or control (N = 137) for a 12-week period. RESULTS: The incidence of acquiring one or more common cold episode was reduced from 67% in the control group to 55% in the probiotic group (p < 0.05). Also, the number of days with common cold symptoms were significantly (p < 0.05) reduced from 8.6 days in the control group to 6.2 days, in the probiotic group, during the 12-week period. The total symptom score was reduced during the study period from a mean of 44.4 for the control group to 33.6 for the probiotic group. The reduction in pharyngeal symptoms was significant (p < 0.05). In addition, the proliferation of B lymphocytes was significantly counteracted in the probiotic group (p < 0.05) in comparison with the control group. CONCLUSION: In conclusion, intake of the probiotic strains Lactobacillus plantarum HEAL 9 (DSM 15312) and Lactobacillus paracasei 8700:2 (DSM 13434) reduces the risk of acquiring common cold infections.",
"title": "Randomised, double-blind and placebo-controlled study using new probiotic lactobacilli for strengthening the body immune defence against viral infe..."
},
{
"docid": "MED-3926",
"text": "Sixteen parkinsonian patients with daily fluctuations in the clinical response to levodopa have been placed on a redistribution protein diet. The diet was virtually protein-free until the evening meal and then unrestricted until bedtime. While on the redistribution protein diet, a group of patients (5 out of 16) had a clear and significant benefit from dietary therapy showing a definite reduction of diurnal motor performance fluctuations. In addition, all patients tended to show an improvement and a more constant response to levodopa treatment. A trial of redistribution protein diet appears a simple, reasonable, worthwhile approach to PD patients who begin to experience oscillating clinical response to levodopa treatment.",
"title": "Protein redistribution diet and antiparkinsonian response to levodopa."
},
{
"docid": "MED-3617",
"text": "Background: Dietary antioxidants may protect against DNA damage induced by endogenous and exogenous sources, including ionizing radiation (IR), but data from IR-exposed human populations are limited. Objective: The objective was to examine the association between the frequency of chromosome translocations, as a biomarker of cumulative DNA damage, and intakes of vitamins C and E and carotenoids in 82 male airline pilots. Design: Dietary intakes were estimated by using a self-administered semiquantitative food-frequency questionnaire. Translocations were scored by using fluorescence in situ hybridization with whole chromosome paints. Negative binomial regression was used to estimate rate ratios and 95% CIs, adjusted for potential confounders. Results: Significant and inverse associations were observed between translocation frequency and intakes of vitamin C, β-carotene, β-cryptoxanthin, and lutein-zeaxanthin from food (P < 0.05). Translocation frequency was not associated with the intake of vitamin E, α-carotene, or lycopene from food; total vitamin C or E from food and supplements; or vitamin C or E or multivitamin supplements. The adjusted rate ratios (95% CI) for ≥median compared with <median servings per week of high–vitamin C fruit and vegetables, citrus fruit, and green leafy vegetables were 0.61 (0.43, 0.86), 0.64 (0.46, 0.89), and 0.59 (0.43, 0.81), respectively. The strongest inverse association was observed for ≥median compared with <median combined intakes of vitamins C and E, β-carotene, β-cryptoxanthin, and lutein-zeaxanthin from food: 0.27 (0.14, 0.55). Conclusion: High combined intakes of vitamins C and E, β-carotene, β-cryptoxanthin, and lutein-zeaxanthin from food, or a diet high in their food sources, may protect against cumulative DNA damage in IR-exposed persons.",
"title": "High dietary antioxidant intakes are associated with decreased chromosome translocation frequency in airline pilots"
},
{
"docid": "MED-1433",
"text": "Advanced glycation end products (AGEs) are a heterogeneous, complex group of compounds that are formed when reducing sugar reacts in a non-enzymatic way with amino acids in proteins and other macromolecules. This occurs both exogenously (in food) and endogenously (in humans) with greater concentrations found in older adults. While higher AGEs occur in both healthy older adults and those with chronic diseases, research is progressing to both quantify AGEs in food and in people, and to identify mechanisms that would explain why some human tissues are damaged, and others are not. In the last twenty years, there has been increased evidence that AGEs could be implicated in the development of chronic degenerative diseases of aging, such as cardiovascular disease, Alzheimer’s disease and with complications of diabetes mellitus. Results of several studies in animal models and humans show that the restriction of dietary AGEs has positive effects on wound healing, insulin resistance and cardiovascular diseases. Recently, the effect of restriction in AGEs intake has been reported to increase the lifespan in animal models. This paper will summarize the work that has been published for both food AGEs and in vivo AGEs and their relation with aging, as well as provide suggestions for future research.",
"title": "Dietary Advanced Glycation End Products and Aging"
},
{
"docid": "MED-5101",
"text": "When making food choices, consumers are faced with the dilemma of reconciling differences between health benefits and exposure to potential toxins. Analyses to estimate likely intake and exposure outcomes for young children and women of child-bearing age shows that seafood, chicken, and beef, while approximately equivalent in protein, vary in key nutrients of importance as well as in levels of certain contaminants. Increasing the variety of choices among meats, poultry, and seafood and consuming them in amounts consistent with current dietary guidelines and advisories will contribute toward meeting nutritional needs while reducing exposure to any single type of contaminant.",
"title": "Nutrient and contaminant tradeoffs: exchanging meat, poultry, or seafood for dietary protein."
},
{
"docid": "MED-954",
"text": "It has been speculated that maternal phthalate exposure may affect reproductive development in human newborns. However, the mechanism awaits further investigation. The aim is to evaluate the association between maternal phthalate exposure and cord sex steroid hormones in pregnant women and their newborns from the general population. A total of 155 maternal and infant pair were recruited and analyzed. Levels of urinary phthalate metabolites and sex steroid hormones were determined using liquid chromatography/electrospray tandem mass spectrometry (LC-ESI-MS/MS) and radioimmunoassay (RIA), respectively. No significant correlation was found between each steroid hormones and phthalate metabolites for male newborns, except MMP was marginally significantly correlated with E(2). After adjusting for maternal age, estradiol (E(2)) levels in cord serum from male newborns were not correlated with maternal urinary phthalate metabolites. In female newborns, the maternal urinary levels of mono-(2-ethylhexyl) phthalate (MEHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP) were negatively correlated with the free testosterone (fT) and fT/E(2) levels in cord serum with Pearson correlation coefficients ranging between -0.24 and -0.29 (p<0.05). Additionally, after gestational age was adjusted, the maternal urinary level of DEHP was negatively correlated with the free testosterone (fT) and fT/E(2) levels in cord serum. We suggest that maternal exposure to phthalates may affect sex steroid hormones status in fetal and newborn stage. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Associations between maternal phthalate exposure and cord sex hormones in human infants."
},
{
"docid": "MED-4949",
"text": "Methyl mercury is a developmental neurotoxicant. Exposure results principally from consumption by pregnant women of seafood contaminated by mercury from anthropogenic (70%) and natural (30%) sources. Throughout the 1990s, the U.S. Environmental Protection Agency (EPA) made steady progress in reducing mercury emissions from anthropogenic sources, especially from power plants, which account for 41% of anthropogenic emissions. However, the U.S. EPA recently proposed to slow this progress, citing high costs of pollution abatement. To put into perspective the costs of controlling emissions from American power plants, we have estimated the economic costs of methyl mercury toxicity attributable to mercury from these plants. We used an environmentally attributable fraction model and limited our analysis to the neurodevelopmental impacts—specifically loss of intelligence. Using national blood mercury prevalence data from the Centers for Disease Control and Prevention, we found that between 316,588 and 637,233 children each year have cord blood mercury levels > 5.8 μg/L, a level associated with loss of IQ. The resulting loss of intelligence causes diminished economic productivity that persists over the entire lifetime of these children. This lost productivity is the major cost of methyl mercury toxicity, and it amounts to $8.7 billion annually (range, $2.2–43.8 billion; all costs are in 2000 US$). Of this total, $1.3 billion (range, $0.1–6.5 billion) each year is attributable to mercury emissions from American power plants. This significant toll threatens the economic health and security of the United States and should be considered in the debate on mercury pollution controls.",
"title": "Public Health and Economic Consequences of Methyl Mercury Toxicity to the Developing Brain"
},
{
"docid": "MED-2651",
"text": "The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.",
"title": "Alkylphenols in human milk and their relations to dietary habits in central Taiwan."
},
{
"docid": "MED-3441",
"text": "As modern lifestyles and new feeding habits settle in the world, noncommunicable diseases (NCDs) have evolved to be major causes of disability in developing as well as developed countries. As a concomitant effect, there is a growing interest in natural, healthy food and an increasing awareness of risk factors and determinants of disease. This chapter describes some nutritional facts about seaweeds, which have been used as food since ancient times in China, Japan, Egypt, and India and comments on the potential utilization of marine algae as functional foods. This concept and the description of metabolic syndrome are used as a basis to comprehension of seaweeds against two dreadful illnesses of our times: high blood pressure and cancer. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Marine edible algae as disease preventers."
},
{
"docid": "MED-3589",
"text": "OBJECTIVE: To compare dietary habits in normospermic and oligoasthenoteratospermic patients attending a reproductive assisted clinic. DESIGN: An observational, analytical case-control study. SETTING: Private fertility clinics. PATIENT(S): Thirty men with poor semen quality (cases) and 31 normospermic control couples attending our fertility clinics. INTERVENTION(S): We recorded dietary habits and food consumption using a food frequency questionnaire adapted to meet specific study objectives. Analysis of semen parameters, hormone levels, Y microdeletions, and karyotypes were also carried out. MAIN OUTCOME MEASURE(S): Frequency of intake food items were registered in a scale with nine categories ranging from no consumption to repeated daily consumption. RESULT(S): Controls had a higher intake of skimmed milk, shellfish, tomatoes, and lettuce, and cases consumed more yogurt, meat products, and potatoes. In the logistic regression model cases had lower intake of lettuce and tomatoes, fruits (apricots and peaches), and significantly higher intake of dairy and meat processed products. CONCLUSION(S): Frequent intake of lipophilic foods like meat products or milk may negatively affect semen quality in humans, whereas some fruits or vegetables may maintain or improve semen quality.",
"title": "Food intake and its relationship with semen quality: a case-control study."
},
{
"docid": "MED-1031",
"text": "Primary (simple) constipation is a consequence of habitual bowel elimination on common toilet seats. A considerable proportion of the population with normal bowel movement frequency has difficulty emptying their bowels, the principal cause of which is the obstructive nature of the recto-anal angle and its association with the sitting posture normally used in defecation. The only natural defecation posture for a human being is squatting. The alignment of the recto-anal angle associated with squatting permits smooth bowel elimination. This prevents excessive straining with the potential for resultant damage to the recto-anal region and, possibly, to the colon and other organs. There is no evidence that habitual bowel elimination at a given time each day contributes considerably to the final act of rectal emptying. The natural behavior to empty the bowels in response to a strong defecation reflex alleviates bowel emptying by means of the recto anal inhibitory reflex.",
"title": "Primary constipation: an underlying mechanism."
},
{
"docid": "MED-3847",
"text": "In our laboratories, for several years, two phenolic compounds have been detected during gas chromatographic-mass spectrometric analysis of urinary steroid extracts from human and animal species. Although features of the mass spectra of their trimethylsilyl (TMS) ether derivatives resembled those of oestrogens, they were atypical of steroids. The possibility that they were artefacts of the isolation procedures was discounted after careful studies with blanks, by varying the extraction method and because they were present almost exclusively as conjugates of glucuronic acid. Several of the general characteristics of the unknown compounds were reported after one (referred to as compound 180/442) was found to have a cyclic pattern of excretion during the menstrual cycle of an adult vervet monkey (Fig. 1). An investigation of the nature and distribution of the compounds has shown them to be urinary constituents in humans, baboons, vervet monkeys and rats, and further related compounds have been detected, so far only in vervet monkey urine. We now report spectroscopic and chemical studies that show the two original compounds to be lignans, which have a 2,3-dibenzylbutane skeleton as their basic structure. Unlike all previously known natural lignans, invariably of plant origin, the two mammalian compounds carry phenolic hydroxy groups only in the meta position of the aromatic rings.",
"title": "Lignans in man and in animal species."
},
{
"docid": "MED-5320",
"text": "Increased (18)F-FDG activity in fatty tissue has previously been reported with PET/CT. We previously named this activity uptake in supraclavicular area fat (\"USA-Fat\"). We and others have speculated that this uptake exists in metabolically active brown adipose tissue (BAT). Such tissue might be expected to have varying metabolic activity depending on the ambient temperature. The purpose of this study was to evaluate the frequency of USA-Fat and its relationship to the outdoor temperature. METHODS: Between July 2001 and June 2002, 1,017 consecutive whole-body scans were obtained with a PET/CT scanner and (18)F-FDG for clinical patients. PET images were reviewed for the presence of USA-Fat. RESULTS: USA-Fat was observed in 68 scans obtained from 62 patients (51 female and 11 male). The incidence of USA-Fat was highest, at 13.7%, in January through March, while outside temperatures were low, and was significantly lower, at 4.1%, during the rest of the year. CONCLUSION: The incidence of USA-Fat is clearly increased during the cooler period of the year. This finding suggests that stimulation by cold temperatures increases the frequency with which USA-Fat occurs, supporting underlying BAT as the etiology for this activity.",
"title": "\"USA-Fat\": prevalence is related to ambient outdoor temperature-evaluation with 18F-FDG PET/CT."
},
{
"docid": "MED-828",
"text": "Background Maca (Lepidium meyenii) is an Andean plant of the brassica (mustard) family. Preparations from maca root have been reported to improve sexual function. The aim of this review was to assess the clinical evidence for or against the effectiveness of the maca plant as a treatment for sexual dysfunction. Methods We searched 17 databases from their inception to April 2010 and included all randomised clinical trials (RCTs) of any type of maca compared to a placebo for the treatment of healthy people or human patients with sexual dysfunction. The risk of bias for each study was assessed using Cochrane criteria, and statistical pooling of data was performed where possible. The selection of studies, data extraction, and validations were performed independently by two authors. Discrepancies were resolved through discussion by the two authors. Results Four RCTs met all the inclusion criteria. Two RCTs suggested a significant positive effect of maca on sexual dysfunction or sexual desire in healthy menopausal women or healthy adult men, respectively, while the other RCT failed to show any effects in healthy cyclists. The further RCT assessed the effects of maca in patients with erectile dysfunction using the International Index of Erectile Dysfunction-5 and showed significant effects. Conclusion The results of our systematic review provide limited evidence for the effectiveness of maca in improving sexual function. However, the total number of trials, the total sample size, and the average methodological quality of the primary studies were too limited to draw firm conclusions. More rigorous studies are warranted.",
"title": "Maca (L. meyenii) for improving sexual function: a systematic review"
},
{
"docid": "MED-4300",
"text": "BACKGROUND AND AIMS: Nuts have been part of the human diet since prehistoric times. The aim of the present article is to describe the most important historical and cultural aspects of nut consumption throughout history. DATA SYNTHESIS: We discuss the following historical aspects of nuts originating in the Mediterranean: prehistory, the Egyptian civilization, their spread through the Mediterranean region by the Greek, Phoenician and Roman civilizations, and their reintroduction into Europe by means of the Al-Andalus culture. Particular emphasis is placed on the healthy and nutritional attributes that nuts have had throughout history. We also consider the role of the first globalization of food--the exchange of nuts between continents--and discuss the symbolism that nuts have had for humans throughout history in the context of cultural aspects of the Mediterranean region. CONCLUSIONS: Nuts and fruits are probably the earliest foods consumed by humans and are considered to be important because of their nutritional properties. Nuts have also been used in the past by different civilizations as drugs to prevent or treat several diseases. Copyright © 2010 Elsevier B.V. All rights reserved.",
"title": "Cultural and historical aspects of Mediterranean nuts with emphasis on their attributed healthy and nutritional properties."
},
{
"docid": "MED-5023",
"text": "Infection by unicellular green algae has not been described in humans. A case is reported in a 30-year-old woman who developed persistent infection of a healing operative wound on the dorsum of the right foot, after possible contamination by river water while canoeing. The wound was debrided 2 months later. Histologically, infected tissues contained mixed suppurative and granulomatous inflammation associated with endosporulating, round to oval microorganisms, ranging from 6-9 microns in diameter. Many of these organisms contained multiple, strongly periodic acid-Schiff, Gomori methenamine-silver, and Gridley fungus-positive granules in the cytoplasm. The organisms in tissue did not stain with fluorescent antibody conjugates specific for the two known pathogenic Prototheca species. In some organisms, electron microscopy revealed membranous cytoplasmic profiles considered to be remnants of degenerated chloroplasts. These findings are consistent with the presence of a green algal infection.",
"title": "Green algal infection in a human."
},
{
"docid": "MED-2132",
"text": "The mammalian target of rapamycin (mTOR) is a protein kinase that plays key roles in cellular regulation. It forms complexes with additional proteins. The best-understood one is mTOR complex 1 (mTORC1). The regulation and cellular functions of mTORC1 have been the subjects of intense study; despite this, many questions remain to be answered. They include questions about the actual mechanisms by which mTORC1 signaling is stimulated by hormones and growth factors, which involves the small GTPase Rheb, and by amino acids, which involves other GTPase proteins. The control of Rheb and the mechanism by which it activates mTORC1 remain incompletely understood. Although it has been known for many years that rapamycin interferes with some functions of mTORC1, it is not known how it does this, or why only some functions of mTORC1 are affected. mTORC1 regulates diverse cellular functions. Several mTORC1 substrates are now known, although in several cases their physiological roles are poorly or incompletely understood. In the case of several processes, although it is clear that they are regulated by mTORC1, it is not known how mTORC1 does this. Lastly, mTORC1 is implicated in ageing, but again it is unclear what mechanisms account for this. Given the importance of mTORC1 signaling both for cellular functions and in human disease, it is a high priority to gain further insights into the control of mTORC1 signaling and the mechanisms by which it controls cellular functions and animal physiology.",
"title": "mTORC1 signaling: what we still don't know."
},
{
"docid": "MED-4664",
"text": "We report a series of cases of thyroid dysfunction in adults associated with ingestion of a brand of soy milk manufactured with kombu (seaweed), and a case of hypothyroidism in a neonate whose mother had been drinking this milk. We also report two cases of neonatal hypothyroidism linked to maternal ingestion of seaweed made into soup. These products were found to contain high levels of iodine. Despite increasing awareness of iodine deficiency, the potential for iodine toxicity, particularly from sources such as seaweed, is less well recognised.",
"title": "Iodine toxicity from soy milk and seaweed ingestion is associated with serious thyroid dysfunction."
},
{
"docid": "MED-5076",
"text": "The objective of the present study was to evaluate the effect of three common cooking practices (i.e., boiling, steaming, and frying) on phytochemical contents (i.e., polyphenols, carotenoids, glucosinolates, and ascorbic acid), total antioxidant capacities (TAC), as measured by three different analytical assays [Trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP), ferric reducing antioxidant power (FRAP)] and physicochemical parameters of three vegetables (carrots, courgettes, and broccoli). Water-cooking treatments better preserved the antioxidant compounds, particularly carotenoids, in all vegetables analyzed and ascorbic acid in carrots and courgettes. Steamed vegetables maintained a better texture quality than boiled ones, whereas boiled vegetables showed limited discoloration. Fried vegetables showed the lowest degree of softening, even though antioxidant compounds were less retained. An overall increase of TEAC, FRAP, and TRAP values was observed in all cooked vegetables, probably because of matrix softening and increased extractability of compounds, which could be partially converted into more antioxidant chemical species. Our findings defy the notion that processed vegetables offer lower nutritional quality and also suggest that for each vegetable a cooking method would be preferred to preserve the nutritional and physicochemical qualities.",
"title": "Effects of different cooking methods on nutritional and physicochemical characteristics of selected vegetables."
},
{
"docid": "MED-4321",
"text": "PURPOSE OF REVIEW: Levels of dehydroepiandrosterone (DHEA) are known to decline with age. In an era of increasing use of supplements to better life, the benefits of DHEA in the aging female population are controversial. The goal of this article is to critically review published studies to determine if there is a role for DHEA supplementation in postmenopausal women. RECENT FINDINGS: Daily administration of oral DHEA achieves serum concentrations similar to those of women in their 20s. Several observational studies have shown that lower DHEA levels are associated with increased cardiovascular risk in women; however, interventional trials show no improvement in atherosclerosis or cardiovascular risk factors, and a lowering of HDL cholesterol levels. DHEA supplementation modestly increases bone mineral density in conjunction with adjuvant therapies and improves cognition in those with mild-to-moderate cognitive impairment, but does not affect cognition in unimpaired women. Use of intravaginal DHEA, but not oral DHEA, alleviates vaginal atrophy and improves sexual function in postmenopausal women. SUMMARY: On the basis of current evidence, there is no role for oral DHEA supplementation in healthy, postmenopausal women. Where benefits have been shown, long-term studies are needed to confirm these benefits and verify the safety profile of DHEA.",
"title": "Dehydroepiandrosterone sulfate and postmenopausal women."
},
{
"docid": "MED-2679",
"text": "Commercial aqueous wood-smoke flavouring induced significant increases in the 6-thioguanine resistance mutation frequency of TK6 human lymphoblasts at 0.1 microliter flavouring/ml of cell suspension. This corresponds to 6 micrograms/ml of dissolved 'solids' as determined by fully drying the aqueous flavouring in a vacuum desiccator. In AHH-1 human lymphoblasts, which contain a cytochrome P-450 monooxygenase system, mutations were induced at 0.3 microliter/ml, corresponding to 18 microliters/ml of dissolved 'solids'. The flavouring did not induce 8-azaguanine resistant mutations in Salmonella typhimurium at concentrations up to 1.5 microliter/ml. At higher concentrations the flavouring was toxic to bacteria. The flavouring did not induce lung adenomas or other tumours in newborn mice when injected ip with total doses of up to 26 microliters over a 3-wk period. Toxicity to the kidney, colon and rectum was observed in some mice at 15 wk of age.",
"title": "Commercial hickory-smoke flavouring is a human lymphoblast mutagen but does not induce lung adenomas in newborn mice."
},
{
"docid": "MED-2711",
"text": "Oil of bergamot is an extract from the rind of bergamot orange (Citrus aurantium ssp bergamia) that has a pleasant, refreshing scent; until a few years ago it had been widely used as an ingredient in cosmetics but was restricted or banned in most countries because of certain adverse effects. More recently, oil of bergamot preparations have been gaining renewed popularity in aromatherapy. Oil of bergamot possesses photosensitive and melanogenic properties because of the presence of furocoumarins, primarily bergapten (5-methoxypsoralen [5-MOP]). However, 5-MOP is also potentially phototoxic and photomutagenic. Despite its increasing application, there are only a few recent reports of phototoxic reactions to bergamot aromatherapy oil. We describe two patients with localized and disseminated bullous phototoxic skin reactions developing within 48 to 72 hours after exposure to bergamot aromatherapy oil and subsequent ultraviolet exposure. One patient (case 2) had no history of direct contact with aromatherapy oil but developed bullous skin lesions after exposure to aerosolized (evaporated) aromatherapy oil in a sauna and subsequent UVA radiation in a tanning salon. This report highlights the potential health hazard related to the increasing use of psoralen-containing aromatherapy oils.",
"title": "Accidental bullous phototoxic reactions to bergamot aromatherapy oil."
},
{
"docid": "MED-2089",
"text": "In this study, genotoxicity of two mouthwash products (chlorexidin, benzidamine-HCl) were investigated in the Drosophila Wing-Spot Test which makes use of the wing cell markers multiple wing hairs (mwh) and flare (flr) and detects both mitotic recombination and various types of mutational events. Induced mutations are detected as single mosaic spots on the wing blade of surviving adults that show either the multiple wing hairs or flare phenotype. Induced recombination leads to mwh and flr twin spots and also, to some extent, to mwh single spots. Recording of the frequency and the size of different spots is allowed for a quantitative determination of the mutagenic and recombinogenic effects. Trans-heterozygous third-instar larvae were treated at different concentrations of the mouthwash products. Chlorexidin exposure concentrations were 0.5, 1 and 2mg/ml. Benzidamine-HCl exposure concentrations were 0.38, 0.75 and 1.5mg/ml. In addition, the observed mutations were classified according to size and type of mutation per wing. Both chlorexidin and benzidamine-HCl were genotoxic in terms of total mutations per wing at the highest doses. Survival rates of flies used in the experiments were significantly lower than those of the control group, with both mouthwash products showing toxic effects on Drosophila melanogaster larvae. Copyright (c) 2010 Elsevier Ltd. All rights reserved.",
"title": "Genotoxicity of two mouthwash products in the Drosophila Wing-Spot Test."
},
{
"docid": "MED-3853",
"text": "PURPOSE: Lignans--plant-derived compounds with estrogen-dependent and -independent anticarcinogenic properties--have been associated with postmenopausal breast cancer risk, but data are limited regarding their effect on survival. Dietary lignans are metabolized to enterolignans, which are subsequently absorbed and become bioavailable. PATIENTS AND METHODS: We assessed the prognosis of 1,140 postmenopausal patients with breast cancer age 50 to 74 years who were diagnosed between 2002 and 2005. Vital status through the end of 2009 was ascertained via local population registries, and deaths were verified by death certificates. Information on recurrences and secondary tumors was verified by clinical records and attending physicians. Associations of postdiagnostic serum enterolactone (a biomarker for dietary lignans) with overall survival and distant disease-free survival were assessed by using Cox proportional hazards models stratified by age at diagnosis and adjusted for prognostic factors. RESULTS: Median enterolactone levels for deceased patients and those still alive were 17.0 and 21.4 nmol/L, respectively. During a median of 6.1 years of follow-up after diagnosis, 162 deaths were confirmed. Higher serum enterolactone levels were associated with significantly reduced hazard ratios (HRs) for death (HR per 10 nmol/L increment, 0.94; P = .04; HR for the highest quartile, 0.58; 95% CI, 0.34 to 0.99). For distant disease, HR was 0.94 per 10 nmol/L increment (P = .08) and 0.62 (95% CI, 0.35 to 1.09) for the highest quartile. The highest quartile of serum enterolactone was associated with a significantly reduced risk of death only for estrogen receptor-negative tumors (HR, 0.27; 95% CI, 0.08 to 0.87) but not for estrogen receptor-positive tumors (HR, 0.91; 95% CI, 0.45 to 1.84: P for heterogeneity = .09). CONCLUSION: Postmenopausal patients with breast cancer who have high serum enterolactone levels may have better survival.",
"title": "Serum enterolactone and prognosis of postmenopausal breast cancer."
},
{
"docid": "MED-2258",
"text": "Breast cancer is the most prevalent women's cancer, with an age-adjusted incidence of 122.9 per 100,000 US women. Cadmium, a ubiquitous carcinogenic pollutant with multiple biological effects, has been reported to be associated with breast cancer in one US regional case-control study. We examined the association of breast cancer with urinary cadmium (UCd), in a case-control sample of women living on Long Island (LI), NY (100 with breast cancer and 98 without), a region with an especially high rate of breast cancer (142.7 per 100,000 in Suffolk County) and in a representative sample of US women (NHANES 1999-2008, 92 with breast cancer and 2,884 without). In a multivariable logistic model, both samples showed a significant trend for increased odds of breast cancer across increasing UCd quartiles (NHANES, p=0.039 and LI, p=0.023). Compared to those in the lowest quartile, LI women in the highest quartile had increased risk for breast cancer (OR=2.69; 95% CI=1.07, 6.78) and US women in the two highest quartiles had increased risk (OR=2.50; 95% CI=1.11, 5.63 and OR=2.22; 95% CI=.89, 5.52, respectively). Further research is warranted on the impact of environmental cadmium on breast cancer risk in specific populations and on identifying the underlying molecular mechanisms.",
"title": "Environmental cadmium and breast cancer risk"
},
{
"docid": "MED-1571",
"text": "One hundred and fifty-nine ichtyosarcotoxic outbreaks, including 477 people, were recorded in the island of Réunion (SW Indian ocean) between 1986 and 1994. Ciguatera outbreaks represented 78.6% of the total cases and its annual incidence rate was estimated to be 0.78/10,000 residents. Symptoms caused by ciguatera poisoning are not different from those reported in Pacific and Caribbean islands, except for the additional symptoms of hallucinatory poisoning in 16% of the patients. Serranidae fish, including species of great commercial value, were the most commonly incriminated accounting for 50% of the outbreaks.",
"title": "Ciguatera in Réunion Island (SW Indian Ocean): epidemiology and clinical patterns."
}
] |
94916
|
Conan O'Brien died in 1962.
|
[
{
"docid": "Conan_O'Brien",
"text": "Conan Christopher O'Brien ( born April 18 , 1963 ) is an American television host , comedian , and television producer . He is best known for hosting several late-night talk shows ; since 2010 he has hosted Conan on the cable channel TBS . O'Brien was born in Brookline , Massachusetts , and was raised in an Irish Catholic family . He served as president of The Harvard Lampoon while attending Harvard University , and was a writer for the sketch comedy series Not Necessarily the News . After writing for several comedy shows in Los Angeles , he joined the writing staff of Saturday Night Live . O'Brien was a writer and producer for The Simpsons for two seasons until he was commissioned by NBC to take over David Letterman 's position as host of Late Night in 1993 . A virtual unknown to the public , O'Brien 's initial Late Night tenure received unfavorable reviews and remained on a multiweek renewal cycle during its early years . The show generally improved over time and was highly regarded by the time of his departure in 2009 . Afterwards , O'Brien relocated from New York to Los Angeles to host his own incarnation of The Tonight Show for seven months until network politics prompted a host change in 2010 . Known for his spontaneous hosting style , which has been characterized as `` awkward , self-deprecating humor '' , O'Brien 's late-night programs combine the `` lewd and wacky with more elegant , narrative-driven short films ( remotes ) '' . He has hosted Conan since 2010 and has also hosted such events as the Emmy Awards and Christmas in Washington . O'Brien has been the subject of a documentary , Conan O'Brien Ca n't Stop ( 2011 ) , and has also hosted a 32-city live comedy tour . With the retirement of David Letterman on May 20 , 2015 , O'Brien became the longest-working of all current late-night talk show hosts in the United States , at 22 years .",
"title": ""
}
] |
[
{
"docid": "Lists_of_Conan_O'Brien_sketches",
"text": "Sketch comedy segments have appeared on each of the three late-night comedy shows hosted by Conan O'Brien . They are listed in the following articles : List of Late Night with Conan O'Brien sketches , for sketches on Late Night with Conan O'Brien List of The Tonight Show with Conan O'Brien sketches , for sketches on The Tonight Show with Conan O'Brien List of Conan sketches , for sketches on Conan Category : Conan O'Brien",
"title": ""
},
{
"docid": "Conan_O'Brien_Show",
"text": "Conan O'Brien Show may refer to : Late Night with Conan O'Brien ( 1993 -- 2009 ) , NBC The Tonight Show with Conan O'Brien ( 2009 -- 2010 ) , NBC Conan ( talk show ) ( 2010 -- present ) , a show currently running on TBS that began in November 2010 . The Legally Prohibited from Being Funny on Television Tour ( 2010 ) , a live comedy show across the US and Canada",
"title": ""
},
{
"docid": "Conan_O'Brien_Can't_Stop",
"text": "Conan O'Brien Ca n't Stop is a 2011 documentary film by Rodman Flender featuring Conan O'Brien and focusing on his comedy tour , The Legally Prohibited from Being Funny on Television Tour , which took place in 2010 following his departure from The Tonight Show with Conan O'Brien due to a scheduling dispute . Flender is O'Brien 's friend and Harvard classmate .",
"title": ""
},
{
"docid": "Brian_Stack",
"text": "Brian Stack ( born August 18 , 1967 ) is an American actor , comedian , and writer best known for his sketch comedy work on all three Conan O'Brien late-night talk shows , previously working on Late Night with Conan O'Brien and The Tonight Show with Conan O'Brien , and on O'Brien 's current talk show , Conan on TBS . Stack left Conan in April 2015 to join the writing staff of the CBS series The Late Show with Stephen Colbert .",
"title": ""
},
{
"docid": "List_of_Conan_episodes",
"text": "Conan is a current television program on TBS hosted by Conan O'Brien . O'Brien previously served as host of Late Night with Conan O'Brien for sixteen years , and as host of The Tonight Show with Conan O'Brien from June 1 , 2009 until January 22 , 2010 when the show was canceled amidst the 2010 Tonight Show conflict . The conflict resulted in the former host , Jay Leno , being reinstated following the 2010 Winter Olympics on NBC , and O'Brien touring the country on his Legally Prohibited from Being Funny on Television Tour . The series is an American late-night talk show , which began on November 8 , 2010 , and airs four nights a week . The show is filmed on Stage 15 at Warner Bros. ' studio in Burbank , California . The series is scripted by a team of writers , with Mike Sweeney serving as head writer for the show . Shortly after O'Brien 's departure from Tonight , the show , along with several of the show 's production staff , was nominated for four Emmy Awards , including Outstanding Variety , Music or Comedy Series . In addition to O'Brien serving as host , comedian Andy Richter serves as the show 's announcer , and as a sidekick to O'Brien . Jimmy Vivino and the Basic Cable Band , formerly known as `` The Max Weinberg 7 '' and briefly as `` Max Weinberg and The Tonight Show Band '' , serves as the house band . The show follows the established six-piece format used during Conan O'Brien 's tenure as host of The Tonight Show . The first two segments includes a monologue by O'Brien , sometimes accompanied by altered news clips , or several brief comedy sketches . Interview with two guests will likely follow , as well as a musical or comedy performance . Unusual for a talk show , the titles for each episode ( a la Quinn Martin ) are often offbeat in nature . However , since January 29 , 2014 , the titles have been removed due to a shortened intro .",
"title": ""
},
{
"docid": "Brian_McCann_(actor)",
"text": "Brian McCann ( born August 16 , 1965 ) is an American Emmy and WGA award-winning writer , actor , and comedian best known for his sketch comedy work on the late night talk show , Late Night with Conan O'Brien , and more recently on The Tonight Show with Conan O'Brien and Conan . After 17 years working with Conan O'Brien , McCann left Conan due to his plans to return to New York City . His final day on the show was August 30 , 2012 . McCann has since gone on to write for shows such as Nikki & Sara Live and Totally Biased with W. Kamau Bell .",
"title": ""
},
{
"docid": "Max_Weinberg",
"text": "Max Weinberg ( born April 13 , 1951 ) is an American drummer and television personality , most widely known as the longtime drummer for Bruce Springsteen 's E Street Band and as the bandleader for Conan O'Brien on Late Night with Conan O'Brien and The Tonight Show with Conan O'Brien . Weinberg grew up in suburban New Jersey and began drumming at an early age . He attended college planning to be a lawyer but got his big break in music in 1974 when he won an audition to become the drummer for Springsteen . Weinberg became a mainstay of Springsteen 's long concert performances . Springsteen dissolved the band in 1989 , and Weinberg spent several years considering a law career and trying the business end of the music industry before deciding he wanted to continue with drumming . In 1993 , Weinberg got the role as bandleader of The Max Weinberg 7 for Late Night with Conan O'Brien . Weinberg 's drums-driven jump blues sound and his role as a comic foil prospered along with the show , giving him a second career . In 1999 , Springsteen re-formed the E Street Band for a series of tours and albums ; Weinberg worked out an arrangement that allowed him to play with both O'Brien and Springsteen . In 2009 , Weinberg moved to the short-lived Tonight Show with Conan O'Brien as leader of Max Weinberg and The Tonight Show Band . After that ended , he began touring with his own ensembles , and in 2010 chose not to follow O'Brien to the new Conan show . Weinberg continued playing with Springsteen , and in 2014 was inducted into the Rock and Roll Hall of Fame as a member of the E Street Band .",
"title": ""
},
{
"docid": "Scott_Healy",
"text": "Scott Healy is a Grammy nominated Los Angeles-based pianist , multi-keyboardist and composer best known as the keyboardist for the Jimmy Vivino and the Basic Cable Band on Conan on TBS . His long association with O'Brien dates back to the original Late Night with Conan O'Brien show in 1993 , and the subsequent The Tonight Show with Conan O'Brien .",
"title": ""
},
{
"docid": "Andrew_Weinberg",
"text": "Andrew Weinberg ( born 1976 ) is an American television writer , known for his work on Late Night with Conan O'Brien and The Tonight Show with Conan O'Brien . He is also a co-creator and co-writer of the television series Eagleheart ( TV series ) . The quarter-hour series is a parody of action crime dramas like Walker , Texas Ranger and originated in Conan O'Brien 's Conaco Prods .",
"title": ""
},
{
"docid": "James_Wormworth",
"text": "James Wormworth is an American drummer and percussionist . Wormworth is a member of Jimmy Vivino and the Basic Cable Band on the TBS late night comedy program , Conan . Wormworth often appeared as house drummer during the band 's run as The Max Weinberg 7 on Late Night with Conan O'Brien . Wormworth joined the band as a full-time member when O'Brien became the host of The Tonight Show with Conan O'Brien . Wormworth is the band 's full-time drummer on O'Brien 's TBS talk show Conan ( talk show ) . Wormworth has a strong preference toward playing the drums with his feet completely bare , as exhibited when he wears a full suit with bare feet while playing on television . He is the son of the legendary jazz drummer Jimmy Wormworth and the brother of bass guitarist Tracy Wormworth .",
"title": ""
},
{
"docid": "Tommy_Blacha",
"text": "Thomas `` Tommy '' Blacha ( born August 25 , 1962 ) is an American comedy writer , working for shows such as Metalocalypse , Da Ali G Show and Late Night with Conan O'Brien '' .",
"title": ""
},
{
"docid": "The_Legally_Prohibited_from_Being_Funny_on_Television_Tour",
"text": "The Legally Prohibited from Being Funny on Television Tour ( also known as the Prohibited Tour ) was a comedy tour by American comedian and talk show host Conan O'Brien . Its title is a reference to the 2010 Tonight Show host and timeslot conflict , which resulted in O'Brien resigning from his position as host of The Tonight Show in January 2010 . O'Brien reached a settlement with NBC that barred him from appearing on television until September 2010 , but it did not bar him from performing before a live audience in a concert setting . From April through June 2010 , O'Brien performed 42 shows in the United States and Canada . O'Brien announced on March 11 , 2010 via his Twitter account that he would embark on a 30-city live tour beginning April 12 . Even with the unconventional marketing campaign of a single Twitter announcement , many locations sold out within hours of the tweet and additional shows were added on to meet demand . During the tour , O'Brien announced that his new show , Conan , would debut on TBS in November 2010 . A documentary following O'Brien during the tour , Conan O'Brien Ca n't Stop , was released in June 2011 .",
"title": ""
},
{
"docid": "List_of_Late_Night_with_Conan_O'Brien_sketches",
"text": "The following is a list of sketches which debuted on Late Night with Conan O'Brien on NBC .",
"title": ""
},
{
"docid": "List_of_The_Tonight_Show_with_Conan_O'Brien_sketches",
"text": "The following is a list of sketches which debuted on The Tonight Show with Conan O'Brien on NBC .",
"title": ""
},
{
"docid": "Late_Night_with_Conan_O'Brien",
"text": "Late Night with Conan O'Brien is an American late-night talk show hosted by Conan O'Brien that aired 2,725 episodes on NBC between 1993 and 2009 . The show featured varied comedic material , celebrity interviews , and musical and comedy performances . Late Night aired weeknights at 12:37 am Eastern/11 :37 pm Central and 12:37 am Mountain in the United States . From 1993 until 2000 , Andy Richter served as O'Brien 's sidekick ; following his departure , O'Brien was the show 's sole featured performer . The show 's house musical act was The Max Weinberg 7 , led by E Street Band drummer Max Weinberg . The second incarnation of NBC 's Late Night franchise , O'Brien 's debuted in 1993 after David Letterman , who hosted the first incarnation of Late Night , moved to CBS to host Late Show opposite The Tonight Show . In 2004 , as part of a deal to secure a new contract , NBC announced that O'Brien would leave Late Night in 2009 to succeed Jay Leno as the host of The Tonight Show . Jimmy Fallon began hosting his version of Late Night on March 2 , 2009 .",
"title": ""
},
{
"docid": "The_Tonight_Show_with_Conan_O'Brien",
"text": "The Tonight Show with Conan O'Brien was an American late-night talk show that featured Conan O'Brien as host from June 1 , 2009 , to January 22 , 2010 , as part of NBC 's long-running Tonight Show franchise . O'Brien previously hosted NBC 's Late Night with Conan O'Brien , which followed The Tonight Show with Jay Leno for 16 years , until his brief succession over Leno . Many members of the Late Night cast and crew made the transition to The Tonight Show . The Max Weinberg 7 , the house band from O'Brien 's Late Night , served as the house band under the new name , Max Weinberg and The Tonight Show Band . Andy Richter returned to the show as announcer , and also began resuming his role as sidekick , shortly before the show 's conclusion . The opening and closing theme song from Late Night was also carried over to Tonight , in a slightly altered form . In January 2010 , after the show had been on the air for seven months , it was announced that NBC was intending to move Jay Leno from primetime back to his original timeslot at 11:35 pm , with O'Brien 's show starting shortly after midnight . In response to the announcement , O'Brien released a press statement saying that he would not continue as host of The Tonight Show if it was moved to any time after midnight to accommodate The Jay Leno Show . He feared it would ruin the long and rich tradition of The Tonight Show , which had been on after the late local newscasts from the beginning . After two weeks of negotiations , NBC announced that they had paid $ 45 million to buy out O'Brien 's contract , ending both his tenure as host as well as his relationship with NBC after 22 years . Conan O'Brien 's final Tonight Show was broadcast on January 22 , 2010 , with Jay Leno officially resuming his role as host on March 1 , 2010 , immediately following the conclusion of the 2010 Winter Olympics . It later received four Primetime Emmy nominations , including Outstanding Variety , Music or Comedy Series , the first time The Tonight Show received a nomination for this particular award after 2003 . At only 146 episodes ( 145 aired ) over the course of seven months and three weeks , it is the shortest-running iteration in the sixty-year history of The Tonight Show .",
"title": ""
},
{
"docid": "List_of_The_Tonight_Show_with_Conan_O'Brien_episodes",
"text": "This is the list of episodes for The Tonight Show with Conan O'Brien airing from June 1 , 2009 , to January 22 , 2010 .",
"title": ""
},
{
"docid": "List_of_awards_and_nominations_received_by_Conan_O'Brien",
"text": "The following is a list of awards and nominations received by television host , comedian , writer , producer , musician , and voice actor Conan O'Brien .",
"title": ""
},
{
"docid": "List_of_Late_Night_with_Conan_O'Brien_characters",
"text": "The following is a list of characters on the late night program Late Night with Conan O'Brien , which aired on NBC from 1993 to 2009 .",
"title": ""
},
{
"docid": "List_of_Late_Night_with_Conan_O'Brien_episodes",
"text": "This is a list of episodes for Late Night with Conan O'Brien , which aired from September 13 , 1993 to February 20 , 2009 . __ NOTOC __",
"title": ""
},
{
"docid": "Jerry_Vivino",
"text": "Jerry Vivino ( born January 8 , 1954 in Paterson , New Jersey ) is an American musician . He is currently a member of the Basic Cable Band , the house band for the TBS late night program Conan . He was also a member of The Tonight Show Band , the house band on The Tonight Show with Conan O'Brien and its predecessor , Late Night with Conan O'Brien on NBC . Vivino provides saxophone , woodwinds and vocals .",
"title": ""
},
{
"docid": "List_of_Late_Night_with_Conan_O'Brien_episodes_(season_1)",
"text": "This is a list of episodes for Season 1 of Late Night with Conan O'Brien , which aired from September 13 , 1993 , to September 9 , 1994 .",
"title": ""
},
{
"docid": "List_of_Late_Night_with_Conan_O'Brien_episodes_(season_10)",
"text": "This is a list of episodes for Season 10 of Late Night with Conan O'Brien , which aired from September 3 , 2002 to August 14 , 2003 .",
"title": ""
},
{
"docid": "List_of_Late_Night_with_Conan_O'Brien_episodes_(season_11)",
"text": "This is a list of episodes for Season 11 of Late Night with Conan O'Brien , which aired from September 3 , 2003 to August 13 , 2004 .",
"title": ""
},
{
"docid": "List_of_Late_Night_with_Conan_O'Brien_episodes_(season_12)",
"text": "This is a list of episodes for Season 12 of Late Night with Conan O'Brien , which aired from August 31 , 2004 to August 19 , 2005 .",
"title": ""
},
{
"docid": "List_of_Late_Night_with_Conan_O'Brien_episodes_(season_13)",
"text": "This is a list of episodes for Season 13 of Late Night with Conan O'Brien , which aired from September 6 , 2005 , to September 15 , 2006 .",
"title": ""
},
{
"docid": "List_of_Late_Night_with_Conan_O'Brien_episodes_(season_14)",
"text": "This is a list of episodes for Season 14 of Late Night with Conan O'Brien , which aired from September 18 , 2006 to October 19 , 2007 .",
"title": ""
},
{
"docid": "List_of_Late_Night_with_Conan_O'Brien_episodes_(season_2)",
"text": "This is a list of episodes for Season 2 of Late Night with Conan O'Brien , which aired from September 13 , 1994 , to September 8 , 1995 .",
"title": ""
},
{
"docid": "List_of_Late_Night_with_Conan_O'Brien_episodes_(season_3)",
"text": "This is a list of episodes for Season 3 of Late Night with Conan O'Brien , which aired from September 11 , 1995 , to September 13 , 1996 .",
"title": ""
},
{
"docid": "List_of_Late_Night_with_Conan_O'Brien_episodes_(season_4)",
"text": "This is a list of episodes for Season 4 of Late Night with Conan O'Brien , which aired from September 17 , 1996 to August 22 , 1997 .",
"title": ""
}
] |
929
|
Patients with microcytosis and higher erythrocyte count were more resistant to severe malarial anaemia when infected with Plasmodium falciparum.
|
[
{
"docid": "18174210",
"text": "BACKGROUND The heritable haemoglobinopathy alpha(+)-thalassaemia is caused by the reduced synthesis of alpha-globin chains that form part of normal adult haemoglobin (Hb). Individuals homozygous for alpha(+)-thalassaemia have microcytosis and an increased erythrocyte count. Alpha(+)-thalassaemia homozygosity confers considerable protection against severe malaria, including severe malarial anaemia (SMA) (Hb concentration < 50 g/l), but does not influence parasite count. We tested the hypothesis that the erythrocyte indices associated with alpha(+)-thalassaemia homozygosity provide a haematological benefit during acute malaria. METHODS AND FINDINGS Data from children living on the north coast of Papua New Guinea who had participated in a case-control study of the protection afforded by alpha(+)-thalassaemia against severe malaria were reanalysed to assess the genotype-specific reduction in erythrocyte count and Hb levels associated with acute malarial disease. We observed a reduction in median erythrocyte count of approximately 1.5 x 10(12)/l in all children with acute falciparum malaria relative to values in community children (p < 0.001). We developed a simple mathematical model of the linear relationship between Hb concentration and erythrocyte count. This model predicted that children homozygous for alpha(+)-thalassaemia lose less Hb than children of normal genotype for a reduction in erythrocyte count of >1.1 x 10(12)/l as a result of the reduced mean cell Hb in homozygous alpha(+)-thalassaemia. In addition, children homozygous for alpha(+)-thalassaemia require a 10% greater reduction in erythrocyte count than children of normal genotype (p = 0.02) for Hb concentration to fall to 50 g/l, the cutoff for SMA. We estimated that the haematological profile in children homozygous for alpha(+)-thalassaemia reduces the risk of SMA during acute malaria compared to children of normal genotype (relative risk 0.52; 95% confidence interval [CI] 0.24-1.12, p = 0.09). CONCLUSIONS The increased erythrocyte count and microcytosis in children homozygous for alpha(+)-thalassaemia may contribute substantially to their protection against SMA. A lower concentration of Hb per erythrocyte and a larger population of erythrocytes may be a biologically advantageous strategy against the significant reduction in erythrocyte count that occurs during acute infection with the malaria parasite Plasmodium falciparum. This haematological profile may reduce the risk of anaemia by other Plasmodium species, as well as other causes of anaemia. Other host polymorphisms that induce an increased erythrocyte count and microcytosis may confer a similar advantage.",
"title": "Increased Microerythrocyte Count in Homozygous α+-Thalassaemia Contributes to Protection against Severe Malarial Anaemia"
}
] |
[
{
"docid": "2460304",
"text": "Erythrocytes carrying a variant hemoglobin allele (HbS), which causes sickle cell disease and resists infection by the malaria parasite Plasmodium falciparum. The molecular basis of this resistance, which has long been recognized as multifactorial, remains incompletely understood. Here we show that the dysregulated microRNA (miRNA) composition, of either heterozygous HbAS or homozygous HbSS erythrocytes, contributes to resistance against P. falciparum. During the intraerythrocytic life cycle of P. falciparum, a subset of erythrocyte miRNAs translocate into the parasite. Two miRNAs, miR-451 and let-7i, were highly enriched in HbAS and HbSS erythrocytes, and these miRNAs, along with miR-223, negatively regulated parasite growth. Surprisingly, we found that miR-451 and let-7i integrated into essential parasite messenger RNAs and, via impaired ribosomal loading, resulted in translational inhibition. Hence, sickle cell erythrocytes exhibit cell-intrinsic resistance to malaria in part through an atypical miRNA activity, which may represent a unique host defense strategy against complex eukaryotic pathogens.",
"title": "Translocation of sickle cell erythrocyte microRNAs into Plasmodium falciparum inhibits parasite translation and contributes to malaria resistance."
},
{
"docid": "9254550",
"text": "BACKGROUND & OBJECTIVES Anaemia is commonly observed in children with malaria, but reports on leucocyte and platelet count abnormalities associated with malaria are inconsistent. This study examined the effect of age, gender, parasite density and temperature on haematological parameters in children with acute uncomplicated malaria. METHODS Haematological parameters were determined in children with acute uncomplicated malaria, and these were correlated with age, sex, temperature and parasite density. Statistical analysis was done using SAS 9.1. RESULTS Six hundred and ninety five children with acute uncomplicated malaria participated in the study. The mean age was 51.7 months +/- 33.8. At presentation, anaemia occurred in 43.8% of the patients and children <5 yr had a significantly lower haematocrit (28.4% +/- 4.8) than that of older children (32.8% +/- 4.8) (p <0.001), but the haematocrit was not significantly different by days 14 and 28. There was no difference between both sexes. Leucocytosis was more frequently seen than leucopenia (9.5% vs 3%). Thrombocytopenia was found in 59.3% of enrolled patients. More than half of the patients with thrombocytopenia had recovered by Day 28. Baseline platelet count was related to Day 14 (r = 0.6, p < 0.0001) and Day 28 (r = 0.2, p = 0.0015) and the haematocrit on Day 28 (r = 0.12, p = 0.00197). Platelet count showed no correlation with temperature, parasite density and leucocyte count. Haematocrit correlated with age (r = 0.4, p < 0.0001); but not with parasite density or temperature. Leucocyte count showed no correlation with age or parasite density. CONCLUSION While thrombocytopenia was the most common haematological finding and may be of diagnostic importance, anaemia and leucocytosis were more common in the under fives.",
"title": "Age as a risk factor for thrombocytopenia and anaemia in children treated for acute uncomplicated falciparum malaria."
},
{
"docid": "25420421",
"text": "Little is known about the changes in white blood cells and platelets in children with falciparum malaria in endemic areas. We measured the white cell count (WCC) and platelets of 230 healthy children from the community, 1369 children admitted to hospital with symptomatic malaria, and 1461 children with other medical conditions. Children with malaria had a higher WCC compared with community controls, and leucocytosis was strongly associated with younger age, deep breathing, severe anaemia, thrombocytopenia and death. The WCC was not associated with a positive blood culture. In children with malaria, high lymphocyte and low monocyte counts were independently associated with mortality. A platelet count of less than 150 x 109/l was found in 56.7% of children with malaria, and was associated with age, prostration and parasite density, but not with bleeding problems or mortality. The mean platelet volume was also higher in children with malaria compared with other medical conditions. This may reflect early release from the bone marrow in response to peripheral platelet destruction. Thus, leucocytosis was associated with both severity and mortality in children with falciparum malaria, irrespective of bacteraemia, whereas thrombocytopenia, although very common, was not associated with adverse outcome.",
"title": "Changes in white blood cells and platelets in children with falciparum malaria: relationship to disease outcome."
},
{
"docid": "25938221",
"text": "A specific retinopathy has been described in African children with cerebral malaria, but in adults this has not been extensively studied. Since the structure and function of the retinal vasculature greatly resembles the cerebral vasculature, study of retinal changes can reveal insights into the pathophysiology of cerebral malaria. A detailed observational study of malarial retinopathy in Bangladeshi adults was performed using high-definition portable retinal photography. Retinopathy was present in 17/27 adults (63%) with severe malaria and 14/20 adults (70%) with cerebral malaria. Moderate or severe retinopathy was more frequent in cerebral malaria (11/20, 55%) than in uncomplicated malaria (3/15, 20%; P=0.039), bacterial sepsis (0/5, 0%; P=0.038) or healthy controls (0/18, 0%; P<0.001). The spectrum of malarial retinopathy was similar to that previously described in African children, but no vessel discolouration was observed. The severity of retinal whitening correlated with admission venous plasma lactate (P=0.046), suggesting that retinal ischaemia represents systemic ischaemia. In conclusion, retinal changes related to microvascular obstruction were common in adults with severe falciparum malaria and correlated with disease severity and coma, suggesting that a compromised microcirculation has important pathophysiological significance in severe and cerebral malaria. Portable retinal photography has potential as a valuable tool to study malarial retinopathy.",
"title": "The spectrum of retinopathy in adults with Plasmodium falciparum malaria"
},
{
"docid": "17168045",
"text": "BACKGROUND This study sought to describe and quantify microcirculatory changes in the mucosal surfaces of patients with severe malaria, by direct in vivo observation using orthogonal polarization spectral (OPS) imaging. METHODS The microcirculation in the rectal mucosa of adult patients with severe malaria was assessed by use of OPS imaging, at admission and then daily. Comparison groups comprised patients with uncomplicated falciparum malaria, patients with bacterial sepsis, and healthy individuals. RESULTS Erythrocyte velocities were measured directly in 43 adult patients with severe falciparum malaria, of whom 20 died. Microcirculatory blood flow was markedly disturbed, with heterogeneous obstruction that was proportional to severity of disease. Blocked capillaries were found in 29 patients (67%) and were associated with concurrent hyperdynamic blood flow (erythrocyte velocity, >750 mm/s) in adjacent vessels in 27 patients (93%). The proportion of blocked capillaries correlated with the base deficit in plasma and with the concentration of lactate. Abnormalities disappeared when the patients recovered. In healthy individuals and in patients with uncomplicated malaria or sepsis, no stagnant erythrocytes were detected, and, in patients with sepsis, hyperdynamic blood flow was prominent. CONCLUSION Patients with severe falciparum malaria show extensive microvascular obstruction that is proportional to the severity of the disease. This finding underscores the prominent role that microvascular obstruction plays in the pathophysiology of severe malaria and illustrates the fundamental difference between the microvascular pathophysiology of malaria and that of bacterial sepsis.",
"title": "Direct in vivo assessment of microcirculatory dysfunction in severe falciparum malaria."
},
{
"docid": "3929361",
"text": "BACKGROUND Malaria elimination requires a variety of approaches individually optimized for different transmission settings. A recent field study in an area of low seasonal transmission in South West Cambodia demonstrated dramatic reductions in malaria parasite prevalence following both mass drug administration (MDA) and high treatment coverage of symptomatic patients with artemisinin-piperaquine plus primaquine. This study employed multiple combined strategies and it was unclear what contribution each made to the reductions in malaria. METHOD AND FINDINGS A mathematical model fitted to the trial results was used to assess the effects of the various components of these interventions, design optimal elimination strategies, and explore their interactions with artemisinin resistance, which has recently been discovered in Western Cambodia. The modelling indicated that most of the initial reduction of P. falciparum malaria resulted from MDA with artemisinin-piperaquine. The subsequent continued decline and near elimination resulted mainly from high coverage with artemisinin-piperaquine treatment. Both these strategies were more effective with the addition of primaquine. MDA with artemisinin combination therapy (ACT) increased the proportion of artemisinin resistant infections, although much less than treatment of symptomatic cases with ACT, and this increase was slowed by adding primaquine. Artemisinin resistance reduced the effectiveness of interventions using ACT when the prevalence of resistance was very high. The main results were robust to assumptions about primaquine action, and immunity. CONCLUSIONS The key messages of these modelling results for policy makers were: high coverage with ACT treatment can produce a long-term reduction in malaria whereas the impact of MDA is generally only short-term; primaquine enhances the effect of ACT in eliminating malaria and reduces the increase in proportion of artemisinin resistant infections; parasite prevalence is a better surveillance measure for elimination programmes than numbers of symptomatic cases; combinations of interventions are most effective and sustained efforts are crucial for successful elimination.",
"title": "Optimising Strategies for Plasmodium falciparum Malaria Elimination in Cambodia: Primaquine, Mass Drug Administration and Artemisinin Resistance"
},
{
"docid": "13959707",
"text": "BACKGROUND Plasmodium falciparum malaria remains a major cause of illness and death in sub-Saharan Africa. Young children bear the brunt of the disease and though older children and adults suffer relatively fewer clinical attacks, they remain susceptible to asymptomatic P. falciparum infection. A better understanding of the host factors associated with immunity to clinical malaria and the ability to sustain asymptomatic P. falciparum infection will aid the development of improved strategies for disease prevention. METHODS AND FINDINGS Here we investigate whether full differential blood counts can predict susceptibility to clinical malaria among Kenyan children sampled at five annual cross-sectional surveys. We find that the ratio of monocytes to lymphocytes, measured in peripheral blood at the time of survey, directly correlates with risk of clinical malaria during follow-up. This association is evident among children with asymptomatic P. falciparum infection at the time the cell counts are measured (Hazard ratio (HR) = 2.7 (95% CI 1.42, 5.01, P = 0.002) but not in those without detectable parasitaemia (HR = 1.0 (95% CI 0.74, 1.42, P = 0.9). CONCLUSIONS We propose that the monocyte to lymphocyte ratio, which is easily derived from routine full differential blood counts, reflects an individual's capacity to mount an effective immune response to P. falciparum infection.",
"title": "The Ratio of Monocytes to Lymphocytes in Peripheral Blood Correlates with Increased Susceptibility to Clinical Malaria in Kenyan Children"
},
{
"docid": "40900567",
"text": "The multiplication rates and invasiveness of Plasmodium falciparum parasites isolated from adult Thai patients hospitalized with uncomplicated malaria (n=34) were compared with those from persons with severe malaria (n=42). To simulate severe malaria and control for host effects, the in vitro cultures were adjusted to 1% parasitemia and used the same red blood cell donor. P. falciparum isolates from persons with severe malaria had initial cycle multiplication rates in vitro that were 3-fold higher than those from uncomplicated malaria (median [95% confidence interval], 8.3 [7. 1-10.5] vs. 2.8 [1.7-3.9]; P=.001). Parasites causing severe malaria exhibited unrestricted red blood cell invasion, whereas those from uncomplicated malaria were restricted to a geometric mean of 40 (31%-53%) of red blood cells. P. falciparum parasites causing severe malaria were less selective and multiplied more at high parasitemias than those causing uncomplicated malaria.",
"title": "Parasite multiplication potential and the severity of Falciparum malaria."
},
{
"docid": "17925632",
"text": "We assessed monthly doses of tafenoquine for preventing Plasmodium vivax and multidrug-resistant P. falciparum malaria. In a randomized, double-blind, placebo-controlled study, 205 Thai soldiers received either a loading dose of tafenoquine 400 mg (base) daily for 3 days, followed by single monthly 400-mg doses (n = 104), or placebo (n = 101), for up to 5 consecutive months. In volunteers completing follow-up (96 tafenoquine and 91 placebo recipients), there were 22 P. vivax, 8 P. falciparum, and 1 mixed infection. All infections except 1 P. vivax occurred in placebo recipients, giving tafenoquine a protective efficacy of 97% for all malaria (95% confidence interval [CI], 82%-99%), 96% for P. vivax malaria (95% CI, 76%-99%), and 100% for P. falciparum malaria (95% CI, 60%-100%). Monthly tafenoquine was safe, well tolerated, and highly effective in preventing P. vivax and multidrug-resistant P. falciparum malaria in Thai soldiers during 6 months of prophylaxis.",
"title": "Efficacy of monthly tafenoquine for prophylaxis of Plasmodium vivax and multidrug-resistant P. falciparum malaria."
},
{
"docid": "27889071",
"text": "The high prevalence of microcytosis (defined here as mean cell haemoglobin<27 pg) with no other abnormality is a principal cause of confusion in screening for haemoglobin disorders. Here we report the results of a small pilot study aiming to resolve this confusion by routinely proceeding to plasma ferritin and HPLC assay, using the original sequestrene blood sample, when microcytosis is detected. Participants comprised a random sample of 1,302 people referred for a full blood count by their General Practitioner (GP) to the laboratory of a North London district general hospital serving a multi-ethnic inner-city population. Ethnicity was established by questionnaire. In North Europeans, microcytosis was present in 3% of males (half were iron-deficient) and 11% of females (most were iron-deficient). Among ethnic minorities, microcytosis was present in 35% of males (one tenth were iron-deficient), and 45% of females (less than half were iron-deficient): an exclusion diagnosis of \"probable alpha thalassaemia\" could be made in the remainder. We conclude that when microcytosis is present, routine further analysis of the original sequestrene sample by plasma ferritin assay and haemoglobinopathy screening could lead to a more efficient and cost-effective laboratory service for primary care and maternity services.",
"title": "Microcytosis, iron deficiency and thalassaemia in a multi-ethnic community: a pilot study."
},
{
"docid": "42373943",
"text": "BACKGROUND Malaria is considered as the main differential diagnosis of acute febrile illness in the tropics, and alteration of various hematological parameters has been observed in patients with malaria. AIM To ascertain if certain hematological parameters increase the probability of malaria in patients with acute febrile illnesses. SETTINGS AND DESIGN Hospital based, prospective cohort study. METHODS AND MATERIAL All consecutive in patients with fever of less than seven days in duration were included in the study. Patients where localizing cause for fever could be determined were excluded. Hematological parameters (Hemoglobin, Red cell distribution width (RDW), Leukocyte count, and platelet counts) were determined by using automated counter, and peripheral smear examination for malarial parasite was taken as gold standard for the diagnosis of malaria. STATISTICAL ANALYSIS USED Diagnostic accuracy was measured by computing sensitivity, specificity, predictive values and likelihood ratios. The precision of these estimates was evaluated using 95% confidence intervals. RESULTS AND CONCLUSIONS A total of 184 patients were included in the study and 70 (38%) had a positive peripheral smear for malarial parasite. Thrombocytopenia alone (platelet countless than 150,000/mm3) was a predictor for malaria (Sn 60%, Sp 88%, LR+ 5.04) and in combination with anemia (Hb < 10 g/dl) it was next best parameter (Sn 69%, Sp 74%, LR+ 2.77). RDW and leukocyte count were not predictive. The conclusion of this study is that the presence of thrombocytopenia in a patient with acute febrile illness increases the probability of malarial infection.",
"title": "Can hematological parameters discriminate malaria from nonmalarious acute febrile illness in the tropics?"
},
{
"docid": "1805641",
"text": "BACKGROUND Artemisinin derivatives used in recently introduced combination therapies (ACTs) for Plasmodium falciparum malaria significantly lower patient infectiousness and have the potential to reduce population-level transmission of the parasite. With the increased interest in malaria elimination, understanding the impact on transmission of ACT and other antimalarial drugs with different pharmacodynamics becomes a key issue. This study estimates the reduction in transmission that may be achieved by introducing different types of treatment for symptomatic P. falciparum malaria in endemic areas. METHODS AND FINDINGS We developed a mathematical model to predict the potential impact on transmission outcomes of introducing ACT as first-line treatment for uncomplicated malaria in six areas of varying transmission intensity in Tanzania. We also estimated the impact that could be achieved by antimalarials with different efficacy, prophylactic time, and gametocytocidal effects. Rates of treatment, asymptomatic infection, and symptomatic infection in the six study areas were estimated using the model together with data from a cross-sectional survey of 5,667 individuals conducted prior to policy change from sulfadoxine-pyrimethamine to ACT. The effects of ACT and other drug types on gametocytaemia and infectiousness to mosquitoes were independently estimated from clinical trial data. Predicted percentage reductions in prevalence of infection and incidence of clinical episodes achieved by ACT were highest in the areas with low initial transmission. A 53% reduction in prevalence of infection was seen if 100% of current treatment was switched to ACT in the area where baseline slide-prevalence of parasitaemia was lowest (3.7%), compared to an 11% reduction in the highest-transmission setting (baseline slide prevalence = 57.1%). Estimated percentage reductions in incidence of clinical episodes were similar. The absolute size of the public health impact, however, was greater in the highest-transmission area, with 54 clinical episodes per 100 persons per year averted compared to five per 100 persons per year in the lowest-transmission area. High coverage was important. Reducing presumptive treatment through improved diagnosis substantially reduced the number of treatment courses required per clinical episode averted in the lower-transmission settings although there was some loss of overall impact on transmission. An efficacious antimalarial regimen with no specific gametocytocidal properties but a long prophylactic time was estimated to be more effective at reducing transmission than a short-acting ACT in the highest-transmission setting. CONCLUSIONS Our results suggest that ACTs have the potential for transmission reductions approaching those achieved by insecticide-treated nets in lower-transmission settings. ACT partner drugs and nonartemisinin regimens with longer prophylactic times could result in a larger impact in higher-transmission settings, although their long term benefit must be evaluated in relation to the risk of development of parasite resistance.",
"title": "Modelling the Impact of Artemisinin Combination Therapy and Long-Acting Treatments on Malaria Transmission Intensity"
},
{
"docid": "6503185",
"text": "Plasmodium falciparum malaria, an infectious disease caused by a parasitic protozoan, claims the lives of nearly a million children each year in Africa alone and is a top public health concern. Evidence is accumulating that resistance to artemisinin derivatives, the frontline therapy for the asexual blood stage of the infection, is developing in southeast Asia. Renewed initiatives to eliminate malaria will benefit from an expanded repertoire of antimalarials, including new drugs that kill circulating P. falciparum gametocytes, thereby preventing transmission. Our current understanding of the biology of asexual blood-stage parasites and gametocytes and the ability to culture them in vitro lends optimism that high-throughput screenings of large chemical libraries will produce a new generation of antimalarial drugs. There is also a need for new therapies to reduce the high mortality of severe malaria. An understanding of the pathophysiology of severe disease may identify rational targets for drugs that improve survival.",
"title": "Malaria biology and disease pathogenesis: insights for new treatments"
},
{
"docid": "20761364",
"text": "Artemisinins are peroxidic antimalarial drugs known to be very potent but highly chemically unstable; they degrade in the presence of ferrous iron, Fe(II)-heme, or biological reductants. Less documented is how this translates into chemical stability and antimalarial activity across a range of conditions applying to in vitro testing and clinical situations. Dihydroartemisinin (DHA) is studied here because it is an antimalarial drug on its own and the main metabolite of other artemisinins. The behaviors of DHA in phosphate-buffered saline, plasma, or erythrocyte lysate at different temperatures and pH ranges were examined. The antimalarial activity of the residual drug was evaluated using the chemosensitivity assay on Plasmodium falciparum, and the extent of decomposition of DHA was established through use of high-performance liquid chromatography with electrochemical detection analysis. The role of the Fe(II)-heme was investigated by blocking its reactivity using carbon monoxide (CO). A significant reduction in the antimalarial activity of DHA was seen after incubation in plasma and to a lesser extent in erythrocyte lysate. Activity was reduced by half after 3 h and almost completely abolished after 24 h. Serum-enriched media also affected DHA activity. Effects were temperature and pH dependent and paralleled the increased rate of decomposition of DHA from pH 7 upwards and in plasma. These results suggest that particular care should be taken in conducting and interpreting in vitro studies, prone as their results are to experimental and drug storage conditions. Disorders such as fever, hemolysis, or acidosis associated with malaria severity may contribute to artemisinin instability and reduce their clinical efficacy.",
"title": "Stability of the antimalarial drug dihydroartemisinin under physiologically relevant conditions: implications for clinical treatment and pharmacokinetic and in vitro assays."
},
{
"docid": "2264455",
"text": "There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates.",
"title": "Vaccines against malaria"
},
{
"docid": "37205685",
"text": "Malaria resistant to chloroquine has now been confirmed in more than 40 countries. The drug was introduced in 1934, but was not in large-scale use until the early 1950s. Anecdotal reports suggest that resistance emerged as early as 1957 both in Colombia and along the then Cambodia-Thailand border area. But by 1960, resistance in these areas was confirmed - and may represent two separate events. Resistance spread rapidly, with a new focus of resistance confirmed in East Africa by 1977. Chloroquine resistance represents a severe problem both for prophylaxis and treatment of malaria. In this aricle, David Payne traces the spread of resistance and discusses some of its implications.",
"title": "Spread of chloroquine resistance in Plasmodium falciparum."
},
{
"docid": "12409683",
"text": "BACKGROUND Artemisinin combination therapies (ACT), which are increasingly being introduced for treatment of Plasmodium falciparum malaria, are more effective against sexual stage parasites (gametocytes) than previous first-line antimalarials and therefore have the potential to reduce parasite transmission. The size of this effect is estimated in symptomatic P. falciparum infections. METHODS Data on 3,174 patients were pooled from six antimalarial trials conducted in The Gambia and Kenya. Multivariable regression was used to investigate the role of ACT versus non-artemisinin antimalarial treatment, treatment failure, presence of pre-treatment gametocytes and submicroscopic gametocytaemia on transmission to mosquitoes and the area under the curve (AUC) of gametocyte density during the 28 days of follow up. RESULTS ACT treatment was associated with a significant reduction in the probability of being gametocytaemic on the day of transmission experiments (OR 0.20 95% CI 0.16-0.26), transmission to mosquitoes by slide-positive gametocyte carriers (OR mosquito infection 0.49 95% CI 0.33-0.73) and AUC of gametocyte density (ratio of means 0.35 95% CI 0.31-0.41). Parasitological treatment failure did not account for the difference between ACT and non-artemisinin impact. The presence of slide-positive gametocytaemia prior to treatment significantly reduced ACT impact on gametocytaemia (p < 0.001). Taking account of submicroscopic gametocytaemia reduced estimates of ACT impact in a high transmission setting in Kenya, but not in a lower transmission setting in the Gambia. CONCLUSION Treatment with ACT significantly reduces infectiousness of individual patients with uncomplicated falciparum malaria compared to previous first line treatments. Rapid treatment of cases before gametocytaemia is well developed may enhance the impact of ACT on transmission.",
"title": "Reduction of transmission from malaria patients by artemisinin combination therapies: a pooled analysis of six randomized trials"
},
{
"docid": "4336849",
"text": "CHLOROQUINE is thought to act against falciparum malaria by accumulating in the acid vesicles of the parasite and interfering with their function14. Parasites resistant to chloroquine expel the drug rapidly in an unaltered form, thereby reducing levels of accumulation in the vesicles5. The discovery that verapamil partially reverses chloroquine resistance in vitro 6 led to the proposal that efflux may involve an ATP-driven P-glycoprotein pump similar to that in mammalian multidrug-resistant (mdr) tumor cell lines. Indeed, Plasmodium falciparum contains at least two mdr-like genes7,8, one of which has been suggested to confer the chloroquine resistant (CQR) phenotype7,9,10. To determine if either of these genes is linked to chloroquine resistance, we performed a genetic cross between CQR and chloroquine-susceptible (CQS) clones of P. falciparum. Examination of 16 independent recombinant progeny indicated that the rapid efflux phenotype is controlled by a single gene or a closely linked group of genes. But, there was no linkage between the rapid efflux, CQR phenotype and either of the mdr-like P. falciparum genes or amplification of those genes. These data indicate that the genetic locus governing chloroquine efflux and resistance is independent of the known mdr-like genes.",
"title": "Chloroquine resistance not linked to mdr-like genes in a Plasmodium falciparum cross"
},
{
"docid": "8373753",
"text": "The seasonal dynamics and spatial distributions of Anopheles mosquitoes and Plasmodium falciparum parasites were studied for one year at 30 villages in Malindi, Kilifi, and Kwale Districts along the coast of Kenya. Anopheline mosquitoes were sampled inside houses at each site once every two months and malaria parasite prevalence in local school children was determined at the end of the entomologic survey. A total of 5,476 Anopheles gambiae s.l. and 3,461 An. funestus were collected. Species in the An. gambiae complex, identified by a polymerase chain reaction, included 81.9% An. gambiae s.s., 12.8% An. arabiensis, and 5.3% An. merus. Anopheles gambiae s.s. contributed most to the transmission of P. falciparum along the coast as a whole, while An. funestus accounted for more than 50% of all transmission in Kwale District. Large spatial heterogeneity of transmission intensity (< 1 up to 120 infective bites per person per year) resulted in correspondingly large and significantly related variations in parasite prevalence (range = 38-83%). Thirty-two percent of the sites (7 of 22 sites) with malaria prevalences ranging from 38% to 70% had annual entomologic inoculation rates (EIR) less than five infective bites per person per year. Anopheles gambiae s.l. and An. funestus densities in Kwale were not significantly influenced by rainfall. However, both were positively correlated with rainfall one and three months previously in Malindi and Kilifi Districts, respectively. These unexpected variations in the relationship between mosquito populations and rainfall suggest environmental heterogeneity in the predominant aquatic habitats in each district. One important conclusion is that the highly non-linear relationship between EIRs and prevalence indicates that the consistent pattern of high prevalence might be governed by substantial variation in transmission intensity measured by entomologic surveys. The field-based estimate of entomologic parameters on a district level does not provide a sensitive indicator of transmission intensity in this study.",
"title": "Spatial and temporal heterogeneity of Anopheles mosquitoes and Plasmodium falciparum transmission along the Kenyan coast."
},
{
"docid": "10617916",
"text": "Background. Artemisinin-based combination therapy (ACT) reduces microscopically confirmed gametocytemia and mosquito infection. However, molecular techniques have recently revealed high prevalences of submicroscopic gametocytemia. Our objective here was to determine the effect of sulfadoxine-pyrimethamine (SP) monotherapy and treatment with SP plus amodiaquine (AQ), SP plus artesunate (AS), and artemether-lumefantrine (AL; Coartem) on submicroscopic gametocytemia and infectiousness. Methods. Kenyan children (n=528) 6 months-10 years of age were randomized to 4 treatment arms. Gametocytemia was determined by both microscopy and Pfs25 RNA-based quantitative nucleic acid sequence-based amplification (Pfs25 QT-NASBA). Transmission was determined by membrane-feeding assays. Results. Gametocyte prevalence, as determined by Pfs25 QT-NASBA, was 89.4% (219/245) at enrollment and decreased after treatment with SP plus AS, SP plus AQ, and AL. Membrane-feeding assays for a group of randomly selected children revealed that the proportion of infectious children was as much as 4-fold higher than expected when based on microscopy. ACT did not significantly reduce the proportion of infectious children but did reduce the proportion of infected mosquitoes. Conclusions. Submicroscopic gametocytemia is common after treatment and contributes considerably to mosquito infection. Our findings should be interpreted in the context of transmission intensity, but the effect of ACT on malaria transmission appears to be moderate and restricted to the duration of gametocyte carriage and the proportion of mosquitoes that are infected by carriers.",
"title": "Moderate effect of artemisinin-based combination therapy on transmission of Plasmodium falciparum."
},
{
"docid": "25069745",
"text": "OBJECTIVE To describe the epidemiology of urban malaria, an emerging problem in sub-Saharan Africa. METHOD Cross-sectional surveys of communities in Accra and Kumasi, Ghana, determining risk factors for malaria infection and anaemia in children aged 6-60 months. RESULTS Malaria prevalence rates ranged from 2% to 33% between urban communities. 47.1% of children were anaemic (Hb<11.0 g/dl). Factors associated with malaria prevalence were low socio-economic status, age and anaemia. The attributable risks of anaemia and severe anaemia (Hb<8.0 g/dl) caused by malaria were 5% and 23% respectively. CONCLUSIONS Malaria in urban areas displayed a heterogeneity and complexity that differed from the rural environment, which has important implications for malaria control. Marked intra-city variation indicates the importance of targeting specific areas or districts. The most vulnerable group, the urban poor, should be prioritized when designing control measures. This would require careful assessment of the malaria risk pattern in any city to guide an integrated control program.",
"title": "Urban malaria and anaemia in children: a cross-sectional survey in two cities of Ghana."
},
{
"docid": "14806256",
"text": "CONTEXT Use of antiretroviral drugs, including protease inhibitors, for treatment of human immunodeficiency virus (HIV) infection has been anecdotally associated with hepatotoxicity, particularly in persons coinfected with hepatitis C or B virus. OBJECTIVES To ascertain if incidence of severe hepatotoxicity during antiretroviral therapy is similar for all antiretroviral drug combinations, and to define the role of chronic viral hepatitis in its development. DESIGN Prospective cohort study. SETTING University-based urban HIV clinic. PATIENTS A total of 298 patients who were prescribed new antiretroviral therapies between January 1996 and January 1998, 211 (71%) of whom received protease inhibitors as part of combination therapy (median follow-up, 182 days) and 87 (29%) of whom received dual nucleoside analog regimens (median follow-up, 167 days). Chronic hepatitis C and B virus infection was present in 154 (52%) and 8 (2.7%) patients, respectively. MAIN OUTCOME MEASURE Severe hepatotoxicity, defined as a grade 3 or 4 change in levels of serum alanine aminotransferase and aspartate aminotransferase, evaluated before and during therapy. RESULTS Severe hepatotoxicity was observed in 31 (10.4%) of 298 patients (95% confidence interval [CI], 7.2%-14.4%). Ritonavir use was associated with a higher incidence of toxicity (30%; 95% CI, 17.9% -44.6%). However, no significant difference was detected in hepatotoxicity incidence in other treatment groups, ie, nucleoside analogs (5.7%; 95% CI, 1.2%-12.9%), nelfinavir (5.9%; 95% CI, 1.2%-16.2%), saquinavir (5.9%; 95% CI, 0.15%-28.7%), and indinavir(6.8%; 95% CI, 3.0%-13.1 %). Although chronicviral hepatitis was associated with an increased risk of severe hepatotoxicity among patients prescribed nonritonavir regimens (relative risk, 3.7; 95% CI, 1.0-11.8), most patients with chronic hepatitis C or B virus infection (88%) did not experience significant toxic effects. Rate of severe toxicity with use of any protease inhibitor in patients with hepatitis C infection was 12.2% (13/107; 95% CI, 6.6%-19.9%). In multivariate logistic regression, only ritonavir (adjusted odds ratio [AOR], 8.6; 95% CI, 3.0-24.6) and a CD4 cell count increase of more than 0.05 x 10(9)/L (AOR, 3.6; 95% CI, 1.0-12.9) were associated with severe hepatotoxicity. No irreversible outcomes were seen in patients with severe hepatotoxicity. CONCLUSIONS Our data indicate that use of ritonavir may increase risk of severe hepatotoxicity. Although hepatotoxicity may be more common in persons with chronic viral hepatitis, these data do not support withholding protease inhibitor therapy from persons coinfected with hepatitis B or C virus.",
"title": "Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection."
},
{
"docid": "18344910",
"text": "Objectives. To evaluate the predictive value of thrombocytopenia in malaria. Patients and Methods. It was a prospective observational study on all febrile patients with thrombocytopenia presenting to the Medical Unit of Hayat Abad Medical Complex during November 2008 to November 2010. Results. Of the total of 228 patients with fever and thrombocytopenia, 121 patients (53%) proved to be suffering from malaria. Of them 82 patients (68%) had falciparum malaria while 39 patients (32%) had vivax infection. Of these 121 patients, platelet counts ranged between 25,000 and 150,000/dL with a mean value of 101,000/dL (SD ± 47, 500) and a median of 75,000/dL. Of the 107 patients who were not suffering from malaria, the counts ranged between 10,000 and 150,000/dL with a mean value of 58,000/dL (SD ± 54, 000) and median of 50,000/dL. Conclusions. The presence of thrombocytopenia may be a predictor of malaria in adult population.",
"title": "Thrombocytopenia as an Indicator of Malaria in Adult Population"
},
{
"docid": "45218443",
"text": "The hemoglobinopathies are probably the world's most common genetic diseases: The World Health Organization has estimated that at least 5% of the population are carriers for one or other of the most serious forms, the alpha- and beta-thalassemias and the structural variant hemoglobins S, C, and E, which are found at polymorphic frequencies in many countries. All these hemoglobinopathies are believed to provide protection against malaria, and it is thought that, in malarial regions of the world, natural selection has been responsible for elevating and maintaining their gene frequencies, an idea first proposed 50 years ago by J.B.S. Haldane. Epidemiological studies undertaken in the 1950s on hemoglobin S in Africa provided support for the \"malaria hypothesis,\" but until recently it has proved extremely difficult to verify it for the thalassemias. The application of molecular methods has, however, provided new opportunities to address this old question. Population and molecular genetic analysis of thalassemia variants, and microepidemiological studies of the relationship between alpha-thalassemia and malaria in the southwest Pacific, have provided unequivocal evidence for protection. Surprisingly, some of this protection appears to derive from enhanced susceptibility in very young thalassemic children to both Plasmodium falciparum and, especially, P. vivax, and this early exposure appears to provide the basis for better protection in later life.",
"title": "Thalassemia and malaria: new insights into an old problem."
},
{
"docid": "17077004",
"text": "OBJECTIVES To explore the association between a stable partnership and clinical outcome in HIV infected patients receiving highly active antiretroviral therapy (HAART). DESIGN Prospective cohort study of adults with HIV (Swiss HIV cohort study). SETTING Seven outpatient clinics throughout Switzerland. PARTICIPANTS The 3736 patients in the cohort who started HAART before 2002 (median age 36 years, 29% female, median follow up 3.6 years). MAIN OUTCOME MEASURES Time to AIDS or death (primary endpoint), death alone, increases in CD4 cell count of at least 50 and 100 above baseline, optimal viral suppression (a viral load below 400 copies/ml), and viral rebound. RESULTS During follow up 2985 (80%) participants reported a stable partnership on at least one occasion. When starting HAART, 52% (545/1042) of participants reported a stable partnership; after five years of follow up 46% (190/412) of participants reported a stable partnership. In an analysis stratified by previous antiretroviral therapy and clinical stage when starting HAART (US Centers for Disease Control and Prevention group A, B, or C), the adjusted hazard ratio for progression to AIDS or death was 0.79 (95% confidence interval 0.63 to 0.98) for participants with a stable partnership compared with those without. Adjusted hazards ratios for other endpoints were 0.59 (0.44 to 0.79) for progression to death, 1.15 (1.06 to 1.24) for an increase in CD4 cells of 100 counts/microl or more, and 1.06 (0.98 to 1.14) for optimal viral suppression. CONCLUSIONS A stable partnership is associated with a slower rate of progression to AIDS or death in HIV infected patients receiving HAART.",
"title": "Stable partnership and progression to AIDS or death in HIV infected patients receiving highly active antiretroviral therapy: Swiss HIV cohort study."
},
{
"docid": "17433284",
"text": "BACKGROUND According to willingness of the Ministry of Health, Iran and presence of appropriate conditions for disease elimination, national malaria control program decided to conduct a research to clarify malaria status in 2007 and to provide required information to perform the elimination program. This review is comprised of the basis of national malaria elimination program in vision of 2025, which was started in 2010. METHODS In this descriptive study, data were analyzed by applications of different variables at district level. All districts in the three south eastern provinces, in which malaria has local transmission, were considered. Malaria cases has been determined and studied based on the national malaria surveillance system. RESULTS Since vivax malaria is predominant in Sistan & Baluchestan Province, number of vivax cases is equal to malaria positive cases approximately. The important point is that Nikshahr contains the maximum number of local vivax cases in this province and the maximum number of falciparum cases is reported from Sarbaz district. Among all districts of Hormozgan Province, no case of autochthonous falciparum was detected except in Bandar Jask and one case in Minab. There was no case of autochthonous falciparum in Kerman Province, except in Kahnoj and Ghale Ganj that each of them had one case in 2007. CONCLUSION It appears that the report of locally transmitted cases in Iran is increasing over the past few years, before starting malaria elimination plan. Since the Afghan refugees started to return to their own country so the main source of reporting of imported malaria cases reduced and local cases would be demonstrated more clearly.",
"title": "Determination of Malaria Epidemiological Status in Iran’s Malarious Areas as Baseline Information for Implementation of Malaria Elimination Program in Iran"
},
{
"docid": "21479231",
"text": "RATIONALE The outcome of fully intermittent thrice-weekly antituberculosis treatment of various durations in HIV-associated tuberculosis is unclear. OBJECTIVES To compare the efficacy of an intermittent 6-month regimen (Reg6M: 2EHRZ(3)/4HR(3) [ethambutol, 1,200 mg; isoniazid, 600 mg; rifampicin, 450 or 600 mg depending on body weight <60 or > or =60 kg; and pyrazinamide, 1,500 mg for 2 mo; followed by 4 mo of isoniazid and rifampicin at the same doses]) versus a 9-month regimen (Reg9M: 2EHRZ(3)/7HR(3)) in HIV/tuberculosis (TB). METHODS HIV-infected patients with newly diagnosed pulmonary or extrapulmonary TB were randomly assigned to Reg6M (n = 167) or Reg9M (n = 160) and monitored by determination of clinical, immunological, and bacteriological parameters for 36 months. Primary outcomes included favorable responses at the end of treatment and recurrences during follow-up, whereas the secondary outcome was death. Intent-to-treat and on-treatment analyses were performed. All patients were antiretroviral treatment-naive during treatment. MEASUREMENTS AND MAIN RESULTS Of the patients, 70% had culture-positive pulmonary TB; the median viral load was 155,000 copies/ml and the CD4(+) cell count was 160 cells/mm(3). Favorable response to antituberculosis treatment was similar by intent to treat (Reg6M, 83% and Reg9M, 76%; P = not significant). Bacteriological recurrences occurred significantly more often in Reg6M than in Reg9M (15 vs. 7%; P < 0.05) although overall recurrences were not significantly different (Reg6M, 19% vs. Reg9M, 13%). By 36 months, 36% of patients undergoing Reg6M and 35% undergoing Reg9M had died, with no significant difference between regimens. All 19 patients who failed treatment developed acquired rifamycin resistance (ARR), the main risk factor being baseline isoniazid resistance. CONCLUSIONS Among antiretroviral treatment-naive HIV-infected patients with TB, a 9-month regimen resulted in a similar outcome at the end of treatment but a significantly lower bacteriological recurrence rate compared with a 6-month thrice-weekly regimen. ARR was high with these intermittent regimens and neither mortality nor ARR was altered by lengthening TB treatment. Clinical Trials Registry Information: ID# NCT00376012 registered at www.clinicaltrials.gov.",
"title": "Efficacy of a 6-month versus 9-month intermittent treatment regimen in HIV-infected patients with tuberculosis: a randomized clinical trial."
},
{
"docid": "1173667",
"text": "Experience gained from the Global Malaria Eradication Program (1955-72) identified a set of shared technical and operational factors that enabled some countries to successfully eliminate malaria. Spatial data for these factors were assembled for all malaria-endemic countries and combined to provide an objective, relative ranking of countries by technical, operational, and combined elimination feasibility. The analysis was done separately for Plasmodium falciparum and Plasmodium vivax, and the limitations of the approach were discussed. The relative rankings suggested that malaria elimination would be most feasible in countries in the Americas and Asia, and least feasible in countries in central and west Africa. The results differed when feasibility was measured by technical or operational factors, highlighting the different types of challenge faced by each country. The results are not intended to be prescriptive, predictive, or to provide absolute assessments of feasibility, but they do show that spatial information is available to facilitate evidence-based assessments of the relative feasibility of malaria elimination by country that can be rapidly updated.",
"title": "Ranking of elimination feasibility between malaria-endemic countries"
},
{
"docid": "2526777",
"text": "Falciparum malaria kills, and it particularly kills the rural poor. Artemisinin derivatives, such as artesunate, are a vital component of Plasmodium falciparum malaria treatment and control in the face of globally increasing antimalarial drug resistance. Since 1998 a worsening epidemic of sophisticated counterfeit “artesunate” tablets (containing no artesunate) has plagued mainland Southeast Asia (see Figure S1). In some countries, most of the available artesunate is fake [ 1–5]. Artemisinin derivatives are remarkably rapid in their antimalarial effects, and they are very well tolerated. So where these medicines are available, they are sought after. But as they are relatively expensive, a demand is created for cheaper versions amongst the poorest and most vulnerable people, upon whom the counterfeiters have preyed–with fatal results.",
"title": "Manslaughter by Fake Artesunate in Asia—Will Africa Be Next?"
},
{
"docid": "28806780",
"text": "Despite combination antiretroviral therapy (ART), HIV infected people have higher mortality than non-infected. Lower socioeconomic status (SES) predicts higher mortality in many chronic illnesses but data in people with HIV is limited. We evaluated 878 HIV infected individuals followed from 1995 to 2005. Cox proportional hazards for all-cause mortality were estimated for SES measures and other factors. Mixed effects analyses examined how SES impacts factors predicting death. The 200 who died were older, had lower CD4 counts, and higher viral loads (VL). Age, transmission category, education, albumin, CD4 counts, VL, hunger, and poverty predicted death in univariate analyses; age, CD4 counts, albumin, VL, and poverty in the multivariable model. Mixed models showed associations between (1) CD4 counts with education and hunger; (2) albumin with education, homelessness, and poverty; and (3) VL with education and hunger. SES contributes to mortality in HIV infected persons directly and indirectly, and should be a target of health policy in this population.",
"title": "Poverty, Hunger, Education, and Residential Status Impact Survival in HIV"
}
] |
PLAIN-646
|
baked beans
|
[
{
"docid": "MED-4509",
"text": "Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease. Some, but not all, studies have shown that soy protein intake decreases total and low-density lipoprotein cholesterol and triglycerides and increases high-density lipoprotein cholesterol. The objective of this meta-analysis was to examine the effect of soy protein supplementation on serum lipid levels in adults. English language articles were retrieved by searching MEDLINE (1966 to February 2005) and the bibliographies of the retrieved articles. A total of 41 randomized controlled trials in which isolated soy protein supplementation was the only intervention and the net changes in serum lipids during intervention were reported. Information on study design, sample size, participant characteristics, intervention, follow-up duration, and treatment outcomes was independently abstracted using a standardized protocol. Using a random-effects model, data from each study were pooled and weighted by the inverse of their variance. Soy protein supplementation was associated with a significant reduction in mean serum total cholesterol (-5.26 mg/dl, 95% confidence interval [CI] -7.14 to -3.38), low-density lipoprotein cholesterol (-4.25 mg/dl, 95% CI -6.00 to -2.50), and triglycerides (-6.26 mg/dl, 95% CI -9.14 to -3.38) and a significant increase in high-density lipoprotein cholesterol (0.77 mg/dl, 95% CI 0.20 to 1.34). Meta-regression analyses showed a dose-response relation between soy protein and isoflavone supplementation and net changes in serum lipids. These results indicate that soy protein supplementation reduces serum lipids among adults with or without hypercholesterolemia. In conclusion, replacing foods high in saturated fat, trans-saturated fat, and cholesterol with soy protein may have a beneficial effect on coronary risk factors.",
"title": "A meta-analysis of the effect of soy protein supplementation on serum lipids."
},
{
"docid": "MED-4510",
"text": "Background and Aims Studies evaluating the effect of legume consumption on cholesterol have focused on soybeans, however non-soy legumes, such as a variety of beans, peas, and some seeds, are commonly consumed in Western countries. We conducted a meta-analysis of randomized controlled trials evaluating the effects of non-soy legume consumption on blood lipids. Methods and Results Studies were retrieved by searching MEDLINE (from January 1966 through July 2009), EMBASE (from January 1980 to July 2009), and the Cochrane Collaboration's Central Register of Controlled Clinical Trials using the following terms as medical subject headings and keywords: fabaceae not soybeans not isoflavones and diet or dietary fiber and cholesterol or hypercholesterolemia or triglycerides or cardiovascular diseases. Bibliographies of all retrieved articles were also searched. From 140 relevant reports, 10 randomized clinical trials were selected which compared a non-soy legume diet to control, had a minimum duration of 3 weeks, and reported blood lipid changes during intervention and control. Data on sample size, participant characteristics, study design, intervention methods, duration, and treatment results were independently abstracted by 2 investigators using a standardized protocol. Data from 10 trials representing 268 participants were examined using a random-effects model. Pooled mean net change in total cholesterol for those treated with a legume diet compared to control was −11.8 mg/dL (95% confidence interval [CI], −16.1 to −7.5); mean net change in low density lipoprotein cholesterol was −8.0 mg/dL (95% CI, −11.4 to −4.6). Conclusion These results indicate that a diet rich in legumes other than soy decreases total and LDL cholesterol.",
"title": "Non-Soy Legume Consumption Lowers Cholesterol Levels: A Meta-Analysis of Randomized Controlled Trials"
}
] |
[
{
"docid": "MED-3138",
"text": "Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.",
"title": "Perceptions of flatulence from bean consumption among adults in 3 feeding studies"
},
{
"docid": "MED-4991",
"text": "BACKGROUND: Epidemiological studies have shown positive findings associated with legume consumption and measures of cardiovascular disease and obesity. However, few observational trials have examined beans as a separate food variable when determining associations with health parameters. OBJECTIVE: To determine the association of consuming beans on nutrient intakes and physiological parameters using the National Health and Examination Survey (NHANES) 1999-2002. METHODS: Using data from NHANES 1999-2002, a secondary analysis was completed with a reliable 24-hour dietary recall where three groups of bean consumers were identified (N = 1,475). We determined mean nutrient intakes and physiological values between bean consumers and non-consumers. Least square means, standard errors and ANOVA were calculated using appropriate sample weights following adjustment for age, gender, ethnicity and energy. RESULTS: Relative to non-consumers, bean consumers had higher intakes of dietary fiber, potassium, magnesium, iron, and copper (p's < 0.05). Those consuming beans had a lower body weight (p = 0.008) and a smaller waist size (p = 0.043) relative to non-consumers. Additionally, consumers of beans had a 23% reduced risk of increased waist size (p = 0.018) and a 22% reduced risk of being obese (p = 0.026). Also, baked bean consumption was associated with a lower systolic blood pressure. CONCLUSIONS: Bean consumers had better overall nutrient intake levels, better body weights and waist circumferences, and lower systolic blood pressure in comparison to non-consumers. These data support the benefits of bean consumption on improving nutrient intake and health parameters.",
"title": "Bean consumption is associated with greater nutrient intake, reduced systolic blood pressure, lower body weight, and a smaller waist circumference ..."
},
{
"docid": "MED-925",
"text": "We present a case of a six-week-old infant who developed life-threatening complications after unintentional sodium bicarbonate intoxication. Baking soda was being used by the mother as a home remedy to \"help the baby burp.\" A review of the literature regarding the use (or misuse) of baking soda follows. Our patient, along with the other noted case reports, emphasizes the need for warnings on baking soda products whose labels recommend its use as an antacid. Poisonings must be high in the differential diagnosis of any patient, regardless of age, who presents with altered mental status or status epilepticus.",
"title": "Baking soda: a potentially fatal home remedy."
},
{
"docid": "MED-2191",
"text": "The effects of baking and boiling on the nutritional and antioxidant properties of three sweet potato cultivars (Beniazuma, Koganesengan, Kotobuki) cultivated in Turkey were investigated. The samples were analyzed for proximate composition, total phenolic content, ascorbic acid, β-carotene, antiradical activity, and free sugars. The dry matter, protein, and starch contents of the sweet potatoes were significantly changed by the treatments while the ash and crude fiber contents did not differ as significantly. The β-carotene contents of baked and boiled sweet potatoes were lower than those of fresh sweet potatoes; however, the total phenolic and ascorbic acid contents of the baked and boiled sweet potatoes were higher than those of the fresh samples. Generally, the antiradical activity of the sweet potatoes increased with the treatments. Sucrose, glucose, and fructose were quantified as free sugars in all fresh sweet potatoes; however, maltose was determined in the treated samples. In terms of the analyzed parameters, there were no explicit differences among the sweet potato cultivars.",
"title": "Effects of baking and boiling on the nutritional and antioxidant properties of sweet potato [Ipomoea batatas (L.) Lam.] cultivars."
},
{
"docid": "MED-4782",
"text": "A survey of a broad range of chocolate- and cocoa-containing products marketed in the United States was conducted to provide a more detailed analysis of flavan-3-ol monomers, oligomers, and polymers, which can be grouped into a class of compounds called procyanidins. Samples consisted of the three or four top-selling products within the following six categories: natural cocoa powder, unsweetened baking chocolate, dark chocolate, semisweet baking chips, milk chocolate, and chocolate syrup. Composite samples were characterized for percent fat (% fat), percent nonfat cocoa solids (% NFCS), antioxidant level by ORAC, total polyphenols, epicatechin, catechin, total monomers, and flavan-3-ol oligomers and polymers (procyanidins). On a gram weight basis epicatechin and catechin content of the products follow in decreasing order: cocoa powder > baking chocolate > dark chocolate = baking chips > milk chocolate > chocolate syrup. Analysis of the monomer and oligomer profiles within product categories shows there are two types of profiles: (1) products that have high monomers with decreasing levels of oligomers and (2) products in which the level of dimers is equal to or greater than the monomers. Results show a strong correlation (R(2) = 0.834) of epicatechin to the level of % NFCS and also very good correlations for N = 2-5 oligomers to % NFCS. A weaker correlation was observed for catechin to % NFCS (R(2) = 0.680). Other analyses show a similar high degree of correlation with epicatechin and N = 2-5 oligomers to total polyphenols, with catechin being less well correlated to total polyphenols. A lesser but still good correlation exists between the calculated percent cacao (calcd % cacao) content, a proxy for percent cacao, and these same flavanol measures, with catechin again showing a lesser degree of correlation to calcd % cacao. Principal component analysis (PCA) shows that the products group discretely into five classes: (1) cocoa powder, (2) baking chocolate, (3) dark chocolate and semisweet chips, (4) milk chocolates, and (5) syrup. PCA also shows that most factors group closely together including the antioxidant activity, total polyphenols, and the flavan-3-ol measures with the exception of catechin and % fat in the product, which group separately. Because catechin distribution appears to be different from the other flavan-3-ol measures, an analysis of the epicatechin to catechin ratio was done, indicating there is a >5-fold variation in this measure across the products studied. The cocoa-containing products tested range from cocoa powder with 227.34 +/- 17.23 mg of procyanidins per serving to 25.75 +/- 9.91 mg of procyanidins per serving for chocolate syrup. These results are discussed with respect to other studies on commercial products, the bioavailability of the flavanols, and the possible role of processing on the amount of catechin in products.",
"title": "Survey of commercially available chocolate- and cocoa-containing products in the United States. 2. Comparison of flavan-3-ol content with nonfat co..."
},
{
"docid": "MED-924",
"text": "Oral ingestion of baking soda (sodium bicarbonate) has been used for decades as a home remedy for acid indigestion. Excessive bicarbonate ingestion places patients at risk for a variety of metabolic derangements including metabolic alkalosis, hypokalemia, hypernatremia, and even hypoxia. The clinical presentation is highly variable but can include seizures, dysrhythmias, and cardiopulmonary arrest. We present two cases of severe metabolic alkalosis in patients with unsuspected antacid overdose. The presentation and pathophysiology of antacid-related metabolic alkalosis is reviewed.",
"title": "Severe metabolic alkalosis due to baking soda ingestion: case reports of two patients with unsuspected antacid overdose."
},
{
"docid": "MED-3584",
"text": "Background: A high intake of white rice is associated with the metabolic syndrome and type 2 diabetes. Costa Ricans follow a staple dietary pattern that includes white rice and beans, yet the combined role of these foods on cardiometabolic risk factors has not been studied. Objective: We aimed to determine the association between intake of white rice and beans and the metabolic syndrome and its components in Costa Rican adults (n = 1879) without diabetes. Design: Multivariate-adjusted means were calculated for components of the metabolic syndrome by daily servings of white rice and beans (<1, 1, or >1) and by the ratio of beans to white rice. The OR for the metabolic syndrome was calculated by substituting one serving of beans for one serving of white rice. Results: An increase in daily servings of white rice was positively associated with systolic blood pressure (BP), triglycerides, and fasting glucose and inversely associated with HDL cholesterol (P-trend <0.01 for all). An increase in servings of beans was inversely associated with diastolic BP (P = 0.049). Significant trends for higher HDL cholesterol and lower BP and triglycerides were observed for 1:3, 1:2, 1:1, and 2:1 ratios of beans to white rice. Substituting one serving of beans for one serving of white rice was associated with a 35% (95% CI: 15%, 50%) lower risk of the metabolic syndrome. Conclusion: Increasing the ratio of beans to white rice, or limiting the intake of white rice by substituting beans, may lower cardiometabolic risk factors.",
"title": "A higher ratio of beans to white rice is associated with lower cardiometabolic risk factors in Costa Rican adults"
},
{
"docid": "MED-2140",
"text": "Background Around the world, beans and rice are commonly consumed together as a meal. With type 2 diabetes increasing, the effect of this traditional diet pattern on glycemic response has not been studied fully. Methods We evaluated the glycemic response of bean and rice traditional meals compared to rice alone in adults with type 2 diabetes. Seventeen men and women with type 2 diabetes controlled by metformin (n = 14) or diet/exercise (n = 3) aged 35–70 years participated in the randomized 4 × 4 crossover trial. The white long grain rice control, pinto beans/rice, black beans/rice, red kidney beans/rice test meals, matched for 50 grams of available carbohydrate, were consumed at breakfast after a 12 hour fast. Capillary blood glucose concentrations at baseline and at 30 minute intervals up to 180 minutes postprandial were collected. MANOVA for repeated measures established glucose differences between treatments. Paired t tests identified differences between bean types and the rice control following a significant MANOVA. Results Postprandial net glucose values were significantly lower for the three bean/rice treatments in contrast to the rice control at 90, 120 and 150 minutes. Incremental area under the curve values were significantly lower for the pinto and black bean/rice meals compared to rice alone, but not for kidney beans. Conclusions Pinto, dark red kidney and black beans with rice attenuate the glycemic response compared to rice alone. Promotion of traditional foods may provide non-pharmaceutical management of type 2 diabetes and improve dietary adherence with cultural groups. Trial registration Clinical Trials number NCT01241253",
"title": "Bean and rice meals reduce postprandial glycemic response in adults with type 2 diabetes: a cross-over study"
},
{
"docid": "MED-2209",
"text": "This study investigated the effect of different traditional cooking methods on glycemic index (GI) and glycemic response of ten Sweet potato (Ipomoea batatas) cultivars commonly eaten in Jamaica. Matured tubers were cooked by roasting, baking, frying, or boiling then immediately consumed by the ten nondiabetic test subjects (5 males and 5 females; mean age of 27 ± 2 years). The GI varied between 41 ± 5–93 ± 5 for the tubers studied. Samples prepared by boiling had the lowest GI (41 ± 5–50 ± 3), while those processed by baking (82 ± 3–94 ± 3) and roasting (79 ± 4–93 ± 2) had the highest GI values. The study indicates that the glycemic index of Jamaican sweet potatoes varies significantly with the method of preparation and to a lesser extent on intravarietal differences. Consumption of boiled sweet potatoes could minimize postprandial blood glucose spikes and therefore, may prove to be more efficacious in the management of type 2 diabetes mellitus.",
"title": "Relationship between Processing Method and the Glycemic Indices of Ten Sweet Potato (Ipomoea batatas) Cultivars Commonly Consumed in Jamaica"
},
{
"docid": "MED-1880",
"text": "Legumes are the basés diet in several countries. They hold a high nutritional value, but other properties related to human health are nowadays being studied. The aim of this work was to study the influence of processes (boiling or germination) on the phenolic composition of dark beans (Phaseolus vulgaris L. c.v. Tolosana) and their effect on their antioxidant, neuroprotective and anticancer ability. Phenolic composition of raw and processed dark beans was analysed by HPLC-PAD and HPLC-ESI/MS. The antioxidant activity was evaluated by ORAC. Astrocytes cultures (U-373) have been used to test their neuroprotective effect. Anticancer activities were evaluated on three different cell lines (renal adenocarcinoma (TK-10), breast adenocarcinoma (MCF-7) and melanoma (UACC-62)) by sulphorhodamine B method. Qualitative and quantitative differences in phenolic composition have been observed between raw and processed dark beans that influence the antioxidant activity, mainly for germinated samples which show a decrease of antioxidant capacity. Although every assayed extracts decreased reactive oxygen species release and exhibited cytotoxicity activities on cancer cell lines, raw beans proved to be the most active in neuroprotective and antitumoral effects; this sample is especially rich in phenolic compounds, mainly anthocyanins. This study further demonstrated that phenolic composition of dark beans is related with cooking process and so with their neuroprotective and anticancer activity; cooking of dark beans improves their digestion and absorption at intestinal level, while maintaining its protective ability on oxidative process at cellular level. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Effect of cooking and germination on phenolic composition and biological properties of dark beans (Phaseolus vulgaris L.)."
},
{
"docid": "MED-3141",
"text": "OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.",
"title": "A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome."
},
{
"docid": "MED-5079",
"text": "OBJECTIVE: To determine effects of daily intake of 1/2 cup pinto beans, black-eyed peas or carrots (placebo) on risk factors for coronary heart disease (CHD) and diabetes mellitus (DM) in free-living, mildly insulin resistant adults over an 8 week period. METHODS: Randomized, crossover 3x3 block design. Sixteen participants (7 men, 9 women) received each treatment for eight-weeks with two-week washouts. Fasting blood samples collected at beginning and end of periods were analyzed for total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, triacylglycerols, high-sensitivity C-reactive protein, insulin, glucose, and hemoglobin A1c. RESULTS: A significant treatment-by-time effect impacted serum TC (p = 0.026) and LDL (p = 0.033) after eight weeks. Paired t-tests indicated that pinto beans were responsible for this effect (p = 0.003; p = 0.008). Mean change of serum TC for pinto bean, black-eyed pea and placebo were -19 +/- 5, 2.5 +/- 6, and 1 +/- 5 mg/dL, respectively (p = 0.011). Mean change of serum LDL-C for pinto bean, black-eyed pea and placebo were -14 +/- 4, 4 +/- 5, and 1 +/- 4 mg/dL, in that order (p = 0.013). Pinto beans differed significantly from placebo (p = 0.021). No significant differences were seen with other blood concentrations across the 3 treatment periods. CONCLUSIONS: Pinto bean intake should be encouraged to lower serum TC and LDL-C, thereby reducing risk for CHD.",
"title": "Pinto bean consumption reduces biomarkers for heart disease risk."
},
{
"docid": "MED-2570",
"text": "The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.",
"title": "In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ..."
},
{
"docid": "MED-4916",
"text": "Agaritine (N-(gamma-L(+)-glutamyl)-4-hydroxymethyl-phenylhydrazine) was identified and quantified by high-pressure liquid chromatography and used as a marker for the occurrence of phenylhydrazine derivatives in the cultivated Agaricus bitorquis and A. garicus hortensis mushrooms. Although relatively high levels of agaritine (around 700 mg kg(-1)) could be found in freshly harvested A. bitorquis from early flushes, samples from supermarkets contained less agaritine. The content of 28 samples varied between 165 and 457 mg kg(-1), on average being 272 +/- 69 mg kg(-1). The highest amounts of agaritine were found in the skin of the cap and in the gills, the lowest being in the stem. There was no significant difference in agaritine content of the two mushroom species in our study. Pronounced reduction in agaritine content was observed during storage of mushrooms in the refrigerator or freezer, as well as during drying of the mushrooms. The degree of reduction was dependent on the length and condition of storage and was usually in the region 20-75%. No reduction in agaritine content was observed during freeze-drying. Depending on the cooking procedure, household processing of cultivated Agaricus mushrooms reduced the agaritine content to various degrees. Boiling extracted around 50% of the agaritine content into the cooking broth within 5min and degraded 20-25% of the original agaritine content of the mushrooms. Prolonged boiling, as when preparing a sauce, reduced the content in the solid mushroom further (around 10% left after 2h). Dry baking of the cultivated mushroom, a process similar to pizza baking, reduced the agaritine content by approximately 25%, whereas frying in oil or butter or deep frying resulted in a more marked reduction (35-70%). Microwave processing of the cultivated mushrooms reduced the agaritine content to one-third of the original level. Thus, the exposure to agaritine was substantially less when consuming processed Agaricus mushrooms as compared with consuming the raw mushrooms. However, it is not yet known to what extent agaritine and other phenylhydrazine derivatives occurring in the cultivated mushroom are degraded into other biologically active compounds during the cooking procedure.",
"title": "Influence of storage and household processing on the agaritine content of the cultivated Agaricus mushroom."
},
{
"docid": "MED-3136",
"text": "The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.",
"title": "Influence of frequent and long-term bean consumption on colonic function and fermentation."
},
{
"docid": "MED-2147",
"text": "Consumption of Phaseolus vulgaris bean species such as pinto, black, navy or kidney may be beneficial in the prevention and treatment of chronic diseases. In particular, conditions that are promoted by increased glycaemic stress (hyperglycaemia and hyperinsulinaemia) including diabetes, CVD and cancer seem to be reduced in individuals who eat more of these beans. The present paper discusses the influence of P. vulgaris species on glycaemic response and the impact that relationship may have on the risk of developing diabetes, CVD and cancer.",
"title": "Phaseolus beans: impact on glycaemic response and chronic disease risk in human subjects."
},
{
"docid": "MED-2580",
"text": "Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.",
"title": "High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial"
},
{
"docid": "MED-2144",
"text": "Bean pods (Phaseolus vulgaris) are among the most widely used traditional remedies against diabetes mellitus. Historical knowledge is summarized and compared to recent study results. Reports dating from the first half of the 20(th) century as well as recent publications show contradictory results. It seems that Phaseolus preparations should not be considered the first choice in phytopharmaceutical treatment of diabetes or lead structure research. To be effective, fairly high doses of aqueous extracts need to be given. Because of their fiber content and an alpha-amylase inhibitory effect, beans might be more useful as food components in preventing or ameliorating type 2 diabetes.",
"title": "Beans and diabetes: Phaseolus vulgaris preparations as antihyperglycemic agents."
},
{
"docid": "MED-2010",
"text": "Legumes (including alfalfa, clover, lupins, green beans and peas, peanuts, soybeans, dry beans, broad beans, dry peas, chickpeas, and lentils) represent an important component of the human diet in several areas of the world, especially in the developing countries, where they complement the lack of proteins from cereals, roots, and tubers. In some regions of the world, legume seeds are the only protein supply in the diet. The health benefits of legume consumption have received rising interest from researchers, and their consumption and production extends worldwide. Among European countries, higher legume consumption is observed around the Mediterranean, with per capita daily consumption between 8 and 23 g, while in Northern Europe, the daily consumption is less than 5 g per capita. The physiological effects of different legumes vary significantly. These differences may result from the polysaccharides composition, in particular, the quantity and variety of dietary fibers and starch, protein make-up, and variability in phytochemical content. The majority of legumes contain phytochemicals: bioactive compounds, including enzyme inhibitors, phytohemagglutinins (lectins), phytoestrogens, oligosaccharides, saponins, and phenolic compounds, which play metabolic roles in humans who frequently consume these foods. Dietary intake of phytochemicals may provide health benefits, protecting against numerous diseases or disorders, such as coronary heart disease, diabetes, high blood pressure and inflammation. The synergistic or antagonistic effects of these phytochemical mixtures from food legumes, their interaction with other components of the diet, and the mechanism of their action have remained a challenge with regard to understanding the role of phytochemicals in health and diseases. Their mitigating effects and the mechanism of their action need to be further addressed if we are to understand the role of phytochemicals in health and diseases. This review provides an overview of the nutritional quality of legumes and their potential contribution in cardiometabolic risk prevention.",
"title": "Nutritional quality of legumes, and their role in cardiometabolic risk prevention: a review."
},
{
"docid": "MED-5078",
"text": "In this study, solid fermentation of steamed black soybean with various GRAS (Generally recognized as safe) filamentious-fungi including Aspergillus awamori, Aspergillus oryzae BCRC 30222, Aspergillus sojae BCRC 30103, Rhizopus azygosporus BCRC 31158 and Rhizopus sp. No. 2 was performed. Mutagenicity and antimutagenicity of the methanol extracts of unfermented and fermented steamed black soybeans against 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen and Benzo[a]pyrene (B[a]P), an indirect mutagen, on Salmonella Typhimurium TA100 and TA 98, were examined. The methanol extracts of unfermented and fermented steamed black soybeans show no mutagenic activity for either test strains at the doses tested. The extracts inhibited mutagenesis by either 4-NQO or B[a]P in S. Typhimurium TA100 and TA98. Fermentation with fungi also enhanced the antimutagenic effect of black soybean while the antimutagenic effect of the fermented black soybeans extract varied with the starter organism, mutagen, and test strain of S. Typhimurium examined. Generally, the extracts of A. awamori-fermented black soybean exhibited the highest antimutagenic effect. With strain TA100, the inhibitory effects of 5.0 mg of A. awamori-fermented black soybean extract per plate on the mutagenic effects of 4-NQO and B[a]P were 92% and 89%, respectively, while the corresponding rates for extract of unfermented were 41% and 63%, respectively. With strain 98, the inhibition rates were 94 and 81% for the fermented bean extract and 58% and 44% for the unfermented bean extracts. Testing of extracts prepared from black soybean by A. awamori at temperatures 25, 30 and 35 degrees C and for times of 1-5 days revealed that, generally, the extract prepared from beans fermented at 30 degrees C for 3 days exhibited the greatest inhibition against the mutagenic effects of 4-NQO and B[a]P.",
"title": "Mutagenic and antimutagenic effects of methanol extracts of unfermented and fermented black soybeans."
},
{
"docid": "MED-2141",
"text": "We investigated the association between dietary patterns and insulin resistance in the 3871 healthy Korean adults from the 2007 to 2008 Korea National Health and Nutrition Examination Survey. The whole grains and beans pattern was associated with lower prevalence of insulin resistance (OR for highest quintile=0.80, 95% CI=0.61-1.03, P for trend=0.013). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.",
"title": "High intake of whole grains and beans pattern is inversely associated with insulin resistance in healthy Korean adult population."
},
{
"docid": "MED-5080",
"text": "Bioactivity-guided fractionation of black bean (Phaseolus vulgaris) seed coats was used to determine the chemical identity of bioactive constituents, which showed potent antiproliferative and antioxidative activities. Twenty-four compounds including 12 triterpenoids, 7 flavonoids, and 5 other phytochemicals were isolated using gradient solvent fractionation, silica gel and ODS columns, and semipreparative and preparative HPLC. Their chemical structures were identified using MS, NMR, and X-ray diffraction analysis. Antiproliferative activities of isolated compounds against Caco-2 human colon cancer cells, HepG2 human liver cancer cells, and MCF-7 human breast cancer cells were evaluated. Among the compounds isolated, compounds 1, 2, 6, 7, 8, 13, 14, 15, 16, 19, and 20 showed potent inhibitory activities against the proliferation of HepG2 cells, with EC50 values of 238.8 +/- 19.2, 120.6 +/- 7.3, 94.4 +/- 3.4, 98.9 +/- 3.3, 32.1 +/- 6.3, 306.4 +/- 131.3, 156.9 +/- 11.8, 410.3 +/- 17.4, 435.9 +/- 47.7, 202.3 +/- 42.9, and 779.3 +/- 37.4 microM, respectively. Compounds 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 14, 15, 19, and 20 showed potent antiproliferative activities against Caco-2 cell growth, with EC50 values of 179.9 +/- 16.9, 128.8 +/- 11.6, 197.8 +/- 4.2, 105.9 +/- 4.7, 13.9 +/- 2.8, 35.1 +/- 2.9, 31.2 +/- 0.5, 71.1 +/- 11.9, 40.8 +/- 4.1, 55.7 +/- 8.1, 299.8 +/- 17.3, 533.3 +/- 126.0, 291.2 +/- 1.0, and 717.2 +/- 104.8 microM, respectively. Compounds 5, 7, 8, 9, 11, 19, 20 showed potent antiproliferative activities against MCF-7 cell growth in a dose-dependent manner, with EC50 values of 129.4 +/- 9.0, 79.5 +/- 1.0, 140.1 +/- 31.8, 119.0 +/- 7.2, 84.6 +/- 1.7, 186.6 +/- 21.1, and 1308 +/- 69.9 microM, respectively. Six flavonoids (compounds 14-19) showed potent antioxidant activity. These results showed the phytochemical extracts of black bean seed coats have potent antioxidant and antiproliferative activities.",
"title": "Phytochemicals of black bean seed coats: isolation, structure elucidation, and their antiproliferative and antioxidative activities."
},
{
"docid": "MED-926",
"text": "A case of severe metabolic alkalosis (MA) resulting from ingestion of baking soda (sodium bicarbonate) is presented. On admission to the emergency department, the patient was alert and stable with an initial examination that was remarkable only for carpopedal spasm. Shortly thereafter, the patient had a sudden, unexpected cardiopulmonary arrest. Following resuscitation, without administration of sodium bicarbonate, the arterial blood gas revealed a pH of 7.73, pO2 of 51 mm Hg, and pCO2 of 52 mm Hg. After admission to the intensive care unit, the patient's MA was corrected using IV 0.25 N hydrochloric acid. The patient remained comatose as a result of severe anoxic encephalopathy and died two weeks after admission. We believe this is the first reported case of severe MA resulting in sudden cardiopulmonary arrest in a previously ambulatory patient.",
"title": "Severe metabolic alkalosis in the emergency department."
},
{
"docid": "MED-3810",
"text": "The typical spices used in winter include nutmeg, cinnamon, clove and anise. These spices contain two groups of chemicals, the allylbenzenes and their isomers, the propenylbenzenes. It was suggested 40 years ago by Alexander Shulgin that these substances act as metabolic precursors of amphetamines. The biotransformation of these precursors to nitrogen-containing metabolites is reviewed. These reactions have not been reported in humans. Whether or not the pharmacology and toxicology of spices such as nutmeg can be explained on the basis of their allylbenzene or propenylbenzene content is speculative. Humans may be exposed to amphetamines derived from these precursors in forno, the formation during baking and cooking, for example in the preparation of Lebkuchen, or Christmas gingerbread. It is possible that this may be responsible, in part, for uplifting our mood in winter. However, the role of these aromatic substances, acting simply as odours, evoking old memories of winters past, cannot be ignored. Whether spices have a true pharmacological effect or they act as aromatherapy remains to be elucidated through clinical and laboratory studies.",
"title": "Christmas gingerbread (Lebkuchen) and Christmas cheer--review of the potential role of mood elevating amphetamine-like compounds formed in vivo and..."
},
{
"docid": "MED-884",
"text": "Approximately 75% of all kidney stones are composed primarily of calcium oxalate, and hyperoxaluria is a primary risk factor for this disorder. Nine types of raw and cooked vegetables were analyzed for oxalate using an enzymatic method. There was a high proportion of water-soluble oxalate in most of the tested raw vegetables. Boiling markedly reduced soluble oxalate content by 30-87% and was more effective than steaming (5-53%) and baking (used only for potatoes, no oxalate loss). An assessment of the oxalate content of cooking water used for boiling and steaming revealed an approximately 100% recovery of oxalate losses. The losses of insoluble oxalate during cooking varied greatly, ranging from 0 to 74%. Because soluble sources of oxalate appear to be better absorbed than insoluble sources, employing cooking methods that significantly reduce soluble oxalate may be an effective strategy for decreasing oxaluria in individuals predisposed to the development of kidney stones.",
"title": "Effect of different cooking methods on vegetable oxalate content."
},
{
"docid": "MED-2185",
"text": "Orange fleshed sweet potato (OFSP) has been identified as a good source of beta-carotene but the beta-carotene bioaccessibility is affected by processing. In this study, the effect of traditional heat processing methods on the microstructure and in vitro bioaccessibility of beta-carotene from OFSP were investigated. Bioaccessibility was determined using simulated in vitro digestion model followed by membrane filtration to separate the micellar fraction containing bioaccessible beta-carotene. Processing led to decrease in the amount of all-trans-beta-carotene and increase in 13-cis-beta-carotene. Processed OFSP had significantly higher (P < 0.05) bioaccessible beta-carotene compared to the raw forms. Bioaccessibility varied with processing treatments in the order; raw < baked < steamed/boiled < deep fried. Light microscopy showed that the microstructure of OFSP was disrupted by the processing methods employed. The cell walls of OFSP were sloughed by the traditional heat processing methods applied. The findings show that heat processing improves bioaccessibility of beta-carotene in OFSP and this was probably due to disruption of the tissue microstructure.",
"title": "Microstructure and in vitro beta carotene bioaccessibility of heat processed orange fleshed sweet potato."
},
{
"docid": "MED-3132",
"text": "Little is known about dietitians current practice in counselling clients about the use of legumes in a low fat, high fibre diet. An exploratory e-mail questionnaire was sent to members of Dietitians of Canada to assess: dietitian use and preferences for legumes, dietitian practice, opinions about clients attitudes and preferences, and resource needs. Counsellors (n=256) had high personal use of legumes (64% > or = 1 serving/week) and frequently recommended legumes in counselling. The legumes most preferred by respondents and their clients were: peanuts, kidney beans, split peas, chickpeas, and lentils. Respondents often recommended canned bean products (76%) and tofu (61%), but other legume grocery products were less often recommended. The most common client issues identified were: flatulence (87% agreed), lack of familiarity (85%), and knowledge of preparation (82%). Dietitians were not satisfied with current resources to support practice, especially those respondents providing primarily clinical counselling services. The most requested resources were: recipes (90%), pamphlets (82%), food demonstrations (75%) and Internet sites (63%). Client level research is now needed to confirm the importance of the issues identified and to develop and test strategies for legume promotion in counselling.",
"title": "Legume promotion in counselling: an e-mail survey of dietitians."
},
{
"docid": "MED-4053",
"text": "Heterocyclic amines (HCAs), potent mutagens and a risk factor for human cancers, are produced in meats cooked at high temperature. The aim of this study was to determine the HCA content in cooked meat products (beef, chicken, pork, fish) prepared by various cooking methods (pan frying, oven broiling, and oven baking at 170 to 230°C) that are preferred by U.S. meat consumers. The primary HCAs in these samples were PhIP (2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine) (1.49-10.89ng/g), MeIQx (2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline) (not detected-4.0ng/g), and DiMeIQx (2-amino-3,4,8-trimethyl-imidazo [4,5-f]quinoxaline) (not detected-3.57ng/g). Type and content of HCAs in cooked meat samples were highly dependent on cooking conditions. The total HCA content in well-done meat was 3.5 times higher than that of medium-rare meat. Fried pork (13.91ng/g) had higher levels of total HCAs than fried beef (8.92ng/g) and fried chicken (7.00ng/g). Among the samples, fried bacon contained the highest total HCA content (17.59ng/g). Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Occurrence of heterocyclic amines in cooked meat products."
},
{
"docid": "MED-2085",
"text": "A diet rich in fruits and vegetables is known to decrease the risk of cardiovascular disease. However, the information regarding the antithrombotic activity (antiplatelet, anticoagulant, and fibrinolytic) of fruits and vegetables is scarce. The aim of this study was to assess the antithrombotic activity of extracts from fruits and vegetables widely consumed in central Chile. The study included samples of 19 fruits and 26 vegetables, representative of the local diet. The extracts prepared from each sample included an aqueous (juice or pressed solubles) and/or methanol-soluble fraction. The extracts were evaluated for antiplatelet, anticoagulant, and fibrinolytic activity in vitro at a final concentration of 1 mg/ml. The antiplatelet activity was assessed by platelet aggregation inhibition; anticoagulant activity was measured by the prothrombin time (PT), diluted prothrombin time (dPT), activated partial thromboplastin time (APTT), kaolin clotting time (KCT), and thrombin time. The fibrinolytic effect was determined with the euglobin clot lysis time and fibrin plate methods. Extracts of green beans and tomatoes inhibited platelet aggregation induced by ADP and arachidonic acid, in a concentration-dependent manner. The methanolic extracts of grapes prolonged the PT and dPT. Finally, extracts of raspberry prolonged the APTT and also presented fibrinolytic activity. In conclusion, from a screening that included a variety of fruits and vegetables, we found antiplatelet activity in green beans and tomatoes, anticoagulant activities in grapes and raspberries, whereas fibrinolytic activity was observed only in raspberries. Further investigations are necessary to advance in knowledge of the active compounds of these fruits and vegetables and their mechanisms of action.",
"title": "Antiplatelet, anticoagulant, and fibrinolytic activity in vitro of extracts from selected fruits and vegetables."
},
{
"docid": "MED-5118",
"text": "OBJECTIVE: To compare the effects of two commercially available soy milks (one made using whole soy beans, the other using soy protein isolate) with low-fat dairy milk on plasma lipid, insulin, and glucose responses. DESIGN: Randomized clinical trial, cross-over design. SUBJECTS: Participants were 30-65 years of age, n = 28, with pre-study LDL-cholesterol (LDL-C) concentrations of 160-220 mg/dL, not on lipid lowering medications, and with an overall Framingham risk score of <or=10%. INTERVENTION: Participants were required to consume sufficient milk to provide 25 g protein/d from each source. The protocol included three 4-week treatment phases, each separated from the next by a wash-out period of >or=4 weeks. RESULTS: Mean LDL-C concentration at the end of each phase (+/- SD) was 161 +/- 20, 161 +/- 26 and 170 +/- 24 mg/dL for the whole bean soy milk, the soy protein isolate milk, and the dairy milk, respectively (p = 0.9 between soy milks, p = 0.02 for each soy milk vs. dairy milk). No significant differences by type of milk were observed for HDL-cholesterol, triacylglycerols, insulin, or glucose. CONCLUSION: A 25 g dose of daily soy protein from soy milk led to a modest 5% lowering of LDL-C relative to dairy milk among adults with elevated LDL-C. The effect did not differ by type of soy milk and neither soy milk significantly affected other lipid variables, insulin or glucose.",
"title": "Effect of two types of soy milk and dairy milk on plasma lipids in hypercholesterolemic adults: a randomized trial."
}
] |
PLAIN-780
|
burgers
|
[
{
"docid": "MED-4450",
"text": "Little is known about the effects of diet after breast cancer diagnosis on survival. We prospectively examined the relation between post-diagnosis dietary factors and breast cancer and all-cause survival in women with a history of invasive breast cancer diagnosed between 1987 and 1999 (at ages 20–79 years). Diet after breast cancer diagnosis was measured using a 126-item food frequency questionnaire. Among 4,441 women without a history of breast cancer recurrence prior to completing the questionnaire, 137 subsequently died from breast cancer within 7 years of enrollment. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for intake of macronutrients as well as selected micronutrients and food groups from Cox proportional hazards regression models. After adjustment for factors at diagnosis (age, state of residence, menopausal status, smoking, breast cancer stage, alcohol, history of hormone replacement therapy), interval between diagnosis and diet assessment, and at follow-up (energy intake, breast cancer treatment, body mass index, and physical activity), women in the highest compared to lowest quintile of intake of saturated fat and trans fat had a significantly higher risk of dying from any cause (HR = 1.41, 95% CI = 1.06 to 1.87, P-trend = 0.03) for saturated fat; (HR = 1.78, 95% CI = 1.35 to 2.32, P-trend = 0.01) for trans fat intake. Associations were similar, though did not achieve statistical significance, for breast cancer survival. This study suggests that lower intake of saturated and trans fat in the post-diagnosis diet is associated with improved survival after breast cancer diagnosis.",
"title": "Post-diagnosis dietary factors and survival after invasive breast cancer"
},
{
"docid": "MED-3053",
"text": "BACKGROUND: The hypothalamus is the central homeostatic control region of the brain and, therefore, highly influenced by nutrients such as glucose and fat. Immediate and prolonged homeostatic effects of glucose ingestion have been well characterized. However, studies that used stimulation with fat have mainly investigated immediate perceptional processes. Besides homeostatic processes, the gustatory cortex, including parts of the insular cortex, is crucial for the processing of food items. OBJECTIVE: The aim of this study was to investigate the effect of high- compared with low-fat meals on the hypothalamus and the insular cortex. DESIGN: Eleven healthy men participated in a single-blinded, functional MRI study of high- and low-fat meals on 2 measurement days. Cerebral blood flow (CBF) was measured before and 30 and 120 min after intake of high- and low-fat yogurts. Hunger was rated and blood samples were taken before each CBF measurement. RESULTS: High-fat yogurt induced a pronounced decrease in CBF in the hypothalamus, and the corresponding CBF change correlated positively with the insulin change. Furthermore, insular activity increased after 120 min in the low-fat condition only. The CBF change in both regions correlated positively in the high-fat condition. CONCLUSIONS: The decrease in hypothalamic activity and the interaction with the insular cortex elicited by fat may contribute to an efficient energy homeostasis. Therefore, fat might be a modulator of homeostatic and gustatory brain regions and their interaction. This trial was registered at clinicaltrials.gov as NCT01516021.",
"title": "Fat intake modulates cerebral blood flow in homeostatic and gustatory brain areas in humans."
},
{
"docid": "MED-1253",
"text": "OBJECTIVES: To investigate the effect of replacing lean meat with a soy product, tofu, on serum lipoprotein concentrations. STUDY AND DESIGN: Randomized cross-over dietary intervention study. SUBJECTS: Forty-two free-living healthy males aged 35-62 y completed the dietary intervention. Three additional subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing lean meat (150 g/d) was compared with one with 290 g/d tofu in an isocaloric and isoprotein substitution. Both diet periods were 1 month, and fat intake was carefully controlled. RESULTS: Seven-day diet records showed the two diets were similar in energy, macronutrients and fibre. Total cholesterol (mean difference 0.23 mmol/l, 95% CI 0.02, 0.43; P=0.03) and triglycerides (mean difference 0.15 mmol/l, 95% CI 0.02, 0.31; P=0.017) were significantly lower on the tofu diet than the lean meat diet. However, HDL-C was also significantly lower on the tofu diet (mean difference 0.08 mmol/l, 95% CI 0.02, 0.14; P=0.01) although the LDL-C:HDL-C ratio was similar. CONCLUSION: The effect on HDL-C and the small LDL-C reduction differ from some other studies, where fat was often less controlled, and the comparison was of soy as textured protein or soymilk against casein. This suggests a differential effect of the various proteins compared to the soy may influence the findings. In practice, the replacement of meat with tofu would usually be associated with a decrease in saturated fat and an increase in polyunsaturated fat and this should enhance any small benefits due to the soy protein. SPONSOR: Deakin University with some contribution from a Commonwealth Department of Veterans Affairs research grant. European Journal of Clinical Nutrition (2000) 54, 14-19",
"title": "Effects of soy as tofu vs meat on lipoprotein concentrations."
},
{
"docid": "MED-1615",
"text": "Hyperinsulinemia, hypertension, hypertriglyceridemia and obesity are independent risk factors for coronary artery disease and are often found in the same person. This study investigated the effects of an intensive, 3-week, dietary and exercise program on these risk factors. The group was divided into diabetic patients (non-insulin-dependent diabetes mellitus [NIDDM], n = 13), insulin-resistant persons (n = 29) and those with normal insulin, less than or equal to 10 microU/ml (n = 30). The normal groups had very small but statistically significant decreases in all of the risk factors. The patients with NIDDM had the greatest decreases. Insulin was reduced from 40 +/- 15 to 27 +/- 11 microU/ml, blood pressure from 142 +/- 9/83 +/- 3 to 132 +/- 6/71 +/- 3 mm Hg, triglycerides from 353 +/- 76 to 196 +/- 31 mg/dl and body mass index from 31.1 +/- 4.0 to 29.7 +/- 3.7 kg/m2. Although there was a significant weight loss for the group with NIDDM, resulting in the decrease in body mass index, 8 of 9 patients who were initially overweight were still overweight at the end of the program, and 5 of the 8 were still obese (body mass index greater than 30 kg/m2), indicating that normalization of body weight is not a requisite for a reduction or normalization of other risk factors. Insulin was reduced from 18.2 +/- 1.8 to 11.6 +/- 1.2 microU/ml in the insulin-resistant group, with 17 of the 29 subjects achieving normal fasting insulin (less than 10 microU/ml).(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Role of diet and exercise in the management of hyperinsulinemia and associated atherosclerotic risk factors."
},
{
"docid": "MED-1252",
"text": "The effect of substituting soy for animal protein in mixed diets was determined in young men with mildly elevated plasma cholesterol, 218 to 307 mg/dl. The diets were low in cholesterol, 200 mg/day, with 13 to 16% of energy as protein, 30 to 35% as fat, and a polyunsaturated to saturated fat ratio of 0.5. Of protein 65% was from either mixed animal proteins or isolated soy protein products made comparable by the addition of extracted animal fats. Fresh egg yolk was added to balance the cholesterol content of the diets. Proteins from grains and vegetables were identical in both menus and contributed about 35% of dietary protein. Twenty of 24 subjects decreased plasma cholesterol at the end of the protocol. Subjects were classified as responders or nonresponders as a function of greater or lesser than mean reduction in cholesterol for the groups. Mean decreases in plasma cholesterol, 16 and 13%, for responders in the animal and soy groups were significant, p less than 0.01 and 0.05, respectively. Responders in both groups had higher initial plasma cholesterol values than nonresponders. Although plasma high-density lipoprotein cholesterol decreased slightly, the high-density lipoprotein cholesterol to cholesterol ratio (high-density lipoprotein cholesterol/total cholesterol) remained constant for most individuals. The hypocholesterolemic effects were similar for both animal and soy protein (p less than 0.05) and fat (p less than 0.05) while on the experimental diet. All groups significantly decreased dietary cholesterol (p less than 0.001).",
"title": "Determinants of hypocholesterolemic response to soy and animal protein-based diets."
},
{
"docid": "MED-1257",
"text": "Meat protein is associated with an increase in risk of heart disease. Recent data have shown that meat protein appeared to be associated with weight gain over 6.5 years, with 1 kg of weight increase per 125 g of meat per day. In the Nurses' Health Study, diets low in red meat, containing nuts, low-fat dairy, poultry, or fish, were associated with a 13% to 30% lower risk of CHD compared with diets high in meat. Low-carbohydrate diets high in animal protein were associated with a 23% higher total mortality rate whereas low-carbohydrate diets high in vegetable protein were associated with a 20% lower total mortality rate. Recent soy interventions have been assessed by the American Heart Association and found to be associated with only small reductions in LDL cholesterol. Although dairy intake has been associated with a lower weight and lower insulin resistance and metabolic syndrome, the only long-term (6 months) dairy intervention performed so far has shown no effects on these parameters.",
"title": "Protein and coronary heart disease: the role of different protein sources."
},
{
"docid": "MED-1492",
"text": "BACKGROUND: The benefits of reducing blood pressure are well established, but there remains uncertainty about whether the magnitude of the effect varies with the initial blood pressure level. The objective was to compare the risk reductions achieved by different blood pressure-lowering regimens among individuals with different baseline blood pressures. METHODS: Thirty-two randomized controlled trials were included and seven comparisons between different types of treatments were made. For each comparison, the primary prespecified analysis included calculation of summary estimates of effect using random-effects meta-analysis for major cardiovascular events in four groups defined by baseline SBP (<140, 140-159, 160-179, and ≥ 180 mmHg). RESULTS: There were 201 566 participants among whom 20 079 primary outcome events were observed. There was no evidence of differences in the proportionate risk reductions achieved with different blood pressure-lowering regimens across groups defined according to higher or lower levels of baseline SBP (all P for trend > 0.17). This finding was broadly consistent for comparisons of different regimens, for DBP categories, and for commonly used blood pressure cut-points. CONCLUSION: It appears unlikely that the effectiveness of blood pressure-lowering treatments depends substantively upon starting blood pressure level. As the majority of patients in the trials contributing to these overviews had a history of hypertension or were receiving background blood pressure-lowering therapy, the findings suggest that additional blood pressure reduction in hypertensive patients meeting initial blood pressure targets will produce further benefits. More broadly, the data are supportive of the utilization of blood pressure-lowering regimens in high-risk patients with and without hypertension.",
"title": "The effects of blood pressure reduction and of different blood pressure-lowering regimens on major cardiovascular events according to baseline bloo..."
},
{
"docid": "MED-1858",
"text": "As a hard tissue dental disease, dental erosion has a multifactorial etiology. The majority of dental erosion that originates from extrinsic sources is the result of dietary intake, particularly acidic beverages. Several preventive means have been proposed to minimize the damage to the dentition, including a reduction in the consumption of causative beverages and the adoption of a specific method of drinking, utilizing a straw instead of a cup. This article presents two cases involving the clinical and radiographic features of erosion lesions associated with chronic and excessive intake of acidic carbonated beverages. These examples embody how drinking patterns influence the formation of erosion lesions in various anatomic locations within the dentition. The clinical and radiographic evidence presented in this report cautions against the use of nonspecific terms, such as \"cup versus straw,\" and instead suggests implementing a more precise description of the suggested method. In view of the extensive damage inflicted by the chronic, excessive intake of carbonated beverages, preventive measures are considered to be the only effective course of management. This article offers illustrative examples of erosion lesions associated with long-term excessive intake of carbonated beverages. The influence of the drinking method--that is, a straw positioned into the labial vestibule versus a cup--on the anatomic location of the erosion lesions will be demonstrated through clinical and radiographic evidence.",
"title": "Influence of drinking patterns of carbonated beverages on dental erosion."
},
{
"docid": "MED-4746",
"text": "Americans consume about 5 billion hamburgers a year. It is presumed that most hamburgers are composed primarily of meat. The purpose of this study is to assess the content of 8 fast food hamburger brands using histologic methods. Eight different brands of hamburgers were evaluated for water content by weight and microscopically for recognizable tissue types. Glial fibrillary acidic protein (GFAP) staining was used to evaluate for brain tissue. Water content by weight ranged from 37.7% to 62.4% (mean, 49%). Meat content in the hamburgers ranged from 2.1% to 14.8% (median, 12.1%). The cost per gram of hamburger ranged from $0.02 to $0.16 (median, $0.03) and did not correlate with meat content. Electron microscopy showed relatively preserved skeletal muscle. A variety of tissue types besides skeletal muscle were observed including connective tissue (n = 8), blood vessels (n = 8), peripheral nerve (n = 8), adipose tissue (n = 7), plant material (n = 4), cartilage (n = 3), and bone (n = 2). In 2 hamburgers, intracellular parasites (Sarcocystis) were identified. The GFAP immunostaining was not observed in any of the hamburgers. Lipid content on oil-red-O staining was graded as 1+ (moderate) in 6 burgers and 2+ (marked) in 2 burgers. Fast food hamburgers are comprised of little meat (median, 12.1%). Approximately half of their weight is made up of water. Unexpected tissue types found in some hamburgers included bone, cartilage, and plant material; no brain tissue was present. Sarcocystis parasites were discovered in 2 hamburgers.",
"title": "Fast food hamburgers: what are we really eating?"
},
{
"docid": "MED-4602",
"text": "The strategy of \"manufacturing uncertainty\" has been used with great success by polluters and manufacturers of dangerous products to oppose public health and environmental regulation. This strategy entails questioning the validity of scientific evidence on which the regulation is based. While this approach is most identified with the tobacco industry, it has been used by producers of asbestos, benzene, beryllium, chromium, diesel exhaust, lead, plastics, and other hazardous products to avoid environmental and occupational health regulation. It is also central to the debate on global warming. The approach is now so common that it is unusual for the science not to be challenged by an industry facing regulation. Manufacturing uncertainty has become a business in itself; numerous technical consulting firms provide a service often called \"product defense\" or \"litigation support.\" As these names imply, the usual objective of these activities is not to generate knowledge to protect public health but to protect a corporation whose products are alleged to have toxic properties. Evidence in the scientific literature of the funding effect--the close correlation between the results of a study desired by a study's funder and the reported results of that study--suggests that the financial interest of a study's sponsors should be taken into account when considering the study's findings. Similarly, the interpretation of data by scientists with financial conflicts should be seen in this light. Manufacturing uncertainty is antithetical to the public health principle that decisions be made using the best evidence currently available.",
"title": "Manufactured uncertainty: protecting public health in the age of contested science and product defense."
},
{
"docid": "MED-1609",
"text": "To examine extra-alimentary effects of high-carbohydrate, high-fiber (HCF) diets, insulin-mediated glucose disposal employing the euglycemic clamp and hepatic glucose output (HGO) employing [6,6-2H2]glucose were measured in 12 healthy young and old individuals before and after 21-28 d of an HCF diet. Diet lowered fasting concentrations of glucose from 5.3 +/- 0.2 to 5.1 +/- 0.1 mmol/L (p less than 0.01) and insulin from 66.0 +/- 7.9 to 49.5 +/- 5.7 pmol/L (p less than 0.01). Fasting serum cholesterol decreased from 5.17 +/- 0.18 to 3.80 +/- 0.20 mmol/L (p less than 0.01) in young individuals and from 6.15 +/- 0.52 to 4.99 +/- 0.49 mmol/L (p less than 0.01) in elderly individuals. Fasting serum triglyceride concentrations, basal HGO, and insulin suppression of HGO were unchanged by the diet. Glucose disposal rates increased from 18.87 +/- 1.66 before 23.87 +/- 2.78 mumol.kg-1.min-1 after the diet (p less than 0.02). Therefore, HCF diets may improve carbohydrate economy by enhanced peripheral sensitivity to insulin.",
"title": "High-carbohydrate, high-fiber diets increase peripheral insulin sensitivity in healthy young and old adults."
},
{
"docid": "MED-702",
"text": "AIM OF THE REVIEW: To systematically analyze the efficacy and safety of liraglutide for the treatment of diabetes mellitus in comparison to other mono- and combination therapies. METHOD: PubMed (any date) and EMBASE (all years) search was conducted with liraglutide as a search term. Phase III clinical trials retrieved by the two databases and resources posted in Drug@FDA website were evaluated with regard to outcomes of efficacy and safety. RESULTS: Eight Phase III clinical studies compared the efficacy and safety of liraglutide to other monotherapies or combinations. Liraglutide as monotherapy in doses of 0.9 mg or above showed a significantly superior reduction in HbA1C compared to monotherapies with glimepiride or glyburide. When liraglutide was used as add-on therapy to glimepiride in doses of 1.2 mg or above, the reduction of HbA1C was greater than that in the combination therapy of glimepiride and rosiglitazone. However, liraglutide as add-on therapy to metformin failed to show benefit over combination of metformin and glimepiride. Triple therapy of using liraglutide in addition to metformin plus either glimepiride or rosiglitazone resulted in additional benefit in HbA1C reduction. Most common adverse events were gastrointestinal disturbance such as nausea, vomit, diarrhea, and constipation. During the eight clinical studies, six cases of pancreatitis and five cases of cancer were reported in liraglutide arm, whereas there was one case of each of pancreatitis in exenatide and glimepiride arms, respectively, and one case of cancer in metformin plus sitagliptin arm. CONCLUSION: Liraglutide is a new therapeutic option to improve glycemic control in patients with type 2 diabetes. However, the present lack of evidence of durability of efficacy and long-term safety appear to limit its utility in the general treatment of type 2 diabetes at this time.",
"title": "The efficacy and safety of liraglutide."
},
{
"docid": "MED-4451",
"text": "Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public about how to reduce the carcinogenic load imposed by HCAs would be an important contribution to cancer prevention.",
"title": "Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish."
},
{
"docid": "MED-3228",
"text": "A precise understanding of the role of dietary protein in bone health has been evasive despite decades of research. It is known that a dietary acid load is harmful to bone, and sulfur-containing amino acids are metabolized to provide such an acid load. It is also known that protein elevates urine calcium loss. However, recent clinical studies and a meta-analysis have indicated either no effect or a modest benefit associated with higher protein intakes. These contradictory considerations may be explained by the existence of a two-faced relationship between protein and bone, with simultaneous positive and negative pathways. In opposition to the negative effects of dietary acid load, protein may exert positive effects related to improving calcium absorption, increasing insulin-like growth factor 1, or improving lean body mass, which, in turn, improves bone strength. Putative mechanisms behind these pathways are reviewed here, and some limitations in the historical literature as well as suggested measures to counter these in the future are identified. When positive and negative pathways are considered in tandem, protein may offer modest benefits to bone in the presence of adequate dietary calcium and acid-neutralizing fruits and vegetables. © 2011 International Life Sciences Institute.",
"title": "Dietary protein and bone health: harmonizing conflicting theories."
},
{
"docid": "MED-2726",
"text": "The 2011 UN high-level meeting on non-communicable diseases (NCDs) called for multisectoral action including with the private sector and industry. However, through the sale and promotion of tobacco, alcohol, and ultra-processed food and drink (unhealthy commodities), transnational corporations are major drivers of global epidemics of NCDs. What role then should these industries have in NCD prevention and control? We emphasise the rise in sales of these unhealthy commodities in low-income and middle-income countries, and consider the common strategies that the transnational corporations use to undermine NCD prevention and control. We assess the effectiveness of self-regulation, public-private partnerships, and public regulation models of interaction with these industries and conclude that unhealthy commodity industries should have no role in the formation of national or international NCD policy. Despite the common reliance on industry self-regulation and public-private partnerships, there is no evidence of their effectiveness or safety. Public regulation and market intervention are the only evidence-based mechanisms to prevent harm caused by the unhealthy commodity industries. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Profits and pandemics: prevention of harmful effects of tobacco, alcohol, and ultra-processed food and drink industries."
},
{
"docid": "MED-4560",
"text": "The good news about coronary atherosclerosis is that it takes an awful lot of plaque before symptoms of myocardial ischemia occur. The bad news is that despite the need for large quantities of plaque for symptoms to occur, nevertheless nearly half of us in the United States eventually have the necessary quantity. Atherosclerosis is infrequently hereditary in origin. Most of us get atherosclerosis because we consume too much fat, cholesterol, and calories. The consequence is an elevated ( > 150 mg/dl) serum total cholesterol level, and the higher the number is above 150, the greater is the quantity of plaque deposited in our arteries. If the serum total cholesterol level can be prevented from rising to more than 150 mg/dl, plaques are not laid down; if elevated levels are lowered to 150 mg/dl, further plaque does not form, and parts of those present may vanish. A fruit-vegetarian-starch diet is necessary as a rule to achieve the 150 mg/dl level in most adults. Lipid-lowering drugs are required in the patients with familial hypercholesterolemia and in most patients with atherosclerotic events. The best news about atherosclerosis is that it can be prevented in those without the hereditary form, and it can be arrested by lowering elevated serum total (and LDL) cholesterol to the 150 mg/dl level.",
"title": "Preventing and arresting coronary atherosclerosis."
},
{
"docid": "MED-1611",
"text": "A growing body of evidence from observational studies and meta-analyses of the data suggest that diabetes mellitus is associated with an increased risk of cancer. Meta-analyses have shown that diabetes increases the risks of total cancer, and of site-specific cancers of the breast, endometrium, bladder, liver, colorectum and pancreas, and that it decreases the risk of prostate cancer. Insulin resistance and secondary hyperinsulinemia is the most frequently proposed hypothesis, and hyperglycemia itself might promote carcinogenesis. In addition to several facets of lifestyle including obesity, smoking and lack of exercise, treatment for diabetes might affect the risk of cancer. For instance, metformin, an insulin sensitizer, reportedly has a potential anticancer effect. In light of the exploding global epidemic of diabetes, even a modest increase in the cancer risk will translate into a substantial socioeconomic burden. The current insights underscore the need for clinical attention and better-designed studies of the complex interactions between diabetes and cancer.",
"title": "Latest insights into the risk of cancer in diabetes"
},
{
"docid": "MED-4027",
"text": "Objectives To study the dietary behavior and knowledge about dental erosion and self-reported symptoms that can be related to dental erosion among Chinese adults in Hong Kong. Methods Chinese adults aged 25-45 years were randomly selected from a list of registered telephone numbers generated by computer. A telephone survey was administered to obtain information on demographic characteristics, dietary habits, dental visits, and knowledge of and presence of self-reported symptoms that can be related to dental erosion. Results A total of 520 participants were interviewed (response rate, 75%; sampling error, ± 4.4%) and their mean age was 37. Most respondents (79%) had ever had caries, and about two thirds (64%) attended dental check-ups at least once a year. Respondents had a mean of 5.4 meals per day and 36% had at least 6 meals per day. Fruit (89%) and lemon tea/water (41%) were the most commonly consumed acidic food and beverage. When asked if they ever noticed changes in their teeth, most respondents (92%) said they had experienced change that can be related to erosion. However, many (71%) had never heard about dental erosion and 53% mixed up dental erosion with dental caries. Conclusion Hong Kong Chinese adults have frequent intake of food and many have experienced symptoms that can be related to dental erosion. Their level of awareness of and knowledge about dental erosion is generally low, despite most of them have regular dental check-ups. Dental health education is essential to help the public understand dental erosion and its damaging effects.",
"title": "Dietary behavior and knowledge of dental erosion among Chinese adults"
},
{
"docid": "MED-4205",
"text": "Since the Second World War the consumer behaviour in developed countries changed drastically. Primarily there existed the demand for sufficient food after a period of starvation, afterwards the desire for higher quality was arising, whereas today most people ask for safe and healthy food with high quality. Therefore a united approach comprising consistent standards, sound science and robust controls is required to ensure consumers' health and to maintain consumers' confidence and satisfaction. Chemical analysis along the whole food chain downstream (tracking) from primary production to the consumer and upstream (tracing) from the consumer to primary production is an important prerequisite to ensure food safety and quality. In this frame the focus of the following paper is the \"chemical safety of meat and meat products\" taking into account inorganic as well as organic residues and contaminants, the use of nitrite in meat products, the incidence of veterinary drugs, as well as a Failure Mode and Effect Analysis (FMEA) system assessing (prioritizing) vulnerable food chain steps to decrease or eliminate vulnerability.",
"title": "Chemical safety of meat and meat products."
},
{
"docid": "MED-2221",
"text": "Context: In 1954 the tobacco industry paid to publish the “Frank Statement to Cigarette Smokers” in hundreds of U.S. newspapers. It stated that the public's health was the industry's concern above all others and promised a variety of good-faith changes. What followed were decades of deceit and actions that cost millions of lives. In the hope that the food history will be written differently, this article both highlights important lessons that can be learned from the tobacco experience and recommends actions for the food industry. Methods: A review and analysis of empirical and historical evidence pertaining to tobacco and food industry practices, messages, and strategies to influence public opinion, legislation and regulation, litigation, and the conduct of science. Findings: The tobacco industry had a playbook, a script, that emphasized personal responsibility, paying scientists who delivered research that instilled doubt, criticizing the “junk” science that found harms associated with smoking, making self-regulatory pledges, lobbying with massive resources to stifle government action, introducing “safer” products, and simultaneously manipulating and denying both the addictive nature of their products and their marketing to children. The script of the food industry is both similar to and different from the tobacco industry script. Conclusions: Food is obviously different from tobacco, and the food industry differs from tobacco companies in important ways, but there also are significant similarities in the actions that these industries have taken in response to concern that their products cause harm. Because obesity is now a major global problem, the world cannot afford a repeat of the tobacco history, in which industry talks about the moral high ground but does not occupy it.",
"title": "The Perils of Ignoring History: Big Tobacco Played Dirty and Millions Died. How Similar Is Big Food?"
},
{
"docid": "MED-4472",
"text": "N-Nitroso compounds were known almost 40 years ago to be present in food treated with sodium nitrite, which made fish meal hepatotoxic to animals through formation of nitrosodimethylamine (NDMA). Since that time, N-nitroso compounds have been shown in animal experiments to be the most broadly acting and the most potent group of carcinogens. The key role of nitrite and nitrogen oxides in forming N-nitroso compounds by interaction with secondary and tertiary amino compounds has led to the examination worldwide of foods for the presence of N-nitroso compounds, which have been found almost exclusively in those foods containing nitrite or which have become exposed to nitrogen oxides. Among these are cured meats, especially bacon-and especially when cooked; concentrations of 100 micrograms kg(-1) have been found or, more usually, near 10 micrograms kg(-1). This would correspond to consumption of 1 microgram of NDMA in a 100-g portion. Much higher concentrations of NDMA (but lower ones of other nitrosamines) have been found in Japanese smoked and cured fish (more than 100 micrograms kg(-1)). Beer is one source of NDMA, in which as much as 70 micrograms l(-1) has been reported in some types of German beer, although usual levels are much lower (10 or 5 micrograms l(-1)); this could mean a considerable intake for a heavy beer drinker of several liters per day. Levels of nitrosamines have been declining during the past three decades, concurrent with a lowering of the nitrite used in food and greater control of exposure of malt to nitrogen oxides in beer making. There have been declines of N-nitroso compound concentrations in many foods during the past two decades. The small amounts of nitrosamines in food are nonetheless significant because of the possibility-even likelihood-that humans are more sensitive to these carcinogens than are laboratory rodents. Although it is probable that alkylnitrosamides (which induce brain tumors in rodents) are present in cured meats and other potentially nitrosated products in spite of much searching, there has been only limited indirect evidence of their presence. Copyright 1999 Elsevier Science B.V.",
"title": "N-Nitroso compounds in the diet."
},
{
"docid": "MED-1801",
"text": "OBJECTIVE: In 1976, the Royal College of Physicians and the British Cardiac Society recommended eating less fatty red meat and more poultry instead because it was lean. However, the situation has changed since that time, with a striking increase in fat content of the standard broiler chicken. The aim of the present study was to report a snapshot of data on fat in chickens now sold to the public. DESIGN: Samples were obtained randomly between 2004 and 2008 from UK supermarkets, farm shops and a football club. The amount of chicken fat was estimated by emulsification and chloroform/methanol extraction. SETTING: Food sold in supermarkets and farms in England. SUBJECTS: Chicken samples. RESULTS: The fat energy exceeded that of protein. There has been a loss of n-3 fatty acids. The n-6:n-3 ratio was found to be as high as 9:1, as opposed to the recommendation of about 2:1. Moreover, the TAG level in the meat and whole bird mostly exceeded the proportion of phospholipids, which should be the higher for muscle function. The n-3 fatty acid docosapentaenoic acid (DPA, 22 : 5n-3) was in excess of DHA (22 : 6n-3). Previous analyses had, as usual for birds, more DHA than DPA. CONCLUSIONS: Traditional poultry and eggs were one of the few land-based sources of long-chain n-3 fatty acids, especially DHA, which is synthesized from its parent precursor in the green food chain. In view of the obesity epidemic, chickens that provide several times the fat energy compared with protein seem illogical. This type of chicken husbandry needs to be reviewed with regard to its implications for animal welfare and human nutrition.",
"title": "Modern organic and broiler chickens sold for human consumption provide more energy from fat than protein."
},
{
"docid": "MED-3054",
"text": "The relationship between overeating, substance abuse and (behavioral) addiction is controversial. Medically established forms of addiction so far pertain to substance use disorders only. But the preliminary Diagnostic and Statistical Manual for Mental Disorders V (DSM V) suggests replacing the previous category 'Substance-Related Disorders' with 'Addiction and Related Disorders', thus for the first time allowing the diagnosis of behavioral addictions. In the past psychiatrists and psychologists have been reluctant to systematically delineate and classify the term behavioral addiction. However, there is a broad overlap between chemical and behavioral addiction including phenomenological, therapeutic, genetic, and neurobiological aspects. It is of interest to point out that the hormone leptin in itself has a pronounced effect on the reward system, thus suggesting an indirect link between overeating and 'chemical' addiction. Thus, leptin-deficient individuals could be classified as fulfilling criteria for food addiction. In our overview we first review psychological findings in chemical (substance-based) and subsequently in behavioral addiction to analyze the overlap. We discuss the diagnostic validity of food addiction, which in theory can be chemically and/or behaviorally based. Copyright © 2012 S. Karger GmbH, Freiburg.",
"title": "Does food addiction exist? A phenomenological discussion based on the psychiatric classification of substance-related disorders and addiction."
},
{
"docid": "MED-3237",
"text": "The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products, generating the accumulation of non-metabolizable anions and a lifespan state of overlooked metabolic acidosis, whose magnitude increases progressively with aging due to the physiological decline in kidney function. In response to this state of diet-derived metabolic acidosis, the kidney implements compensating mechanisms aimed to restore the acid-base balance, such as the removal of the non-metabolizable anions, the conservation of citrate, and the enhancement of kidney ammoniagenesis and urinary excretion of ammonium ions. These adaptive processes lower the urine pH and induce an extensive change in urine composition, including hypocitraturia, hypercalciuria, and nitrogen and phosphate wasting. Low urine pH predisposes to uric acid stone formation. Hypocitraturia and hypercalciuria are risk factors for calcium stone disease. Even a very mild degree of metabolic acidosis induces skeletal muscle resistance to the insulin action and dietary acid load may be an important variable in predicting the metabolic abnormalities and the cardiovascular risk of the general population, the overweight and obese persons, and other patient populations including diabetes and chronic kidney failure. High dietary acid load is more likely to result in diabetes and systemic hypertension and may increase the cardiovascular risk. Results of recent observational studies confirm an association between insulin resistance and metabolic acidosis markers, including low serum bicarbonate, high serum anion gap, hypocitraturia, and low urine pH. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.",
"title": "Diet-induced metabolic acidosis."
},
{
"docid": "MED-5090",
"text": "OBJECTIVE: To examine associations between the prevalence of degenerative arthritis and soft tissue disorders and consumption of meat and other foods among participants in the Adventist Health Study. METHODS: Unconditional logistic regression analysis is used to examine cross-sectional associations, adjusting for the effects of age, smoking, alcohol consumption, body mass index, use of sex hormones and parity. RESULTS: The prevalence of degenerative arthritis and soft tissue disorders was 22.60 percent. Women had a higher prevalence than men and prevalence increased greatly with age. Smoking, higher body mass index, never use of contraceptive pills, and current hormone replacement therapy are associated with a higher prevalence of these disorders on multivariate analysis. Multivariate OR's comparing consumption of meat < 1/week; >or= 1/week; with the reference being no meat, were 1.31(95% CI: 1.21,1.43) and 1.49(1.31, 1.70) in women; and 1.19 (95% CI: 1.05,1.34) and 1.43(1.20, 1.70) in men. Dairy fat and fruit consumption were weakly associated with increased risk. There were protective associations with nut and salad consumption. CONCLUSIONS: Greater meat consumption is associated with a higher prevalence of degenerative arthritis and soft tissue disorders in both male and female subjects of this population, as is hormone replacement therapy in women.",
"title": "Associations between meat consumption and the prevalence of degenerative arthritis and soft tissue disorders in the adventist health study, Califor..."
},
{
"docid": "MED-1619",
"text": "BACKGROUND: Diets rich in carbohydrates with a low glycemic index and with high fiber content are associated with flat post-prandial rises of blood glucose, minimal post-prandial insulin secretion and maintenance of insulin sensitivity. Protective food commodities in the prevention of cardiovascular disease, insulin resistance syndrome or diabetes are crucial components of the vegetarian diet. AIM OF THE STUDY: Insulin resistance values were assessed in relation to different nutrition. Metabolic abnormality is a predictor of age-related diseases and can be more pronounced in obese subjects. Insulin resistance values in normal weight subjects of two different nutritional habits were correlated with age. METHODS: Fasting concentrations of glucose and insulin as well as calculated values of insulin resistance IR (HOMA) were assessed in two nutritional groups of apparently healthy adult subjects (age range 19 - 64 years) with normal weight (body mass index 18.6 - 25.0 kg/m(2)): a vegetarian group (95 long-term lacto-ovo-vegetarians; duration of vegetarianism 10.2 +/- 0.5 years) and a non-vegetarian control group (107 subjects of general population on traditional western diet). Intake of energy and main nutrients (fats, saccharides, proteins) was similar in both groups. RESULTS: Glucose and insulin concentrations and IR (HOMA) values were significantly lower in vegetarians (glucose 4.47 +/- 0.05 vs. 4.71 +/- 0.07 mmol/l; insulin 4.96 +/- 0.23 vs. 7.32 +/- 0.41 mU/l; IR (HOMA) 0.99 +/- 0.05 vs. 1.59 +/- 0.10). IR (HOMA) dependence on age was only significant in subjects on a western diet. A significant increase of IR was found already in the age range 31-40 years, compared to vegetarians and it continued in later age decades. Age independent and low insulin resistance values in vegetarians are a consequence of an effective diet prevention by long-term frequent consumption of protective food. Vegetarians had a significantly higher consumption of whole grain products, pulses, products from oat and barley. CONCLUSION: The results of age independent and low values of insulin resistance document a beneficial effect of long-term vegetarian nutrition in prevention of metabolic syndrome, diabetes and cardiovascular disease.",
"title": "No evidence of insulin resistance in normal weight vegetarians. A case control study."
},
{
"docid": "MED-3226",
"text": "Context and Objective: Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria. Design and Setting: In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins. Participants and Interventions: Eleven healthy volunteers were evaluated at the end of each of four phases while consuming metabolic diets with fixed calcium and sodium content. Phases 1 and 3 consisted of a control diet (CD). Phases 2 and 4 consisted of a eucaloric HPD (60 g/d animal proteins added to CD). Along with HPD in phases 2 and 4, subjects ingested 30 mEq twice daily of either potassium citrate (KCitrate, alkaline salt) or potassium chloride (KCl, control neutral salt). Results: KCitrate completely neutralized the acid load imparted by HPD (based on changes in urine pH and net acid excretion) and increased urinary citrate. Urinary calcium increased during both HPD phases compared with CD but was not significantly different between the HPD + KCl and HPD + KCitrate phases (182 ± 85 vs. 170 ± 85 mg/d; P = 0.28). Increased urinary saturation with respect to calcium oxalate and uric acid with HPD was abrogated by KCitrate. Conclusions: This study suggests that, at least in the short-term, mechanism(s) other than acid load account for hypercalciuria induced by HPD. The beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate.",
"title": "Hypercalciuria Associated with High Dietary Protein Intake Is Not Due to Acid Load"
},
{
"docid": "MED-3052",
"text": "Drug addiction and obesity appear to share several properties. Both can be defined as disorders in which the saliency of a specific type of reward (food or drug) becomes exaggerated relative to, and at the expense of others rewards. Both drugs and food have powerful reinforcing effects, which are in part mediated by abrupt dopamine increases in the brain reward centres. The abrupt dopamine increases, in vulnerable individuals, can override the brain's homeostatic control mechanisms. These parallels have generated interest in understanding the shared vulnerabilities between addiction and obesity. Predictably, they also engendered a heated debate. Specifically, brain imaging studies are beginning to uncover common features between these two conditions and delineate some of the overlapping brain circuits whose dysfunctions may underlie the observed deficits. The combined results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning, self-control, stress reactivity and interoceptive awareness. In parallel, studies are also delineating differences between them that centre on the key role that peripheral signals involved with homeostatic control exert on food intake. Here, we focus on the shared neurobiological substrates of obesity and addiction. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.",
"title": "Obesity and addiction: neurobiological overlaps."
},
{
"docid": "MED-1134",
"text": "BACKGROUND: The purpose of this article is to evaluate the impact of low protein and high fiber intakes on risk factors of stone recurrence in idiopathic calcium stone formers (ICSFs). METHODS: Ninety-six ICSFs were randomly assigned a low animal protein diet (< 10% of total energy), a high-fiber diet (> 25 g/day), or a usual diet (control group); all patients were recommended to increase their fluid intake. Their daily urine compositions were analyzed at baseline and at four months. Compliance with dietary recommendations was checked by validated food frequency questionnaires. Compliance with total and animal protein intakes was assessed by 24-hour urea and sulfate outputs, respectively. The nutritional intervention (oral instructions, written leaflet, phoning) and food assessment were carried out by a research dietitian. RESULTS: At baseline, diets and the daily urine composition did not differ between the three groups. At four months, while diets differed significantly, the 24-hour output of calcium and oxalate did not differ significantly within and between groups after adjustment for potential confounders (age, sex, and personal and family history of calcium stones) and baseline values. However, as many as 12 out of 31 ICSFs (95% CI, 22 to 58%) assigned to a low animal protein diet achieved a reduction in the urine urea excretion rate of more than 50 mmol/day and also exhibited a significant decrease in urinary calcium excretion that averaged 1.8 mmol/day. A significant correlation between urea and calcium outputs was observed only among patients with hypercalciuria. CONCLUSIONS: These results show that only ICSFs who markedly decrease their animal protein intake, especially those with hypercalciuria, can expect to benefit from dietary recommendations.",
"title": "Effects of low animal protein or high-fiber diets on urine composition in calcium nephrolithiasis."
},
{
"docid": "MED-3058",
"text": "Recent research indicates similarities between obesity and addictive disorders on both the phenomenological and neurobiological level. In particular, neuroendocrine and imaging studies suggest a close link between the homeostatic regulation of appetite on the on hand, and motivation and reward expectancy on the other. In addition, findings from neuropsychological studies additionally demonstrate alterations of cognitive function in both obesity and addictive disorders that possibly contribute to a lack of control in resisting consumption. In this review, recent findings on overlapping neurobiological and phenomenological pathways are summarized and the impact with regard to new treatment approaches for obesity is discussed. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.",
"title": "Implications from addiction research towards the understanding and treatment of obesity."
},
{
"docid": "MED-1254",
"text": "OBJECTIVE: To investigate the effect of replacing lean meat with a soy product, tofu, on coronary heart disease risk factors including serum lipoproteins, lipoprotein (a), factor VII, fibrinogen and in vitro susceptibility of LDL to oxidation. DESIGN: A randomized cross over dietary intervention study. SETTING: Free-living individuals studied at Deakin University. SUBJECTS: Forty-five free-living healthy males aged 35 to 62 years completed the dietary intervention. Three subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing 150 grams of lean meat per day was compared to a diet containing 290 grams of tofu per day in an isocaloric and isoprotein substitution. Each dietary period was one month duration. RESULTS: Analysis of the seven-day diet record showed that diets were similar in energy, protein, carbohydrate, total fat, saturated and unsaturated fat, polyunsaturated to saturated fat ratio, alcohol and fiber. Total cholesterol and triglycerides were significantly lower, and in vitro LDL oxidation lag phase was significantly longer on the tofu diet compared to the meat diet. The hemostatic factors, factor VII and fibrinogen, and lipoprotein(a) were not significantly affected by the tofu diet. CONCLUSIONS: The increase in LDL oxidation lag phase would be expected to be associated with a decrease in coronary heart disease risk.",
"title": "Effect of meat replacement by tofu on CHD risk factors including copper induced LDL oxidation."
},
{
"docid": "MED-1853",
"text": "PURPOSE: To measure the pH, titratable acidity, fluoride concentration and erosive potential of brewed teas. METHODS: Bag teas were purchased to represent black, green, citrus, fruity, and floral tea flavors from Tulsi, Bigelow, HyVee, Tazo, and Yogi brands and brewed (1 bag/240 ml) in boiling water for 3 minutes. The pH, titratable acidity, and fluoride concentrations were measured. Following these measurements, a representative tea from each flavor was selected for investigation of erosion potential. Six extracted human molars were randomly assigned to each tea. Teeth were painted with fingernail polish to expose a 1 x 4 mm window and then soaked in tea for a total of 25 hours with teas refreshed every 5 hours. Teeth were then sectioned using a microtome and photographed using a polarized light microscope. Lesion depths (i.e., eroded surfaces) were measured using Image Pro Plus software. Differences in physiochemical properties and lesion depths between beverages were investigated using one-way ANOVA with post-hoc Tukey's HSD test. Relationships among lesion depths and physiochemical properties were evaluated using the Pearson correlation test. RESULTS: pH, titratable acidity and fluoride concentrations differed between tea flavors (P < 0.05) and between brands (P < 0.05). Lesion depths produced by the citrus tea (83.1 +/- 10.3 microm) were greater than those produced by the fruity tea (56.5 +/- 6.1 microm); both teas produced greater depths than black (30.1 +/- 7.4 microm), floral (25.0 +/- 3.2 microm) or green (22.3 +/- 6.3 microm) teas (P < 0.05). pH (r = -0.96; P = 0.009) was inversely and titratable acidity (r = 0.97; P = 0.006) was positively associated with lesion depths.",
"title": "Erosive potentials of brewed teas."
},
{
"docid": "MED-4408",
"text": "The influence of protein oxidation, as measured by the dinitrophenylhydrazine (DNPH) method, on colour and texture changes during chill storage (2 degrees C, 12days) of cooked burger patties was studied. Extracts from arbutus-berries (Arbutus unedoL., AU), common hawthorns (Crataegus monogynaL., CM), dog roses (Rosa caninaL., RC) and elm-leaf blackberries (Rubus ulmifoliusSchott., RU) were prepared, added to burger patties (3% of total weight) and evaluated as inhibitors of protein oxidation and colour and texture changes. Negative (no added extract, C) and positive control (added quercetin; 230mg/kg, Q) groups were also considered. The significant increase of protein carbonyls during chill storage of control burger patties reflect the intense oxidative degradation of the muscle proteins. Concomitantly, an intense loss of redness and increase of hardness was found to take place in burger patties throughout refrigerated storage. Most fruit extracts as well as Q significantly reduced the formation of protein carbonyls and inhibited colour and texture deterioration during chill storage. Likely mechanisms through which protein oxidation could play a major role on colour and texture changes during chill storage of burger patties are discussed. Amongst the extracts, RC was most suitable for use as a functional ingredient in processed meats since it enhanced oxidative stability, colour and texture properties of burger patties with no apparent drawbacks. Copyright 2010 Elsevier Ltd. All rights reserved.",
"title": "Protein oxidation in emulsified cooked burger patties with added fruit extracts: Influence on colour and texture deterioration during chill storage."
},
{
"docid": "MED-3230",
"text": "OBJECTIVE: Diet affects urine pH and acid-base balance. Both excess acid/alkaline ash (EAA) and estimated net acid excretion (NAE) calculations have been used to estimate the effects of diet on urine pH. This study's goal was to determine if free-living vegans, lacto-ovo vegetarians, and omnivores have increasingly acidic urine, and to assess the ability of EAA and estimated NAE calculations to predict urine pH. DESIGN: This study used a cross-sectional design. SETTING AND PARTICIPANTS: This study assessed urine samples of 10 vegan, 16 lacto-ovo vegetarian, and 16 healthy omnivorous women in the Boston metropolitan area. Six 3-day food records from each dietary group were analyzed for EAA content and estimated NAE, and correlations with measured urine pH were calculated. RESULTS: The mean (+/- SD) urine pH was 6.15 +/- 0.40 for vegans, 5.90 +/- 0.36 for lacto-ovo vegetarians, and 5.74 +/- 0.21 for omnivores (analysis of variance, P = .013). Calculated EAA values were not significantly different among the three groups, whereas mean estimated NAE values were significantly different: 17.3 +/- 14.5 mEq/day for vegans, 31.3 +/- 8.5 mEq/day for lacto-ovo vegetarians, and 42.6 +/- 13.2 mEq/day for omnivores (analysis of variance, P = .01). The average deattenuated correlation between urine pH and EAA was 0.333; this value was -0.768 for estimated NAE and urine pH, with a regression equation of pH = 6.33 - 0.014 NAE (P = .02, r = -0.54). CONCLUSIONS: Habitual diet and estimated NAE calculations indicate the probable ranking of urine pH by dietary groups, and may be used to determine the likely acid-base status of an individual; EAA calculations were not predictive of urine pH.",
"title": "Estimated net acid excretion inversely correlates with urine pH in vegans, lacto-ovo vegetarians, and omnivores."
},
{
"docid": "MED-3235",
"text": "Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.",
"title": "Alkaline diets favor lean tissue mass in older adults"
},
{
"docid": "MED-1618",
"text": "To study the effect of a moderate increase in insulin secretion produced by an increased daily protein intake on dehydroepiandrosterone sulfate (DHEAS), a balanced randomized crossover trial consisting of three strictly controlled dietary regimens was performed in six healthy male volunteers. The basic diet (B) contained 50 g protein/d; diets P and M (also basic diets) were enriched with either 32 g protein/d (P) or 10 mmol L-methionine/d (M). Methionine was given (as a specific nonprotein source of endogenously derived sulfate) to control for possible confounding effects on DHEAS due to an increased sulfate supply. At the end of each 4-day diet period, blood and 24-hour urine samples were collected. Fasting plasma levels of testosterone, cortisol, insulin-like growth factor-I (IGF-I), and insulin, as well as urinary output of total (hot acid-cleaved) testosterone conjugates and 3alpha-androstanediol glucuronide, did not show significant changes in response to dietary manipulations. Endogenous sulfate availability (as reflected by renal sulfate output per 24 hours) approximately doubled with diets P and M. However, plasma levels (6.3 +/- 1.5, 6.8 +/- 1.8, and 6.9 +/- 2.1 micromol/L for B, P, and M, respectively) and urinary excretion (8.8 +/- 9.8, 9.4 +/- 11.2, 8.0 +/- 8.3 micromol/d) of DHEAS remained unaffected. Considering the clear increments (P < .01) in urinary C-peptide excretion with diet P (20.4 +/- 10.3 nmol/d) versus diets B and M (12.6 +/- 5.1 and 13.2 +/- 3.6 nmol/d), respectively, our results suggest that a moderately strong diet-induced increase in daily insulin secretion does not alter urinary and plasma levels of DHEAS.",
"title": "A moderate increase in daily protein intake causing an enhanced endogenous insulin secretion does not alter circulating levels or urinary excretion..."
},
{
"docid": "MED-4203",
"text": "Oxygen is vital for most organisms but, paradoxically, damages key biological sites. Oxygenic threat is met by antioxidants that evolved in parallel with our oxygenic atmosphere. Plants employ antioxidants to defend their structures against reactive oxygen species (ROS; oxidants) produced during photosynthesis. The human body is exposed to these same oxidants, and we have also evolved an effective antioxidant system. However, this is not infallible. ROS breach defences, oxidative damage ensues, accumulates with age, and causes a variety of pathological changes. Plant-based, antioxidant-rich foods traditionally formed the major part of the human diet, and plant-based dietary antioxidants are hypothesized to have an important role in maintaining human health. This hypothesis is logical in evolutionary terms, especially when we consider the relatively hypoxic environment in which humans may have evolved. In this paper, the human diet is discussed briefly in terms of its evolutionary development, different strategies of antioxidant defence are outlined, and evolution of dietary antioxidants is discussed from the perspectives of plant need and our current dietary requirements. Finally, possibilities in regard to dietary antioxidants, evolution, and human health are presented, and an evolutionary cost-benefit analysis is presented in relation to why we lost the ability to make ascorbic acid (vitamin C) although we retained an absolute requirement for it.",
"title": "Evolution of dietary antioxidants."
},
{
"docid": "MED-1494",
"text": "Flaxseed contains ω-3 fatty acids, lignans, and fiber that together may provide benefits to patients with cardiovascular disease. Animal work identified that patients with peripheral artery disease may particularly benefit from dietary supplementation with flaxseed. Hypertension is commonly associated with peripheral artery disease. The purpose of the study was to examine the effects of daily ingestion of flaxseed on systolic (SBP) and diastolic blood pressure (DBP) in peripheral artery disease patients. In this prospective, double-blinded, placebo-controlled, randomized trial, patients (110 in total) ingested a variety of foods that contained 30 g of milled flaxseed or placebo each day over 6 months. Plasma levels of the ω-3 fatty acid α-linolenic acid and enterolignans increased 2- to 50-fold in the flaxseed-fed group but did not increase significantly in the placebo group. Patient body weights were not significantly different between the 2 groups at any time. SBP was ≈ 10 mm Hg lower, and DBP was ≈ 7 mm Hg lower in the flaxseed group compared with placebo after 6 months. Patients who entered the trial with a SBP ≥ 140 mm Hg at baseline obtained a significant reduction of 15 mm Hg in SBP and 7 mm Hg in DBP from flaxseed ingestion. The antihypertensive effect was achieved selectively in hypertensive patients. Circulating α-linolenic acid levels correlated with SBP and DBP, and lignan levels correlated with changes in DBP. In summary, flaxseed induced one of the most potent antihypertensive effects achieved by a dietary intervention.",
"title": "Potent antihypertensive action of dietary flaxseed in hypertensive patients."
},
{
"docid": "MED-1136",
"text": "1. Studies were carried out on six normal male subjects to determine the short-term effect of increasing the dietary consumption of animal protein on the urinary risk factors for stone-formation, namely, volume, pH, calcium oxalate, uric acid and glycosaminoglycans. 2. An increase of 34 g/day of animal protein in the diet significantly increased urinary calcium (23%) and oxalate (24%). Total urinary nitrogen increased by an average of 368 mmol/day. The accompanying increase in dietary purine (11 mmol of purine nitrogen/day) caused a 48% increase in the excretion of uric acid. 3. The overall relative probability of forming stones, calculated from a combination of the risk factors, was markedly increased (250%) throughout the period of high animal protein ingestion.",
"title": "The effect of high animal protein intake on the risk of calcium stone-formation in the urinary tract."
},
{
"docid": "MED-1137",
"text": "The lifetime prevalence of kidney stones is around 10 % and incidence rates are increasing. Diet may be an important determinant of kidney stone development. Our objective was to investigate the association between diet and kidney stone risk in a population with a wide range of diets. This association was examined among 51,336 participants in the Oxford arm of the European Prospective Investigation into Cancer and Nutrition using data from Hospital Episode Statistics in England and Scottish Morbidity Records. In the cohort, 303 participants attended hospital with a new kidney stone episode. Cox proportional hazards regression was performed to calculate hazard ratios (HR) and their 95 % confidence intervals (95 % CI). Compared to those with high intake of meat (>100 g/day), the HR estimates for moderate meat-eaters (50-99 g/day), low meat-eaters (<50 g/day), fish-eaters and vegetarians were 0.80 (95 % CI 0.57-1.11), 0.52 (95 % CI 0.35-0.8), 0.73 (95 % CI 0.48-1.11) and 0.69 (95 % CI 0.48-0.98), respectively. High intakes of fresh fruit, fibre from wholegrain cereals and magnesium were also associated with a lower risk of kidney stone formation. A high intake of zinc was associated with a higher risk. In conclusion, vegetarians have a lower risk of developing kidney stones compared with those who eat a high meat diet. This information may be important to advise the public about prevention of kidney stone formation.",
"title": "Diet and risk of kidney stones in the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)."
},
{
"docid": "MED-1610",
"text": "The effects of three different meat-containing breakfast meals (pork, beef or chicken) on acute satiety and appetite regulatory hormones were compared using a within-subjects study design. Thirty fasting non-smoking pre-menopausal women attended a research centre on three test days to consume, a meat-containing meal matched in energy (kJ) and protein content, palatability, and appearance. No difference was found between meat groups for either energy intake or macronutrient profile of food consumed at a subsequent ad libitum buffet lunch, or over the rest of the day. Visual Analogue Scale (VAS) ratings for hunger and satiety over an 180 min period did not differ between test meals. After consumption of the test meals, a significant difference was found in PYY response between pork and chicken meals (P=0.027) but not for levels of CCK, ghrelin, insulin or glucose. This study positions pork, beef, and chicken as equal in their effect on satiety and release of appetite-related intestinal hormones and of insulin. Copyright © 2010 Elsevier Ltd. All rights reserved.",
"title": "Pork, beef and chicken have similar effects on acute satiety and hormonal markers of appetite."
},
{
"docid": "MED-3051",
"text": "The hypothalamus is intimately involved in the regulation of food intake, integrating multiple neural and hormonal signals. Several hypothalamic nuclei contain glucose-sensitive neurons, which play a crucial role in energy homeostasis. Although a few functional magnetic resonance imaging (fMRI) studies have indicated that glucose consumption has some effect on the neuronal activity levels in the hypothalamus, this matter has not been investigated extensively yet. For instance, dose-dependency of the hypothalamic responses to glucose ingestion has not been addressed. We measured the effects of two different glucose loads on neuronal activity levels in the human hypothalamus using fMRI. After an overnight fast, the hypothalamus of 15 normal weight men was scanned continuously for 37 min. After 7 min, subjects ingested either water or a glucose solution containing 25 or 75 g of glucose. We observed a prolonged decrease of the fMRI signal in the hypothalamus, which started shortly after subjects began drinking the glucose solution and lasted for at least 30 min. Moreover, the observed response was dose-dependent: a larger glucose load resulted in a larger signal decrease. This effect was most pronounced in the upper anterior hypothalamus. In the upper posterior hypothalamus, the signal decrease was similar for both glucose loads. No effect was found in the lower hypothalamus. We suggest a possible relation between the observed hypothalamic response and changes in the blood insulin concentration.",
"title": "Functional MRI of human hypothalamic responses following glucose ingestion."
},
{
"docid": "MED-4471",
"text": "Some indoor activities increase the number concentration of small particles and, hence, enhance the dose delivered to the lungs. The received particle dose indoors may exceed noticeably the dose from ambient air under routine in-house activities like cooking. In the present work, the internal dose by inhalation of ultrafine and fine particles is assessed, using an appropriate mechanistic model of lung deposition, accommodating aerosol, and inhalation dynamics. The analysis is based on size distribution measurements (10-350 nm) of indoor and outdoor aerosol number concentrations in a typical residence in Athens, Greece. Four different cases are examined, namely, a cooking event, a no activity period indoors and the equivalent time periods outdoors. When the cooking event (frying of bacon-eggs with a gas fire) occurred, the amount of deposited particles deep into the lung of an individual indoors exceeded by up to 10 times the amount received by an individual at the same time period outdoors. The fine particle deposition depends on the level of physical exertion and the hygroscopic properties of the inhaled aerosol. The dose is not found linearly dependant on the indoor/outdoor concentrations during the cooking event, whereas it is during the no activity period. PRACTICAL IMPLICATIONS: The necessity for determining the dose in specific regions of the human lung, as well as the non-linear relationship between aerosol concentration and internal dose makes the application of dosimetry models important. Lung dose of fine and ultrafine particles, during a cooking event, is compared with the dose at no indoor activity and the dose received under outdoor exposure conditions. The dose is expressed in terms of number or surface of deposited particles. This permits to address the dosimetry of very small particles, which are released by many indoor sources but represent a slight fraction of the particulate matter mass. The enhancement of the internal dose resulting from fine and ultrafine particles generated during the cooking event vs. the dose when no indoor source is active is assessed. The results for those cases are also compared with the dose calculated for the measured aerosol outdoors.",
"title": "Lung deposition of fine and ultrafine particles outdoors and indoors during a cooking event and a no activity period."
},
{
"docid": "MED-4355",
"text": "Sixty percent of the U.S. population experiences acute diarrheal illness each year, but little is understood regarding public knowledge and beliefs about the causes and treatment of these diseases. We performed a telephone survey of 2117 Tennessee residents regarding knowledge and practices associated with diarrheal illness. Bloody stool, dehydration, and persistent symptoms were the most common reasons for which the respondents would seek medical care. Although most acute diarrheal disease is self-limited, overuse of antimicrobials for treatment is common. Few people believed that stool cultures (4.5%) or antibiotics (6.9%) are routinely necessary for diarrhea. Over 60% of respondents believed that food is the most common source of diarrhea. Three-fourths believed that it is normal for uncooked meat to contain bacteria, and 45% believed it is legal to sell such products. These results have implications for medical providers, regulators, and public health in the management and prevention of diarrheal disease.",
"title": "Public knowledge and beliefs about diarrheal disease."
},
{
"docid": "MED-3046",
"text": "Tobacco smoking is the most frequent form of substance abuse. Several studies have shown that the addictive action of nicotine is mediated by the mesolimbic dopamine system. This system is implicated in reward processing. In order to better understand the relationship between nicotine addiction and reward in humans, we investigated differences between smokers and nonsmokers in the activation of brain regions involved in processing reward information. Using [H2(15O)] positron emission tomography (PET), we measured regional cerebral blood flow (rCBF) in healthy smokers and nonsmokers while they performed a prelearned, pattern-recognition task. We compared two conditions involving nonmonetary reinforcement or monetary reward with a baseline condition in which nonsense feedback was presented. With monetary reward, we found activation in the frontal and orbitofrontal cortex, occipital cortex, cingulate gyrus, cerebellum, and midbrain in both groups. Additionally, monetary reward activated typical dopaminergic regions such as the striatum in nonsmokers but not in smokers. We found a similar pattern of activation associated with nonmonetary reinforcement in nonsmokers, whereas activation was found in smokers only in the cerebellum. The different patterns of activation suggest that the brains of smokers react in a different way to reward than those of nonsmokers. This difference involves in particular the regions of the dopaminergic system including the striatum. In principle these observations could be interpreted either as a consequence of tobacco use or as a primitive condition of the brain that led people to smoke. Supported by related nonimaging studies, we interpret these differences as a consequence of tobacco smoking, even if a short-term effect of smoking prior to the experiment cannot be excluded.",
"title": "Changes in brain activation associated with reward processing in smokers and nonsmokers. A positron emission tomography study."
},
{
"docid": "MED-3059",
"text": "AIMS: In animals, intracerebroventricular glucose and fructose have opposing effects on appetite and weight regulation. In humans, functional brain magnetic resonance imaging (fMRI) studies during glucose ingestion or infusion have demonstrated suppression of hypothalamic signalling, but no studies have compared the effects of glucose and fructose. We therefore sought to determine if the brain response differed to glucose vs. fructose in humans independently of the ingestive process. METHODS: Nine healthy, normal weight subjects underwent blood oxygenation level dependent (BOLD) fMRI measurements during either intravenous (IV) glucose (0.3 mg/kg), fructose (0.3 mg/kg) or saline, administered over 2 min in a randomized, double-blind, crossover study. Blood was sampled every 5 min during a baseline period and following infusion for 60 min in total for glucose, fructose, lactate and insulin levels. RESULTS: No significant brain BOLD signal changes were detected in response to IV saline. BOLD signal in the cortical control areas increased during glucose infusion (p = 0.002), corresponding with increased plasma glucose and insulin levels. In contrast, BOLD signal decreased in the cortical control areas during fructose infusion (p = 0.006), corresponding with increases of plasma fructose and lactate. Neither glucose nor fructose infusions significantly altered BOLD signal in the hypothalamus. CONCLUSION: In normal weight humans, cortical responses as assessed by BOLD fMRI to infused glucose are opposite to those of fructose. Differential brain responses to these sugars and their metabolites may provide insight into the neurologic basis for dysregulation of food intake during high dietary fructose intake. © 2011 Blackwell Publishing Ltd.",
"title": "Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans."
},
{
"docid": "MED-4407",
"text": "Chronic inhalation of cigarette smoke (CS) induces emphysema by the damage contributed by oxidative stress during inhalation of CS. Ingestion of açai fruits (Euterpe oleracea) in animals has both antioxidant and anti-inflammatory effects. This study compared lung damage in mice induced by chronic (60-day) inhalation of regular CS and smoke from cigarettes containing 100mg of hydroalcoholic extract of açai berry stone (CS + A). Sham smoke-exposed mice served as the control group. Mice were sacrificed on day 60, bronchoalveolar lavage was performed, and the lungs were removed for histological and biochemical analyses. Histopathological investigation showed enlargement of alveolar space in CS mice compared to CS + A and control mice. The increase in leukocytes in the CS group was higher than the increase observed in the CS + A group. Oxidative stress, as evaluated by antioxidant enzyme activities, mieloperoxidase, glutathione, and 4-hydroxynonenal, was reduced in mice exposed to CS+A versus CS. Macrophage and neutrophil elastase levels were reduced in mice exposed to CS + A versus CS. Thus, the presence of açai extract in cigarettes had a protective effect against emphysema in mice, probably by reducing oxidative and inflammatory reactions. These results raise the possibility that addition of açaí extract to normal cigarettes could reduce their harmful effects. Copyright © 2010 Elsevier Ltd. All rights reserved.",
"title": "Addition of açaí (Euterpe oleracea) to cigarettes has a protective effect against emphysema in mice."
},
{
"docid": "MED-1860",
"text": "To compare the antihypertensive effectiveness of sour tea (ST; Hibiscus sabdariffa) with black tea (BT) infusion in diabetic patients, this double-blind randomized controlled trial was carried out. Sixty diabetic patients with mild hypertension, without taking antihypertensive or antihyperlipidaemic medicines, were recruited in the study. The patients were randomly allocated to the ST and BT groups and instructed to drink ST and BT infusions two times a day for 1 month. Their blood pressure (BP) was measured on days 0, 15 and 30 of the study. The mean of systolic BP (SBP) in the ST group decreased from 134.4+/-11.8 mm Hg at the beginning of the study to 112.7+/-5.7 mm Hg after 1 month (P-value <0.001), whereas this measure changed from 118.6+/-14.9 to 127.3+/-8.7 mm Hg (P-value=0.002) in the BT group during the same period. The intervention had no statistically significant effect on the mean of diastolic BP (DBP) in either the ST or BT group. The mean pulse pressure (PP) of the patients in the ST group decreased from 52.2+/-12.2 to 34.5+/-9.3 mm Hg (P-value <0.001) during the study, whereas in the BT group, it increased from 41.9+/-11.7 to 47.3+/-9.6 mm Hg (P-value=0.01). In conclusion, consuming ST infusion had positive effects on BP in type II diabetic patients with mild hypertension. This study supports the results of similar studies in which antihypertensive effects have been shown for ST.",
"title": "The effects of sour tea (Hibiscus sabdariffa) on hypertension in patients with type II diabetes."
},
{
"docid": "MED-1256",
"text": "BACKGROUND: Limited consumption of red meat, including beef, is one of many often-suggested strategies to reduce the risk of coronary heart disease (CHD). However, the role that beef consumption specifically plays in promoting adverse changes in the cardiovascular risk factor profile is unclear. OBJECTIVE: A meta-analysis of randomized, controlled, clinical trials (RCTs) was conducted to evaluate the effects of beef, independent of other red and processed meats, compared with poultry and/or fish consumption, on lipoprotein lipids. METHODS: RCTs published from 1950 to 2010 were considered for inclusion. Studies were included if they reported fasting lipoprotein lipid changes after beef and poultry/fish consumption by subjects free of chronic disease. A total of 124 RCTs were identified, and 8 studies involving 406 subjects met the prespecified entry criteria and were included in the analysis. RESULTS: Relative to the baseline diet, mean ± standard error changes (in mg/dL) after beef versus poultry/fish consumption, respectively, were -8.1 ± 2.8 vs. -6.2 ± 3.1 for total cholesterol (P = .630), -8.2 ± 4.2 vs. -8.9 ± 4.4 for low-density lipoprotein cholesterol (P = .905), -2.3 ± 1.0 vs. -1.9 ± 0.8 for high-density lipoprotein cholesterol (P = .762), and -8.1 ± 3.6 vs. -12.9 ± 4.0 mg/dL for triacylglycerols (P = .367). CONCLUSION: Changes in the fasting lipid profile were not significantly different with beef consumption compared with those with poultry and/or fish consumption. Inclusion of lean beef in the diet increases the variety of available food choices, which may improve long-term adherence with dietary recommendations for lipid management. Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.",
"title": "A meta-analysis of randomized controlled trials that compare the lipid effects of beef versus poultry and/or fish consumption."
},
{
"docid": "MED-3038",
"text": "The effects of 50 mg naltrexone on eating and subjective appetite were assessed in a double-blind placebo-controlled study with 20 male volunteers. Appetite was monitored using a disguised digital balance connected to a micro-computer, which constantly monitored the amount of food remaining, and which automatically interrupted feeding for 30 s after every 50 g consumed to allow appetite ratings to be made. Half the subjects ate pasta with a cheese sauce, and the remainder pasta with a tomato sauce. Subjects ate significantly less of both foods after 50 mg naltrexone than in either the placebo condition or on the initial (familiarisation) day. Naltrexone also reduced the rated pleasantness of both foods, and reduced overall eating rate. When best-fit quadratic functions were used to describe changes in rated hunger in relation to intake within the meal, naltrexone abolished the positive linear component reflecting the initial stimulation of appetite without altering either intercept or the negative quadratic function. Although mood ratings suggested that naltrexone had a mild sedative effect, mood changes alone could not explain the effects of naltrexone on appetite. Overall, these data suggest a specific role for opioids in the stimulation of appetite through palatability.",
"title": "Effects of naltrexone on food intake and changes in subjective appetite during eating: evidence for opioid involvement in the appetizer effect."
},
{
"docid": "MED-1650",
"text": "Short abstract Campaigns to promote healthy eating are undermined by the ubiquity of processed, energy dense foods. A global strategy is now needed to tackle the rising prevalence of obesity",
"title": "Tobacco and obesity epidemics: not so different after all?"
},
{
"docid": "MED-3597",
"text": "Background Dietary trans fatty acids (dTFA) are primarily synthetic compounds that have been introduced only recently; little is known about their behavioral effects. dTFA inhibit production of omega-3 fatty acids, which experimentally have been shown to reduce aggression. Potential behavioral effects of dTFA merit investigation. We sought to determine whether dTFA are associated with aggression/irritability. Methodolgy/Prinicpal Findings We capitalized on baseline dietary and behavioral assessments in an existing clinical trial to analyze the relationship of dTFA to aggression. Of 1,018 broadly sampled baseline subjects, the 945 adult men and women who brought a completed dietary survey to their baseline visit are the target of this analysis. Subjects (seen 1999–2004) were not on lipid medications, and were without LDL-cholesterol extremes, diabetes, HIV, cancer or heart disease. Outcomes assessed adverse behaviors with impact on others: Overt Aggression Scale Modified-aggression subscale (primary behavioral endpoint); Life History of Aggression; Conflict Tactics Scale; and self-rated impatience and irritability. The association of dTFA to aggression was analyzed via regression and ordinal logit, unadjusted and adjusted for potential confounders (sex, age, education, alcohol, and smoking). Additional analyses stratified on sex, age, and ethnicity, and examined the prospective association. Greater dTFA were strongly significantly associated with greater aggression, with dTFA more consistently predictive than other assessed aggression predictors. The relationship was upheld with adjustment for confounders, was preserved across sex, age, and ethnicity strata, and held cross-sectionally and prospectively. Conclusions/Significance This study provides the first evidence linking dTFA with behavioral irritability and aggression. While confounding is always a concern in observational studies, factors including strength and consistency of association, biological gradient, temporality, and biological plausibility add weight to the prospect of a causal connection. Our results may have relevance to public policy determinations regarding dietary trans fats. Clinicaltrials.gov # NCT00330980",
"title": "Trans Fat Consumption and Aggression"
},
{
"docid": "MED-4337",
"text": "The ingestion of fatty meals is associated with a transient, low-grade systemic inflammatory response in human subjects, involving the activation of circulating monocytes and the secretion of pro-inflammatory cytokines. However, it is not yet clear how different foodstuffs may promote inflammatory signalling. In a screen of forty filter-sterilised soluble extracts from common foodstuffs, seven were found to induce the secretion of TNF-α and IL-6 from human monocytes in vitro. To investigate what may differentiate inflammatory from non-inflammatory food extracts, stimulants of Toll-like receptor (TLR) 2 and TLR4 were quantified using human embryonic kidney-293 cells transfected with each TLR, and calibrated with defined bacterial lipopeptide (BLP) and lipopolysaccharide (LPS) standards. These assays revealed that while most foods contained undetectable levels of TLR2 or TLR4 stimulants, all TNF-α-inducing foods contained stimulants of either TLR2 (up to 1100 ng BLP-equivalent/g) or TLR4 (up to 2700 ng LPS-equivalent/g) in both the soluble and insoluble fractions. TLR stimulants were present mainly in meat products and processed foods, but were minimal or undetectable in fresh fruit and vegetables. The capacity of food extracts to induce TNF-α secretion in monocytes correlated with the content of both TLR2 (r 0·837) and TLR4 stimulants (r 0·748), and was completely abolished by specific inhibition of TLR2 and TLR4. LPS and BLP were found to be highly resistant to typical cooking times and temperatures, low pH and protease treatment. In conclusion, apparently unspoiled foodstuffs can contain large quantities of stimulants of TLR2 and TLR4, both of which may regulate their capacity to stimulate inflammatory signalling.",
"title": "The capacity of foodstuffs to induce innate immune activation of human monocytes in vitro is dependent on food content of stimulants of Toll-like r..."
},
{
"docid": "MED-1871",
"text": "In order to compare the antihypertensive effectiveness and tolerability of a standardized extract from Hibiscus sabdariffa with captopril, a controlled and randomized clinical trial was done. Patients from 30 to 80 years old with diagnosed hypertension and without antihypertensive treatment for at least 1 month before were included. The experimental procedure consisted of the administration of an infusion prepared with 10 g of dry calyx from H. sabdariffa on 0.51 water (9.6 mg anthocyanins content), daily before breakfast, or captopril 25 mg twice a day, for 4 weeks. The outcome variables were tolerability, therapeutic effectiveness (diastolic reduction > or = 10 mm Hg) and, in the experimental group, urinary electrolytes modification. Ninety subjects were included, 15 withdrew from the study due to non-medical reasons; so, the analysis included 39 and 36 patients from the experimental and control group, respectively. The results showed that H. sabdariffa was able to decrease the systolic blood pressure (BP) from 139.05 to 123.73mm Hg (ANOVA p < 0.03) and the diastolic BP from 90.81 to 79.52mm Hg (ANOVA p < 0.06). At the end of the study, there were no significant differences between the BP detected in both treatment groups (ANOVA p > 0.25). The rates of therapeutic effectiveness were 0.7895 and 0.8438 with H. sabdariffa and captopril, respectively (chi2, p > 0.560), whilst the tolerability was 100% for both treatments. A natriuretic effect was observed with the experimental treatment. The obtained data confirm that the H. sabdariffa extract, standardized on 9.6mg of total anthocyanins, and captopril 50 mg/day, did not show significant differences relative to hypotensive effect, antihypertensive effectiveness, and tolerability.",
"title": "Effectiveness and tolerability of a standardized extract from Hibiscus sabdariffa in patients with mild to moderate hypertension: a controlled and ..."
},
{
"docid": "MED-1616",
"text": "The role of very-low-carbohydrate ketogenic diets (VLCKD) in the long-term management of obesity is not well established. The present meta-analysis aimed to investigate whether individuals assigned to a VLCKD (i.e. a diet with no more than 50 g carbohydrates/d) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet (LFD; i.e. a restricted-energy diet with less than 30% of energy from fat). Through August 2012, MEDLINE, CENTRAL, ScienceDirect,Scopus, LILACS, SciELO, ClinicalTrials.gov and grey literature databases were searched, using no date or language restrictions, for randomised controlled trials that assigned adults to a VLCKD or a LFD, with 12 months or more of follow-up. The primary outcome was bodyweight. The secondary outcomes were TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), systolic and diastolic blood pressure,glucose, insulin, HbA1c and C-reactive protein levels. A total of thirteen studies met the inclusion/exclusion criteria. In the overall analysis,five outcomes revealed significant results. Individuals assigned to a VLCKD showed decreased body weight (weighted mean difference 20·91 (95% CI 21·65, 20·17) kg, 1415 patients), TAG (weighted mean difference 20·18 (95% CI 20·27, 20·08) mmol/l, 1258 patients)and diastolic blood pressure (weighted mean difference 21·43 (95% CI 22·49, 20·37) mmHg, 1298 patients) while increased HDL-C(weighted mean difference 0·09 (95% CI 0·06, 0·12) mmol/l, 1257 patients) and LDL-C (weighted mean difference 0·12 (95% CI 0·04,0·2) mmol/l, 1255 patients). Individuals assigned to a VLCKD achieve a greater weight loss than those assigned to a LFD in the longterm; hence, a VLCKD may be an alternative tool against obesity.",
"title": "Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials."
},
{
"docid": "MED-4556",
"text": "Tolerable upper intake levels (ULs) set by the Institute of Medicine (IOM) are important, in part because they are used for estimating the percentage of the population at potential risk of adverse effects from excessive nutrient intake. The IOM did not set ULs for trans fat, saturated fat, and cholesterol because any intake level above 0% of energy increased LDL cholesterol concentration and these three food components are unavoidable in ordinary diets. The purpose of the analysis presented in this review was to evaluate clinical trial and prospective observational data that were not previously considered for setting a UL with the aim of determining whether the current UL model could be used for saturated fat, trans fat, and cholesterol. The results of this analysis confirm the limitations of the risk assessment model for setting ULs because of its inability to identify a UL for food components, such as cholesterol, that lack an intake threshold associated with increased chronic disease risk. © 2011 International Life Sciences Institute.",
"title": "Tolerable upper intake levels for trans fat, saturated fat, and cholesterol."
},
{
"docid": "MED-3229",
"text": "High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.",
"title": "Protein intake, calcium balance and health consequences."
},
{
"docid": "MED-1864",
"text": "The effectiveness of Hibiscus sabdariffa L. (HS) in the treatment of risk factors associated with cardiovascular disease is assessed in this review by taking a comprehensive approach to interpreting the randomized clinical trial (RCT) results in the context of the available ethnomedical, phytochemical, pharmacological, and safety and toxicity information. HS decoctions and infusions of calyxes, and on occasion leaves, are used in at least 10 countries worldwide in the treatment of hypertension and hyperlipidemia with no reported adverse events or side effects. HS extracts have a low degree of toxicity with a LD50 ranging from 2,000 to over 5,000 mg/kg/day. There is no evidence of hepatic or renal toxicity as the result of HS extract consumption, except for possible adverse hepatic effects at high doses. There is evidence that HS acts as a diuretic, however in most cases the extract did not significantly influence electrolyte levels. Animal studies have consistently shown that consumption of HS extract reduces blood pressure in a dose dependent manner. In RCTs, the daily consumption of a tea or extract produced from HS calyxes significantly lowered systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults with pre to moderate essential hypertension and type 2 diabetes. In addition, HS tea was as effective at lowering blood pressure as the commonly used blood pressure medication Captropril, but less effective than Lisinopril. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides were lowered in the majority of normolipidemic, hypolipidemic, and diabetic animal models, whereas high-density lipoprotein cholesterol (HDL-C) was generally not affected by the consumption of HS extract. Over half of the RCTs showed that daily consumption of HS tea or extracts had favorable influence on lipid profiles including reduced total cholesterol, LDL-C, triglycerides, as well as increased HDL-C. Anthocyanins found in abundance in HS calyxes are generally considered the phytochemicals responsible for the antihypertensive and hypocholesterolemic effects, however evidence has also been provided for the role of polyphenols and hibiscus acid. A number of potential mechanisms have been proposed to explain the hypotensive and anticholesterol effects, but the most common explanation is the antioxidant effects of the anthocyanins inhibition of LDL-C oxidation, which impedes atherosclerosis, an important cardiovascular risk factor. This comprehensive body of evidence suggests that extracts of HS are promising as a treatment of hypertension and hyperlipidemia, however more high quality animal and human studies informed by actual therapeutic practices are needed to provide recommendations for use that have the potential for widespread public health benefit.",
"title": "Hibiscus sabdariffa L. in the treatment of hypertension and hyperlipidemia: a comprehensive review of animal and human studies"
},
{
"docid": "MED-4976",
"text": "Airborne cooking by-products from frying beef (hamburgers), pork (bacon strips) and soybean-based food (tempeh burgers) were collected, extracted, tested for mutagenicity and chemically analysed. The fumes generated by frying pork and beef were mutagenic, with 4900 and 1300 revertants/g of food cooked, respectively. No mutagenicity was detected in fumes from frying tempeh burgers. Bacon fried to a well-done but non-charred state was eight times more mutagenic in a microsuspension Ames/Salmonella test (TA98 with S-9) than hamburgers and about 350 times more mutagenic than tempeh burgers. Among food samples cooked to a well-done, non-charred state, bacon strips had almost 15-fold more mass (109.5 ng/g) than that of the beef, whereas no heterocyclic amine (HCA) was detected in the fried tempeh burgers. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was the most abundant HCA, followed by 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx). No 2-amino-9H-pyrido[2,3-b]indole (A alpha C) was detected in the food samples fried at about 200 degrees C, although it was present in the collected airborne products. The total amounts of HCAs in the smoke condensates were 3 ng/g from fried bacon, 0.37 ng/g from fried beef and 0.177 ng/g from fried soy-based food. This study indicates that cooks are potentially exposed to relatively high levels of airborne mutagens and carcinogens and that long-term sampling inside restaurants and kitchens may be warranted in order to assess the potential risk of prolonged exposure.",
"title": "Airborne mutagens produced by frying beef, pork and a soy-based food."
},
{
"docid": "MED-4676",
"text": "A widespread misconception has been developing among the Canadian public and among physicians. It is increasingly believed that consumption of dietary cholesterol and egg yolks is harmless. There are good reasons for long-standing recommendations that dietary cholesterol should be limited to less than 200 mg/day; a single large egg yolk contains approximately 275 mg of cholesterol (more than a day’s worth of cholesterol). Although some studies showed no harm from consumption of eggs in healthy people, this outcome may have been due to lack of power to detect clinically relevant increases in a low-risk population. Moreover, the same studies showed that among participants who became diabetic during observation, consumption of one egg a day doubled their risk compared with less than one egg a week. Diet is not just about fasting cholesterol; it is mainly about the postprandial effects of cholesterol, saturated fats, oxidative stress and inflammation. A misplaced focus on fasting lipids obscures three key issues. Dietary cholesterol increases the susceptibility of low-density lipoprotein to oxidation, increases postprandial lipemia and potentiates the adverse effects of dietary saturated fat. Dietary cholesterol, including egg yolks, is harmful to the arteries. Patients at risk of cardiovascular disease should limit their intake of cholesterol. Stopping the consumption of egg yolks after a stroke or myocardial infarction would be like quitting smoking after a diagnosis of lung cancer: a necessary action, but late. The evidence presented in the current review suggests that the widespread perception among the public and health care professionals that dietary cholesterol is benign is misplaced, and that improved education is needed to correct this misconception. Résumé Une idée fausse et généralisée se répand au sein du public canadien et des médecins, qui pensent de plus en plus que la consommation de cholestérol alimentaire et de jaunes d’œuf est inoffensive. Les recommandations de longue date qui préconisent de limiter le cholestérol alimentaire à moins de 200 mg/jour reposent sur de bonnes raisons. Un seul gros jaune d’œuf contient environ 275 mg de cholestérol (plus que la portion quotidienne de cholestérol). Même si certaines études ont démontré que la consommation d’œufs n’est pas nuisible chez les personnes en santé, ce résultat peut découler de l’absence de capacité à déceler des augmentations pertinentes sur le plan clinique au sein d’une population à faible risque. De plus, les mêmes études ont révélé que chez les participants devenus diabétiques pendant la période d’observation, la consommation d’un œuf par jour doublait leur risque par rapport à la consommation de moins d’un œuf par semaine. Le régime ne vise pas à éviter le cholestérol, mais surtout les effets postprandiaux du cholestérol, des gras saturés, du stress oxydant et de l’inflammation. Le fait de se concentrer à tort sur les lipides à jeun occulte trois enjeux. Le cholestérol alimentaire accroît la susceptibilité des lipoprotéines à faible densité à l’oxydation, accroît la lipémie postprandiale et potentialise les effets secondaires des graisses saturées alimentaires. Le cholestérol alimentaire, y compris les jaunes d’œuf, est nuisible pour les artères. Les patients vulnérables aux maladies cardiovasculaires devraient limiter leur consommation de cholestérol. Le fait d’arrêter de consommer des jaunes d’œuf après un accident vasculaire cérébral ou un infarctus du myocarde s’apparenterait à arrêter de fumer après un diagnostic de cancer du poumon : c’est un geste nécessaire, mais entrepris tardivement. D’après les données probantes présentées dans la présente analyse, la perception généralisée du public et des professionnels de la santé selon laquelle le cholestérol alimentaire est un mal bénin est une idée fausse, et une meilleure information s’impose pour la corriger.",
"title": "Dietary cholesterol and egg yolks: Not for patients at risk of vascular disease"
},
{
"docid": "MED-4559",
"text": "The cardiovascular risk reduction associated with different statins for the prevention of cardiovascular disease and the cardiovascular risk increase associated with excess dietary intake of fat have been quantified. However, these relative risks have never been directly juxtaposed to determine whether an increase in relative risk by 1 activity could be neutralized by an opposing change in relative risk from a second activity. The investigators compared the increase in relative risk for cardiovascular disease associated with the total fat and trans fat content of fast foods against the relative risk decrease provided by daily statin consumption from a meta-analysis of statins in primary prevention of coronary artery disease (7 randomized controlled trials including 42,848 patients). The risk reduction associated with the daily consumption of most statins, with the exception of pravastatin, is more powerful than the risk increase caused by the daily extra fat intake associated with a 7-oz hamburger (Quarter Pounder) with cheese and a small milkshake. In conclusion, statin therapy can neutralize the cardiovascular risk caused by harmful diet choices. In other spheres of human activity, individuals choosing risky pursuits (motorcycling, smoking, driving) are advised or compelled to use measures to minimize the risk (safety equipment, filters, seatbelts). Likewise, some individuals eat unhealthily. Routine accessibility of statins in establishments providing unhealthy food might be a rational modern means to offset the cardiovascular risk. Fast food outlets already offer free condiments to supplement meals. A free statin-containing accompaniment would offer cardiovascular benefits, opposite to the effects of equally available salt, sugar, and high-fat condiments. Although no substitute for systematic lifestyle improvements, including healthy diet, regular exercise, weight loss, and smoking cessation, complimentary statin packets would add, at little cost, 1 positive choice to a panoply of negative ones.",
"title": "Can a statin neutralize the cardiovascular risk of unhealthy dietary choices?"
},
{
"docid": "MED-1617",
"text": "Background Dietary modification via caloric restriction is associated with multiple effects related to improved metabolic and cardiovascular health. However, a mandated reduction in kilocalories is not well-tolerated by many individuals, limiting the long-term application of such a plan. The Daniel Fast is a widely utilized fast based on the Biblical book of Daniel. It involves a 21 day ad libitum food intake period, devoid of animal products and preservatives, and inclusive of fruits, vegetables, whole grains, legumes, nuts, and seeds. The purpose of the present study was to determine the efficacy of the Daniel Fast to improve markers of metabolic and cardiovascular disease risk. Methods 43 subjects (13 men; 30 women; 35 ± 1 yrs; range: 20-62 yrs) completed a 21 day period of modified food intake in accordance with detailed guidelines provided by investigators. All subjects purchased and prepared their own food. Following initial screening, subjects were given one week to prepare for the fast, after which time they reported to the lab for their pre-intervention assessment (day 1). After the 21 day fast, subjects reported to the lab for their post-intervention assessment (day 22). For both visits, subjects reported in a 12 hr fasted state, performing no strenuous physical activity during the preceding 24-48 hrs. At each visit, mental and physical health (SF-12 form), resting heart rate and blood pressure, and anthropometric variables were measured. Blood was collected for determination of complete blood count, metabolic panel, lipid panel, insulin, HOMA-IR, and C-reactive protein (CRP). Subjects' self-reported compliance, mood, and satiety in relation to the fast were also recorded. Diet records were maintained by all subjects during the 7 day period immediately prior to the fast (usual intake) and during the final 7 days of the fast. Results Subjects' compliance to the fast was 98.7 ± 0.2% (mean ± SEM). Using a 10 point scale, subjects' mood and satiety were both 7.9 ± 0.2. The following variables were significantly (p < 0.05) lower following the fast as compared to before the fast: white blood cell count (5.68 ± 0.24 vs. 4.99 ± 0.19 103·μL-1), blood urea nitrogen (13.07 ± 0.58 vs. 10.14 ± 0.59 mg·dL-1), blood urea nitrogen/creatinine (14.74 ± 0.59 vs. 11.67 ± 0.68), protein (6.95 ± 0.07 vs. 6.77 ± 0.06 g·dL-1), total cholesterol (171.07 ± 4.57 vs. 138.69 ± 4.39 mg·dL-1), LDL-C (98.38 ± 3.89 vs. 76.07 ± 3.53 mg·dL-1), HDL-C (55.65 ± 2.50 vs. 47.58 ± 2.19 mg·dL-1), SBP (114.65 ± 2.34 vs. 105.93 ± 2.12 mmHg), and DBP (72.23 ± 1.59 vs. 67.00 ± 1.43 mmHg). Insulin (4.42 ± 0.52 vs. 3.37 ± 0.35 μU·mL-1; p = 0.10), HOMA-IR (0.97 ± 0.13 vs.0.72 ± 0.08; p = 0.10), and CRP (3.15 ± 0.91 vs. 1.60 ± 0.42 mg·L-1; p = 0.13), were lowered to a clinically meaningful, albeit statistically insignificant extent. No significant difference was noted for any anthropometric variable (p > 0.05). As expected, multiple differences in dietary intake were noted (p < 0.05), including a reduction in total kilocalorie intake (2185 ± 94 vs. 1722 ± 85). Conclusion A 21 day period of modified dietary intake in accordance with the Daniel Fast is 1) well-tolerated by men and women and 2) improves several risk factors for metabolic and cardiovascular disease. Larger scale, randomized studies, inclusive of a longer time period and possibly a slight modification in food choice in an attempt to maintain HDL cholesterol, are needed to extend these findings.",
"title": "Effect of a 21 day Daniel Fast on metabolic and cardiovascular disease risk factors in men and women"
},
{
"docid": "MED-3599",
"text": "The dietary intake of industrially-produced trans fatty acids (IP-TFA) was estimated for the US population (aged 2 years or more), children (aged 2-5 years) and teenage boys (aged 13-18 years) using the 2003-2006 National Health and Nutrition Examination Survey (NHANES) food consumption database, market share information and trans fat levels based on label survey data and analytical data for packaged and in-store purchased foods. For fast foods, a Monte Carlo model was used to estimate IP-TFA intake. Further, the intake of trans fat was also estimated using trans fat levels reported in the US Department of Agriculture (USDA) National Nutrient Database for Standard Reference, Release 22 (SR 22, 2009) and the 2003-2006 NHANES food consumption database. The cumulative intake of IP-TFA was estimated to be 1.3 g per person per day (g/p/d) at the mean for the US population. Based on this estimate, the mean dietary intake of IP-TFA has decreased significantly from that cited in the 2003 US Food and Drug Administration (FDA) final rule that established labelling requirements for trans fat (4.6 g/p/d for adults). Although the overall intake of IP-TFA has decreased as a result of the implementation of labelling requirements, individuals with certain dietary habits may still consume high levels of IP-TFA if certain brands or types of food products are frequently chosen.",
"title": "Updated estimate of trans fat intake by the US population."
},
{
"docid": "MED-4831",
"text": "Dyslipidemia is a primary risk factor for cardiovascular disease, peripheral vascular disease, and stroke. Current guidelines recommend diet as first-line therapy for patients with elevated plasma cholesterol concentrations. However, what constitutes an optimal dietary regimen remains a matter of controversy. Large prospective trials have demonstrated that populations following plant-based diets, particularly vegetarian and vegan diets, are at lower risk for ischemic heart disease mortality. The investigators therefore reviewed the published scientific research to determine the effectiveness of plant-based diets in modifying plasma lipid concentrations. Twenty-seven randomized controlled and observational trials were included. Of the 4 types of plant-based diets considered, interventions testing a combination diet (a vegetarian or vegan diet combined with nuts, soy, and/or fiber) demonstrated the greatest effects (up to 35% plasma low-density lipoprotein cholesterol reduction), followed by vegan and ovolactovegetarian diets. Interventions allowing small amounts of lean meat demonstrated less dramatic reductions in total cholesterol and low-density lipoprotein levels. In conclusion, plant-based dietary interventions are effective in lowering plasma cholesterol concentrations.",
"title": "Effects of plant-based diets on plasma lipids."
},
{
"docid": "MED-1249",
"text": "The effect of dietary protein on the level of plasma cholesterol in young, healthy, normolipidemic women was investigated in two separate studies by feeding either a conventional diet containing mixed protein, or a plant protein diet in which the animal protein of the first diet was replaced by soy protein meat analogues and soy milk. The diets were similar with respect to carbohydrate, fat and sterol composition. The first study, lasting 73 days and involving six subjects, gave an indication that plasma cholesterol levels were lower on the plant protein diet. The second study, which incorporated a number of improvements based on experience, lasted 78 days and used a cross-over design involving two groups of five subjects each. In this study, the mean plasma cholesterol level was found to be significantly lower on the plant protein diet.",
"title": "Hypocholesterolemic effect of substituting soybean protein for animal protein in the diet of healthy young women."
},
{
"docid": "MED-1613",
"text": "The present study was designed to examine the effects of habitual consumption of Taiwanese vegetarian diets on hormonal secretion, and on lipid and glycaemic control. Of the ninety-eight healthy female adults recruited from Hualien, Taiwan (aged 31-45 years), forty-nine were Buddhist lactovegetarians and forty-nine were omnivores. Dietary intakes were measured, and blood levels of nutrients and hormones were analysed. Vegetarians consumed less energy, fat and protein, but more fibre than the omnivores. Compared with the omnivores, the vegetarians had, on average, lower BMI and smaller waist circumference. Except for slightly lower levels of thyroxine (T4) in vegetarians, vegetarians and omnivores both showed similar levels of triiodothyronine (T3), free T4, thyroid-stimulating hormone, T3:T4 ratio and cortisol. Compared with the omnivores, the vegetarians had significantly lower levels of fasting insulin (median: 35.3 v. 50.6 pmol/l) and plasma glucose (mean: 4.7 (se 0.05) v. 4.9 (se 0.05) mmol/l). Insulin resistance, as calculated by the homeostasis model assessment method, was significantly lower in the vegetarians than in the omnivores (median: 1.10 v. 1.56), while beta-cell function was not different between the two groups. BMI and diet were both independent predictors for insulin resistance, and contributed 18 and 15 % of the variation in insulin resistance, respectively. In conclusion, Taiwanese vegetarians had lower glucose and insulin levels and higher insulin sensitivity than did the omnivores. Diet and lower BMI were partially responsible for the high insulin sensitivity observed in young Taiwanese vegetarians.",
"title": "Taiwanese vegetarians have higher insulin sensitivity than omnivores."
},
{
"docid": "MED-5328",
"text": "Aim To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. Methods and Results Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses. Conclusion Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.",
"title": "Vegetarian diets and incidence of diabetes in the Adventist Health Study-2"
},
{
"docid": "MED-1612",
"text": "Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 +/- 33 microU X h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.",
"title": "Effect of protein ingestion on the glucose and insulin response to a standardized oral glucose load."
},
{
"docid": "MED-1614",
"text": "AIM: To compare the insulin sensitivity indices between Chinese vegetarians and omnivores. METHODS: The study included 36 healthy volunteers (vegetarian, n=19; omnivore, n=17) who had normal fasting plasma glucose levels. Each participant completed an insulin suppression test. We compared steady-state plasma glucose (SSPG), fasting insulin, the homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and beta-cell function (HOMA %beta) between the groups. We also tested the correlation of SSPG with years on a vegetarian diet. RESULTS: The omnivore subjects were younger than the vegetarians (55.7+/-3.7 vs 58.6+/-3.6 year of age, P=0.022). There was no difference between the two groups in sex, blood pressure, renal function tests and lipid profiles. The omnivores had higher serum uric acid levels than vegetarians (5.25+/-0.84 vs 4.54+/-0.75 mg/dl, P=0.011). The results of the indices were different between omnivores and vegetarians (SSPG (mean+/-s.d.) 105.4+/-10.2 vs 80.3+/-11.3 mg/dl, P<0.001; fasting insulin, 4.06+/-0.77 vs 3.02+/-1.19 microU/ml, P=0.004; HOMA-IR, 6.75+/-1.31 vs 4.78+/-2.07, P=0.002; HOMA %S, 159.2+/-31.7 vs 264.3+/-171.7%, P=0.018) except insulin secretion index, HOMA %beta (65.6+/-18.0 vs 58.6+/-14.8%, P=0.208). We found a clear linear relation between years on a vegetarian diet and SSPG (r=-0.541, P=0.017). CONCLUSIONS: The vegetarians were more insulin sensitive than the omnivore counterparts. The degree of insulin sensitivity appeared to be correlated with years on a vegetarian diet.",
"title": "Insulin sensitivity in Chinese ovo-lactovegetarians compared with omnivores."
},
{
"docid": "MED-1250",
"text": "The effect of plant and animal protein on blood lipid levels was investigated in eight healthy normolipidemic men aged 18 to 27 yr. All subjects were fed both plant and animal protein diets in a cross-over design. Each diet was consumed for a 21-day period. Proteins from commonly used plant sources made up the plant protein diet. Beef protein was substituted for 55% of the plant proteins in the animal protein diet. Fasting venous blood samples were collected at the beginning of the study and at 7-day intervals throughout the 42-day study. Serum was analyzed for total cholesterol and triglycerides. Plasma low-density and high-density lipoprotein cholesterol were determined. There were not any statistically significant differences in mean serum total cholesterol or mean plasma low-density lipoprotein cholesterol when subjects consumed the diets. Mean plasma high-density lipoprotein cholesterol levels were significantly (p less than 0.05) elevated at the end of the 21-day period when the animal protein diet was consumed (48 +/- 3 mg/dl) compared to the period when the plant protein diet was fed (42 +/- 2 mg/dl). Mean serum triglyceride values were significantly (p less than 0.05) increased at day 7 of the plant protein diet period (136 +/- 19 mg/dl) compared to the same time period when the animal protein diet was consumed (84 +/- 12 mg/dl). The results of the study indicated that the ingestion of a diet in which 55% of the protein was supplied by beef protein was not associated with a hypercholesterolemic effect in healthy normolipidemic young men.",
"title": "A comparison of the effect of diets containing beef protein and plant proteins on blood lipids of healthy young men."
},
{
"docid": "MED-1857",
"text": "BACKGROUND/OBJECTIVES: Investigations about possible correlations between vegetarian diet and periodontal conditions are rare and characterized by small case numbers. The aim of this clinical study was to investigate the influence of a vegetarian diet on periodontal parameters with an appropriate sample size. SUBJECTS/METHODS: A total of 200 patients, 100 vegetarians and 100 non-vegetarians, were included in the study. All patients were examined including a full mouth assessment of the periodontal and dental conditions. In addition, a questionnaire was handed out to ask for patients' oral hygiene habits and level of education. For statistical analysis the Mann-Whitney Test (χ(2) for analysis of the questionnaire) was applied (level of significance: P<0.05). RESULTS: Well known periodontal risk factors like age, gender and smoking habits were equally distributed within each group (71 females, 29 males, respectively and 10 smokers in each group; mean age: 41.45 years vegetarians versus 41.72 years non-vegetarians). Vegetarians had significantly lower probing pocket depths (P=0.039), bleeding on probing (P=0.001), periodontal screening index (P=0.012), a better hygiene index (P<0.001) and less mobile teeth (P=0.013). Dental examinations revealed significantly less missing teeth (P=0.018) but also more decayed (P=0.001) and eroded (P=0.026) teeth in vegetarians. Furthermore, vegetarians had a higher level of education (P<0.001), but visited dentists significantly less frequent. CONCLUSIONS: Vegetarians revealed better periodontal conditions (less inflammation signs, less periodontal damage and a better dental home care). However, it should be considered that vegetarians are not only avoiding meat in their nutrition but are also characterized by an overall healthier life style.",
"title": "Periodontal conditions in vegetarians: a clinical study."
},
{
"docid": "MED-1620",
"text": "Background The Daniel Fast is a vegan diet that prohibits the consumption of animal products, refined foods, white flour, preservatives, additives, sweeteners, flavorings, caffeine, and alcohol. Following this dietary plan for 21 days has been demonstrated to improve blood pressure, LDL-C, and certain markers of oxidative stress, but it has also been shown to lower HDL-C. Krill oil supplementation has been shown to increase HDL-C. Methods We investigated the effects of following a Daniel Fast dietary plan with either krill oil supplementation (2 g/day) or placebo supplementation (coconut oil; 2 g/day) for 21 days. The subjects in this study (12 men and 27 women) were heterogeneous with respect to body mass index (BMI) (normal weight, overweight, and obese), blood lipids (normolipidemic and hyperlipidemic), blood glucose (normal fasting glucose, impaired fasting glucose, and type 2 diabetic), and blood pressure (normotensive and hypertensive). Results Krill oil supplementation had no effect on any outcome measure (all p > 0.05), and so the data from the krill oil group and the placebo group were collapsed and analyzed to examine the effects of following a 21-day Daniel Fast. Significant reductions were observed in LDL-C (100.6 ± 4.3 mg/dL vs. 80.0 ± 3.7 mg/dL), the LDL:HDL ratio (2.0 ± 0.1 vs. 1.7 ± 0.1), fasting blood glucose (101.4 ± 7.5 mg/dL vs. 91.7 ± 3.4 mg/dL), fasting blood insulin (7.92 ± 0.80 μU/mL vs. 5.76 ± 0.59 μU/mL), homeostasis model assessment of insulin resistance (HOMA-IR) (2.06 ± 0.30 vs. 1.40 ± 0.21), systolic BP (110.7 ± 2.2 mm Hg vs. 105.5 ± 1.7 mm Hg), and body weight (74.1 ± 2.4 kg vs. 71.5 ± 2.3 kg) (all p < 0.05). Conclusion Following a Daniel Fast dietary plan improves a variety of cardiometabolic parameters in a wide range of individuals in as little as 21 days, and these improvements are unaffected by krill oil supplementation. Trial registration Clinicaltrial.govNCT01378767",
"title": "A 21-day Daniel fast with or without krill oil supplementation improves anthropometric parameters and the cardiometabolic profile in men and women"
},
{
"docid": "MED-1133",
"text": "Background The last nationally representative assessment of kidney stone prevalence in the United States occurred in 1994. After a 13-yr hiatus, the National Health and Nutrition Examination Survey (NHANES) reinitiated data collection regarding kidney stone history. Objective Describe the current prevalence of stone disease in the United States, and identify factors associated with a history of kidney stones. Design, setting, and participants A cross-sectional analysis of responses to the 2007–2010 NHANES (n = 12 110). Outcome measurements and statistical analysis Self-reported history of kidney stones. Percent prevalence was calculated and multivariable models were used to identify factors associated with a history of kidney stones. Results and limitations The prevalence of kidney stones was 8.8% (95% confidence interval [CI], 8.1–9.5). Among men, the prevalence of stones was 10.6% (95% CI, 9.4–11.9), compared with 7.1% (95% CI, 6.4–7.8) among women. Kidney stones were more common among obese than normal-weight individuals (11.2% [95% CI, 10.0–12.3] compared with 6.1% [95% CI, 4.8–7.4], respectively; p < 0.001). Black, non-Hispanic and Hispanic individuals were less likely to report a history of stone disease than were white, non-Hispanic individuals (black, non-Hispanic: odds ratio [OR]: 0.37 [95% CI, 0.28–0.49], p < 0.001; Hispanic: OR: 0.60 [95% CI, 0.49–0.73], p < 0.001). Obesity and diabetes were strongly associated with a history of kidney stones in multivariable models. The cross-sectional survey design limits causal inference regarding potential risk factors for kidney stones. Conclusions Kidney stones affect approximately 1 in 11 people in the United States. These data represent a marked increase in stone disease compared with the NHANES III cohort, particularly in black, non-Hispanic and Hispanic individuals. Diet and lifestyle factors likely play an important role in the changing epidemiology of kidney stones.",
"title": "Prevalence of Kidney Stones in the United States"
},
{
"docid": "MED-4975",
"text": "BACKGROUND: Children from low-income families may be subject to high exposures to polycyclic aromatic hydrocarbons (PAH) which can lead to respiratory disorders. This study aims to establish methods for assessing total PAH exposure of asthmatic and non-asthmatic children from low-income families; to estimate serum PAH concentrations of these children, and to estimate the relative importance of the environmental pathways for PAH exposure. MATERIALS AND METHODS: A total of 75 (61 asthmatic, 14 non-asthmatic) Saudi children 15 years old and below were included to participate in this cross-sectional study. Each participant answered a generalized questionnaire with dietary questions. Serum PAH were measured using HPLC with UV detection. RESULTS: Serum naphthalene and pyrene were significantly elevated among asthmatic children (p-values = 0.007 and 0.01, respectively). Serum acenaphthylene, fluorine and 1,2-benzanthracene, on the other hand, were significantly higher among non-asthmatics (p-values = 0.001, 0.04 and 0.03, respectively). There was a significant correlation between the presence of a smoker in the family and serum concentrations of carbazole, pyrene, 1,2-benzanthracene and benzacephenanthrylene (R = 0.37, 0.45, 0.43, 0.33; p-values = 0.01, 0.0002, 0.003 and 0.025, respectively). Significant correlations were elicited between daily meat intake and serum levels of acenaphthylene, benzopyrene and 1,2-benzanthracene (R = 0.27, 0.27, 0.33; p-values = 0.02 and < 0.001, respectively). CONCLUSION: Among the children, serum PAH were significantly correlated to meat intake as well as presence of smokers at home. Public health awareness should be enhanced by educating parents to take certain precautions at home, such as preventing indoor smoking and reducing the intake of grilled and smoked meat by children so as to decrease their exposure to carcinogenic PAH.",
"title": "Serum polycyclic aromatic hydrocarbons among children with and without asthma: correlation to environmental and dietary factors."
},
{
"docid": "MED-1138",
"text": "PURPOSE: We compared the effect of 3 animal protein sources on urinary stone risk. MATERIALS AND METHODS: A total of 15 healthy subjects completed a 3-phase randomized, crossover metabolic study. During each 1-week phase subjects consumed a standard metabolic diet containing beef, chicken or fish. Serum chemistry and 24-hour urine samples collected at the end of each phase were compared using mixed model repeated measures analysis. RESULTS: Serum and urinary uric acid were increased for each phase. Beef was associated with lower serum uric acid than chicken or fish (6.5 vs 7.0 and 7.3 mg/dl, respectively, each p <0.05). Fish was associated with higher urinary uric acid than beef or chicken (741 vs 638 and 641 mg per day, p = 0.003 and 0.04, respectively). No significant difference among phases was noted in urinary pH, sulfate, calcium, citrate, oxalate or sodium. Mean saturation index for calcium oxalate was highest for beef (2.48), although the difference attained significance only compared to chicken (1.67, p = 0.02) but not to fish (1.79, p = 0.08). CONCLUSIONS: Consuming animal protein is associated with increased serum and urine uric acid in healthy individuals. The higher purine content of fish compared to beef or chicken is reflected in higher 24-hour urinary uric acid. However, as reflected in the saturation index, the stone forming propensity is marginally higher for beef compared to fish or chicken. Stone formers should be advised to limit the intake of all animal proteins, including fish. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.",
"title": "Animal protein and the risk of kidney stones: a comparative metabolic study of animal protein sources."
},
{
"docid": "MED-4973",
"text": "Urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) are a class of PAH metabolites used as biomarkers for assessing human exposure to PAHs. The Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey (NHANES) uses OH-PAHs to establish reference range concentrations for the US population, and to set benchmarks for future epidemiologic and biomonitoring studies. For the years 2001 and 2002, 22 OH-PAH metabolites were measured in urine specimens from 2748 NHANES participants. Percentages of samples with detectable levels ranged from nearly 100% for metabolites of naphthalene, fluorene, phenanthrene, and pyrene, to less than 5% for metabolites from parent compounds with higher molecular weight such as chrysene, benzo[c]phenanthrene, and benz[a]anthracene. The geometric mean for 1-hydroxypyrene (1-PYR)--the most commonly used biomarker for PAH exposure--was 49.6 ng/L urine, or 46.4 ng/g creatinine. Children (ages 6-11) generally had higher levels than did adolescents (ages 12-19) or adults (ages 20 and older). Model-adjusted, least-square geometric means for 1-PYR were 87, 53 and 43 ng/L for children, adolescents (ages 12-19) and adults (ages 20 years and older), respectively. Log-transformed concentrations for major detectable OH-PAHs were significantly correlated with each other. The correlation coefficients between 1-PYR and other metabolites ranging from 0.17 to 0.63 support the use of 1-PYR as a useful surrogate representing PAH exposure.",
"title": "Concentration and profile of 22 urinary polycyclic aromatic hydrocarbon metabolites in the US population."
},
{
"docid": "MED-4411",
"text": "Chronic obstructive pulmonary disease (COPD) is characterised by increased oxidative stress. Dietary factors, such as ample consumption of foods rich in antioxidants, such as fruit and vegetables, might have beneficial effects in COPD patients. The association between dietary shift to foods rich in antioxidants and lung function in COPD was investigated in a 3-yr prospective study. A total of 120 COPD patients were randomised to follow either a diet based on increased consumption of fresh fruit and vegetables (intervention group (IG)) or a free diet (control group (CG)). The mean consumption of foods containing antioxidants was higher in the IG than in the CG throughout the study period (p<0.05). The relationship between consumption of foods rich in antioxidants and percentage predicted forced expiratory volume in 1 s was assessed using a general linear model for repeated measures; the two groups overall were different in time (p = 0.03), with the IG showing a better outcome. In investigating the effect of several confounders (sex, age, smoking status, comorbid conditions and exacerbation) of group response over time, nonsignificant interactions were found between confounders, group and time. These findings suggest that a dietary shift to higher-antioxidant food intake may be associated with improvement in lung function, and, in this respect, dietary interventions might be considered in COPD management.",
"title": "Impact of dietary shift to higher-antioxidant foods in COPD: a randomised trial."
},
{
"docid": "MED-3050",
"text": "Background: Weight gain leads to reduced reward-region responsivity to energy-dense food receipt, and consumption of an energy-dense diet compared with an isocaloric, low-energy-density diet leads to reduced dopamine receptors. Furthermore, phasic dopamine signaling to palatable food receipt decreases after repeated intake of that food, which collectively suggests that frequent intake of an energy-dense food may reduce striatal response to receipt of that food. Objective: We tested the hypothesis that frequent ice cream consumption would be associated with reduced activation in reward-related brain regions (eg, striatum) in response to receipt of an ice cream–based milkshake and examined the influence of adipose tissue and the specificity of this relation. Design: Healthy-weight adolescents (n = 151) underwent fMRI during receipt of a milkshake and during receipt of a tasteless solution. Percentage body fat, reported food intake, and food craving and liking were assessed. Results: Milkshake receipt robustly activated the striatal regions, yet frequent ice cream consumption was associated with a reduced response to milkshake receipt in these reward-related brain regions. Percentage body fat, total energy intake, percentage of energy from fat and sugar, and intake of other energy-dense foods were not related to the neural response to milkshake receipt. Conclusions: Our results provide novel evidence that frequent consumption of ice cream, independent of body fat, is related to a reduction in reward-region responsivity in humans, paralleling the tolerance observed in drug addiction. Data also imply that intake of a particular energy-dense food results in attenuated reward-region responsivity specifically to that food, which suggests that sensory aspects of eating and reward learning may drive the specificity.",
"title": "Frequent ice cream consumption is associated with reduced striatal response to receipt of an ice cream–based milkshake"
},
{
"docid": "MED-1651",
"text": "Background Limited information is available regarding the impact of candy consumption on health. The purpose of this study was to investigate associations between typical frequency of candy consumption and body weight status and select cardiovascular risk factors among adults in the United States. Methods Using data collected in the 2003–2006 National Health and Nutrition Examination Surveys (NHANES), adults were categorized as infrequent (≤ 3 eating occasions [EO]/month), moderate (> 3 EO/month and ≤ 3.5 EO/week), or frequent (> 3.5 EO/week) candy consumers based on the combined frequency of chocolate and other candy consumption over the previous 12 months. Weight and adiposity status were analyzed using logistic regression models, and blood pressure, lipids, and insulin sensitivity were analyzed using linear regression models. Models were adjusted for age, sex and race/ethnicity, and also for additional covariates with potential associations with the outcomes. Appropriate statistical weights were used to yield results generalizable to the US population. Results Frequency of candy consumption was not associated with the risk of obesity, overweight/obesity, elevated waist circumference, elevated skinfold thickness, blood pressure, low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol, triglycerides, or insulin resistance. Increased frequency of candy consumption was associated with higher energy intakes and higher energy adjusted intakes of carbohydrates, total sugars and added sugars, total fat, saturated fatty acids and monounsaturated fatty acids (p < 0.05), and lower adjusted intakes of protein and cholesterol (p < 0.001). Conclusions Increased frequency of candy consumption among adults in the United States was not associated with objective measures of adiposity or select cardiovascular risk factors, despite associated dietary differences. Given the cross-sectional study design, however, it cannot be concluded that candy consumption does not cause obesity or untoward levels of cardiovascular risk markers. The lack of an association between frequency of candy consumption and cardiovascular risk factors could be due to reduced intake of candy among the overweight due to dieting or a health professional’s recommendations. Additionally, it is important to note that the analysis was based on frequency of candy consumption and not amount of candy consumed. Longitudinal studies are needed to confirm the lack of associations between frequency of candy consumption and cardiovascular risk factors.",
"title": "Body weight status and cardiovascular risk factors in adults by frequency of candy consumption"
},
{
"docid": "MED-3232",
"text": "High dietary acid load (DAL) may be detrimental to bone mineral density (BMD). The objectives of the study were to: 1) evaluate the cross-sectional relation between DAL and BMD; 2) determine whether calcium intake modifies this association. Men (n=1218) and women (n=907) ≥60y were included from the National Health and Nutrition Examination Survey 2005–2008. Nutrient intake from 2–24h recalls was used to calculate net endogenous acid production (NEAP) and potential renal acid load (PRAL) (mEq/d). PRAL was calculated from dietary calcium (PRALdiet) and diet + supplemental calcium (PRALtotal). Tests for linear trend in adjusted mean BMD of the hip and lumbar spine were performed across energy adjusted NEAP and PRAL quartiles. Modification by calcium intake (dietary or total) above or below 800 mg/d was assessed by interaction terms. Overall, mean age was 69 ± 0.3y. Among women, there was no association between NEAP and BMD. PRALdiet was positively associated with proximal femur BMD (p trend=0.04). No associations were observed with PRALtotal at any BMD site (P-range: 0.38–0.82). Among men, no significant associations were observed of BMD with NEAP or PRAL. However, an interaction between PRALdiet and calcium intake was observed with proximal femur BMD (p=0.08). An inverse association between PRALdiet and proximal femur BMD was detected among men <800 mg/d dietary calcium (p=0.02); and no associations ≥800 mg/d (p=0.98). A significant interaction with PRALtotal was not observed. In conclusion, when supplemental calcium is considered, there is no association between DAL and BMD among adults. Men with low dietary calcium showed an inverse relation with PRAL at the proximal femur; in women no interaction was observed. This study highlights the importance of calcium intakes in counteracting the adverse effect of DAL on bone health. Further research should determine the relation between DAL and change in BMD with very low calcium intake.",
"title": "Dietary acid load is associated with lower bone mineral density in men with low intake of dietary calcium"
},
{
"docid": "MED-4333",
"text": "OBJECTIVE To evaluate the changes in circulating endotoxin after a high–saturated fat meal to determine whether these effects depend on metabolic disease state. RESEARCH DESIGN AND METHODS Subjects (n = 54) were given a high-fat meal (75 g fat, 5 g carbohydrate, 6 g protein) after an overnight fast (nonobese control [NOC]: age 39.9 ± 11.8 years [mean ± SD], BMI 24.9 ± 3.2 kg/m2, n = 9; obese: age 43.8 ± 9.5 years, BMI 33.3 ± 2.5 kg/m2, n = 15; impaired glucose tolerance [IGT]: age 41.7 ± 11.3 years, BMI 32.0 ± 4.5 kg/m2, n = 12; type 2 diabetic: age 45.4 ± 10.1 years, BMI 30.3 ± 4.5 kg/m2, n = 18). Blood was collected before (0 h) and after the meal (1–4 h) for analysis. RESULTS Baseline endotoxin was significantly higher in the type 2 diabetic and IGT subjects than in NOC subjects, with baseline circulating endotoxin levels 60.6% higher in type 2 diabetic subjects than in NOC subjects (P < 0.05). Ingestion of a high-fat meal led to a significant rise in endotoxin levels in type 2 diabetic, IGT, and obese subjects over the 4-h time period (P < 0.05). These findings also showed that, at 4 h after a meal, type 2 diabetic subjects had higher circulating endotoxin levels (125.4%↑) than NOC subjects (P < 0.05). CONCLUSIONS These studies have highlighted that exposure to a high-fat meal elevates circulating endotoxin irrespective of metabolic state, as early as 1 h after a meal. However, this increase is substantial in IGT and type 2 diabetic subjects, suggesting that metabolic endotoxinemia is exacerbated after high fat intake. In conclusion, our data suggest that, in a compromised metabolic state such as type 2 diabetes, a continual snacking routine will cumulatively promote their condition more rapidly than in other individuals because of the greater exposure to endotoxin.",
"title": "High Fat Intake Leads to Acute Postprandial Exposure to Circulating Endotoxin in Type 2 Diabetic Subjects"
},
{
"docid": "MED-3231",
"text": "This review looks at the role of an alkaline diet in health. Pubmed was searched looking for articles on pH, potential renal acid loads, bone health, muscle, growth hormone, back pain, vitamin D and chemotherapy. Many books written in the lay literature on the alkaline diet were also reviewed and evaluated in light of the published medical literature. There may be some value in considering an alkaline diet in reducing morbidity and mortality from chronic diseases and further studies are warranted in this area of medicine.",
"title": "The Alkaline Diet: Is There Evidence That an Alkaline pH Diet Benefits Health?"
},
{
"docid": "MED-4974",
"text": "Roasting is a crucial step for the production of coffee, as it enables the development of color, aroma, and flavor, which are essential for the characterization of the coffee quality. At the same time, roasting may lead to the formation of not desirable compounds, such as polycyclic aromatic hydrocarbons (PAHs). In this paper, we report a method for PAHs determination in coffee brew, based on saponification and liquid-liquid extraction with small volumes of hexane, with exclusion of further processes of purification since we analyze the extract by gas chromatography with mass spectrometric detectors in the single ion monitoring mode (SIM). The total concentration of the 28 compounds investigated, expressed as the sum of concentrations (SigmaPAH), in coffee brew varies from 0.52 to 1.8 microg/l. Carcinogenic PAHs, expressed as B[a]Peq ranged from 0.008 to 0.060 microg/l. The results indicate that coffee contributes with very insignificant quantities to the daily human intake of carcinogenic PAHs. The values of calculated isomeric ratios confirm that the PAHs identified in most of the coffee samples originate from high temperature processes.",
"title": "Polycyclic aromatic hydrocarbons (PAHs) in coffee brew samples: analytical method by GC-MS, profile, levels and sources."
},
{
"docid": "MED-4553",
"text": "Alzheimer's disease (AD) is the most common dementing disorder of late life. Although there might be various different triggering events in the early stages of the disease, they seem to converge on a few characteristic final pathways in the late stages, characterized by inflammation and neurodegeneration. In this review, we put forward the hypothesis that advanced glycation end products (AGEs) and their precursors, including methylglyoxal, are both biomarkers and causative agents (\"gerontotoxins\") characteristic for this disorder. Accumulation of AGEs is a normal feature of aging, but is accelerated in AD, where AGEs can be detected in amyloid plaques and neurofibrillary tangles. AGE modification may explain many of the neuropathological and biochemical features of AD such as extensive protein cross-linking, inflammation, oxidative stress and neuronal cell death. We suggest that methylglyoxal is one of the major carbonyl species responsible for the formation of AGEs. We propose that one promising pharmacological approach to prevent the formation of AGEs would be to lower the methylglyoxal concentration. This can be achieved, for example, by decreasing the concentration of methylglyoxal precursors such as d-glyceraldehyde-3-phosphate by allowing a higher flux through the pentose phosphate pathway or by increasing methylglyoxal detoxification through the glyoxalase system. Alternatively, methylglyoxal could be scavenged by various types of carbonyl scavengers. Copyright © 2010 Elsevier Inc. All rights reserved.",
"title": "Advanced glycation end products as biomarkers and gerontotoxins - A basis to explore methylglyoxal-lowering agents for Alzheimer's disease?"
},
{
"docid": "MED-1495",
"text": "Response surface methodology was used to study the effect of flaxseed flour (FS) and tomato paste (TP) addition, from 0 to 10% and 0 to 20% respectively, on beef patty quality characteristics. The assessed quality characteristics were color (L, a, and b), pH and texture profile analysis (TPA). Also, sensory analysis was performed for the assessment of color, juiciness, firmness, and general acceptance. FS addition reduced L and a values and decreased weight loss of cooked products (P<0.05). An opposite effect was observed when TP was added (P<0.05). All TPA parameters decreased when percentages of FS and TP were increased in the formulation of beef patties. Furthermore, FS and TP addition adversely affected the sensory characteristics of the cooked product (P<0.05); nevertheless, all sensory characteristics evaluated had an acceptable score (>5.6). Thus FS and TP are ingredients that can be used in beef patty preparation. Copyright © 2014 Elsevier Ltd. All rights reserved.",
"title": "Response surface methodology for predicting quality characteristics of beef patties added with flaxseed and tomato paste."
},
{
"docid": "MED-3236",
"text": "A first objective of the present study was to estimate the acid-base balance of the food intake in vegetarians and non-vegetarians. A second objective was to evaluate if additional input of specific food items on the existing potential renal acid load (PRAL) list was necessary for the comparison of the two dietary patterns. Thirty vegetarians between the age of 18 and 30 years were matched for sex, age and BMI with 30 non-vegetarians. Based on the 3-days food diaries the acid-base status of the food intake was estimated using the PRAL method. Mean PRAL values as estimated with the standard table yielded an alkaline load of -5.4 +/- 14.4 mEq/d in the vegetarians compared to an acid load of 10.3 +/- 14.4 mEq/d in the nonvegetarians (p<0.001). Mean PRAL values as estimated with the extended table yielded an alkaline load of -10.9 +/-19.7 mEq/d in the vegetarians compared to an acid load of 13.8 +/- 17.1 mEq/d for the non-vegetarians (p<0.001). The findings of this study indicate that vegetarian food intake produces more alkaline outcomes compared to non-vegetarian diets. The use of the standard PRAL table was sufficient for discrimination between the two diets.",
"title": "Nutrient based estimation of acid-base balance in vegetarians and non-vegetarians."
},
{
"docid": "MED-3227",
"text": "Although high-protein diets induce hypercalciuria in humans, the source of the additional urinary calcium remains unclear. One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone, leading to increased skeletal resorption and hypercalciuria. We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women. The study consisted of 2 wk of a lead-in, well-balanced diet followed by 10 d of an experimental diet containing either moderate (1.0 g/kg) or high (2.1 g/kg) protein. Thirteen healthy women received both levels of protein in random order. Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate (26.2 +/- 1.9% vs. 18.5 +/- 1.6%, P < 0.0001, mean +/- sem) as did urinary calcium (5.23 +/- 0.37 vs. 3.57 +/- 0.35 mmol/d, P < 0.0001, mean +/- sem). The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover. There were no protein-induced effects on net bone balance. These data directly demonstrate that, at least in the short term, high-protein diets are not detrimental to bone.",
"title": "The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women."
},
{
"docid": "MED-1491",
"text": "The potential to increase n-3 fatty acid (FA) intake via flaxseed fed pork is underestimated when restricted to pure longissimus muscle, whereas a combination of muscle and adipose tissue is typically consumed. Presently, the FA content of pigs fed 0%, 5% and 10% dietary flaxseed for 11 weeks was measured in loin, picnic and butt primals (lean muscle with epimysium (L), L plus seam fat (LS), and LS plus 5 mm backfat (LSS)). The n-3 FA content necessary for an enrichment claim in Canada (300 mg/100 g serving) was exceeded in L from all primals when feeding 5% flaxseed, being 4 fold that of controls (P<0.001), with further enrichment from inclusion of associated adipose tissues (P<0.001). Increasing flaxseed feeding levels in combination with adipose tissue inclusion amplified total long chain n-3 FA (P<0.05), particularly 20:5n-3 and 22:5n-3. Flaxseed-fed n-3 FA enriched pork can contribute substantially to daily long chain n-3 FA intakes, particularly for societies with typically low seafood consumption. © 2013.",
"title": "Flaxseed fed pork: n-3 fatty acid enrichment and contribution to dietary recommendations."
},
{
"docid": "MED-3044",
"text": "OBJECTIVE: Cocaine-related cues have been hypothesized to perpetuate drug abuse by inducing a craving response that prompts drug-seeking behavior. However, the mechanisms, underlying neuroanatomy, and specificity of this neuroanatomy are not yet fully understood. METHOD: To address these issues, experienced cocaine users (N=17) and comparison subjects (N=14) underwent functional magnetic resonance imaging while viewing three separate films that portrayed 1 ) individuals smoking crack cocaine, 2) outdoor nature scenes, and 3) explicit sexual content. Candidate craving sites were identified as those that showed significant activation in the cocaine users when viewing the cocaine film. These sites were then required to show significantly greater activation when contrasted with comparison subjects viewing the cocaine film (population specificity) and cocaine users viewing the nature film (content specificity). RESULTS: Brain regions that satisfied these criteria were largely left lateralized and included the frontal lobe (medial and middle frontal gyri, bilateral inferior frontal gyrus), parietal lobe (bilateral inferior parietal lobule), insula, and limbic lobe (anterior and posterior cingulate gyrus). Of the 13 regions identified as putative craving sites, just three (anterior cingulate, right inferior parietal lobule, and the caudate/lateral dorsal nucleus) showed significantly greater activation during the cocaine film than during the sex film in the cocaine users, which suggests that cocaine cues activated similar neuroanatomical substrates as naturally evocative stimuli in the cocaine users. Finally, contrary to the effects of the cocaine film, cocaine users showed a smaller response than the comparison subjects to the sex film. CONCLUSIONS: These data suggest that cocaine craving is not associated with a dedicated and unique neuroanatomical circuitry; instead, unique to the cocaine user is the ability of learned, drug-related cues to produce brain activation comparable to that seen with nondrug evocative stimuli in healthy comparison subjects.",
"title": "Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli."
},
{
"docid": "MED-4206",
"text": "Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.",
"title": "Vegetarian diets and public health: biomarker and redox connections."
},
{
"docid": "MED-4722",
"text": "BACKGROUND: There has been a resurgence of interest in the controversial relation between dietary protein and bone health. OBJECTIVE: This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. DESIGN: The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded. RESULTS: In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD. CONCLUSIONS: A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.",
"title": "Dietary protein and bone health: a systematic review and meta-analysis."
},
{
"docid": "MED-1258",
"text": "Reductions in low-density lipoprotein-cholesterol (LDL-C) result from diets containing almonds, or diets that are either low in saturated fat or high in viscous fibers, soy proteins, or plant sterols. We have therefore combined all of these interventions in a single diet (portfolio diet) to determine whether cholesterol reductions could be achieved of similar magnitude to those reported in recent statin trials which reduced cardiovascular events. Twenty-five hyperlipidemic subjects consumed either a portfolio diet (n=13), very low in saturated fat and high in plant sterols (1.2 g/1,000 kcal), soy protein (16.2 g/1,000 kcal), viscous fibers (8.3 g/1,000 kcal), and almonds (16.6 g/1,000 kcal), or a low-saturated fat diet (n=12) based on whole-wheat cereals and low-fat dairy foods. Fasting blood, blood pressure, and body weight were obtained at weeks 0, 2, and 4 of each phase. LDL-C was reduced by 12.1% +/- 2.4% (P<.001) on the low-fat diet and by 35.0% +/- 3.1% (P<.001) on the portfolio diet, which also reduced the ratio of LDL-C to high-density lipoprotein-cholesterol (HDL-C) significantly (30.0% +/- 3.5%; P<.001). The reductions in LDL-C and the LDL:HDL-C ratio were both significantly lower on the portfolio diet than on the control diet (P<.001 and P<.001, respectively). Mean weight loss was similar on test and control diets (1.0 kg and 0.9 kg, respectively). No difference was seen in blood pressure, HDL-C, serum triglycerides, lipoprotein(a) [Lp(a)], or homocysteine concentrations between diets. Combining a number of foods and food components in a single dietary portfolio may lower LDL-C similarly to statins and so increase the potential effectiveness of dietary therapy.",
"title": "The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia."
},
{
"docid": "MED-1859",
"text": "Response surface methodology was used to investigate the effect and interactions of processing variables such as roselle extract (0.1-1.3%), soybean oil (5-20%) on physicochemical, textural and sensory properties of cooked pork patties. It was found that reduction in thickness, pH, L* and b* values decreased; however, water-holding capacity, reduction in diameter and a* values increased, respectively, as the amount of roselle increased. Soybean oil addition increased water-holding capacity, reduction in thickness, b* values of the patties. The hardness depended on the roselle and soybean oil added, as its linear effect was negative at p<0.01. The preference of color, tenderness, juiciness, and overall quality depend on the addition of roselle and soybean oil. The maximum overall quality score (5.42) was observed when 12.5 g of soybean oil and 0.7 g of roselle extract was added. The results of this optimization study would be useful for meat industry that tends to increase the product yield for patties using the optimum levels of ingredients by RSM. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Roselle (Hibiscus sabdariffa L.) and soybean oil effects on quality characteristics of pork patties studied by response surface methodology."
},
{
"docid": "MED-3057",
"text": "The ongoing epidemics of obesity is one main health concern of the present time. Overeating in some obese individuals shares similarities with the loss of control and compulsive behavior observed in drug-addicted subjects, suggesting that obesity may involve food addiction. Here, we review the contributions provided by the use of positron emission tomography to the current understanding of the cerebral control of obesity and food intake in humans. The available studies have shown that multiple areas in the brain are involved with the reward properties of food, such as prefrontal, orbitofrontal, somatosensory cortices, insula, thalamus, hypothalamus, amygdala, and others. This review summarizes the current evidence, supporting the concepts that i) regions involved in the somatosensory response to food sight, taste, and smell are activated by palatable foods and may be hyperresponsive in obese individuals, ii) areas controlling executive drive seem to overreact to the anticipation of pleasure during cue exposure, and iii) those involved in cognitive control and inhibitory behavior may be resistant to the perception of reward after food exposure in obese subjects. All of these features may stimulate, for different reasons, ingestion of highly palatable and energy-rich foods. Though these same regions are similarly involved in drug abusers and game-addicted individuals, any direct resemblance may be an oversimplification, especially as the heterogeneities between studies and the prevalent exclusion of sensitive groups still limit a coherent interpretation of the findings. Further work is required to comprehensively tackle the multifaceted phenotype of obesity and identify the role of food dependency in its pathophysiology. Copyright © 2012 S. Karger GmbH, Freiburg.",
"title": "Brain PET imaging in obesity and food addiction: current evidence and hypothesis."
},
{
"docid": "MED-1493",
"text": "Presence of omega-3, omega-6 rich oil, alpha-linoleic acid, dietary fibers, secoisolariciresinol diglucoside, protein and minerals in flaxseed constitute a very strong basis for the utilization of flaxseed in various food preparations as a curative agent. An extensive body of literature illustrates that flaxseed has gained a significant position in the domain of nutritional sciences owing to its pivotal role as an antioxidant agent. The review discusses at length, numerous health benefits of flaxseed typically focusing its preventive role against cardiovascular diseases, cancer, diabetes and enhancement of spatial memory. Massive increase in the size of population with a special emphasize to the developing countries, there is an urge for exploration of the alternative dietary resources that can meet the dietary and nutritional needs of forthcoming generations. With respect to its remarkable nutritional importance, the review in question enables researchers engaged in nutritional sciences to further investigate the therapeutic value of flaxseed functional components and their dietary application in various food products and availability in processed foods as well as in the human cell line.",
"title": "Flaxseed - a miraculous defense against some critical maladies."
},
{
"docid": "MED-1135",
"text": "The hypothesis that the incidence of calcium stone disease is related to the consumption of animal protein has been examined. Within the male population, recurrent idiopathic stone formers consumed more animal protein than did normal subjects. Single stone formers had animal protein intakes intermediate between those of normal men and those of recurrent stone formers. A high animal protein intake caused a significant increase in the urinary excretion of calcium, oxalate and uric acid, 3 of the 6 main urinary risk factors for calcium stone formation. The overall relative probability of forming stones, calculated from the combination of the 6 main urinary risk factors, was markedly increased by a high animal protein diet. Conversely, a low animal protein intake, such as taken by vegetarians, was associated with a low excretion of calcium, oxalate and uric acid and a low relative probability of forming stones.",
"title": "Should recurrent calcium oxalate stone formers become vegetarians?"
},
{
"docid": "MED-4299",
"text": "The evolution of the human diet over the past 10,000 years from a Paleolithic diet to our current modern pattern of intake has resulted in profound changes in feeding behavior. Shifts have occurred from diets high in fruits, vegetables, lean meats, and seafood to processed foods high in sodium and hydrogenated fats and low in fiber. These dietary changes have adversely affected dietary parameters known to be related to health, resulting in an increase in obesity and chronic disease, including cardiovascular disease (CVD), diabetes, and cancer. Some intervention trials using Paleolithic dietary patterns have shown promising results with favorable changes in CVD and diabetes risk factors. However, such benefits may be offset by disadvantages of the Paleolithic diet, which is low in vitamin D and calcium and high in fish potentially containing environmental toxins. More advantageous would be promotion of foods and food ingredients from our ancestral era that have been shown to possess health benefits in the form of functional foods. Many studies have investigated the health benefits of various functional food ingredients, including omega-3 fatty acids, polyphenols, fiber, and plant sterols. These bioactive compounds may help to prevent and reduce incidence of chronic diseases, which in turn could lead to health cost savings ranging from $2 to $3 billion per year as estimated by case studies using omega-3 and plant sterols as examples. Thus, public health benefits should result from promotion of the positive components of Paleolithic diets as functional foods.",
"title": "Evolution of the human diet: linking our ancestral diet to modern functional foods as a means of chronic disease prevention."
},
{
"docid": "MED-3055",
"text": "Both drug addiction and obesity can be defined as disorders in which the saliency value of one type of reward (drugs and food, respectively) becomes abnormally enhanced relative to, and at the expense of others. This model is consistent with the fact that both drugs and food have powerful reinforcing effects-partly mediated by dopamine increases in the limbic system-that, under certain circumstances or in vulnerable individuals, could overwhelm the brain's homeostatic control mechanisms. Such parallels have generated significant interest in understanding the shared vulnerabilities and trajectories between addiction and obesity. Now, brain imaging discoveries have started to uncover common features between these two conditions and to delineate some of the overlapping brain circuits whose dysfunctions may explain stereotypic and related behavioral deficits in human subjects. These results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning (memory/learning), impulse control (behavioural inhibition), stress reactivity, and interoceptive awareness. Here, we integrate findings predominantly derived from positron emission tomography that shed light on the role of dopamine in drug addiction and in obesity, and propose an updated working model to help identify treatment strategies that may benefit both of these conditions.",
"title": "Food and drug reward: overlapping circuits in human obesity and addiction."
},
{
"docid": "MED-3056",
"text": "Opioids are important in reward processes leading to addictive behavior such as self-administration of opioids and other drugs of abuse including nicotine and alcohol. Opioids are also involved in a broadly distributed neural network that regulates eating behavior, affecting both homeostatic and hedonic mechanisms. In this sense, opioids are particularly implicated in the modulation of highly palatable foods, and opioid antagonists attenuate both addictive drug taking and appetite for palatable food. Thus, craving for palatable food could be considered as a form of opioid-related addiction. There are three main families of opioid receptors (µ, ĸ, and δ) of which µ-receptors are most strongly implicated in reward. Administration of selective µ-agonists into the NAcc of rodents induces feeding even in satiated animals, while administration of µ-antagonists reduces food intake. Pharmacological studies also suggest a role for ĸ- and δ-opioid receptors. Preliminary data from transgenic knockout models suggest that mice lacking some of these receptors are resistant to high-fat diet-induced obesity. Copyright © 2012 S. Karger GmbH, Freiburg.",
"title": "The opioid system and food intake: homeostatic and hedonic mechanisms."
},
{
"docid": "MED-3233",
"text": "Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load (PRAL) diet on calcium (Ca) absorption and retention and markers of bone metabolism. In a randomized crossover design, 16 postmenopausal women consumed 2 diets: 1 with low protein and low PRAL (LPLP; total protein: 61 g/d; PRAL: -48 mEq/d) and 1 with high protein and high PRAL (HPHP; total protein: 118 g/d; PRAL: 33 mEq/d) for 7 wk each separated by a 1-wk break. Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca. Compared with the LPLP diet, the HPHP diet increased participants' serum IGF-I concentrations (P < 0.0001), decreased serum intact PTH concentrations (P < 0.001), and increased fractional (47)Ca absorption (mean ± pooled SD: 22.3 vs. 26.5 ± 5.4%; P < 0.05) and urinary Ca excretion (156 vs. 203 ± 63 mg/d; P = 0.005). The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods (55 vs. 28 ± 51 mg/d). The dietary treatments did not affect other markers of bone metabolism. In summary, a diet high in protein and PRAL increases the fractional absorption of dietary Ca, which partially compensates for increased urinary Ca, in postmenopausal women. The increased IGF-I and decreased PTH concentrations in serum, with no change in biomarkers of bone resorption or formation, indicate a high-protein diet has no adverse effects on bone health.",
"title": "A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting m..."
},
{
"docid": "MED-3060",
"text": "Context Research has implicated an addictive process in the development and maintenance of obesity. Although parallels in neural functioning between obesity and substance dependence have been found, no studies have examined the neural correlates of addictive-like eating behavior. Objective To test the hypothesis that elevated “food addiction” scores are associated with similar patterns of neural activation as substance dependence. Design Between-Subjects fMRI study. Participants Forty-eight healthy adolescent females ranging from lean to obese recruited for a healthy weight maintenance trial. Main Outcome Measure The relation between elevated “food addiction” scores and blood oxygen level-dependent fMRI activation in response to receipt and anticipated receipt of palatable food (chocolate milkshake). Results Food addiction scores (N = 39) correlated with greater activation in the anterior cingulate cortex (ACC), medial orbitofrontal cortex (OFC), and amygdala in response to anticipated receipt of food (P <0.05, false-discovery rate (FDR) corrected for multiple comparisons in small volumes). Participants with higher (n=15) versus lower (n=11) food addiction scores showed greater activation in the dorsolateral prefrontal cortex (DLPFC) and the caudate in response to anticipated receipt of food, but less activation in the lateral OFC in response to receipt of food (pFDR <0.05). Conclusions Similar patterns of neural activation are implicated in addictive-like eating behavior and substance dependence; elevated activation in reward circuitry in response to food cues and reduced activation of inhibitory regions in response to food intake.",
"title": "The Neural Correlates of “Food Addiction”"
},
{
"docid": "MED-3598",
"text": "Trans-fatty acids (TFA) have adverse effects on blood lipids, but whether TFA from different sources are associated with risk of CVD remains unresolved. The objective of the present study was to evaluate the association between TFA intake from partially hydrogenated vegetable oils (PHVO), partially hydrogenated fish oils (PHFO) and ruminant fat (rTFA) and risks of death of CVD, CHD, cerebrovascular diseases and sudden death in the Norwegian Counties Study, a population-based cohort study. Between 1974 and 1988, participants were examined for up to three times. Fat intake was assessed with a semi-quantitative FFQ. A total of 71,464 men and women were followed up through 2007. Hazard ratios (HR) and 95 % CI were estimated with Cox regression. Energy from TFA was compared to energy from all other sources, carbohydrates or unsaturated cis-fatty acids with different multivariable models. During follow-up, 3870 subjects died of CVD, 2383 of CHD, 732 of cerebrovascular diseases and 243 of sudden death. Significant risks, comparing highest to lowest intake category, were found for: TFA from PHVO and CHD (HR 1.23 (95 % CI 1.00, 1.50)) and cerebrovascular diseases (HR 0.65 (95 % CI 0.45, 0.94)); TFA from PHFO and CVD (HR 1.14 (95 % CI 1.03, 1.26)) and cerebrovascular diseases (HR 1.32 (95 % CI 1.04, 1.69)); and rTFA intake and CVD (HR 1.30 (95 % CI 1.05, 1.61)), CHD (HR 1.50 (95 % CI 1.11, 2.03)) and sudden death (HR 2.73 (95 % CI 1.19, 6.25)) in women. These associations with rTFA intake were not significant in men (P interaction ≥ 0.01). The present study supports that TFA intake, irrespective of source, increases CVD risk. Whether TFA from PHVO decreases risk of cerebrovascular diseases warrants further investigation.",
"title": "A prospective study of intake of trans-fatty acids from ruminant fat, partially hydrogenated vegetable oils, and marine oils and mortality from CVD."
}
] |
[
{
"docid": "MED-4972",
"text": "Heterocyclic amines (HCAs), compounds formed when meat is cooked at high temperatures particularly through pan frying, grilling, or barbequing, pose a potential carcinogenic risk to the public. It is unclear whether there is any level at which consumption of HCAs can be considered safe. Efforts to measure these compounds mainly include cooking studies under laboratory conditions and some measurement of home-cooked foods, but analysis of commercially cooked foods has been minimal. Attempts to estimate exposure of the public to these compounds must take into consideration dining outside the home, which could result in significant exposure for some individuals. We surveyed at least 9 locations each of 7 popular chain restaurants (McDonald's, Burger King, Chick-fil-A, Chili's, TGI Friday's, Outback Steakhouse, and Applebee's) in California, collecting one or two entrees from each location. Entrees were analyzed for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) using high-performance liquid chromatography tandem mass spectrometry. All 100 samples contained PhIP. Concentrations were variable within and between entrees and ranged from 0.08 to 43.2 ng/g. When factoring in the weight of the entrees, absolute levels of PhIP reached over 1,000 ng for some entrees. Potential strategies for reducing exposure include the avoidance of meats cooked using methods that are known to form PhIP.",
"title": "Detection of PhIP in grilled chicken entrées at popular chain restaurants throughout California."
},
{
"docid": "MED-2391",
"text": "Objectives The objective of this article is to extend our previous studies of persistent organic pollutant (POP) contamination of U.S. food by measuring perfluorinated compounds (PFCs), organochlorine pesticides, and polychlorinated biphenyls (PCBs) in composite food samples. This study is part of a larger study reported in two articles, the other of which reports levels of polybrominated diphenyl ethers and hexabromocyclododecane brominated flame retardants in these composite foods [Schecter et al. 2010. Polybrominated diphenyl ethers (PBDEs) and hexabromocyclodecane (HBCD) in composite U.S. food samples, Environ Health Perspect 118:357–362]. Methods In this study we measured concentrations of 32 organochlorine pesticides, 7 PCBs, and 11 PFCs in composite samples of 31 different types of food (310 individual food samples) purchased from supermarkets in Dallas, Texas (USA), in 2009. Dietary intake of these chemicals was calculated for an average American. Results Contamination varied greatly among chemical and food types. The highest level of pesticide contamination was from the dichlorodiphenyltrichloroethane (DDT) metabolite p,p′- dichlorodiphenyldichloroethylene, which ranged from 0.028 ng/g wet weight (ww) in whole milk yogurt to 2.3 ng/g ww in catfish fillets. We found PCB congeners (28, 52, 101, 118, 138, 153, and 180) primarily in fish, with highest levels in salmon (PCB-153, 1.2 ng/g ww; PCB-138, 0.93 ng/g ww). For PFCs, we detected perfluorooctanoic acid (PFOA) in 17 of 31 samples, ranging from 0.07 ng/g in potatoes to 1.80 ng/g in olive oil. In terms of dietary intake, DDT and DDT metabolites, endosulfans, aldrin, PCBs, and PFOA were consumed at the highest levels. Conclusion Despite product bans, we found POPs in U.S. food, and mixtures of these chemicals are consumed by the American public at varying levels. This suggests the need to expand testing of food for chemical contaminants.",
"title": "Perfluorinated Compounds, Polychlorinated Biphenyls, and Organochlorine Pesticide Contamination in Composite Food Samples from Dallas, Texas, USA"
},
{
"docid": "MED-2027",
"text": "Background: Nonceliac gluten sensitivity (NCGS), occurring in patients without celiac disease yet whose gastrointestinal symptoms improve on a gluten-free diet (GFD), is largely a self-reported diagnosis and would appear to be very common. The aims of this study were to characterize patients who believe they have NCGS. Materials and Methods: Advertising was directed toward adults who believed they had NCGS and were willing to participate in a clinical trial. Respondents were asked to complete a questionnaire about symptoms, diet, and celiac investigation. Results: Of 248 respondents, 147 completed the survey. Mean age was 43.5 years, and 130 were women. Seventy-two percent did not meet the description of NCGS due to inadequate exclusion of celiac disease (62%), uncontrolled symptoms despite gluten restriction (24%), and not following a GFD (27%), alone or in combination. The GFD was self-initiated in 44% of respondents; in other respondents it was prescribed by alternative health professionals (21%), dietitians (19%), and general practitioners (16%). No celiac investigations had been performed in 15% of respondents. Of 75 respondents who had duodenal biopsies, 29% had no or inadequate gluten intake at the time of endoscopy. Inadequate celiac investigation was common if the GFD was initiated by self (69%), alternative health professionals (70%), general practitioners (46%), or dietitians (43%). In 40 respondents who fulfilled the criteria for NCGS, their knowledge of and adherence to the GFD were excellent, and 65% identified other food intolerances. Conclusions: Just over 1 in 4 respondents self-reporting as NCGS fulfill criteria for its diagnosis. Initiation of a GFD without adequate exclusion of celiac disease is common. In 1 of 4 respondents, symptoms are poorly controlled despite gluten avoidance. © 2014 American Society for Parenteral and Enteral Nutrition.",
"title": "Characterization of Adults With a Self-Diagnosis of Nonceliac Gluten Sensitivity."
},
{
"docid": "MED-4499",
"text": "Fourier transform infrared (FT-IR) spectroscopy and Raman spectroscopy were used to study the cell injury and inactivation of Campylobacter jejuni from exposure to antioxidants from garlic. C. jejuni was treated with various concentrations of garlic concentrate and garlic-derived organosulfur compounds in growth media and saline at 4, 22, and 35°C. The antimicrobial activities of the diallyl sulfides increased with the number of sulfur atoms (diallyl sulfide < diallyl disulfide < diallyl trisulfide). FT-IR spectroscopy confirmed that organosulfur compounds are responsible for the substantial antimicrobial activity of garlic, much greater than those of garlic phenolic compounds, as indicated by changes in the spectral features of proteins, lipids, and polysaccharides in the bacterial cell membranes. Confocal Raman microscopy (532-nm-gold-particle substrate) and Raman mapping of a single bacterium confirmed the intracellular uptake of sulfur and phenolic components. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were employed to verify cell damage. Principal-component analysis (PCA), discriminant function analysis (DFA), and soft independent modeling of class analogs (SIMCA) were performed, and results were cross validated to differentiate bacteria based upon the degree of cell injury. Partial least-squares regression (PLSR) was employed to quantify and predict actual numbers of healthy and injured bacterial cells remaining following treatment. PLSR-based loading plots were investigated to further verify the changes in the cell membrane of C. jejuni treated with organosulfur compounds. We demonstrated that bacterial injury and inactivation could be accurately investigated by complementary infrared and Raman spectroscopies using a chemical-based, “whole-organism fingerprint” with the aid of chemometrics and electron microscopy.",
"title": "Investigating Antibacterial Effects of Garlic (Allium sativum) Concentrate and Garlic-Derived Organosulfur Compounds on Campylobacter jejuni by Using Fourier Transform Infrared Spectroscopy, Raman Spectroscopy, and Electron Microscopy"
},
{
"docid": "MED-1295",
"text": "A number of polysaccharides with beta-glycosidic linkage are widespread in nature in a variety of sources. All have a common structure and the (1-->3)-beta-D-glucan backbone is essential. They have attracted attention over the years because of their bioactive and medicinal properties. In many cases their functional role is a mystery, in others it is well established. Because of their insoluble chemical nature, particulate (1-->3)-beta-D-glucans are not suitable for many medical applications. Various methods of changing or modifying the beta-D-glucan chemical structure and transforming it to a soluble form have been published. The beta-D-glucan bioactive properties can be affected positively or negatively by such modifications. This review examines beta-glucan sources in nature, health effects and structure-activity relationships. It presents the current state of beta-D-glucan solubilization methods and discusses their effectiveness and application possibilities for the future.",
"title": "Natural and modified (1-->3)-beta-D-glucans in health promotion and disease alleviation."
},
{
"docid": "MED-1185",
"text": "Endogenous sulfite is generated as a consequence of the body's normal processing of sulfur-containing amino acids. Sulfites occur as a consequence of fermentation and also occur naturally in a number of foods and beverages. As food additives, sulfiting agents were first used in 1664 and approved in the United States as long ago as the 1800s. With such long experience with their use, it is easy to understand why these substances have been regarded as safe. They are currently used for a variety of preservative properties, including controlling microbial growth, preventing browning and spoilage, and bleaching some foods. It is estimated that up to 500,000 (< .05% of the population) sulfite-sensitive individuals live in the United States. Sulfite sensitivity occurs most often in asthmatic adults--predominantly women; it is uncommonly reported in preschool children. Adverse reactions to sulfites in nonasthmatics are extremely rare. Asthmatics who are steroid-dependent or who have a higher degree of airway hyperreactivity may be at greater risk of experiencing a reaction to sulfite-containing foods. Even within this limited population, sulfite sensitivity reactions vary widely, ranging from no reaction to severe. The majority of reactions are mild. These manifestations may include dermatologic, respiratory, or gastrointestinal signs and symptoms. Severe nonspecific signs and symptoms occur less commonly. Broncho-constriction is the most common sensitivity response in asthmatics. The precise mechanisms of the sensitivity responses have not been completely elucidated. Inhalation of sulfur dioxide (SO2) generated in the stomach following ingestion of sulfite-containing foods or beverages, a deficiency in a mitochondrial enzyme, and an IgE-mediated immune response have all been implicated.(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Sulfite sensitivity: significance in human health."
},
{
"docid": "MED-5108",
"text": "The effectiveness of high-temperature, short holding time (HTST) pasteurization and homogenization with respect to inactivation of Mycobacterium avium subsp. paratuberculosis was evaluated quantitatively. This allowed a detailed determination of inactivation kinetics. High concentrations of feces from cows with clinical symptoms of Johne's disease were used to contaminate raw milk in order to realistically mimic possible incidents most closely. Final M. avium subsp. paratuberculosis concentrations varying from 102 to 3.5 × 105 cells per ml raw milk were used. Heat treatments including industrial HTST were simulated on a pilot scale with 22 different time-temperature combinations, including 60 to 90°C at holding (mean residence) times of 6 to 15 s. Following 72°C and a holding time of 6 s, 70°C for 10 and 15 s, or under more stringent conditions, no viable M. avium subsp. paratuberculosis cells were recovered, resulting in >4.2- to >7.1-fold reductions, depending on the original inoculum concentrations. Inactivation kinetic modeling of 69 quantitative data points yielded an Ea of 305,635 J/mol and an lnk0 of 107.2, corresponding to a D value of 1.2 s at 72°C and a Z value of 7.7°C. Homogenization did not significantly affect the inactivation. The conclusion can be drawn that HTST pasteurization conditions equal to 15 s at ≥72°C result in a more-than-sevenfold reduction of M. avium subsp. paratuberculosis.",
"title": "Effective Heat Inactivation of Mycobacterium avium subsp. paratuberculosis in Raw Milk Contaminated with Naturally Infected Feces"
},
{
"docid": "MED-4002",
"text": "The effects of dietary supplementation with coconut oil on the biochemical and anthropometric profiles of women presenting waist circumferences (WC) >88 cm (abdominal obesity) were investigated. The randomised, double-blind, clinical trial involved 40 women aged 20-40 years. Groups received daily dietary supplements comprising 30 mL of either soy bean oil (group S; n = 20) or coconut oil (group C; n = 20) over a 12-week period, during which all subjects were instructed to follow a balanced hypocaloric diet and to walk for 50 min per day. Data were collected 1 week before (T1) and 1 week after (T2) dietary intervention. Energy intake and amount of carbohydrate ingested by both groups diminished over the trial, whereas the consumption of protein and fibre increased and lipid ingestion remained unchanged. At T1 there were no differences in biochemical or anthropometric characteristics between the groups, whereas at T2 group C presented a higher level of HDL (48.7 +/- 2.4 vs. 45.00 +/- 5.6; P = 0.01) and a lower LDL:HDL ratio (2.41 +/- 0.8 vs. 3.1 +/- 0.8; P = 0.04). Reductions in BMI were observed in both groups at T2 (P < 0.05), but only group C exhibited a reduction in WC (P = 0.005). Group S presented an increase (P < 0.05) in total cholesterol, LDL and LDL:HDL ratio, whilst HDL diminished (P = 0.03). Such alterations were not observed in group C. It appears that dietetic supplementation with coconut oil does not cause dyslipidemia and seems to promote a reduction in abdominal obesity.",
"title": "Effects of dietary coconut oil on the biochemical and anthropometric profiles of women presenting abdominal obesity."
},
{
"docid": "MED-4933",
"text": "Recently, we reported on the analysis of polychlorinated biphenyls (PCBs) and chlorinated pesticides in farmed Atlantic salmon (Salmo salar) from Maine, eastern Canada, and Norway, and wild Alaskan Chinook salmon (Oncorhynchus tshawytscha). In this paper, we extend the analysis to polybrominated diphenyl ethers (PBDEs) in these samples. Total PBDE concentrations in the farmed salmon (0.4-1.4ng/g, wet weight, ww) were not significantly different from those in the wild Alaskan Chinook samples (0.4-1.2ng/g, ww), nor were significant differences found among regions. However, significant intra-regional variations in concentrations of total PBDEs and tetra-BDE 47 were observed in the salmon from the Canadian farms (p<0.01). Congener profiles were dominated by BDE-47, followed by the penta-BDEs 99 and 100. PBDE concentrations in the Canadian samples were lower than those reported two years earlier. Removal of skin resulted in no overall reduction in PBDE concentrations in our farmed salmon, and in some cases, PBDE concentrations were higher in skin-off samples. PBDEs were correlated with lipids only in the skinned samples, suggesting that there is greater accumulation and retention of PBDEs in muscle lipids than in skin-associated fat. In skin-on samples, modest correlations were observed between concentrations of PBDEs and PCBs (R(2)=0.47) and mono-ortho PCBs (R(2)=0.50), whereas PBDEs were not correlated with non-ortho PCBs.",
"title": "Polybrominated diphenyl ethers (PBDEs) in farmed and wild salmon marketed in the Northeastern United States."
},
{
"docid": "MED-1032",
"text": "To our knowledge, there is no previous clinical description in the literature of patients with defecation syncope. We evaluated 20 patients with this disorder who were a subgroup of a larger, prospective study of syncope, 13 women and seven men, with a mean age of 59 years. Eleven patients had had one episode and nine had experienced multiple episodes. Fourteen patients were recumbent before the urge to defecate, nine of these asleep. The diagnostic evaluation disclosed that two patients had gastrointestinal tract problems, three had cardiac diseases, and one had transient ischemic attacks. Three additional patients had marked orthostatic hypotension. No identifiable cause for defecation syncope was found in 11 patients, but new medical problems were noted in four of those patients. In follow-up at two years, syncope had recurred in ten patients, but the majority of recurrences were unassociated with defecation. Seven patients died during the follow-up period of underlying chronic diseases. We conclude that defecation syncope is not a single distinct clinical entity. Multiple pathologic abnormalities in association with physiologic changes during sleep and defecation may contribute to syncope. Patients with defecation syncope should undergo a careful evaluation for diagnosis of underlying illness causing syncope.",
"title": "Defecation syncope. A symptom with multiple etiologies."
},
{
"docid": "MED-2026",
"text": "OBJECTIVES: The prevalence of celiac disease (CD) in the United States is unknown. We sought to estimate CD prevalence nationwide by using a nationally representative sample. METHODS: This study included 7,798 persons aged 6 years or older who participated in the National Health and Nutrition Examination Survey 2009-2010. Serum samples from all participants were tested for immunoglobulin A (IgA) tissue transglutaminase antibodies and, if findings were abnormal, also for IgA endomysial antibodies. Information about prior diagnosis of CD and use of a gluten-free diet (GFD) was obtained by direct interview. CD was defined as having either double-positive serology (serologically diagnosed CD) or a reported diagnosis of CD by a doctor or other health-care professional and being on a GFD (reported clinical diagnosis of CD). RESULTS: CD was found in 35 participants, 29 of whom were unaware of their diagnosis. Median age was 45 years (interquartile range, 23-66 years); 20 were women and 29 were non-Hispanic white. The prevalence of CD in the United States was 0.71% (95% confidence interval (CI), 0.58-0.86%), with 1.01% (95% CI, 0.78-1.31%) among non-Hispanic whites. In all, 55 participants reported following a GFD, which corresponded to a prevalence of 0.63% (95% CI, 0.36-1.07%). CONCLUSIONS: The prevalence of CD in the United States was 0.71% (1 in 141), similar to that found in several European countries. However, most cases were undiagnosed. CD was rare among minority groups but affected 1% of non-Hispanic whites. Most persons who were following a GFD did not have a diagnosis of CD.",
"title": "The prevalence of celiac disease in the United States."
},
{
"docid": "MED-4237",
"text": "OBJECTIVE: To evaluate the prevalence of benign prostatic hyperplasia (BPH) and prostatic cancer (CaP) in the mainland of China. METHODS: The incidence of BPH and CaP in urological hospital was investigated in 1997 in 26 provinces and 4 metropolises scattered over the mainland of China. The change of hospital incidences of BPH and CaP in the Institute of Urology, Beijing Medical University from 1951 to 1997 was also reviewed. RESULTS: The incidence of BPH and CaP in 1997 in 187 hospitals scattered over the mainland of China was 16.1% (15,459/95,749) and 1.5% (1389/95,749), respectively. The incidence of BPH and CaP in the Institute of Urology, Beijing University from 1951 to 1960 was 7.6% and 0.6%, respectively, while it was 18.5% and 3.4% from 1991 to 1997. CONCLUSION: The hospital incidence of BPH and CaP is rising rapidly in China, but CaP is still not a common disease in China.",
"title": "Epidemiological survey of benign prostatic hyperplasia and prostatic cancer in China."
},
{
"docid": "MED-4957",
"text": "Sarcocystis spp. are parasitic protists acquired when undercooked, cyst-laden meat is consumed. While both Sarcocystis hominis and S. cruzi encyst in beef, only S. hominis is pathogenic to humans. In this study, we used histological methods and novel molecular techniques to determine the regional prevalence and identity of Sarcocystis spp. in retail beef. Of 110 samples, 60 supported amplification of parasite rRNA by PCR. All 41 sequenced representatives were identified as S. cruzi. To compare detection methods, 48 samples were then examined in parallel by histology and PCR, and 16 and 26 samples, respectively, were positive. Five samples positive by initial histologic sections were not amplified by PCR. Fifteen PCR-positive samples did not contain sarcocysts on initial histologic section, but additional sections from these samples revealed sarcocysts in an additional 12 samples. When combined, histology with additional sections and PCR detected 31 positive specimens of the 48 total specimens. We found no evidence of human pathogen S. hominis and confirm that cattle pathogen S. cruzi is highly prevalent in this regional sample. PCR assays may increase the detection sensitivity of Sarcocystis spp. and contribute diagnostic precision.",
"title": "Detection of sarcocystis parasites in retail beef: a regional survey combining histological and genetic detection methods."
},
{
"docid": "MED-4967",
"text": "BACKGROUND: From 2003 through 2007, Vibrio cholerae serogroup O75 strains possessing the cholera toxin gene were isolated from 6 patients with severe diarrhea, including 3 in Georgia, 2 in Alabama, and 1 in South Carolina. These reports represent the first identification of V. cholerae O75 as a cause of illness in the United States. V. cholerae O75 was isolated from a water sample collected from a pond in Louisiana in 2004. Subsequently, 3 V. cholerae isolates from Louisiana (2 from patients with diarrhea in 2000 and 1 from a water sample collected in 1978) that had been previously reported as serogroup O141 were also discovered to be serogroup O75. RESULTS: All 8 patients who were infected with V. cholerae O75 were adults who became ill after consuming seafood; 2 had eaten raw oysters traced back to the Gulf Coast of the United States. All 10 isolates possessed the cholera toxin gene and were susceptible to 10 antimicrobials. One clinical isolate and 1 environmental (water) isolate had the same pulsed-field gel electrophoresis pattern; 4 clinical isolates shared a common pulsed-field gel electrophoresis pattern. CONCLUSIONS: The occurrence of these cases over many years and the concurrent identification of V. cholerae O75 in water from a Gulf Coast state suggest that these strains may survive for long periods in this environment. The patients' exposure histories suggest that infection can be acquired from consumption of raw oysters from the Gulf Coast. Clinicians and public health authorities should be vigilant for the occurrence of new toxigenic serogroups of V. cholerae that are capable of causing severe diarrhea.",
"title": "Severe diarrhea caused by cholera toxin-producing vibrio cholerae serogroup O75 infections acquired in the southeastern United States."
},
{
"docid": "MED-1996",
"text": "Until recently, the majority of cases of diabetes mellitus among children and adolescents were immune-mediated type 1a diabetes. Obesity has led to a dramatic increase in the incidence of type 2 diabetes (T2DM) among children and adolescents over the past 2 decades. Obesity is strongly associated with insulin resistance, which, when coupled with relative insulin deficiency, leads to the development of overt T2DM. Children and adolescents with T2DM may experience the microvascular and macrovascular complications of this disease at younger ages than individuals who develop diabetes in adulthood, including atherosclerotic cardiovascular disease, stroke, myocardial infarction, and sudden death; renal insufficiency and chronic renal failure; limb-threatening neuropathy and vasculopathy; and retinopathy leading to blindness. Health care professionals are advised to perform the appropriate screening in children at risk for T2DM, diagnose the condition as early as possible, and provide rigorous management of the disease.",
"title": "Childhood obesity and type 2 diabetes mellitus."
},
{
"docid": "MED-3987",
"text": "Background: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D]. Objective: The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans. Design: The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials. Results: A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation. Conclusions: This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3 could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.",
"title": "Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis"
},
{
"docid": "MED-5076",
"text": "The objective of the present study was to evaluate the effect of three common cooking practices (i.e., boiling, steaming, and frying) on phytochemical contents (i.e., polyphenols, carotenoids, glucosinolates, and ascorbic acid), total antioxidant capacities (TAC), as measured by three different analytical assays [Trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP), ferric reducing antioxidant power (FRAP)] and physicochemical parameters of three vegetables (carrots, courgettes, and broccoli). Water-cooking treatments better preserved the antioxidant compounds, particularly carotenoids, in all vegetables analyzed and ascorbic acid in carrots and courgettes. Steamed vegetables maintained a better texture quality than boiled ones, whereas boiled vegetables showed limited discoloration. Fried vegetables showed the lowest degree of softening, even though antioxidant compounds were less retained. An overall increase of TEAC, FRAP, and TRAP values was observed in all cooked vegetables, probably because of matrix softening and increased extractability of compounds, which could be partially converted into more antioxidant chemical species. Our findings defy the notion that processed vegetables offer lower nutritional quality and also suggest that for each vegetable a cooking method would be preferred to preserve the nutritional and physicochemical qualities.",
"title": "Effects of different cooking methods on nutritional and physicochemical characteristics of selected vegetables."
},
{
"docid": "MED-4913",
"text": "Potatoes are a source of glycoalkaloids (GAs) represented primarily by alpha-solanine and alpha-chaconine (about 95%). Content of GAs in tubers is usually 10-100 mg/kg and maximum levels do not exceed 200 mg/kg. GAs can be hazardous for human health. Poisoning involve gastrointestinal ailments and neurological symptoms. A single intake of >1-3 mg/kg b.w. is considered a critical effect dose (CED). Probabilistic modelling of acute and chronic (usual) exposure to GAs was performed in the Czech Republic, Sweden and The Netherlands. National databases on individual consumption of foods, data on concentration of GAs in tubers (439 Czech and Swedish results) and processing factors were used for modelling. Results concluded that potatoes currently available at the European market may lead to acute intakes >1 mg GAs/kg b.w./day for upper tail of the intake distribution (0.01% of population) in all three countries. 50 mg GAs/kg raw unpeeled tubers ensures that at least 99.99% of the population does not exceed the CED. Estimated chronic (usual) intake in participating countries was 0.25, 0.29 and 0.56 mg/kg b.w./day (97.5% upper confidence limit). It remains unclear if the incidence of GAs poisoning is underreported or if assumptions are the worst case for extremely sensitive persons.",
"title": "Probabilistic modelling of exposure doses and implications for health risk characterization: glycoalkaloids from potatoes."
},
{
"docid": "MED-2520",
"text": "This article discusses that the traditional analogy of an aging organism with a rusting (albeit self-repairing) car is misleading. The true analogy is a speeding car that enters a low-speed zone and damages itself because it does not and cannot slow down. For such a car without brakes (and actually without a driver), aging from rusting never occurs. Using simple analogies (although turning gerontology upside down), this article discusses the origin of aging, how overactivation of the mTOR (Target of Rapamycin) pathway causes aging, why aging causes damage (organ damage) not damage causes aging, the link between aging and age-related diseases, slow aging versus aging tolerance and suppression of aging with rapamycin.",
"title": "TOR-driven aging: speeding car without brakes."
},
{
"docid": "MED-4789",
"text": "Objectives To examine the effects of aerobic exercise on cognition and other biomarkers associated with Alzheimer disease pathology for older adults with mild cognitive impairment, and assess the role of sex as a predictor of response. Design Six-month, randomized, controlled, clinical trial. Setting Veterans Affairs Puget Sound Health Care System clinical research unit. Participants Thirty-three adults (17 women) with amnestic mild cognitive impairment ranging in age from 55 to 85 years (mean age,70 years). Intervention Participants were randomized either to a high-intensity aerobic exercise or stretching control group. The aerobic group exercised under the supervision of a fitness trainer at 75% to 85% of heart rate reserve for 45 to 60 min/d, 4 d/wk for 6 months. The control group carried out supervised stretching activities according to the same schedule but maintained their heart rate at or below 50% of their heart rate reserve. Before and after the study, glucometabolic and treadmill tests were performed and fat distribution was assessed using dual-energy x-ray absorptiometry. At baseline, month 3, and month 6, blood was collected for assay and cognitive tests were administered. Main Outcome Measures Performance measures on Symbol-Digit Modalities, Verbal Fluency, Stroop, Trails B, Task Switching, Story Recall, and List Learning. Fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulinlike growth factor-I, and β-amyloids 40 and 42. Results Six months of high-intensity aerobic exercise had sex-specific effects on cognition, glucose metabolism, and hypothalamic-pituitary-adrenal axis and trophic activity despite comparable gains in cardiorespiratory fitness and body fat reduction. For women, aerobic exercise improved performance on multiple tests of executive function, increased glucose disposal during the metabolic clamp, and reduced fasting plasma levels of insulin, cortisol, and brain-derived neurotrophic factor. For men, aerobic exercise increased plasma levels of insulinlike growth factor I and had a favorable effect only on Trails B performance. Conclusions This study provides support, using rigorous controlled methodology, for a potent nonpharma-cologic intervention that improves executive control processes for older women at high risk of cognitive decline. Moreover, our results suggest that a sex bias in cognitive response may relate to sex-based differences in glucometabolic and hypothalamic-pituitary-adrenal axis responses to aerobic exercise.",
"title": "Effects of Aerobic Exercise on Mild Cognitive Impairment"
},
{
"docid": "MED-1795",
"text": "Objective To determine whether individual fruits are differentially associated with risk of type 2 diabetes. Design Prospective longitudinal cohort study. Setting Health professionals in the United States. Participants 66 105 women from the Nurses’ Health Study (1984-2008), 85 104 women from the Nurses’ Health Study II (1991-2009), and 36 173 men from the Health Professionals Follow-up Study (1986-2008) who were free of major chronic diseases at baseline in these studies. Main outcome measure Incident cases of type 2 diabetes, identified through self report and confirmed by supplementary questionnaires. Results During 3 464 641 person years of follow-up, 12 198 participants developed type 2 diabetes. After adjustment for personal, lifestyle, and dietary risk factors of diabetes, the pooled hazard ratio of type 2 diabetes for every three servings/week of total whole fruit consumption was 0.98 (95% confidence interval 0.96 to 0.99). With mutual adjustment of individual fruits, the pooled hazard ratios of type 2 diabetes for every three servings/week were 0.74 (0.66 to 0.83) for blueberries, 0.88 (0.83 to 0.93) for grapes and raisins, 0.89 (0.79 to 1.01) for prunes, 0.93 (0.90 to 0.96) for apples and pears, 0.95 (0.91 to 0.98) for bananas, 0.95 (0.91 to 0.99) for grapefruit, 0.97 (0.92 to 1.02) for peaches, plums, and apricots, 0.99 (0.95 to 1.03) for oranges, 1.03 (0.96 to 1.10) for strawberries, and 1.10 (1.02 to 1.18) for cantaloupe. The pooled hazard ratio for the same increment in fruit juice consumption was 1.08 (1.05 to 1.11). The associations with risk of type 2 diabetes differed significantly among individual fruits (P<0.001 in all cohorts). Conclusion Our findings suggest the presence of heterogeneity in the associations between individual fruit consumption and risk of type 2 diabetes. Greater consumption of specific whole fruits, particularly blueberries, grapes, and apples, is significantly associated with a lower risk of type 2 diabetes, whereas greater consumption of fruit juice is associated with a higher risk.",
"title": "Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies"
},
{
"docid": "MED-4714",
"text": "This study investigated the association between pickled vegetable consumption and the risk of breast cancer using a validated food frequency questionnaire. A total of 358 patients with breast cancer who were matched to 360 healthy controls by age (using a 5-yr age distribution) were recruited from the National Cancer Center in South Korea. After adjusting for nondietary risk factors, total vegetable intake was inversely associated with risk of breast cancer. However, unlike nonpickled vegetables, pickled vegetable intake and its proportion relative to total vegetables were positively associated with the risk of breast cancer, and this association was more profound and consistent when pickled vegetable intake was considered as a proportion relative to total vegetables (odds ratio [OR] = 6.24, 95% confidence interval [CI] = 3.55-10.97; P for trend <0.001 for highest vs. lowest quartiles of intake) than as the absolute consumed amount (OR = 2.47, 95% CI = 1.45-4.21; P for trend = 0.015 for highest vs. lowest quartiles of intake). These results suggest that not only the amount of total vegetable intake but also the amounts of different types of vegetable (i.e., pickled or nonpickled) and their proportions relative to total vegetables are significantly associated with the risk of breast cancer.",
"title": "Vegetables, but not pickled vegetables, are negatively associated with the risk of breast cancer."
},
{
"docid": "MED-5035",
"text": "In this study, we examined the association between meat and fish intake and the risk of various cancers. Mailed questionnaires were completed by 19,732 incident, histologically confirmed cases of cancer of the stomach, colon, rectum, pancreas, lung, breast, ovary, prostate, testis, kidney, bladder, brain, non-Hodgkin's lymphomas (NHL), and leukemia and 5,039 population controls between 1994 and 1997 in 8 Canadian provinces. Measurement included information on socioeconomic status, lifestyle habits, and diet. A 69-item food frequency questionnaire provided data on eating habits 2 yr before data collection. Odds ratios and 95% confidence intervals were derived through unconditional logistic regression. Total meat and processed meat were directly related to the risk of stomach, colon, rectum, pancreas, lung, breast (mainly postmenopausal), prostate, testis, kidney, bladder, and leukemia. Red meat was significantly associated with colon, lung (mainly in men), and bladder cancer. No relation was observed for cancer of the ovary, brain, and NHL. No consistent excess risk emerged for fish and poultry, which were inversely related to the risk of a number of cancer sites. These findings add further evidence that meat, specifically red and processed meat, plays an unfavorable role in the risk of several cancers. Fish and poultry appear to be favorable diet indicators.",
"title": "Meat and fish consumption and cancer in Canada."
},
{
"docid": "MED-1997",
"text": "The increased prevalence of childhood overweight and obesity is not unique to industrialized societies; dramatic increases are occurring in urbanized areas of developing countries. In light of the consensus that obesity is a significant public health concern and that many weight-loss interventions have been unsuccessful in the long term, an exploration of food patterns that are beneficial in the primary prevention of obesity is warranted. The focus of this article is to review the relation between vegetarian diets and obesity, particularly as they relate to childhood obesity. Epidemiologic studies indicate that vegetarian diets are associated with a lower body mass index (BMI) and a lower prevalence of obesity in adults and children. A meta-analysis of adult vegetarian diet studies estimated a reduced weight difference of 7.6 kg for men and 3.3 kg for women, which resulted in a 2-point lower BMI (in kg/m(2)). Similarly, compared with nonvegetarians, vegetarian children are leaner, and their BMI difference becomes greater during adolescence. Studies exploring the risk of overweight and food groups and dietary patterns indicate that a plant-based diet seems to be a sensible approach for the prevention of obesity in children. Plant-based diets are low in energy density and high in complex carbohydrate, fiber, and water, which may increase satiety and resting energy expenditure. Plant-based dietary patterns should be encouraged for optimal health and environmental benefits. Food policies are warranted to support social marketing messages and to reduce the cultural and economic forces that make it difficult to promote plant-based dietary patterns.",
"title": "Vegetarian diets and childhood obesity prevention."
},
{
"docid": "MED-1844",
"text": "Total aluminum, chromium, copper, iron, manganese, and nickel were determined in black tea, green tea, Hibiscus sabdariffa, and Ilex paraguariensis (mate) by electrothermal atomic absorption spectrometry after nitric/perchloric acid digestion. In each case, one ground sample of commercially available leafy material was prepared and three 0.5-g subsamples were run in parallel. The infusions were also analyzed and the percentage of each element leached into the liquor was evaluated. The obtained results indicated that hibiscus and mate contained lower levels of aluminum (272+/-19 microg/g and 369+/-22 microg/g, respectively) as referred to black tea (759+/-31 microg/g) or green tea (919micro29 microg/g) and suggested that mate drinking could be a good dietary source of essential micronutrient manganese (total content 2223+/-110 microg/g, 48.1% leached to the infusion). It was also found that the infusion of hibiscus could supply greater amounts of iron (111+/-5 microg/g total, 40.5% leached) and copper (5.9+/-0.3 microg/g total, 93.4% leached) as compared to other infusions. Moreover, it was found that the percentage of element leached to the infusion was strongly related to the tannins content in the beverage (correlation coefficients > 0.82 with the exception for nickel); for lower tannins level, better leaching was observed.",
"title": "Determination of total aluminum, chromium, copper, iron, manganese, and nickel and their fractions leached to the infusions of black tea, green tea..."
},
{
"docid": "MED-1880",
"text": "Legumes are the basés diet in several countries. They hold a high nutritional value, but other properties related to human health are nowadays being studied. The aim of this work was to study the influence of processes (boiling or germination) on the phenolic composition of dark beans (Phaseolus vulgaris L. c.v. Tolosana) and their effect on their antioxidant, neuroprotective and anticancer ability. Phenolic composition of raw and processed dark beans was analysed by HPLC-PAD and HPLC-ESI/MS. The antioxidant activity was evaluated by ORAC. Astrocytes cultures (U-373) have been used to test their neuroprotective effect. Anticancer activities were evaluated on three different cell lines (renal adenocarcinoma (TK-10), breast adenocarcinoma (MCF-7) and melanoma (UACC-62)) by sulphorhodamine B method. Qualitative and quantitative differences in phenolic composition have been observed between raw and processed dark beans that influence the antioxidant activity, mainly for germinated samples which show a decrease of antioxidant capacity. Although every assayed extracts decreased reactive oxygen species release and exhibited cytotoxicity activities on cancer cell lines, raw beans proved to be the most active in neuroprotective and antitumoral effects; this sample is especially rich in phenolic compounds, mainly anthocyanins. This study further demonstrated that phenolic composition of dark beans is related with cooking process and so with their neuroprotective and anticancer activity; cooking of dark beans improves their digestion and absorption at intestinal level, while maintaining its protective ability on oxidative process at cellular level. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Effect of cooking and germination on phenolic composition and biological properties of dark beans (Phaseolus vulgaris L.)."
},
{
"docid": "MED-2519",
"text": "To date, the only intervention that has consistently been shown to slow the rate of aging, and to increase mean and maximum lifespan in short-lived species, is life-long calorie restriction. It is yet unclear whether long-term calorie restriction in longer lived species (i.e. primates and humans) will have a similar effect. In humans, several studies investigating short-term calorie restriction or \"weight loss\" programs suggest beneficial outcomes on parameters of cardiovascular disease. Studies on long-term calorie restriction are performed on a self-selected group of human subjects and show similar effects. However, few studies are currently investigating the quality of life and potential pitfalls of long-term calorie restriction in humans. It is likely that some of the physiological and psychological effects of caloric restriction that occur in animals may impact the human life very differently. For certain, calorie restriction has a plethora of health benefits in mammals, such as a reduction in age-related diseases such as cancer. However, despite the \"magic\" of CR, this intervention in humans may present itself with a number of health concerns, which may not be applicable to or impact the life of experimental animals, but may do so in humans. These potential pitfalls and \"side effects\" are not clearly addressed in the literature and will be a focus of this review.",
"title": "Caloric restriction in humans: potential pitfalls and health concerns."
},
{
"docid": "MED-2476",
"text": "An increase in asthma and atopic disease has been recorded in many countries where society has become more prosperous. We have investigated two possible explanations: a reduction in childhood infections and a change in diet. In a cohort of people followed up since 1964, originally selected as a random sample of primary school children, we have investigated the relevance of family size and the common childhood infectious diseases to development of eczema, hay fever and asthma. Although membership of a large family reduced risks of hay fever and eczema (but not asthma), this was not explained by the infections the child had suffered. Indeed, the more infections the child had had, the greater the likelihood of asthma, although measles gave a modest measure of protection. We have investigated dietary factors in two separate studies. In the first, we have shown the risks of bronchial hyper-reactivity are increased seven-fold among those with the lowest intake of vitamin C, while the lowest intake of saturated fats gave a 10-fold protection. In the second, we have shown that the risk of adult-onset wheezy illness is increased five-fold by the lowest intake of vitamin E and doubled by the lowest intake of vitamin C. These results were supported by direct measurements of the vitamins and triglycerides in plasma. We have proposed that changes in the diet of pregnant women may have reflected those observed in the population as a whole and that these may have resulted in the birth of cohorts of children predisposed to atopy and asthma. The direct test of this is to study the diet and nutritional status of a large cohort of pregnant women and to follow their offspring forward. This is our current research.",
"title": "Diet, infection and wheezy illness: lessons from adults."
},
{
"docid": "MED-2374",
"text": "OBJECTIVES: To assess the dose-response relationship between egg consumption and the risk of cardiovascular diseases (CVD) and diabetes. METHODS: We systematically searched MEDLINE database through December 2012. Fixed- or random-effects model was used to pool the relative risks (RRs) and their 95% confidence intervals (CIs). Subgroup analyses was performed to explore the potential sources of heterogeneity. Weighted linear regression model was used to estimate the dose-response relationship. RESULTS: Fourteen studies involving 320,778 subjects were included. The pooled RRs of the risk of CVD, CVD for separated diabetes patients, and diabetes for the highest vs lowest egg intake were 1.19 (95% CI 1.02-1.38), 1.83 (95% CI 1.42-2.37), 1.68 (95% CI 1.41-2.00), respectively. For each 4/week increment in egg intake, the RRs of the risk for CVD, CVD for separated diabetes patients, diabetes was 1.06 (95% CI 1.03-1.10), 1.40 (95% CI 1.25-1.57), 1.29 (95% CI 1.21-1.37), respectively. Subgroup analyses showed that population in other western countries have increased CVD than ones in USA (RR 2.00, 95% CI 1.14 to 3.51 vs 1.13, 95% CI 0.98 to 1.30, P = 0.02 for subgroup difference). CONCLUSIONS: Our study suggests that there is a dose-response positive association between egg consumption and the risk of CVD and diabetes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.",
"title": "Egg consumption and risk of cardiovascular diseases and diabetes: a meta-analysis."
},
{
"docid": "MED-5337",
"text": "PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.",
"title": "Intensive lifestyle changes may affect the progression of prostate cancer."
}
] |
171706
|
Iain Glen is a television actor and is a film actor.
|
[
{
"docid": "Iain_Glen",
"text": "Iain Glen ( born 24 June 1961 ) is a Scottish film , television , and stage actor . Glen is best known for his roles as Dr. Alexander Isaacs / Tyrant in the Resident Evil films and for portraying Ser Jorah Mormont on Game of Thrones . Other notable roles include John Hanning Speke in Mountains of the Moon , Sir Richard Carlisle in Downton Abbey , the title role in Jack Taylor and Jarrod Slade in Cleverman .",
"title": ""
}
] |
[
{
"docid": "Vaughn_Edwards",
"text": "Vaughn Edwards is a fictional character the BBC television drama Spooks being portrayed by actor Iain Glen . He appears in the ninth series as a mysterious figure from the past of Lucas North . He therefore acts as the series 's main antagonist .",
"title": ""
},
{
"docid": "Edward_Glen",
"text": "Edward Glen ( born 1953 ) , sometimes credited as Eddie Glen , is a Canadian actor and voice actor who has appeared in and provided voices for various television shows , films and video games . He is best known for voicing Thomas the Tank Engine in Thomas and the Magic Railroad .",
"title": ""
},
{
"docid": "Glen_Meadows",
"text": "Glen Paul Meadows ( born January 20 , 1974 ) is an American film and television actor who has primarily appeared in softcore-pornographic films and television series .",
"title": ""
},
{
"docid": "Glen_Barry",
"text": "Glen Barry ( born August 12 , 1982 ) is an Irish film and television actor . Glen Barry was born in Dublin , Ireland . Barry attended the prestigious Dublin Youth Theatre . His first acting job was playing the son of award-winning actress Julie Walters in the TV movie The Return . He is younger brother of actor Jason Barry and Assistant Director Keith Barry . Glen is also an accomplished horseman . In 2016 he portrayed a mummer in the HBO series Game of Thrones in Season 6 .",
"title": ""
},
{
"docid": "Rick_Jay_Glen",
"text": "Rick Jay Glen ( born October 13 , 1981 ) is an American actor , voice actor , singer , songwriter , director , producer , and screenwriter . He is best known for the voice of Briar , from the hit Chinese animated television series Boonie Bears , and the animated films Boonie Bears : To the Rescue ( 2014 ) and Boonie Bears : Mystical Winter ( 2015 ) .",
"title": ""
},
{
"docid": "Iain_De_Caestecker",
"text": "Iain De Caestecker ( -LSB- ` iːən_də _ ` kæskər -RSB- - kər ; born 29 December 1987 ) is a Scottish actor , best known for his roles in films Shell ( 2012 ) , In Fear ( 2013 ) , Not Another Happy Ending ( 2013 ) , Lost River ( 2014 ) and as Agent Leopold Fitz in the television series Agents of S.H.I.E.L.D.",
"title": ""
},
{
"docid": "John_Hannah_(actor)",
"text": "John David Hannah ( born 23 April 1962 ) is a Scottish film and television actor . He came to prominence in Richard Curtis 's Four Weddings and a Funeral ( 1994 ) , for which he was nominated for the BAFTA Award for Best Actor in a Supporting Role . His other film appearances include Sliding Doors ( 1998 ) and the The Mummy trilogy ( 1999 -- 2008 ) . His television roles include : Dr Iain McCallum in McCallum ( 1995 -- 1998 ) ; D.I. John Rebus in Rebus ( 2000 -- 2001 ) ; Jack Roper in New Street Law ( 2006 -- 2007 ) ; Jake Osbourne in Cold Blood ( 2007 -- 2008 ) , Quintus Lentulus Batiatus in Spartacus ( 2010 -- 2011 ) , Jack Cloth in A Touch of Cloth ( 2012 -- 14 ) , Jason 's father ( Aeson ) in the BBC series Atlantis ( 2013 -- 15 ) and Dr. Holden Radcliffe in Agents of S.H.I.E.L.D. ( 2016-2017 ) .",
"title": ""
},
{
"docid": "Iain_McColl",
"text": "Iain McColl ( 27 January 1954 -- 4 July 2013 ) was a Scottish film and television actor , best known for his roles on British television series . McColl starred on City Lights , a BBC Scotland sitcom , from 1984 to 1991 . He then co-starred on the BBC Two sitcom , Rab C Nesbitt during its first run ( 1988-1999 ) . He rejoined the cast of Rab C Nesbitt again when the show was revived in 2008 . Additionally , he appeared in guest spots on numerous other television shows , including Hamish Macbeth , Still Game and Taggart . McColl was also cast in a small role in the 2002 American film , Gangs of New York , directed by Martin Scorsese . McColl died from complications of cancer on 4 July 2013 .",
"title": ""
},
{
"docid": "Glen_Murphy",
"text": "Glen Murphy MBE ( born 6 April 1957 ) is an English actor , and producer , perhaps best known as Firefighter George Green between 1988 and 2002 on the television drama London 's Burning . He was awarded an MBE in 2007 . Glen was the only ever-present actor throughout the run of London 's Burning , which attracted 18.92 million viewers for its 5th series , and averaging 15 million in its 14-year reign . He was the subject of This Is Your Life in 1992 . After London 's Burning he appeared in The Bill , Tank Malling , the Karl Howman directed drama Fathers of Girls , and alongside Joely Richardson in Shoreditch . His later work includes as a producer and lead actor in the film Lords of London ( 2014 ) . It won best film at the New York Hell 's Kitchen Film Festival , and he won the best Actor award at the Abruzzo film festival in Italy ; it is released in the United States by Lionsgate on 1 September 2015 . In 2016 he is in pre-production for Sabini and the Freddie Mills biopic Finger of Suspicion . He had a leading role in the Royal National Theatre production of Patrick Marber 's Dealer 's Choice ( Olivier & Evening Standard Awards ) in the West End of London in 1995 . Glen played the lead in the national tour of A Gentle Hook in 2004/5 . He attended St Bonaventure 's Catholic School in Forest Gate . Glen has a 3rd Dan Black Belt in Karate and has trained in the Martial Arts for over 30 years along with 7th Dan Karate Master Terry Stewart , The Martial Arts Hall of Fame and 7th Dan , Jamie O Keefe and currently trains in the kyokushin style with Liam Keaveney , 7th Dan Chairman of the BKK . He has been a friend of the actor Ray Winstone since childhood . His brother Darren Murphy was in the punk band Wasted Youth . His career began in the play `` Johnny Boxer '' at Half Moon Theatre in Alie st , East London and then on to a ` Guilty Generation '' , staged at his father Terry 's pub Bridge House in Canning Town . and then off down the road to Theatre Royal Stratford London . in their TIE Company Theatre Venture for a year . He was awarded the Freedom of the City of London in 1995 and became a Member of the Order of the British Empire in the 2007 Queen 's Birthday Honours for his charity work .",
"title": ""
},
{
"docid": "Starting_Over_(2007_film)",
"text": "Starting Over is a 2007 Scottish romantic drama television film directed by Giles Foster , produced by the British company Gate Television Productions for the German television channel Zweites Deutsches Fernsehen ( ZDF ) . Based on the 2002 novel of the same name by Robin Pilcher , the film stars Suzanne von Borsody , Iain Glen and Rutger Hauer .",
"title": ""
},
{
"docid": "Jason_Flemyng",
"text": "Jason Iain Flemyng ( born 25 September 1966 ) is an English actor . Flemyng is known for his film work , which has included roles in British films such as Lock , Stock and Two Smoking Barrels ( 1998 ) and Snatch ( 2000 ) , both for Guy Ritchie , as well as Hollywood productions such as Rob Roy ( 1995 ) , the Alan Moore comic book adaptations From Hell ( 2001 ) and The League of Extraordinary Gentlemen ( 2003 ) , and The Curious Case of Benjamin Button ( 2008 ) . He has also appeared in prominent roles in both theatre and television in the UK . Flemyng speaks French fluently , and has made three films in that language . He won the Best Actor Award at the Geneva Film Festival for his role in 1996 's Alive and Kicking .",
"title": ""
},
{
"docid": "Glen_Chin",
"text": "Glen Chin ( born January 27 , 1948 ) is a critically acclaimed American actor who stars in film and television . He is of Chinese descent . Chin has appeared in 50 First Dates as the humorous Hawaiian cafe regular , The Underachievers ( 1987 ) , and After One Cigarette as Shigeru . He is a Chinese actor in such films as Hollywood Hong Kong . Chin 's television credits include Boy Meets World ( the Eskimo ) , Night Stand with Dick Dietrick ( Coco ) , Mighty Max and Seinfeld . In the Seinfeld episode `` The Opera '' , Chin plays Harry Fong , a character who buys a scalped ticket to an opera from George Costanza right before ( or during ) his girlfriend Susan ends up making the opera , so in the end , Jerry Seinfeld , Elaine Benes , Cosmo Kramer , Chin 's character and Susan all end up watching the opera . In Michael Jackson 's music video Black or White , Chin morphs into Tyra Banks .",
"title": ""
},
{
"docid": "Glen_White_(actor)",
"text": "Glen White ( June 13 , 1880 - ? ) was an American actor . He appeared in 50 films between 1912 and 1921 .",
"title": ""
},
{
"docid": "Iain_Rogerson",
"text": "Iain Rogerson is a British actor born ( born October 1960 ) in Cefn-y-bedd , Wrexham , Wales . Rogerson is best known for his portrayal of Harry Flagg in Coronation Street . Alongside appearances in Emmerdale , Doctors , Casualty , Heartbeat , Peak Practice , The Hello Girls , As Time Goes By , The Bill , People Like Us , Drop the Dead Donkey and Bloomin Marvellous , plus numerous film appearances including Chariots Of Fire , Mike Bassett : England Manager , To Kill A King , Bedazzled and Up 'n' Under , he has done extensive theatre work including work with John Godber and Hull Truck Theatre . Iain Rogerson is represented by CV actor management .",
"title": ""
},
{
"docid": "Iain_Fletcher",
"text": "Iain Fletcher is a British television actor , best known for his role as DC Rod Skase in the ITV1 drama series The Bill . He served on the show for 6 years . Other television credits include Family Affairs , Casualty and Doctors . Stage credits include Sam Carmichael in the musical Mamma Mia ! in the West End and Bill Sikes in Cameron Mackintosh 's Production of Oliver ! He can be seen on television regularly appearing on adverts for Wonga .",
"title": ""
},
{
"docid": "Glen_Campbell_(actor)",
"text": "Glen Campbell is a Jamaican actor and comedian , known for his role in the 1980s Jamaica Broadcasting Corporation television series Titus in Town . His first performances were as a high school student in Louis Marriott 's 1981 stage production of Playboy . He also gained national recognition for his performance as the bulging eyed policeman in the Fabulous Five Inc. music video for `` Ring Road '' . He won the Actor Boy Award in 1999 for his roles in Breadfruit Kingdom .",
"title": ""
},
{
"docid": "List_of_Jamaican_actors",
"text": "This a list of notable actors born in Jamaica . Cherine Anderson ( b. 1984 , East Kingston , Jamaica ) , actress and dancehall/reggae vocalist Roxanne Beckford ( b. 1969 , Kingston , Jamaica ) , film and television actress Paul Campbell ( b. Jamaica ) , film and stage actor Sabrina Colie ( b. 1980 , Mandeville , Jamaica ) , actress and director Doña Croll ( b. 1959 , Jamaica ) , television actress Charles Hyatt ( b. 1931 , Kingston , Jamaica ; d. 2007 ) , film and television actor Clifton Jones ( b. 1943 , Jamaica ) , television actor Venice Kong ( b. 1961 , St. Mary , Jamaica ) , model and actress Ky-Mani Marley ( b. 1976 , Falmouth , Jamaica ) , actor and reggae musician Louis Marriott ( b. 1935 , St. Andrew , Jamaica ) , actor , director , writer and broadcaster Yanna McIntosh ( b. Jamaica ) , film , television and stage actress Count Prince Miller ( b. 1935 , Saint Mary Parish , Jamaica ) , actor and musician Evan Parke ( b. 1968 , Kingston , Jamaica ) , film and television actor Keith ` Shebada ' Ramsey ( b. Kingston , Jamaica ) , actor and comedian Audrey Reid ( b. 1970 , East Kingston , Jamaica ) , film actress David Reivers ( b. 1958 , Kingston , Jamaica ) , film and television actor Oliver Samuels ( b. 1948 , St. Mary , Jamaica ) , comedian and television actor Dennis Scott ( b. 1939 , Kingston , Jamaica ; d. 1991 ) , playwright , actor , dancer and poet Madge Sinclair ( b. 1938 , Kingston , Jamaica ; d. 1995 ) , film and television actress Peter Williams ( b. 1957 , Kingston , Jamaica ) , film and television actor",
"title": ""
},
{
"docid": "Lee_Mason_(actor)",
"text": "Lee Mason is an Australian film , television and stage actor from Melbourne . He is probably best known for his lead role in The Independent as naive independent politician Marty Browning . This role garnered Mason many favourable reviews , with James Brown of FilmInk describing Marty as `` the most charming protagonist since Kenny '' . Mason 's most recent work is a production of Glengarry Glen Ross at the Chapel Off Chapel theatre in Prahran .",
"title": ""
},
{
"docid": "Glen_Jensen",
"text": "Glen Jensen ( born March 24 , 1953 ) is an American actor and stand-up comedian . Glen started out performing at various comedy clubs in Philadelphia , New Jersey and New York City . In 2001 , Jensen became a finalist in the Boston Comedy and Film Festival , and in 2003 he went on to win the Philly 's Funniest Comedy Competition . This led to an appearance on the TV show `` Comedy Show 'N Tell '' shot in Las Vegas , Nevada as well as `` Comedy at Club 54 '' in Toronto , Ontario , Canada . Glen began appearing as an opening act for the Doobie Brothers , Spyro Gyra and Al Jarreau . A regular performer in Las Vegas and Atlantic City , New Jersey , his work on the comedy stage can be seen at The Improv , The Funny Bone and Catch a Rising Star . After achieving a strong measure of success with stand-up comedy , Glen decided to throw his hat in the ring as an actor . He played the role of Kowalski in the psychological thriller Fingerprints , sharing the screen with Lou Diamond Phillips , Leah Pipes , Geoffrey Lewis , Sally Kirkland , and Kristin Cavallari . Fingerprints went on to win the Best Feature Film award in the New York City Horror Film Festival . He is known for his role as General Jernigan in Denizen , directed by the newly anointed `` Female Roger Corman '' , J.A. Steel . He received the `` Best Actor in a Feature Film '' Honorable Mention at the world premier of Denizen at the Bare Bones Film Festival .",
"title": ""
},
{
"docid": "Ian_Sinclair_(disambiguation)",
"text": "Ian Sinclair ( born 1929 ) is an Australian politician . Ian Sinclair may also refer to : Ian David Sinclair ( 1913 -- 2006 ) , Canadian businessman and senator Ian Sinclair ( cricketer ) ( born 1933 ) , New Zealand cricketer Ian Sinclair ( broadcaster ) , New Zealand television journalist and reporter Ian Sinclair ( Canadian football ) ( born 1960 ) , Canadian football player Ian Sinclair ( voice actor ) ( born 1984 ) , American voice actor Ian Sinclair ( activist ) , British left-wing activist Iain Sinclair ( born 1943 ) , British writer Iain Sinclair ( rugby union ) ( born 1976 ) , Scottish rugby union player",
"title": ""
},
{
"docid": "Jeff_Bennett",
"text": "Jeffrey Glen `` Jeff '' Bennett ( born October 2 , 1962 ) is an American voice actor and singer . His voice roles include Johnny Bravo in the television series of the same name , Petrie in the Land Before Time films and television series , Mr. Smee and Bones in Jake and the Neverland Pirates , The Man With the Yellow Hat in Curious George , Raj in Camp Lazlo , Kowalski in The Penguins of Madagascar series and various other characters in films , television shows and video games .",
"title": ""
},
{
"docid": "Karan_(name)",
"text": "MdSahmad786 Karan Bajaj , Indian American author Karan Brar , American actor Karan Grover , Indian television actor Karan Johar , an Indian film director and producer Karan Kundra , Indian television actor Karan Malhotra , an Indian filmmaker Karan Mehra , Indian television actor Karan Patel , Indian television actor Karan Sharma , Indian cricketer Karan Sharma , Indian film actor Karan Sharma , Indian television actor Karan Singh , Indian politician Karan Singh Grover , Indian television actor Karan Tacker , Indian television actor Karan Thapar , Indian television commentator and interviewer Karan Wahi , Indian television actor Karanvir Bohra , Indian television actor , formerly known as Manoj Bohra Karan Vohra , Indian television actor Karan Jotwani , Indian television actor",
"title": ""
},
{
"docid": "Game_of_Thrones_(season_1)",
"text": "The first season of the fantasy drama television series Game of Thrones premiered on HBO on April 17 , 2011 , at 9.00 pm in the U.S. , and concluded on June 19 , 2011 . It consists of ten episodes , each of approximately 55 minutes . The series is based on A Game of Thrones , the first novel in the A Song of Ice and Fire series by George R. R. Martin , adapted for television by David Benioff and D. B. Weiss . HBO had ordered a television pilot in November 2008 ; filming began the following year . However , it was deemed unsatisfactory and later reshot with some roles being recast . In March 2010 , HBO ordered the first season , which began filming in July 2010 , primarily in Belfast , Northern Ireland , with additional filming in Malta . The story takes place in a fictional world , primarily upon a continent called Westeros , with one storyline occurring on another continent to the east known as Essos . Like the novel , the season initially focuses on the family of nobleman Eddard Stark , who is asked to become chief advisor to his king and longtime friend , Robert Baratheon . Ned must find out who killed the previous Hand of the King , Jon Arryn , while trying to protect his family from their rivals the Lannisters . He uncovers the dark secrets about the Lannisters that his predecessor died trying to expose . Meanwhile , in Essos , the exiled Viserys Targaryen , son of the former king , believes he still has the rightful claim to the throne . Game of Thrones features a large ensemble cast , including Bean , Addy , Peter Dinklage , Lena Headey , Nikolaj Coster-Waldau , Michelle Fairley and Iain Glen . Newer actors were cast as the younger generation of characters , such as Kit Harington , Sophie Turner and Maisie Williams . Critics praised the show 's production values and cast , with specific accolades for Dinklage 's portrayal of Tyrion Lannister . The first season won two of the thirteen Emmy Awards for which it was nominated , for Outstanding Supporting Actor in a Drama Series ( Dinklage ) and Outstanding Main Title Design . It also received a nomination for Outstanding Drama Series . Bean and Emilia Clarke also received individual accolades , as did Ramin Djawadi for music . U.S. viewership rose by approximately 33 % over the course of the season , from 2.2 million to over 3 million by the finale .",
"title": ""
},
{
"docid": "Iain_Quarrier",
"text": "Iain Quarrier ( born April 12 , 1941 in Montreal ) is a Canadian actor . He appeared in only five movies in the mid to late 1960s before retiring from the film business following the murder of his close friend Sharon Tate in 1969 .",
"title": ""
},
{
"docid": "Ian_McDonald",
"text": "Ian McDonald may refer to : Ian McDonald ( musician ) ( born 1946 ) , member of King Crimson , 1969 -- 70 , and Foreigner , 1977 -- 79 Iain Matthews ( born 1946 ) , previously known as Ian McDonald , member of Fairport Convention Ian McDonald ( cricketer ) ( born 1923 ) , Australian cricketer Ian McDonald ( footballer , born 1951 ) ( born 1951 ) , Scottish football midfielder with Darlington Ian McDonald ( footballer , born 1953 ) , English football midfielder with York City and Aldershot , among others Ian McDonald ( footballer , born 1958 ) ( born 1958 ) , Scottish football midfielder with Partick Thistle and Greenock Morton , among others Ian McDonald ( Guyanese writer ) ( born 1933 ) Ian McDonald ( British author ) ( born 1960 ) , British science fiction novelist Ian Donald Roy McDonald ( 1898 -- 1920 ) , World War I flying ace Ian MacDonald may refer to : Ian MacDonald ( 1948 -- 2003 ) , pen-name for British music critic Ian MacCormick Ian MacDonald ( footballer ) ( born 1953 ) , Scottish football defender with St. Johnstone and Carlisle , among others Ian MacDonald ( oceanographer ) , American Biological Oceanographer , Florida State University Ian MacDonald ( actor ) ( 1914 -- 1978 ) , American actor and producer Ian MacDonald ( politician ) , former public school teacher and former Mayor of Charlottetown , Prince Edward Island , Canada Ian Macdonald ( Australian politician ) ( born 1945 ) , Australian federal politician Ian Macdonald ( Scottish politician ) ( born 1934 ) , Scottish nationalist activist Ian Macdonald ( New South Wales politician ) ( born 1949 ) , former Australian state politician Ian G. Macdonald ( born 1928 ) , British mathematician L. Ian MacDonald ( born 1947 ) , Canadian writer , broadcaster , and diplomat H. Ian Macdonald ( born 1929 ) , Canadian economist , civil servant , and President of York University , 1974 -- 1984 Ian MacDonald ( architect ) ( born 1953 ) , Canadian architect Ian Verner Macdonald , Canadian writer and diplomat Ian Macdonald , character in Annie Laurie ( 1927 film ) Iain MacDonald may refer to : Iain MacDonald ( businessman ) , Irish entrepreneur Iain B. MacDonald , British television director Iain Fraoch MacDonald ( died 1368 ) , founder of Clan MacDonald of Glencoe Iain Sprangach MacDonald ( died 1340 ) , founder of Clan MacDonald of Ardnamurchan Iain McDonald may refer to : Iain McDonald ( born 1952 ) , Scottish football winger with Rangers and Dundee United",
"title": ""
},
{
"docid": "Iain_Anders",
"text": "Iain Anders , ( born Iain Anders Robertson ; 8 February 1933 -- 5 September 1997 ) was an English actor known for his roles in Taggart and A Horseman Riding By . Iain Anders Robertson was born to Scottish parents in 1933 in London . His career as an actor included many crime-related roles , and in this way paralleled his off-screen life , where he worked as a legal executive for a law firm specialising in criminal law , preparing court briefs . On screen , Anders appeared in small parts in many series , often playing either policemen or criminals . Among these were appearances in such shows as Z-Cars , Softly , Softly , and Juliet Bravo . His first screen appearance was as a prison officer in 1965 in Three Clear Sundays , a play in the `` Wednesday Play '' series . He also appeared on stage throughout England and Scotland during the 1950s and 1960s . His first stage appearance was as an extra in a performance of Shakespeare 's Henry V in Birmingham . In 1985 , Anders was also introduced into the television show Taggart , playing Superintendent Jack `` The Biscuit '' McVitie , alongside Mark McManus , who played the title character . It is for this role that he is most widely remembered , playing the role in 40 episodes , three of which did not screen until after his death . In his spare time , Anders was an expert at contract bridge , which he taught at the London School of Bridge .",
"title": ""
},
{
"docid": "Kevin_Weisman",
"text": "Kevin Glen Weisman is an American film , television and stage actor . He is internationally known for his work as Marshall Flinkman on the ABC television series Alias ( 2001 -- 2006 ) , Kives on the HBO television series and movie Hello Ladies ( 2013 -- 14 ) , Ray on the CBS television series Scorpion , Dr. Maynard on the NBC television series The Blacklist , and various other roles over his professional career . Weisman plays Ned Berring in season one of the David E. Kelley series , Goliath , streaming on Amazon Video .",
"title": ""
},
{
"docid": "AACTA_Award_for_Best_Lead_Actor_in_a_Television_Drama",
"text": "The AACTA Award for Best Lead Actor in a Television Drama is an accolade given by the Australian Academy of Cinema and Television Arts ( AACTA ) , a non-profit organisation whose aim is to `` identify , award , promote and celebrate Australia 's greatest achievements in film and television . '' The award is handed out at the annual AACTA Awards , which rewards achievements in Australian feature film , television , documentaries and short films . From 1986 -- 2010 , the category was presented by the Australian Film Institute ( AFI ) , the Academy 's parent organisation , at the annual Australian Film Institute Awards ( known as the AFI Awards ) . When the AFI launched the Academy in 2011 , it changed the annual ceremony to the AACTA Awards , with the current prize being a continuum of the AFI Award for Best Lead Actor in a Television Drama . The award was first presented in 1986 , as two separate categories for performances in a miniseries and tele feature . These were then merged in 1990 to become Best Actor in a Leading Role in a Telefeature or Mini Series , and by 1991 , the award was renamed Best Actor in a Leading Role in a Television Drama . In 2000 , the Best Performance in a Telefeature or Mini Series accolade was re-introduced as a separate prize from the drama award . All of these were then combined in 2002 , under the title Best Actor in a Leading Role in a Television Drama , and two years later , in 2004 , was renamed Best Actor in a Leading Role in a Television Drama or Comedy . A separate comedy award was established in 2006 , and the name reverted to Best Lead Actor in a Television Drama . The AACTA Award for Best Lead Actor in a Television Drama is given for performances in television drama series , miniseries , telefeature , children 's animation or children 's drama series . Candidates for this award must be human and male , and can not be nominated for best guest or supporting actor in a television drama in the same year , for the same production .",
"title": ""
},
{
"docid": "Richard_Roma",
"text": "Richard Roma is a fictional character from David Mamet 's 1982 play Glengarry Glen Ross and its 1992 film adaptation . Roma has been portrayed by a range of actors , including Joe Mantegna , Al Pacino and Liev Schreiber , although the role was originated by Jack Shepherd . Actors portraying Roma have seen multiple stage award wins and nominations -- both Mantegna and Schreiber received a Tony Award for Best Featured Actor in a Play for their depictions , while Shepherd earned a Laurence Olivier Award for Best Actor for his portrayal . In film , Pacino received nominations for both the Academy Award for Best Supporting Actor and the Golden Globe for Best Performance by an Actor In A Supporting Role in a Motion Picture .",
"title": ""
},
{
"docid": "Iain_Armitage",
"text": "Iain Armitage ( born July 15 , 2008 ) is an American theater critic and child actor . He is the son of actor Euan Morton and theater producer Lee Armitage . He is the grandson of government official Richard Lee Armitage . In 2017 , Armitage plays Ziggy Chapman in the HBO miniseries Big Little Lies . He will appear in The Glass Castle , a film adaptation of Jeannette Walls ' memoir of the same name . In January 2017 , Armitage starred in an episode of Law & Order : Special Victims Unit , playing a young child , Theo Lachere , who has been kidnapped . On March 13 , 2017 , CBS announced that it had ordered to series Young Sheldon , a prequel to the sitcom The Big Bang Theory , starring Armitage as the title character .",
"title": ""
}
] |
196
|
C2 works synergistically with A-769662 to activate dephosphorylated AMPK.
|
[
{
"docid": "19313533",
"text": "The metabolic stress-sensing enzyme AMP-activated protein kinase (AMPK) is responsible for regulating metabolism in response to energy supply and demand. Drugs that activate AMPK may be useful in the treatment of metabolic diseases including type 2 diabetes. We have determined the crystal structure of AMPK in complex with its activator 5-(5-hydroxyl-isoxazol-3-yl)-furan-2-phosphonic acid (C2), revealing two C2-binding sites in the γ-subunit distinct from nucleotide sites. C2 acts synergistically with the drug A769662 to activate AMPK α1-containing complexes independent of upstream kinases. Our results show that dual drug therapies could be effective AMPK-targeting strategies to treat metabolic diseases.",
"title": "Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding."
}
] |
[
{
"docid": "24294572",
"text": "The PI3K signaling pathway regulates cell growth and movement and is heavily mutated in cancer. Class I PI3Ks synthesize the lipid messenger PI(3,4,5)P3. PI(3,4,5)P3 can be dephosphorylated by 3- or 5-phosphatases, the latter producing PI(3,4)P2. The PTEN tumor suppressor is thought to function primarily as a PI(3,4,5)P3 3-phosphatase, limiting activation of this pathway. Here we show that PTEN also functions as a PI(3,4)P2 3-phosphatase, both in vitro and in vivo. PTEN is a major PI(3,4)P2 phosphatase in Mcf10a cytosol, and loss of PTEN and INPP4B, a known PI(3,4)P2 4-phosphatase, leads to synergistic accumulation of PI(3,4)P2, which correlated with increased invadopodia in epidermal growth factor (EGF)-stimulated cells. PTEN deletion increased PI(3,4)P2 levels in a mouse model of prostate cancer, and it inversely correlated with PI(3,4)P2 levels across several EGF-stimulated prostate and breast cancer lines. These results point to a role for PI(3,4)P2 in the phenotype caused by loss-of-function mutations or deletions in PTEN.",
"title": "PTEN Regulates PI(3,4)P2 Signaling Downstream of Class I PI3K"
},
{
"docid": "26025820",
"text": "The rat kidney ablation and infarction (A/I) model of subtotal or 5/6th nephrectomy is the most commonly studied model of nondiabetic chronic kidney disease (CKD). The A/I kidney at 1 wk exhibits reductions in kidney function, as determined by glomerular filtration rate, and diminished metabolic efficiency as determined by oxygen consumption per sodium transport (QO2/TNa). As renoprotective AMPK activity is affected by metabolic changes and cellular stress, we evaluated AMPK activity in this model system. We show that these early pathophysiological changes are accompanied by a paradoxical decrease in AMPK activity. Over time, these kidney parameters progressively worsen with extensive kidney structural, functional, metabolic, and fibrotic changes observed at 4 wk after A/I. We show that induction of AMPK activity with either metformin or 5-aminoimidazole-4-carboxamide ribonucleotide increases AMPK activity in this model and also corrects kidney metabolic inefficiency, improves kidney function, and ameliorates kidney fibrosis and structural alterations. We conclude that AMPK activity is reduced in the subtotal nephrectomy model of nondiabetic CKD, that altered regulation of AMPK is coincident with the progression of disease parameters, and that restoration of AMPK activity can suppress the progressive loss of function characteristic of this model. We propose that induction of AMPK activity may prove an effective therapeutic target for the treatment of nondiabetic CKD.",
"title": "Induction of AMPK activity corrects early pathophysiological alterations in the subtotal nephrectomy model of chronic kidney disease."
},
{
"docid": "3973445",
"text": "Adenosine 5′-monophosphate–activated protein kinase (AMPK) is a pivotal regulator of metabolism at cellular and organismal levels. AMPK also suppresses inflammation. We found that pharmacological activation of AMPK rapidly inhibited the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway in various cells. In vitro kinase assays revealed that AMPK directly phosphorylated two residues (Ser515 and Ser518) within the Src homology 2 domain of JAK1. Activation of AMPK enhanced the interaction between JAK1 and 14-3-3 proteins in cultured vascular endothelial cells and fibroblasts, an effect that required the presence of Ser515 and Ser518 and was abolished in cells lacking AMPK catalytic subunits. Mutation of Ser515 and Ser518 abolished AMPK-mediated inhibition of JAK-STAT signaling stimulated by either the sIL-6Rα/IL-6 complex or the expression of a constitutively active V658F-mutant JAK1 in human fibrosarcoma cells. Clinically used AMPK activators metformin and salicylate enhanced the inhibitory phosphorylation of endogenous JAK1 and inhibited STAT3 phosphorylation in primary vascular endothelial cells. Therefore, our findings reveal a mechanism by which JAK1 function and inflammatory signaling may be suppressed in response to metabolic stress and provide a mechanistic rationale for the investigation of AMPK activators in a range of diseases associated with enhanced activation of the JAK-STAT pathway.",
"title": "Phosphorylation of Janus kinase 1 (JAK1) by AMP-activated protein kinase (AMPK) links energy sensing to anti-inflammatory signaling"
},
{
"docid": "9899292",
"text": "Metformin is a widely used drug for treatment of type 2 diabetes with no defined cellular mechanism of action. Its glucose-lowering effect results from decreased hepatic glucose production and increased glucose utilization. Metformin's beneficial effects on circulating lipids have been linked to reduced fatty liver. AMP-activated protein kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism. Here we report that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed. Activation of AMPK by metformin or an adenosine analogue suppresses expression of SREBP-1, a key lipogenic transcription factor. In metformin-treated rats, hepatic expression of SREBP-1 (and other lipogenic) mRNAs and protein is reduced; activity of the AMPK target, ACC, is also reduced. Using a novel AMPK inhibitor, we find that AMPK activation is required for metformin's inhibitory effect on glucose production by hepatocytes. In isolated rat skeletal muscles, metformin stimulates glucose uptake coincident with AMPK activation. Activation of AMPK provides a unified explanation for the pleiotropic beneficial effects of this drug; these results also suggest that alternative means of modulating AMPK should be useful for the treatment of metabolic disorders.",
"title": "Role of AMP-activated protein kinase in mechanism of metformin action."
},
{
"docid": "9752604",
"text": "In light of the emerging interplay between redox and metabolic signaling pathways we investigated the potential cross talk between nuclear factor E2-related factor 2 (Nrf2) and AMP-activated kinase (AMPK), central regulators of the cellular redox and energy balance, respectively. Making use of xanthohumol (XN) as an activator of both the AMPK and the Nrf2 signaling pathway we show that AMPK exerts a positive influence on Nrf2/heme oxygenase (HO)-1 signaling in mouse embryonic fibroblasts. Genetic ablation and pharmacological inhibition of AMPK blunts Nrf2-dependent HO-1 expression by XN already at the mRNA level. XN leads to AMPK activation via interference with mitochondrial function and activation of liver kinase B1 as upstream AMPK kinase. The subsequent AMPK-mediated enhancement of the Nrf2/HO-1 response does not depend on inhibition of the mammalian target of rapamycin, inhibition of glycogen synthase kinase 3β, or altered abundance of Nrf2 (total and nuclear). However, reduced endoplasmic reticulum stress was identified and elaborated as a step in the AMPK-augmented Nrf2/HO-1 response. Overall, we shed more light on the hitherto incompletely understood cross talk between the LKB1/AMPK and the Nrf2/HO-1 axis revealing for the first time involvement of the unfolded protein response as an additional player and suggesting tight cooperation between signaling pathways controlling cellular redox, energy, or protein homeostasis.",
"title": "Activated AMPK boosts the Nrf2/HO-1 signaling axis—A role for the unfolded protein response"
},
{
"docid": "3419709",
"text": "Nonalcoholic fatty liver disease (NAFLD) is a growing worldwide epidemic and an important risk factor for the development of insulin resistance, type 2 diabetes, nonalcoholic steatohepatitis (NASH), and hepatic cellular carcinoma (HCC). Despite the prevalence of NAFLD, lifestyle interventions involving exercise and weight loss are the only accepted treatments for this disease. Over the last decade, numerous experimental compounds have been shown to improve NAFLD in preclinical animal models, and many of these therapeutics have been shown to increase the activity of the cellular energy sensor AMP-activated protein kinase (AMPK). Because AMPK activity is reduced by inflammation, obesity, and diabetes, increasing AMPK activity has been viewed as a viable therapeutic strategy to improve NAFLD. In this review, we propose three primary mechanisms by which AMPK activation may improve NAFLD. In addition, we examine the mechanisms by which AMPK is activated. Finally, we identify 27 studies that have used AMPK activators to reduce NAFLD. Future considerations for studies examining the relationship between AMPK and NAFLD are highlighted.",
"title": "Treatment of nonalcoholic fatty liver disease: role of AMPK."
},
{
"docid": "49556906",
"text": "Fibrosis is a pathological result of a dysfunctional repair response to tissue injury and occurs in a number of organs, including the lungs1. Cellular metabolism regulates tissue repair and remodelling responses to injury2-4. AMPK is a critical sensor of cellular bioenergetics and controls the switch from anabolic to catabolic metabolism5. However, the role of AMPK in fibrosis is not well understood. Here, we demonstrate that in humans with idiopathic pulmonary fibrosis (IPF) and in an experimental mouse model of lung fibrosis, AMPK activity is lower in fibrotic regions associated with metabolically active and apoptosis-resistant myofibroblasts. Pharmacological activation of AMPK in myofibroblasts from lungs of humans with IPF display lower fibrotic activity, along with enhanced mitochondrial biogenesis and normalization of sensitivity to apoptosis. In a bleomycin model of lung fibrosis in mice, metformin therapeutically accelerates the resolution of well-established fibrosis in an AMPK-dependent manner. These studies implicate deficient AMPK activation in non-resolving, pathologic fibrotic processes, and support a role for metformin (or other AMPK activators) to reverse established fibrosis by facilitating deactivation and apoptosis of myofibroblasts.",
"title": "Metformin reverses established lung fibrosis in a bleomycin model"
},
{
"docid": "23974474",
"text": "AMP-activated protein kinase (AMPK) is an energy-sensing enzyme whose activity is inhibited in settings of insulin resistance. Exposure to a high glucose concentration has recently been shown to increase phosphorylation of AMPK at Ser(485/491) of its α1/α2 subunit; however, the mechanism by which it does so is not known. Diacylglycerol (DAG), which is also increased in muscle exposed to high glucose, activates a number of signaling molecules including protein kinase (PK)C and PKD1. We sought to determine whether PKC or PKD1 is involved in inhibition of AMPK by causing Ser(485/491) phosphorylation in skeletal muscle cells. C2C12 myotubes were treated with the PKC/D1 activator phorbol 12-myristate 13-acetate (PMA), which acts as a DAG mimetic. This caused dose- and time-dependent increases in AMPK Ser(485/491) phosphorylation, which was associated with a ∼60% decrease in AMPKα2 activity. Expression of a phosphodefective AMPKα2 mutant (S491A) prevented the PMA-induced reduction in AMPK activity. Serine phosphorylation and inhibition of AMPK activity were partially prevented by the broad PKC inhibitor Gö6983 and fully prevented by the specific PKD1 inhibitor CRT0066101. Genetic knockdown of PKD1 also prevented Ser(485/491) phosphorylation of AMPK. Inhibition of previously identified kinases that phosphorylate AMPK at this site (Akt, S6K, and ERK) did not prevent these events. PMA treatment also caused impairments in insulin-signaling through Akt, which were prevented by PKD1 inhibition. Finally, recombinant PKD1 phosphorylated AMPKα2 at Ser(491) in cell-free conditions. These results identify PKD1 as a novel upstream kinase of AMPKα2 Ser(491) that plays a negative role in insulin signaling in muscle cells.",
"title": "PKD1 Inhibits AMPKα2 through Phosphorylation of Serine 491 and Impairs Insulin Signaling in Skeletal Muscle Cells."
},
{
"docid": "24721866",
"text": "Macrophage-derived foam cells play important roles in the progression of atherosclerosis. We reported previously that ERK1/2-dependent granulocyte/macrophage colony-stimulating factor (GM-CSF) expression, leading to p38 MAPK/ Akt signaling, is important for oxidized low density lipoprotein (Ox-LDL)-induced macrophage proliferation. Here, we investigated whether activation of AMP-activated protein kinase (AMPK) could suppress macrophage proliferation. Ox-LDL-induced proliferation of mouse peritoneal macrophages was assessed by [(3)H]thymidine incorporation and cell counting assays. The proliferation was significantly inhibited by the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and restored by dominant-negative AMPKalpha1, suggesting that AMPK activation suppressed macrophage proliferation. AICAR partially suppressed Ox-LDL-induced ERK1/2 phosphorylation and GM-CSF expression, suggesting that another mechanism is also involved in the AICAR-mediated suppression of macrophage proliferation. AICAR suppressed GM-CSF-induced macrophage proliferation without suppressing p38 MAPK/Akt signaling. GM-CSF suppressed p53 phosphorylation and expression and induced Rb phosphorylation. Overexpression of p53 or p27(kip) suppressed GM-CSF-induced macrophage proliferation. AICAR induced cell cycle arrest, increased p53 phosphorylation and expression, and suppressed GM-CSF-induced Rb phosphorylation via AMPK activation. Moreover, AICAR induced p21(cip) and p27(kip) expression via AMPK activation, and small interfering RNA (siRNA) of p21(cip) and p27(kip) restored AICAR-mediated suppression of macrophage proliferation. In conclusion, AMPK activation suppressed Ox-LDL-induced macrophage proliferation by suppressing GM-CSF expression and inducing cell cycle arrest. These effects of AMPK activation may represent therapeutic targets for atherosclerosis.",
"title": "Activation of AMP-activated protein kinase suppresses oxidized low-density lipoprotein-induced macrophage proliferation."
},
{
"docid": "1590744",
"text": "The AMP-activated protein kinase (AMPK) is a key regulator of cellular and whole-body energy homeostasis, which acts to restore energy homoeostasis whenever cellular energy charge is depleted. Over the last 2 decades, it has become apparent that AMPK regulates several other cellular functions and has specific roles in cardiovascular tissues, acting to regulate cardiac metabolism and contractile function, as well as promoting anticontractile, anti-inflammatory, and antiatherogenic actions in blood vessels. In this review, we discuss the role of AMPK in the cardiovascular system, including the molecular basis of mutations in AMPK that alter cardiac physiology and the proposed mechanisms by which AMPK regulates vascular function under physiological and pathophysiological conditions.",
"title": "AMP-Activated Protein Kinase: An Ubiquitous Signaling Pathway With Key Roles in the Cardiovascular System"
},
{
"docid": "3504761",
"text": "The MAP kinase kinase kinase TGFβ-activated kinase 1 (TAK1) is activated by TLRs, IL-1, TNF, and TGFβ and in turn activates IKK-NF-κB and JNK, which regulate cell survival, growth, tumorigenesis, and metabolism. TAK1 signaling also upregulates AMPK activity and autophagy. Here, we investigated TAK1-dependent regulation of autophagy, lipid metabolism, and tumorigenesis in the liver. Fasted mice with hepatocyte-specific deletion of Tak1 exhibited severe hepatosteatosis with increased mTORC1 activity and suppression of autophagy compared with their WT counterparts. TAK1-deficient hepatocytes exhibited suppressed AMPK activity and autophagy in response to starvation or metformin treatment; however, ectopic activation of AMPK restored autophagy in these cells. Peroxisome proliferator-activated receptor α (PPARα) target genes and β-oxidation, which regulate hepatic lipid degradation, were also suppressed in hepatocytes lacking TAK1. Due to suppression of autophagy and β-oxidation, a high-fat diet challenge aggravated steatohepatitis in mice with hepatocyte-specific deletion of Tak1. Notably, inhibition of mTORC1 restored autophagy and PPARα target gene expression in TAK1-deficient livers, indicating that TAK1 acts upstream of mTORC1. mTORC1 inhibition also suppressed spontaneous liver fibrosis and hepatocarcinogenesis in animals with hepatocyte-specific deletion of Tak1. These data indicate that TAK1 regulates hepatic lipid metabolism and tumorigenesis via the AMPK/mTORC1 axis, affecting both autophagy and PPARα activity.",
"title": "TAK1-mediated autophagy and fatty acid oxidation prevent hepatosteatosis and tumorigenesis."
},
{
"docid": "3761017",
"text": "BACKGROUND Metformin, a widely used hypoglycemic drug, reduces stroke incidence and alleviates chronic inflammation in clinical trials. However, the effect of metformin in ischemic stroke is unclear. Here, we investigated the effect of metformin on ischemic stroke in mice and further explored the possible underlying mechanisms. METHODS Ninety-eight adult male CD-1 mice underwent 90-minute transient middle cerebral artery occlusion (tMCAO). Metformin (200 mg/kg) was administrated for up to 14 days. Neurobehavioral outcomes, brain infarct volume, inflammatory factors, blood-brain barrier (BBB) permeability and AMPK signaling pathways were evaluated following tMCAO. Oxygen glucose deprivation was performed on bEND.3 cells to explore the mechanisms of metformin in inhibiting inflammatory signaling pathways. RESULTS Infarct volume was reduced in metformin-treated mice compared to the control group following tMCAO (P < 0.05). Neurobehavioral outcomes were greatly improved in metformin-treated mice (P < 0.05). MPO+ cells, Gr1+ cells, MPO activity and BBB permeability were decreased after metformin administration (P < 0.05). In addition, metformin activated AMPK phosphorylation, inhibited NF-κB activation, down-regulated cytokine (IL-1β, IL-6, TNF-α) and ICAM-1 expression following tMCAO (P < 0.05). Furthermore, metformin activated AMPK signaling pathway and alleviated oxygen-glucose deprivation-induced ICAM-1 expression in bEND.3 cells (P < 0.05). Compound C, a selective AMPK inhibitor, eliminated this promotional effect. CONCLUSIONS Metformin down-regulated ICAM-1 in an AMPK-dependent manner, which could effectively prevent ischemia-induced brain injury by alleviating neutrophil infiltration, suggesting that metformin is a promising therapeutic agent in stroke therapy.",
"title": "Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion"
},
{
"docid": "22036571",
"text": "The AMP-activated protein kinase (AMPK) is a ubiquitous mammalian protein kinase important in the adaptation of cells to metabolic stress. The enzyme is a heterotrimer, consisting of a catalytic alpha subunit and regulatory beta and gamma subunits, each of which is a member of a larger isoform family. The enzyme is allosterically regulated by AMP and by phosphorylation of the alpha subunit. The beta subunit is post-translationally modified by myristoylation and multi-site phosphorylation. In the present study, we have examined the impact of post-translational modification of the beta-1 subunit on enzyme activity, heterotrimer assembly and subcellular localization, using site-directed mutagenesis and expression of subunits in mammalian cells. Removal of the myristoylation site (G2A mutant) results in a 4-fold activation of the enzyme and relocalization of the beta subunit from a particulate extranuclear distribution to a more homogenous cell distribution. Mutation of the serine-108 phosphorylation site to alanine is associated with enzyme inhibition, but no change in cell localization. In contrast, the phosphorylation site mutations, SS24, 25AA and S182A, while having no effects on enzyme activity, are associated with nuclear redistribution of the subunit. Taken together, these results indicate that both myristoylation and phosphorylation of the beta subunit of AMPK modulate enzyme activity and subunit cellular localization, increasing the complexity of AMPK regulation.",
"title": "Post-translational modifications of the beta-1 subunit of AMP-activated protein kinase affect enzyme activity and cellular localization."
},
{
"docid": "1686997",
"text": "The oxidative pentose phosphate pathway (PPP) contributes to tumour growth, but the precise contribution of 6-phosphogluconate dehydrogenase (6PGD), the third enzyme in this pathway, to tumorigenesis remains unclear. We found that suppression of 6PGD decreased lipogenesis and RNA biosynthesis and elevated ROS levels in cancer cells, attenuating cell proliferation and tumour growth. 6PGD-mediated production of ribulose-5-phosphate (Ru-5-P) inhibits AMPK activation by disrupting the active LKB1 complex, thereby activating acetyl-CoA carboxylase 1 and lipogenesis. Ru-5-P and NADPH are thought to be precursors in RNA biosynthesis and lipogenesis, respectively; thus, our findings provide an additional link between the oxidative PPP and lipogenesis through Ru-5-P-dependent inhibition of LKB1-AMPK signalling. Moreover, we identified and developed 6PGD inhibitors, physcion and its derivative S3, that effectively inhibited 6PGD, cancer cell proliferation and tumour growth in nude mice xenografts without obvious toxicity, suggesting that 6PGD could be an anticancer target.",
"title": "6-phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumor growth by inhibiting LKB1-AMPK signaling"
},
{
"docid": "14541844",
"text": "Highly conserved among eukaryotic cells, the AMP-activated kinase (AMPK) is a central regulator of carbon metabolism. To map the complete network of interactions around AMPK in yeast (Snf1) and to evaluate the role of its regulatory subunit Snf4, we measured global mRNA, protein and metabolite levels in wild type, Deltasnf1, Deltasnf4, and Deltasnf1Deltasnf4 knockout strains. Using four newly developed computational tools, including novel DOGMA sub-network analysis, we showed the benefits of three-level ome-data integration to uncover the global Snf1 kinase role in yeast. We for the first time identified Snf1's global regulation on gene and protein expression levels, and showed that yeast Snf1 has a far more extensive function in controlling energy metabolism than reported earlier. Additionally, we identified complementary roles of Snf1 and Snf4. Similar to the function of AMPK in humans, our findings showed that Snf1 is a low-energy checkpoint and that yeast can be used more extensively as a model system for studying the molecular mechanisms underlying the global regulation of AMPK in mammals, failure of which leads to metabolic diseases.",
"title": "Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator"
},
{
"docid": "1605196",
"text": "Successful generation of induced pluripotent stem cells entails a major metabolic switch from mitochondrial oxidative phosphorylation to glycolysis during the reprogramming process. The mechanism of this metabolic reprogramming, however, remains elusive. Here, our results suggest that an Atg5-independent autophagic process mediates mitochondrial clearance, a characteristic event involved in the metabolic switch. We found that blocking such autophagy, but not canonical autophagy, inhibits mitochondrial clearance, in turn, preventing iPSC induction. Furthermore, AMPK seems to be upstream of this autophagic pathway and can be targeted by small molecules to modulate mitochondrial clearance during metabolic reprogramming. Our work not only reveals that the Atg5-independent autophagy is crucial for establishing pluripotency, but it also suggests that iPSC generation and tumorigenesis share a similar metabolic switch.",
"title": "Atg5-independent autophagy regulates mitochondrial clearance and is essential for iPSC reprogramming"
},
{
"docid": "4695107",
"text": "The problem of antibiotic resistance, which has limited the use of cheap and old antibiotics, has necessitated the need for a continued search for new antimicrobial compounds. Understanding the mechanisms of resistance is important in the development of strategies to solving the problem. Active efflux of drugs, alteration of target sites and enzymatic degradations are the strategies by which pathogenic bacteria acquire or develop intrinsic resistance to antibiotics. Multi-drug resistance (MDR) pumps, capable of recognizing and expelling a variety of structurally unrelated compounds from the bacterial cell and conferring resistance to a wide range of antibiotics have since been characterized in many gram positive and gram negative pathogens like Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and, more recently, in mycobacteria. The ability of some chemical compounds (called MDR inhibitors or resistance modifying agents) to modify the resistance phenotype in bacteria by working synergistically with antibiotics in vitro has since been observed. The search for such compounds which can be combined with antibiotics in the treatment of drug resistant infections may be an alternative to overcoming the problem of resistance in bacteria. Crude extracts of medicinal plants stand out as veritable sources of potential resistance modifying agents and the African biosphere promises to be a potential source of such compounds owing to its rich plant species diversity.",
"title": "The challenges of overcoming antibiotic resistance: Plant extracts as potential sources of antimicrobial and resistance modifying agents"
},
{
"docid": "38533515",
"text": "The SNF1/AMP-activated protein kinase (AMPK) family maintains the balance between ATP production and consumption in all eukaryotic cells. The kinases are heterotrimers that comprise a catalytic subunit and regulatory subunits that sense cellular energy levels. When energy status is compromised, the system activates catabolic pathways and switches off protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. Surprisingly, recent results indicate that the AMPK system is also important in functions that go beyond the regulation of energy homeostasis, such as the maintenance of cell polarity in epithelial cells.",
"title": "AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy"
},
{
"docid": "9021186",
"text": "The persistence of transcriptionally silent but replication-competent HIV-1 reservoirs in Highly Active Anti-Retroviral Therapy (HAART)-treated infected individuals, represents a major hurdle to virus eradication. Activation of HIV-1 gene expression in these cells together with an efficient HAART has been proposed as an adjuvant therapy aimed at decreasing the pool of latent viral reservoirs. Using the latently-infected U1 monocytic cell line and latently-infected J-Lat T-cell clones, we here demonstrated a strong synergistic activation of HIV-1 production by clinically used histone deacetylase inhibitors (HDACIs) combined with prostratin, a non-tumor-promoting nuclear factor (NF)- kappaB inducer. In J-Lat cells, we showed that this synergism was due, at least partially, to the synergistic recruitment of unresponsive cells into the expressing cell population. A combination of prostratin+HDACI synergistically activated the 5' Long Terminal Repeat (5'LTR) from HIV-1 Major group subtypes representing the most prevalent viral genetic forms, as shown by transient transfection reporter assays. Mechanistically, HDACIs increased prostratin-induced DNA-binding activity of nuclear NF-kappaB and degradation of cytoplasmic NF-kappaB inhibitor, IkappaBalpha . Moreover, the combined treatment prostratin+HDACI caused a more pronounced nucleosomal remodeling in the U1 viral promoter region than the treatments with the compounds alone. This more pronounced remodeling correlated with a synergistic reactivation of HIV-1 transcription following the combined treatment prostratin+HDACI, as demonstrated by measuring recruitment of RNA polymerase II to the 5'LTR and both initiated and elongated transcripts. The physiological relevance of the prostratin+HDACI synergism was shown in CD8(+)-depleted peripheral blood mononuclear cells from HAART-treated patients with undetectable viral load. Moreover, this combined treatment reactivated viral replication in resting CD4(+) T cells isolated from similar patients. Our results suggest that combinations of different kinds of proviral activators may have important implications for reducing the size of latent HIV-1 reservoirs in HAART-treated patients.",
"title": "Synergistic Activation of HIV-1 Expression by Deacetylase Inhibitors and Prostratin: Implications for Treatment of Latent Infection"
},
{
"docid": "5108807",
"text": "Ciliary neurotrophic factor (CNTF) induces weight loss and improves glucose tolerance in humans and rodents. CNTF is thought to act centrally by inducing hypothalamic neurogenesis to modulate food intake and peripherally by altering hepatic gene expression, in a manner similar to that of leptin. Here, we show that CNTF signals through the CNTFRα–IL-6R–gp130β receptor complex to increase fatty-acid oxidation and reduce insulin resistance in skeletal muscle by activating AMP-activated protein kinase (AMPK), independent of signaling through the brain. Thus, our findings further show that the antiobesogenic effects of CNTF in the periphery result from direct effects on skeletal muscle, and that these peripheral effects are not suppressed by diet-induced or genetic models of obesity, an essential requirement for the therapeutic treatment of obesity-related diseases.",
"title": "CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK"
},
{
"docid": "14874811",
"text": "Oxygen (O2) deprivation, or hypoxia, has profound effects on cell metabolism and growth. Cells can adapt to low O2 in part through activation of hypoxia-inducible factor (HIF). We report here that hypoxia inhibits mRNA translation by suppressing multiple key regulators, including eIF2alpha, eEF2, and the mammalian target of rapamycin (mTOR) effectors 4EBP1, p70S6K, and rpS6, independent of HIF. Hypoxia results in energy starvation and activation of the AMPK/TSC2/Rheb/mTOR pathway. Hypoxic AMP-activated protein kinase (AMPK) activation also leads to eEF2 inhibition. Moreover, hypoxic effects on cellular bioenergetics and mTOR inhibition increase over time. Mutation of the TSC2 tumor suppressor gene confers a growth advantage to cells by repressing hypoxic mTOR inhibition and hypoxia-induced G1 arrest. Together, eIF2alpha, eEF2, and mTOR inhibition represent important HIF-independent mechanisms of energy conservation that promote survival under low O2 conditions.",
"title": "Hypoxia-induced energy stress regulates mRNA translation and cell growth."
},
{
"docid": "22185730",
"text": "Abnormal hyperphosphorylation of tau appears to be crucial in neurofibrillary degeneration in Alzheimer's disease (AD). Previous studies suggest that a down-regulation of protein phosphatase 2A (PP2A), the major tau phosphatase in human brain, contributes to tau hyperphosphorylation in AD. However, the effects of PP2A down-regulation on site-specific tau hyperphosphorylation is not well understood. In the present study, we showed that PP2A dephosphorylated tau at several phosphorylation sites with different efficiencies. Among the sites studied, Thr205, Thr212, Ser214, and Ser262 were the most favorable sites, and Ser199 and Ser404 were the least favorable sites for PP2A in vitro. Inhibition of PP2A with okadaic acid in metabolically active rat brain slices caused inhibition of glycogen synthase kinase-3beta (GSK-3beta) via an increase in its phosphorylation at Ser9. GSK-3beta phosphorylated tau at many sites, with Ser199, Thr205, and Ser396 being the most favorable sites in cells. The overall alterations in tau phosphorylation induced by PP2A inhibition were the result of the combined effects of both reduced tau dephosphorylation due to PP2A inhibition directly and reduced phosphorylation by GSK-3beta due to its inhibition. Because the impacts of tau phosphorylation on its biological activity and on neurofibrillary degeneration are site-specific, this study provides a new insight into the role of PP2A down-regulation in neurofibrillary degeneration in AD.",
"title": "PP2A regulates tau phosphorylation directly and also indirectly via activating GSK-3beta."
},
{
"docid": "350542",
"text": "BACKGROUND Pleurocidin, a 25-mer antimicrobial peptide (AMP), is known to exert bactericidal activity. However, the synergistic activity and mechanism(s) of pleurocidin in combination with conventional antibiotics, and the antibiofilm effect of the peptide are poorly understood. METHODS The interaction between pleurocidin and antibiotics was evaluated using checkerboard assay. To study the mechanism(s) involved in their synergism, we detected hydroxyl radical formation using 3'-(p-hydroxyphenyl) fluorescein, measured the NAD(+)/NADH ratio by NAD(+) cycling assay, observed change in bacterial viability with the hydroxyl radical scavenger thiourea, and investigated cytoplasmic membrane damage using propidium iodide. Also, the antibiofilm effect of pleurocidin was examined with the tissue culture plate method. RESULTS All combinations of pleurocidin and antibiotics showed synergistic interaction against bacterial strains (fractional inhibitory concentration index (FICI)≤0.5) except for Enterococcus faecium treated with a combination of the peptide and ampicillin (FICI=0.75). We identified that pleurocidin alone and in combinations with antibiotics induced formation of hydroxyl radicals. The oxidative stress was caused by a transient NADH depletion and the addition of thiourea prevented bacterial death, especially in the case of the combined treatment of pleurocidin and ampicillin showing synergisms. The combination of pleurocidin and erythromycin increased permeability of bacterial cytoplasmic membrane. Additionally, pleurocidin exhibited a potent inhibitory effect on preformed biofilm of bacterial organisms. In conclusion, pleurocidin synergized with antibiotics through hydroxyl radical formation and membrane-active mechanism, and exerted antibiofilm activity. GENERAL SIGNIFICANCE The synergistic effect between pleurocidin and antibiotics suggests the AMP is a potential therapeutic agent and adjuvant for antimicrobial chemotherapy.",
"title": "Antimicrobial peptide pleurocidin synergizes with antibiotics through hydroxyl radical formation and membrane damage, and exerts antibiofilm activity."
},
{
"docid": "17194716",
"text": "In this study, the mechanisms of actin-bundling in filopodia were examined. Analysis of cellular localization of known actin cross-linking proteins in mouse melanoma B16F1 cells revealed that fascin was specifically localized along the entire length of all filopodia, whereas other actin cross-linkers were not. RNA interference of fascin reduced the number of filopodia, and remaining filopodia had abnormal morphology with wavy and loosely bundled actin organization. Dephosphorylation of serine 39 likely determined cellular filopodia frequency. The constitutively active fascin mutant S39A increased the number and length of filopodia, whereas the inactive fascin mutant S39E reduced filopodia frequency. Fluorescence recovery after photobleaching of GFP-tagged wild-type and S39A fascin showed that dephosphorylated fascin underwent rapid cycles of association to and dissociation from actin filaments in filopodia, with t1/2 < 10 s. We propose that fascin is a key specific actin cross-linker, providing stiffness for filopodial bundles, and that its dynamic behavior allows for efficient coordination between elongation and bundling of filopodial actin filaments.",
"title": "Role of fascin in filopodial protrusion"
},
{
"docid": "18473550",
"text": "Bisphosphonates are widely used agents for the treatment of malignant bone disease. They inhibit osteoclast-mediated bone resorption and can have direct effects on cancer cells. In this study, we investigated whether the anticancer activity of the third-generation bisphosphonate zoledronic acid (ZOL) could be enhanced by combination with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). We found that ZOL and SAHA cooperated to induce cell death in the prostate cancer cell lines LNCaP and PC-3. The effect was synergistic, as evidenced by combination index isobologram analysis. ZOL and SAHA synergized to induce dissipation of the mitochondrial transmembrane potential, to activate caspase-3, and to trigger DNA fragmentation, showing that the combination of ZOL and SAHA resulted in the initiation of apoptosis. Because ZOL acts by inhibiting the mevalonate pathway, thereby preventing protein prenylation, we explored whether the mevalonate pathway was also the target of the cooperative action of ZOL and SAHA. We found that geranylgeraniol, but not farnesol, significantly reduced ZOL/SAHA-induced cell death, indicating that the synergistic action of the agents was due to the inhibition of geranylgeranylation. Consistently, a direct inhibitor of geranylgeranylation, GGTI-298, synergized with SAHA to induce cell death, whereas an inhibitor of farnesylation, FTI-277, had no effect. In addition, SAHA synergized with mevastatin, an inhibitor of the proximal enzyme in the mevalonate pathway. These in vitro findings provide a rationale for an in vivo exploration into the potential of combining SAHA and ZOL, or other inhibitors of the mevalonate pathway, as an effective strategy for anticancer therapy.",
"title": "Synergistic activity of the histone deacetylase inhibitor suberoylanilide hydroxamic acid and the bisphosphonate zoledronic acid against prostate cancer cells in vitro."
},
{
"docid": "14328288",
"text": "BACKGROUND Mammalian phosphoinositide 3-kinases (PI 3-kinases) are involved in receptor-mediated signal transduction and have been implicated in processes such as transformation and mitogenesis through their role in elevating cellular phosphatidylinositol (3,4,5)-trisphosphate. Additionally, a PI 3-kinase activity which generates phosphatidylinositol 3-phosphate has been shown to be required for protein trafficking in yeast. RESULTS We have identified a family of three distinct PI 3-kinases in Drosophila, using an approach based on the polymerase chain reaction to amplify a region corresponding to the conserved catalytic domain of PI 3-kinases. One of these family members, PI3K_92D, is closely related to the prototypical PI 3-kinase, p110 alpha; PI3K_59F is homologous to Vps34p, whereas the third, PI3K_68D, is a novel PI 3-kinase which is widely expressed throughout the Drosophila life cycle. The PI3K_68D cDNA encodes a protein of 210 kDa, which lacks sequences implicated in linking p110 PI 3-kinases to p85 adaptor proteins, but contains an amino-terminal proline-rich sequence, which could bind to SH3 domains, and a carboxy-terminal C2 domain. Biochemical analyses demonstrate that PI3K_68D has a novel substrate specificity in vitro, restricted to phosphatidylinositol and phosphatidylinositol 4-phosphate, and is unable to phosphorylate phosphatidylinositol (4,5)-bisphosphate, the implied in vivo substrate for p110. CONCLUSIONS A family of PI 3-kinases in Drosophila, including a novel class represented by PI3K_68D, is described. PI3K_68D has the potential to bind to signalling molecules containing SH3 domains, lacks p85-adaptor-binding sequences, has a Ca(2+)-independent phospholipid-binding domain and displays a restricted in vitro substrate specificity, so it could define a novel signal transduction pathway.",
"title": "A family of phosphoinositide 3-kinases in Drosophila identifies a new mediator of signal transduction"
},
{
"docid": "6157371",
"text": "Actin and its key regulatory component, cofilin, are found together in large rod-shaped assemblies in neurons subjected to energy stress. Such inclusions are also enriched in Alzheimer's disease brain, and appear in transgenic models of neurodegeneration. Neuronal insults, such as energy loss and/or oxidative stress, result in rapid dephosphorylation of the cellular cofilin pool prior to its assembly into rod-shaped inclusions. Although these events implicate a role for phosphatases in cofilin rod formation, a mechanism linking energy stress, phosphocofilin turnover, and subsequent rod assembly has been elusive. We demonstrate the ATP-sensitive interaction of the cofilin phosphatase chronophin (CIN) with the chaperone hsp90 to form a biosensor that mediates cofilin/actin rod formation. Our results suggest a model whereby attenuated interactions between CIN and hsp90 during ATP depletion enhance CIN-dependent cofilin dephosphorylation and consequent rod assembly, thereby providing a mechanism for the formation of pathological actin/cofilin aggregates during neurodegenerative energy flux.",
"title": "Chronophin mediates an ATP-sensing mechanism for cofilin dephosphorylation and neuronal cofilin-actin rod formation."
},
{
"docid": "44614949",
"text": "OBJECTIVE To investigate the role of skeletal muscle (SkM) interleukin (IL)-6 in the regulation of adipose tissue metabolism. METHODS Muscle-specific IL-6 knockout (IL-6 MKO) and IL-6(loxP/loxP) (Floxed) mice were subjected to standard rodent diet (Chow), high-fat diet (HFD), or HFD in combination with exercise training (HFD ExTr) for 16 weeks. RESULTS Total fat mass increased (P < 0.05) in both genotypes with HFD. However, HFD IL-6 MKO mice had lower (P < 0.05) inguinal adipose tissue (iWAT) mass than HFD Floxed mice. Accordingly, iWAT glucose transporter 4 (GLUT4) protein content, 5'AMP activated protein kinase (AMPK)(Thr172) phosphorylation, and fatty acid synthase (FAS) mRNA content were lower (P < 0.05) in IL-6 MKO than Floxed mice on Chow. In addition, iWAT AMPK(Thr172) and hormone-sensitive lipase (HSL)(Ser565) phosphorylation as well as perilipin protein content was higher (P < 0.05) in HFD IL-6 MKO than HFD Floxed mice, and pyruvate dehydrogenase E1α (PDH-E1α) protein content was higher (P < 0.05) in HFD ExTr IL-6 MKO than HFD ExTr Floxed mice. CONCLUSIONS These findings indicate that SkM IL-6 affects iWAT mass through regulation of glucose uptake capacity as well as lipogenic and lipolytic factors.",
"title": "Skeletal muscle interleukin‐6 regulates metabolic factors in iWAT during HFD and exercise training"
},
{
"docid": "4688340",
"text": "BACKGROUND Resistance to radiotherapy continues to be a limiting factor in the treatment of cancer including head and neck squamous cell carcinoma (HNSCC). Simultaneous targeting of β1 integrin and EGFR was shown to have a higher radiosensitizing potential than mono-targeting in the majority of tested HNSCC cancer models. As tumor-initiating cells (TIC) are thought to play a key role for therapy resistance and recurrence and can be enriched in sphere forming conditions, this study investigated the efficacy of β1 integrin/EGFR targeting without and in combination with X-ray irradiation on the behavior of sphere-forming cells (SFC). METHODS HNSCC cell lines (UTSCC15, UTSCC5, Cal33, SAS) were injected subcutaneously into nude mice for tumor up-take and plated for primary and secondary sphere formation under non-adhesive conditions which is thought to reflect the enrichment of SFC and their self-renewal capacity, respectively. Treatment was accomplished by inhibitory antibodies for β1 integrin (AIIB2) and EGFR (Cetuximab) as well as X-ray irradiation (2 - 6 Gy single doses). Further, flow cytometry for TIC marker expression and cell cycling as well as Western blotting for DNA repair protein expression and phosphorylation were employed. RESULTS We found higher primary and secondary sphere forming capacity of SAS cells relative to other HNSCC cell lines, which was in line with the tumor up-take rates of SAS versus UTSCC15 cells. AIIB2 and Cetuximab administration had minor cytotoxic and no radiosensitizing effects on SFC. Intriguingly, secondary SAS spheres, representing the fraction of surviving SFC upon passaging, showed greatly enhanced radiosensitivity compared to primary spheres. Intriguingly, neither AIIB2 nor Cetuximab significantly altered basal sphere forming capacity and radiosensitivity. While an increased accumulation of G0/G1 phase cells was observable in secondary SAS spheres, DNA double strand break repair indicated no difference on the basis of significantly enhanced ATM and Chk2 dephosphorylation upon irradiation. CONCLUSIONS In the HNSCC model, sphere-forming conditions select for cells, which are unsusceptible to both anti-β1 integrin and anti-EGFR inhibitory antibodies. With regard to primary and secondary sphere formation, our data suggest that both of these SFC fractions express distinct survival strategies independent from β1 integrin and EGFR and that future work is warranted to better understand SFC survival and enrichment before and after treatment to untangle the underlying mechanisms for identifying novel, druggable cancer targets in SFC.",
"title": "Efficacy of Beta1 Integrin and EGFR Targeting in Sphere-Forming Human Head and Neck Cancer Cells"
},
{
"docid": "14482051",
"text": "BACKGROUND Panobinostat is a histone deacetylase inhibitor with antineoplastic and antiangiogenic effects in glioma that may work synergistically with bevacizumab. We conducted a multicenter phase II trial of panobinostat combined with bevacizumab in patients with recurrent high-grade glioma (HGG). METHODS Patients with recurrent HGG were treated with oral panobinostat 30 mg 3 times per week, every other week, in combination with bevacizumab 10 mg/kg every other week. The primary endpoint was a 6-month progression-fee survival (PFS6) rate for participants with recurrent glioblastoma (GBM). Patients with recurrent anaplastic glioma (AG) were evaluated as an exploratory arm of the study. RESULTS At interim analysis, the GBM arm did not meet criteria for continued accrual, and the GBM arm was closed. A total of 24 patients with GBM were accrued prior to closure. The PFS6 rate was 30.4% (95%, CI 12.4%-50.7%), median PFS was 5 months (range, 3-9 months), and median overall survival (OS) was 9 months (range, 6-19 months). Accrual in the AG arm continued to completion, and a total of 15 patients were enrolled. The PFS6 rate was 46.7% (range, 21%-73%), median PFS was 7 months (range, 2-10 months), and median OS was 17 months (range, 5 months-27 months). CONCLUSIONS This phase II study of panobinostat and bevacizumab in participants with recurrent GBM did not meet criteria for continued accrual, and the GBM cohort of the study was closed. Although it was reasonably well tolerated, the addition of panobinostat to bevacizumab did not significantly improve PFS6 compared with historical controls of bevacizumab monotherapy in either cohort.",
"title": "Phase II study of panobinostat in combination with bevacizumab for recurrent glioblastoma and anaplastic glioma."
}
] |
13811
|
Sons of Anarchy is a television series.
|
[
{
"docid": "Sons_of_Anarchy",
"text": "Sons of Anarchy is an American crime drama television series created by Kurt Sutter , which aired from 2008 to 2014 . It follows the lives of a close-knit outlaw motorcycle club operating in Charming , a fictional town in California 's Central Valley . The show stars Charlie Hunnam as Jackson `` Jax '' Teller , initially the vice president , who begins questioning the club and himself . Brotherhood , loyalty and redemption are constant themes . Sons of Anarchy premiered on September 3 , 2008 , on cable network FX . The series 's third season attracted an average of 4.9 million weekly viewers , making it FX 's highest rated series and surpassing its other hits The Shield , Nip/Tuck and Rescue Me . The season four and five premieres were the two highest-rated telecasts in FX 's history . The sixth season aired from September 10 , 2013 , through December 10 , 2013 . The seventh and final season of the series premiered on September 9 , 2014 . The series finale premiered on December 9 , 2014 . The series explores vigilantism , government corruption and racism , and depicts an outlaw motorcycle club as an analogy for human transformation . Real life Oakland Hell 's Angel David Labrava served as a technical adviser , and also played one of the main characters , Happy Lowman , the club 's assassin . In November 2013 , Sutter indicated he was in talks with FX to make a Sons of Anarchy prequel set in the 1960s . In February 2015 , he said he would not work on the prequel , likely to be titled `` The First 9 '' , before 2017 . In November 2016 FX announced the development of a spin off series Mayans MC , centered around Latino culture , which will likely include past SOA characters in cameo roles .",
"title": ""
}
] |
[
{
"docid": "Charming_(Sons_of_Anarchy)",
"text": "Charming is a fictional town in the television series Sons of Anarchy .",
"title": ""
},
{
"docid": "List_of_Sons_of_Anarchy_episodes",
"text": "Sons of Anarchy , a television drama series created by Kurt Sutter , premiered on September 3 , 2008 on the cable network FX in the United States . The series concluded on December 9 , 2014 , after 92 episodes broadcast over seven seasons . Sons of Anarchy tells the story of an outlaw motorcycle club based in the fictional small town of Charming , California . The show follows protagonist Jackson `` Jax '' Teller ( Charlie Hunnam ) , son of the deceased founding president John Teller , who begins questioning the club and the direction in which they should be heading .",
"title": ""
},
{
"docid": "Happy_(Sons_of_Anarchy)",
"text": "Happy Lowman is a fictional character on the FX television series Sons of Anarchy , with his name based on the character in the famous play `` Death of a Salesman '' . Happy Lowman is an ironic name based on his lack of happiness , played by real-life Hells Angel David Labrava . He is enforcer for Sons of Anarchy Motorcycle Club , and is affiliated with the Tacoma , Washington charter at the beginning of the series , but later becomes a Nomad , meaning he has no permanent charter . As of the episode `` The Push '' , he is now an official member of the Redwood Original . As of Season 6 he is the Sergeant-at-arms for the mother charter .",
"title": ""
},
{
"docid": "Sons_of_Anarchy_(season_1)",
"text": "The first season of the American television drama series Sons of Anarchy created by Kurt Sutter , about the lives of a close-knit outlaw motorcycle club operating in Charming , a fictional town in California 's Central Valley . The show centers on protagonist Jackson `` Jax '' Teller ( Charlie Hunnam ) , the then -- vice president of the club , who begins questioning the club and himself . Sons of Anarchy premiered on September 3 , 2008 , on cable network FX .",
"title": ""
},
{
"docid": "Sons_of_Anarchy_(season_2)",
"text": "The second season of the American television drama series Sons of Anarchy created by Kurt Sutter , about the lives of a close-knit outlaw motorcycle club operating in Charming , a fictional town in California 's Central Valley . The show centers on protagonist Jackson `` Jax '' Teller ( Charlie Hunnam ) , the vice president of the club , who begins questioning the club and himself . Season Two of Sons of Anarchy premiered on September 8 , 2009 , on cable network FX .",
"title": ""
},
{
"docid": "Sons_of_Anarchy_(season_3)",
"text": "The third season of the American television drama series Sons of Anarchy created by Kurt Sutter about the lives of a close-knit outlaw motorcycle club operating in Charming , a fictional town in California 's Central Valley . The show centers on protagonist Jackson `` Jax '' Teller ( Charlie Hunnam ) , the then -- vice president of the club , who begins questioning the club and himself . Sons of Anarchy premiered on September 7 , 2010 , on cable network FX . Season Three attracted an average of 4.9 million viewers per week , making it FX 's highest rated series ever at the time , surpassing FX 's other hits The Shield , Nip/Tuck , and Rescue Me .",
"title": ""
},
{
"docid": "Piney_Winston",
"text": "Piermont `` Piney '' Winston is a fictional character on the FX television series Sons of Anarchy , played by William Lucking . He was a member of the Sons of Anarchy Motorcycle Club and was one of the Club 's founders , along with John Teller .",
"title": ""
},
{
"docid": "Sons_of_Anarchy:_Songs_of_Anarchy_Vol._4",
"text": "Sons of Anarchy : Songs of Anarchy Vol . 4 is a soundtrack album featuring music from the FX television program Sons of Anarchy , and is a follow-up to the 2013 release Sons of Anarchy : Songs of Anarchy Vol . 3 and several earlier EPs from the popular show .",
"title": ""
},
{
"docid": "Sons_of_Anarchy:_Songs_of_Anarchy_Vol._3",
"text": "Sons of Anarchy : Songs of Anarchy Vol . 3 is a soundtrack album featuring music from the FX television program Sons of Anarchy , and is a follow-up to the 2012 release Sons of Anarchy : Songs of Anarchy Vol . 2 and several earlier EPs from the popular show . The album has sold 23,000 copies in the United States as of February 2015 .",
"title": ""
},
{
"docid": "Marcus_Álvarez",
"text": "Marcus Álvarez is a fictional character on the FX television series Sons of Anarchy and it 's spinoff Mayans MC , played by Emilio Rivera . He initially serves as an antagonist on the show but gradually comes to a less hostile relation with the Sons of Anarchy . He is the leader of the Mayans , a Mexican-American biker gang .",
"title": ""
},
{
"docid": "Sons_of_Anarchy:_Songs_of_Anarchy_Vol._2",
"text": "Sons of Anarchy : Songs of Anarchy Vol . 2 is a soundtrack album featuring music from the FX television program Sons of Anarchy , and is a follow-up to the 2011 release Songs of Anarchy : Music from Sons of Anarchy Seasons 1 -- 4 and several earlier EPs from the popular show . Songs include covers of `` Sympathy for the Devil , '' `` Higher Ground , '' and `` Travelin ' Band , '' as well as several original tracks . Performers include Jane 's Addiction , with most tracks performed by longtime SOA contributors The Forest Rangers .",
"title": ""
},
{
"docid": "Bobby_Munson",
"text": "Robert `` Bobby '' Munson , is a fictional character on the FX television series Sons of Anarchy , played by Mark Boone Junior . He was the Secretary and former vice-president of the Sons of Anarchy Motorcycle Club 's Charming , California chapter . Bobby is intelligent and even-tempered ( an uncommon trait among his club-mates ) , but unafraid of using violence when necessary .",
"title": ""
},
{
"docid": "Sons_of_Anarchy_(season_6)",
"text": "The sixth season of the American television drama series Sons of Anarchy created by Kurt Sutter about the lives of a close-knit outlaw motorcycle club operating in Charming , a fictional town in California 's Central Valley . The show centers on protagonist Jackson `` Jax '' Teller ( Charlie Hunnam ) , the president of the club , who begins questioning the club and himself . Season Six aired from September 10 through December 10 , 2013 . The season finale was the second-most watched episode of the season and the most-watched finale in the series history .",
"title": ""
},
{
"docid": "Sons_of_Anarchy_(season_4)",
"text": "The fourth season of the American television drama series Sons of Anarchy created by Kurt Sutter about the lives of a close-knit outlaw motorcycle club operating in Charming , a fictional town in California 's Central Valley . The show centers on protagonist Jackson `` Jax '' Teller ( Charlie Hunnam ) , the then -- vice president of the club , who begins questioning the club and himself . Season Four premiered on September 6 , 2011 , on cable network FX . The season premiere ( `` Out '' ) by series executive producer and principal director Paris Barclay and written by series creator and executive producer Kurt Sutter was one of the highest-rated telecasts in FX 's history .",
"title": ""
},
{
"docid": "David_Hale_(Sons_of_Anarchy)",
"text": "Deputy Chief David Hale is a fictional character on the FX television series Sons of Anarchy , played by Taylor Sheridan . He was the Deputy Chief of Police in the small Northern Californian town of Charming . The Chief , Wayne Unser , nicknamed him `` Captain America '' for his black and white views and squeaky-clean adherence to the law , and possibly because of his square jawed all-American looks .",
"title": ""
},
{
"docid": "Half-Sack_Epps",
"text": "Edward Kip `` Half Sack '' Epps is a fictional character on the FX television series Sons of Anarchy , played by Johnny Lewis . He is a prospect ( prospective member ) of the Sons of Anarchy Motorcycle Club , which often results in hazing and his being given undesirable tasks . The other members generally have a good-natured attitude towards Half Sack when giving him these difficult tasks .",
"title": ""
},
{
"docid": "Songs_of_Anarchy:_Music_from_Sons_of_Anarchy_Seasons_1–4",
"text": "Songs of Anarchy : Music from Sons of Anarchy Seasons 1 -- 4 is a soundtrack album featuring music from FX television program Sons of Anarchy . The album consists of songs recorded for the show as well as those previously released through a number of EPs ; Sons of Anarchy : North Country ( 2009 ) , Sons of Anarchy : Shelter ( 2009 ) and Sons of Anarchy : The King is Gone ( 2010 ) . Songs include covers of `` What a Wonderful World '' , `` Forever Young '' , `` John the Revelator and the Emmy nominated theme song `` This Life '' ( performed by Curtis Stigers and the Forest Rangers ) . Musicians performing on the album include Anvil , Franky Perez ( of Scars on Broadway ) , Lions , Alison Mosshart ( of The Kills and The Dead Weather ) and actress Katey Sagal , who plays Gemma Teller Morrow in the show , among others . The album was released on November 29 , 2011 , through Columbia Records .",
"title": ""
},
{
"docid": "Sons_of_Anarchy_(season_5)",
"text": "The fifth season of the American television drama series Sons of Anarchy created by Kurt Sutter about the lives of a close-knit outlaw motorcycle club operating in Charming , a fictional town in California 's Central Valley . The show centers on protagonist Jackson `` Jax '' Teller ( Charlie Hunnam ) , first shown as vice president then as president of the club , who begins questioning the club and himself . Season Five premiered on September 11 , 2012 on cable network FX . The premiere ( `` Sovereign '' ) , directed by series executive producer and principal director Paris Barclay and written by series creator and executive producer Kurt Sutter , was one of the highest-rated telecasts in FX 's history .",
"title": ""
},
{
"docid": "Sons_of_Anarchy_(season_7)",
"text": "The seventh and final season of the American television drama series Sons of Anarchy created by Kurt Sutter about the lives of a close-knit outlaw motorcycle club operating in Charming , a fictional town in California 's Central Valley . The show centers on protagonist Jackson `` Jax '' Teller ( Charlie Hunnam ) , the President of the club , who begins questioning the club and himself . Season 7 premiered on September 9 , 2014 , and concluded on December 9 , 2014 .",
"title": ""
},
{
"docid": "June_Stahl",
"text": "Agent June Stahl is a fictional character on the FX television series Sons of Anarchy and a major antagonist of the series , played by Ally Walker . She was a Stockton , California-based Agent of the Bureau of Alcohol , Tobacco , Firearms and Explosives investigating the Sons of Anarchy Motorcycle Club in Charming , California . She is portrayed as being bisexual . Stahl 's methods are often ruthless , and include murdering her own girlfriend to get what she wants . Her actions have led to the deaths of two people associated with SAMCRO as well as the kidnapping of Abel Teller . She also killed an admitted gunrunner and then framed Gemma Teller Morrow , making the shooting seem unlawful .",
"title": ""
},
{
"docid": "Dave_Erickson",
"text": "Dave Erickson is an American television writer and producer , best known for co-creating Fear the Walking Dead with Robert Kirkman , which he is currently the showrunner for . He also created the television series Canterbury 's Law , and wrote and produced for television series Sons of Anarchy and Low Winter Sun .",
"title": ""
},
{
"docid": "Tig_Trager",
"text": "Alexander `` Tig '' Trager is a fictional character on the FX television series Sons of Anarchy , played by Kim Coates . He is the current Vice President of the Sons of Anarchy Motorcycle Club 's Charming , California chapter and is the gang 's most violent member . He was extremely loyal to Clay Morrow , the club 's former President , Clay 's wife Gemma , and the club itself . He has at times had a strained relationship with the former President , Jax Teller , arising from his use of violence in situations which may not call for it .",
"title": ""
},
{
"docid": "Niko_Nicotera",
"text": "Niko Nicotera is an American film and television actor best known for playing Ratboy in the series Sons of Anarchy .",
"title": ""
},
{
"docid": "Chris_Collins_(writer)",
"text": "Chris Collins is an American television writer and producer . He has worked on the HBO dramas The Sopranos and The Wire . He was an executive story editor for the Starz drama series Crash . He is a producer and writer for the FX series Sons of Anarchy .",
"title": ""
},
{
"docid": "Chad_Lindberg",
"text": "Chad Tyler Lindberg ( born November 1 , 1976 ) is an American actor . He is known for his film roles in The Fast and the Furious and October Sky , as well as television roles on Sons of Anarchy and Supernatural . Lindberg was the co-host of the television series , Ghost Stalkers .",
"title": ""
},
{
"docid": "Billy_Gierhart",
"text": "Bill `` Billy '' Gierhart is an American television director and former steadicam operator . For many years he worked a steadicam operator on the television series Pacific Blue , Huff , Swingtown and The Shield , making his directorial debut on the latter series penultimate episode `` Possible Kill Screen '' in 2008 . His other credits as a television director include , Lone Star , Terriers , The Chicago Code , Sons of Anarchy , Torchwood , Breakout Kings , The Walking Dead and Agents of S.H.I.E.L.D. .",
"title": ""
},
{
"docid": "Make_It_Rain_(Foy_Vance_song)",
"text": "`` Make It Rain '' is a song by Northern Irish musician Foy Vance . It was made famous by Ed Sheeran in 2014 when it was used in the television series Sons of Anarchy .",
"title": ""
},
{
"docid": "Donal_Logue",
"text": "Donal Francis Logue ( born February 27 , 1966 ) is an Irish-Canadian film and television actor , producer and writer . His notable roles include starring in the film The Tao of Steve , Sons of Anarchy , Vikings , the sitcom Grounded for Life , the television series Copper and the detective series Terriers . He currently stars as detective Harvey Bullock in Fox 's Gotham and had a recurring role in NBC 's Law & Order : Special Victims Unit as Lt. Declan Murphy .",
"title": ""
},
{
"docid": "Billy_Brown_(actor)",
"text": "Not to be confused with actor Billy Aaron Brown . Billy Brown is an American actor . In 2014 , Brown began starring as Detective Nate Lahey in the Shonda Rhimes drama series , How to Get Away with Murder . He is also known for his roles in the television series Lights Out , Dexter , Sons of Anarchy , and Hostages .",
"title": ""
},
{
"docid": "Roberto_Patino",
"text": "Roberto Patino is an American screenwriter and television writer , known for writing the film Cut Bank , starring Liam Hemsworth , John Malkovich and Billy Bob Thornton . He has written on the NBC series Prime Suspect . He is a writer for the FX series Sons of Anarchy . He graduated from Harvard University in 2006 .",
"title": ""
}
] |
246
|
Charcoal shows no benefit for acute paraquat poisoning.
|
[
{
"docid": "8447873",
"text": "BACKGROUND Organophosphorus pesticide (OP) self-poisoning is a major problem in the developing rural world. There is little clinical trial data to guide therapy, hindering the identification of best therapy. Despite the recognition of adverse effects, gastric lavage is commonly done in Asia. We aimed to identify studies assessing its effectiveness. METHOD We systematically searched the literature for controlled clinical studies that assessed the effect of gastric lavage in OP pesticide self-poisoning. RESULTS All 56 studies identified were Chinese and reported benefit from the intervention studied, including multiple gastric lavages, use of norepinephrine or pralidoxime in the lavage fluid, concurrent treatment with naloxone or scopolamine, insertion of the gastric tube via a laparotomy incision, and lavage later than 12 h post-ingestion. However, only 23 were RCTs and none presented adequate methodology for their quality to be assessed. The patient population and study treatment protocol were not defined - large variation in case fatality in the control arm of the studies (from 4.5 to 93%) suggests marked variation between studies and likely between study arms. No study compared an intervention against a control group receiving no gastric lavage or provided any data to indicate whether a significant quantity of poison was removed. CONCLUSION Despite widespread use of multiple gastric lavages for OP pesticide poisoning across Asia, there is currently no high-quality evidence to support its clinical effectiveness. There is a need for studies to identify in which patients and for what duration gastric lavage is able to remove significant quantities of poison. Following these studies, large clinical trials will be required to address the effectiveness and safety of gastric lavage (either single or multiple) in acute OP pesticide poisoning.",
"title": "Systematic review of controlled clinical trials of gastric lavage in acute organophosphorus pesticide poisoning."
},
{
"docid": "3430789",
"text": "The present study retrospectively analyzed 19 patients diagnosed with paraquat (PQ) poisoning with the aim to investigate the effect of activated charcoal hemoperfusion on renal function and PQ elimination. The results indicated that 7 patients died and 12 survived. Non-oliguric renal failure occurred in all of the 7 patients who died. Among the 12 surviving patients, 10 had normal renal function and 2 developed non-oliguric renal failure. There was a linear correlation between plasma and urine paraquat concentration prior to and during activated charcoal hemoperfusion. The equation parameters together with the correlation coefficient on admission were as follows: Y=0.5820+1.7348X (R2=0.678; F=35.768; P<0.0001). The equation parameters together with the correlation coefficient were as follows during activated charcoal hemoperfusion: Y=0.6827+1.2649X (R2=0.626; F=50.308; P<0.0001). Therefore, it was concluded that in patients with normal renal function, the elimination kinetics of PQ by the kidneys were only associated with the plasma PQ concentration. Activated charcoal hemoperfusion had little effect on avoiding acute kidney injury in patients with severe PQ poisoning.",
"title": "Effect of activated charcoal hemoperfusion on renal function in patients with paraquat poisoning."
}
] |
[
{
"docid": "25104843",
"text": "We report on a patient treated with hemoperfusion-hemodialysis (HP-HD) for severe paraquat poisoning. This procedure was adopted since the combination of adsorption and dialysis may improve overall drug removal. On admission blood paraquat was 15.8 micrograms/ml. He received conventional treatment and combined HP-HD which started within 3 hours after ingestion of the chemical and lasted 5 hours. Blood samples were obtained during and after HP-HD. The samples during HP-HD were taken before the charcoal column, between the charcoal column and the artificial kidney and after the artificial kidney. Blood clearances of paraquat were 116 +/- 32 ml/min (n=6) for the charcoal column (HP), 90 +/- 54 ml/min (n=6) for the artificial kidney (HD) and 151 +/- 37 ml/min (n=6) for the combined systems (HP-HD). After HP-HD a limited rebound of blood paraquat level was seen. One day after admission renal and hepatic failure had developed, and the patient died after 5 days. Tissue paraquat levels (microgram/g wet tissue) were: skeletal muscle 9.4, pancreas 6.0, prostate 5.6, thyroid 4.2, lungs 4.0, bone marrow 4.0, kidney 3.1, spleen 2.9, adrenal 2.9, heart 2.8, liver 2.3, stomach and testis below 1.0. Measurements of blood levels demonstrated the efficient clearances of paraquat with HP-HD from the central (plasma) compartment. However, the present results confirmed those previously reported which suggest that the efficiency of short HP-HD in treating severe paraquat poisoning is questionable since paraquat levels in the peripheral (tissue) compartment remain elevated.",
"title": "Hemoperfusion-hemodialysis ineffective for paraquat removal in life-threatening poisoning?"
},
{
"docid": "12209494",
"text": "BACKGROUND The case-fatality for intentional self-poisoning in the rural developing world is 10-50-fold higher than that in industrialised countries, mostly because of the use of highly toxic pesticides and plants. We therefore aimed to assess whether routine treatment with multiple-dose activated charcoal, to interrupt enterovascular or enterohepatic circulations, offers benefit compared with no charcoal in such an environment. METHODS We did an open-label, parallel group, randomised, controlled trial of six 50 g doses of activated charcoal at 4-h intervals versus no charcoal versus one 50 g dose of activated charcoal in three Sri Lankan hospitals. 4632 patients were randomised to receive no charcoal (n=1554), one dose of charcoal (n=1545), or six doses of charcoal (n=1533); outcomes were available for 4629 patients. 2338 (51%) individuals had ingested pesticides, whereas 1647 (36%) had ingested yellow oleander (Thevetia peruviana) seeds. Mortality was the primary outcome measure. Analysis was by intention to treat. The trial is registered with controlled-trials.com as ISRCTN02920054. FINDINGS Mortality did not differ between the groups. 97 (6.3%) of 1531 participants in the multiple-dose group died, compared with 105 (6.8%) of 1554 in the no charcoal group (adjusted odds ratio 0.96, 95% CI 0.70-1.33). No differences were noted for patients who took particular poisons, were severely ill on admission, or who presented early. INTERPRETATION We cannot recommend the routine use of multiple-dose activated charcoal in rural Asia Pacific; although further studies of early charcoal administration might be useful, effective affordable treatments are urgently needed.",
"title": "Multiple-dose activated charcoal in acute self-poisoning: a randomised controlled trial"
},
{
"docid": "22547508",
"text": "Acute paraquat poisoning is often fatal. Many studies have investigated successful treatment modalities, but no standard treatment yet exists. The purpose of this study was to determine the predictors of survival after acute paraquat poisoning in 602 patients. The paraquat exposure was assessed based on the amount of ingested paraquat and a semiquantitative measure of the urine level of paraquat. Initial clinical parameters including vital signs, hemoglobin, white-blood-cell count, pH, PaCO2, PaO2, blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, total bilirubin, amylase, and glucose were obtained at the time of arrival at the emergency room. Outcomes after acute paraquat poisoning were categorized as survivors and nonsurvivors. Multiple logistic regression analysis was applied to assess the predictors of survival after acute paraquat poisoning. Some patients (55.5%) survived after oral ingestion of paraquat, whereas all those exposed to paraquat percutaneous or inhalational route survived. The amount of paraquat (24.5% concentrate of 1,1'-dimethyl-4,4'-bipyridium dichloride) ingested was 45.6 +/- 74.1 mL (mean +/- SD). In addition to degree of paraquat exposure, survival after acute paraquat poisoning was associated with age, respiratory rate, pH, PaCO2, hemoglobin, white-blood-cell count, blood urea nitrogen, amylase, and the number of failed organs in multiple logistic regression analysis. In conclusion, young age, percutaneous or inhalational route, exposure to less paraquat, and lesser degrees of leukocytosis, acidosis, and renal, hepatic, and pancreatic failures on admission are good prognostic factors of survival after acute paraquat poisoning.",
"title": "Predictors of survival after acute paraquat poisoning."
},
{
"docid": "24097933",
"text": "Paraquat poisoning is characterized by multiorgan failure and pulmonary fibrosis with respiratory failure. Multiorgan failure with circulatory collapse is a major cause of early death within 3 days of paraquat ingestion. Recent studies suggested that continuous venovenous hemofiltration (CVVH) had a role in the treatment of multiorgan failure by promoting hemodynamic stability. We therefore evaluated the effect of prophylactic CVVH in 80 patients with paraquat poisoning (August 1996 to February 1999). The amount ingested was 2.1 +/- 1.0 mouthfuls (as 20% concentrate). All patients were treated with hemoperfusion (HP; duration, 6.4 +/- 3.0 hours) within 24 hours of ingestion and then randomly assigned to the HP-alone or HP-CVVH group. Forty-four patients underwent HP only, and 36 patients underwent CVVH (duration, 57.4 +/- 31.3 hours; ultrafiltration volume, 40.2 +/- 4.8 L/d) after HP. Although time to death after ingestion was significantly longer in the HP-CVVH than HP group (5.0 +/- 5.0 versus 2.5 +/- 2.1 days; P < 0.05), there was no difference in mortality rates between the two groups (66.7% versus 63.6%; P = 0.82). In the HP group, early circulatory collapse was a major cause of death compared with the HP-CVVH group, in which late respiratory failure was a major cause of death. In conclusion, prophylactic CVVH after HP prevented early death caused by circulatory collapse and prolonged survival time. However, it could not prevent late death caused by respiratory failure and did not provide a survival benefit in acute paraquat poisoning.",
"title": "Failure of continuous venovenous hemofiltration to prevent death in paraquat poisoning."
},
{
"docid": "19132741",
"text": "Paraquat, a quarternary nitrogen herbicide, is a highly toxic compound for humans and animals and many cases of acute poisoning and death have been reported over the past few decades. The mechanisms of paraquat toxicity involve: the generation of the superoxide anion, which can lead to the formation of more toxic reactive oxygen species, such as hydrogen peroxide and hydroxyl radical; and the oxidation of the cellular NADPH, the major source of reducing equivalents for the intracellular reduction of paraquat, which results in the disruption of important NADPH-requiring biochemical processes. The major cause of death in paraquat poisoning is respiratory failure due to an oxidative insult to the alveolar epithelium with subsequent obliterating fibrosis. Management of paraquat poisoning has remained mostly supportive and has been directed towards the modification of the toxicokinetics of the poison. Currently, there are no true pharmacological antagonists for paraquat and there are no chelating agents capable of binding the poison in the blood or other tissues. Recognizing the fact that paraquat induces its toxic effects via oxidative stress-mediated mechanisms, innovations in the management of paraquat poisoning are directed towards the use of antioxidants. In this review, the status of antioxidants in ameliorating or treating the toxic effects produced by paraquat is presented.",
"title": "Role of antioxidants in paraquat toxicity."
},
{
"docid": "33203108",
"text": "INTRODUCTION Paraquat is a commonly ingested poison especially in Southern India. There is no antidote for paraquat poison and consumption is often fatal. The usual cause of death is either acute lung injury or multi-organ failure. AIM To evaluate the role of early haemoperfusion as a therapy in paraquat poisoned patients. MATERIALS AND METHODS This study was a retrospective analysis of patients admitted to a Tertiary Medical College Hospital between January 2012 and December 2015 with history of paraquat consumption, comparing outcomes in those who received only gastric lavage and symptomatic treatment with those who received haemoperfusion as a therapy. The role of early haemoperfusion (≤ 6 hours) vs late haemoperfusion (> 6 hours) in paraquat poisoned patients was also compared. The data of these patients was extracted and analysed with respect to age, sex, mode of treatment, the outcome in patients who received early and late haemoperfusion. RESULTS A total of 101 patients were studied out of which 62 died. Deaths were more in those patients who received only gastric lavage with symptomatic treatment as therapy compared to those who received haemoperfusion i.e., 92.1% vs 42.9% respectively. We also found that, the survival rate was better in patients who received early haemoperfusion. CONCLUSION Early haemoperfusion was helpful in the management of severe paraquat poisoning and improved the survival rate in these patients.",
"title": "Golden Hours in Severe Paraquat Poisoning-The Role of Early Haemoperfusion Therapy."
},
{
"docid": "40005757",
"text": "Serious exposure to the herbicide paraquat usually results in death, either due to gastrointestinal caustic lesions, shock, and acute respiratory distress syndrome or related to the progressive development of pulmonary fibrosis associated with refractory hypoxemia. We report a case of suicidal paraquat ingestion in a 59-year-old man. Most of the indicators of poor prognosis were encountered in this patient. Treatment consisted of early digestive decontamination and hemodialysis, followed by antioxidant therapy, including the administration of deferoxamine (100 mg/kg in 24 h) and a continuous infusion of acetylcysteine (300 mg/kg/d during 3 weeks). The patient only developed a nonoliguric acute renal failure, a mild alteration of liver tests, and an impairment of CO transfer factor without any respiratory complaint. Renal and hepatic disturbances completely resolved within 1 month, whereas CO transfer factor remained altered 14 months later. This observation suggests that early administration of an antioxidant therapy, including deferoxamine and acetylcysteine could be usefully associated with measures that prevent digestive absorption or enhance elimination to limit systemic toxicity in potentially fatal paraquat poisoning.",
"title": "Survival in a case of massive paraquat ingestion."
},
{
"docid": "41294031",
"text": "BACKGROUND Paraquat is an effective and widely used herbicide but is also a lethal poison. In many developing countries paraquat is widely available and inexpensive, making poisoning prevention difficult. However most of the people who become poisoned from paraquat have taken it as a means of suicide. Standard treatment for paraquat poisoning both prevents further absorption and reduces the load of paraquat in the blood through haemoperfusion or haemodialysis. The effectiveness of standard treatments is extremely limited. The immune system plays an important role in exacerbating paraquat-induced lung fibrosis. Immunosuppressive treatment using glucocorticoid and cyclophosphamide in combination is being developed and studied. OBJECTIVES To assess the effects of glucocorticoid with cyclophosphamide on mortality in patients with paraquat-induced lung fibrosis. SEARCH METHODS To identify randomised controlled trials (RCTs) on this topic, we searched the Cochrane Injuries Group's Specialised Register (searched 1 February 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1), MEDLINE (Ovid SP) (1946 January Week 3 2012), EMBASE (Ovid SP) (1947 to Week 4 2012), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to January 2012), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to January 2012), Chinese Biomedical Literature and Retrieval System (CBM) (1978 to April 2012), Chinese Medical Current Contents (CMCC) (1995 to April 2012), and Chinese Medical Academic Conference (CMAC) (1994 to April 2012). Searches were completed on English language databases on 1 February 2012 and on Chinese language databases on 12 April 2012. SELECTION CRITERIA RCTs were included in this review. All patients were to receive standard care, plus the intervention or control. The intervention was glucocorticoid with cyclophosphamide in combination versus a control of a placebo, standard care alone or any other therapy in addition to standard care. DATA COLLECTION AND ANALYSIS The mortality risk ratio (RR) and 95% confidence interval (CI) was calculated for each study on an intention-to-treat basis. Data for all-cause mortality at final follow-up were summarised in a meta-analysis using a fixed-effect model. MAIN RESULTS This systematic review includes three trials with a combined total of 164 participants who had moderate to severe paraquat poisoning. Patients who received glucocorticoid with cyclophosphamide in addition to standard care had a lower risk of death at final follow-up than those receiving standard care only (RR 0.72; 95% CI 0.59 to 0.89). AUTHORS' CONCLUSIONS Based on the findings of three small RCTs of moderate to severely poisoned patients, glucocorticoid with cyclophosphamide in addition to standard care may be a beneficial treatment for patients with paraquat-induced lung fibrosis. To enable further study of the effects of glucocorticoid with cyclophosphamide for patients with moderate to severe paraquat poisoning, hospitals may provide this treatment as part of an RCT with allocation concealment.",
"title": "Glucocorticoid with cyclophosphamide for paraquat-induced lung fibrosis."
},
{
"docid": "24525112",
"text": "Paraquat intoxication is a fatal problem. Most paraquat intoxications happen through oral administration. We report a case of death after intravenous paraquat injection. There is little clinical data on parenteral paraquat exposure, and we describe this case and fatal progression. Toxic symptoms and severe organ function impairment developed soon after injection. Treatment with repeated activated charcoal hemoperfusion with pulse steroids, cyclophosphamide, and antioxidants was attempted. The patient died from multiple organ failure 3 days after intoxication. This case indicates that paraquat intoxication via intravenous injection, even in very small amounts, has an extremely poor prognosis.",
"title": "A case of paraquat intoxication caused by intravenous injection."
},
{
"docid": "9976969",
"text": "Psychiatric illness is a significant risk factor for both attempted and completed suicide and psychotropic medications account for 80% of all drug overdoses involving prescription medications. One challenge facing clinicians is to balance the benefit of treatment against the risk of drug overdose. The aim of the present study was to compare the age and gender distribution of patients prescribed psychotropic drugs with patients attempting and completing suicide with these drugs. Data were obtained from the Australian census and studies of general practitioner prescribing, patients who committed suicide or presented with self-poisoning within a defined geographic area. The characteristics of these populations were compared to calculate odds ratios for attempting or completing suicide with psychotropic drugs, before and after correction for rates of prescription, in different age and gender groups. The odds ratios (ORs) for self-poisoning were higher for those aged less than 45 years and yet this group was least likely to be prescribed psychotropic drugs. Men had a much higher rate of completed suicide using more lethal methods. The ORs for self-poisoning and suicide with psychotropic drugs, after correction for prescription rates, for those aged 15 to 24 years were 11.1 and 1.7, respectively. Those aged 25 to 44 years had ORs of 4.9 and 4.3, and, by contrast, those over 75 years had ORs of 0.03 and 0. Women were slightly more likely to poison themselves with psychotropic drugs (OR 1.2). However, the situation reversed after correction for prescription rates (OR 0.69). It is concluded that greater caution should be exercised in prescribing for those under 45 years of age, given their relatively higher risk of drug overdose, and that the least toxic compounds should be used. The risk (of self-poisoning) among the elderly may have been overstated, so that some patients may have been denied the benefit of adequate treatment.",
"title": "An analysis of age and gender influences on the relative risk for suicide and psychotropic drug self-poisoning."
},
{
"docid": "80109277",
"text": "© Joanna Moncrieff 2013. All rights reserved. A challenging reappraisal of the history of antipsychotics, revealing how they were transformed from neurological poisons into magical cures, their benefits exaggerated and their toxic effects minimized or ignored.",
"title": "The Bitterest Pills: The Troubling Story of Antipsychotic Drugs"
},
{
"docid": "32450297",
"text": "THE herbicide paraquat (N,N′-dimethyl 4,4′-bipyridilium) can produce widespread oedema and fibrosis in the human lung after accidental ingestion1–3. In those cases where death occurs after several weeks, there are no apparent pulmonary changes during the first few days following ingestion. Animal experiments in a variety of species have shown the lung to be the major target organ4–6. After administration of paraquat to animals, the lung has a high initial concentration and retains paraquat7–9. This retention appears to be related to the development of lung damage7 (L. L. Smith and M. S. Rose, unpublished work). The mechanism of retention of paraquat by the lung is at present not understood.",
"title": "Evidence for energy-dependent accumulation of paraquat into rat lung"
},
{
"docid": "14361849",
"text": "IntroductionWe conducted the present study to investigate the potential beneficial and adverse effects of continuous positive airway pressure (CPAP) compared with bi-level positive airway pressure (BiPAP) noninvasive ventilation in patients with cardiogenic pulmonary oedema. MethodWe included randomized controlled studies comparing CPAP and BiPAP treatment in patients with cardiogenic pulmonary oedema from the Cochrane Controlled Trials Register (2005 issue 3), and EMBASE and MEDLINE databases (1966 to 1 December 2005), without language restriction. Two reviewers reviewed the quality of the studies and independently performed data extraction. ResultsSeven randomized controlled studies, including a total of 290 patients with cardiogenic pulmonary oedema, were considered. The hospital mortality (relative risk [RR] 0.76, 95% confidence interval [CI] 0.32–1.78; P = 0.52; I2 = 0%) and risk for requiring invasive ventilation (RR 0.80, 95% CI 0.33–1.94; P = 0.62; I2 = 0%) were not significantly different between patients treated with CPAP and those treated with BiPAP. Stratifying studies that used either fixed or titrated pressure during BiPAP treatment and studies involving patients with or without hypercapnia did not change the results. The duration of noninvasive ventilation required until the pulmonary oedema resolved (weighted mean difference [WMD] in hours = 3.65, 95% CI -12.12 to +19.43; P = 0.65, I2 = 0%) and length of hospital stay (WMD in days = -0.04, 95% CI -2.57 to +2.48; P = 0.97, I2 = 0%) were also not significantly different between the two groups. Based on the limited data available, there was an insignificant trend toward an increase in new onset acute myocardial infarction in patients treated with BiPAP (RR 2.10, 95% CI 0.91–4.84; P = 0.08; I2 = 25.3%).ConclusionBiPAP does not offer any significant clinical benefits over CPAP in patients with acute cardiogenic pulmonary oedema. Until a large randomized controlled trial shows significant clinical benefit and cost-effectiveness of BiPAP versus CPAP in patients with acute cardiogenic pulmonary oedema, the choice of modality will depend mainly on the equipment available.",
"title": "A comparison of continuous and bi-level positive airway pressure non-invasive ventilation in patients with acute cardiogenic pulmonary oedema: a meta-analysis"
},
{
"docid": "7873737",
"text": "BACKGROUND Diabetes mellitus is a major risk factor for adverse outcomes after acute coronary syndromes (ACS). Because this disease may be associated with increased platelet aggregation, we investigated whether diabetic patients with ACS derive particular benefit from platelet glycoprotein (GP) IIb/IIIa receptor inhibition. METHODS AND RESULTS We performed a meta-analysis of the diabetic populations enrolled in the 6 large-scale platelet GP IIb/IIIa inhibitor ACS trials: PRISM, PRISM-PLUS, PARAGON A, PARAGON B, PURSUIT, and GUSTO IV. Among 6458 diabetic patients, platelet GP IIb/IIIa inhibition was associated with a significant mortality reduction at 30 days, from 6.2% to 4.6% (OR 0.74; 95% CI 0.59 to 0.92; P=0.007). Conversely, 23 072 nondiabetic patients had no survival benefit (3.0% versus 3.0%). The interaction between platelet GP IIb/IIIa inhibition and diabetic status was statistically significant (P=0.036). Among 1279 diabetic patients undergoing percutaneous coronary intervention (PCI) during index hospitalization, the use of these agents was associated with a mortality reduction at 30 days from 4.0% to 1.2% (OR 0.30; 95% CI 0.14 to 0.69; P=0.002). CONCLUSIONS This meta-analysis, including the entire large-scale trial experience of intravenous platelet GP IIb/IIIa inhibitors for the medical management of non-ST-segment-elevation ACS, shows that these agents may significantly reduce mortality at 30 days in diabetic patients. Although not based on a randomized assessment, the survival benefit appears to be of greater magnitude in patients undergoing PCI. Therefore, the use of platelet GP IIb/IIIa inhibitors should be strongly considered in diabetic patients with ACS.",
"title": "Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes."
},
{
"docid": "12442311",
"text": "BACKGROUND The analgesic co-proxamol (paracetamol/dextropropoxyphene combination) has been widely involved in fatal poisoning. Concerns about its safety/effectiveness profile and widespread use for suicidal poisoning prompted its withdrawal in the UK in 2005, with partial withdrawal between 2005 and 2007, and full withdrawal in 2008. Our objective in this study was to assess the association between co-proxamol withdrawal and prescribing and deaths in England and Wales in 2005-2010 compared with 1998-2004, including estimation of possible substitution effects by other analgesics. METHODS AND FINDINGS We obtained prescribing data from the NHS Health and Social Care Information Centre (England) and Prescribing Services Partneriaeth Cydwasanaethau GIG Cymru (Wales), and mortality data from the Office for National Statistics. We carried out an interrupted time-series analysis of prescribing and deaths (suicide, open verdicts, accidental poisonings) involving single analgesics. The reduction in prescribing of co-proxamol following its withdrawal in 2005 was accompanied by increases in prescribing of several other analgesics (co-codamol, paracetamol, codeine, co-dydramol, tramadol, oxycodone, and morphine) during 2005-2010 compared with 1998-2004. These changes were associated with major reductions in deaths due to poisoning with co-proxamol receiving verdicts of suicide and undetermined cause of -21 deaths (95% CI -34 to -8) per quarter, equating to approximately 500 fewer suicide deaths (-61%) over the 6 years 2005-2010, and -25 deaths (95% CI -38 to -12) per quarter, equating to 600 fewer deaths (-62%) when accidental poisoning deaths were included. There was little observed change in deaths involving other analgesics, apart from an increase in oxycodone poisonings, but numbers were small. Limitations were that the study was based on deaths involving single drugs alone and changes in deaths involving prescribed morphine could not be assessed. CONCLUSIONS During the 6 years following the withdrawal of co-proxamol in the UK, there was a major reduction in poisoning deaths involving this drug, without apparent significant increase in deaths involving other analgesics.",
"title": "Six-Year Follow-Up of Impact of Co-proxamol Withdrawal in England and Wales on Prescribing and Deaths: Time-Series Study"
},
{
"docid": "29526125",
"text": "BACKGROUND A major challenge for physicians is to identify patients with acute coronary syndromes who may benefit from treatment with glycoprotein-IIb/IIIa-receptor antagonists. We investigated whether troponin concentrations can be used to stratify patients for benefit from treatment with tirofiban. METHODS We enrolled 2222 patients of the Platelet Receptor Inhibition in Ischemic Syndrome Management study with coronary artery disease and who had had chest pain in the previous 24 h. All patients received aspirin and were randomly assigned treatment with tirofiban or heparin. We took baseline measurements of troponin I and troponin T. We recorded death, myocardial infarction, or recurrent ischaemia after 48 h infusion treatment and at 7 days and 30 days. FINDINGS 629 (28.3%) patients had troponin I concentrations higher than the diagnostic threshold of 1.0 microg/L and 644 (29.0%) troponin T concentrations higher than 0.1 microg/L. 30-day event rates (death, myocardial infarction) were 13.0% for troponin-I-positive patients compared with 4.9% for troponin-I-negative patients (p<0.0001), and 13.7% compared wth 3.5% for troponin T (p<0.001). At 30 days, in troponin-I-positive patients, tirofiban had lowered the risk of death (adjusted hazard ratio 0.25 [95% CI 0.09-0.68], p=0.004) and myocardial infarction (0.37 [0.16-0.84], p=0.01). This benefit was seen in medically managed patients (0.30 [0.10-0.84], p=0.004) and those undergoing revascularisation (0.37 [0.15-0.93] p=0.02) after 48 h infusion treatment. By contrast, no treatment effect was seen for troponin-I-negative patients. Similar benefits were seen for troponin-T-positive patients. INTERPRETATION Troponin I and troponin T reliably identified high-risk patients with acute coronary syndromes, managed medically and by revascularisation, who would benefit from tirofiban.",
"title": "Troponin concentrations for stratification of patients with acute coronary syndromes in relation to therapeutic efficacy of tirofiban. PRISM Study Investigators. Platelet Receptor Inhibition in Ischemic Syndrome Management."
},
{
"docid": "46346525",
"text": "Mu transposons carrying the chloramphenicol resistance marker have been inserted into the cloned Escherichia coli genes sodA and sodB coding for manganese superoxide dismutase (MnSOD) and iron superoxide dismutase (FeSOD) respectively, creating mutations and gene fusions. The mutated sodA or sodB genes were introduced into the bacterial chromosome by allelic exchange. The resulting mutants were shown to lack the corresponding SOD by activity measurements and immunoblot analysis. Aerobically, in rich medium, the absence of FeSOD or MnSOD had no major effect on growth or sensitivity to the superoxide generator, paraquat. In minimal medium aerobic growth was not affected, but the sensitivity to paraquat was increased, especially in the sodA mutant. A sodA sodB double mutant completely devoid of SOD was also obtained. It was able to grow aerobically in rich medium, its catalase level was unaffected and it was highly sensitive to paraquat and hydrogen peroxide; the double mutant was unable to grow aerobically on minimal glucose medium. Growth could be restored by removing oxygen, by providing an SOD-overproducing plasmid or by supplementing the medium with the 20 amino acids. It is concluded that the total absence of SOD in E. coli creates a conditional sensitivity to oxygen.",
"title": "Isolation of superoxide dismutase mutants in Escherichia coli: is superoxide dismutase necessary for aerobic life?"
},
{
"docid": "6158879",
"text": "BACKGROUND Patients with diabetes mellitus (DM) are at high risk for recurrent cardiovascular events after acute coronary syndromes, in part because of increased platelet reactivity. The Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) showed an overall reduction in ischemic events with more intensive antiplatelet therapy with prasugrel than with clopidogrel but with more bleeding. We compared prasugrel with clopidogrel among subjects with DM in TRITON-TIMI 38. METHODS AND RESULTS We classified 13 608 subjects on the basis of preexisting history of DM and further according to insulin use. Prespecified analyses of the primary (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and key secondary end points, including net clinical benefit (death, nonfatal myocardial infarction, nonfatal stroke, and nonfatal TIMI major bleeding) were compared by use of the log-rank test. We found that 3146 subjects had a preexisting history of DM, including 776 receiving insulin. The primary end point was reduced significantly with prasugrel among subjects without DM (9.2% versus 10.6%; hazard ratio [HR], 0.86; P=0.02) and with DM (12.2% versus 17.0%; HR, 0.70; P<0.001, P(interaction)=0.09). A benefit for prasugrel was observed among DM subjects on insulin (14.3% versus 22.2%; HR, 0.63; P=0.009) and those not on insulin (11.5% versus 15.3%; HR, 0.74; P=0.009). Myocardial infarction was reduced with prasugrel by 18% among subjects without DM (7.2% versus 8.7%; HR, 0.82; P=0.006) and by 40% among subjects with DM (8.2% versus 13.2%; HR, 0.60; P<0.001, P(interaction)=0.02). Although TIMI major hemorrhage was increased among subjects without DM on prasugrel (1.6% versus 2.4%; HR, 1.43; P=0.02), the rates were similar among subjects with DM for clopidogrel and prasugrel (2.6% versus 2.5%; HR, 1.06; P=0.81, P(interaction)=0.29). Net clinical benefit with prasugrel was greater for subjects with DM (14.6% versus 19.2%; HR, 0.74; P=0.001) than for subjects without DM (11.5% versus 12.3%; HR, 0.92; P=0.16, P(interaction)=0.05). CONCLUSIONS Subjects with DM tended to have a greater reduction in ischemic events without an observed increase in TIMI major bleeding and therefore a greater net treatment benefit with prasugrel compared with clopidogrel. These data demonstrate that the more intensive oral antiplatelet therapy provided with prasugrel is of particular benefit to patients with DM.",
"title": "Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-Thrombolysis in Myocardial Infarction 38."
},
{
"docid": "471735",
"text": "Escherichia coli responds to the redox stress imposed by superoxide-generating agents such as paraquat by activating the synthesis of as many as 80 polypeptides. Expression of a key group of these inducible proteins is controlled at the transcriptional level by the soxRS locus (the soxRS regulon). A two-stage control system was hypothesized for soxRS, in which an intracellular redox signal would trigger the SoxR protein as a transcriptional activator of the soxS gene and the resulting increased levels of SoxS protein would activate transcription of the various soxRS regulon genes (B. Demple and C.F. Amábile Cuevas, Cell 67:837-839, 1990). We have constructed operon fusions of the E. coli lac genes to the soxS promoter to monitor soxS transcription. Expression from the soxS promoter is strongly inducible by paraquat in a manner strictly dependent on a functional soxR gene. Several other superoxide-generating agents also trigger soxR(+)-dependent soxS expression, and the inductions by paraquat and phenazine methosulfate were dependent on the presence of oxygen. Numerous other oxidative stress agents (H2O2, gamma rays, heat shock, etc.) failed to induce soxS, while aerobic growth of superoxide dismutase-deficient bacteria triggered soxR-dependent soxS expression. These results indicate a specific redox signal for soxS induction. A direct role for SoxR protein in the activation of the soxS gene is indicated by band-shift and DNase I footprinting experiments that demonstrate specific binding of the SoxR protein in cell extracts to the soxS promoter. The mode of SoxR binding to DNA appears to be similar to that of its homolog MerR in that the SoxR footprint spans the -10 to -35 region of the soxS promoter.",
"title": "Two-stage control of an oxidative stress regulon: the Escherichia coli SoxR protein triggers redox-inducible expression of the soxS regulatory gene."
},
{
"docid": "5573975",
"text": "Molecules associated with the transforming growth factor β (TGF-β) superfamily, such as bone morphogenic proteins (BMPs) and TGF-β, are key regulators of inflammation, apoptosis and cellular transitions. Here we show that the BMP receptor activin-like kinase 3 (Alk3) is elevated early in diseased kidneys after injury. We also found that its deletion in the tubular epithelium leads to enhanced TGF-β1-Smad family member 3 (Smad3) signaling, epithelial damage and fibrosis, suggesting a protective role for Alk3-mediated signaling in the kidney. A structure-function analysis of the BMP-Alk3-BMP receptor, type 2 (BMPR2) ligand-receptor complex, along with synthetic organic chemistry, led us to construct a library of small peptide agonists of BMP signaling that function through the Alk3 receptor. One such peptide agonist, THR-123, suppressed inflammation, apoptosis and the epithelial-to-mesenchymal transition program and reversed established fibrosis in five mouse models of acute and chronic renal injury. THR-123 acts specifically through Alk3 signaling, as mice with a targeted deletion for Alk3 in their tubular epithelium did not respond to therapy with THR-123. Combining THR-123 and the angiotensin-converting enzyme inhibitor captopril had an additive therapeutic benefit in controlling renal fibrosis. Our studies show that BMP signaling agonists constitute a new line of therapeutic agents with potential utility in the clinic to induce regeneration, repair and reverse established fibrosis.",
"title": "Activin–like kinase–3 activity is important for kidney regeneration and reversal of fibrosis"
},
{
"docid": "6277638",
"text": "The target of rapamycin (TOR) pathway is a major nutrient-sensing pathway that, when genetically downregulated, increases life span in evolutionarily diverse organisms including mammals. The central component of this pathway, TOR kinase, is the target of the inhibitory drug rapamycin, a highly specific and well-described drug approved for human use. We show here that feeding rapamycin to adult Drosophila produces the life span extension seen in some TOR mutants. Increase in life span by rapamycin was associated with increased resistance to both starvation and paraquat. Analysis of the underlying mechanisms revealed that rapamycin increased longevity specifically through the TORC1 branch of the TOR pathway, through alterations to both autophagy and translation. Rapamycin could increase life span of weak insulin/Igf signaling (IIS) pathway mutants and of flies with life span maximized by dietary restriction, indicating additional mechanisms.",
"title": "Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster"
},
{
"docid": "39970500",
"text": "PURPOSE This study assessed psychiatric medications and their potential lethality in a representative sample of suicide attempts. MATERIALS AND METHODS During 1996-98, 563 suicide attempts were studied in a general hospital in Madrid (Spain). Medication overdose was used in 456 suicide attempts (81%). The ratio between dose taken and maximum prescription dose recommended was used to evaluate the medication toxicity. RESULTS Benzodiazepines were the drugs most often used in self-poisoning (65% of overdoses), followed by new antidepressants (11%), tricyclic antidepressants (TCAs) (10%), and antipsychotics (8%). An overdose with any of the three latter psychiatric medications was significantly more frequent in patients prescribed those medications. The overdoses for TCA were potentially lethal in 47% of the cases. However, all patients who overdosed on psychiatric medications recovered well and were discharged without any sequelae. DISCUSSION This study suggests that psychiatric medications, particularly benzodiazepines, new antidepressants and antipsychotics, are relatively safe when they are used for self-poisoning. If patients with mental illnesses are under treated, there is a clear and documented higher risk for suicide. CONCLUSION It is better to prescribe psychiatric medications, particularly the new ones, rather than withhold them due to an exaggerated fear of a lethal overdose",
"title": "How safe are psychiatric medications after a voluntary overdose?"
},
{
"docid": "18174210",
"text": "BACKGROUND The heritable haemoglobinopathy alpha(+)-thalassaemia is caused by the reduced synthesis of alpha-globin chains that form part of normal adult haemoglobin (Hb). Individuals homozygous for alpha(+)-thalassaemia have microcytosis and an increased erythrocyte count. Alpha(+)-thalassaemia homozygosity confers considerable protection against severe malaria, including severe malarial anaemia (SMA) (Hb concentration < 50 g/l), but does not influence parasite count. We tested the hypothesis that the erythrocyte indices associated with alpha(+)-thalassaemia homozygosity provide a haematological benefit during acute malaria. METHODS AND FINDINGS Data from children living on the north coast of Papua New Guinea who had participated in a case-control study of the protection afforded by alpha(+)-thalassaemia against severe malaria were reanalysed to assess the genotype-specific reduction in erythrocyte count and Hb levels associated with acute malarial disease. We observed a reduction in median erythrocyte count of approximately 1.5 x 10(12)/l in all children with acute falciparum malaria relative to values in community children (p < 0.001). We developed a simple mathematical model of the linear relationship between Hb concentration and erythrocyte count. This model predicted that children homozygous for alpha(+)-thalassaemia lose less Hb than children of normal genotype for a reduction in erythrocyte count of >1.1 x 10(12)/l as a result of the reduced mean cell Hb in homozygous alpha(+)-thalassaemia. In addition, children homozygous for alpha(+)-thalassaemia require a 10% greater reduction in erythrocyte count than children of normal genotype (p = 0.02) for Hb concentration to fall to 50 g/l, the cutoff for SMA. We estimated that the haematological profile in children homozygous for alpha(+)-thalassaemia reduces the risk of SMA during acute malaria compared to children of normal genotype (relative risk 0.52; 95% confidence interval [CI] 0.24-1.12, p = 0.09). CONCLUSIONS The increased erythrocyte count and microcytosis in children homozygous for alpha(+)-thalassaemia may contribute substantially to their protection against SMA. A lower concentration of Hb per erythrocyte and a larger population of erythrocytes may be a biologically advantageous strategy against the significant reduction in erythrocyte count that occurs during acute infection with the malaria parasite Plasmodium falciparum. This haematological profile may reduce the risk of anaemia by other Plasmodium species, as well as other causes of anaemia. Other host polymorphisms that induce an increased erythrocyte count and microcytosis may confer a similar advantage.",
"title": "Increased Microerythrocyte Count in Homozygous α+-Thalassaemia Contributes to Protection against Severe Malarial Anaemia"
},
{
"docid": "36033696",
"text": "OBJECTIVE The purpose of this project was to educate inpatients with psychotic disorders, many of whom were taking second-generation antipsychotics, about lifestyle changes they can make to combat weight gain. METHOD All inpatients on a Veterans Affairs acute inpatient schizophrenia treatment unit were invited to a 30-minute, didactic presentation given by a medical student and a psychology student under the supervision of the primary investigator. The topics covered included the health benefits of maintaining an ideal body weight by selecting foods according to the USDA Food Pyramid, determining adequate food portions, choosing healthy meals outside the home, and beginning and adhering to an exercise program. Subjects completed a 13-item quiz concerning their knowledge of food and nutrition before and after the presentation to determine its efficacy in teaching patients the material. RESULTS Fifty patients completed both the pre- and post-presentation tests. The mean percentage of correct answers on the pre-test was 85.6%, which rose to 89.3% on the post-test. This difference of 3.7% was statistically significant (t = 2.43, df = 49, p < 0.02), and the mean percent of improvement was 6.1%. CONCLUSIONS This study demonstrates that psychotic individuals are able to benefit from educational presentations about nutrition and a healthy lifestyle. A statistically significant improvement in test scores suggests that subjects gained an understanding of basic concepts related to food choices and fitness.",
"title": "A wellness class for inpatients with psychotic disorders."
},
{
"docid": "4678846",
"text": "CONTEXT The antioxidant acetylcysteine prevents acute contrast nephrotoxicity in patients with impaired renal function who undergo computed tomography scanning. However, its role in coronary angiography is unclear. OBJECTIVE To determine whether oral acetylcysteine prevents acute deterioration in renal function in patients with moderate renal insufficiency who undergo elective coronary angiography. DESIGN AND SETTING Prospective, randomized, double-blind, placebo-controlled trial conducted from May 2000 to December 2001 at the Grantham Hospital at the University of Hong Kong. PARTICIPANTS Two hundred Chinese patients aged mean (SD) 68 (6.5) years with stable moderate renal insufficiency (creatinine clearance <60 mL/min [1.00 mL/s]) who were undergoing elective coronary angiography with or without intervention. INTERVENTION Participants were randomly assigned to receive oral acetylcysteine(600 mg twice per day; n = 102) or matching placebo tablets (n = 98) on the day before and the day of angiography. All patients received low-osmolality contrast agent. MAIN OUTCOME MEASURES Occurrence of more than a 25% increase in serum creatinine level within 48 hours after contrast administration; change in creatinine clearance and serum creatinine level. RESULTS Twelve control patients (12%) and 4 acetylcysteine patients (4%) developed a more than 25% increase in serum creatinine level within 48 hours after contrast administration (relative risk, 0.32; 95% confidence interval [CI], 0.10-0.96; P =.03). Serum creatinine was lower in the acetylcysteine group (1.22 mg/dL [107.8 micromol/L]; 95% CI, 1.11-1.33 mg/dL vs 1.38 mg/dL [122.9 micromol/L]; 95% CI, 1.27-1.49 mg/dL; P =.006) during the first 48 hours after angiography. Acetylcysteine treatment significantly increased creatinine clearance from 44.8 mL/min (0.75 mL/s) (95% CI, 42.7-47.6 mL/min) to 58.9 mL/min (0.98 mL/s) (95% CI, 55.6-62.3 mL/min) 2 days after the contrast administration (P<.001). The increase was not significant in the control group (from 42.1 to 44.1 mL/min [0.70 to 0.74 mL/s]; P =.15). The benefit of acetylcysteine was consistent among various patient subgroups and persistent for at least 7 days. There were no major treatment-related adverse events. CONCLUSION Acetylcysteine protects patients with moderate chronic renal insufficiency from contrast-induced deterioration in renal function after coronary angiographic procedures, with minimal adverse effects and at a low cost.",
"title": "Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: a randomized controlled trial."
},
{
"docid": "7552147",
"text": "The pancreas is an organ containing two distinct populations of cells, the exocrine cells that secrete enzymes into the digestive tract, and the endocrine cells that secrete hormones into the bloodstream. It arises from the endoderm as a dorsal and a ventral bud which fuse together to form the single organ. Mammals, birds, reptiles and amphibians have a pancreas with similar histology and mode of development, while in some fish, the islet cells are segregated as Brockmann bodies. Invertebrates do not have a pancreas, but comparable endocrine cells may be found in the gut or the brain. The early pancreatic bud shows uniform expression of the homeobox gene IPF-1 (also known as IDX-1, STF-1 or PDX), which when mutated to inactivity leads to total absence of the organ. The occurrence of heterotopic pancreas in the embryo, and also the metaplasias that can be displayed by a regenerating pancreas in the adult, both suggest that only a few gene products distinguish the pancreatic cell state from that of the surrounding tissues of duodenum, gall bladder and liver. In the developing pancreatic buds, the endocrine cells start to differentiate before the exocrine cells, and co-expression of different hormones by the same cell is often observed at early stages. Although pancreatic endocrine cells produce many gene products also characteristic of neurons, evidence from in vitro cultures and from quailchick grafts shows that they are of endogenous and not of neural crest origin. Observational studies suggest strongly that both endocrine and exocrine cells arise from the same endodermal rudiment. Development of the pancreas in embryonic life requires a trophic stimulus from the associated mesenchyme. In postnatal life, all cell types in the pancreas continue to grow. Destruction of acinar tissue by duct ligation or ethionine treatment is followed by rapid regeneration. Surgical removal of parts of the pancreas is followed by moderate but incomplete regeneration of both acini and islets. Poisoning with alloxan or streptozotocin can lead to permanent depletion of beta cells. Although the cell kinetics of the pancreas are not understood, it seems likely that there is a continuous slow turnover of cells, fed from a stem cells population in the ducts, and that the controls on the production rate of each cell type are local rather than systemic.",
"title": "Developmental biology of the pancreas."
},
{
"docid": "22401061",
"text": "The marginal costs and benefits of converting malaria programmes from a control to an elimination goal are central to strategic decisions, but empirical evidence is scarce. We present a conceptual framework to assess the economics of elimination and analyse a central component of that framework-potential short-term to medium-term financial savings. After a review that showed a dearth of existing evidence, the net present value of elimination in five sites was calculated and compared with effective control. The probability that elimination would be cost-saving over 50 years ranged from 0% to 42%, with only one site achieving cost-savings in the base case. These findings show that financial savings should not be a primary rationale for elimination, but that elimination might still be a worthy investment if total benefits are sufficient to outweigh marginal costs. Robust research into these elimination benefits is urgently needed.",
"title": "Costs and financial feasibility of malaria elimination"
},
{
"docid": "32421068",
"text": "Objective To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe. Design Retrospective cohort study. Setting Publicly accessible regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013.Main outcome measures Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after market entry. Validated European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) used to assess the clinical value of the reported gains in published studies of cancer drugs. Results From 2009 to 2013, the EMA approved the use of 48 cancer drugs for 68 indications. Of these, eight indications (12%) were approved on the basis of a single arm study. At the time of market approval, there was significant prolongation of survival in 24 of the 68 (35%). The magnitude of the benefit on overall survival ranged from 1.0 to 5.8 months (median 2.7 months). At the time of market approval, there was an improvement in quality of life in seven of 68 indications (10%). Out of 44 indications for which there was no evidence of a survival gain at the time of market authorisation, in the subsequent postmarketing period there was evidence for extension of life in three (7%) and reported benefit on quality of life in five (11%). Of the 68 cancer indications with EMA approval, and with a median of 5.4 years' follow-up (minimum 3.3 years, maximum 8.1 years), only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (49%) remained uncertain. Of 23 indications associated with a survival benefit that could be scored with the ESMO-MCBS tool, the benefit was judged to be clinically meaningful in less than half (11/23, 48%).Conclusions This systematic evaluation of oncology approvals by the EMA in 2009-13 shows that most drugs entered the market without evidence of benefit on survival or quality of life. At a minimum of 3.3 years after market entry, there was still no conclusive evidence that these drugs either extended or improved life for most cancer indications. When there were survival gains over existing treatment options or placebo, they were often marginal.",
"title": "Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13"
},
{
"docid": "46353045",
"text": "Late presentation remains a major concern despite the dramatically improved prognosis realized by ART. We define a first presentation for HIV care during the course of HIV infection as 'late' if an AIDS-defining opportunistic disease is apparent, or if CD4+ T-cells are <200/microl. In the Western world, approximately 10 and 30% of HIV-infected individuals still present with CD4+ T-cells <50 and <200/microl, respectively; estimates are substantially higher for developing countries. Diagnosis and treatment of opportunistic diseases and intense supportive in-hospital care take precedence over ART. Benefits of starting ART without delay, that is, when opportunistic diseases are still active, include faster resolution of opportunistic diseases and a decreased risk of recurrence. The downside of starting ART without delay could include toxicity, drug interactions and immune reconstitution inflammatory syndrome (IRIS). Among asymptomatic or oligosymptomatic individuals presenting late, where ART and primary prophylaxis are initiated, approximately 10-20% will become symptomatic from drug toxicity or undiagnosed opportunistic complications, including IRIS, which require appropriate therapies. In this review we describe late presentation to HIV care, the scale of the problem, the evaluation of a late-presenting patient and challenges associated with initiation of potent antiretroviral therapy (ART) in the setting of acute opportunistic infections and other comorbidities.",
"title": "Late presentation of HIV-infected individuals."
},
{
"docid": "26067999",
"text": "The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms. It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment. The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms. Summary of Recommendation and Evidence The USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) See the Clinical Considerations section for suggestions for implementation in practice. See the Figure for a summary of the recommendation and suggestions for clinical practice. Figure. Screening for lung cancer: clinical summary of U.S. Preventive Services Task Force recommendation. Appendix Table 1 describes the USPSTF grades, and Appendix Table 2 describes the USPSTF classification of levels of certainty about net benefit. Appendix Table 1. What the USPSTF Grades Mean and Suggestions for Practice Appendix Table 2. USPSTF Levels of Certainty Regarding Net Benefit Supplement. Consumer Fact Sheet. Rationale Importance Lung cancer is the third most common cancer and the leading cause of cancer-related death in the United States (1). The most important risk factor for lung cancer is smoking, which results in approximately 85% of all U.S. lung cancer cases (2). Although the prevalence of smoking has decreased, approximately 37% of U.S. adults are current or former smokers (2). The incidence of lung cancer increases with age and occurs most commonly in persons aged 55 years or older. Increasing age and cumulative exposure to tobacco smoke are the 2 most common risk factors for lung cancer. Lung cancer has a poor prognosis, and nearly 90% of persons with lung cancer die of the disease. However, early-stage nonsmall cell lung cancer (NSCLC) has a better prognosis and can be treated with surgical resection. Detection Most lung cancer cases are NSCLC, and most screening programs focus on the detection and treatment of early-stage NSCLC. Although chest radiography and sputum cytologic evaluation have been used to screen for lung cancer, LDCT has greater sensitivity for detecting early-stage cancer (3). Benefits of Detection and Early Treatment Although lung cancer screening is not an alternative to smoking cessation, the USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancerrelated deaths. Direct evidence from a large, well-conducted, randomized, controlled trial (RCT) provides moderate certainty of the benefit of lung cancer screening with LDCT in this population (4). The magnitude of benefit to the person depends on that person's risk for lung cancer because those who are at highest risk are most likely to benefit. Screening cannot prevent most lung cancerrelated deaths, and smoking cessation remains essential. Harms of Detection and Early Intervention and Treatment The harms associated with LDCT screening include false-negative and false-positive results, incidental findings, overdiagnosis, and radiation exposure. False-positive LDCT results occur in a substantial proportion of screened persons; 95% of all positive results do not lead to a diagnosis of cancer. In a high-quality screening program, further imaging can resolve most false-positive results; however, some patients may require invasive procedures. The USPSTF found insufficient evidence on the harms associated with incidental findings. Overdiagnosis of lung cancer occurs, but its precise magnitude is uncertain. A modeling study performed for the USPSTF estimated that 10% to 12% of screen-detected cancer cases are overdiagnosedthat is, they would not have been detected in the patient's lifetime without screening. Radiation harms, including cancer resulting from cumulative exposure to radiation, vary depending on the age at the start of screening; the number of scans received; and the person's exposure to other sources of radiation, particularly other medical imaging. USPSTF Assessment The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT is of moderate net benefit in asymptomatic persons who are at high risk for lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. The moderate net benefit of screening depends on limiting screening to persons who are at high risk, the accuracy of image interpretation being similar to that found in the NLST (National Lung Screening Trial), and the resolution of most false-positive results without invasive procedures (4). Clinical Considerations Patient Population Under Consideration The risk for lung cancer increases with age and cumulative exposure to tobacco smoke and decreases with time since quitting smoking. The best evidence for the benefit of screening comes from the NLST, which enrolled adults aged 55 to 74 years who had at least a 30 pack-year smoking history and were current smokers or had quit within the past 15 years. As with all screening trials, the NLST tested a specific intervention over a finite period. Because initial eligibility extended through age 74 years and participants received 3 annual screening computed tomographic scans, the oldest participants in the trial were aged 77 years. The USPSTF used modeling studies to predict the benefits and harms of screening programs that use different screening intervals, age ranges, smoking histories, and times since quitting. A program that annually screens adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years is projected to have a reasonable balance of benefits and harms. The model assumes that persons who achieve 15 years of smoking cessation during the screening program discontinue screening. This model predicts the outcomes of continuing the screening program used in the NLST through age 80 years. Screening may not be appropriate for patients with substantial comorbid conditions, particularly those at the upper end of the screening age range. The NLST excluded persons who were unlikely to complete curative lung cancer surgery and those with medical conditions that posed a substantial risk for death during the 8-year trial. The baseline characteristics of the NLST showed a relatively healthy sample, and fewer than 10% of enrolled participants were older than 70 years (5). Persons with serious comorbid conditions may experience net harm, no net benefit, or at least substantially less net benefit. Similarly, persons who are unwilling to have curative lung surgery are unlikely to benefit from a screening program. Assessment of Risk Age, total exposure to tobacco smoke, and years since quitting smoking are important risk factors for lung cancer and were used to determine eligibility in the NLST. Other risk factors include specific occupational exposures, radon exposure, family history, and history of pulmonary fibrosis or chronic obstructive lung disease. The incidence of lung cancer is relatively low in persons younger than 50 years but increases with age, especially after age 60 years. In current and former smokers, age-specific incidence rates increase with age and cumulative exposure to tobacco smoke. Smoking cessation substantially reduces a person's risk for developing and dying of lung cancer. Among persons enrolled in the NLST, those who were at highest risk because of additional risk factors or a greater cumulative exposure to tobacco smoke experienced most of the benefit (6). A validated multivariate model showed that persons in the highest 60% of risk accounted for 88% of all deaths preventable by screening. Screening Tests Low-dose computed tomography has shown high sensitivity and acceptable specificity for the detection of lung cancer in high-risk persons. Chest radiography and sputum cytologic evaluation have not shown adequate sensitivity or specificity as screening tests. Therefore, LDCT is currently the only recommended screening test for lung cancer. Treatment Surgical resection is the current standard of care for localized NSCLC. This type of cancer is treated with surgical resection when possible and also with radiation and chemotherapy. Annual LDCT screening may not be useful for patients with life-limiting comorbid conditions or poor functional status who may not be candidates for surgery. Other Approaches to Prevention Smoking cessation is the most important intervention to prevent NSCLC. Advising smokers to stop smoking and preventing nonsmokers from being exposed to tobacco smoke are the most effective ways to decrease the morbidity and mortality associated with lung cancer. Current smokers should be informed of their continuing risk for lung cancer and offered cessation treatments. Screening with LDCT should be viewed as an adjunct to tobacco cessation interventions. Useful Resources Clinicians have many resources to help patients stop smoking. The Centers for Disease Control and Prevention has developed a Web site with many such resources, including information on tobacco quit lines, available in several languages (www.cdc.gov/tobacco/campaign/tips). Quit l",
"title": "Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation Statement"
}
] |
740
|
MUC1-C activates the NF-κB p65 signaling pathway by interacting with IκB kinase ß.
|
[
{
"docid": "23078022",
"text": "Nuclear factor-κB (NF-κB) is constitutively activated in diverse human malignancies by mechanisms that are not understood. The MUC1 oncoprotein is aberrantly overexpressed by most human carcinomas and, similarly to NF-κB, blocks apoptosis and induces transformation. This study demonstrates that overexpression of MUC1 in human carcinoma cells is associated with constitutive activation of NF-κB p65. We show that MUC1 interacts with the high-molecular-weight IκB kinase (IKK) complex in vivo and that the MUC1 cytoplasmic domain binds directly to IKKβ and IKKγ. Interaction of MUC1 with both IKKβ and IKKγ is necessary for IKKβ activation, resulting in phosphorylation and degradation of IκBα. Studies in non-malignant epithelial cells show that MUC1 is recruited to the TNF-R1 complex and interacts with IKKβ–IKKγ in response to TNFα stimulation. TNFα-induced recruitment of MUC1 is dependent on TRADD and TRAF2, but not the death-domain kinase RIP1. In addition, MUC1-mediated activation of IKKβ is dependent on TAK1 and TAB2. These findings indicate that MUC1 is important for physiological activation of IKKβ and that overexpression of MUC1, as found in human cancers, confers sustained induction of the IKKβ–NF-κB p65 pathway.",
"title": "MUC1 oncoprotein activates the IκB kinase β complex and constitutive NF-κB signalling"
}
] |
[
{
"docid": "83308790",
"text": "In mammals, the canonical nuclear factor κB (NF-κB) signaling pathway activated in response to infections is based on degradation of IκB inhibitors. This pathway depends on the IκB kinase (IKK), which contains two catalytic subunits, IKKα and IKKβ. IKKβ is essential for inducible IκB phosphorylation and degradation, whereas IKKα is not. Here we show that IKKα is required for B cell maturation, formation of secondary lymphoid organs, increased expression of certain NF-κB target genes, and processing of the NF-κB2 (p100) precursor. IKKα preferentially phosphorylates NF-κB2, and this activity requires its phosphorylation by upstream kinases, one of which may be NF-κB–inducing kinase (NIK). IKKα is therefore a pivotal component of a second NF-κB activation pathway based on regulated NF-κB2 processing rather than IκB degradation.",
"title": "Activation by IKKα of a second, evolutionary conserved, NF-κB signaling pathway"
},
{
"docid": "27093166",
"text": "BACKGROUND Ketamine, as an anesthetic agent, has an anti-inflammatory effect. In the present study, we investigated whether ketamine inhibits release of high mobility group box 1 (HMGB1), a late-phase cytokine of sepsis, in lipopolysaccharide (LPS)-stimulated macrophages through heme oxygenase-1 (HO-1) induction. METHODS Macrophages were preincubated with various concentrations of ketamine and then treated with LPS (1 μg/mL). The cell culture supernatants were collected to measure inflammatory mediators (HMGB1, nitric oxide, tumor necrosis factor-α, and interleukin 1β) by enzyme-linked immunosorbent assay. Moreover, HO-1 protein expression, the phosphorylation and degradation of IκB-α, and the nuclear translocation of nuclear factor E2-related factor 2 and nuclear factor κB (NF-κB) p65 were tested by Western blot analysis. In addition, to further identify the role of HO-1 in this process, tin protoporphyrin (SnPP), an HO-1 inhibitor, was used. RESULTS Ketamine treatment dose-dependently attenuated the increased levels of proinflammatory mediators (HMGB1, nitric oxide, tumor necrosis factor α, and interleukin 1β) and increased the HO-1 protein expression in LPS-activated macrophages. Furthermore, ketamine suppressed the phosphorylation and degradation of IκB-α as well as the LPS-stimulated nuclear translocation of NF-κB p65 in macrophages. In addition, the present study also demonstrated that ketamine induced HO-1 expression through the nuclear translocation of nuclear factor E2-related factor 2 in macrophages. The effects of ketamine on LPS-induced proinflammatory cytokines production were partially reversed by the HO inhibitor tin protoporphyrin (SnPP). CONCLUSION Ketamine inhibits the release of HMGB1 in LPS-stimulated macrophages, and this effect is at least partly mediated by the activation of the Nrf2/HO-1 pathway and NF-κB suppression.",
"title": "Ketamine reduces LPS-induced HMGB1 via activation of the Nrf2/HO-1 pathway and NF-κB suppression."
},
{
"docid": "39424916",
"text": "Wedelolactone is a major coumarin of Eclipta prostrata, which is used for preventing liver damage. However the effects of wedelolactone on hepatic fibrosis remained unexplored. The purpose of this study was to demonstrate the anti-fibrotic effects of wedelolactone on activated human hepatic stellate cell (HSC) line LX-2 and the possible underlying mechanisms by means of MTT assay, Hoechst staining, as well as real-time quantitative PCR and western blot. The results showed that wedelolactone reduced the cellular viability of LX-2 in a time and dose-dependent manner. After treatment of wedelolactone, the expressions of collagen I and α-smooth muscle actin, two biomarkers of LX-2 activation, were remarkably decreased. The apoptosis of LX-2 cells was induced by wedelolactone accompanied with the decreasing expression of anti-apoptotic Bcl-2 and increasing expression of pro-apoptotic Bax. In addition, phosphorylated status of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) was up-regulated, but not in p38. Moreover, wedelolactone significantly repressed the level of phosphorylated inhibitor of nuclear factor κB (IκB) and p65 in nucleus in spite of tumor necrosis factor-α stimulation. In conclusion, wedelolactone could significantly inhibit the activation of LX-2 cells, the underlying mechanisms of which included inducing Bcl-2 family involved apoptosis, up-regulating phosphorylated status of ERK and JNK expressions, and inhibiting nuclear factor-κB (NF-κB) mediated activity. Wedelolactone might present as a useful tool for the prevention and treatment of hepatic fibrosis.",
"title": "Wedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2."
},
{
"docid": "23737024",
"text": "Two studies were performed to investigate the effects of an acute bout of physical exercise on the nuclear protein kappaB (NF-kappaB) signaling pathway in rat skeletal muscle. In Study 1, a group of rats (n=6) was run on the treadmill at 25 m/min, 5% grade, for 1 h or until exhaustion (Ex), and compared with a second group (n=6) injected with two doses of pyrrolidine dithiocarbamate (PDTC, 100 mg/kg, i.p.) 24 and 1 h prior to the acute exercise bout. Three additional groups of rats (n=6) were injected with either 8 mg/kg (i.p.) of lipopolysaccharide (LPS), 1 mmol/kg (i.p.) t-butylhydroperoxide (tBHP), or saline (C) and killed at resting condition. Ex rats showed higher levels of NF-kappaB binding and P50 protein content in muscle nuclear extracts compared with C rats. Cytosolic IkappaBalpha and IkappaB kinase (IKK) contents were decreased, whereas phospho-IkappaBalpha and phospho-IKK contents were increased, comparing Ex vs. C. The exercise-induced activation of NF-kappaB signaling cascade was partially abolished by PDTC treatment. LPS, but not tBHP, treatment mimicked and exaggerated the effects observed in Ex rats. In Study 2, the time course of exercise-induced NF-kappaB activation was examined. Highest levels of NF-kappaB binding were observed at 2 h postexercise. Decreased cytosolic IkappaBalpha and increased phosphor-IkappaBalpha content were found 0-1 h postexercise whereas P65 reached peak levels at 2-4 h. These data suggest that the NF-kappaB signaling pathway can be activated in a redox-sensitive manner during muscular contraction, presumably due to increased oxidant production. The cascade of intracellular events may be the overture to elevated gene expression of manganese superoxide dismutase reported earlier (Pfluegers Arch. 442, 426-434, 2001).",
"title": "Acute exercise activates nuclear factor (NF)-kappaB signaling pathway in rat skeletal muscle."
},
{
"docid": "41913714",
"text": "Digitoxin and structurally related cardiac glycoside drugs potently block activation of the TNF-α/NF-κB signaling pathway. We have hypothesized that the mechanism might be discovered by searching systematically for selective inhibitory action through the entire pathway. We report that the common action of these drugs is to block the TNF-α-dependent binding of TNF receptor 1 to TNF receptor-associated death domain. This drug action can be observed with native cells, such as HeLa, and reconstituted systems prepared in HEK293 cells. All other antiinflammatory effects of digitoxin on NF-κB and c-Jun N-terminal kinase pathways appear to follow from the blockade of this initial upstream signaling event.",
"title": "Cardiac glycosides inhibit TNF-α/NF-κB signaling by blocking recruitment of TNF receptor-associated death domain to the TNF receptor"
},
{
"docid": "9956893",
"text": "OBJECTIVE Advances made in the past ten years highlight the notion that peroxisome proliferator-activated receptors gamma (PPARγ) has protective properties in the pathophysiology of osteoarthritis (OA). The aim of this study was to define the roles of PPARγ in AGEs-induced inflammatory response in human chondrocytes. METHODS Primary human chondrocytes were stimulated with AGEs in the presence or absence of neutralizing antibody against RAGE (anti-RAGE), MAPK specific inhibitors and PPARγ agonist pioglitazone. The expression of IL-1, MMP-13, TNF-α, PPARγ, nuclear NF-κB p65 and cytosol IκBα was determined by western blotting and real-time PCR. RESULTS AGEs could enhance the expression of IL-1, TNF-α, and MMP-13, but the level of PPARγ was decreased in a time- and dose-dependent manner, which was inhibited by anti-RAGE, SB203580 (P38 MAPK specific inhibitor) and SP600125 (a selective inhibitor of JNK). PPARγ agonist pioglitazone could inhibit the effects of AGEs-induced inflammatory response and PPARγ down-regulation. In human chondrocytes, AGEs could induce cytosol IκBα degradation and increase the level of nuclear NF-κB p65, which was inhibited by PPARγ agonist pioglitazone. CONCLUSIONS In primary human chondrocytes, AGEs could down-regulate PPARγ expression and increase the inflammatory mediators, which could be reversed by PPARγ agonist pioglitazone. Activation of RAGE by AGEs triggers a cascade of downstream signaling, including MAPK JNK/ p38, PPARγ and NF-κB. Taken together, PPARγ could be a potential target for pharmacologic intervention in the treatment of OA.",
"title": "The Role of PPARγ in Advanced Glycation End Products-Induced Inflammatory Response in Human Chondrocytes"
},
{
"docid": "364522",
"text": "OBJECTIVES Calcific aortic valve (AV) disease is known to be an inflammation-related process. High-mobility group box-1 (HMGB1) protein and Toll-like receptor 4 (TLR4) have been reported to participate in several inflammatory diseases. The purpose of the present study was to determine whether the HMGB1-TLR4 axis is involved in calcific AV disease, and to evaluate the effect of HMGB1, and its potential mechanisms, on the pro-osteogenic phenotype change of valvular interstitial cells (VICs). METHODS Expression of HMGB1 and TLR4 in human calcific AVs was evaluated using immunohistochemical staining and immunoblotting. Cultured VICs were used as an in vitro model. The VICs were stimulated with HMGB1 for analysis, with versus without TLR4 small interfering ribonucleic acid (siRNA), c-Jun N-terminal kinase mitogen-activated protein kinase (JNK MAPK), and nuclear factor kappa-B (NF-κB) inhibitors. RESULTS Enhanced accumulation of HMGB1 and TLR4 was observed in calcific valves. Moreover, we found that HMGB1 induced high levels of pro-inflammatory cytokine production and promoted the osteoblastic differentiation and calcification of VICs. In addition, HMGB1 induced phosphorylation of JNK MAPK and NF-κB. However, these effects were markedly suppressed by siRNA silencing of TLR4. In addition, blockade of JNK MAPK and NF-κB phosphorylation prohibited HMGB1-induced production of pro-osteogenic factors, and mineralization of VICs. CONCLUSIONS The HMGB1 protein may promote osteoblastic differentiation and calcification of VICs, through the TLR4-JNK-NF-κB signaling pathway.",
"title": "High-mobility group box-1 protein induces osteogenic phenotype changes in aortic valve interstitial cells."
},
{
"docid": "18956141",
"text": "Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired epithelial responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD). IEC-specific ablation of nuclear factor κB (NF-κB) essential modulator (NEMO) caused Paneth cell apoptosis and impaired antimicrobial factor expression in the ileum, as well as colonocyte apoptosis and microbiota-driven chronic inflammation in the colon. Combined RelA, c-Rel, and RelB deficiency in IECs caused Paneth cell apoptosis but not colitis, suggesting that NEMO prevents colon inflammation by NF-κB-independent functions. Inhibition of receptor-interacting protein kinase 1 (RIPK1) kinase activity or combined deficiency of Fas-associated via death domain protein (FADD) and RIPK3 prevented epithelial cell death, Paneth cell loss, and colitis development in mice with epithelial NEMO deficiency. Therefore, NEMO prevents intestinal inflammation by inhibiting RIPK1 kinase activity-mediated IEC death, suggesting that RIPK1 inhibitors could be effective in the treatment of colitis in patients with NEMO mutations and possibly in IBD.",
"title": "NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions"
},
{
"docid": "1044552",
"text": "Proteinase-activated receptors (PARs) belong to a family of G protein-coupled receptors. PARs are activated by a serine-dependent cleavage generating a tethered activating ligand. PAR-2 was shown to be involved in inflammatory pathways. We investigated the in situ levels and modulation of PAR-2 in human normal and osteoarthritis (OA) cartilage/chondrocytes. Furthermore, we evaluated the role of PAR-2 on the synthesis of the major catabolic factors in OA cartilage, including metalloproteinase (MMP)-1 and MMP-13 and the inflammatory mediator cyclooxygenase 2 (COX-2), as well as the PAR-2-activated signalling pathways in OA chondrocytes. PAR-2 expression was determined using real-time reverse transcription-polymerase chain reaction and protein levels by immunohistochemistry in normal and OA cartilage. Protein modulation was investigated in OA cartilage explants treated with a specific PAR-2-activating peptide (PAR-2-AP), SLIGKV-NH2 (1 to 400 μM), interleukin 1 beta (IL-1β) (100 pg/mL), tumor necrosis factor-alpha (TNF-α) (5 ng/mL), transforming growth factor-beta-1 (TGF-β1) (10 ng/mL), or the signalling pathway inhibitors of p38 (SB202190), MEK1/2 (mitogen-activated protein kinase kinase) (PD98059), and nuclear factor-kappa B (NF-κB) (SN50), and PAR-2 levels were determined by immunohistochemistry. Signalling pathways were analyzed on OA chondrocytes by Western blot using specific phospho-antibodies against extracellular signal-regulated kinase 1/2 (Erk1/2), p38, JNK (c-jun N-terminal kinase), and NF-κB in the presence or absence of the PAR-2-AP and/or IL-1β. PAR-2-induced MMP and COX-2 levels in cartilage were determined by immunohistochemistry. PAR-2 is produced by human chondrocytes and is significantly upregulated in OA compared with normal chondrocytes (p < 0.04 and p < 0.03, respectively). The receptor levels were significantly upregulated by IL-1β (p < 0.006) and TNF-α (p < 0.002) as well as by the PAR-2-AP at 10, 100, and 400 μM (p < 0.02) and were downregulated by the inhibition of p38. After 48 hours of incubation, PAR-2 activation significantly induced MMP-1 and COX-2 starting at 10 μM (both p < 0.005) and MMP-13 at 100 μM (p < 0.02) as well as the phosphorylation of Erk1/2 and p38 within 5 minutes of incubation (p < 0.03). Though not statistically significant, IL-1β produced an additional effect on the activation of Erk1/2 and p38. This study documents, for the first time, functional consequences of PAR-2 activation in human OA cartilage, identifies p38 as the major signalling pathway regulating its synthesis, and demonstrates that specific PAR-2 activation induces Erk1/2 and p38 in OA chondrocytes. These results suggest PAR-2 as a potential new therapeutic target for the treatment of OA.",
"title": "Activation of proteinase-activated receptor 2 in human osteoarthritic cartilage upregulates catabolic and proinflammatory pathways capable of inducing cartilage degradation: a basic science study"
},
{
"docid": "6690087",
"text": "We addressed the regulatory function of mammalian target of rapamycin (mTOR) in the mechanism of thrombin-induced ICAM-1 gene expression in endothelial cells. Pretreatment of HUVECs with rapamycin, an inhibitor of mTOR, augmented thrombin-induced ICAM-1 expression. Inhibition of mTOR by this approach promoted whereas over-expression of mTOR inhibited thrombin-induced transcriptional activity of NF-kappaB, an essential regulator of ICAM-1 transcription. Analysis of the NF-kappaB signaling pathway revealed that inhibition of mTOR potentiated IkappaB kinase activation resulting in a rapid and persistent phosphorylation of IkappaBalpha on Ser32 and Ser36, a requirement for IkappaBalpha degradation. Consistent with these data, we observed a more efficient and stable nuclear localization of RelA/p65 and, subsequently, the DNA binding activity of NF-kappaB by thrombin following mTOR inhibition. These data define a novel role of mTOR in down-regulating thrombin-induced ICAM-1 expression in endothelial cells by controlling a delayed and transient activation of NF-kappaB.",
"title": "Inhibition of mammalian target of rapamycin potentiates thrombin-induced intercellular adhesion molecule-1 expression by accelerating and stabilizing NF-kappa B activation in endothelial cells."
},
{
"docid": "52925737",
"text": "BACKGROUND Exosomes are extracellular vesicles that mediate cellular communication in health and diseases. Neutrophils could be polarized to a pro-tumor phenotype by tumor. The function of tumor-derived exosomes in neutrophil regulation remains unclear. METHODS We investigated the effects of gastric cancer cell-derived exosomes (GC-Ex) on the pro-tumor activation of neutrophils and elucidated the underlying mechanisms. RESULTS GC-Ex prolonged neutrophil survival and induced expression of inflammatory factors in neutrophils. GC-Ex-activated neutrophils, in turn, promoted gastric cancer cell migration. GC-Ex transported high mobility group box-1 (HMGB1) that activated NF-κB pathway through interaction with TLR4, resulting in an increased autophagic response in neutrophils. Blocking HMGB1/TLR4 interaction, NF-κB pathway, and autophagy reversed GC-Ex-induced neutrophil activation. Silencing HMGB1 in gastric cancer cells confirmed HMGB1 as a key factor for GC-Ex-mediated neutrophil activation. Furthermore, HMGB1 expression was upregulated in gastric cancer tissues. Increased HMGB1 expression was associated with poor prognosis in patients with gastric cancer. Finally, gastric cancer tissue-derived exosomes acted similarly as exosomes derived from gastric cancer cell lines in neutrophil activation. CONCLUSION We demonstrate that gastric cancer cell-derived exosomes induce autophagy and pro-tumor activation of neutrophils via HMGB1/TLR4/NF-κB signaling, which provides new insights into mechanisms for neutrophil regulation in cancer and sheds lights on the multifaceted role of exosomes in reshaping tumor microenvironment.",
"title": "Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration"
},
{
"docid": "52873726",
"text": "The Hippo pathway controls organ size and tissue homeostasis, with deregulation leading to cancer. The core Hippo components in mammals are composed of the upstream serine/threonine kinases Mst1/2, MAPK4Ks and Lats1/2. Inactivation of these upstream kinases leads to dephosphorylation, stabilization, nuclear translocation and thus activation of the major functional transducers of the Hippo pathway, YAP and its paralogue TAZ. YAP/TAZ are transcription co-activators that regulate gene expression primarily through interaction with the TEA domain DNA-binding family of transcription factors (TEAD). The current paradigm for regulation of this pathway centres on phosphorylation-dependent nucleocytoplasmic shuttling of YAP/TAZ through a complex network of upstream components. However, unlike other transcription factors, such as SMAD, NF-κB, NFAT and STAT, the regulation of TEAD nucleocytoplasmic shuttling has been largely overlooked. In the present study, we show that environmental stress promotes TEAD cytoplasmic translocation via p38 MAPK in a Hippo-independent manner. Importantly, stress-induced TEAD inhibition predominates YAP-activating signals and selectively suppresses YAP-driven cancer cell growth. Our data reveal a mechanism governing TEAD nucleocytoplasmic shuttling and show that TEAD localization is a critical determinant of Hippo signalling output.",
"title": "Regulation of Hippo pathway transcription factor TEAD by p38 MAPK-induced cytoplasmic translocation"
},
{
"docid": "22210434",
"text": "The kinase TAK1 is critical for innate and B cell immunity. The function of TAK1 in T cells is unclear, however. We show here that T cell–specific deletion of the gene encoding TAK1 resulted in reduced development of thymocytes, especially of regulatory T cells expressing the transcription factor Foxp3. In mature thymocytes, TAK1 was required for interleukin 7–mediated survival and T cell receptor–dependent activation of transcription factor NF-κB and the kinase Jnk. In effector T cells, TAK1 was dispensable for T cell receptor–dependent NF-κB activation and cytokine production, but was important for proliferation and activation of the kinase p38 in response to interleukins 2, 7 and 15. Thus, TAK1 is essential for the integration of T cell receptor and cytokine signals to regulate the development, survival and function of T cells.",
"title": "The kinase TAK1 integrates antigen and cytokine receptor signaling for T cell development, survival and function"
},
{
"docid": "6936141",
"text": "The HIV-1 protein Nef enhances viral pathogenicity and accelerates disease progression in vivo. Nef potentiates T cell activation by an unknown mechanism, probably by optimizing the intracellular environment for HIV replication. Using a new T cell reporter system, we have found that Nef more than doubles the number of cells expressing the transcription factors NF-kappaB and NFAT after TCR stimulation. This Nef-induced priming of TCR signaling pathways occurred independently of calcium signaling and involved a very proximal step before protein kinase C activation. Engagement of the TCR by MHC-bound Ag triggers the formation of the immunological synapse by recruiting detergent-resistant membrane microdomains, termed lipid rafts. Approximately 5-10% of the total cellular pool of Nef is localized within lipid rafts. Using confocal and real-time microscopy, we found that Nef in lipid rafts was recruited into the immunological synapse within minutes after Ab engagement of the TCR/CD3 and CD28 receptors. This recruitment was dependent on the N-terminal domain of Nef encompassing its myristoylation. Nef did not increase the number of cell surface lipid rafts or immunological synapses. Recently, studies have shown a specific interaction of Nef with an active subpopulation of p21-activated kinase-2 found only in the lipid rafts. Thus, the corecruitment of Nef and key cellular partners (e.g., activated p21-activated kinase-2) into the immunological synapse may underlie the increased frequency of cells expressing transcriptionally active forms of NF-kappaB and NFAT and the resultant changes in T cell activation.",
"title": "Nef is physically recruited into the immunological synapse and potentiates T cell activation early after TCR engagement."
},
{
"docid": "22703082",
"text": "Infection with Helicobacter pylori (H. pylori) is a risk factor for the development of gastric cancer. Here we show that infection of gastric epithelial cells with 'cag' pathogenicity island (cagPAI)-positive H. pylori induced aberrant expression of activation-induced cytidine deaminase (AID), a member of the cytidine-deaminase family that acts as a DNA- and RNA-editing enzyme, via the IκB kinase–dependent nuclear factor-κB activation pathway. H. pylori–mediated upregulation of AID resulted in the accumulation of nucleotide alterations in the TP53 tumor suppressor gene in gastric cells in vitro. Our findings provide evidence that aberrant AID expression caused by H. pylori infection might be a mechanism of mutation accumulation in the gastric mucosa during H. pylori–associated gastric carcinogenesis.",
"title": "Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium"
},
{
"docid": "4702639",
"text": "Tumour cells, with stem-like properties, are highly aggressive and often show drug resistance. Here, we reveal that integrin αvβ3 serves as a marker of breast, lung and pancreatic carcinomas with stem-like properties that are highly resistant to receptor tyrosine kinase inhibitors such as erlotinib. This was observed in vitro and in mice bearing patient-derived tumour xenografts or in clinical specimens from lung cancer patients who had progressed on erlotinib. Mechanistically, αvβ3, in the unliganded state, recruits KRAS and RalB to the tumour cell plasma membrane, leading to the activation of TBK1 and NF-κB. In fact, αvβ3 expression and the resulting KRAS–RalB–NF-κB pathway were both necessary and sufficient for tumour initiation, anchorage independence, self-renewal and erlotinib resistance. Pharmacological targeting of this pathway with bortezomib reversed both tumour stemness and erlotinib resistance. These findings not only identify αvβ3 as a marker/driver of carcinoma stemness but also reveal a therapeutic strategy to sensitize such tumours to RTK inhibition.",
"title": "An integrin β3–KRAS–RalB complex drives tumour stemness and resistance to EGFR inhibition"
},
{
"docid": "23305884",
"text": "Epstein-Barr virus (EBV) is an oncogenic human herpesvirus that dramatically reorganizes host gene expression to immortalize primary B cells. In this study, we analyzed EBV-regulated host gene expression changes following primary B-cell infection, both during initial proliferation and through transformation into lymphoblastoid cell lines (LCLs). While most EBV-regulated mRNAs were changed during the transition from resting, uninfected B cells through initial B-cell proliferation, a substantial number of mRNAs changed uniquely from early proliferation through LCL outgrowth. We identified constitutively and dynamically EBV-regulated biological processes, protein classes, and targets of specific transcription factors. Early after infection, genes associated with proliferation, stress responses, and the p53 pathway were highly enriched. However, the transition from early to long-term outgrowth was characterized by genes involved in the inhibition of apoptosis, the actin cytoskeleton, and NF-κB activity. It was previously thought that the major viral protein responsible for NF-κB activation, latent membrane protein 1 (LMP1), is expressed within 2 days after infection. Our data indicate that while this is true, LCL-level LMP1 expression and NF-κB activity are not evident until 3 weeks after primary B-cell infection. Furthermore, heterologous NF-κB activation during the first week after infection increased the transformation efficiency, while early NF-κB inhibition had no effect on transformation. Rather, inhibition of NF-κB was not toxic to EBV-infected cells until LMP1 levels and NF-κB activity were high. These data collectively highlight the dynamic nature of EBV-regulated host gene expression and support the notion that early EBV-infected proliferating B cells have a fundamentally distinct growth and survival phenotype from that of LCLs.",
"title": "Analysis of Epstein-Barr virus-regulated host gene expression changes through primary B-cell outgrowth reveals delayed kinetics of latent membrane protein 1-mediated NF-κB activation."
},
{
"docid": "29509926",
"text": "Membrane cholesterol modulates a variety of cell signaling pathways and functions. While cholesterol depletion by high-density lipoproteins (HDLs) has potent anti-inflammatory effects in various cell types, its effects on inflammatory responses in macrophages remain elusive. Here we show overt pro-inflammatory effects of HDL-mediated passive cholesterol depletion and lipid raft disruption in murine and human primary macrophages in vitro. These pro-inflammatory effects were confirmed in vivo in peritoneal macrophages from apoA-I transgenic mice, which have elevated HDL levels. In line with these findings, the innate immune responses required for clearance of P. aeruginosa bacterial infection in lung were compromised in mice with low HDL levels. Expression analysis, ChIP-PCR, and combinatorial pharmacological and genetic intervention studies unveiled that both native and reconstituted HDL enhance Toll-like-receptor-induced signaling by activating a PKC-NF-κB/STAT1-IRF1 axis, leading to increased inflammatory cytokine expression. HDL's pro-inflammatory activity supports proper functioning of macrophage immune responses.",
"title": "High-Density Lipoproteins Exert Pro-inflammatory Effects on Macrophages via Passive Cholesterol Depletion and PKC-NF-κB/STAT1-IRF1 Signaling."
},
{
"docid": "4345315",
"text": "Missense mutations in the CIAS1 gene cause three autoinflammatory disorders: familial cold autoinflammatory syndrome, Muckle–Wells syndrome and neonatal-onset multiple-system inflammatory disease. Cryopyrin (also called Nalp3), the product of CIAS1, is a member of the NOD-LRR protein family that has been linked to the activation of intracellular host defence signalling pathways. Cryopyrin forms a multi-protein complex termed ‘the inflammasome’, which contains the apoptosis-associated speck-like protein (ASC) and caspase-1, and promotes caspase-1 activation and processing of pro-interleukin (IL)-1β (ref. 4). Here we show the effect of cryopyrin deficiency on inflammasome function and immune responses. Cryopyrin and ASC are essential for caspase-1 activation and IL-1β and IL-18 production in response to bacterial RNA and the imidazoquinoline compounds R837 and R848. In contrast, secretion of tumour-necrosis factor-α and IL-6, as well as activation of NF-κB and mitogen-activated protein kinases (MAPKs) were unaffected by cryopyrin deficiency. Furthermore, we show that Toll-like receptors and cryopyrin control the secretion of IL-1β and IL-18 through different intracellular pathways. These results reveal a critical role for cryopyrin in host defence through bacterial RNA-mediated activation of caspase-1, and provide insights regarding the pathogenesis of autoinflammatory syndromes.",
"title": "Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3"
},
{
"docid": "37138639",
"text": "The IKK kinase complex is the core element of the NF-kappaB cascade. It is essentially made of two kinases (IKKalpha and IKKbeta) and a regulatory subunit, NEMO/IKKgamma. Additional components may exist, transiently or permanently, but their characterization is still unsure. In addition, it has been shown that two separate NF-kappaB pathways exist, depending on the activating signal and the cell type, the canonical (depending on IKKbeta and NEMO) and the noncanonical pathway (depending solely on IKKalpha). The main question, which is still only partially answered, is to understand how an NF-kappaB activating signal leads to the activation of the kinase subunits, allowing them to phosphorylate their targets and eventually induce nuclear translocation of the NF-kappaB dimers. I will review here the genetic, biochemical, and structural data accumulated during the last 10 yr regarding the function of the three IKK subunits.",
"title": "The IKK complex, a central regulator of NF-kappaB activation."
},
{
"docid": "3118719",
"text": "E-cadherin is best characterized as adherens junction protein, which through homotypic interactions contributes to the maintenance of the epithelial barrier function. In epithelial cells, the cytoplasmic tail of E-cadherin forms a dynamic complex with catenins and regulates several intracellular signal transduction pathways, including Wnt/β-catenin, PI3K/Akt, Rho GTPase, and NF-κB signaling. Recent progress uncovered a novel and critical role for this adhesion molecule in mononuclear phagocyte functions. E-cadherin regulates the maturation and migration of Langerhans cells, and its ligation prevents the induction of a tolerogenic state in bone marrow-derived dendritic cells (DCs). In this respect, the functionality of β-catenin could be instrumental in determining the balance between immunogenicity and tolerogenicity of DCs in vitro and in vivo. Fusion of alternatively activated macrophages and osteoclasts is also E-cadherin-dependent. In addition, the E-cadherin ligands CD103 and KLRG1 are expressed on DC-, T-, and NK-cell subsets and contribute to their interaction with E-cadherin-expressing DCs and macrophages. Here we discuss the regulation, function, and implications of E-cadherin expression in these central orchestrators of the immune system.",
"title": "Regulation and function of the E-cadherin/catenin complex in cells of the monocyte-macrophage lineage and DCs."
},
{
"docid": "3761017",
"text": "BACKGROUND Metformin, a widely used hypoglycemic drug, reduces stroke incidence and alleviates chronic inflammation in clinical trials. However, the effect of metformin in ischemic stroke is unclear. Here, we investigated the effect of metformin on ischemic stroke in mice and further explored the possible underlying mechanisms. METHODS Ninety-eight adult male CD-1 mice underwent 90-minute transient middle cerebral artery occlusion (tMCAO). Metformin (200 mg/kg) was administrated for up to 14 days. Neurobehavioral outcomes, brain infarct volume, inflammatory factors, blood-brain barrier (BBB) permeability and AMPK signaling pathways were evaluated following tMCAO. Oxygen glucose deprivation was performed on bEND.3 cells to explore the mechanisms of metformin in inhibiting inflammatory signaling pathways. RESULTS Infarct volume was reduced in metformin-treated mice compared to the control group following tMCAO (P < 0.05). Neurobehavioral outcomes were greatly improved in metformin-treated mice (P < 0.05). MPO+ cells, Gr1+ cells, MPO activity and BBB permeability were decreased after metformin administration (P < 0.05). In addition, metformin activated AMPK phosphorylation, inhibited NF-κB activation, down-regulated cytokine (IL-1β, IL-6, TNF-α) and ICAM-1 expression following tMCAO (P < 0.05). Furthermore, metformin activated AMPK signaling pathway and alleviated oxygen-glucose deprivation-induced ICAM-1 expression in bEND.3 cells (P < 0.05). Compound C, a selective AMPK inhibitor, eliminated this promotional effect. CONCLUSIONS Metformin down-regulated ICAM-1 in an AMPK-dependent manner, which could effectively prevent ischemia-induced brain injury by alleviating neutrophil infiltration, suggesting that metformin is a promising therapeutic agent in stroke therapy.",
"title": "Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion"
},
{
"docid": "30224907",
"text": "The c-Abl tyrosine kinase and its transforming variants have been implicated in tumorigenesis and in many important cellular processes. c-Abl is localized in the nucleus and the cytoplasm, where it plays distinct roles. The effects of c-Abl are mediated by multiple protein-protein and protein-DNA interactions and its tyrosine kinase domain. At the biochemical level, the mechanism of c-Abl kinase activation and the identification of its target proteins and cellular machineries have in part been solved. However, the phenotypic outcomes of these molecular events remained in large elusive. c-Abl has been shown to regulate the cell cycle and to induce under certain conditions cell growth arrest and apoptosis. In this respect the interaction of c-Abl with p53 and p73 has attracted particular attention. Recent findings have implicated c-Abl in an ionizing irradiation signaling pathway that elicits apoptosis. In this pathway p73 is an important immediate downstream effector. Here I review the current knowledge about these nuclear processes in which c-Abl is engaged and discuss some of their possible implications on cell physiology.",
"title": "c-Abl: activation and nuclear targets"
},
{
"docid": "12785130",
"text": "Src family kinases (SFKs) play critical roles in the regulation of many cellular functions by growth factors, G-protein-coupled receptors and ligand-gated ion channels. Recent data have shown that SFKs serve as a convergent point of multiple signaling pathways regulating N-methyl-d-aspartate (NMDA) receptors in the central nervous system. Multiple SFK molecules, such as Src and Fyn, closely associate with their substrate, NMDA receptors, via indirect and direct binding mechanisms. The NMDA receptor is associated with an SFK signaling complex consisting of SFKs; the SFK-activating phosphatase, protein tyrosine phosphatase α; and the SFK-inactivating kinase, C-terminal Src kinase. Early studies have demonstrated that intramolecular interactions with the SH2 or SH3 domain lock SFKs in a closed conformation. Disruption of the interdomain interactions can induce the activation of SFKs with multiple signaling pathways involved in regulation of this process. The enzyme activity of SFKs appears 'graded', exhibiting different levels coinciding with activation states. It has also been proposed that the SH2 and SH3 domains may stimulate catalytic activity of protein tyrosine kinases, such as Abl. Recently, it has been found that the enzyme activity of neuronal Src protein is associated with its stability, and that the SH2 and SH3 domain interactions may act not only to constrain the activation of neuronal Src, but also to regulate the enzyme activity of active neuronal Src. Collectively, these findings demonstrate novel mechanisms underlying the regulation of SFKs.",
"title": "The regulation of N-methyl-D-aspartate receptors by Src kinase."
},
{
"docid": "28644298",
"text": "Epstein-Barr virus (EBV) latency III infection converts B lymphocytes into lymphoblastoid cell lines (LCLs) by expressing EBV nuclear and membrane proteins, EBNAs, and latent membrane proteins (LMPs), which regulate transcription through Notch and tumor necrosis factor receptor pathways. The role of NF-kappa B in LMP1 and overall EBV latency III transcriptional effects was investigated by treating LCLs with BAY11-7082 (BAY11). BAY11 rapidly and irreversibly inhibited NF-kappa B, decreased mitochondrial membrane potential, induced apoptosis, and altered LCL gene expression. BAY11 effects were similar to those of an NF-kappa B inhibitor, Delta N-I kappa B alpha, in effecting decreased JNK1 expression and in microarray analyses. More than 80% of array elements that decreased with Delta N-I kappa B alpha expression decreased with BAY11 treatment. Newly identified NF-kappa B-induced, LMP1-induced, and EBV-induced genes included pleckstrin, Jun-B, c-FLIP, CIP4, and I kappa B epsilon. Of 776 significantly changed array elements, 134 were fourfold upregulated in EBV latency III, and 74 were fourfold upregulated with LMP1 expression alone, whereas only 28 were more than fourfold downregulated by EBV latency III. EBV latency III-regulated gene products mediate cell migration (EBI2, CCR7, RGS1, RANTES, MIP1 alpha, MIP1 beta, CXCR5, and RGS13), antigen presentation (major histocompatibility complex proteins and JAW1), mitogen-activated protein kinase pathway (DUSP5 and p62Dok), and interferon (IFN) signaling (IFN-gamma R alpha, IRF-4, and STAT1). Comparison of EBV latency III LCL gene expression to immunoglobulin M (IgM)-stimulated B cells, germinal-center B cells, and germinal-center-derived lymphomas clustered LCLs with IgM-stimulated B cells separately from germinal-center cells or germinal-center lymphoma cells. Expression of IRF-2, AIM1, ASK1, SNF2L2, and components of IFN signaling pathways further distinguished EBV latency III-infected B cells from IgM-stimulated or germinal-center B cells.",
"title": "Role of NF-kappa B in cell survival and transcription of latent membrane protein 1-expressing or Epstein-Barr virus latency III-infected cells."
},
{
"docid": "28006126",
"text": "CD28 is one of the most important costimulatory receptors necessary for full T lymphocyte activation. The CD28 receptor can enhance T cell antigen receptor (TCR) signals, as well as deliver independent signals. Indeed, CD28 engagement by B7 can generate TCR-independent signals leading to IkappaB kinase and NF-kappaB activation. Here we demonstrate that the TCR-independent CD28 signal leads to the selective transcription of survival (Bcl-xL) and inflammatory (IL-8 and B cell activation factor, but not proliferative (IL-2), genes, in a NF-kappaB-dependent manner. CD28-stimulated T cells actively secrete IL-8, and Bcl-xL up-regulation protects T cells from radiation-induced apoptosis. The transcription of CD28-induced genes is mediated by the specific recruitment of RelA and p52 NF-kappaB subunits to target promoters. In contrast, p50 and c-Rel, which preferentially bind NF-kappaB sites on the IL-2 gene promoter after anti-CD3 stimulation, are not involved. Thus, we identify CD28 as a key regulator of genes important for both survival and inflammation.",
"title": "CD28 delivers a unique signal leading to the selective recruitment of RelA and p52 NF-kappaB subunits on IL-8 and Bcl-xL gene promoters."
},
{
"docid": "3504761",
"text": "The MAP kinase kinase kinase TGFβ-activated kinase 1 (TAK1) is activated by TLRs, IL-1, TNF, and TGFβ and in turn activates IKK-NF-κB and JNK, which regulate cell survival, growth, tumorigenesis, and metabolism. TAK1 signaling also upregulates AMPK activity and autophagy. Here, we investigated TAK1-dependent regulation of autophagy, lipid metabolism, and tumorigenesis in the liver. Fasted mice with hepatocyte-specific deletion of Tak1 exhibited severe hepatosteatosis with increased mTORC1 activity and suppression of autophagy compared with their WT counterparts. TAK1-deficient hepatocytes exhibited suppressed AMPK activity and autophagy in response to starvation or metformin treatment; however, ectopic activation of AMPK restored autophagy in these cells. Peroxisome proliferator-activated receptor α (PPARα) target genes and β-oxidation, which regulate hepatic lipid degradation, were also suppressed in hepatocytes lacking TAK1. Due to suppression of autophagy and β-oxidation, a high-fat diet challenge aggravated steatohepatitis in mice with hepatocyte-specific deletion of Tak1. Notably, inhibition of mTORC1 restored autophagy and PPARα target gene expression in TAK1-deficient livers, indicating that TAK1 acts upstream of mTORC1. mTORC1 inhibition also suppressed spontaneous liver fibrosis and hepatocarcinogenesis in animals with hepatocyte-specific deletion of Tak1. These data indicate that TAK1 regulates hepatic lipid metabolism and tumorigenesis via the AMPK/mTORC1 axis, affecting both autophagy and PPARα activity.",
"title": "TAK1-mediated autophagy and fatty acid oxidation prevent hepatosteatosis and tumorigenesis."
},
{
"docid": "54482327",
"text": "Background/Aims: Osteoarthritis (OA) is a multifactorial disease that is associated with inflammation in joints. The purpose of the present study was to investigate the anti-inflammatory activity and mechanism of morin on human osteoarthritis chondrocytes stimulated by IL-1β. Methods: The levels of NO and PGE2 were measured by the Griess method and ELISA. The levels of MMP1, MMP3, and MMP13 were also measured by ELISA. Results: The results revealed that IL-1β significantly increased the production of NO, PGE2, MMP1, MMP3, and MMP13. Additionally, the increases were significantly attenuated by treatment with morin. Furthermore, IL-1β-induced NF-κB activation was suppressed by morin. In addition, the expression of Nrf2 and HO-1 were increased by morin and knockdown of Nrf2 could prevent the anti-inflammatory effects of morin. Conclusion: In conclusion, this study suggested that morin attenuated IL-1β-induced inflammation by activating the Nrf2 signaling pathway.",
"title": "Morin Exhibits Anti-Inflammatory Effects on IL-1β-Stimulated Human Osteoarthritis Chondrocytes by Activating the Nrf2 Signaling Pathway"
},
{
"docid": "27403802",
"text": "The NF-kappaB signaling pathway plays a crucial role in the immune, inflammatory, and apoptotic responses. Recently, we identified the NF-kappaB Essential Modulator (NEMO) as an essential component of this pathway. NEMO is a structural and regulatory subunit of the high molecular kinase complex (IKK) responsible for the phosphorylation of NF-kappaB inhibitors. Data base searching led to the isolation of a cDNA encoding a protein we called NRP (NEMO-related protein), which shows a strong homology to NEMO. Here we show that NRP is present in a novel high molecular weight complex, that contains none of the known members of the IKK complex. Consistently, we could not observe any effect of NRP on NF-kappaB signaling. Nonetheless, we could demonstrate that treatment with phorbol esters induces NRP phosphorylation and decreases its half-life. This phosphorylation event could only be inhibited by K-252a and stauroporin. We also show that de novo expression of NRP can be induced by interferon and tumor necrosis factor alpha and that these two stimuli have a synergistic effect on NRP expression. In addition, we observed that endogenous NRP is associated with the Golgi apparatus. Analogous to NEMO, we find that NRP is associated in a complex with two kinases, suggesting that NRP could play a similar role in another signaling pathway.",
"title": "Phorbol esters and cytokines regulate the expression of the NEMO-related protein, a molecule involved in a NF-kappa B-independent pathway."
},
{
"docid": "14615911",
"text": "We developed a novel mouse model of malignant pleural effusion (MPE) by injecting Lewis lung cancer (LLC) cells directly into the pleural space of syngeneic C57B/6 mice. The pleural effusions in this model share common cellular and biochemical features with human MPEs. Implantation and growth of pleural tumors triggers a host inflammatory response characterized by a mixed inflammatory cell influx into the pleural fluid. LLC cells exhibited high basal nuclear factor (NF)-κB activity in vitro and in vivo, which we used to drive expression of a NF-κB–dependent green fluorescent protein-firefly luciferase fusion reporter construct. NF-κB–dependent reporter expression allowed intravital tracing of pleural tumors. Inhibition of NF-κB in LLC cells did not affect cell viability in culture; however, injection of LLC cells expressing a dominant NF-κB inhibitor resulted in decreased tumor burden, decreased pleural effusion volume, and decreased pleural effusion TNF-α levels. These studies indicate that tumor NF-κB a...",
"title": "Nuclear Factor-�B Affects Tumor Progression in a Mouse Model of Malignant Pleural Effusion"
}
] |
391
|
Ethanol stress increases the expression of SRL in bacteria.
|
[
{
"docid": "1148122",
"text": "Understanding the genetic basis of adaptation is a central problem in biology. However, revealing the underlying molecular mechanisms has been challenging as changes in fitness may result from perturbations to many pathways, any of which may contribute relatively little. We have developed a combined experimental/computational framework to address this problem and used it to understand the genetic basis of ethanol tolerance in Escherichia coli. We used fitness profiling to measure the consequences of single-locus perturbations in the context of ethanol exposure. A module-level computational analysis was then used to reveal the organization of the contributing loci into cellular processes and regulatory pathways (e.g. osmoregulation and cell-wall biogenesis) whose modifications significantly affect ethanol tolerance. Strikingly, we discovered that a dominant component of adaptation involves metabolic rewiring that boosts intracellular ethanol degradation and assimilation. Through phenotypic and metabolomic analysis of laboratory-evolved ethanol-tolerant strains, we investigated naturally accessible pathways of ethanol tolerance. Remarkably, these laboratory-evolved strains, by and large, follow the same adaptive paths as inferred from our coarse-grained search of the fitness landscape.",
"title": "Regulatory and metabolic rewiring during laboratory evolution of ethanol tolerance in E. coli"
}
] |
[
{
"docid": "21602220",
"text": "The physiology of ethanologenic Escherichia coli grown anaerobically in alkali-pretreated plant hydrolysates is complex and not well studied. To gain insight into how E. coli responds to such hydrolysates, we studied an E. coli K-12 ethanologen fermenting a hydrolysate prepared from corn stover pretreated by ammonia fiber expansion. Despite the high sugar content (∼6% glucose, 3% xylose) and relatively low toxicity of this hydrolysate, E. coli ceased growth long before glucose was depleted. Nevertheless, the cells remained metabolically active and continued conversion of glucose to ethanol until all glucose was consumed. Gene expression profiling revealed complex and changing patterns of metabolic physiology and cellular stress responses during an exponential growth phase, a transition phase, and the glycolytically active stationary phase. During the exponential and transition phases, high cell maintenance and stress response costs were mitigated, in part, by free amino acids available in the hydrolysate. However, after the majority of amino acids were depleted, the cells entered stationary phase, and ATP derived from glucose fermentation was consumed entirely by the demands of cell maintenance in the hydrolysate. Comparative gene expression profiling and metabolic modeling of the ethanologen suggested that the high energetic cost of mitigating osmotic, lignotoxin, and ethanol stress collectively limits growth, sugar utilization rates, and ethanol yields in alkali-pretreated lignocellulosic hydrolysates.",
"title": "Complex physiology and compound stress responses during fermentation of alkali-pretreated corn stover hydrolysate by an Escherichia coli ethanologen."
},
{
"docid": "24019260",
"text": "Alcohol dependence is a disease that impacts millions of individuals worldwide. There has been some progress with pharmacotherapy for alcohol-dependent individuals; however, there remains a critical need for the development of novel and additional therapeutic approaches. Alcohol and nicotine are commonly abused together, and there is evidence that neuronal nicotinic acetylcholine receptors (nAChRs) play a role in both alcohol and nicotine dependence. Varenicline, a partial agonist at the alpha4beta2 nAChRs, reduces nicotine intake and was recently approved as a smoking cessation aid. We have investigated the role of varenicline in the modulation of ethanol consumption and seeking using three different animal models of drinking. We show that acute administration of varenicline, in doses reported to reduce nicotine reward, selectively reduced ethanol but not sucrose seeking using an operant self-administration drinking paradigm and also decreased voluntary ethanol but not water consumption in animals chronically exposed to ethanol for 2 months before varenicline treatment. Furthermore, chronic varenicline administration decreased ethanol consumption, which did not result in a rebound increase in ethanol intake when the varenicline was no longer administered. The data suggest that the alpha4beta2 nAChRs may play a role in ethanol-seeking behaviors in animals chronically exposed to ethanol. The selectivity of varenicline in decreasing ethanol consumption combined with its reported safety profile and mild side effects in humans suggest that varenicline may prove to be a treatment for alcohol dependence.",
"title": "Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking."
},
{
"docid": "471735",
"text": "Escherichia coli responds to the redox stress imposed by superoxide-generating agents such as paraquat by activating the synthesis of as many as 80 polypeptides. Expression of a key group of these inducible proteins is controlled at the transcriptional level by the soxRS locus (the soxRS regulon). A two-stage control system was hypothesized for soxRS, in which an intracellular redox signal would trigger the SoxR protein as a transcriptional activator of the soxS gene and the resulting increased levels of SoxS protein would activate transcription of the various soxRS regulon genes (B. Demple and C.F. Amábile Cuevas, Cell 67:837-839, 1990). We have constructed operon fusions of the E. coli lac genes to the soxS promoter to monitor soxS transcription. Expression from the soxS promoter is strongly inducible by paraquat in a manner strictly dependent on a functional soxR gene. Several other superoxide-generating agents also trigger soxR(+)-dependent soxS expression, and the inductions by paraquat and phenazine methosulfate were dependent on the presence of oxygen. Numerous other oxidative stress agents (H2O2, gamma rays, heat shock, etc.) failed to induce soxS, while aerobic growth of superoxide dismutase-deficient bacteria triggered soxR-dependent soxS expression. These results indicate a specific redox signal for soxS induction. A direct role for SoxR protein in the activation of the soxS gene is indicated by band-shift and DNase I footprinting experiments that demonstrate specific binding of the SoxR protein in cell extracts to the soxS promoter. The mode of SoxR binding to DNA appears to be similar to that of its homolog MerR in that the SoxR footprint spans the -10 to -35 region of the soxS promoter.",
"title": "Two-stage control of an oxidative stress regulon: the Escherichia coli SoxR protein triggers redox-inducible expression of the soxS regulatory gene."
},
{
"docid": "28025754",
"text": "TO enable staining of insoluble calcium salts with glyoxal bis(2-hydroxyanil) (GBHA), the original solution containing 2 ml of 0.4% GBHA in absolute ethanol, and 0.3 ml of aqueous 5% NaOH, and limited to staining only soluble calcium salts, was modified as follows: 1, 2 ml of 0.4% GBHA in absolute ethanol in 0.6 ml of 10% aqueous NaOH; 11, 0.1 gm GBHA in 2 ml of 3.4% NaOH in 75% ethanol. To prevent diffusion and loss of calcium, the tissues were processed by the freeze-substitution or freeze-dry method and sections stained without removing the paraffin. Modification I is effective only when 1 or 2 drops placed on the section are evaporated gradually to dryness, concentrating the GBHA and NaOH on the insoluble calcium salts. Modification II is effective when dried or poured on the the section and allowed to stain for 5 min. The stained slides are immersed for 15 min in 90% ethanol saturated with KCN and Na2CO3 for specificity to calcium; rinsed and counterstained in 95% ethanol containing 0.1% each of fast...",
"title": "THE GLYOXAL BIS(2-HYDROXYANIL) METHOD MODIFIED FOR LOCALIZING INSOLUBLE CALCIUM SALTS."
},
{
"docid": "22908536",
"text": "Nonreplicating and metabolically quiescent bacteria are implicated in latent tuberculosis infections and relapses following \"sterilizing\" chemotherapy. However, evidence linking bacterial dormancy and persistence in vivo is largely inconclusive. Here we measure the single-cell dynamics of Mycobacterium tuberculosis replication and ribosomal activity using quantitative time-lapse microscopy and a reporter of ribosomal RNA gene expression. Single-cell dynamics exhibit heterogeneity under standard growth conditions, which is amplified by stressful conditions such as nutrient limitation, stationary phase, intracellular replication, and growth in mouse lungs. Additionally, the lungs of chronically infected mice harbor a subpopulation of nongrowing but metabolically active bacteria, which are absent in mice lacking interferon-γ, a cytokine essential for antituberculosis immunity. These cryptic bacterial forms are prominent in mice treated with the antituberculosis drug isoniazid, suggesting a role in postchemotherapeutic relapses. Thus, amplification of bacterial phenotypic heterogeneity in response to host immunity and drug pressure may contribute to tuberculosis persistence.",
"title": "Stress and host immunity amplify Mycobacterium tuberculosis phenotypic heterogeneity and induce nongrowing metabolically active forms."
},
{
"docid": "6251620",
"text": "Antineutrophil cytoplasmic antibodies (ANCA) are a sensitive and specific marker for ANCA-associated systemic vasculitis. Using indirect immunofluorescence on ethanol-fixed neutrophils, two major fluoroscopic patterns can be recognised: a diffuse cytoplasmic staining (C-ANCA), and a perinuclear/nuclear staining (P-ANCA). In patients with vasculitis, more of 90% of C-ANCA are directed against proteinase 3 (PR3-ANCA) whereas approximately 80-90% of P-ANCA recognise myelperoxidase (MPO-ANCA). Although C-ANCA (PR3-ANCA) is preferentially associated with Wegener's granulomatosis (WG), and P-ANCA (MPO-ANCA) with microscopic polyangiitis (MPA), idiopathic necrotising crescentic glomerulonephritis (iNCGN) and Churg-Strauss syndrome (CSS), there is not absolute specificity. Between 10-20% of patients with classical WG show P-ANCA (MPO-ANCA), and even a larger percentage of patients with MPA or CSS have C-ANCA (PR3-ANCA). Furthermore, it should be stressed that approximately 10-20% of patients with WG or MPA (and 40-50% of cases of CSS) have negative assay for ANCA. The best diagnostic performance is obtained when indirect immunofluorescence is combined with PR3 and MPO-specific ELISAs. ANCA with different and unknown antigen specificity are found in a variety of conditions other than AASV, including inflammatory bowel diseases, other autoimmune diseases, and infections where their clinical significance is unclear. ANCA levels are useful to monitor disease activity but should not be used by themselves to guide treatment. A significant increase in ANCA titres, or the reappearance of ANCA, should alert the clinicians and lead to a stricter patient control.",
"title": "Antineutrophil cytoplasmic antibodies (ANCA)."
},
{
"docid": "4641348",
"text": "BACKGROUND/OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is closely associated with metabolic syndrome. In the present study, we observed the effect of ethanol extract of Allium fistulosum (EAF) on NAFLD and have suggested the possibility of using EAF as a natural product for application in the development of a treatment for NAFLD. MATERIALS/METHODS The preventive effect on hepatic lipid accumulation was estimated by using an oleic acid (OA)-induced NAFLD model in vitro and a Western diet (high-fat high-sucrose; WD)-induced obese mouse model. Animals were divided into three groups (n = 7): normal diet group (ND), WD group, and WD plus 1% EAF group. RESULTS EAF reduced OA-stimulated lipid accumulation in HepG2 cells in the absence of cellular cytotoxicity and significantly blocked transcriptional activation of sterol regulatory element-binding protein 1 and fatty acid synthase genes. Subsequently, we investigated these effects in vivo in mice fed either ND or WD in the presence or absence of EAF supplementation. In comparison to the ND controls, the WD-fed mice exhibited increases in body weight, liver weight, epididymal fat weight, and accumulation of fat in hepatocytes, and these effects were significantly attenuated by EAF supplementation. CONCLUSIONS Allium fistulosum attenuates the development of NAFLD, and EAF elicits anti-lipogenic activity in liver. Therefore, EAF represents a promising candidate for use in the development of novel therapeutic drugs or drug combinations for the prevention and treatment of NAFLD.",
"title": "Ethanol extract of Allium fistulosum inhibits development of non-alcoholic fatty liver disease"
},
{
"docid": "21373821",
"text": "A series of 33 patients with combined (injurious) sleepwalking, sleep terrors, and rapid eye movement (REM) sleep behavior disorder (viz. \"parasomnia overlap disorder\") was gathered over an 8-year period. Patients underwent clinical and polysomnographic evaluations. Mean age was 34 +/- 14 (SD) years; mean age of parasomnia onset was 15 +/- 16 years (range 1-66); 70% (n = 23) were males. An idiopathic subgroup (n = 22) had a significantly earlier mean age of parasomnia onset (9 +/- 7 years) than a symptomatic subgroup (n = 11) (27 +/- 23 years, p = 0.002), whose parasomnia began with either of the following: neurologic disorders, n = 6 [congenital Mobius syndrome, narcolepsy, multiple sclerosis, brain tumor (and treatment), brain trauma, indeterminate disorder (exaggerated startle response/atypical cataplexy)]; nocturnal paroxysmal atrial fibrillation, n = 1; posttraumatic stress disorder/major depression, n = 1; chronic ethanol/amphetamine abuse and withdrawal, n = 1; or mixed disorders (schizophrenia, brain trauma, substance abuse), n = 2. The rate of DSM-III-R (Diagnostic and Statistical Manual, 3rd edition, revised) Axis 1 psychiatric disorders was not elevated; group scores on various psychometric tests were not elevated. Forty-five percent (n = 15) had previously received psychologic or psychiatric therapy for their parasomnia, without benefit. Treatment outcome was available for n = 20 patients; 90% (n = 18) had substantial parasomnia control with bedtime clonazepam (n = 13), alprazolam and/or carbamazepine (n = 4), or self-hypnosis (n = 1). Thus, \"parasomnia overlap disorder\" is a treatable condition that emerges in various clinical settings and can be understood within the context of current knowledge on parasomnias and motor control/dyscontrol during sleep.",
"title": "A parasomnia overlap disorder involving sleepwalking, sleep terrors, and REM sleep behavior disorder in 33 polysomnographically confirmed cases."
},
{
"docid": "27396415",
"text": "OBJECTIVE To establish high cell density cultivation process of recombinant Helicobacter pylori multi-epitope vaccine engineering bacteria BIB. METHODS Based on the results of shake flask fermentation, the process was magnified into volume of a 50 L fermenter to optimize and verify the factors affecting the yield of the target protein, such as the fermentation medium, working seed inoculation amount, inducer concentration, induction starting time, induction duration, inducer adding mode and feeding strategy. RESULTS After activated in modified TB medium at 37°C for 8 h, the BIB working seed was inoculated at 5% (v/v) and was induced for expression for another 11 h by the final concentration of 5 mmol/L lactose. In growth phase, glucose at rate of 80 ml/h was used as carbon source, and in induction phase, glycerol at rate of 40 ml/h was used as carbon source; ammonia water was added dropwise to control pH at about 7.0, and revolution speed is adjusted to control the dissolved oxygen at above 30%; ultimately the output of bacterial body was 70 g/L and protein expression amount was about 32%. CONCLUSION After high cell density cultivation of the recombinant engineering bacteria, expression and yield of the target protein rBIB significantly increased.",
"title": "A study of high cell density cultivation process of recombinant Helicobacter pylori multi-epitope vaccine engineering bacteria."
},
{
"docid": "25293721",
"text": "Placental oxidative stress plays a key role in the pathophysiology of placenta-related disorders, most notably preeclampsia (PE) and intrauterine growth restriction (IUGR). Oxidative stress occurs when accumulation of reactive oxygen species (ROS) damages DNA, proteins and lipids, an outcome that is limited by antioxidant enzymes; mitochondrial uncoupling protein 2 (UCP2) may also limit oxidative stress by reducing ROS production. Here we characterized placental antioxidant defenses during normal gestation and following glucocorticoid-induced IUGR. Placentas were collected on Days 16 and 22 of normal rat pregnancy (term = Day 23) and at Day 22 after dexamethasone treatment from Day 13. Expression of several genes encoding antioxidant enzymes (Sod1, Sod2, Sod3, Cat, Gpx3, Txn1, Txnrd1, Txnrd2, and Txnrd3) and Ucp2 was measured by quantitative RT-PCR in the labyrinth (LZ) and junctional zones (JZ) of the placenta. Expression of Sod1 and Ucp2 mRNAs and the activity of xanthine oxidase, a source of ROS, all increased from Days 16 to 22 in both placental zones, whereas Sod2 and Gpx3 increased only in the rapidly growing LZ. In contrast, Sod3 and Txnrd1 expression fell in the LZ over this period, whereas total superoxide dismutase activity remained stable. Dexamethasone treatment reduced fetal-placental growth and LZ expression of Ucp2 but increased JZ expression of Txn1. Indices of placental oxidative damage (TBARS, F2-isoprostanes, and 8-OHdG) did not change with gestational age or dexamethasone, indicative of adequate antioxidant protection. Overall, our data suggest that the rat placenta is protected from oxidative stress by the dynamic zone- and stage-dependent expression of antioxidant defense genes.",
"title": "Antioxidant Defenses in the Rat Placenta in Late Gestation: Increased Labyrinthine Expression of Superoxide Dismutases, Glutathione Peroxidase 3, and Uncoupling Protein 21"
},
{
"docid": "25510546",
"text": "Increased lipid supply causes beta cell death, which may contribute to reduced beta cell mass in type 2 diabetes. We investigated whether endoplasmic reticulum (ER) stress is necessary for lipid-induced apoptosis in beta cells and also whether ER stress is present in islets of an animal model of diabetes and of humans with type 2 diabetes. Expression of genes involved in ER stress was evaluated in insulin-secreting MIN6 cells exposed to elevated lipids, in islets isolated from db/db mice and in pancreas sections of humans with type 2 diabetes. Overproduction of the ER chaperone heat shock 70 kDa protein 5 (HSPA5, previously known as immunoglobulin heavy chain binding protein [BIP]) was performed to assess whether attenuation of ER stress affected lipid-induced apoptosis. We demonstrated that the pro-apoptotic fatty acid palmitate triggers a comprehensive ER stress response in MIN6 cells, which was virtually absent using non-apoptotic fatty acid oleate. Time-dependent increases in mRNA levels for activating transcription factor 4 (Atf4), DNA-damage inducible transcript 3 (Ddit3, previously known as C/EBP homologous protein [Chop]) and DnaJ homologue (HSP40) C3 (Dnajc3, previously known as p58) correlated with increased apoptosis in palmitate- but not in oleate-treated MIN6 cells. Attenuation of ER stress by overproduction of HSPA5 in MIN6 cells significantly protected against lipid-induced apoptosis. In islets of db/db mice, a variety of marker genes of ER stress were also upregulated. Increased processing (activation) of X-box binding protein 1 (Xbp1) mRNA was also observed, confirming the existence of ER stress. Finally, we observed increased islet protein production of HSPA5, DDIT3, DNAJC3 and BCL2-associated X protein in human pancreas sections of type 2 diabetes subjects. Our results provide evidence that ER stress occurs in type 2 diabetes and is required for aspects of the underlying beta cell failure.",
"title": "Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes"
},
{
"docid": "44562221",
"text": "Endogenous glucocorticoids (GC) play an important role in the termination of the inflammatory response following infection and tissue injury. However, recent findings indicate that stress can impair the anti-inflammatory capacities of these hormones. Lipopolysaccharide (LPS)-stimulated splenocytes of mice that were repeatedly subjected to social disruption (SDR) stress were less sensitive to the immunosuppressive effects of corticosterone (CORT) as demonstrated by an increased production of pro-inflammatory cytokines and enhanced cell survival. Myeloid cells expressing the marker CD11b were shown to play a key role in this process. Here we investigated the role of the bone marrow as a potential source of the GC-insensitive cells. The study revealed that LPS-stimulated bone marrow cells, in the absence of experimental stress, were virtually GC-resistant and retained high levels of cell viability after treatment with CORT. Recurrent exposure to the acute stressor over a period of 2, 4 or 6 days led to an increase in the GC sensitivity of the bone marrow cells. This increase in GC sensitivity was associated with enhanced mRNA expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), an increase in the number of myeloid progenitors, and a decrease in the proportion of mature CD11b+ cells. The changes in the cellular composition of the bone marrow were accompanied by an increase in splenic CD11b+ cell numbers. Simultaneous assessment of the GC sensitivity in bone marrow and spleen revealed a significant negative correlation between both tissues suggesting that social stress causes the redistribution of GC-insensitive myeloid cells from the bone marrow to the spleen.",
"title": "Tissue-specific alterations in the glucocorticoid sensitivity of immune cells following repeated social defeat in mice"
},
{
"docid": "9588931",
"text": "Vascular calcification is a strong independent predictor of increased cardiovascular morbidity and mortality and has a high prevalence among patients with chronic kidney disease. The present study investigated the effects of quercetin on vascular calcification caused by oxidative stress and abnormal mitochondrial dynamics both in vitro and in vivo. Calcifying vascular smooth muscle cells (VSMCs) treated with inorganic phosphate (Pi) exhibited mitochondrial dysfunction, as demonstrated by decreased mitochondrial potential and ATP production. Disruption of mitochondrial structural integrity was also observed in a rat model of adenine-induced aortic calcification. Increased production of reactive oxygen species, enhanced expression and phosphorylation of Drp1, and excessive mitochondrial fragmentation were also observed in Pi-treated VSMCs. These effects were accompanied by mitochondria-dependent apoptotic events, including release of cytochrome c from the mitochondria into the cytosol and subsequent activation of caspase-3. Quercetin was shown to block Pi-induced apoptosis and calcification of VSMCs by inhibiting oxidative stress and decreasing mitochondrial fission by inhibiting the expression and phosphorylation of Drp1. Quercetin also significantly ameliorated adenine-induced aortic calcification in rats. In summary, our findings suggest that quercetin attenuates calcification by reducing apoptosis of VSMCs by blocking oxidative stress and inhibiting mitochondrial fission.",
"title": "Quercetin attenuates vascular calcification by inhibiting oxidative stress and mitochondrial fission."
},
{
"docid": "12658073",
"text": "The gut microbiota has been proposed as an environmental factor that affects the development of metabolic and inflammatory diseases in mammals. Recent reports indicate that gut bacteria-derived lipopolysaccharide (LPS) can initiate obesity and insulin resistance in mice; however, the molecular interactions responsible for microbial regulation of host metabolism and mediators of inflammation have not been studied in detail. Hepatic serum amyloid A (SAA) proteins are markers and proposed mediators of inflammation that exhibit increased levels in serum of insulin-resistant mice. Adipose tissue-derived SAA3 displays monocyte chemotactic activity and may play a role in metabolic inflammation associated with obesity and insulin resistance. To investigate a potential mechanistic link between the intestinal microbiota and induction of proinflammatory host factors, we performed molecular analyses of germ-free, conventionally raised and genetically modified Myd88-/- mouse models. SAA3 expression was determined to be significantly augmented in adipose (9.9+/-1.9-fold; P<0.001) and colonic tissue (7.0+/-2.3-fold; P<0.05) by the presence of intestinal microbes. In the colon, we provided evidence that SAA3 is partially regulated through the Toll-like receptor (TLR)/MyD88/NF-kappaB signaling axis. We identified epithelial cells and macrophages as cellular sources of SAA3 in the colon and found that colonic epithelial expression of SAA3 may be part of an NF-kappaB-dependent response to LPS from gut bacteria. In vitro experiments showed that LPS treatments of both epithelial cells and macrophages induced SAA3 expression (27.1+/-2.5-fold vs. 1.6+/-0.1-fold, respectively). Our data suggest that LPS, and potentially other products of the indigenous gut microbiota, might elevate cytokine expression in tissues and thus exacerbate chronic low-grade inflammation observed in obesity.",
"title": "Regulation of Serum Amyloid A3 (SAA3) in Mouse Colonic Epithelium and Adipose Tissue by the Intestinal Microbiota"
},
{
"docid": "12903921",
"text": "It has been proved that oxidative stress increases when leukemia is accompanied by depression. This fact may indicate the role of oxidative stress in the development of depression in cancer patients. The aim of this study was to determine whether the acute myeloid leukemia of Brown Norway rats, which is accompanied by oxidative stress, evoked behavioral and receptor changes resembling alterations characteristic of rat models of depression. The rats were divided into two groups: leukemic rats and healthy control. Leukemia was induced through intraperitoneal injection of 10(7) promyelocytic leukemia cells to the Brown Norway rats. Depression-like behavior was evaluated in the forced swim test at 30 or 34 days after leukemic cells injection. The rats were killed after the evaluation and the spleen, brain cortex and hippocampus were excised. The red-ox state was assessed in homogenates of tissues by measuring total glutathione (GSH) content, the ferric ion reducing ability of plasma (FRAP) level, expression of heme oxygenase-1 (HO-1), biliverdin reductase (BvR) and ferritin mRNA, superoxide dismutase (SOD) activity, as well as malondialdehyde (MDA) concentration. Radioligand binding assay was used to assess of the effect of leukemia on cortical receptors. Leukemic cells were identified using RM-124 antibody by FACS Calibur flow cytometry. Leukemia influenced locomotory activity as well as forced swim test behavior in a 34-day series of experiments. Signs of oxidative stress in leukemic rats were observed in each examined stage of leukemia development. The FRAP values and glutathione contents, were significantly lowered whereas HO-1 mRNA expression, and malonodialdehyde concentrations were significantly increased in the spleen and brain structures of leukemic rats in comparison with the healthy controls. A significant increase in the potency of glycine to displace [(3)H]L-689,560 from the strychnine-insensitive glycine site of the N-methyl-D-aspartic (NMDA) receptors receptor complex in cortical homogenates of the leukemic rats in 30- and 34-day experimental series was observed in comparison with the control. Upregulation of 5-HT(2A) receptors was observed in rat cortex after 30 days of leukemia development but not in 34-days series compared with the control. It is concluded that disturbances in antioxidant system in brain cortex were accompanied by an activation of glycine sites of the NMDA receptor complex, regardless of stage of leukemia development, which are characteristic of model of depression. Findings of our study demonstrate the link between glutamatergic activity, oxidative stress and leukemia.",
"title": "Evaluation of oxidative status and depression-like responses in Brown Norway rats with acute myeloid leukemia"
},
{
"docid": "28517384",
"text": "Myeloid differentiation factor-2 (MD-2) is a lipopolysaccharide (LPS)-binding protein usually coexpressed with and binding to Toll-like receptor 4 (TLR4), conferring LPS responsiveness of immune cells. MD-2 is also found as a soluble protein. Soluble MD-2 (sMD-2) levels are markedly elevated in plasma from patients with severe infections, and in other fluids from inflamed tissues. We show that sMD-2 is a type II acute-phase protein. Soluble MD-2 mRNA and protein levels are up-regulated in mouse liver after the induction of an acute-phase response. It is secreted by human hepatocytic cells and up-regulated by interleukin-6. Soluble MD-2 binds to Gram-negative but not Gram-positive bacteria, and sMD-2 secreted by hepatocytic cells is an essential cofactor for the activation of TLR4-expressing cells by Gram-negative bacteria. Soluble MD-2 opsonization of Gram-negative bacteria accelerates and enhances phagocytosis, principally by polymorphonuclear neutrophils. In summary, our results demonstrate that sMD-2 is a newly recognized type II acute-phase reactant, an opsonin for Gram-negative bacteria, and a cofactor essential for the activation of TLR4-expressing cells. This suggests that sMD-2 plays a key role in the host innate immune response to Gram-negative infections.",
"title": "Soluble MD-2 is an acute-phase protein and an opsonin for Gram-negative bacteria."
},
{
"docid": "7506409",
"text": "Human mesenchymal stem cells (hMSCs) have been widely studied as a source of primary adult stem cells for cell therapy because of their multidifferentiation potential; however, the growth arrest (also known as \"premature senescence\") often found in hMSCs cultured in vitro has been a major obstacle to the in-depth characterization of these cells. In addition, the inability to maintain constant cell growth hampers the development of additional genetic modifications aimed at achieving desired levels of differentiation to specific tissues; however, the molecular mechanisms that govern this phenomenon remain unclear, with the exception of a few studies demonstrating that induction of p16INK4a is responsible for this senescence-like event. Here, we observed that the premature growth arrest in hMSCs occurs in parallel with the induction of p16INK4a, following abrogation of inhibitory phosphorylation of retinoblastoma protein. These stress responses were concurrent with increased formation of reactive oxygen species (ROSs) from mitochondria and increased p38 mitogen-activated protein kinase (MAPK) activity. The introduction of Wip1 (wild-type p53 inducible phosphatase-1), a well-studied stress modulator, significantly lowered p16INK4a expression and led to p38 MAPK inactivation, although it failed to affect the levels of ROSs. Moreover, the suppression of stress responses by Wip1 apparently extended the life span of hMSCs, compared with control conditions, while maintaining their multilineage differentiation potential. Based on these results, we suggest that senescent growth arrest in hMSCs may result from activation of stress signaling pathways and consequent onset of stress responses, due in part to ROS production during prolonged in vitro culture.",
"title": "Senescent growth arrest in mesenchymal stem cells is bypassed by Wip1-mediated downregulation of intrinsic stress signaling pathways."
},
{
"docid": "24349992",
"text": "Loss of stromal fibroblast caveolin-1 (Cav-1) is a powerful single independent predictor of poor prognosis in human breast cancer patients, and is associated with early tumor recurrence, lymph node metastasis and tamoxifen-resistance. We developed a novel co-culture system to understand the mechanism(s) by which a loss of stromal fibroblast Cav-1 induces a \"lethal tumor micro-environment. \" Here, we propose a new paradigm to explain the powerful prognostic value of stromal Cav-1. In this model, cancer cells induce oxidative stress in cancer-associated fibroblasts, which then acts as a \"metabolic\" and \"mutagenic\" motor to drive tumor-stroma co-evolution, DNA damage and aneuploidy in cancer cells. More specifically, we show that an acute loss of Cav-1 expression leads to mitochondrial dysfunction, oxidative stress and aerobic glycolysis in cancer associated fibroblasts. Also, we propose that defective mitochondria are removed from cancer-associated fibroblasts by autophagy/mitophagy that is induced by oxidative stress. As a consequence, cancer associated fibroblasts provide nutrients (such as lactate) to stimulate mitochondrial biogenesis and oxidative metabolism in adjacent cancer cells (the \"Reverse Warburg Effect\"). We provide evidence that oxidative stress in cancer-associated fibroblasts is sufficient to induce genomic instability in adjacent cancer cells, via a bystander effect, potentially increasing their aggressive behavior. Finally, we directly demonstrate that nitric oxide (NO) over-production, secondary to Cav-1 loss, is the root cause for mitochondrial dysfunction in cancer associated fibroblasts. In support of this notion, treatment with anti-oxidants (such as N-acetyl-cysteine, metformin and quercetin) or NO inhibitors (L-NAME) was sufficient to reverse many of the cancer-associated fibroblast phenotypes that we describe. Thus, cancer cells use \"oxidative stress\" in adjacent fibroblasts (i) as an \"engine\" to fuel their own survival via the stromal production of nutrients and (ii) to drive their own mutagenic evolution towards a more aggressive phenotype, by promoting genomic instability. We also present evidence that the \"field effect\" in cancer biology could also be related to the stromal production of ROS and NO species. eNOS-expressing fibroblasts have the ability to downregulate Cav-1 and induce mitochondrial dysfunction in adjacent fibroblasts that do not express eNOS. As such, the effects of stromal oxidative stress can be laterally propagated, amplified and are effectively \"contagious\"--spread from cell-to-cell like a virus--creating an \"oncogenic/mutagenic\" field promoting widespread DNA damage.",
"title": "Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells."
},
{
"docid": "12909503",
"text": "DNA damage encountered by DNA replication forks poses risks of genome destabilization, a precursor to carcinogenesis. Damage checkpoint systems cause cell cycle arrest, promote repair and induce programed cell death when damage is severe. Checkpoints are critical parts of the DNA damage response network that act to suppress cancer. DNA damage and perturbation of replication machinery causes replication stress, characterized by accumulation of single-stranded DNA bound by replication protein A (RPA), which triggers activation of ataxia telangiectasia and Rad3 related (ATR) and phosphorylation of the RPA32, subunit of RPA, leading to Chk1 activation and arrest. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) [a kinase related to ataxia telangiectasia mutated (ATM) and ATR] has well characterized roles in DNA double-strand break repair, but poorly understood roles in replication stress-induced RPA phosphorylation. We show that DNA-PKcs mutant cells fail to arrest replication following stress, and mutations in RPA32 phosphorylation sites targeted by DNA-PKcs increase the proportion of cells in mitosis, impair ATR signaling to Chk1 and confer a G2/M arrest defect. Inhibition of ATR and DNA-PK (but not ATM), mimic the defects observed in cells expressing mutant RPA32. Cells expressing mutant RPA32 or DNA-PKcs show sustained H2AX phosphorylation in response to replication stress that persists in cells entering mitosis, indicating inappropriate mitotic entry with unrepaired damage.",
"title": "Distinct roles for DNA-PK, ATM and ATR in RPA phosphorylation and checkpoint activation in response to replication stress"
},
{
"docid": "6259170",
"text": "Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) was originally identified as a positive regulator of drug detoxifying enzyme gene expression during exposure to environmental electrophiles. Currently, Nrf2 is known to regulate the expression of hundreds of cytoprotective genes to counteract endogenously or exogenously generated oxidative stress. Furthermore, when activated in human tumors by somatic mutations, Nrf2 confers growth advantages and chemoresistance by regulating genes involved in various processes such as the pentose phosphate pathway and nucleotide synthesis in addition to antioxidant proteins. Interestingly, increasing evidence shows that Nrf2 is associated with mitochondrial biogenesis during environmental stresses in certain tissues such as the heart. Furthermore, SKN-1, a functional homolog of Nrf2 in C. elegans, is activated by mitochondrial reactive oxygen species and extends life span by promoting mitochondrial homeostasis (i.e., mitohormesis). Similarly, Nrf2 activation was recently observed in the heart of surfeit locus protein 1 (Surf1) -/- mice in which cellular respiration was decreased due to cytochrome c oxidase defects. In this review, we critically examine the relationship between Nrf2 and mitochondria and argue that the Nrf2 stress pathway intimately communicates with mitochondria to maintain cellular homeostasis during oxidative stress.",
"title": "Emerging functional cross-talk between the Keap1-Nrf2 system and mitochondria"
},
{
"docid": "3943235",
"text": "During physiological or psychological stress, catecholamines produced by the sympathetic nervous system (SNS) regulate the immune system. Previous studies report that the activation of β-adrenergic receptors (βARs) mediates the actions of catecholamines and increases pro-inflammatory cytokine production in a number of different cell types. The impact of the SNS on the immune modulation of social defeat has not been examined. The following studies were designed to determine whether SNS activation during social disruption stress (SDR) influences anxiety-like behavior as well as the activation, priming, and glucocorticoid resistance of splenocytes after social stress. CD-1 mice were exposed to one, three, or six cycles of SDR and HPLC analysis of the plasma and spleen revealed an increase in catecholamines. After six cycles of SDR the open field test was used to measure behaviors characteristic of anxiety and indicated that the social defeat induced increase in anxiety-like behavior was blocked by pre-treatment with the β-adrenergic antagonist propranolol. Pre-treatment with the β-adrenergic antagonist propranolol did not significantly alter corticosterone levels indicating no difference in activation of the hypothalamic-pituitary-adrenal axis. In addition to anxiety-like behavior the SDR induced splenomegaly and increase in plasma IL-6, TNFα, and MCP-1 were each reversed by pre-treatment with propranolol. Furthermore, flow cytometric analysis of cells from propranolol pretreated mice reduced the SDR-induced increase in the percentage of CD11b(+) splenic macrophages and significantly decreased the expression of TLR2, TLR4, and CD86 on the surface of these cells. In addition, supernatants from 18h LPS-stimulated ex vivo cultures of splenocytes from propranolol-treated SDR mice contained less IL-6. Likewise propranolol pre-treatment abrogated the glucocorticoid insensitivity of CD11b(+) cells ex vivo when compared to splenocytes from SDR vehicle-treated mice. Together, this study demonstrates that the immune activation and priming effects of SDR result, in part, as a consequence of SNS activation.",
"title": "Beta adrenergic blockade decreases the immunomodulatory effects of social disruption stress"
},
{
"docid": "22153455",
"text": "Although gram-positive infections account for the majority of cases of sepsis, the molecular mechanisms underlying their effects remains poorly understood. We investigated how cell wall components of gram-positive bacteria contribute to the development of sepsis. Experimental observations derived from cultured primary macrophages and the cell line indicate that gram-positive bacterial endotoxins induce hypoxia-inducible factor 1α (HIF-1α) mRNA and protein expression. Inoculation of live or heat-inactivated gram-positive bacteria with macrophages induced HIF-1 transcriptional activity in macrophages. Concordant with these results, myeloid deficiency of HIF-1α attenuated gram-positive bacterial endotoxin-induced cellular motility and proinflammatory gene expression in macrophages. Conversely, gram-positive bacteria and their endotoxins reduced expression of the myeloid anti-inflammatory transcription factor Krüppel-like transcription factor 2 (KLF2). Sustained expression of KLF2 reduced and deficiency of KLF2 enhanced gram-positive endotoxins induced HIF-1α mRNA and protein expression in macrophages. More importantly, KLF2 attenuated gram-positive endotoxins induced cellular motility and proinflammatory gene expression in myeloid cells. Consistent with these results, mice deficient in myeloid HIF-1α were protected from gram-positive endotoxin-induced sepsis mortality and clinical symptomatology. By contrast, myeloid KLF2-deficient mice were susceptible to gram-positive sepsis induced mortality and clinical symptoms. Collectively, these observations identify HIF-1α and KLF2 as critical regulators of gram-positive endotoxin-mediated sepsis.",
"title": "A myeloid hypoxia-inducible factor 1α-Krüppel-like factor 2 pathway regulates gram-positive endotoxin-mediated sepsis."
},
{
"docid": "1887056",
"text": "OBJECTIVE The authors sought to determine innate immune system activation following psychosocial stress in patients with major depression and increased early life stress. METHOD Plasma interleukin (IL)-6, lymphocyte subsets, and DNA binding of nuclear factor (NF)-kB in peripheral blood mononuclear cells were compared in medically healthy male subjects with current major depression and increased early life stress (N=14) versus nondepressed male comparison subjects (N=14) before and after completion of the Trier Social Stress Test. RESULTS Trier Social Stress Test-induced increases in IL-6 and NF-kappaB DNA-binding were greater in major depression patients with increased early life stress and independently correlated with depression severity, but not early life stress. Natural killer (NK) cell percentages also increased following stress. However, there were no differences between groups and no correlation between NK cell percentage and stress-induced NF-kappaB DNA-binding or IL-6. CONCLUSIONS Male major depression patients with increased early life stress exhibit enhanced inflammatory responsiveness to psychosocial stress, providing preliminary indication of a link between major depression, early life stress and adverse health outcomes in diseases associated with inflammation.",
"title": "Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress."
},
{
"docid": "16546131",
"text": "Hydroxyurea is a potent teratogen; free radical scavengers or antioxidants reduce its teratogenicity. Activator Protein-1 (AP-1) and NF-kappaB are redox-sensitive transcription factors with important roles in normal development and the stress response. This study was designed to determine if exposure to teratogenic doses of hydroxyurea induces oxidative stress and alters gene expression by activating these transcription factors. Pregnant mice were treated with saline or hydroxyurea (400, 500, or 600 mg/kg) on gestation day 9 (GD 9) and killed either on GD 9, 0.5, 3, or 6 h after treatment, to assess oxidative stress and transcription factor activities, or on GD 18, to assess fetal development. Exposure to 400 mg/kg hydroxyurea did not affect the progeny, whereas exposure to 500 or 600 mg/kg resulted in dose-dependent increases in fetal resorptions and malformations, including curly tails, abnormal limbs (oligodactyly, hemimelia, and amelia), and short ribs. Hydroxyurea did not induce oxidative stress, as assessed by the ratio of oxidized to reduced glutathione, nor did it alter NF-kappaB DNA binding activity in the GD 9 conceptus. In contrast, exposure to hydroxyurea at any dose increased AP-1 DNA binding activity in embryos and yolk sacs 0.5 or 3 h after treatment. Hydroxyurea-induced c-Fos heterodimer activity in the embryo peaked 3-4-fold above control at 3 h and remained elevated by 6 h; in contrast, the activity of c-Jun dimers was not altered by drug exposure. A dramatic and region-specific increase in c-Fos immunoreactivity was found in hydroxyurea-treated embryos. The induction of AP-1 DNA binding activity by hydroxyurea represents an early, sensitive marker of the embryonic response to insult.",
"title": "Activator protein-1 (AP-1) DNA binding activity is induced by hydroxyurea in organogenesis stage mouse embryos"
},
{
"docid": "35085326",
"text": "A previously unknown protein, designated SvpA (surface virulence-associated protein) and implicated in the virulence of the intracellular pathogen Listeria monocytogenes, was identified. This 64 kDa protein, encoded by svpA, is both secreted in culture supernatants and surface-exposed, as shown by immunogold labelling of whole bacteria with an anti-SvpA antibody. Analysis of the peptide sequence revealed that SvpA contains a leader peptide, a predicted C-terminal transmembrane region and a positively charged tail resembling that of the surface protein ActA, suggesting that SvpA might partially reassociate with the bacterial surface by its C-terminal membrane anchor. An allelic mutant was constructed by disrupting svpA in the wild-type strain LO28. The virulence of this mutant was strongly attenuated in the mouse, with a 2 log decrease in the LD50 and restricted bacterial growth in organs as compared to the wild-type strain. This reduced virulence was not related either to a loss of adherence or to a lower expression of known virulence factors, which remained unaffected in the svpA mutant. It was caused by a restriction of intracellular growth of mutant bacteria. By following the intracellular behaviour of bacteria within bone-marrow-derived macrophages by confocal and electron microscopy studies, it was found that most svpA mutant bacteria remained confined within phagosomes, in contrast to wild-type bacteria which rapidly escaped to the cytoplasm. The regulation of svpA was independent of PrfA, the transcriptional activator of virulence genes in L. monocytogenes. In fact, SvpA was down-regulated by MecA, ClpC and ClpP, which are highly homologous to proteins of Bacillus subtilis forming a regulatory complex controlling the competence state of this saprophyte. The results indicate that: (i) SvpA is a novel factor involved in the virulence of L. monocytogenes, promoting bacterial escape from phagosomes of macrophages; (ii) SvpA is, at least partially, associated with the surface of bacteria; and (iii) SvpA is PrfA-independent and controlled by a MecA-dependent regulatory network.",
"title": "SvpA, a novel surface virulence-associated protein required for intracellular survival of Listeria monocytogenes."
},
{
"docid": "9194077",
"text": "Pathogenesis of Alzheimer’s disease (AD), which is characterised by accumulation of extracellular deposits of β-amyloid peptide (Aβ) in the brain, has recently been linked to vascular disorders such as ischemia and stroke. Aβ is constantly produced in the brain from amyloid precursor protein (APP) through its cleavage by β- and γ-secretases and certain Aβ species are toxic for neurones. The brain has an endogenous mechanism of Aβ removal via proteolytic degradation and the zinc metalloproteinase neprilysin (NEP) is a critical regulator of Aβ concentration. Down-regulation of NEP could predispose to AD. By comparing the effects of hypoxia and oxidative stress on expression and activity of the Aβ-degrading enzyme NEP in human neuroblastoma NB7 cells and rat primary cortical neurones we have demonstrated that hypoxia reduced NEP expression at the protein and mRNA levels as well as its activity. On contrary in astrocytes hypoxia increased NEP mRNA expression.",
"title": "Effects of Hypoxia and Oxidative Stress on Expression of Neprilysin in Human Neuroblastoma Cells and Rat Cortical Neurones and Astrocytes"
},
{
"docid": "34386619",
"text": "The Bacillus subtilis clpC operon is regulated by two stress induction pathways relying on either sigmaB or a class III stress induction mechanism acting at a sigmaA-like promoter. When the clpC operon was placed under the control of the isopropyl-beta-D-thiogalactopyranoside (IPTG)-inducible Pspac promoter, dramatic repression of the natural clpC promoters fused to a lacZ reporter gene was noticed after IPTG induction. This result strongly indicated negative regulation of the clpC operon by one of its gene products. Indeed, the negative regulator could be identified which is encoded by the first gene of the clpC operon, ctsR, containing a predicted helix-turn-helix DNA-binding motif. Deletion of ctsR abolished the negative regulation and resulted in high expression of both the clpC operon and the clpP gene under nonstressed conditions. Nevertheless, a further increase in clpC and clpP mRNA levels was observed after heat shock, even in the absence of sigmaB, suggesting a second induction mechanism at the vegetative promoter. Two-dimensional gel analysis and mRNA studies showed that the expression of other class III stress genes was at least partially influenced by the ctsR deletion. Studies with different clpC promoter fragments either fused to the reporter gene bgaB or used in gel mobility shift experiments with the purified CtsR protein revealed a possible target region where the repressor seemed to bind in vivo and in vitro. Our data demonstrate that the CtsR protein acts as a global repressor of the clpC operon, as well as other class III heat shock genes, by preventing unstressed transcription from either the sigmaB- or sigmaA-dependent promoter and might be inactivated or dissociate under inducing stress conditions.",
"title": "The first gene of the Bacillus subtilis clpC operon, ctsR, encodes a negative regulator of its own operon and other class III heat shock genes."
},
{
"docid": "22312627",
"text": "Previous results have demonstrated that the silencing of adjacent genes encoding NADPH-dependent furfural oxidoreductases (yqhD dkgA) is responsible for increased furfural tolerance in an E. coli strain EMFR9 [Miller et al., Appl Environ Microbiol 75:4315–4323, 2009]. This gene silencing is now reported to result from the spontaneous insertion of an IS10 into the coding region of yqhC, an upstream gene. YqhC shares homology with transcriptional regulators belonging to the AraC/XylS family and was shown to act as a positive regulator of the adjacent operon encoding YqhD and DkgA. Regulation was demonstrated by constructing a chromosomal deletion of yqhC, a firefly luciferase reporter plasmid for yqhC, and by a direct comparison of furfural resistance and NADPH-dependent furfural reductase activity. Closely related bacteria contain yqhC, yqhD, and dkgA orthologs in the same arrangement as in E. coli LY180. Orthologs of yqhC are also present in more distantly related Gram-negative bacteria. Disruption of yqhC offers a useful approach to increase furfural tolerance in bacteria.",
"title": "YqhC regulates transcription of the adjacent Escherichia coli genes yqhD and dkgA that are involved in furfural tolerance"
},
{
"docid": "25488034",
"text": "Increases in the intracellular levels of reactive oxygen species (ROS), frequently referred to as oxidative stress, represents a potentially toxic insult which if not counteracted will lead to membrane dysfunction, DNA damage and inactivation of proteins. Chronic oxidative stress has numerous pathological consequences including cancer, arthritis and neurodegenerative disease. Glutathione-associated metabolism is a major mechanism for cellular protection against agents which generate oxidative stress. It is becoming increasingly apparent that the glutathione tripeptide is central to a complex multifaceted detoxification system, where there is substantial inter-dependence between separate component members. Glutathione participates in detoxification at several different levels, and may scavenge free radicals, reduce peroxides or be conjugated with electrophilic compounds. Thus, glutathione provides the cell with multiple defences not only against ROS but also against their toxic products. This article discusses how glutathione biosynthesis, glutathione peroxidases, glutathione S-transferases and glutathione S-conjugate efflux pumps function in an integrated fashion to allow cellular adaption to oxidative stress. Co-ordination of this response is achieved, at least in part, through the antioxidant responsive element (ARE) which is found in the promoters of many of the genes that are inducible by oxidative and chemical stress. Transcriptional activation through this enhancer appears to be mediated by basic leucine zipper transcription factors such as Nrf and small Maf proteins. The nature of the intracellular sensor(s) for ROS and thiol-active chemicals which induce genes through the ARE is described. Gene activation through the ARE appears to account for the enhanced antioxidant and detoxification capacity of normal cells effected by many cancer chemopreventive agents. In certain instances it may also account for acquired resistance of tumours to cancer chemotherapeutic drugs. It is therefore clear that determining the mechanisms involved in regulation of ARE-driven gene expression has enormous medical implications.",
"title": "Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress."
},
{
"docid": "32454714",
"text": "Mucosal tolerance has been considered a potentially important pathway for the treatment of autoimmune disease, including human multiple sclerosis and experimental conditions such as experimental autoimmune encephalomyelitis (EAE). There is limited information on the capacity of commensal gut bacteria to induce and maintain peripheral immune tolerance. Inbred SJL and C57BL/6 mice were treated orally with a broad spectrum of antibiotics to reduce gut microflora. Reduction of gut commensal bacteria impaired the development of EAE. Intraperitoneal antibiotic-treated mice showed no significant decline in the gut microflora and developed EAE similar to untreated mice, suggesting that reduction in disease activity was related to alterations in the gut bacterial population. Protection was associated with a reduction of proinflammatory cytokines and increases in IL-10 and IL-13. Adoptive transfer of low numbers of IL-10-producing CD25(+)CD4(+) T cells (>75% FoxP3(+)) purified from cervical lymph nodes of commensal bacteria reduced mice and in vivo neutralization of CD25(+) cells suggested the role of regulatory T cells maintaining peripheral immune homeostasis. Our data demonstrate that antibiotic modification of gut commensal bacteria can modulate peripheral immune tolerance that can protect against EAE. This approach may offer a new therapeutic paradigm in the treatment of multiple sclerosis and perhaps other autoimmune conditions.",
"title": "Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis."
}
] |
PLAIN-3158
|
Egg Industry Blind Spot
|
[
{
"docid": "MED-3780",
"text": "Metabolomics studies hold promise for discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. A metabolomics approach was used to generate unbiased small molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine, namely choline, trimethylamine N-oxide (TMAO), and betaine, were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted up-regulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases (FMOs), an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidemic mice. Discovery of a relationship between gut flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for development of both novel diagnostic tests and therapeutic approaches for atherosclerotic heart disease.",
"title": "Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease"
},
{
"docid": "MED-2371",
"text": "Background Limiting consumption of eggs, which are high in cholesterol, is generally recommended to reduce risk of cardiovascular disease. However, recent evidence suggests that dietary cholesterol has limited influence on serum cholesterol or cardiac risk. Objective To assess the effects of egg consumption on endothelial function and serum lipids in hyperlipidemic adults. Methods Randomized, placebo-controlled crossover trial of 40 hyperlipidemic adults (24 women, 16 men; average age = 59.9 ± 9.6 years; weight = 76.3 ± 21.8 kilograms; total cholesterol = 244 ± 24 mg/dL). In the acute phase, participants were randomly assigned to one of the two sequences of a single dose of three medium hardboiled eggs and a sausage/cheese breakfast sandwich. In the sustained phase, participants were then randomly assigned to one of the two sequences of two medium hardboiled eggs and 1/2 cup of egg substitute daily for six weeks. Each treatment assignment was separated by a four-week washout period. Outcome measures of interest were endothelial function measured as flow mediated dilatation (FMD) and lipid panel. Results Single dose egg consumption had no effects on endothelial function as compared to sausage/cheese (0.4 ± 1.9 vs. 0.4 ± 2.4%; p = 0.99). Daily consumption of egg substitute for 6 weeks significantly improved endothelial function as compared to egg (1.0 ± 1.2% vs. -0.1 ± 1.5%; p < 0.01) and lowered serum total cholesterol (-18 ± 18 vs. -5 ± 21 mg/dL; p < 0.01) and LDL (-14 ± 20 vs. -2 ± 19 mg/dL; p = 0.01). Study results (positive or negative) are expressed in terms of change relative to baseline. Conclusions Egg consumption was found to be non-detrimental to endothelial function and serum lipids in hyperlipidemic adults, while egg substitute consumption was beneficial.",
"title": "Daily egg consumption in hyperlipidemic adults - Effects on endothelial function and cardiovascular risk"
},
{
"docid": "MED-3789",
"text": "Background: Meat, milk, and eggs have been inconsistently associated with the risk of advanced prostate cancer. These foods are sources of choline—a nutrient that may affect prostate cancer progression through cell membrane function and one-carbon metabolism. No study has examined dietary choline and the risk of lethal prostate cancer. Objective: Our objective was to examine whether dietary choline, choline-containing compounds, and betaine (a choline metabolite) increase the risk of lethal prostate cancer. Design: We prospectively examined the intake of these nutrients and the risk of lethal prostate cancer among 47,896 men in the Health Professionals Follow-Up Study. In a case-only survival analysis, we examined the postdiagnostic intake of these nutrients and the risk of lethal prostate cancer among 4282 men with an initial diagnosis of nonmetastatic disease during follow-up. Diet was assessed with a validated questionnaire 6 times during 22 y of follow-up. Results: In the incidence analysis, we observed 695 lethal prostate cancers during 879,627 person-years. Men in the highest quintile of choline intake had a 70% increased risk of lethal prostate cancer (HR: 1.70; 95% CI: 1.18, 2.45; P-trend = 0.005). In the case-only survival analysis, we observed 271 lethal cases during 33,679 person-years. Postdiagnostic choline intake was not statistically significantly associated with the risk of lethal prostate cancer (HR for quintile 5 compared with quintile 1: 1.69; 95% CI: 0.93, 3.09; P-trend = 0.20). Conclusion: Of the 47,896 men in our study population, choline intake was associated with an increased risk of lethal prostate cancer.",
"title": "Choline intake and risk of lethal prostate cancer: incidence and survival"
},
{
"docid": "MED-3786",
"text": "This article describes the development of a series of choline- and betaine-controlled diets that were served to research subjects as part of an ongoing study of diet requirements in humans. These diets were developed based on the analysis of choline and betaine in individual foods. The calculated diets were compared with analyses of all foods combined into a single sample for each day. The laboratory analyses of choline and betaine in the whole-diet aliquots matched the estimated amounts in the diets that were calculated from the analyses of individual foods. These diets were adjusted for several levels of choline and betaine and were well accepted by research subjects who consumed them for a time period of up to 2 months. This article describes applications of this diet for use in clinical research on methyl-group requirements in humans and for use in clinical practice for counseling the client who requires a choline-controlled diet.",
"title": "Choline- and betaine-defined diets for use in clinical research and for the management of trimethylaminuria."
},
{
"docid": "MED-2372",
"text": "BACKGROUND: Because of egg cholesterol content, reduction in egg consumption is generally recommended to reduce risk of cardiovascular disease. Recently, however, evidence has been accumulating to suggest that dietary cholesterol is less relevant to cardiovascular risk than dietary saturated fat. This randomized controlled crossover trial was conducted to determine the effects of egg ingestion on endothelial function, a reliable index of cardiovascular risk. METHODS: Forty-nine healthy adults (mean age 56 years, 40% females) underwent a baseline brachial artery reactivity study (BARS), and were assigned to two eggs or oats daily for 6 weeks in random sequence with a 4-week washout. A BARS was done at the end of each treatment phase, measuring flow-mediated vasodilation (FMD) in the brachial artery using a high-frequency ultrasound. RESULTS: FMD was stable in both egg and oat groups, and between-treatment differences were not significant (egg -0.96%, oatmeal -0.79%; p value >0.05). Six weeks of egg ingestion had no effect on total cholesterol (baseline: 203.8 mg/dl; post-treatment: 205.3) or LDL (baseline: 124.8 mg/dl; post-treatment: 129.1). In contrast, 6 weeks of oats lowered total cholesterol (to 194 mg/dl; p = 0.0017) and LDL (to 116.6 mg/dl; p = 0.012). There were no differences in body mass index (BMI), triglyceride, HDL or SBP levels between egg and oat treatment assignments. CONCLUSION: Short-term egg consumption does not adversely affect endothelial function in healthy adults, supporting the view that dietary cholesterol may be less detrimental to cardiovascular health than previously thought.",
"title": "Egg consumption and endothelial function: a randomized controlled crossover trial."
},
{
"docid": "MED-3781",
"text": "In this study, a panel of normal human prostate cells (HPCs) and tumor cells derived from metastases were studied by (1)H NMR spectroscopy to determine whether the malignant transformation of HPCs results in the elevation of choline compounds. Although an elevated choline signal has been observed previously in clinical studies, the contribution of the different Cho compounds to this elevation, as well as their quantification, has not been established until now. Here we have shown that HPCs derived from metastases exhibit significantly higher phosphocholine as well as glycerophosphocholine levels compared with normal prostate epithelial and stromal cells. Thus the elevation of the choline peak observed clinically in prostate cancer is attributable to an alteration of phospholipid metabolism and not simply to increased cell density, doubling time, or other nonspecific effects. Androgen deprivation of the androgen receptor-positive cell lines resulted in a significant increase of choline compounds after chronic androgen deprivation of the LNCaP cell line and in a decrease of choline compounds after a more acute androgen deprivation of the LAPC-4 cell line. These data strongly support the use of proton magnetic resonance spectroscopic imaging to detect the presence of prostate cancer for diagnosis, to detect response subsequent to androgen ablation therapy, and to detect recurrence.",
"title": "Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prosta..."
},
{
"docid": "MED-3784",
"text": "Dietary choline and betaine have been hypothesized to decrease the risk of cancer because of their role as methyl donors in the one-carbon metabolism. However, it remains unknown whether dietary intake of choline and betaine is associated with colorectal cancer risk. We prospectively examined the associations between dietary choline and betaine intake and risk of colorectal cancer in men in the Health Professionals Follow-up Study. We followed 47,302 men and identified a total of 987 incident colorectal cancer cases from 1986 to 2004. We assessed dietary and supplemental choline and betaine intake every four years using a validated semi-quantitative food frequency questionnaire. The Cox proportional hazards model was used to estimate multivariate relative risks (RRs) and 95% confidence intervals (95% CIs). All statistical tests were two-sided. We did not find any statistically significant associations between choline intake or betaine intake and risk of colorectal cancer. Comparing the top quintile with bottom quintile, multivariate RRs (95% CI) were 0.97 (0.79-1.20; Ptrend = 0.87) for choline intake and 0.94 (0.77-1.16; Ptrend = 0.79) for betaine intake. Similarly, we observed no associations between colorectal cancer risk and choline from free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine, or sphingomyelin. Our data do not support that choline and betaine intake is inversely associated with colorectal cancer risk.",
"title": "Choline and betaine intake and the risk of colorectal cancer in men"
},
{
"docid": "MED-3782",
"text": "Red and processed meat may increase risk of advanced prostate cancer. Data on post-diagnostic diet and prostate cancer are sparse, but post-diagnostic intake of poultry with skin and eggs may increase risk of disease progression. Therefore, we prospectively examined total, unprocessed, and processed red meat, poultry, and eggs in relation to risk of lethal prostate cancer (e.g. men without cancer at baseline who developed distant organ metastases or died from prostate cancer during follow-up) among 27, 607 men followed from 1994–2008. We also performed a case-only survival analysis to examine post-diagnostic consumption of these foods and risk of lethal prostate cancer among the 3,127 men initially diagnosed with non-metastatic prostate cancer during follow-up. In the incidence analysis, we observed 199 events during 306,715 person-years. Men who consumed 2.5 or more eggs per week had an 81% increased risk of lethal prostate cancer compared to men who consumed less than 0.5 eggs per week (HR: 1.81; 95% confidence interval (CI): 1.13, 2.89; p-trend: 0.01). In the case-only survival analysis, we observed 123 events during 19,354 person-years. There were suggestive, but not statistically significant, positive associations between post-diagnostic poultry (HR ≥3.5 vs. <1.5 servings per week: 1.69; 95%CI: 0.96, 2.99; p-trend: 0.07) and post-diagnostic processed red meat (HR ≥3 vs. <0.5 servings per week: 1.45; 95%CI: 0.73, 2.87; p-trend: 0.08) and risk of progression of localized prostate cancer to lethal disease. In conclusion, consumption of eggs may increase risk of developing a lethal-form of prostate cancer among healthy men.",
"title": "Egg, red meat, and poultry intake and risk of lethal prostate cancer in the prostate specific antigen-era: incidence and survival"
},
{
"docid": "MED-3193",
"text": "Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.",
"title": "11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma"
},
{
"docid": "MED-3783",
"text": "Fish odour syndrome (trimethylaminuria) is a metabolic syndrome caused by abnormal excretion of trimethylamine in the breath, urine, sweat, saliva and vaginal secretions. Trimethylamine is derived from the intestinal bacterial degradation of foods rich in choline and carnitine and is normally oxidised by the liver to odourless trimethylamine N-oxide which is then excreted in the urine. Impaired oxidation of trimethylamine is thought to be the cause of the fish odour syndrome and is responsible for the smell of rotting fish. Certain foods rich in choline exacerbate the condition and the patients have a variety of psychological problems. Recognition of the condition is important as dietary adjustments reduce the excretion of trimethylamine and may reduce the odour. Occasionally, a short course of metronidazole, neomycin and lactulose may suppress production of trimethylamine by reducing the activity of gut microflora. Keywords: fish odour syndrome; trimethylaminuria",
"title": "Fish odour syndrome"
},
{
"docid": "MED-3787",
"text": "Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.",
"title": "11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma"
},
{
"docid": "MED-3785",
"text": "PURPOSE: Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before. MATERIALS AND METHODS: We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression. RESULTS: Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; P(trend) = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; P(trend) = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; P(trend) = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk. CONCLUSION: The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation.",
"title": "One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites."
},
{
"docid": "MED-4324",
"text": "BACKGROUND: Increasingly the potential harm from high cholesterol intake, and specifically from egg yolks, is considered insignificant. We therefore assessed total plaque area (TPA) in patients attending Canadian vascular prevention clinics to determine if the atherosclerosis burden, as a marker of arterial damage, was related to egg intake. To provide perspective on the magnitude of the effect, we also analysed the effect of smoking (pack-years). METHODS: Consecutive patients attending vascular prevention clinics at University Hospital had baseline measurement of TPA by duplex ultrasound, and filled out questionnaires regarding their lifestyle and medications, including pack-years of smoking, and the number of egg yolks consumed per week times the number of years consumed (egg-yolk years). RESULTS: Data were available in 1262 patients; mean (SD) age was 61.5 (14.8) years; 47% were women. Carotid plaque area increased linearly with age after age 40, but increased exponentially with pack-years of smoking and with egg-yolk years. Plaque area in patients consuming <2 eggs per week (n = 388) was 125 ± 129 mm(2), versus 132 ± 142 mm(2) in those consuming 3 or more eggs per week (n = 603); (p < 0.0001 after adjustment for age). In multiple regression, egg-yolk years remained significant after adjusting for coronary risk factors. INTERPRETATION: Our findings suggest that regular consumption of egg yolk should be avoided by persons at risk of cardiovascular disease. This hypothesis should be tested in a prospective study with more detailed information about diet, and other possible confounders such as exercise and waist circumference. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.",
"title": "Egg yolk consumption and carotid plaque."
},
{
"docid": "MED-4385",
"text": "The idea that normal constituents of the diet can influence visual function is not new. As early as 1782, Buzzi identified the yellow of the macula and Schulze (1866) specifically postulated that the yellow pigments led to improvements in human vision. These pigments were later found to be derived from dietary lutein and zeaxanthin that are known to be oxygenated carotenoids (xanthophylls). Walls and Judd (1933) postulated that these yellow intraocular pigments could improve visual performance by absorbing light scattered both within (for example, glare) and outside of the eye (increasing visual range by absorbing blue light scattered in the atmosphere), and by improving spatial vision through enhancing contrast and reducing chromatic blur. In this article, evidence for these ideas is reviewed with particular emphasis towards more recent data on glare effects.",
"title": "The influence of dietary lutein and zeaxanthin on visual performance."
},
{
"docid": "MED-2370",
"text": "In this third installment of the series, we point out that the absence of an explicit, detailed and plausible hypothesis linking hypercholesterolemia to the events in the artery wall was probably an important reason for continuing skepticism and for failure to treat elevated blood cholesterol levels. The rapid advances in understanding of lipoprotein metabolism in the 1950s and 1960s and the application of modern cellular biology in the 1970s provided the context for a modern consensus on pathogenetic mechanisms of atherogenesis.",
"title": "Thematic review series: the pathogenesis of atherosclerosis: an interpretive history of the cholesterol controversy, part III: mechanistically defi..."
},
{
"docid": "MED-3790",
"text": "Background: Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. Objective: We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. Design: We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004–2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. Results: We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Conclusions: Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk.",
"title": "Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression"
}
] |
[
{
"docid": "MED-5216",
"text": "Vitamin A deficiency (VAD) has been recognized as a public-health issue in developing countries. Economic constraints, sociocultural limitations, insufficient dietary intake, and poor absorption leading to depleted vitamin A stores in the body have been regarded as potential determinants of the prevalence of VAD in South Asian developing countries. VAD is exacerbated by lack of education, poor sanitation, absence of new legislation and enforcement of existing food laws, and week monitoring and surveillance system. Several recent estimates confirmed higher morbidly and mortality rate among children and pregnant and non-pregnant women of childbearing age. Xerophthalmia is the leading cause of preventable childhood blindness with its earliest manifestations as night blindness and Bitot's spots, followed by blinding keratomalacia, all of which are the ocular manifestations of VAD. Children need additional vitamin A because they do not consume enough in their normal diet. There are three general ways for improving vitamin A status: supplementation, fortification, and dietary diversification. These approaches have not solved the problem in South Asian countries to the desired extent because of poor governmental support and supervision of vitamin A supplementation twice a year. An extensive review of the extant literature was carried out, and the data under various sections were identified by using a computerized bibliographic search via PubMed, Web of Science, and Google Scholar. All abstracts and full-text articles were examined, and the most relevant articles were selected for screening and inclusion in this review. Conclusively, high prevalence of VAD in South Asian developing countries leads to increased morbidity and mortality among infants, children, and pregnant women. Therefore, stern efforts are needed to address this issue of public-health significance at local and international level in lower- and middle-income countries of South Asia.",
"title": "Prevalence of Vitamin A Deficiency in South Asia: Causes, Outcomes, and Possible Remedies"
},
{
"docid": "MED-2089",
"text": "In this study, genotoxicity of two mouthwash products (chlorexidin, benzidamine-HCl) were investigated in the Drosophila Wing-Spot Test which makes use of the wing cell markers multiple wing hairs (mwh) and flare (flr) and detects both mitotic recombination and various types of mutational events. Induced mutations are detected as single mosaic spots on the wing blade of surviving adults that show either the multiple wing hairs or flare phenotype. Induced recombination leads to mwh and flr twin spots and also, to some extent, to mwh single spots. Recording of the frequency and the size of different spots is allowed for a quantitative determination of the mutagenic and recombinogenic effects. Trans-heterozygous third-instar larvae were treated at different concentrations of the mouthwash products. Chlorexidin exposure concentrations were 0.5, 1 and 2mg/ml. Benzidamine-HCl exposure concentrations were 0.38, 0.75 and 1.5mg/ml. In addition, the observed mutations were classified according to size and type of mutation per wing. Both chlorexidin and benzidamine-HCl were genotoxic in terms of total mutations per wing at the highest doses. Survival rates of flies used in the experiments were significantly lower than those of the control group, with both mouthwash products showing toxic effects on Drosophila melanogaster larvae. Copyright (c) 2010 Elsevier Ltd. All rights reserved.",
"title": "Genotoxicity of two mouthwash products in the Drosophila Wing-Spot Test."
},
{
"docid": "MED-2475",
"text": "Current understanding of the use of exclusion diets in the management of asthma in children is limited and controversial. The aim of this study was to examine the effects of excluding eggs and milk on the occurrence of symptoms in children with asthma and involved 22 children aged between three and 14 years clinically diagnosed as having mild to moderate disease. The investigation was single blind and prospective, and parents were given the option of volunteering to join the 'experiment' group, avoiding eggs, milk and their products for eight weeks, or the 'control' group, who consumed their customary food. Thirteen children were recruited to the experimental group and nine to the control group. A trained paediatrician at the beginning and end of the study period assessed the children. A seven-day assessment of food intake was made before, during and immediately after the period of dietary intervention in both groups. A blood sample was taken from each child for determination of food specific antibodies and in those children who could do so, the peak expiratory flow rate (PEFR) was measured. Based on the recommended nutrient intake (RNI), the mean percentage energy intake of the children in the experimental group was significantly lower (p < 0.05) in the experimental group. After the eight-week study period and compared with baseline values, the mean serum anti-ovalbumin IgG and anti-beta lactoglobulin IgG concentrations were statistically significantly reduced (p < 0.05) for both in the experimental group. In contrast, the values for anti-ovalbumin IgG in the control group were significantly increased and those for anti-beta lactoglobulin IgG were practically unchanged. The total IgE values were unchanged in both groups. Over the study period, the PEFR in those children in the experimental group able to perform the test was significantly increased, but no such change was noted in the children in the control group who could do the test. These results suggest that even over the short time period of eight weeks, an egg- and milk-free diet can reduce atopic symptoms and improve lung function in asthmatic children.",
"title": "The effects of exclusion of dietary egg and milk in the management of asthmatic children: a pilot study."
},
{
"docid": "MED-4980",
"text": "Feasibility of fluorescence imaging technique for the detection of diluted fecal matters from various parts of the digestive tract, including colon, ceca, small intestine, and duodenum, on poultry carcasses was investigated. One of the challenges for using fluorescence imaging for inspection of agricultural material is the low fluorescence yield in that fluorescence can be masked by ambient light. A laser-induced fluorescence imaging system (LIFIS) developed by our group allowed acquisition of fluorescence from feces-contaminated poultry carcasses in ambient light. Fluorescence emission images at 630 nm were captured with 415-nm laser excitation. Image processing algorithms including threshold and image erosion were used to identify fecal spots diluted up to 1: 10 by weight with double distilled water. Feces spots on the carcasses, without dilution and up to 1: 5 dilutions, could be detected with 100% accuracy regardless of feces type. Detection accuracy for fecal matters diluted up to 1: 10 was 96.6%. The results demonstrated good potential of the LIFIS for detection of diluted poultry fecal matter, which can harbor pathogens, on poultry carcasses.",
"title": "Detection of fecal residue on poultry carcasses by laser-induced fluorescence imaging."
},
{
"docid": "MED-4032",
"text": "AIM: The aim of this study was to investigate oral changes in subjects who have assumed a vegan diet for a long time (at least 18 months), that is to say, a diet completely lacking in meat and animal derivatives. METHODS: A sample of 15 subjects was analyzed, all from northern Italy and aged 24 to 60 year, composed of 11 men and 4 women who had been following a vegan diet for a minimum of 18 months to a maximum of 20 years. In parallel with the study sample, a control group (15 subjects) with the same criteria of age, sex, and place of origin all following an omnivorous diet was chosen. The sample answered a questionnaire that investigated their eating habits, the frequency with which they eat meals, the main foodstuffs assumed, oral hygiene habits, and any painful symptomatology of the teeth or more general problems in the oral cavity. The sample was then subject to objective examination in which the saliva pH was measured and the teeth were checked for demineralization of the enamel, white spots, and caries (using KaVo DIAGNOdent) with particular attention being paid to the localization of these lesions, and lastly, sounding was carried out to detect any osseous defects and periodontal pockets. RESULTS: The study revealed greater incidence of demineralization and white spots in the vegan subjects compared to the omnivorous ones localized at the neck of the teeth and on the vestibular surfaces of dental elements (with the exception of the lower anterior group). The saliva pH, more acid in the omnivorous patients, ranged between four and six. Changes in oral conditions in both groups of subjects were observed. CONCLUSION: In order to research into the cause-effect relationship of the vegan diet on the oral cavity effectively, the sample needs to be studied for a longer period of time and the results re-evaluated.",
"title": "Oral implications of the vegan diet: observational study."
},
{
"docid": "MED-4747",
"text": "In contrast to the use of hormonal doping agents in sports to enhance the performance of athletes, in the livestock industry hormonal growth promoters (\"anabolics\") are used to increase the production of muscle meat. This leads to international disputes about the safety of meat originating from animals treated with such anabolics.As a consequence of the total ban in the EU of all hormonal active growth promoters (\"hormones\") in livestock production, in contrast to their legal use [e.g. of five such hormones (17beta-estradiol, testosterone, progesterone, trenbolone and zeranol) as small solid ear implants and two hormones as feed additives for feedlot heifers (melengestrol acetate) and for swine (ractopamine) in the USA], the regulatory controls also differ sharply between the EU and the USA.In the EU the treatment of slaughter animals is the regulatory offence that has to be controlled in inspection programs. In the USA testing for compliance of a regulatory maximum residue level in the edible product (muscle, fat, liver or kidney) is the purpose of the inspection program (if any).The EU inspection programs focus on sample materials that are more suitable for testing for banned substances, especially if the animals are still on the farm, such as urine and feces or hair. In the case of slaughtered animals, the more favored sample materials are bile, blood, eyes and sometimes liver. Only in rare occasions is muscle meat sampled. This happens only in the case of import controls or in monitoring programs of meat sampled in butcher shops or supermarkets.As a result, data on hormone concentrations in muscle meat samples from the EU market are very rare and are obtained in most cases from small programs on an ad hoc basis. EU data for natural hormones in meat are even rarer because of the absence of \"legal natural levels\" for these hormones in compliance testing. With the exception of samples from the application sites - in the EU the site of injection of liquid hormone preparations or the site of application of \"pour on\" preparations - the hormone concentrations observed in meat samples of illegally treated animals are typically in the range of a few micrograms per kilogram (ppb) down to a few tenths of a microgram per kilogram. In the EU dozens of illegal hormones are used and the number of active compounds is still expanding. Besides estrogenic, androgenic and progestagenic compounds also thyreostatic, corticosteroidal and beta-adrenergic compounds are used alone or in \"smart\" combinations.An overview is given of the compounds identified on the EU black market. An estimate is also given of the probability of consumption in the EU of \"highly\" contaminated meat from the application sites in cattle. Finally some data are presented on the concentration of estradiol in bovine meat from animals treated and not treated with hormone implants. These data are compared with the recent findings for estradiol concentrations in hen's eggs. From this comparison, the preliminary conclusion is that hen's eggs are the major source of 17alpha- and 17beta-estradiol in the consumer's daily \"normal\" diet.",
"title": "Hormonal growth promoting agents in food producing animals."
},
{
"docid": "MED-936",
"text": "BACKGROUND: The contribution of ascorbate to urinary oxalate is controversial. The present study aimed to determine whether urinary oxalate and pH may be affected by vitamin C supplementation in calcium stone-forming patients. METHODS: Forty-seven adult calcium stone-forming patients received either 1 g (N=23) or 2 g (N=24) of vitamin C supplement for 3 days and 20 healthy subjects received 1 g. A 24-hour urine sample was obtained both before and after vitamin C for calcium, oxalate, magnesium, citrate, sodium, potassium, and creatinine determination. The Tiselius index was used as a calcium oxalate crystallization index. A spot fasting morning urine sample was also obtained to determine the urinary pH before and after vitamin C. RESULTS: Fasting urinary pH did not change after 1 g (5.8 +/- 0.6 vs. 5.8 +/- 0.7) or 2 g vitamin C (5.8 +/- 0.8 vs. 5.8 +/- 0.7). A significant increase in mean urinary oxalate was observed in calcium stone-forming patients receiving either 1 g (50 +/- 16 vs. 31 +/- 12 mg/24 hours) or 2 g (48 +/- 21 vs. 34 +/- 12 mg/24 hours) of vitamin C and in healthy subjects (25 +/- 12 vs. 39 +/- 13 mg/24 hours). A significant increase in mean Tiselius index was observed in calcium stone-forming patients after 1 g (1.43 +/- 0.70 vs. 0.92 +/- 0.65) or 2 g vitamin C (1.61 +/- 1.05 vs. 0.99 +/- 0.55) and in healthy subjects (1.50 +/- 0.69 vs. 0.91 +/- 0.46). Ancillary analyses of spot urine obtained after vitamin C were performed in 15 control subjects in vessels with or without ethylenediaminetetraacetic acid (EDTA) with no difference in urinary oxalate between them (28 +/- 23 vs. 26 +/- 21 mg/L), suggesting that the in vitro conversion of ascorbate to oxalate did not occur. CONCLUSION: These data suggest that vitamin C supplementation may increase urinary oxalate excretion and the risk of calcium oxalate crystallization in calcium stone-forming patients.",
"title": "Effect of vitamin C supplements on urinary oxalate and pH in calcium stone-forming patients."
},
{
"docid": "MED-4625",
"text": "Arachidonic acid (ARA) is considered to be a minor contributor to the diet. Previous reports regarding the effect of ARA supplementation on the composition of long-chain polyunsaturated fatty acids (LCPUFA) in the blood of humans are extremely limited. In the present study, we conducted a crossover double-blind, placebo-control study. Twenty-three young Japanese women consumed one capsule containing triacylglycerol enriched with 80 mg ARA, equivalent to the amount in one egg, daily for 3 weeks. Blood samples were drawn before and after treatment periods, and the compositions of the LCPUFA in blood lipid fractions were measured. The supplementation of ARA increased the composition of ARA, but did not decrease the composition of n-3LCPUFA in erythrocyte phospholipids and plasma phospholipids, esterified cholesterol, and triacylglycerol. We found that dietary ARA increased the ARA level in all lipid fractions of the blood, even at a very low dose. (c) 2010 Elsevier Ltd. All rights reserved.",
"title": "Low-dose arachidonic acid intake increases erythrocytes and plasma arachidonic acid in young women."
},
{
"docid": "MED-2884",
"text": "Two carotenoids found in egg yolk, lutein and zeaxanthin, accumulate in the macular retina where they may reduce photostress. Increases in serum lutein and zeaxanthin were observed in previous egg interventions, but no study measured macular carotenoids. The objective of this project was to determine whether increased consumption of eggs would increase retinal lutein and zeaxanthin, or macular pigment. Twenty-four females, between 24 and 59 y, were assigned to a pill treatment (PILL) or 1 of 2 egg treatments for 12 wk. Individuals in the PILL treatment consumed 1 sugar-filled capsule/d. Individuals in the egg treatments consumed 6 eggs/wk, containing either 331 microg (EGG 1) or 964 microg (EGG 2) of lutein and zeaxanthin/yolk. Serum cholesterol, serum carotenoids, and macular pigment OD (MPOD) were measured at baseline and after 4, 8, and 12 wk of intervention. Serum cholesterol concentrations did not change in either egg treatment group, but total cholesterol (P = 0.04) and triglycerides (P = 0.02) increased in the PILL group. Serum zeaxanthin, but not serum lutein, increased in both the EGG 1 (P = 0.04) and EGG 2 (P = 0.01) groups. Likewise, MPOD increased in both the EGG 1 (P = 0.001) and EGG 2 (P = 0.049) groups. Although the aggregate concentration of carotenoid in 1 egg yolk may be modest relative to other sources, such as spinach, their bioavailability to the retina appears to be high. Increasing egg consumption to 6 eggs/wk may be an effective method to increase MPOD.",
"title": "A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical density in women."
},
{
"docid": "MED-963",
"text": "The public perceives that the nutritional quality of eggs produced as free range is superior to that of eggs produced in cages. Therefore, this study compared the nutrient content of free-range vs. cage-produced shell eggs by examining the effects of the laboratory, production environment, and hen age. A flock of 500 Hy-Line Brown layers were hatched simultaneously and received the same care (i.e., vaccination, lighting, and feeding regimen), with the only difference being access to the range. The nutrient content of the eggs was analyzed for cholesterol, n-3 fatty acids, saturated fat, monounsaturated fat, polyunsaturated fat, β-carotene, vitamin A, and vitamin E. The same egg pool was divided and sent to 4 different laboratories for analysis. The laboratory was found to have a significant effect on the content of all nutrients in the analysis except for cholesterol. Total fat content in the samples varied (P < 0.001) from a high of 8.88% to a low of 6.76% in laboratories D and C, respectively. Eggs from the range production environment had more total fat (P < 0.05), monounsaturated fat (P < 0.05), and polyunsaturated fat (P < 0.001) than eggs produced by caged hens. Levels of n-3 fatty acids were also higher (P < 0.05), at 0.17% in range eggs vs. 0.14% in cage eggs. The range environment had no effect on cholesterol (163.42 and 165.38 mg/50 g in eggs from caged and range hens, respectively). Vitamin A and E levels were not affected by the husbandry to which the hens were exposed but were lowest at 62 wk of age. The age of the hens did not influence the fat levels in the egg, but cholesterol levels were highest (P < 0.001) at 62 wk of age (172.54 mg/50 g). Although range production did not influence the cholesterol level in the egg, there was an increase in fat levels in eggs produced on the range.",
"title": "Comparison of fatty acid, cholesterol, and vitamin A and E composition in eggs from hens housed in conventional cage and range production facilities."
},
{
"docid": "MED-2976",
"text": "Background: Type 2 diabetes (T2D) remains an important public health issue in the United States. There are limited and inconsistent data on the association between egg consumption and fasting glucose or incident diabetes. Objectives: We assessed the association between egg intake and incident diabetes in older adults. Design: In this prospective study of 3898 men and women from the Cardiovascular Health Study (1989–2007), we assessed egg consumption by using a picture-sorted food questionnaire and ascertained incident T2D annually by using information on hypoglycemic agents and plasma glucose. We used Cox proportional hazards models to estimate adjusted relative risks. Results: During a mean follow-up of 11.3 y, 313 new cases of T2D occurred. Crude incidence rates of T2D were 7.39, 6.83, 7.00, 6.72, and 12.20 per 1000 person-years in people who reported egg consumption of never, <1 egg/mo, 1–3 eggs/mo, 1–4 eggs/wk, and almost daily, respectively. In multivariable-adjusted models, there was no association between egg consumption and increased risk of T2D in either sex and overall. In a secondary analysis, dietary cholesterol was not associated with incident diabetes (P for trend = 0.47). In addition, egg consumption was not associated with clinically meaningful differences in fasting glucose, fasting insulin, or measures of insulin resistance despite small absolute analytic differences that were significant. Conclusion: In this cohort of older adults with limited egg intake, there was no association between egg consumption or dietary cholesterol and increased risk of incident T2D.",
"title": "Egg consumption and risk of type 2 diabetes in older adults"
},
{
"docid": "MED-5124",
"text": "Background Reduction in dietary cholesterol is recommended to prevent cardiovascular disease (CVD). Although eggs are important sources of cholesterol and other nutrients, limited and inconsistent data are available on the effects of egg consumption on the risk of CVD and mortality. Objectives To examine the association between egg consumption and the risk of CVD and mortality. Design Prospective cohort study of 21,327 participants from the Physicians' Health Study I. Egg consumption was assessed using a simple abbreviated food questionnaire. We used Cox regression to estimate relative risks. Results After an average follow up of 20 years, a total of 1,550 new myocardial infarction (MI), 1,342 incident strokes, and 5,169 deaths occurred in this cohort. Egg consumption was not associated with incident MI or stroke in a multivariable Cox regression. In contrast, adjusted hazard ratios (95% CI) for mortality were 1.0 (reference), 0.94 (0.87-1.02), 1.03 (0.95-1.11), 1.05 (0.93-1.19), and 1.23 (1.11-1.36) for egg consumption of <1, 1, 2-4, 5-6, and 7+ per week, respectively, (p for trend <0.0001). This association was stronger among diabetic subjects with a 2-fold increased risk of death comparing the highest to the lowest category of egg consumption than non-diabetic subjects (HR: 1.22 (1.09-1.35) (p for interaction 0.09). Conclusions Our data suggest that infrequent egg consumption does not influence the risk of CVD and only confers a modest increased risk for total mortality in male physicians. In addition, egg consumption was positively related to mortality and such relation was stronger among diabetic subjects in this selective population.",
"title": "Egg Consumption and Cardiovascular Disease and Mortality The Physicians' Health Study"
},
{
"docid": "MED-3774",
"text": "While dehydration has well-documented negative effects on adult cognition, there is little research on hydration and cognitive performance in children. We investigated whether having a drink of water improved children's performance on cognitive tasks. Fifty-eight children aged 7-9 years old were randomly allocated to a group that received additional water or a group that did not. Results showed that children who drank additional water rated themselves as significantly less thirsty than the comparison group (p=0.002), and they performed better on visual attention tasks (letter cancellation, p=0.02; spot the difference memory tasks, ps=0.019 and 0.014).",
"title": "Should children drink more water?: the effects of drinking water on cognition in children."
},
{
"docid": "MED-1884",
"text": "We previously evaluated the responses to dietary cholesterol in children and young adults. In this study, the effects of dietary cholesterol on plasma lipids and LDL atherogenicity were evaluated in 42 elderly subjects (29 postmenopausal women and 13 men > 60 y old). Our exclusion criteria were diabetes, heart disease, and the use of reductase inhibitors. The study followed a randomized crossover design in which subjects were assigned to consume the equivalent of 3 large eggs (EGG) daily or the same amount of a cholesterol-free, fat-free egg substitute (SUB) for a 1-mo period. After a 3-wk washout period, subjects were assigned to the alternate treatment. The concentration of plasma cholesterol after the EGG period varied among subjects. When all subjects were evaluated, there were significant increases in LDL cholesterol (LDL-C) (P < 0.05) and HDL-C (P < 0.001) for both men and women during the EGG period, resulting in no alterations in the LDL-C:HDL-C or the total cholesterol:HDL-C ratios. In addition, the LDL peak diameter was increased during the EGG period for all subjects. In contrast, the measured parameters of LDL oxidation, conjugated diene formation, and LDL lag time did not differ between the EGG and the SUB periods. We conclude from this study that dietary cholesterol provided by eggs does not increase the risk for heart disease in a healthy elderly population.",
"title": "Maintenance of the LDL cholesterol:HDL cholesterol ratio in an elderly population given a dietary cholesterol challenge."
},
{
"docid": "MED-2849",
"text": "Higher egg and cholesterol intakes are associated with increased risk of type 2 diabetes mellitus. However, their association with gestational diabetes mellitus (GDM) has not been evaluated. The authors assessed such associations in both a prospective cohort study (1996–2008; 3,158 participants) and a case-control study (1998–2002; 185 cases, 411 controls). A food frequency questionnaire was used to assess maternal diet. Multivariable models were used to derive relative risks and 95% confidence intervals. Compared with no egg consumption, adjusted relative risks for GDM were 0.94, 1.01, 1.12, 1.54, and 2.52 for consumption of ≤1, 2–3, 4–6, 7–9, and ≥10 eggs/week, respectively (P for trend = 0.008). Women with high egg consumption (≥7/week) had a 1.77-fold increased risk compared with women with lower consumption (95% confidence interval (CI): 1.19, 2.63). The relative risk for the highest quartile of cholesterol intake (≥294 mg/day) versus the lowest (<151 mg/day) was 2.35 (95% CI: 1.35, 4.09). In the case-control study, the adjusted odds ratio for consuming ≥7 eggs/week versus <7 eggs/week was 2.65 (95% CI: 1.48, 4.72), and the odds of GDM increased with increasing cholesterol intake (P for trend = 0.021). In conclusion, high egg and cholesterol intakes before and during pregnancy are associated with increased risk of GDM.",
"title": "Risk of Gestational Diabetes Mellitus in Relation to Maternal Egg and Cholesterol Intake"
},
{
"docid": "MED-2975",
"text": "BACKGROUND: Although egg consumption has been associated with elevated plasma levels of cholesterol and triglyceride and with risk of cardiovascular disease in some populations, epidemiologic studies on egg consumption and the risk of diabetes are extremely sparse, particularly in the Chinese population. METHOD: Data from a household survey in the year 2002 among 2849 adults aged ≥20 y from a nationally representative sample in Jiangsu Province, China, were used. Dietary information was assessed by a validated food frequency questionnaire and 3 d weighed food records. Fasting blood specimens were collected. RESULTS: After the adjustment for age, total calorie intake, education, smoking, family history of diabetes, and sedentary activity, egg consumption was significantly and positively associated with diabetes risk, particularly in women. The odds ratios (OR) (95% CI) of diabetes associated with egg consumption <2/wk, 2-6/wk, and ≥1/d in the total sample were 1.00, 1.75, 2.28 (1.14-4.54), respectively (P for trend 0.029). Corresponding ORs (95% CI) in women were 1.00, 1.66, and 3.01 (1.12, 8.12), respectively (P for trend 0.022). Additional adjustment of body mass index attenuated the association, but it remained significant. There was a similar, however, not statistically significant association in men. In addition, plasma triglyceride and total cholesterol levels were significantly higher in women who consumed ≥2 eggs/wk than those who consumed eggs less often. CONCLUSION: Egg consumption was positively associated with the risk of diabetes among the Chinese, particularly in women. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Egg consumption and the risk of diabetes in adults, Jiangsu, China."
},
{
"docid": "MED-1889",
"text": "Consumption of eggs for a long period was shown to result in hypercholesterolemia and is generally restricted for this reason. In the present study we analyzed the effect of eggs consumption for 3 weeks on lipoprotein atherogenicity. Consumption of 2 eggs per day with the meals, for 3 weeks resulted in a minor elevation in plasma glucose and urea concentrations. Plasma cholesterol concentration increased by 11% (p < 0.05) as a result of increased plasma low-density lipoprotein (LDL) cholesterol levels. Plasma triglycerides decreased by 13% (p < 0.01), but there were no significant alterations in plasma apolipoproteins A-I or B-100 concentrations. Plasma high-density lipoprotein (HDL) cholesterol decreased by 11% (p < 0.05). There was a 13% reduction, though not significant, in the cholesterol efflux from J-774 A.1 macrophages by HDL that was derived after eggs consumption in comparison to HDL that was obtained at baseline. The susceptibility of plasma [using 100 mM of 2,2' azobis 2-amidinopropane (AAPH)] as well as that of LDL (using 10 microM of copper ions) to lipid peroxidation was increased by 42% and 34%, respectively, as measured by the thiobarbituric acid reactive substance (TBARS) assay (p < 0.01). Kinetic analysis of LDL oxidation by copper ions revealed a 37% reduction in the lag time required for the initiation of LDL oxidation after 3 weeks of eggs consumption. The total plasma fatty acids concentration increased from 2.2 +/- 0.5 to 3.2 +/- 0.6 mg/ml. The plasma antioxidants, vitamin E and carotenoids were not significantly affected by eggs consumption. We conclude that eggs consumption, in addition to its hypercholesterolemic effect, increases plasma and LDL oxidizability, a phenomenon which was shown to enhance the progression of atherosclerosis. The atherogenic properties may contribute to the accelerated atherosclerosis prevalent in populations with high cholesterol intake.",
"title": "Consumption of eggs with meals increases the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation."
},
{
"docid": "MED-2977",
"text": "OBJECTIVE—Whereas limited and inconsistent findings have been reported on the relation between dietary cholesterol or egg consumption and fasting glucose, no previous study has examined the association between egg consumption and type 2 diabetes. This project sought to examine the relation between egg intake and the risk of type 2 diabetes in two large prospective cohorts. RESEARCH DESIGN AND METHODS—In this prospective study, we used data from two completed randomized trials: 20,703 men from the Physicians' Health Study I (1982–2007) and 36,295 women from the Women's Health Study (1992–2007). Egg consumption was ascertained using questionnaires, and we used the Cox proportional hazard model to estimate relative risks of type 2 diabetes. RESULTS—During mean follow-up of 20.0 years in men and 11.7 years in women, 1,921 men and 2,112 women developed type 2 diabetes. Compared with no egg consumption, multivariable adjusted hazard ratios for type 2 diabetes were 1.09 (95% CI 0.87–1.37), 1.09 (0.88–1.34), 1.18 (0.95–1.45), 1.46 (1.14–1.86), and 1.58 (1.25–2.01) for consumption of <1, 1, 2–4, 5–6, and ≥7 eggs/week, respectively, in men (P for trend <0.0001). Corresponding multivariable hazard ratios for women were 1.06 (0.92–1.22), 0.97 (0.83–1.12), 1.19 (1.03–1.38), 1.18 (0.88–1.58), and 1.77 (1.28–2.43), respectively (P for trend <0.0001). CONCLUSIONS—These data suggest that high levels of egg consumption (daily) are associated with an increased risk of type 2 diabetes in men and women. Confirmation of these findings in other populations is warranted.",
"title": "Egg Consumption and Risk of Type 2 Diabetes in Men and Women"
},
{
"docid": "MED-4892",
"text": "OBJECTIVE—Whereas limited and inconsistent findings have been reported on the relation between dietary cholesterol or egg consumption and fasting glucose, no previous study has examined the association between egg consumption and type 2 diabetes. This project sought to examine the relation between egg intake and the risk of type 2 diabetes in two large prospective cohorts. RESEARCH DESIGN AND METHODS—In this prospective study, we used data from two completed randomized trials: 20,703 men from the Physicians' Health Study I (1982–2007) and 36,295 women from the Women's Health Study (1992–2007). Egg consumption was ascertained using questionnaires, and we used the Cox proportional hazard model to estimate relative risks of type 2 diabetes. RESULTS—During mean follow-up of 20.0 years in men and 11.7 years in women, 1,921 men and 2,112 women developed type 2 diabetes. Compared with no egg consumption, multivariable adjusted hazard ratios for type 2 diabetes were 1.09 (95% CI 0.87–1.37), 1.09 (0.88–1.34), 1.18 (0.95–1.45), 1.46 (1.14–1.86), and 1.58 (1.25–2.01) for consumption of <1, 1, 2–4, 5–6, and ≥7 eggs/week, respectively, in men (P for trend <0.0001). Corresponding multivariable hazard ratios for women were 1.06 (0.92–1.22), 0.97 (0.83–1.12), 1.19 (1.03–1.38), 1.18 (0.88–1.58), and 1.77 (1.28–2.43), respectively (P for trend <0.0001). CONCLUSIONS—These data suggest that high levels of egg consumption (daily) are associated with an increased risk of type 2 diabetes in men and women. Confirmation of these findings in other populations is warranted.",
"title": "Egg Consumption and Risk of Type 2 Diabetes in Men and Women"
},
{
"docid": "MED-4429",
"text": "Epidemiological studies show that poultry meat and eggs are important sources for consumers' exposure to pathogens such as Salmonella and Campylobacter. There is a focus in many countries to reduce the level of human illness from food-borne pathogens. Reduction of the prevalence of contaminated poultry meat or eggs is one major area of focus. The other is risk communication to the consumer, where information aimed at changing the food preparation behaviour has been utilised as a risk management tool. The efficacy of messages such as 'cook poultry meat and eggs thoroughly' or 'wash your hands' will depend both on the ability to change consumer behaviour as well as where the risk can best be mitigated. In order to prioritise what message should be given to the consumer, the relative contribution of different exposure pathways finally leading to ingestion of the pathogens and resulting in illness needs to be known. It is important to know whether cross-contamination events or undercooking are the greatest risk lurking in consumers' kitchens. A review of studies looking at the location of pathogens in food products has been performed and data regarding internal and external (surface) contamination of poultry meat with Salmonella spp. and Campylobacter jejuni and C. coli is presented. In the case of eggs, data on internal contamination with Salmonella and for contamination of egg shells with Salmonella and Campylobacter are discussed. The results from published risk assessments for these pathogen-food commodity combinations have been evaluated and conclusions regarding the relative risk of internal and external contamination of poultry meat and eggs were drawn. In conclusion, cross-contamination events from activities such as use of the same cutting board for chicken meat and salad without intermediate cleaning or spreading of pathogens via the kitchen environment seem to be of greater importance than the risk associated with undercooking of poultry meat or eggs. Risk management options are discussed against the background of risk communication strategies used in different countries.",
"title": "Cross-contamination versus undercooking of poultry meat or eggs - which risks need to be managed first?"
},
{
"docid": "MED-4175",
"text": "In this study, 10 perfluorochemicals (PFCs) were measured in meat, meat products, and eggs, and in indoor dust, collected in China. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were the most frequently detected PFCs in these samples. Mean concentrations of PFOS and PFOA in foodstuffs were in the range of 0.05-1.99 ng/g fresh wt and 0.06-12.5 ng/g fresh wt, respectively. The mean concentrations of PFOA, perfluoroheptanoic acid (PFHpA), and PFOS in indoor dust were 205, 14.0, and 4.86 ng/g, dry wt, respectively. The estimated daily intake of PFOS and PFOA from meat, meat products and eggs (EDI(meat&eggs)) ranged from 6.00 to 9.64 ng/d and from 254 to 576 ng/d, respectively, when the values below the limit of quantitation (LOQ) were assigned as 0, and from 8.80 to 15.0 ng/d and from 255 to 577 ng/d, respectively, when the values below the LOQ were set at 1/2LOQ. The EDI(meat&eggs) of PFOS and PFOA increased with increasing family income. The estimated daily intake of PFOS and PFOA through inhalation of dust (EDI(dust)) ranged from 0.23 to 0.31 ng/d and from 9.68 to 13.4 ng/d, respectively. The daily intakes of PFOS and PFOA from the consumption of meat, meat products, and eggs, and from dust ingestion, as calculated from our samples in this study, were compared with estimated daily intake of PFCs reported from the concentrations in drinking water, fish and seafood from China. Our calculations indicate that dietary sources (EDI(dietary)) account for the overwhelming proportion of (>99% for PFOS and 98% for PFOA) total daily intake (TDI) in adults. The analyzed foodstuffs (meat, meat products, and eggs) were not the major contributors to dietary exposure to PFOS, whereas, meat was the primary contributor to dietary exposure to PFOA.",
"title": "Perfluorochemicals in meat, eggs and indoor dust in China: assessment of sources and pathways of human exposure to perfluorochemicals."
},
{
"docid": "MED-2973",
"text": "OBJECTIVE: Type 2 diabetes mellitus appears to involve an interaction between susceptible genetic backgrounds and environmental factors including highly calorific diets. As it is important to identify modifiable risk factors that may help reduce the risk of type 2 diabetes mellitus, the aim of the present study was to determine the association between egg consumption and the risk of type 2 diabetes mellitus. DESIGN: A specifically designed questionnaire was used to collect information on possible risk factors of type 2 diabetes mellitus. The odds ratios and 95 % confidence intervals for type 2 diabetes mellitus were calculated by conditional logistic regression. SETTING: A case-control study in a Lithuanian out-patient clinic was performed in 2001. SUBJECTS: A total of 234 cases with a newly confirmed diagnosis of type 2 diabetes mellitus and 468 controls free of the disease. RESULTS: Variables such as BMI, family history of diabetes, cigarette smoking, education, morning exercise and plasma TAG level were retained in multivariate logistic regression models as confounders because their inclusion changed the value of the odds ratio by more than 10 % in any exposure category. After adjustment for possible confounders more than twofold increased risk of type 2 diabetes mellitus was determined for individuals consuming 3-4·9 eggs/week (OR = 2·60; 95 % CI 1·34, 5·08) and threefold increased risk of the disease was determined for individuals consuming ≥5 eggs/week (OR = 3·02; 95 % CI 1·14, 7·98) compared with those eating <1 egg/week. CONCLUSIONS: Our data support a possible relationship of egg consumption and increased risk of type 2 diabetes mellitus.",
"title": "Egg consumption and the risk of type 2 diabetes mellitus: a case-control study."
},
{
"docid": "MED-1956",
"text": "The U.S. Food and Drug Administration (FDA) terminated the use of ball clay from a mine in Mississippi as an additive in animal feed after discovering nanogram per gram concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). The FDA collected chicken eggs and farm-raised catfish in affected areas and throughout the remaining continental United States to assess levels of 2,3,7,8-TCDD. A new method using quadrupole ion storage tandem-in-time mass spectrometry (QISTMS) measured the 2,3,7,8-TCDD levels in 42 catfish fillet composites, 3 Tilapia fillet composites, 46 chicken egg samples, and 6 chicken feeds. Six catfish composites and 20 egg samples had 2,3,7,8-TCDD concentrations significantly above 1.0 pg/g wet weight of fillet or whole egg. Farm-raised catfish not exposed to feed containing ball clay had a mean 2,3,7,8-TCDD concentration of 0.12 pg/g. The TCDD isomer pattern in ball clay differed from the TCDD isomer pattern in a fly ash sample and from the \"chick edema factor\" TCDD pattern in a sample of reference toxic fat used as a feed ingredient in the 1950s.",
"title": "Elevated TCDD in chicken eggs and farm-raised catfish fed a diet with ball clay from a Southern United States mine."
},
{
"docid": "MED-4741",
"text": "BACKGROUND: Previous studies have suggested that egg consumption may increase the risk of colorectal cancer and some other cancers. However, the evidence is still limited. To further explore the association between egg intake and cancer risk we conducted a case-control study of 11 cancer sites in Uruguay between 1996 and 2004, including 3,539 cancer cases and 2,032 hospital controls. RESULTS: In the multivariable model with adjustment for age, sex (when applicable), residence, education, income, interviewer, smoking, alcohol intake, intake of fruits and vegetables, grains, dairy products, fatty foods, meat, energy intake and BMI, there was a significant increase in the odds of cancers of the oral cavity and pharynx (OR= 2.02, 95% CI: 1.19-3.44), upper aerodigestive tract (OR= 1.67, 95% CI: 1.17-2.37), colorectum (OR= 1.64, 95% CI: 1.02-2.63), lung (OR= 1.59, 95% CI: 1.10-2.29), breast (OR= 2.86, 95% CI: 1.66-4.92), prostate (OR= 1.89, 95% CI: 1.15-3.10), bladder (OR= 2.23, 95% CI: 1.30-3.83) and all cancer sites combined (OR= 1.71, 95% CI: 1.35-2.17) with a high vs low egg intake. CONCLUSIONS: We found an association between higher intake of eggs and increased risk of several cancers. Further prospective studies of these associations are warranted.",
"title": "Egg consumption and the risk of cancer: a multisite case-control study in Uruguay."
},
{
"docid": "MED-2374",
"text": "OBJECTIVES: To assess the dose-response relationship between egg consumption and the risk of cardiovascular diseases (CVD) and diabetes. METHODS: We systematically searched MEDLINE database through December 2012. Fixed- or random-effects model was used to pool the relative risks (RRs) and their 95% confidence intervals (CIs). Subgroup analyses was performed to explore the potential sources of heterogeneity. Weighted linear regression model was used to estimate the dose-response relationship. RESULTS: Fourteen studies involving 320,778 subjects were included. The pooled RRs of the risk of CVD, CVD for separated diabetes patients, and diabetes for the highest vs lowest egg intake were 1.19 (95% CI 1.02-1.38), 1.83 (95% CI 1.42-2.37), 1.68 (95% CI 1.41-2.00), respectively. For each 4/week increment in egg intake, the RRs of the risk for CVD, CVD for separated diabetes patients, diabetes was 1.06 (95% CI 1.03-1.10), 1.40 (95% CI 1.25-1.57), 1.29 (95% CI 1.21-1.37), respectively. Subgroup analyses showed that population in other western countries have increased CVD than ones in USA (RR 2.00, 95% CI 1.14 to 3.51 vs 1.13, 95% CI 0.98 to 1.30, P = 0.02 for subgroup difference). CONCLUSIONS: Our study suggests that there is a dose-response positive association between egg consumption and the risk of CVD and diabetes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.",
"title": "Egg consumption and risk of cardiovascular diseases and diabetes: a meta-analysis."
},
{
"docid": "MED-1890",
"text": "BACKGROUND: Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. OBJECTIVE: The objective was to review the effect of dietary cholesterol on the ratio of total to HDL cholesterol. DESIGN: Studies were identified by MEDLINE and Biological s searches (from 1974 to June 1999) and by reviewing reference lists. In addition, we included data from a more recently published study. Studies were included if they had a crossover or parallel design with a control group, if the experimental diets differed only in the amount of dietary cholesterol or number of eggs and were fed for > or =14 d, and if HDL-cholesterol concentrations were reported. Of the 222 studies identified, 17 studies involving 556 subjects met these criteria. RESULTS: The addition of 100 mg dietary cholesterol/d increased the ratio of total to HDL cholesterol by 0.020 units (95% CI: 0.010, 0.030), total cholesterol concentrations by 0.056 mmol/L (2.2 mg/dL) (95% CI: 0.046, 0.065 mmol/L; 1.8, 2.5 mg/dL), and HDL-cholesterol concentrations by 0.008 mmol/L (0.3 mg/dL) (95% CI: 0.005, 0.010 mmol/L; 0.2, 0.4 mg/dL). CONCLUSIONS: Dietary cholesterol raises the ratio of total to HDL cholesterol and, therefore, adversely affects the cholesterol profile. The advice to limit cholesterol intake by reducing consumption of eggs and other cholesterol-rich foods may therefore still be valid.",
"title": "Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans: a meta-analysis."
},
{
"docid": "MED-1174",
"text": "We used a novel study design to measure dietary organophosphorus pesticide exposure in a group of 23 elementary school-age children through urinary biomonitoring. We substituted most of children’s conventional diets with organic food items for 5 consecutive days and collected two spot daily urine samples, first-morning and before-bedtime voids, throughout the 15-day study period. We found that the median urinary concentrations of the specific metabolites for malathion and chlorpyrifos decreased to the nondetect levels immediately after the introduction of organic diets and remained nondetectable until the conventional diets were reintroduced. The median concentrations for other organophosphorus pesticide metabolites were also lower in the organic diet consumption days; however, the detection of those metabolites was not frequent enough to show any statistical significance. In conclusion, we were able to demonstrate that an organic diet provides a dramatic and immediate protective effect against exposures to organophosphorus pesticides that are commonly used in agricultural production. We also concluded that these children were most likely exposed to these organophosphorus pesticides exclusively through their diet. To our knowledge, this is the first study to employ a longitudinal design with a dietary intervention to assess children’s exposure to pesticides. It provides new and persuasive evidence of the effectiveness of this intervention.",
"title": "Organic Diets Significantly Lower Children’s Dietary Exposure to Organophosphorus Pesticides"
},
{
"docid": "MED-751",
"text": "BACKGROUND AND AIMS Although dietary fats and cholesterol have previously been associated with risk of cardiovascular disease (CVD) in middle aged populations, less is known among older adults. The purpose of this study was to determine the association between dietary fats, cholesterol, and eggs and CVD risk among community-dwelling adults aged 70–79 in the Health, Aging and Body Composition Study. METHODS AND RESULTS Diet was assessed using an interviewer-administered 108-item food frequency questionnaire (n=1,941). CVD events were defined as a confirmed myocardial infarction, coronary death, or stroke. Relative rates of CVD over 9 years of follow-up were estimated using Cox proportional hazards models. During follow-up, there were 203 incident cases of CVD. There were no significant associations between dietary fats and CVD risk. Dietary cholesterol (HR (95% CI): 1.47 (0.93, 2.32) for the upper vs. lower tertile; P for trend, 0.10) and egg consumption (HR (95% CI): 1.68 (1.12, 2.51) for 3+/week vs. <1/week); P for trend, 0.01) were associated with increased CVD risk. However, in subgroup analyses, dietary cholesterol and egg consumption were associated with increased CVD risk only among older adults with type 2 diabetes (HR (95% CI): 3.66 (1.09, 12.29) and 5.02 (1.63, 15.52), respectively, for the upper vs. lower tertile/group). CONCLUSIONS Dietary cholesterol and egg consumption were associated with increased CVD risk among older, community-dwelling adults with type 2 diabetes. Further research on the biological mechanism(s) for the increased CVD risk with higher dietary cholesterol and frequent egg consumption among older adults with diabetes is warranted.",
"title": "Dietary Fat and Cholesterol and Risk of Cardiovascular Disease in Older Adults: the Health ABC Study"
},
{
"docid": "MED-4676",
"text": "A widespread misconception has been developing among the Canadian public and among physicians. It is increasingly believed that consumption of dietary cholesterol and egg yolks is harmless. There are good reasons for long-standing recommendations that dietary cholesterol should be limited to less than 200 mg/day; a single large egg yolk contains approximately 275 mg of cholesterol (more than a day’s worth of cholesterol). Although some studies showed no harm from consumption of eggs in healthy people, this outcome may have been due to lack of power to detect clinically relevant increases in a low-risk population. Moreover, the same studies showed that among participants who became diabetic during observation, consumption of one egg a day doubled their risk compared with less than one egg a week. Diet is not just about fasting cholesterol; it is mainly about the postprandial effects of cholesterol, saturated fats, oxidative stress and inflammation. A misplaced focus on fasting lipids obscures three key issues. Dietary cholesterol increases the susceptibility of low-density lipoprotein to oxidation, increases postprandial lipemia and potentiates the adverse effects of dietary saturated fat. Dietary cholesterol, including egg yolks, is harmful to the arteries. Patients at risk of cardiovascular disease should limit their intake of cholesterol. Stopping the consumption of egg yolks after a stroke or myocardial infarction would be like quitting smoking after a diagnosis of lung cancer: a necessary action, but late. The evidence presented in the current review suggests that the widespread perception among the public and health care professionals that dietary cholesterol is benign is misplaced, and that improved education is needed to correct this misconception. Résumé Une idée fausse et généralisée se répand au sein du public canadien et des médecins, qui pensent de plus en plus que la consommation de cholestérol alimentaire et de jaunes d’œuf est inoffensive. Les recommandations de longue date qui préconisent de limiter le cholestérol alimentaire à moins de 200 mg/jour reposent sur de bonnes raisons. Un seul gros jaune d’œuf contient environ 275 mg de cholestérol (plus que la portion quotidienne de cholestérol). Même si certaines études ont démontré que la consommation d’œufs n’est pas nuisible chez les personnes en santé, ce résultat peut découler de l’absence de capacité à déceler des augmentations pertinentes sur le plan clinique au sein d’une population à faible risque. De plus, les mêmes études ont révélé que chez les participants devenus diabétiques pendant la période d’observation, la consommation d’un œuf par jour doublait leur risque par rapport à la consommation de moins d’un œuf par semaine. Le régime ne vise pas à éviter le cholestérol, mais surtout les effets postprandiaux du cholestérol, des gras saturés, du stress oxydant et de l’inflammation. Le fait de se concentrer à tort sur les lipides à jeun occulte trois enjeux. Le cholestérol alimentaire accroît la susceptibilité des lipoprotéines à faible densité à l’oxydation, accroît la lipémie postprandiale et potentialise les effets secondaires des graisses saturées alimentaires. Le cholestérol alimentaire, y compris les jaunes d’œuf, est nuisible pour les artères. Les patients vulnérables aux maladies cardiovasculaires devraient limiter leur consommation de cholestérol. Le fait d’arrêter de consommer des jaunes d’œuf après un accident vasculaire cérébral ou un infarctus du myocarde s’apparenterait à arrêter de fumer après un diagnostic de cancer du poumon : c’est un geste nécessaire, mais entrepris tardivement. D’après les données probantes présentées dans la présente analyse, la perception généralisée du public et des professionnels de la santé selon laquelle le cholestérol alimentaire est un mal bénin est une idée fausse, et une meilleure information s’impose pour la corriger.",
"title": "Dietary cholesterol and egg yolks: Not for patients at risk of vascular disease"
},
{
"docid": "MED-2221",
"text": "Context: In 1954 the tobacco industry paid to publish the “Frank Statement to Cigarette Smokers” in hundreds of U.S. newspapers. It stated that the public's health was the industry's concern above all others and promised a variety of good-faith changes. What followed were decades of deceit and actions that cost millions of lives. In the hope that the food history will be written differently, this article both highlights important lessons that can be learned from the tobacco experience and recommends actions for the food industry. Methods: A review and analysis of empirical and historical evidence pertaining to tobacco and food industry practices, messages, and strategies to influence public opinion, legislation and regulation, litigation, and the conduct of science. Findings: The tobacco industry had a playbook, a script, that emphasized personal responsibility, paying scientists who delivered research that instilled doubt, criticizing the “junk” science that found harms associated with smoking, making self-regulatory pledges, lobbying with massive resources to stifle government action, introducing “safer” products, and simultaneously manipulating and denying both the addictive nature of their products and their marketing to children. The script of the food industry is both similar to and different from the tobacco industry script. Conclusions: Food is obviously different from tobacco, and the food industry differs from tobacco companies in important ways, but there also are significant similarities in the actions that these industries have taken in response to concern that their products cause harm. Because obesity is now a major global problem, the world cannot afford a repeat of the tobacco history, in which industry talks about the moral high ground but does not occupy it.",
"title": "The Perils of Ignoring History: Big Tobacco Played Dirty and Millions Died. How Similar Is Big Food?"
}
] |
140147
|
Bob Arum worked independently his whole life.
|
[
{
"docid": "Bob_Arum",
"text": "Robert Arum ( born December 8 , 1931 ) is an American lawyer , boxing promoter and businessman . He is the founder and CEO of Top Rank , a professional boxing promotion company based in Las Vegas . He also worked for the US Attorney 's Office for the southern district of New York in the tax division during his legal career before moving into boxing promotion .",
"title": ""
}
] |
[
{
"docid": "Marley_(soundtrack)",
"text": "Marley is a posthumous two-disc soundtrack album by Bob Marley & The Wailers . It was released by Island Records and Tuff Gong Records . The soundtrack features music from the whole career of Bob Marley , his first recorded song , `` Judge Not '' , to the last album he released in his lifetime , `` Uprising '' . Marley was released to coincide with the release of Marley , a biographical film documenting the life of Bob Marley . The album features 24 of the 66 tracks used in the film .",
"title": ""
},
{
"docid": "Steve_Eisner",
"text": "Steve Eisner ( 1929 -- 2003 ) was a boxing promoter ; an entrepreneur ; a dealer in fine art and antiquities ; the owner of record stores and drive-in movie theaters ; a street scrapper ; a professional boxer ; a cryptographer for the army ; a merchant marine ; a philosopher ( earning his Ph.B . from the University of Detroit ) ; the editor of Fresco , a literary magazine ; a poet and a punster ; and the father of four children . He became very well known as the premier boxing promoter in the state of Arizona , where he lived in Scottsdale during the last decades of his life with his wife , Nancy . As a boxing manager/promoter , Eisner worked closely with many of the sport 's top names including Bob Arum 's Top Rank Inc. and Emanuel Steward 's Kronk Boxing Team . In 1979 Steve sold his record shop `` rolling stone records and tapes '' located in flagstaff az . which was later destroyed in a fire some believed to be arson . The new owner of ( LA records and tapes ) only known by LEONARD also disappeared shortly after the fire . Eisner guided the careers of many fighters , including Jerry Schoolboy Cheatham , Edgar Wallace , Ramon Olivas , Chuck Walker , and Paea Wolfgramm . Eisner was born in New York City , but raised in Detroit where as a young adult he became friends with legendary pimp/hustler ` Diamond ' Jim Riley . He had a fascination with history , and a thirst for knowledge . He penned such masterpieces of pun and fun as the following : `` Wilt thou , '' he said In a voice softly lilted `` Wilt thou , '' he said With his head slightly tilted `` Wilt thou , '' he said As he looked into her eyes `` Wilt thou , '' he said And much to his surprise ... She wilted ! Steve Eisner lost his brief fight to cancer on August 30 , 2003 .",
"title": ""
},
{
"docid": "Robert_Marcelonis",
"text": "Robert ( `` Bob '' ) Marcelonis ( June 2 , 1953 to March 30 , 1995 ) was an American musician and artist , based in Philadelphia . Marcelonis was known in the Philadelphia arts community as a songwriter , playwright and founder of several improvisational comedy groups . Naturally gifted and raised in a religious family , Bob had composed Masses , Ave Maria 's and commemorative pieces for the canonization of Saint John Neumann . He sang in the choir of the Basilica of Saints Peter and Paul . As well as playing various instruments , composing and orchestrating , Bob had an incredible voice and a natural singing ability . He graduated from Temple University 's School of Music in May 1975 , as a music composition major . He was interested in of all types of music and cultures , which would often influence his musical compositions . Though classically trained , he participated in the folk festival every year . And as well as masses , wrote inane lyrics and silly songs , always happy to make people laugh or to laugh himself . As is often the case with artists , Marcelonis had to find work outside of the arts in order to make ends meet . He became an accomplished computer systems analyst in a matter of months through self-study and was able to maintain a comfortable lifestyle through this work . During the late-1970s and early-1980s Marcelonis wrote scores of songs and played the local coffeehouse circuit both as a solo act and with his band , Melisma . He lived for several years during the late-1970s and early-1980s in Los Angeles where he worked with `` The Groundlings '' learning the craft of improvisational comedy . His mother was diagnosed with cancer just as Bob was starting to break through in both his musical and comedic talents . He returned home to Germantown , in Philadelphia , to care for his mother until she died . He remained in the home where he grew up never returning to California . Upon returning home to Philadelphia he soon started his own series of improv groups . Some of the descendants of these groups are still performing in Philadelphia and other areas , to this day . He was thought of by many as a `` catalyst '' ; bringing creative people together and initiating the creative process in music , comedy and various artistic media . Bob wrote a lot of comedy and could find humor in all of life . Bob used to justify his wit with his famous phrase : `` Didja laugh ?? Well , then !! '' Always , with a smile , a joke , a song -- Bob was a man of many talents and a very simplistic , uncomplicated life view . In the early-1990s , Bob 's life would change drastically when he learned he was HIV positive . Bob fought hard for his life but came to accept his pending death as certain , as his illness would infiltrate his body and he would get AIDS , suffering greatly . At first he feared admitting his illness and losing his family and friends . But in the end , pure love overcame fear and as he told each of his family and friends , all embraced him and all were with him to the very end . Bob used his illness as inspiration and motivation to complete his vision of two plays . One , Fables , based on Aesop 's fables , was a continual work in progress from High School until he was forty . His artist friends came together and performed the play to standing room only audiences , sold out for its run . Aids now had the upper hand on Bob but he had desire to complete one more play , Copernicus , an ironic twist since Nicolaus Copernicus the astronomer had leprosy , the AIDS of 15th century . He wrote constantly , as he could feel himself getting weaker . It may be that his need to write the play , compose the music and the scores , is what got him through the ever darkening days of his health . His music 's inspiration and aware of his time limitations , Bob made this not only a mission but his final work . Copernicus was a masterpiece of all his talents , music , composition , writing , comedy , love , life and death . Bob paralleled the story to living with AIDS and used his play as a project for an AIDS fundraiser , `` The Copernicus Project . '' Artists came from all over the world to mount this play . The hand sewn costumes were brilliant , a gift from Catherine Jansen , a well-respected mixed media artist shown in many galleries . Opera singers came from all over the globe to give Bob 's play the best it could have . As he was writing the play his illness progressed . He lost vision in one eye and suffered terrible pain in his body . But love and passion kept his fire ever burning and he worked night and day on Copernicus , his gift to us , his love story . He once said to a friend : `` I am sick with a deadly disease , I am weak and dying , this I know . But I also know that I am very blessed to be loved unconditionally , no matter what . And you know what ? Right now , with my play being produced and all my friends and family here and to be so loved ... even with AIDS , knowing I am dying , I would n't trade places with anyone at this moment ! '' And he would not have . A man of great ability and the capacity to love and to be loved . He never had an agenda , just a passion for life , laughter and music . Marcelonis died in his home in the Germantown section of Philadelphia in March 1995 after a prolonged struggle with AIDS . Category :1953 births Category :1995 deaths Category : American male musicians Category :20 th-century American musicians",
"title": ""
},
{
"docid": "The_Battle_of_the_Champions_(boxing)",
"text": "The Battle of the Champions , was a term used by promoter Bob Arum regarding the November 12 , 1982 boxing match between Aaron Pryor and Alexis Argüello .",
"title": ""
},
{
"docid": "Roberto_Marroquin",
"text": "Roberto Marroquin ( born August 21 , 1989 in Dallas , Texas ) is a Mexican American boxer in the super bantamweight division and he is signed to Bob Arum 's Top Rank .",
"title": ""
},
{
"docid": "Brad_Solomon",
"text": "Brad Solomon ( born May 29 , 1983 in Lafayette , Louisiana ) is an American professional boxer in the welterweight division . He is seen as one of the best boxing prospects in the welterweight division and is currently promoted by Bob Arum 's Top Rank .",
"title": ""
},
{
"docid": "Richard_Arum",
"text": "Richard Arum ( born 1963 ) is an American sociologist of education and stratification , best known for his research on student learning , school discipline , race , and inequality in K-12 and higher education . Arum has a B.A. in Political Science from Tufts University , an M.Ed . in Teaching and Curriculum from the Harvard University Graduate School of Education , and a Ph.D. in Sociology from the University of California , Berkeley . He is currently dean of the University of California , Irvine School of Education , as well as a senior fellow at the Bill and Melinda Gates Foundation .",
"title": ""
},
{
"docid": "Piophila",
"text": "Piophila is a genus of small two-winged flies which includes the species known as the cheese fly . As a whole , the genus is often called wine flies ; they prefer fermented foodstuffs to deposit their eggs . Piophila vulgaris visits Arum maculatum flowers in England . The genus is found in the Palearctic .",
"title": ""
},
{
"docid": "Shaheed_Udham_Singh_(film)",
"text": "Shaheed Udham Singh is a 2000 revolutionary movie based on the life of the son of Hindustani soil , Shaheed Udham Singh who spent his whole life to punish Michael O'Dwyer , the British Lieutenant Governor of the Punjab who ordered the massacre of a thousand people at Jallianwala Bagh in Amritsar . The film was screened retrospective on August 13 , 2016 at the Independence Day Film Festival jointly presented by the Indian Directorate of Film Festivals and Ministry of Defense , commemorating 70th Indian Independence Day .",
"title": ""
},
{
"docid": "Arum_(disambiguation)",
"text": "Arum is a plant genus . Arum may also refer to : Araceae , a family of plants called the `` arum family ''",
"title": ""
},
{
"docid": "Bob_Kilger",
"text": "Bob Kilger ( born June 29 , 1944 ) is a Canadian politician . Born in Cornwall , Ontario , Kilger is the former Liberal member of Parliament for the Cornwall region , representing the riding Stormont -- Dundas -- South Glengarry from 2000 to 2004 , and Stormont -- Dundas from 1988 to 2000 . He was Chief Government Whip , and Deputy Speaker and Chairman of Committees of the Whole of the House of Commons . He lost his seat in the 2004 election to Conservative candidate Guy Lauzon . Prior to his political life , he was a businessman and coached the Cornwall Royals to a Memorial Cup victory in 1981 . He also was a referee in the NHL . His son is retired Toronto Maple Leafs forward Chad Kilger . Kilger was elected Mayor of the City of Cornwall on November 13 , 2006 with 49.4 % of the popular vote . He was re-elected on October 25 , 2010 . On October 27 , 2014 , Kilger lost the 2014 mayoral race to Leslie O'Shaughnessy by nearly 1000 votes .",
"title": ""
},
{
"docid": "Francesco_Signorelli",
"text": "Francesco Signorelli ( c. 1495 -- 1553 ) was a 16th-century Italian Renaissance painter . Not much is known about Signorelli 's life except through his works . He was born , and lived and worked his whole life in and around Cortona . He primarily painted religious-themed paintings for church commissions . One work executed by Francesco Signorelli Madonna and Child is part of the National Museums Liverpool collection .",
"title": ""
},
{
"docid": "Arum_frog",
"text": "The arum frog , Horstock 's arum-frog , arum lily frog , or Horstock 's reed frog ( Hyperolius horstockii ) is a species of frog in the family Hyperoliidae . It is endemic to South Africa .",
"title": ""
},
{
"docid": "Alamat_ng_Gubat",
"text": "Alamat ng Gubat ( Legend of the Forest ) is the fourth book published in 2003 by Bob Ong , a Filipino contemporary author noted for using conversational Filipino to create humorous and reflective depictions of life as a Filipino . Among Bob Ong 's works , it is notable for being the first one to be a self-contained straightforward narrative rather than a collection of anecdotes . Bob Ong later came up with another book written as a straightforward narrative , MacArthur , but it is a very different work because it does not have Bob Ong 's signature humorous tone . The story is about a little crab named `` Tong '' searching for a banana heart to cure his father from sickness . While he begins his journey he finds he and his friends also fight the evil animals in the forest . Alamat ng Gubat is notable for its allegorical references to Philippine society .",
"title": ""
},
{
"docid": "Arum_alpinum",
"text": "Arum alpinum , commonly known as mountain arum , is a member the plant family Araceae . Certain occurrences of this plant in Denmark were previously labelled as the subspecies A. alpinum ssp . danicum , but these are now recognized as Arum cylindraceum . Category : Aroideae",
"title": ""
},
{
"docid": "Bob_Parent_(photographer)",
"text": "Bob Parent ( 1923 -- 1987 ) was a Canadian-born photographer who specialized in photographing the Jazz musicians of New York City . His phototgraphs often appeared in Life , Down Beat and Metronome magazines , in books and album covers . He also designed LP jackets for independent recording companies , such as Miles Davis ' Conception for Prestige . During the 1960s , he turned to social and political photojournalism . He died from a brain tumor in 1987 .",
"title": ""
},
{
"docid": "Bob:_A_Life_in_Five_Acts",
"text": "Bob : A Life in Five Acts is a play written by actor and playwright Peter Sinn Nachtrieb . The play was the winner of the 2010 Barrie and Bernice Stavis Award from the National Theatre Conference . It follows the life and adventures of Bob , a man certain of his destiny for greatness , as he struggles to find his purpose . Divided into five acts , each section of the play corresponds with a period in Bob 's life . In 2012 , it was published by Dramatists Play Service , Inc. .",
"title": ""
},
{
"docid": "Arumer_Zwarte_Hoop",
"text": "The Arumer Zwarte Hoop ( meaning `` Black Heap of Arum '' ; Swarte Heap ) was an army of peasant rebels and mercenaries in Friesland fighting the Habsburg authorities from 1515 to 1523 . The leader was the farmer Pier Gerlofs Donia , whose farm had been burned down and whose kinfolk had been killed by a marauding Landsknecht regiment . Since the regiment had been employed by the Habsburg authorities to suppress the civil war of the Vetkopers and Schieringers , Donia put the blame on the authorities . After this he gathered angry peasants and some petty noblemen from Frisia and Gelderland and formed the Arumer Zwarte Hoop . Under the leadership of Donia ( nicknamed Greate Pier for his size ) , they employed guerrilla tactics and achieved several victories such as the successful siege of two Hollandic castles and the city of Medemblik . The greatest success however came on sea , where Donia sank 28 Dutch ships , earning him the title `` Cross of the Dutchmen '' . The rebels also received financial support from Charles II , Duke of Guelders , who claimed the Duchy of Guelders in opposition to the House of Habsburg . Charles also employed mercenaries under command of his military commander Maarten van Rossum in their support . However , when the tides turned against the rebels after 1520 , Charles withdrew his support . The rebels lost their financial support and could then no longer afford to pay their mercenary army . At about the same time the Arumer Zwarte Hoop also lost their leader . In 1519 , Donia 's health deteriorated . He retired to his farm where he died in 1520 . He is buried in Sneek in the 15th-century Groote Kerk ( also called the Martinikerk ) . Donia 's lieutenant Wijerd Jelckama took over the command of his armies , which then comprised over 4,000 soldiers . Jelckama also achieved some minor victories , but proved to be a less competent commander and slowly lost men . Jelckama and his soldiers indulged in acts of piracy and sacked many villages in the Frisian lands , losing trust and support of their own people . The fact that Jelckama was less charismatic also cost him : he forged less fruitful alliances and lost more than he made . After a series of defeats , he and the remainder of the Frisian army were captured in 1523 . Jelckama and the remaining Frisian and Gelderian rebels were decapitated , putting the rebellion to an end .",
"title": ""
},
{
"docid": "Hardcore_Holly",
"text": "Robert William `` Bob '' Howard ( born January 29 , 1963 ) is a semi-retired American professional wrestler and actor . He is best known for his 15-year career with the World Wrestling Federation/World Wrestling Entertainment ( WWF/E ) under the ring names Thurman `` Sparky '' Plugg , Bob `` Spark Plug '' Holly , Bombastic Bob and Hardcore Holly . After debuting in 1990 , Holly worked for Smoky Mountain Wrestling and other independent promotions , before joining WWE full-time in 1994 . Initially portraying the character of a NASCAR driver , Thurman `` Sparky '' Plugg , his name was soon changed to Bob `` Spark Plug '' Holly . In 1998 , he formed a team with Bart Gunn , known as The New Midnight Express . After becoming known simply as `` Hardcore Holly '' in 1999 , he was joined by on-screen cousins , Crash and Molly . In 2002 , he suffered a broken neck , which sidelined him for over a year . Upon his return , he engaged in minor feuds with wrestlers such as Mr. Kennedy and Rob Van Dam , before forming a tag team with Cody Rhodes in 2007 . Holly departed WWE in 2009 , wrestling intermittently on the independent circuit . He published his autobiography , The Hardcore Truth : The Bob Holly Story , in 2013 . Championships held by Holly over the course of his career include the WWF/E World Tag Team Championship , NWA World Tag Team Championship , and WWF/E Hardcore Championship .",
"title": ""
},
{
"docid": "O'Neal_Compton",
"text": "O'Neal Compton ( born February 5 , 1951 ) is an American film and television actor . He was born Belton O'Neal Compton , Jr. in Sumter , South Carolina , the son of educators . O'Neal Compton is best known as a character actor in films and television ( Life , Nixon , Nell , Primary Colors , Deep Impact , Seinfeld , Diabolique . ) He is also an award-winning writer , producer , photographer and director of television commercials . Compton was badly injured ( and partially paralyzed ) in a fall while working in Florianopolis , Brazil in May , 2003 , and had to stop working as an actor in films for a while . He has spent much of the last 5 years writing screenplays and a book about his life . He also writes a popular political blog , `` The Whole American Hog '' . O'Neal 's art photography has been featured in exhibitions at the Michael Hoppen Gallery ( London ) , Castle Haggenberg ( Vienna ) and in private galleries in Los Angeles , New York , Chicago , New Orleans and South Carolina . His photographs hang in the collections of many celebrities including Morgan Freeman , Johnny Depp , Billy Bob Thornton , Sir Anthony Hopkins , Sharon Stone , Elizabeth Taylor , John Travolta , Emma Thompson and Oliver Stone . O'Neal was commissioned by Jerry Seinfeld to create a series of his `` slow speed '' natural light portraits of the cast and crew in the last year of that show . O'Neal attended Clemson University , The University of South Carolina , Gupton-Jones College of Mortuary Science , and finally , Wofford College , where he discovered the Wofford Theatre Workshop and was thus , saved from a normal life . For the past 33 years , O'Neal has made his living as a film and television actor , screenwriter , photographer , and also as a commercial producer and director . His work has taken him to some of the most exciting cities in the Americas and Europe . He has lived in Charleston , Atlanta , New York , Los Angeles , Buenos Aires , São Paulo , Rio de Janeiro Brazil , London , Dublin , Paris , Vienna , Zurich and Mondello ( Sicily . ) For the past four years , O'Neal has made his home on the Ashley River in Charleston , South Carolina . He is n't quite retired , but he 's close .",
"title": ""
},
{
"docid": "Arum_maculatum",
"text": "Arum maculatum is a common woodland plant species of the Araceae family . It is widespread across most of Europe , as well as Turkey and the Caucasus . It is known by an abundance of common names including snakeshead , adder 's root , arum , wild arum , arum lily , lords-and-ladies , devils and angels , cows and bulls , cuckoo-pint , Adam and Eve , bobbins , naked girls , naked boys , starch-root , wake robin , friar 's cowl , jack in the pulpit and cheese and toast . The name `` lords-and-ladies '' and other gender-related names refer to the plant 's likeness to male and female genitalia symbolising copulation .",
"title": ""
},
{
"docid": "Bob_Rose_(Manitoba_Liberal)",
"text": "Robert D. ( Bob ) Rose ( born July 16 , 1931 in Winnipeg , Manitoba ) is a politician in Manitoba , Canada . He was a member of the Legislative Assembly of Manitoba from 1988 to 1990 , representing the Winnipeg riding of St. Vital for the Manitoba Liberal Party . He should not be confused with another Bob Rose , who sat as a Progressive Conservative in the Manitoba legislature from 1990 to 1995 . Rose worked as a broker before entering political life . He began his political career as a school trustee , and also served as a Winnipeg City Councillor from 1986 to 1988 . Rose was elected to the Manitoba legislature in the 1988 provincial election , defeating Progressive Conservative candidate Paul Herriot . The Liberals increased their legislative strength from one to twenty in this election , and Rose sat as a member of the official opposition for the next two years . In the election of 1990 , he was defeated by Tory Shirley Render . amid a general decline in support for his party . He has not sought a return to political life since this life .",
"title": ""
},
{
"docid": "They_Called_Me_the_Catch_Me_Killer",
"text": "They Called Me the Catch Me Killer is an autobiographical book written by Bob Erler with the help of John C. Souter . Bob Erler was working as a policeman when he was charged and convicted of murder , though it is heavily implied that he is innocent . The book then follows Bob through his years in prison and his escape that ends after a great while with being shot by the police and met with the compassion of the local sheriff . Bob then turns to Jesus and claims to be a Christian , but gradually loses his devotion to Jesus as it seems that he might be released . He then comes back to Christ and his guilt regarding the murder he actually committed makes him withdraw from the juridical process of having the trial 's decision overturned . He then proceeds with his life in prison and becomes a spiritual leader in the prison , converting many inmates and even prison guards to Jesus Christ . Bob Erler was eventually released and became a Christian evangelist . Category : Christian literature Category : Memoirs of imprisonment",
"title": ""
},
{
"docid": "The_Cambridge_Companion_to_Bob_Dylan",
"text": "The Cambridge Companion to Bob Dylan is book published by Cambridge University Press intended to analyze the work of American singer-songwriter Bob Dylan . It is the fourth book of Cambridge Companion to American Studies . This book is edited by Kevin J. Dettmar and contains seventeen essays , each written by a different person . The whole book is divided in two sections . The first one , containing nine essays , attempts to describe different sides Dylan 's work . The next section describes eight landmark Dylan albums . Category : Bob Dylan Category :2009 books Category : Cambridge University Press books Category : Music books",
"title": ""
},
{
"docid": "The_Heart_of_No_Place",
"text": "The Heart of No Place is a 2009 independent film written and directed by Rika Ohara , based on reinterpretation of Yoko Ono 's life and work . Shot entirely on Digital 8 on location in Los Angeles , Berlin , Tokyo , Liverpool and Ho Chi Minh City , and with participation of many Los Angeles - and German artists and musicians , the film won the Best Film ( International ) award at the London Independent Film Festival 2010 . The film 's soundtrack was composed by John Payne and features songs by Yoko Ono , Dieter Moebius , The Dark Bob and Anna Homler .",
"title": ""
},
{
"docid": "Autobiographies_of_Isaac_Asimov",
"text": "Isaac Asimov ( 1920 -- 1992 ) wrote three volumes of autobiography . In Memory Yet Green ( 1979 ) and In Joy Still Felt ( 1980 ) were a two-volume work , covering his life up to 1978 . The third volume , I Asimov : A Memoir ( 1994 ) , published after his death , was not a sequel but a new work which covered his whole life . This third book won a Hugo Award . Before writing these books , Asimov also published three anthologies of science fiction stories which contained autobiographical accounts of his life in the introductions to the stories : The Early Asimov ( 1972 ) , Before the Golden Age ( 1974 ) , and Buy Jupiter and Other Stories ( 1975 ) .",
"title": ""
},
{
"docid": "Arum_Rae",
"text": "Arum Rae ( Latin for waterlily ) is a singer-songwriter based in Brooklyn , New York . Her full birth name is Arum Rae Valkonen ( valkoinen means `` white '' in Finnish ) and she is from Colorado Springs , Colorado . Her sound is heavily influenced by jazz singers like Ella Fitzgerald and Nina Simone . Her style blends heavy , nocturnal beats with auto-tuned soul singing . Arum began performing by driving up to three hours from Virginia to play at various open mics in Washington , D.C. and Frederick , Maryland , which would then open the door for her to return as an opener , and finally performing as the headlining act . Arum now resides in New York City .",
"title": ""
},
{
"docid": "Chris_Salewicz",
"text": "Chris Salewicz is a journalist , broadcaster and novelist who lives in London . He was as a senior features writer for the New Musical Express from 1975 to 1981 where under tutelage of editor Neil Spencer he and other journalists were said to have re-written the book on music journalism . The period Chris spent at NME is regarded by some as a ` Golden Age of Music Journalism ' , where , fuelled by the punk rock explosion the whole genre changed into a complex revolutionary socio economic critique rather than the fan club style journalism of the previous decades . Along with other NME '' 's illumini ( Tony Parsons and Julie Burchill ) of that period Chris 's work soon found its way into serious mainstream publications the Sunday Times , the Independent , the Daily Telegraph , Conde Nast Traveller , Q , Mojo and Time Out , he also wrote for The Face magazine . Salewicz 's time at the NME helped him forge a unique relationship and friendship with two men who would reshape music in the 1970s , 1980s and 1990s : Joe Strummer ( of the Clash ) and Bob Marley . His journeys with these two men from Trenchtown Ghetto , Jamaican Gun Court to Zimbabwean independence , from Maida Vale Squat to Groucho Club to the search for Garcia Lorca 's bones in Andalucía , continued to redefine music journalism . As his subjects influence expanded beyond musical spheres Salewicz 's writing and subsequent books on Joe Strummer ( Redemption Song ) and Bob Marley ( The Untold Story ) would also expand beyond the music into what made Joe and Bob political and cultural icons . 1995 he and film director Don Letts moved to Jamaica for two years to develop film ideas . Drawing on extensive research , Salewicz embarked on the writing of Third World Cop the most successful film ever in the Caribbean when it was released in 1999 . Salewicz is the author of fifteen books , including the acclaimed Rude Boy : Once Upon a Time in Jamaica ; Redemption Song : the Definitive Biography of Joe Strummer , an exhaustive , epic biography of the Clash frontman , and Bob Marley : The Untold Story . He was the on-screen narrator in 2010 's , a documentary feature film -- a cinematically-released documentary in Poland - about how Polish rock 'n' roll helped bring down Communism . The same year he went into Tivoli Gardens in Kingston to report on the `` Dudus affair '' for The Wall Street Journal '' .",
"title": ""
},
{
"docid": "Bob_Golub",
"text": "Bob Golub ( born September 6 , 1957 ) is an American comedian , actor , writer , and filmmaker of Polish descent , whose work is largely inspired from his true-life childhood experiences of growing up in a dysfunctional home located in the steel-mill town of Farrell , Pennsylvania .",
"title": ""
},
{
"docid": "Fighting_Tommy_Riley",
"text": "Fighting Tommy Riley is a 2004 American independent film that tells the story of Tommy Riley and Marty Goldberg , a boxer and his trainer , as they work to secure a title shot for Tommy . Their plans are complicated by the unrequited feelings Marty develops for Tommy . When a big-time promoter seeks to acquire Tommy 's contract , Tommy endangers his future career because of his loyalty to Marty . Marty , seeing only one way to free Tommy to take his shot , takes his own life . Directed by Eddie O'Flaherty , the film was written by J. P. Davis , who sold the script only on the condition that he himself would play Tommy . It also stars Eddie Jones as Marty , Christina Chambers as Stephanie , Diane Tayler as Diane Stone , and Paul Raci as Bob Silver . Fighting Tommy Riley opened in limited release on May 6 , 2005 to generally positive reviews , with Jones 's performance as Marty frequently singled out for praise .",
"title": ""
}
] |
640
|
Inside the body, falciparum parasites reproduce asexually.
|
[
{
"docid": "6503185",
"text": "Plasmodium falciparum malaria, an infectious disease caused by a parasitic protozoan, claims the lives of nearly a million children each year in Africa alone and is a top public health concern. Evidence is accumulating that resistance to artemisinin derivatives, the frontline therapy for the asexual blood stage of the infection, is developing in southeast Asia. Renewed initiatives to eliminate malaria will benefit from an expanded repertoire of antimalarials, including new drugs that kill circulating P. falciparum gametocytes, thereby preventing transmission. Our current understanding of the biology of asexual blood-stage parasites and gametocytes and the ability to culture them in vitro lends optimism that high-throughput screenings of large chemical libraries will produce a new generation of antimalarial drugs. There is also a need for new therapies to reduce the high mortality of severe malaria. An understanding of the pathophysiology of severe disease may identify rational targets for drugs that improve survival.",
"title": "Malaria biology and disease pathogenesis: insights for new treatments"
}
] |
[
{
"docid": "8373753",
"text": "The seasonal dynamics and spatial distributions of Anopheles mosquitoes and Plasmodium falciparum parasites were studied for one year at 30 villages in Malindi, Kilifi, and Kwale Districts along the coast of Kenya. Anopheline mosquitoes were sampled inside houses at each site once every two months and malaria parasite prevalence in local school children was determined at the end of the entomologic survey. A total of 5,476 Anopheles gambiae s.l. and 3,461 An. funestus were collected. Species in the An. gambiae complex, identified by a polymerase chain reaction, included 81.9% An. gambiae s.s., 12.8% An. arabiensis, and 5.3% An. merus. Anopheles gambiae s.s. contributed most to the transmission of P. falciparum along the coast as a whole, while An. funestus accounted for more than 50% of all transmission in Kwale District. Large spatial heterogeneity of transmission intensity (< 1 up to 120 infective bites per person per year) resulted in correspondingly large and significantly related variations in parasite prevalence (range = 38-83%). Thirty-two percent of the sites (7 of 22 sites) with malaria prevalences ranging from 38% to 70% had annual entomologic inoculation rates (EIR) less than five infective bites per person per year. Anopheles gambiae s.l. and An. funestus densities in Kwale were not significantly influenced by rainfall. However, both were positively correlated with rainfall one and three months previously in Malindi and Kilifi Districts, respectively. These unexpected variations in the relationship between mosquito populations and rainfall suggest environmental heterogeneity in the predominant aquatic habitats in each district. One important conclusion is that the highly non-linear relationship between EIRs and prevalence indicates that the consistent pattern of high prevalence might be governed by substantial variation in transmission intensity measured by entomologic surveys. The field-based estimate of entomologic parameters on a district level does not provide a sensitive indicator of transmission intensity in this study.",
"title": "Spatial and temporal heterogeneity of Anopheles mosquitoes and Plasmodium falciparum transmission along the Kenyan coast."
},
{
"docid": "25499612",
"text": "Despite its key role in determining the stability and intensity of malaria transmission, the infectiousness of human populations to mosquitoes has rarely been estimated. Field-based analyses of malaria transmission have frequently relied on the prevalence of asexual parasites or gametocytes as proxies for infectiousness. We now summarize empirical data on human infectiousness from Africa and Papua New Guinea. Over a wide range of transmission intensities there is little relationship between the infectiousness of human populations to vector mosquitoes and mosquito-to-human transmission intensity. We compare these data with the predictions of a stochastic simulation model of Plasmodium falciparum epidemiology. This model predicted little variation in the infectiousness of the human population for entomologic inoculation rates (EIRs) greater than approximately 10 infectious bites per year, demonstrating that the lack of relationship between the EIR and the infectious reservoir can be explained without invoking any effects of acquired transmission-blocking immunity. The near absence of field data from areas with an EIR < 10 per year precluded validation of the model predictions for low EIR values. These results suggest that interventions reducing mosquito-to-human transmission will have little or no effect on human infectiousness at the levels of transmission found in most rural areas of sub-Saharan Africa. Unless very large reductions in transmission can be achieved, measures to prevent mosquito-to-human transmission need to be complemented with interventions that reduce the density or infectiousness of blood stage parasites.",
"title": "Infectiousness of malaria-endemic human populations to vectors."
},
{
"docid": "2460304",
"text": "Erythrocytes carrying a variant hemoglobin allele (HbS), which causes sickle cell disease and resists infection by the malaria parasite Plasmodium falciparum. The molecular basis of this resistance, which has long been recognized as multifactorial, remains incompletely understood. Here we show that the dysregulated microRNA (miRNA) composition, of either heterozygous HbAS or homozygous HbSS erythrocytes, contributes to resistance against P. falciparum. During the intraerythrocytic life cycle of P. falciparum, a subset of erythrocyte miRNAs translocate into the parasite. Two miRNAs, miR-451 and let-7i, were highly enriched in HbAS and HbSS erythrocytes, and these miRNAs, along with miR-223, negatively regulated parasite growth. Surprisingly, we found that miR-451 and let-7i integrated into essential parasite messenger RNAs and, via impaired ribosomal loading, resulted in translational inhibition. Hence, sickle cell erythrocytes exhibit cell-intrinsic resistance to malaria in part through an atypical miRNA activity, which may represent a unique host defense strategy against complex eukaryotic pathogens.",
"title": "Translocation of sickle cell erythrocyte microRNAs into Plasmodium falciparum inhibits parasite translation and contributes to malaria resistance."
},
{
"docid": "40900567",
"text": "The multiplication rates and invasiveness of Plasmodium falciparum parasites isolated from adult Thai patients hospitalized with uncomplicated malaria (n=34) were compared with those from persons with severe malaria (n=42). To simulate severe malaria and control for host effects, the in vitro cultures were adjusted to 1% parasitemia and used the same red blood cell donor. P. falciparum isolates from persons with severe malaria had initial cycle multiplication rates in vitro that were 3-fold higher than those from uncomplicated malaria (median [95% confidence interval], 8.3 [7. 1-10.5] vs. 2.8 [1.7-3.9]; P=.001). Parasites causing severe malaria exhibited unrestricted red blood cell invasion, whereas those from uncomplicated malaria were restricted to a geometric mean of 40 (31%-53%) of red blood cells. P. falciparum parasites causing severe malaria were less selective and multiplied more at high parasitemias than those causing uncomplicated malaria.",
"title": "Parasite multiplication potential and the severity of Falciparum malaria."
},
{
"docid": "21392703",
"text": "All organisms must trade off resource allocation between different life processes that determine their survival and reproduction. Malaria parasites replicate asexually in the host but must produce sexual stages to transmit between hosts. Because different specialized stages are required for these functions, the division of resources between these life-history components is a key problem for natural selection to solve. Despite the medical and economic importance of these parasites, their reproductive strategies remain poorly understood and often seem counterintuitive. Here, we tested recent theory predicting that in-host competition shapes how parasites trade off investment in in-host replication relative to between-host transmission. We demonstrate, across several genotypes, that Plasmodium chabaudi parasites detect the presence of competing genotypes and facultatively respond by reducing their investment in sexual stages in the manner predicted to maximize their competitive ability. Furthermore, we show that genotypes adjust their allocation to sexual stages in line with the availability of exploitable red blood cell resources. Our findings are predicted by evolutionary theory developed to explain life-history trade-offs in more traditionally studied multicellular taxa and suggest that the answer to the long-standing question of why so few transmission stages are produced is that in most natural infections heavy investment in reproduction may compromise in-host survival.",
"title": "Competition and the evolution of reproductive restraint in malaria parasites."
},
{
"docid": "4336849",
"text": "CHLOROQUINE is thought to act against falciparum malaria by accumulating in the acid vesicles of the parasite and interfering with their function14. Parasites resistant to chloroquine expel the drug rapidly in an unaltered form, thereby reducing levels of accumulation in the vesicles5. The discovery that verapamil partially reverses chloroquine resistance in vitro 6 led to the proposal that efflux may involve an ATP-driven P-glycoprotein pump similar to that in mammalian multidrug-resistant (mdr) tumor cell lines. Indeed, Plasmodium falciparum contains at least two mdr-like genes7,8, one of which has been suggested to confer the chloroquine resistant (CQR) phenotype7,9,10. To determine if either of these genes is linked to chloroquine resistance, we performed a genetic cross between CQR and chloroquine-susceptible (CQS) clones of P. falciparum. Examination of 16 independent recombinant progeny indicated that the rapid efflux phenotype is controlled by a single gene or a closely linked group of genes. But, there was no linkage between the rapid efflux, CQR phenotype and either of the mdr-like P. falciparum genes or amplification of those genes. These data indicate that the genetic locus governing chloroquine efflux and resistance is independent of the known mdr-like genes.",
"title": "Chloroquine resistance not linked to mdr-like genes in a Plasmodium falciparum cross"
},
{
"docid": "18074797",
"text": "BACKGROUND Over the past decade malaria intervention coverage has been scaled up across Africa. However, it remains unclear what overall reduction in transmission is achievable using currently available tools. METHODS AND FINDINGS We developed an individual-based simulation model for Plasmodium falciparum transmission in an African context incorporating the three major vector species (Anopheles gambiae s.s., An. arabiensis, and An. funestus) with parameters obtained by fitting to parasite prevalence data from 34 transmission settings across Africa. We incorporated the effect of the switch to artemisinin-combination therapy (ACT) and increasing coverage of long-lasting insecticide treated nets (LLINs) from the year 2000 onwards. We then explored the impact on transmission of continued roll-out of LLINs, additional rounds of indoor residual spraying (IRS), mass screening and treatment (MSAT), and a future RTS,S/AS01 vaccine in six representative settings with varying transmission intensity (as summarized by the annual entomological inoculation rate, EIR: 1 setting with low, 3 with moderate, and 2 with high EIRs), vector-species combinations, and patterns of seasonality. In all settings we considered a realistic target of 80% coverage of interventions. In the low-transmission setting (EIR approximately 3 ibppy [infectious bites per person per year]), LLINs have the potential to reduce malaria transmission to low levels (<1% parasite prevalence in all age-groups) provided usage levels are high and sustained. In two of the moderate-transmission settings (EIR approximately 43 and 81 ibppy), additional rounds of IRS with DDT coupled with MSAT could drive parasite prevalence below a 1% threshold. However, in the third (EIR = 46) with An. arabiensis prevailing, these interventions are insufficient to reach this threshold. In both high-transmission settings (EIR approximately 586 and 675 ibppy), either unrealistically high coverage levels (>90%) or novel tools and/or substantial social improvements will be required, although considerable reductions in prevalence can be achieved with existing tools and realistic coverage levels. CONCLUSIONS Interventions using current tools can result in major reductions in P. falciparum malaria transmission and the associated disease burden in Africa. Reduction to the 1% parasite prevalence threshold is possible in low- to moderate-transmission settings when vectors are primarily endophilic (indoor-resting), provided a comprehensive and sustained intervention program is achieved through roll-out of interventions. In high-transmission settings and those in which vectors are mainly exophilic (outdoor-resting), additional new tools that target exophagic (outdoor-biting), exophilic, and partly zoophagic mosquitoes will be required.",
"title": "Reducing Plasmodium falciparum Malaria Transmission in Africa: A Model-Based Evaluation of Intervention Strategies"
},
{
"docid": "12409683",
"text": "BACKGROUND Artemisinin combination therapies (ACT), which are increasingly being introduced for treatment of Plasmodium falciparum malaria, are more effective against sexual stage parasites (gametocytes) than previous first-line antimalarials and therefore have the potential to reduce parasite transmission. The size of this effect is estimated in symptomatic P. falciparum infections. METHODS Data on 3,174 patients were pooled from six antimalarial trials conducted in The Gambia and Kenya. Multivariable regression was used to investigate the role of ACT versus non-artemisinin antimalarial treatment, treatment failure, presence of pre-treatment gametocytes and submicroscopic gametocytaemia on transmission to mosquitoes and the area under the curve (AUC) of gametocyte density during the 28 days of follow up. RESULTS ACT treatment was associated with a significant reduction in the probability of being gametocytaemic on the day of transmission experiments (OR 0.20 95% CI 0.16-0.26), transmission to mosquitoes by slide-positive gametocyte carriers (OR mosquito infection 0.49 95% CI 0.33-0.73) and AUC of gametocyte density (ratio of means 0.35 95% CI 0.31-0.41). Parasitological treatment failure did not account for the difference between ACT and non-artemisinin impact. The presence of slide-positive gametocytaemia prior to treatment significantly reduced ACT impact on gametocytaemia (p < 0.001). Taking account of submicroscopic gametocytaemia reduced estimates of ACT impact in a high transmission setting in Kenya, but not in a lower transmission setting in the Gambia. CONCLUSION Treatment with ACT significantly reduces infectiousness of individual patients with uncomplicated falciparum malaria compared to previous first line treatments. Rapid treatment of cases before gametocytaemia is well developed may enhance the impact of ACT on transmission.",
"title": "Reduction of transmission from malaria patients by artemisinin combination therapies: a pooled analysis of six randomized trials"
},
{
"docid": "9254550",
"text": "BACKGROUND & OBJECTIVES Anaemia is commonly observed in children with malaria, but reports on leucocyte and platelet count abnormalities associated with malaria are inconsistent. This study examined the effect of age, gender, parasite density and temperature on haematological parameters in children with acute uncomplicated malaria. METHODS Haematological parameters were determined in children with acute uncomplicated malaria, and these were correlated with age, sex, temperature and parasite density. Statistical analysis was done using SAS 9.1. RESULTS Six hundred and ninety five children with acute uncomplicated malaria participated in the study. The mean age was 51.7 months +/- 33.8. At presentation, anaemia occurred in 43.8% of the patients and children <5 yr had a significantly lower haematocrit (28.4% +/- 4.8) than that of older children (32.8% +/- 4.8) (p <0.001), but the haematocrit was not significantly different by days 14 and 28. There was no difference between both sexes. Leucocytosis was more frequently seen than leucopenia (9.5% vs 3%). Thrombocytopenia was found in 59.3% of enrolled patients. More than half of the patients with thrombocytopenia had recovered by Day 28. Baseline platelet count was related to Day 14 (r = 0.6, p < 0.0001) and Day 28 (r = 0.2, p = 0.0015) and the haematocrit on Day 28 (r = 0.12, p = 0.00197). Platelet count showed no correlation with temperature, parasite density and leucocyte count. Haematocrit correlated with age (r = 0.4, p < 0.0001); but not with parasite density or temperature. Leucocyte count showed no correlation with age or parasite density. CONCLUSION While thrombocytopenia was the most common haematological finding and may be of diagnostic importance, anaemia and leucocytosis were more common in the under fives.",
"title": "Age as a risk factor for thrombocytopenia and anaemia in children treated for acute uncomplicated falciparum malaria."
},
{
"docid": "25420421",
"text": "Little is known about the changes in white blood cells and platelets in children with falciparum malaria in endemic areas. We measured the white cell count (WCC) and platelets of 230 healthy children from the community, 1369 children admitted to hospital with symptomatic malaria, and 1461 children with other medical conditions. Children with malaria had a higher WCC compared with community controls, and leucocytosis was strongly associated with younger age, deep breathing, severe anaemia, thrombocytopenia and death. The WCC was not associated with a positive blood culture. In children with malaria, high lymphocyte and low monocyte counts were independently associated with mortality. A platelet count of less than 150 x 109/l was found in 56.7% of children with malaria, and was associated with age, prostration and parasite density, but not with bleeding problems or mortality. The mean platelet volume was also higher in children with malaria compared with other medical conditions. This may reflect early release from the bone marrow in response to peripheral platelet destruction. Thus, leucocytosis was associated with both severity and mortality in children with falciparum malaria, irrespective of bacteraemia, whereas thrombocytopenia, although very common, was not associated with adverse outcome.",
"title": "Changes in white blood cells and platelets in children with falciparum malaria: relationship to disease outcome."
},
{
"docid": "3929361",
"text": "BACKGROUND Malaria elimination requires a variety of approaches individually optimized for different transmission settings. A recent field study in an area of low seasonal transmission in South West Cambodia demonstrated dramatic reductions in malaria parasite prevalence following both mass drug administration (MDA) and high treatment coverage of symptomatic patients with artemisinin-piperaquine plus primaquine. This study employed multiple combined strategies and it was unclear what contribution each made to the reductions in malaria. METHOD AND FINDINGS A mathematical model fitted to the trial results was used to assess the effects of the various components of these interventions, design optimal elimination strategies, and explore their interactions with artemisinin resistance, which has recently been discovered in Western Cambodia. The modelling indicated that most of the initial reduction of P. falciparum malaria resulted from MDA with artemisinin-piperaquine. The subsequent continued decline and near elimination resulted mainly from high coverage with artemisinin-piperaquine treatment. Both these strategies were more effective with the addition of primaquine. MDA with artemisinin combination therapy (ACT) increased the proportion of artemisinin resistant infections, although much less than treatment of symptomatic cases with ACT, and this increase was slowed by adding primaquine. Artemisinin resistance reduced the effectiveness of interventions using ACT when the prevalence of resistance was very high. The main results were robust to assumptions about primaquine action, and immunity. CONCLUSIONS The key messages of these modelling results for policy makers were: high coverage with ACT treatment can produce a long-term reduction in malaria whereas the impact of MDA is generally only short-term; primaquine enhances the effect of ACT in eliminating malaria and reduces the increase in proportion of artemisinin resistant infections; parasite prevalence is a better surveillance measure for elimination programmes than numbers of symptomatic cases; combinations of interventions are most effective and sustained efforts are crucial for successful elimination.",
"title": "Optimising Strategies for Plasmodium falciparum Malaria Elimination in Cambodia: Primaquine, Mass Drug Administration and Artemisinin Resistance"
},
{
"docid": "2264455",
"text": "There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates.",
"title": "Vaccines against malaria"
},
{
"docid": "18174210",
"text": "BACKGROUND The heritable haemoglobinopathy alpha(+)-thalassaemia is caused by the reduced synthesis of alpha-globin chains that form part of normal adult haemoglobin (Hb). Individuals homozygous for alpha(+)-thalassaemia have microcytosis and an increased erythrocyte count. Alpha(+)-thalassaemia homozygosity confers considerable protection against severe malaria, including severe malarial anaemia (SMA) (Hb concentration < 50 g/l), but does not influence parasite count. We tested the hypothesis that the erythrocyte indices associated with alpha(+)-thalassaemia homozygosity provide a haematological benefit during acute malaria. METHODS AND FINDINGS Data from children living on the north coast of Papua New Guinea who had participated in a case-control study of the protection afforded by alpha(+)-thalassaemia against severe malaria were reanalysed to assess the genotype-specific reduction in erythrocyte count and Hb levels associated with acute malarial disease. We observed a reduction in median erythrocyte count of approximately 1.5 x 10(12)/l in all children with acute falciparum malaria relative to values in community children (p < 0.001). We developed a simple mathematical model of the linear relationship between Hb concentration and erythrocyte count. This model predicted that children homozygous for alpha(+)-thalassaemia lose less Hb than children of normal genotype for a reduction in erythrocyte count of >1.1 x 10(12)/l as a result of the reduced mean cell Hb in homozygous alpha(+)-thalassaemia. In addition, children homozygous for alpha(+)-thalassaemia require a 10% greater reduction in erythrocyte count than children of normal genotype (p = 0.02) for Hb concentration to fall to 50 g/l, the cutoff for SMA. We estimated that the haematological profile in children homozygous for alpha(+)-thalassaemia reduces the risk of SMA during acute malaria compared to children of normal genotype (relative risk 0.52; 95% confidence interval [CI] 0.24-1.12, p = 0.09). CONCLUSIONS The increased erythrocyte count and microcytosis in children homozygous for alpha(+)-thalassaemia may contribute substantially to their protection against SMA. A lower concentration of Hb per erythrocyte and a larger population of erythrocytes may be a biologically advantageous strategy against the significant reduction in erythrocyte count that occurs during acute infection with the malaria parasite Plasmodium falciparum. This haematological profile may reduce the risk of anaemia by other Plasmodium species, as well as other causes of anaemia. Other host polymorphisms that induce an increased erythrocyte count and microcytosis may confer a similar advantage.",
"title": "Increased Microerythrocyte Count in Homozygous α+-Thalassaemia Contributes to Protection against Severe Malarial Anaemia"
},
{
"docid": "7486516",
"text": "Asexuals are an important test case for theories of why species exist. If asexual clades displayed the same pattern of discrete variation as sexual clades, this would challenge the traditional view that sex is necessary for diversification into species. However, critical evidence has been lacking: all putative examples have involved organisms with recent or ongoing histories of recombination and have relied on visual interpretation of patterns of genetic and phenotypic variation rather than on formal tests of alternative evolutionary scenarios. Here we show that a classic asexual clade, the bdelloid rotifers, has diversified into distinct evolutionary species. Intensive sampling of the genus Rotaria reveals the presence of well-separated genetic clusters indicative of independent evolution. Moreover, combined genetic and morphological analyses reveal divergent selection in feeding morphology, indicative of niche divergence. Some of the morphologically coherent groups experiencing divergent selection contain several genetic clusters, in common with findings of cryptic species in sexual organisms. Our results show that the main causes of speciation in sexual organisms, population isolation and divergent selection, have the same qualitative effects in an asexual clade. The study also demonstrates how combined molecular and morphological analyses can shed new light on the evolutionary nature of species.",
"title": "Independently Evolving Species in Asexual Bdelloid Rotifers"
},
{
"docid": "1805641",
"text": "BACKGROUND Artemisinin derivatives used in recently introduced combination therapies (ACTs) for Plasmodium falciparum malaria significantly lower patient infectiousness and have the potential to reduce population-level transmission of the parasite. With the increased interest in malaria elimination, understanding the impact on transmission of ACT and other antimalarial drugs with different pharmacodynamics becomes a key issue. This study estimates the reduction in transmission that may be achieved by introducing different types of treatment for symptomatic P. falciparum malaria in endemic areas. METHODS AND FINDINGS We developed a mathematical model to predict the potential impact on transmission outcomes of introducing ACT as first-line treatment for uncomplicated malaria in six areas of varying transmission intensity in Tanzania. We also estimated the impact that could be achieved by antimalarials with different efficacy, prophylactic time, and gametocytocidal effects. Rates of treatment, asymptomatic infection, and symptomatic infection in the six study areas were estimated using the model together with data from a cross-sectional survey of 5,667 individuals conducted prior to policy change from sulfadoxine-pyrimethamine to ACT. The effects of ACT and other drug types on gametocytaemia and infectiousness to mosquitoes were independently estimated from clinical trial data. Predicted percentage reductions in prevalence of infection and incidence of clinical episodes achieved by ACT were highest in the areas with low initial transmission. A 53% reduction in prevalence of infection was seen if 100% of current treatment was switched to ACT in the area where baseline slide-prevalence of parasitaemia was lowest (3.7%), compared to an 11% reduction in the highest-transmission setting (baseline slide prevalence = 57.1%). Estimated percentage reductions in incidence of clinical episodes were similar. The absolute size of the public health impact, however, was greater in the highest-transmission area, with 54 clinical episodes per 100 persons per year averted compared to five per 100 persons per year in the lowest-transmission area. High coverage was important. Reducing presumptive treatment through improved diagnosis substantially reduced the number of treatment courses required per clinical episode averted in the lower-transmission settings although there was some loss of overall impact on transmission. An efficacious antimalarial regimen with no specific gametocytocidal properties but a long prophylactic time was estimated to be more effective at reducing transmission than a short-acting ACT in the highest-transmission setting. CONCLUSIONS Our results suggest that ACTs have the potential for transmission reductions approaching those achieved by insecticide-treated nets in lower-transmission settings. ACT partner drugs and nonartemisinin regimens with longer prophylactic times could result in a larger impact in higher-transmission settings, although their long term benefit must be evaluated in relation to the risk of development of parasite resistance.",
"title": "Modelling the Impact of Artemisinin Combination Therapy and Long-Acting Treatments on Malaria Transmission Intensity"
},
{
"docid": "7734150",
"text": "Pulmonary hypertension (PH) causes loss of body weight and inspiratory (diaphragm) muscle dysfunction. A model of PH induced by drug (monocrotaline, MCT) has been extensively used in mice to examine the etiology of PH. However, it is unclear if PH induced by MCT in mice reproduces the loss of body weight and diaphragm muscle dysfunction seen in patients. This is a pre-requisite for widespread use of mice to examine mechanisms of cachexia and diaphragm abnormalities in PH. Thus, we measured body and soleus muscle weight, food intake, and diaphragm contractile properties in mice after 6-8 weeks of saline (control) or MCT (600 mg/kg) injections. Body weight progressively decreased in PH mice, while food intake was similar in both groups. PH decreased (P<0.05) diaphragm maximal isometric specific force, maximal shortening velocity, and peak power. Protein carbonyls in whole-diaphragm lysates and the abundance of select myofibrillar proteins were unchanged by PH. Our findings show diaphragm isometric and isotonic contractile abnormalities in a murine model of PH induced by MCT. Overall, the murine model of PH elicited by MCT mimics loss of body weight and diaphragm muscle weakness reported in PH patients.",
"title": "Diaphragm Atrophy and Contractile Dysfunction in a Murine Model of Pulmonary Hypertension"
},
{
"docid": "3770726",
"text": "BACKGROUND Microfluidic platforms for quantitative evaluation of cell biologic processes allow low cost and time efficient research studies of biological and pathological events, such as monitoring cell migration by real-time imaging. In healthy and disease states, cell migration is crucial in development and wound healing, as well as to maintain the body's homeostasis. NEW METHOD The microfluidic chambers allow precise measurements to investigate whether fibroblasts carrying a mutation in the TOR1A gene, underlying the hereditary neurologic disease--DYT1 dystonia, have decreased migration properties when compared to control cells. RESULTS We observed that fibroblasts from DYT1 patients showed abnormalities in basic features of cell migration, such as reduced velocity and persistence of movement. COMPARISON WITH EXISTING METHOD The microfluidic method enabled us to demonstrate reduced polarization of the nucleus and abnormal orientation of nuclei and Golgi inside the moving DYT1 patient cells compared to control cells, as well as vectorial movement of single cells. CONCLUSION We report here different assays useful in determining various parameters of cell migration in DYT1 patient cells as a consequence of the TOR1A gene mutation, including a microfluidic platform, which provides a means to evaluate real-time vectorial movement with single cell resolution in a three-dimensional environment.",
"title": "Microfluidic platform to evaluate migration of cells from patients with DYT1 dystonia."
},
{
"docid": "17925632",
"text": "We assessed monthly doses of tafenoquine for preventing Plasmodium vivax and multidrug-resistant P. falciparum malaria. In a randomized, double-blind, placebo-controlled study, 205 Thai soldiers received either a loading dose of tafenoquine 400 mg (base) daily for 3 days, followed by single monthly 400-mg doses (n = 104), or placebo (n = 101), for up to 5 consecutive months. In volunteers completing follow-up (96 tafenoquine and 91 placebo recipients), there were 22 P. vivax, 8 P. falciparum, and 1 mixed infection. All infections except 1 P. vivax occurred in placebo recipients, giving tafenoquine a protective efficacy of 97% for all malaria (95% confidence interval [CI], 82%-99%), 96% for P. vivax malaria (95% CI, 76%-99%), and 100% for P. falciparum malaria (95% CI, 60%-100%). Monthly tafenoquine was safe, well tolerated, and highly effective in preventing P. vivax and multidrug-resistant P. falciparum malaria in Thai soldiers during 6 months of prophylaxis.",
"title": "Efficacy of monthly tafenoquine for prophylaxis of Plasmodium vivax and multidrug-resistant P. falciparum malaria."
},
{
"docid": "13959707",
"text": "BACKGROUND Plasmodium falciparum malaria remains a major cause of illness and death in sub-Saharan Africa. Young children bear the brunt of the disease and though older children and adults suffer relatively fewer clinical attacks, they remain susceptible to asymptomatic P. falciparum infection. A better understanding of the host factors associated with immunity to clinical malaria and the ability to sustain asymptomatic P. falciparum infection will aid the development of improved strategies for disease prevention. METHODS AND FINDINGS Here we investigate whether full differential blood counts can predict susceptibility to clinical malaria among Kenyan children sampled at five annual cross-sectional surveys. We find that the ratio of monocytes to lymphocytes, measured in peripheral blood at the time of survey, directly correlates with risk of clinical malaria during follow-up. This association is evident among children with asymptomatic P. falciparum infection at the time the cell counts are measured (Hazard ratio (HR) = 2.7 (95% CI 1.42, 5.01, P = 0.002) but not in those without detectable parasitaemia (HR = 1.0 (95% CI 0.74, 1.42, P = 0.9). CONCLUSIONS We propose that the monocyte to lymphocyte ratio, which is easily derived from routine full differential blood counts, reflects an individual's capacity to mount an effective immune response to P. falciparum infection.",
"title": "The Ratio of Monocytes to Lymphocytes in Peripheral Blood Correlates with Increased Susceptibility to Clinical Malaria in Kenyan Children"
},
{
"docid": "20221907",
"text": "BACKGROUND Most gynecologists determine therapy based on current International Society of Gynecologic Pathologists (ISGP)/World Health Organization classification of endometrial hyperplasia, the reproducibility of which has been questioned. The Gynecologic Oncology Group (GOG) initiated a protocol to assess the efficacy of hormonal therapy of atypical endometrial hyperplasia (AEH). Primary goals of the first phase (Part A) were to prospectively determine reproducibility of referring institution's pathologist's diagnosis of AEH by a panel of 3 gynecologic pathologists and to determine reproducibility of diagnoses by panel members. METHODS Three hundred six women were entered on this protocol with a referring institution's pathologist diagnosis of AEH based on biopsy or curettage. Available slides were assessed independently and interpreted by each of a panel of 3 gynecologic pathologists who used International Society of Gynecologic Pathologists (ISGP)/World Health Organization criteria. The majority diagnosis was based on diagnostic concordance by at least 2 of the 3 panelists. RESULTS The referring institution's pathologist's diagnosis of AEH was supported by the majority of the panel in only 38% of cases. Overall kappa value for the panel diagnosis of AEH was 0.28. The majority diagnosis was adenocarcinoma in 29%, cycling endometrium in 7%, and nonatypical hyperplasia in 18% of cases. Unanimous agreement for any diagnosis was reached among all 3 of the panel in 40% of cases. For the panel, paired kappa values for any diagnosis ranged 0.34-0.43, with an overall kappa value of 0.40. CONCLUSION Reproducibility of referring institution's pathologists' diagnosis of AEH by a panel of gynecologic pathologists is poor. Both underestimation and overestimation of the severity of the lesion are very common. The level of reproducibility among subspecialist panel members for diagnosis of AEH in these specimens also is poor. Better criteria and better sampling are needed to improve reproducibility of this diagnosis, particularly if it is to be used for clinical decisions.",
"title": "Reproducibility of the diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study."
},
{
"docid": "1852826",
"text": "Interactions between hosts and parasites provide an ongoing source of selection that promotes the evolution of a variety of features in the interacting species. Here, we use a genetically explicit mathematical model to explore how patterns of gene expression evolve at genetic loci responsible for host resistance and parasite infection. Our results reveal the striking yet intuitive conclusion that gene expression should evolve along very different trajectories in the two interacting species. Specifically, host resistance loci should frequently evolve to co-express alleles, whereas parasite infection loci should evolve to express only a single allele. This result arises because hosts that co-express resistance alleles are able to recognize and clear a greater diversity of parasite genotypes. By the same token, parasites that co-express antigen or elicitor alleles are more likely to be recognized and cleared by the host, and this favours the expression of only a single allele. Our model provides testable predictions that can help interpret accumulating data on expression levels for genes relevant to host−parasite interactions.",
"title": "Host–Parasite Interactions and the Evolution of Gene Expression"
},
{
"docid": "15194125",
"text": "This study investigated interobserver (two observers) and intrasubject (two measurements) reproducibility of QT dispersion from abnormal electrocardiograms in patients with previous myocardial infarction, and compared a user-interactive with an automatic measurement system. Standard 12-lead electrocardiograms, recorded at 25 mm.s-1, were randomly chosen from 70 patients following myocardial infarction. These were scanned into a personal computer, and specially designed software skeletonized and joined each image. The images were then available for user-interactive (mouse and computer screen), or automatic measurements using a specially designed algorithm. For all methods reproducibility of the RR interval was excellent (mean absolute errors 3-4 ms, relative errors 0.3-0.5%). Reproducibility of the mean QT interval was good; intrasubject error was 6 ms (relative error 1.4%), interobserver error was 7 ms (1.8%), and observers' vs automatic measurement errors were 10 and 11 ms (2.5, 2.8%). However QTc dispersion measurements had large errors for all methods; intrasubject error was 12 ms (17.3%), interobserver error was 15 ms (22.1%), and observers' vs automatic measurement were errors 30 and 28 ms (35.4, 31.9%). QT dispersion measurements rely on the most difficult to measure QT intervals, resulting in a problem of reproducibility. Any automatic system must not only recognize common T wave morphologies, but also these more difficult T waves, if it is to be useful for measuring QT dispersion. The poor reproducibility of QT dispersion limits its role as a useful clinical tool, particularly as a predictor of events.",
"title": "Reproducibility and automatic measurement of QT dispersion."
},
{
"docid": "26474812",
"text": "Malaria parasites and immune responses in an infected human interact on a dynamic landscape, in which a population of replicating parasites depletes a population of replenishing red blood cells (RBCs). These underlying dynamics receive relatively little attention, but they offer unique insights into the processes that control most malaria infections. Here, we focus on the observation that three of the four malaria-parasite species that infect humans are restricted to particular age classes of RBC. We explicitly incorporate this observation in models of infection dynamics to distinguish common from species-specific pressures on host immune responses, and we find that age structuring has profound effects on the course of infection. For all four species conditions exist under which the parasites may persist at low densities, or may clear, even in the absence of an immune response. Catastrophic anemia can occur even with the two species that attack only the youngest RBCs, although only a small fraction of cells are parasitized at any point. Furthermore, with these two, compensatory erythropoetic responses in the host accelerate parasite population growth. A \"basic reproduction rate\" characterizes these differences in outcomes.",
"title": "Age-structured red blood cell susceptibility and the dynamics of malaria infections."
},
{
"docid": "17168045",
"text": "BACKGROUND This study sought to describe and quantify microcirculatory changes in the mucosal surfaces of patients with severe malaria, by direct in vivo observation using orthogonal polarization spectral (OPS) imaging. METHODS The microcirculation in the rectal mucosa of adult patients with severe malaria was assessed by use of OPS imaging, at admission and then daily. Comparison groups comprised patients with uncomplicated falciparum malaria, patients with bacterial sepsis, and healthy individuals. RESULTS Erythrocyte velocities were measured directly in 43 adult patients with severe falciparum malaria, of whom 20 died. Microcirculatory blood flow was markedly disturbed, with heterogeneous obstruction that was proportional to severity of disease. Blocked capillaries were found in 29 patients (67%) and were associated with concurrent hyperdynamic blood flow (erythrocyte velocity, >750 mm/s) in adjacent vessels in 27 patients (93%). The proportion of blocked capillaries correlated with the base deficit in plasma and with the concentration of lactate. Abnormalities disappeared when the patients recovered. In healthy individuals and in patients with uncomplicated malaria or sepsis, no stagnant erythrocytes were detected, and, in patients with sepsis, hyperdynamic blood flow was prominent. CONCLUSION Patients with severe falciparum malaria show extensive microvascular obstruction that is proportional to the severity of the disease. This finding underscores the prominent role that microvascular obstruction plays in the pathophysiology of severe malaria and illustrates the fundamental difference between the microvascular pathophysiology of malaria and that of bacterial sepsis.",
"title": "Direct in vivo assessment of microcirculatory dysfunction in severe falciparum malaria."
},
{
"docid": "8133050",
"text": "Many microparasites infect new hosts with specialized life stages, requiring a subset of the parasite population to forgo proliferation and develop into transmission forms. Transmission stage production influences infectivity, host exploitation, and the impact of medical interventions like drug treatment. Predicting how parasites will respond to public health efforts on both epidemiological and evolutionary timescales requires understanding transmission strategies. These strategies can rarely be observed directly and must typically be inferred from infection dynamics. Using malaria as a case study, we test previously described methods for inferring transmission stage investment against simulated data generated with a model of within-host infection dynamics, where the true transmission investment is known. We show that existing methods are inadequate and potentially very misleading. The key difficulty lies in separating transmission stages produced by different generations of parasites. We develop a new approach that performs much better on simulated data. Applying this approach to real data from mice infected with a single Plasmodium chabaudi strain, we estimate that transmission investment varies from zero to 20%, with evidence for variable investment over time in some hosts, but not others. These patterns suggest that, even in experimental infections where host genetics and other environmental factors are controlled, parasites may exhibit remarkably different patterns of transmission investment.",
"title": "Quantifying Transmission Investment in Malaria Parasites"
},
{
"docid": "3930020",
"text": "Epidermal Langerhans cells (LCs) play a key role in immune defense mechanisms and in numerous immunological disorders. In this report, we show that percutaneous infection of C57BL/6 mice with the helminth parasite Schistosoma mansoni leads to the activation of LCs but, surprisingly, to their retention in the epidermis. Moreover, using an experimental model of LC migration induced by tumor necrosis factor (TNF)-α, we show that parasites transiently impair the departure of LCs from the epidermis and their subsequent accumulation as dendritic cells in the draining lymph nodes. The inhibitory effect is mediated by soluble lipophilic factors released by the parasites and not by host-derived antiinflammatory cytokines, such as interleukin-10. We find that prostaglandin (PG)D2, but not the other major eicosanoids produced by the parasites, specifically impedes the TNF-α–triggered migration of LCs through the adenylate cyclase–coupled PGD2 receptor (DP receptor). Moreover, the potent DP receptor antagonist BW A868C restores LC migration in infected mice. Finally, in a model of contact allergen-induced LC migration, we show that activation of the DP receptor not only inhibits LC emigration but also dramatically reduces the contact hypersensitivity responses after challenge. Taken together, we propose that the inhibition of LC migration could represent an additional stratagem for the schistosomes to escape the host immune system and that PGD2 may play a key role in the control of cutaneous immune responses.",
"title": "Role of the Parasite-Derived Prostaglandin D2 in the Inhibition of Epidermal Langerhans Cell Migration during Schistosomiasis Infection"
},
{
"docid": "20419913",
"text": "The debate around the frequency and importance of genetic exchange in parasitic protozoa is now several decades old. Recently, fresh assertions have been made that predominant clonal evolution explains the population structures of several key protozoan pathogens. Here, we present an alternative perspective. On the assumption that much apparent clonality may be an artefact of inadequate sampling and study design, we review current research to define why sex might be so difficult to detect in protozoan parasite populations. In doing so, we contrast laboratory models of genetic exchange in parasitic protozoa with natural patterns of genetic diversity and consider the fitness advantage of sex at different evolutionary scales. We discuss approaches to improve the accuracy of efforts to characterize genetic exchange in the field. We also examine the implications of the first population genomic studies for the debate around sex and clonality in parasitic protozoa and discuss caveats for the future.",
"title": "Reproductive clonality in protozoan pathogens--truth or artefact?"
},
{
"docid": "5289038",
"text": "Immune clearance and resource limitation (via red blood cell depletion) shape the peaks and troughs of malaria parasitemia, which in turn affect disease severity and transmission. Quantitatively partitioning the relative roles of these effects through time is challenging. Using data from rodent malaria, we estimated the effective propagation number, which reflects the relative importance of contrasting within-host control mechanisms through time and is sensitive to the inoculating parasite dose. Our analysis showed that the capacity of innate responses to restrict initial parasite growth saturates with parasite dose and that experimentally enhanced innate immunity can affect parasite density indirectly via resource depletion. Such a statistical approach offers a tool to improve targeting of drugs or vaccines for human therapy by revealing the dynamics and interactions of within-host regulatory mechanisms.",
"title": "Partitioning regulatory mechanisms of within-host malaria dynamics using the effective propagation number."
},
{
"docid": "24721347",
"text": "The founding fathers of malariology combined scientific originality, perseverance in research, strong characters, breadth of interest and social concern. A hundred years later research and understanding has made immense progress but the world still bears a huge burden of malaria. For the next century research requires both more specialism and a holistic range if it is to be used in control, requiring multidisciplinary team work. Environmental changes and interventions produce a dynamic and changing pattern of malaria, not the static one of the past. From the original parasite life cycle, research has analysed a series of other cycles at electron microscope, biochemical and genome levels on decreasing size scales and quantitative epidemiological cycles for control. Recent additions to these concepts have been stage-specific antigens, cycles of disease rather than parasites alone, considering populations of parasites rather than just cases, and also genetic variation in each component of the parasite-human host-vector triad. In this volume there emerges for the first time a coherent overall picture of the biomedical aspects of basic malariology as the interacting population genetics of malaria parasites, anophelines and people. This provides a coherent model for the new century dealing with the great biological malaria problems of drug resistance, vaccine development, insecticidal and net control and can feed, with socio-economic work, into the gathering renewal of control efforts. New work on large-scale changes of malaria in space and time enables us to be precise about effects of local and global environmental changes to predict epidemics. Future research will be as much about linking these different scales of understanding as control will be about linking different levels of the health system. The grim situation in poor holoendemic countries also requires practical support of the type that the founders of malariology were involved in. A coherent understanding needs to feed into the new control efforts, from Roll Back Malaria onwards, for the next century.",
"title": "The last and the next hundred years of malariology."
},
{
"docid": "20999249",
"text": "BACKGROUND Falciparum malaria or malaria tropica is one of the leading causes of childhood mortality worldwide. Malaria-related deaths occur mainly in sub-Saharan Africa, where an estimated 365 million clinical cases of Plasmodium falciparum malaria occur each year. In Europe, imported malaria cases occur due to returning travellers or immigration mostly from African countries. Children are more at risk than adults. The objective of this study was to identify high risk groups for imported childhood malaria in Europe in order to guide development of strategies for prevention, early recognition and management. METHODS In the period May 2003-January 2005 we reviewed all cases of paediatric malaria in the Netherlands notified by the Dutch Paediatric Surveillance System (Nederland Signalerings Centrum Kindergeneeskunde, NSCK) and the literature on imported malaria in children in Europe published between 1996 and 2006. RESULTS Malaria occurred mainly in children of long-term (n = 15, 47%) and new (n = 8, 25%) immigrants and was mostly acquired in sub-Saharan Africa. The dominant species was P. falciparum. Only one quarter of children had used adequate malaria chemoprophylaxis. Complicated disease occurred in 10 (31%) of cases. We also reviewed the literature and found 6082 reported cases of imported malaria among children in Europe; among these, four died and only one was reported to develop neurological sequelae. CONCLUSION Imported malaria in children remains an important problem and is unlikely to decrease unless the reasons for inadequate prophylaxis are addressed.",
"title": "Imported malaria in children: a national surveillance in the Netherlands and a review of European studies."
}
] |
1084
|
Side effects associated with antidepressants increases risk of stroke.
|
[
{
"docid": "5691302",
"text": "OBJECTIVES To investigate the association between antidepressant treatment and risk of several potential adverse outcomes in older people with depression and to examine risks by class of antidepressant, duration of use, and dose. DESIGN Cohort study of people aged 65 and over diagnosed as having depression. SETTING 570 general practices in the United Kingdom supplying data to the QResearch primary care database. PARTICIPANTS 60,746 patients diagnosed as having a new episode of depression between the ages of 65 and 100 years from 1 January 1996 to 31 December 2007 and followed up until 31 December 2008. MAIN OUTCOME MEASURES Hazard ratios associated with antidepressant use for all cause mortality, attempted suicide/self harm, myocardial infarction, stroke/transient ischaemic attack, falls, fractures, upper gastrointestinal bleeding, epilepsy/seizures, road traffic accidents, adverse drug reactions, and hyponatraemia, adjusted for a range of potential confounding variables. Hazard ratios were calculated for antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, and duration of use and for commonly prescribed individual drugs. RESULTS 54,038 (89.0%) patients received at least one prescription for an antidepressant during follow-up. A total of 1,398,359 antidepressant prescriptions were issued: 764,659 (54.7%) for selective serotonin reuptake inhibitors, 442,192 (31.6%) for tricyclic antidepressants, 2203 (0.2%) for monoamine oxidase inhibitors, and 189,305 (13.5%) for the group of other antidepressants. The associations with the adverse outcomes differed significantly between the antidepressant classes for seven outcomes. Selective serotonin reuptake inhibitors were associated with the highest adjusted hazard ratios for falls (1.66, 95% confidence interval 1.58 to 1.73) and hyponatraemia (1.52, 1.33 to 1.75) compared with when antidepressants were not being used. The group of other antidepressants was associated with the highest adjusted hazard ratios for all cause mortality (1.66, 1.56 to 1.77), attempted suicide/self harm (5.16, 3.90 to 6.83), stroke/transient ischaemic attack (1.37, 1.22 to 1.55), fracture (1.64, 1.46 to 1.84), and epilepsy/seizures (2.24, 1.60 to 3.15), compared with when antidepressants were not being used. Tricyclic antidepressants did not have the highest hazard ratio for any of the outcomes. Significantly different associations also existed between the individual drugs for the same seven outcomes; trazodone (tricyclic antidepressant), mirtazapine, and venlafaxine (both in the group of other antidepressants) were associated with the highest rates for some of these outcomes. Absolute risks over 1 year for all cause mortality were 7.04% for patients while not taking antidepressants, 8.12% for those taking tricyclic antidepressants, 10.61% for selective serotonin reuptake inhibitors, and 11.43% for other antidepressants. CONCLUSIONS Selective serotonin reuptake inhibitors and drugs in the group of other antidepressants were associated with an increased risk of several adverse outcomes compared with tricyclic antidepressants. Among individual drugs, trazodone, mirtazapine, and venlafaxine were associated with the highest risks for some outcomes. As this is an observational study, it is susceptible to confounding by indication, channelling bias, and residual confounding, so differences in characteristics between patients prescribed different antidepressant drugs that could account for some of the associations between the drugs and the adverse outcomes may remain. Further research is needed to confirm these findings, but the risks and benefits of different antidepressants should be carefully evaluated when these drugs are prescribed to older people.",
"title": "Antidepressant use and risk of adverse outcomes in older people: population based cohort study"
}
] |
[
{
"docid": "24494539",
"text": "OBJECTIVE To observe the clinical effects of acupuncture combined with auricular point sticking based on the western medication for post stroke depression (PSD). METHODS Sixty patients with PSD were randomly assigned into an acupuncture plus auricular application group (a combination group) and a medication group, 30 cases in each one. 20 mg paroxetine hydrochloride was prescribed orally in the medication group, once a day for continuous 8 weeks. Based on the above treatment, 30-minute acupuncture was used in the combination group for 8 weeks at Baihui (GV 20), Sishencong (EX-HN 1), Shenting (GV 24), Yintang (GV 29), Shenmen (HT 7), Neiguan (PC 6), Taichong (LR 3), Hegu (LI 4), Zusanli (ST 36), Sanyinjiao (SP 6) and Fenglong (ST 40), once the other day and three times a week. Auricular point sticking therapy for 8 weeks was applied at shenmen (TF4), pizhixia (AT4), xin (CO15), and gan (CO12), with pressing 3 times a day and once 3-5 days. The total score and each factor scores of Hamilton's depression scale (HAMD) were observed in the two groups before and after treatment, and Asberg's antidepressant side-effect rating scale (SERS) and clinical effect were evaluated. RESULTS After treatment, the total HAMD scores of the two groups decreased compared with those before treatment (both P<0.05), with better effect in the combination group (P<0.05). The scores of the combination group after treatment were lower than those in the medication group, including the anxiety/somatization factor, sleep disturbance factor, hopelessness factor (all P<0.05). The total effective rate of the combination group was 86.7% (26/30), which was better than 66.7% (20/30) of the medication group (P<0.05). The SERS score of the combination group was lower than that of the medication group (P<0.05). CONCLUSIONS Acupuncture combined with auricular point sticking can improve the clinical symptoms and are effective and safe for PSD.",
"title": "[Acupuncture combined with auricular point sticking therapy for post stroke depression:a randomized controlled trial]."
},
{
"docid": "8595678",
"text": "BACKGROUND The MTHFR 677C→T polymorphism has been associated with raised homocysteine concentration and increased risk of stroke. A previous overview showed that the effects were greatest in regions with low dietary folate consumption, but differentiation between the effect of folate and small-study bias was difficult. A meta-analysis of randomised trials of homocysteine-lowering interventions showed no reduction in coronary heart disease events or stroke, but the trials were generally set in populations with high folate consumption. We aimed to reduce the effect of small-study bias and investigate whether folate status modifies the association between MTHFR 677C→T and stroke in a genetic analysis and meta-analysis of randomised controlled trials. METHODS We established a collaboration of genetic studies consisting of 237 datasets including 59,995 individuals with data for homocysteine and 20,885 stroke events. We compared the genetic findings with a meta-analysis of 13 randomised trials of homocysteine-lowering treatments and stroke risk (45,549 individuals, 2314 stroke events, 269 transient ischaemic attacks). FINDINGS The effect of the MTHFR 677C→T variant on homocysteine concentration was larger in low folate regions (Asia; difference between individuals with TT versus CC genotype, 3·12 μmol/L, 95% CI 2·23 to 4·01) than in areas with folate fortification (America, Australia, and New Zealand, high; 0·13 μmol/L, -0·85 to 1·11). The odds ratio (OR) for stroke was also higher in Asia (1·68, 95% CI 1·44 to 1·97) than in America, Australia, and New Zealand, high (1·03, 0·84 to 1·25). Most randomised trials took place in regions with high or increasing population folate concentrations. The summary relative risk (RR) of stroke in trials of homocysteine-lowering interventions (0·94, 95% CI 0·85 to 1·04) was similar to that predicted for the same extent of homocysteine reduction in large genetic studies in populations with similar folate status (predicted RR 1·00, 95% CI 0·90 to 1·11). Although the predicted effect of homocysteine reduction from large genetic studies in low folate regions (Asia) was larger (RR 0·78, 95% CI 0·68 to 0·90), no trial has evaluated the effect of lowering of homocysteine on stroke risk exclusively in a low folate region. INTERPRETATION In regions with increasing levels or established policies of population folate supplementation, evidence from genetic studies and randomised trials is concordant in suggesting an absence of benefit from lowering of homocysteine for prevention of stroke. Further large-scale genetic studies of the association between MTHFR 677C→T and stroke in low folate settings are needed to distinguish effect modification by folate from small-study bias. If future randomised trials of homocysteine-lowering interventions for stroke prevention are undertaken, they should take place in regions with low folate consumption. FUNDING Full funding sources listed at end of paper (see Acknowledgments).",
"title": "Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials"
},
{
"docid": "37424881",
"text": "OBJECTIVE Folate and vitamin B12 are two vital regulators in the metabolic process of homocysteine, which is a risk factor of atherothrombotic events. Low folate intake or low plasma folate concentration is associated with increased stroke risk. Previous randomized controlled trials presented discordant findings in the effect of folic acid supplementation-based homocysteine lowering on stroke risk. The aim of the present review was to perform a meta-analysis of relevant randomized controlled trials to check the how different folate fortification status might affect the effects of folic acid supplementation in lowering homocysteine and reducing stroke risk. DESIGN Relevant randomized controlled trials were identified through formal literature search. Homocysteine reduction was compared in subgroups stratified by folate fortification status. Relative risks with 95 % confidence intervals were used as a measure to assess the association between folic acid supplementation and stroke risk. SETTING The meta-analysis included fourteen randomized controlled trials, SUBJECTS A total of 39 420 patients. RESULTS Homocysteine reductions were 26·99 (sd 1·91) %, 18·38 (sd 3·82) % and 21·30 (sd 1·98) %, respectively, in the subgroups without folate fortification, with folate fortification and with partial folate fortification. Significant difference was observed between the subgroups with folate fortification and without folate fortification (P=0·05). The relative risk of stroke was 0·88 (95 % CI 0·77, 1·00, P=0·05) in the subgroup without folate fortification, 0·94 (95 % CI 0·58, 1·54, P=0·82) in the subgroup with folate fortification and 0·91 (95 % CI 0·82, 1·01, P=0·09) in the subgroup with partial folate fortification. CONCLUSIONS Folic acid supplementation might have a modest benefit on stroke prevention in regions without folate fortification.",
"title": "The effect of folate fortification on folic acid-based homocysteine-lowering intervention and stroke risk: a meta-analysis."
},
{
"docid": "23627419",
"text": "RATIONALE Although obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population. OBJECTIVES To quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea. METHODS Baseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea-hypopnea index (OAHI) and outcome was incident ischemic stroke. MEASUREMENTS AND MAIN RESULTS A total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P = 0.016). Men in the highest OAHI quartile (>19) had an adjusted hazard ratio of 2.86 (95% confidence interval, 1.1-7.4). In the mild to moderate range (OAHI, 5-25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6% (95% confidence interval, 2-10%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25. CONCLUSIONS The strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials.",
"title": "Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study."
},
{
"docid": "18256197",
"text": "BACKGROUND AND PURPOSE The level of total homocysteine (tHcy) that confers a risk of ischemic stroke is unsettled, and no prospective cohort studies have included sufficient elderly minority subjects. We investigated the association between mild to moderate fasting tHcy level and the incidence of ischemic stroke, myocardial infarction, and vascular death in a multiethnic prospective study. METHODS A population-based cohort was followed for vascular events (stroke, myocardial infarction, and vascular death). Baseline values of tHcy and methylmalonic acid were measured among 2939 subjects (mean age, 69+/-10; 61% women, 53% Hispanics, 24% blacks, and 20% whites). Cox proportional models were used to calculate hazard ratios (HRs) and 95% CIs in tHcy categories after adjusting for age, race, education, renal insufficiency, B12 deficiency, and other risk factors. RESULTS The adjusted HR for a tHcy level > or =15 micromol/L compared with <10 micromol/L was greatest for vascular death (HR=6.04; 95% CI, 3.44 to 10.60), followed by combined vascular events (HR=2.27; 95% CI, 1.51 to 3.43), ischemic stroke (HR=2.01; 95% CI, 1.00 to 4.05), and nonvascular death (HR=2.02; 95% CI, 1.31 to 3.14). Mild to moderate elevations of tHcy of 10 to 15 micromol/L were not significantly predictive of ischemic stroke, but increased the risk of vascular death (2.27; 95% CI, 1.44 to 3.60) and combined vascular events (1.42; 95% CI, 1.06 to 1.88). The effect of tHcy was stronger among whites and Hispanics, but not a significant risk factor for blacks. CONCLUSIONS Total Hcy elevations above 15 micromol/L are an independent risk factor for ischemic stroke, whereas mild elevations of tHcy of 10 to 15 micromol/L are less predictive. The vascular effects of tHcy are greatest among whites and Hispanics, and less among blacks.",
"title": "Homocysteine and the risk of ischemic stroke in a triethnic cohort: the NOrthern MAnhattan Study."
},
{
"docid": "32328114",
"text": "Stroke ranks as the third leading cause of death in the United States. It is now estimated that there are more than 700 000 incident strokes annually and 4.4 million stroke survivors.1 2 The economic burden of stroke was estimated by the American Heart Association to be $51 billion (direct and indirect costs) in 1999.3 Despite the advent of treatment of selected patients with acute ischemic stroke with tissue plasminogen activator and the promise of other experimental therapies, the best approach to reducing the burden of stroke remains prevention.4 5 High-risk or stroke-prone individuals can be identified and targeted for specific interventions.6 This is important because epidemiological data suggest a substantial leveling off of prior declines in stroke-related mortality and a possible increase in stroke incidence.7 8 The Stroke Council of the American Heart Association formed an ad hoc writing group to provide a clear and concise overview of the evidence regarding various established and potential stroke risk factors. The writing group was chosen based on expertise in specific subject areas, and it used literature review, reference to previously published guidelines, and expert opinion to summarize existing evidence and formulate recommendations (Table 1⇓). View this table: Table 1. Levels of Evidence and Grading of Recommendations As given in Tables 2 through 4⇓⇓⇓, risk factors or risk markers for a first stroke were classified according to potential for modification (nonmodifiable, modifiable, or potentially modifiable) and strength of evidence (well documented, less well documented).5 The tables give the estimated prevalence, population attributable risk, relative risk, and risk reduction with treatment for each factor when known. Population attributable risk reflects the proportion of ischemic strokes in the population that can be attributed to a particular risk factor and is given by the formula 100×[prevalence(relative risk−1)/prevalence(relative risk−1)+1]). …",
"title": "Primary prevention of ischemic stroke: A statement for healthcare professionals from the Stroke Council of the American Heart Association."
},
{
"docid": "14606752",
"text": "OBJECTIVE To evaluate the efficacy and relative adverse effects of tricyclic antidepressants in the treatment of migraine, tension-type, and mixed headaches. DESIGN Meta-analysis. DATA SOURCES Medline, Embase, the Cochrane Trials Registry, and PsycLIT. Studies reviewed Randomised trials of adults receiving tricyclics as only treatment for a minimum of four weeks. DATA EXTRACTION Frequency of headaches (number of headache attacks for migraine and number of days with headache for tension-type headaches), intensity of headache, and headache index. RESULTS 37 studies met the inclusion criteria. Tricyclics significantly reduced the number of days with tension-type headache and number of headache attacks from migraine than placebo (average standardised mean difference -1.29, 95% confidence interval -2.18 to -0.39 and -0.70, -0.93 to -0.48) but not compared with selective serotonin reuptake inhibitors (-0.80, -2.63 to 0.02 and -0.20, -0.60 to 0.19). The effect of tricyclics increased with longer duration of treatment (β=-0.11, 95% confidence interval -0.63 to -0.15; P<0.0005). Tricyclics were also more likely to reduce the intensity of headaches by at least 50% than either placebo (tension-type: relative risk 1.41, 95% confidence interval 1.02 to 1.89; migraine: 1.80, 1.24 to 2.62) or selective serotonin reuptake inhibitors (1.73, 1.34 to 2.22 and 1.72, 1.15 to 2.55). Tricyclics were more likely to cause adverse effects than placebo (1.53, 95% confidence interval 1.11 to 2.12) and selective serotonin reuptake inhibitors (2.22, 1.52 to 3.32), including dry mouth (P<0.0005 for both), drowsiness (P<0.0005 for both), and weight gain (P<0.001 for both), but did not increase dropout rates (placebo: 1.22, 0.83 to 1.80, selective serotonin reuptake inhibitors: 1.16, 0.81 to 2.97). CONCLUSIONS Tricyclic antidepressants are effective in preventing migraine and tension-type headaches and are more effective than selective serotonin reuptake inhibitors, although with greater adverse effects. The effectiveness of tricyclics seems to increase over time.",
"title": "Tricyclic antidepressants and headaches: systematic review and meta-analysis"
},
{
"docid": "9813098",
"text": "Young patients with an ischaemic stroke or transient ischaemic attack (TIA) often have no vascular risk factors. Hyperhomocysteinaemia is an established risk factor for stroke in elderly patients but it is uncertain whether it is also important for the prognosis of young ischaemic stroke and TIA patients. We examined the possible effect of the plasma homocysteine level on the risk of recurrent vascular events in patients between 18 and 45 years of age. The study population consisted of 161 consecutive patients with a recent cerebral infarction or TIA. Data on the primary event and the homocysteine level were collected retrospectively from hospital records. General practitioners and patients were contacted by telephone to record vascular events and the type of medication used during the follow–up period. Vascular events included cerebral infarction, TIA, pulmonary embolism, venous thrombosis, myocardial infarction and peripheral arterial disease. A Kaplan- Meier curve showed a dose effect relationship between event-free survival time and tertiles of the homocysteine level (Log rank statistic 5.91; p = 0.05). The Cox hazard ratio, after adjustment for homocysteine lowering treatment, was 1.7 (95 % CI, 1.1 to 2.8) for any vascular outcome event, 1.9 (95% CI, 1.1 to 3.0) for arterial outcome events and 1.8 (95 % CI, 1.1 to 2.9) for cerebral outcome events. In spite of our small number of outcome events we found a significant association at the 95% confidence level between homocysteine level and the risk of recurrent vascular events in young patients with an ischaemic stroke or TIA. The association is of the same magnitude as in elderly people.",
"title": "Plasma homocysteine is a risk factor for recurrent vascular events in young patients with an ischaemic stroke or TIA"
},
{
"docid": "37619697",
"text": "BACKGROUND Phenylpropanolamine is commonly found in appetite suppressants and cough or cold remedies. Case reports have linked the use of products containing phenylpropanolamine to hemorrhagic stroke, often after the first use of these products. To study the association, we designed a case-control study. METHODS Men and women 18 to 49 years of age were recruited from 43 U.S. hospitals. Eligibility criteria included the occurrence of a subarachnoid or intracerebral hemorrhage within 30 days before enrollment and the absence of a previously diagnosed brain lesion. Random-digit dialing identified two matched control subjects per patient. RESULTS There were 702 patients and 1376 control subjects. For women, the adjusted odds ratio was 16.58 (95 percent confidence interval, 1.51 to 182.21; P=0.02) for the association between the use of appetite suppressants containing phenylpropanolamine and the risk of a hemorrhagic stroke and 3.13 (95 percent confidence interval, 0.86 to 11.46; P=0.08) for the association with the first use of a product containing phenylpropanolamine. All first uses of phenylpropanolamine involved cough or cold remedies. For men and women combined, the adjusted odds ratio was 1.49 (95 percent confidence interval, 0.84 to 2.64; P=0.17) for the association between the use of a product containing phenylpropanolamine and the risk of a hemorrhagic stroke, 1.23 (95 percent confidence interval, 0.68 to 2.24; P=0.49) for the association with the use of cough or cold remedies that contained phenylpropanolamine, and 15.92 (95 percent confidence interval, 1.38 to 184.13; P=0.03) for the association with the use of appetite suppressants that contained phenylpropanolamine. An analysis in men showed no increased risk of a hemorrhagic stroke in association with the use of cough or cold remedies containing phenylpropanolamine. No men reported the use of appetite suppressants. CONCLUSIONS The results suggest that phenylpropanolamine in appetite suppressants, and possibly in cough and cold remedies, is an independent risk factor for hemorrhagic stroke in women.",
"title": "Phenylpropanolamine and the risk of hemorrhagic stroke."
},
{
"docid": "14566771",
"text": "The relationship of migraine and stroke is complex. Stroke may be coincidental with migraine but migraine may confer an increased risk of stroke in women under 45 years of age and possibly in men who have migraine with aura. Stroke may mimic migraine but migraine syndromes may be symptomatic of underlying cerebrovascular disorders. True migraine-induced stroke is rare. The mechanisms of stroke induced during a migraine attack remain to be determined but probably involve an interaction between the dynamic shifts in cerebral blood flow and stroke risk factors.",
"title": "Stroke and migraine--the spectrum of cause and effect."
},
{
"docid": "37065914",
"text": "BACKGROUND AND PURPOSE Soluble corin was decreased in coronary heart disease. Given the connections between cardiac dysfunction and stroke, circulating corin might be a candidate marker of stroke risk. However, the association between circulating corin and stroke has not yet been studied in humans. Here, we aimed to examine the association in patients wtith stroke and community-based healthy controls. METHODS Four hundred eighty-one patients with ischemic stroke, 116 patients with hemorrhagic stroke, and 2498 healthy controls were studied. Serum soluble corin and some conventional risk factors of stroke were examined. Because circulating corin was reported to be varied between men and women, the association between serum soluble corin and stroke was evaluated in men and women, respectively. RESULTS Patients with ischemic and hemorrhagic stroke had a significantly lower level of serum soluble corin than healthy controls in men and women (all P values, <0.05). In multivariate analysis, men in the lowest quartile of serum soluble corin were more likely to have ischemic (odds ratio [OR], 4.90; 95% confidence interval, 2.99-8.03) and hemorrhagic (OR, 17.57; 95% confidence interval, 4.85-63.71) stroke than men in the highest quartile. Women in the lowest quartile of serum soluble corin were also more likely to have ischemic (OR, 3.10; 95% confidence interval, 1.76-5.44) and hemorrhagic (OR, 8.54; 95% confidence interval, 2.35-31.02) stroke than women in the highest quartile. ORs of ischemic and hemorrhagic stroke were significantly increased with the decreasing levels of serum soluble corin in men and women (all P values for trend, <0.001). CONCLUSIONS Serum soluble corin was decreased in patients with stroke compared with healthy controls. Our findings raise the possibility that serum soluble corin may have a pathogenic role in stroke.",
"title": "Serum Soluble Corin is Decreased in Stroke."
},
{
"docid": "15984735",
"text": "OBJECTIVE To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease. DESIGN Systematic review and meta-analysis. DATA SOURCES Electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included studies and reviews published until January 2009. Selection criteria Case-control and cohort studies investigating the association between any migraine or specific migraine subtypes and cardiovascular disease. Review methods Two investigators independently assessed eligibility of identified studies in a two step approach. Disagreements were resolved by consensus. Studies were grouped according to a priori categories on migraine and cardiovascular disease. DATA EXTRACTION Two investigators extracted data. Pooled relative risks and 95% confidence intervals were calculated. RESULTS Studies were heterogeneous for participant characteristics and definition of cardiovascular disease. Nine studies investigated the association between any migraine and ischaemic stroke (pooled relative risk 1.73, 95% confidence interval 1.31 to 2.29). Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02). Furthermore, results suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men (1.37, 0.89 to 2.11). Age less than 45 years, smoking, and oral contraceptive use further increased the risk. Eight studies investigated the association between migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine and death due to cardiovascular disease (1.03, 0.79 to 1.34). Only one study investigated the association between women who had migraine with aura and myocardial infarction and death due to cardiovascular disease, showing a twofold increased risk. CONCLUSION Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura. Our results also suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives. We did not find an overall association between any migraine and myocardial infarction or death due to cardiovascular disease. Too few studies are available to reliably evaluate the impact of modifying factors, such as migraine aura, on these associations.",
"title": "Migraine and cardiovascular disease: systematic review and meta-analysis."
},
{
"docid": "39281140",
"text": "CONTEXT Sexual dysfunction is a common adverse effect of antidepressants that frequently results in treatment noncompliance. OBJECTIVE To assess the efficacy of sildenafil citrate in men with sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants. DESIGN, SETTING, AND PATIENTS Prospective, parallel-group, randomized, double-blind, placebo-controlled trial conducted between November 1, 2000, and January 1, 2001, at 3 US university medical centers among 90 male outpatients (mean [SD] age, 45 [8] years) with major depression in remission and sexual dysfunction associated with SRI antidepressant treatment. INTERVENTION Patients were randomly assigned to take sildenafil (n = 45) or placebo (n = 45) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks. MAIN OUTCOME MEASURES The primary outcome measure was score on the Clinical Global Impression-Sexual Function (CGI-SF); secondary measures were scores on the International Index of Erectile Function, Arizona Sexual Experience Scale, Massachusetts General Hospital-Sexual Functioning Questionnaire, and Hamilton Rating Scale for Depression (HAM-D). RESULTS Among the 90 randomized patients, 93% (83/89) of patients treated per protocol took at least 1 dose of study drug and 85% (76/89) completed week 6 end-point assessments with last observation carried forward analyses. At a CGI-SF score of 2 or lower, 54.5% (24/44) of sildenafil compared with 4.4% (2/45) of placebo patients were much or very much improved (P<.001). Erectile function, arousal, ejaculation, orgasm, and overall satisfaction domain measures improved significantly in sildenafil compared with placebo patients. Mean depression scores remained consistent with remission (HAM-D score < or =10) in both groups for the study duration. CONCLUSION In our study, sildenafil effectively improved erectile function and other aspects of sexual function in men with sexual dysfunction associated with the use of SRI antidepressants. These improvements may allow patients to maintain adherence with effective antidepressant treatment.",
"title": "Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial."
},
{
"docid": "6083952",
"text": "1. Incubation of LMCAT fibroblast cells with antidepressants potentiates glucocorticoid receptor (GR)-mediated gene transcription in the presence of dexamethasone and cortisol, but not of corticosterone. We have shown that antidepressants do so by inhibiting the LMCAT cell membrane steroid transporter (which is virtually identical to the multidrug resistance P-glycoprotein) and thus by increasing dexamethasone or cortisol intracellular concentrations. However, previous experiments with the antidepressant fluoxetine in the presence of dexamethasone have produced negative results (Pariante et al. (2001). Br. J. Pharmacol., 134, 1335-1343). 2. We have since re-examined the effects of fluoxetine on GR-mediated gene transcription in the presence of dexamethasone. Moreover, we have examined the effects of fluoxetine on GR-mediated gene transcription in the presence of cortisol and corticosterone, and on the intracellular accumulation of radioactive cortisol and corticosterone. Finally, we have examined the effects of fluoxetine on inhibition of P-glycoprotein activity in Caco-2 cells. 3. We now find that fluoxetine (1-10 micro M) enhances GR-mediated gene transcription in the presence of dexamethasone and cortisol (+140-170%), but not of corticosterone, and increases the intracellular accumulation of (3)H-cortisol (+5-15%), but not of (3)H-corticosterone. Moreover, fluoxetine (10 micro M) induces approximately 30% inhibition of PGP activity in Caco-2 cells. 4. Our results show that fluoxetine, like other antidepressants, inhibits membrane steroid transporters.",
"title": "Antidepressant fluoxetine enhances glucocorticoid receptor function in vitro by modulating membrane steroid transporters."
},
{
"docid": "16180601",
"text": "OBJECTIVE Serum soluble corin has been associated with stroke. However, whether it is associated with stroke prognosis has not yet been studied. Therefore, we aimed to study the association of serum soluble corin with risk of poor outcomes within 3 months after stroke. METHODS We followed 522 stroke patients for 3 months to identify major disability, death and vascular events. Serum soluble corin was measured at baseline for all participants. Logistic regression was used to examine the associations of baseline serum soluble corin with outcomes of stroke, adjusting for age, sex, baseline NIHSS score, hours from onset to hospitalization, smoking, drinking, hypertension, diabetes, coronary heart disease, atrial fibrillation, family history of stroke, and stroke subtype. RESULTS Patients with high corin had a significantly lower crude risk for the composite outcome of major disability or death (OR = 0.64, 95%CI: 0.43-0.96) than patients with low corin (the lowest tertile). After adjustment for age and baseline NIHSS score, patients with high corin still had a significantly lower risk for the composite outcome of major disability or death (OR = 0.60, 95%CI: 0.36-0.99). This association became bottom line significant after additionally adjusting for other conventional factors (OR = 0.61, P = 0.058). No association was found between serum soluble corin and other composite outcomes. CONCLUSION Serum soluble corin deficiency predicted risk for major disability within 3 months after stroke, independent of baseline neurological deficient. Our results may indicate a probable role of corin in stroke prognosis.",
"title": "Serum Soluble Corin Deficiency Predicts Major Disability within 3 Months after Acute Stroke"
},
{
"docid": "5551138",
"text": "This article reviews the efficacy of nortriptyline for smoking cessation based on a meta-analysis of the Cochrane Library. Six placebo-controlled trials have shown nortriptyline (75-100 mg) doubles quit rates (OR = 2.1). Between 4% and 12% of smokers dropped out because of adverse events, but no serious adverse events occurred. The efficacy of nortriptyline did not appear to be related to its antidepressant actions. Nortriptyline is an efficacious aid to smoking cessation with a magnitude of effect similar to that for bupropion and nicotine replacement therapies. Whether nortriptyline produces serious side effects at these doses in healthy, nondepressed smokers remains unclear because it has been tested in only 500 smokers. The finding that nortriptyline and bupropion are effective for smoking cessation but that selective serotonin-reuptake inhibitors are not suggests that dopaminergic or adrenergic, but not serotonergic, activity is important for cessation efficacy. Until further studies can verify a low incidence of significant adverse events, nortriptyline should be a second-line treatment for smoking cessation.",
"title": "Nortriptyline for smoking cessation: a review."
},
{
"docid": "21571708",
"text": "CONTEXT Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein-like particle, may be associated with risk of coronary heart disease (CHD) and stroke. OBJECTIVE To assess the relationship of Lp(a) concentration with risk of major vascular and nonvascular outcomes. STUDY SELECTION Long-term prospective studies that recorded Lp(a) concentration and subsequent major vascular morbidity and/or cause-specific mortality published between January 1970 and March 2009 were identified through electronic searches of MEDLINE and other databases, manual searches of reference lists, and discussion with collaborators. DATA EXTRACTION Individual records were provided for each of 126,634 participants in 36 prospective studies. During 1.3 million person-years of follow-up, 22,076 first-ever fatal or nonfatal vascular disease outcomes or nonvascular deaths were recorded, including 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause. Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. Analyses excluded participants with known preexisting CHD or stroke at baseline. DATA SYNTHESIS Lipoprotein(a) concentration was weakly correlated with several conventional vascular risk factors and it was highly consistent within individuals over several years. Associations of Lp(a) with CHD risk were broadly continuous in shape. In the 24 cohort studies, the rates of CHD in the top and bottom thirds of baseline Lp(a) distributions, respectively, were 5.6 (95% confidence interval [CI], 5.4-5.9) per 1000 person-years and 4.4 (95% CI, 4.2-4.6) per 1000 person-years. The risk ratio for CHD, adjusted for age and sex only, was 1.16 (95% CI, 1.11-1.22) per 3.5-fold higher usual Lp(a) concentration (ie, per 1 SD), and it was 1.13 (95% CI, 1.09-1.18) following further adjustment for lipids and other conventional risk factors. The corresponding adjusted risk ratios were 1.10 (95% CI, 1.02-1.18) for ischemic stroke, 1.01 (95% CI, 0.98-1.05) for the aggregate of nonvascular mortality, 1.00 (95% CI, 0.97-1.04) for cancer deaths, and 1.00 (95% CI, 0.95-1.06) for nonvascular deaths other than cancer. CONCLUSION Under a wide range of circumstances, there are continuous, independent, and modest associations of Lp(a) concentration with risk of CHD and stroke that appear exclusive to vascular outcomes.",
"title": "Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality."
},
{
"docid": "3868322",
"text": "Polymorphisms in and around the Cholesteryl Ester Transfer Protein (CETP) gene have been associated with HDL levels, risk for coronary artery disease (CAD), and response to therapy. The mechanism of action of these polymorphisms has yet to be defined. We used mRNA allelic expression and splice isoform measurements in human liver tissues to identify the genetic variants affecting CETP levels. Allelic CETP mRNA expression ratios in 56 human livers were strongly associated with several variants 2.5-7 kb upstream of the transcription start site (e.g., rs247616 p = 6.4 × 10(-5), allele frequency 33%). In addition, a common alternatively spliced CETP isoform lacking exon 9 (Δ9), has been shown to prevent CETP secretion in a dominant-negative manner. The Δ 9 expression ranged from 10 to 48% of total CETP mRNA in 94 livers. Increased formation of this isoform was exclusively associated with an exon 9 polymorphism rs5883-C>T (p = 6.8 × 10(-10)) and intron 8 polymorphism rs9930761-T>C (5.6 × 10(-8)) (in high linkage disequilibrium with allele frequencies 6-7%). rs9930761 changes a key splicing branch point nucleotide in intron 8, while rs5883 alters an exonic splicing enhancer sequence in exon 9.The effect of these polymorphisms was evaluated in two clinical studies. In the Whitehall II study of 4745 subjects, both rs247616 and rs5883T/rs9930761C were independently associated with increased HDL-C levels in males with similar effect size (rs247616 p = 9.6 × 10(-28) and rs5883 p = 8.6 × 10(-10), adjusted for rs247616). In an independent multiethnic US cohort of hypertensive subjects with CAD (INVEST-GENE), rs5883T/rs9930761C alone were significantly associated with increased incidence of MI, stroke, and all-cause mortality in males (rs5883: OR 2.36 (CI 1.29-4.30), p = 0.005, n = 866). These variants did not reach significance in females in either study. Similar to earlier results linking low CETP activity with poor outcomes in males, our results suggest genetic, sex-dependent CETP splicing effects on cardiovascular risk by a mechanism independent of circulating HDL-C levels.",
"title": "Cholesteryl Ester Transfer Protein (CETP) Polymorphisms Affect mRNA Splicing, HDL Levels, and Sex-Dependent Cardiovascular Risk"
},
{
"docid": "1495563",
"text": "OBJECTIVE To observe the therapeutic effect of \"Xingnao Kaiqiao Zhenfa\" (Acupuncture Technique for Restoring Consciousness) in the treatment of post-stroke depression. METHODS A total of 256 stroke patients were divided into acupuncture group (n = 180, male 138, female 42) and medication group (n = 76, male 57 and female 19) according to their visiting sequence to our hospital. Acupoints used were Neiguan (PC 6), Renzhong (GV 26), Baihui (GV 20), Yintang (EX-HN 3) and Sanyinjiao (SP 6,the affected side) and the needles were retained for 20 min every time. Patients of medication group were asked to take Amitriptyline (50 mg/d at first, 200 mg/d). Acupuncture treatment was conducted twice daily, and after one month's treatment the therapeutic effect was evaluated. Self-Rating Depression Scale (SDS) and Hamilton Rating Scale for Depression (HRSD) were used to assess the patient's state of depression. RESULTS After the treatment, of the 180 and 76 cases in acupuncture and medication groups, 31 (17.2%) and 13 (17.1%) were cured, 73 (40.6%) and 18 (23.7%) had a marked improvement in their depression state, 27 (15.0%) and 12 (15.8%) had an improvement, 49 (27.2%) and 33 (43.4%) failed, with the effective rates being 72.8% and 56.6% respectively. The markedly effective rate and the total effective rate of acupuncture group were significantly higher than those of medication group (P < 0.05). After the treatment, the total scores of SDS and HRSD and the severity index of two groups decreased pronouncedly in comparison with those of their individual pre-treatment; and the therapeutic effects of acupuncture group were significantly better than those of medication group in reducing SDS, HRSD and severity index (P < 0 .05). In addition, the decreased values of depression, pessimistic mood and irritability of acupuncture group were all bigger than those of medication group (P < 0.05). No significant difference was found between two groups in the decreased value of insomnia (P > 0.05). CONCLUSION \"Acupuncture Technique for Restoring Consciousness\" can effectively improve depression patients' symptoms and the therapeutic effect of acupuncture is markedly superior to that of medication for post-stroke patients.",
"title": "[Clinical study on the therapeutic effect of acupuncture in the treatment of post-stroke depression]."
},
{
"docid": "14827874",
"text": "CONTEXT For the last 40 yr, the first line of treatment for anovulation in infertile women has been clomiphene citrate (CC). CC is a safe, effective oral agent but is known to have relatively common antiestrogenic endometrial and cervical mucous side effects that could prevent pregnancy in the face of successful ovulation. In addition, there is a significant risk of multiple pregnancy with CC, compared with natural cycles. Because of these problems, we proposed the concept of aromatase inhibition as a new method of ovulation induction that could avoid many of the adverse effects of CC. The objective of this review was to describe the different physiological mechanisms of action for CC and aromatase inhibitors (AIs) and compare studies of efficacy for both agents for ovulation induction. EVIDENCE ACQUISITION We conducted a systematic review of all the published studies, both controlled and noncontrolled, comparing CC and AI treatment, either alone or in combination with gonadotropins, for ovulation induction or augmentation, identified through the Entrez-PubMed search engine. EVIDENCE SYNTHESIS Because of the recent acceptance of the concept of using AIs for ovulation induction, few controlled studies were identified, and the rest of the studies were pilot or preliminary comparisons. Based on these studies, it appears that AIs are as effective as CC in inducing ovulation, are devoid of any antiestrogenic side effects, result in lower serum estrogen concentrations, and are associated with good pregnancy rates with a lower incidence of multiple pregnancy than CC. When combined with gonadotropins for assisted reproductive technologies, AIs reduce the dose of FSH required for optimal follicle recruitment and improve the response to FSH in poor responders. CONCLUSIONS Preliminary evidence suggests that AIs may replace CC in the future because of similar efficacy with a reduced side effect profile. Although worldwide experience with AIs for ovulation induction is increasing, at present, definitive studies in the form of randomized controlled trials comparing CC with AIs are lacking.",
"title": "0021-972X/06/$15.00/0 The Journal of Clinical Endocrinology & Metabolism 91(3):760–771 Printed in U.S.A. Copyright © 2006 by The Endocrine Society doi: 10.1210/jc.2005-1923 REVIEW: Aromatase Inhibitors for Ovulation Induction"
},
{
"docid": "1428840",
"text": "BACKGROUND It has been suggested that identified risk factors for endometrial cancer operate through a single etiologic pathway, i.e., exposure to relatively high levels of unopposed estrogen (estrogen in the absence of progestins). Only a few studies, however, have addressed this issue directly. PURPOSE We assessed the risk of developing endometrial cancer among both premenopausal and postmenopausal women in relation to the circulating levels of steroid hormones and sex hormone-binding globulin (SHBG). The independent effect of hormones was assessed after adjustment for other known risk factors. METHODS The data used in the analysis are from a case-control study conducted in five geographic regions in the United States. Incident cases were newly diagnosed during the period from June 1, 1987, through May 15, 1990. The case patients, aged 20-74 years, were matched to control subjects by age, race, and geographic region. The community control subjects were obtained by random-digit-dialing procedures (for subjects 20-64 years old) and from files of the Health Care Financing Administration (for subjects > or = 65 years old). Additional control subjects who were having a hysterectomy performed for benign conditions were obtained from the participating centers. Women reporting use of exogenous estrogens or oral contraceptives within 6 months of interview were excluded, resulting in 68 case patients and 107 control subjects among premenopausal women and 208 case patients and 209 control subjects among postmenopausal women. The hormone analyses were performed on blood samples obtained from case patients or from hysterectomy control subjects before surgery. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of an unconditional logistic regression analysis after we controlled for matching variables and potential confounders. All P values were two-sided. RESULTS High circulating levels of androstenedione were associated with 3.6-fold and 2.8-fold increased risks among premenopausal and postmenopausal women, respectively, after adjustment for other factors (P for trend = .01 and < .001, respectively). Risks related to other hormone fractions varied by menopausal status. Among postmenopausal women, a reduced risk was associated with high SHBG levels and persisted after adjustment was made for obesity and other factors (OR = 0.51; 95% CI = 0.27-0.95). High estrone levels were associated with increased risk (OR = 3.8; 95% CI = 2.2-6.6), although adjustment for other risk factors (particularly body mass index) diminished the effect (OR = 2.2; 95% CI = 1.2-4.4). Albumin-bound estradiol (E2), a marker of the bioavailable fraction, also remained an important risk factor after adjustment was made for other factors (OR = 2.0; 95% CI = 1.0-3.9). In contrast, high concentrations of total, free, and albumin-bound E2 were unrelated to increased risk in premenopausal women. In both premenopausal and postmenopausal groups, risks associated with obesity and fat distribution were not affected by adjustment for hormones. CONCLUSION High endogenous levels of unopposed estrogen are related to increased risk of endometrial cancer, but their independence from other risk factors is inconsistent with being a common underlying biologic pathway through which all risk factors for endometrial cancer operate. IMPLICATIONS Further research should focus on alternative endocrinologic mechanisms for risk associated with obesity and body fat distribution and for the biologic relevance of the increased risk associated with androstenedione in both premenopausal and postmenopausal disease.",
"title": "Case-control study of endogenous steroid hormones and endometrial cancer."
},
{
"docid": "10984005",
"text": "CONTEXT More than 1.5 million US adults use stimulants and other medications labeled for treatment of attention-deficit/hyperactivity disorder (ADHD). These agents can increase heart rate and blood pressure, raising concerns about their cardiovascular safety. OBJECTIVE To examine whether current use of medications prescribed primarily to treat ADHD is associated with increased risk of serious cardiovascular events in young and middle-aged adults. DESIGN, SETTING, AND PARTICIPANTS Retrospective, population-based cohort study using electronic health care records from 4 study sites (OptumInsight Epidemiology, Tennessee Medicaid, Kaiser Permanente California, and the HMO Research Network), starting in 1986 at 1 site and ending in 2005 at all sites, with additional covariate assessment using 2007 survey data. Participants were adults aged 25 through 64 years with dispensed prescriptions for methylphenidate, amphetamine, or atomoxetine at baseline. Each medication user (n = 150,359) was matched to 2 nonusers on study site, birth year, sex, and calendar year (443,198 total users and nonusers). MAIN OUTCOME MEASURES Serious cardiovascular events, including myocardial infarction (MI), sudden cardiac death (SCD), or stroke, with comparison between current or new users and remote users to account for potential healthy-user bias. RESULTS During 806,182 person-years of follow-up (median, 1.3 years per person), 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use (median, 0.33 years), with a crude incidence per 1000 person-years of 1.34 (95% CI, 1.14-1.57) for MI, 0.30 (95% CI, 0.20-0.42) for SCD, and 0.56 (95% CI, 0.43-0.72) for stroke. The multivariable-adjusted rate ratio (RR) of serious cardiovascular events for current use vs nonuse of ADHD medications was 0.83 (95% CI, 0.72-0.96). Among new users of ADHD medications, the adjusted RR was 0.77 (95% CI, 0.63-0.94). The adjusted RR for current use vs remote use was 1.03 (95% CI, 0.86-1.24); for new use vs remote use, the adjusted RR was 1.02 (95% CI, 0.82-1.28); the upper limit of 1.28 corresponds to an additional 0.19 events per 1000 person-years at ages 25-44 years and 0.77 events per 1000 person-years at ages 45-64 years. CONCLUSIONS Among young and middle-aged adults, current or new use of ADHD medications, compared with nonuse or remote use, was not associated with an increased risk of serious cardiovascular events. Apparent protective associations likely represent healthy-user bias.",
"title": "ADHD medications and risk of serious cardiovascular events in young and middle-aged adults."
},
{
"docid": "16701509",
"text": "BACKGROUND The prevalence of metabolic syndrome (obesity, glucose intolerance, low serum high-density lipoprotein cholesterol [HDL-C], high serum triglycerides, hypertension) is high and increasing in parallel with an increasing breast cancer incidence worldwide. HDL-C represents an important aspect of the syndrome, yet its role in breast cancer is still undefined. METHODS In two population-based screening surveys during 1977-1983 and 1985-1987, serum HDL-C was assayed enzymatically among 38,823 Norwegian women aged 17-54 years at entry. Height, weight, blood pressure, serum lipids, fat and energy intake, physical activity, parity, oral contraceptive use, hormone therapy use, alcohol intake, and tobacco use were also assessed. We used Cox proportional hazards modeling to estimate the relative risk (RR) of breast cancer associated with serum HDL-C levels and to adjust for potential confounding variables. We performed stratified analyses to evaluate effect modification by body mass index (BMI) and menopausal status. All statistical tests were two-sided. RESULTS During a median follow-up of 17.2 years, we identified 708 cases of invasive breast cancer. In multivariable analysis, the risk of postmenopausal breast cancer was inversely related to quartile of HDL-C (P(trend) =.02). Among women with HDL-C above 1.64 mmol/L (highest quartile) versus below 1.20 mmol/L (lowest quartile), the relative risk was 0.75 (95% confidence interval [CI] = 0.58 to 0.97). The HDL-C association was confined to women in the heavier subgroup (BMI > or =25 kg/m2), for whom the relative risk of postmenopausal breast cancer in those with HDL-C above 1.64 mmol/L versus below 1.20 mmol/L was 0.43 (95% CI = 0.28 to 0.67; P(trend)<.001; P(interaction) =.001). CONCLUSION Low HDL-C, as part of the metabolic syndrome, is associated with increased postmenopausal breast cancer risk.",
"title": "Serum high-density lipoprotein cholesterol, metabolic profile, and breast cancer risk."
},
{
"docid": "11718220",
"text": "BACKGROUND Deep vein thrombosis (DVT) and pulmonary embolism are common after stroke. In small trials of patients undergoing surgery, graduated compression stockings (GCS) reduce the risk of DVT. National stroke guidelines extrapolating from these trials recommend their use in patients with stroke despite insufficient evidence. We assessed the effectiveness of thigh-length GCS to reduce DVT after stroke. METHODS In this outcome-blinded, randomised controlled trial, 2518 patients who were admitted to hospital within 1 week of an acute stroke and who were immobile were enrolled from 64 centres in the UK, Italy, and Australia. Patients were allocated via a central randomisation system to routine care plus thigh-length GCS (n=1256) or to routine care plus avoidance of GCS (n=1262). A technician who was blinded to treatment allocation undertook compression Doppler ultrasound of both legs at about 7-10 days and, when practical, again at 25-30 days after enrolment. The primary outcome was the occurrence of symptomatic or asymptomatic DVT in the popliteal or femoral veins. Analyses were by intention to treat. This study is registered, number ISRCTN28163533. FINDINGS All patients were included in the analyses. The primary outcome occurred in 126 (10.0%) patients allocated to thigh-length GCS and in 133 (10.5%) allocated to avoid GCS, resulting in a non-significant absolute reduction in risk of 0.5% (95% CI -1.9% to 2.9%). Skin breaks, ulcers, blisters, and skin necrosis were significantly more common in patients allocated to GCS than in those allocated to avoid their use (64 [5%] vs 16 [1%]; odds ratio 4.18, 95% CI 2.40-7.27). INTERPRETATION These data do not lend support to the use of thigh-length GCS in patients admitted to hospital with acute stroke. National guidelines for stroke might need to be revised on the basis of these results. FUNDING Medical Research Council (UK), Chief Scientist Office of Scottish Government, Chest Heart and Stroke Scotland, Tyco Healthcare (Covidien) USA, and UK Stroke Research Network.",
"title": "Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial"
},
{
"docid": "13097856",
"text": "CONTEXT In 2002, an estimated 877,000 lives were lost worldwide through suicide. Some developed nations have implemented national suicide prevention plans. Although these plans generally propose multiple interventions, their effectiveness is rarely evaluated. OBJECTIVES To examine evidence for the effectiveness of specific suicide-preventive interventions and to make recommendations for future prevention programs and research. DATA SOURCES AND STUDY SELECTION Relevant publications were identified via electronic searches of MEDLINE, the Cochrane Library, and PsychINFO databases using multiple search terms related to suicide prevention. Studies, published between 1966 and June 2005, included those that evaluated preventative interventions in major domains; education and awareness for the general public and for professionals; screening tools for at-risk individuals; treatment of psychiatric disorders; restricting access to lethal means; and responsible media reporting of suicide. DATA EXTRACTION Data were extracted on primary outcomes of interest: suicidal behavior (completion, attempt, ideation), intermediary or secondary outcomes (treatment seeking, identification of at-risk individuals, antidepressant prescription/use rates, referrals), or both. Experts from 15 countries reviewed all studies. Included articles were those that reported on completed and attempted suicide and suicidal ideation; or, where applicable, intermediate outcomes, including help-seeking behavior, identification of at-risk individuals, entry into treatment, and antidepressant prescription rates. We included 3 major types of studies for which the research question was clearly defined: systematic reviews and meta-analyses (n = 10); quantitative studies, either randomized controlled trials (n = 18) or cohort studies (n = 24); and ecological, or population- based studies (n = 41). Heterogeneity of study populations and methodology did not permit formal meta-analysis; thus, a narrative synthesis is presented. DATA SYNTHESIS Education of physicians and restricting access to lethal means were found to prevent suicide. Other methods including public education, screening programs, and media education need more testing. CONCLUSIONS Physician education in depression recognition and treatment and restricting access to lethal methods reduce suicide rates. Other interventions need more evidence of efficacy. Ascertaining which components of suicide prevention programs are effective in reducing rates of suicide and suicide attempt is essential in order to optimize use of limited resources.",
"title": "Suicide prevention strategies: a systematic review."
},
{
"docid": "6945285",
"text": "OBJECTIVE To assess the effect of bezafibrate on the risk of coronary heart disease and stroke in men with lower extremity arterial disease. DESIGN Double blind placebo controlled randomised trial. SETTING 85 general practices and nine hospital vascular clinics. PARTICIPANTS 1568 men, mean age 68.2 years (range 35 to 92) at recruitment. INTERVENTIONS Bezafibrate 400 mg daily (783 men) or placebo (785 men). MAIN OUTCOME MEASURES Combination of coronary heart disease and of stroke. All coronary events, fatal and non-fatal coronary events separately, and strokes alone (secondary end points). RESULTS Bezafibrate did not reduce the incidence of coronary heart disease and stroke. There were 150 and 160 events in the active and placebo groups respectively (relative risk 0.96, 95% confidence interval 0.76 to 1.21). There were 90 and 111 major coronary events in the active and placebo groups respectively (0.81, 0.60 to 1.08), of which 64 and 65 were fatal (0.95, 0.66 to 1.37) and 26 and 46 non-fatal (0.60, 0.36 to 0.99). Beneficial effects on non-fatal events were greatest in men aged <65 years at entry, in whom benefit was also seen for all coronary events (0.38, 0.20 to 0.72). There were no significant effects in older men. There were 60 strokes in those on active treatment and 49 in those on placebo (1.34, 0.80 to 2.01). There were 204 and 195 deaths from all causes in the two groups respectively (1.03, 0.83 to 1.26). Bezafibrate reduced the severity of intermittent claudication for up to three years. CONCLUSIONS Bezafibrate has no effect on the incidence of coronary heart disease and of stroke combined but may reduce the incidence of non-fatal coronary events, particularly in those aged <65 years at entry, in whom all coronary events may also be reduced.",
"title": "Bezafibrate in men with lower extremity arterial disease: randomised controlled trial."
},
{
"docid": "12438901",
"text": "BACKGROUND For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. METHODS In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. FINDINGS Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). INTERPRETATION For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. FUNDING Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.",
"title": "Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial"
},
{
"docid": "6191684",
"text": "CONTEXT Chronic tension-type headaches are characterized by near-daily headaches and often are difficult to manage in primary practice. Behavioral and pharmacological therapies each appear modestly effective, but data are lacking on their separate and combined effects. OBJECTIVE To evaluate the clinical efficacy of behavioral and pharmacological therapies, singly and combined, for chronic tension-type headaches. DESIGN AND SETTING Randomized placebo-controlled trial conducted from August 1995 to January 1998 at 2 outpatient sites in Ohio. PARTICIPANTS Two hundred three adults (mean age, 37 years; 76% women) with diagnosis of chronic tension-type headaches (mean, 26 headache d/mo). INTERVENTIONS Participants were randomly assigned to receive tricyclic antidepressant (amitriptyline hydrochloride, up to 100 mg/d, or nortriptyline hydrochloride, up to 75 mg/d) medication (n = 53), placebo (n = 48), stress management (eg, relaxation, cognitive coping) therapy (3 sessions and 2 telephone contacts) plus placebo (n = 49), or stress management therapy plus antidepressant medication (n = 53). MAIN OUTCOME MEASURES Monthly headache index scores calculated as the mean of pain ratings (0-10 scale) recorded by participants in a daily diary 4 times per day; number of days per month with at least moderate pain (pain rating >/=5), analgesic medication use, and Headache Disability Inventory scores, compared by intervention group. RESULTS Tricyclic antidepressant medication and stress management therapy each produced larger reductions in headache activity, analgesic medication use, and headache-related disability than placebo, but antidepressant medication yielded more rapid improvements in headache activity. Combined therapy was more likely to produce clinically significant (>/=50%) reductions in headache index scores (64% of participants) than antidepressant medication (38% of participants; P =.006), stress management therapy (35%; P =.003), or placebo (29%; P =.001). On other measures the combined therapy and its 2 component therapies produced similar outcomes. CONCLUSIONS Our results indicate that antidepressant medication and stress management therapy are each modestly effective in treating chronic tension-type headaches. Combined therapy may improve outcome relative to monotherapy.",
"title": "Management of chronic tension-type headache with tricyclic antidepressant medication, stress management therapy, and their combination: a randomized controlled trial."
},
{
"docid": "6327940",
"text": "Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.",
"title": "Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity."
},
{
"docid": "13883546",
"text": "The term antidepressant refers to a drug that helps to rectify specific biological abnormalities that give rise to the symptoms of depression. This exemplifies what we have called the “disease-centred” model of psychotropic drug action [ 1]. Modelled on paradigmatic situations in general medicine—such as the use of insulin in diabetes, antibiotics in infectious disease, chemotherapy in cancer—the disease-centred model suggests that antidepressants help restore normal functioning by acting on the neuropathology of depression or of depressive symptoms. In contrast, we propose in this Essay that an alternative “drug-centred” model can better explain observed drug effects in psychiatric conditions. This drug-centred model suggests that instead of relieving a hypothetical biochemical abnormality, drugs themselves cause abnormal states, which may coincidentally relieve psychiatric symptoms ( Table 1). Alcohol's disinhibiting effects may relieve symptoms of social phobia, but that does not imply that alcohol corrects a chemical imbalance underlying social phobia. Sedation may lessen high arousal, present in many acute psychiatric situations. Drugs that induce indifference, such as neuroleptics or opiates, may help reduce the distress of acute psychotic symptoms. Low-dose stimulants may help improve attention and concentration in the short term. Table 1 Main Assumptions of Two Models of Psychotropic Drug Action The disease-centred model in psychiatry leads researchers to infer antidepressant effects from patients' scores on symptom rating scales presumed to assess the manifestations of the disease. The drug-centred model, on the other hand, suggests that physiological and subjective effects of drugs should be examined in their own right. These effects include various forms of sedation, stimulation, and a plethora of biopsychological states. Depending on individual inclination and context (including a person's emotional state upon drug ingestion), intoxication with some drugs produces euphoria or mood elevation. Because tolerance develops, however, euphoriant effects do not persist with long-term use. If antidepressants or any other psychotropic drugs could be shown to have mood-elevating effects that were long-term and not diminished by being in a depressed emotional state, this would distinguish them from psychotropic drugs that cause euphoria and might prove uniquely useful in depressed patients (see Sidebar).",
"title": "Do Antidepressants Cure or Create Abnormal Brain States?"
}
] |
PLAIN-1649
|
Monsanto
|
[
{
"docid": "MED-1733",
"text": "INTRODUCTION: Glyphosate-surfactant herbicide (GlySH) is widely used as a non-selective herbicide. Most intoxicated cases are from ingestion, inhalation, and skin exposure. Intramuscular injection of GlySH has never been reported. We present a case of GlySH intoxication via intramuscular injection. CASE REPORT: A 42-year-old woman came to the emergency department complaining of painful swelling of left upper limb for 12 h. She had performed an intramuscular injection of 6 mL of GlySH over the lateral aspect of the left elbow 15 h previously. Physical examination disclosed painful swelling over left distal arm, elbow, and forearm with three needle punctures. CT scan revealed ill-defined areas of heterogeneous high density with marked swelling at subcutaneous tissue over posterior aspect of the elbow. DISCUSSION: The mechanism of toxicity of GlySH is complicated and surfactant was thought to play an important role in GlySH intoxication. Intramuscular GlySH poisoning is different from oral GlySH intoxication. Care should be taken when monitoring acute rhabdomyolysis and compartment syndrome, which may develop rapidly and contribute to the surfactant component of glyphosate formulation.",
"title": "Rhabdomyolysis from an intramuscular injection of glyphosate-surfactant herbicide."
},
{
"docid": "MED-3935",
"text": "Background Parkinson’s disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk. Methods In June 2007, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, to assess what is known about the contribution of environmental factors to PD. Results We describe the conclusions around which they came to consensus with respect to environmental contributors to PD risk. We conclude with a brief summary of research needs. Conclusions PD is a complex disorder, and multiple different pathogenic pathways and mechanisms can ultimately lead to PD. Within the individual there are many determinants of PD risk, and within populations, the causes of PD are heterogeneous. Although rare recognized genetic mutations are sufficient to cause PD, these account for < 10% of PD in the U.S. population, and incomplete penetrance suggests that environmental factors may be involved. Indeed, interplay among environmental factors and genetic makeup likely influences the risk of developing PD. There is a need for further understanding of how risk factors interact, and studying PD is likely to increase understanding of other neurodegenerative disorders.",
"title": "Meeting Report: Consensus Statement—Parkinson’s Disease and the Environment: Collaborative on Health and the Environment and Parkinson’s Action Network (CHE PAN) Conference 26–28 June 2007"
},
{
"docid": "MED-1744",
"text": "Eighty percent of (commercial) genetically engineered seeds (GES) are designed only to resist herbicides. Letting farmers use more chemicals, they cut labor costs. But developing nations say GES cause food shortages, unemployment, resistant weeds, and extinction of native cultivars when \"volunteers\" drift nearby. While GES patents are reasonable, this paper argues many patent policies are not. The paper surveys GE technology, outlines John Locke's classic account of property rights, and argues that current patent policies must be revised to take account of Lockean ethical constraints. After answering a key objection, it provides concrete suggestions for implementing its ethical conclusions.",
"title": "Property rights and genetic engineering: developing nations at risk."
},
{
"docid": "MED-1729",
"text": "We previously demonstrated that the frequency of birth defects among children of residents of the Red River Valley (RRV), Minnesota, USA, was significantly higher than in other major agricultural regions of the state during the years 1989-1991, with children born to male pesticide applicators having the highest risk. The present, smaller cross-sectional study of 695 families and 1,532 children, conducted during 1997-1998, provides a more detailed examination of reproductive health outcomes in farm families ascertained from parent-reported birth defects. In the present study, in the first year of life, the birth defect rate was 31.3 births per 1,000, with 83% of the total reported birth defects confirmed by medical records. Inclusion of children identified with birth or developmental disorders within the first 3 years of life and later led to a rate of 47.0 per 1,000 (72 children from 1,532 live births). Conceptions in spring resulted in significantly more children with birth defects than found in any other season (7.6 vs. 3.7%). Twelve families had more than one child with a birth defect (n = 28 children). Forty-two percent of the children from families with recurrent birth defects were conceived in spring, a significantly higher rate than that for any other season. Three families in the kinships defined contributed a first-degree relative other than a sibling with the same or similar birth defect, consistent with a Mendelian inheritance pattern. The remaining nine families did not follow a Mendelian inheritance pattern. The sex ratio of children with birth defects born to applicator families shows a male predominance (1.75 to 1) across specific pesticide class use and exposure categories exclusive of fungicides. In the fungicide exposure category, normal female births significantly exceed male births (1.25 to 1). Similarly, the proportion of male to female children with birth defects is significantly lower (0.57 to 1; p = 0.02). Adverse neurologic and neurobehavioral developmental effects clustered among the children born to applicators of the fumigant phosphine (odds ratio [OR] = 2.48; confidence interval [CI], 1.2-5.1). Use of the herbicide glyphosate yielded an OR of 3.6 (CI, 1.3-9.6) in the neurobehavioral category. Finally, these studies point out that (a) herbicides applied in the spring may be a factor in the birth defects observed and (b) fungicides can be a significant factor in the determination of sex of the children of the families of the RRV. Thus, two distinct classes of pesticides seem to have adverse effects on different reproductive outcomes. Biologically based confirmatory studies are needed.",
"title": "Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA."
},
{
"docid": "MED-1740",
"text": "To assess human health risk from environmental chemicals, we have studied the effect on cell cycle regulation of the widely used glyphosate-containing pesticide Roundup. As a model system we have used sea urchin embryonic first divisions following fertilization, which are appropriate for the study of universal cell cycle regulation without interference with transcription. We show that 0.8% Roundup (containing 8 mM glyphosate) induces a delay in the kinetic of the first cell cleavage of sea urchin embryos. The delay is dependent on the concentration of Roundup. The delay in the cell cycle could be induced using increasing glyphosate concentrations (1-10 mM) in the presence of a subthreshold concentration of Roundup 0.2%, while glyphosate alone was ineffective, thus indicating synergy between glyphosate and Roundup formulation products. The effect of Roundup was not lethal and involved a delay in entry into M-phase of the cell cycle, as judged cytologically. Since CDK1/cyclin B regulates universally the M-phase of the cell cycle, we analyzed CDK1/cyclin B activation during the first division of early development. Roundup delayed the activation of CDK1/cyclin B in vivo. Roundup inhibited also the global protein synthetic rate without preventing the accumulation of cyclin B. In summary, Roundup affects cell cycle regulation by delaying activation of the CDK1/cyclin B complex, by synergic effect of glyphosate and formulation products. Considering the universality among species of the CDK1/cyclin B regulator, our results question the safety of glyphosate and Roundup on human health.",
"title": "Pesticide Roundup provokes cell division dysfunction at the level of CDK1/cyclin B activation."
},
{
"docid": "MED-1736",
"text": "Glyphosate is a herbicide widely used to kill weeds both in agricultural and non-agricultural landscapes. Its reproductive toxicity is related to the inhibition of a StAR protein and an aromatase enzyme, which causes an in vitro reduction in testosterone and estradiol synthesis. Studies in vivo about this herbicide effects in prepubertal Wistar rats reproductive development were not performed at this moment. Evaluations included the progression of puberty, body development, the hormonal production of testosterone, estradiol and corticosterone, and the morphology of the testis. Results showed that the herbicide (1) significantly changed the progression of puberty in a dose-dependent manner; (2) reduced the testosterone production, in semineferous tubules' morphology, decreased significantly the epithelium height (P < 0.001; control = 85.8 +/- 2.8 microm; 5 mg/kg = 71.9 +/- 5.3 microm; 50 mg/kg = 69.1 +/- 1.7 microm; 250 mg/kg = 65.2 +/- 1.3 microm) and increased the luminal diameter (P < 0.01; control = 94.0 +/- 5.7 microm; 5 mg/kg = 116.6 +/- 6.6 microm; 50 mg/kg = 114.3 +/- 3.1 microm; 250 mg/kg = 130.3 +/- 4.8 microm); (4) no difference in tubular diameter was observed; and (5) relative to the controls, no differences in serum corticosterone or estradiol levels were detected, but the concentrations of testosterone serum were lower in all treated groups (P < 0.001; control = 154.5 +/- 12.9 ng/dL; 5 mg/kg = 108.6 +/- 19.6 ng/dL; 50 mg/dL = 84.5 +/- 12.2 ng/dL; 250 mg/kg = 76.9 +/- 14.2 ng/dL). These results suggest that commercial formulation of glyphosate is a potent endocrine disruptor in vivo, causing disturbances in the reproductive development of rats when the exposure was performed during the puberty period.",
"title": "Prepubertal exposure to commercial formulation of the herbicide glyphosate alters testosterone levels and testicular morphology."
},
{
"docid": "MED-3940",
"text": "Objective: To determine whether evidence of neuronal dysfunction or demise preceded deposition of Lewy pathology in vulnerable neurons in Parkinson disease (PD). Methods: We examined the extent of nigral dysfunction and degeneration among 63 normal, incidental Lewy body disease (ILBD), and PD cases based on tyrosine hydroxylase (TH) immunoreactivity and neuron densities, respectively. The relationship between these markers and Lewy pathology (LP) burden in the substantia nigra (SN) and Braak PD stage was assessed. Results: Compared with normal subjects, ILBD cases displayed a significantly higher percentage of TH-negative cells and lower neuronal densities in the SN as early as Braak PD stages 1 and 2, before LP deposition in the nigrostriatal system. ILBD nigral neuron densities were intermediate between normal subjects and PD cases, and TH-negative percentages were higher in ILBD than either normal or PD cases. Furthermore, neuron density and neuronal dysfunction levels remained relatively constant across Braak PD stages in ILBD. Conclusions: These results suggest that significant neurodegeneration and cellular dysfunction precede LP in the SN, challenging the pathogenic role of LP in PD and the assumption that ILBD always represents preclinical PD.",
"title": "Lewy pathology is not the first sign of degeneration in vulnerable neurons in Parkinson disease"
},
{
"docid": "MED-1749",
"text": "Pesticides associated to genetically modified foods (PAGMF), are engineered to tolerate herbicides such as glyphosate (GLYP) and gluphosinate (GLUF) or insecticides such as the bacterial toxin bacillus thuringiensis (Bt). The aim of this study was to evaluate the correlation between maternal and fetal exposure, and to determine exposure levels of GLYP and its metabolite aminomethyl phosphoric acid (AMPA), GLUF and its metabolite 3-methylphosphinicopropionic acid (3-MPPA) and Cry1Ab protein (a Bt toxin) in Eastern Townships of Quebec, Canada. Blood of thirty pregnant women (PW) and thirty-nine nonpregnant women (NPW) were studied. Serum GLYP and GLUF were detected in NPW and not detected in PW. Serum 3-MPPA and CryAb1 toxin were detected in PW, their fetuses and NPW. This is the first study to reveal the presence of circulating PAGMF in women with and without pregnancy, paving the way for a new field in reproductive toxicology including nutrition and utero-placental toxicities. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada."
},
{
"docid": "MED-3937",
"text": "BACKGROUND: The goal of the present study was to analyze the epidemiology and specific risk factors of traumatic brain injury (TBI) in the Asterix illustrated comic books. Among the illustrated literature, TBI is a predominating injury pattern. METHODS: A retrospective analysis of TBI in all 34 Asterix comic books was performed by examining the initial neurological status and signs of TBI. Clinical data were correlated to information regarding the trauma mechanism, the sociocultural background of victims and offenders, and the circumstances of the traumata, to identify specific risk factors. RESULTS: Seven hundred and four TBIs were identified. The majority of persons involved were adult and male. The major cause of trauma was assault (98.8%). Traumata were classified to be severe in over 50% (GCS 3-8). Different neurological deficits and signs of basal skull fractures were identified. Although over half of head-injury victims had a severe initial impairment of consciousness, no case of death or permanent neurological deficit was found. The largest group of head-injured characters was constituted by Romans (63.9%), while Gauls caused nearly 90% of the TBIs. A helmet had been worn by 70.5% of victims but had been lost in the vast majority of cases (87.7%). In 83% of cases, TBIs were caused under the influence of a doping agent called \"the magic potion\". CONCLUSIONS: Although over half of patients had an initially severe impairment of consciousness after TBI, no permanent deficit could be found. Roman nationality, hypoglossal paresis, lost helmet, and ingestion of the magic potion were significantly correlated with severe initial impairment of consciousness (p ≤ 0.05).",
"title": "Traumatic brain injuries in illustrated literature: experience from a series of over 700 head injuries in the Asterix comic books."
},
{
"docid": "MED-1743",
"text": "This article describes the nutrient and elemental composition, including residues of herbicides and pesticides, of 31 soybean batches from Iowa, USA. The soy samples were grouped into three different categories: (i) genetically modified, glyphosate-tolerant soy (GM-soy); (ii) unmodified soy cultivated using a conventional \"chemical\" cultivation regime; and (iii) unmodified soy cultivated using an organic cultivation regime. Organic soybeans showed the healthiest nutritional profile with more sugars, such as glucose, fructose, sucrose and maltose, significantly more total protein, zinc and less fibre than both conventional and GM-soy. Organic soybeans also contained less total saturated fat and total omega-6 fatty acids than both conventional and GM-soy. GM-soy contained high residues of glyphosate and AMPA (mean 3.3 and 5.7 mg/kg, respectively). Conventional and organic soybean batches contained none of these agrochemicals. Using 35 different nutritional and elemental variables to characterise each soy sample, we were able to discriminate GM, conventional and organic soybeans without exception, demonstrating \"substantial non-equivalence\" in compositional characteristics for 'ready-to-market' soybeans. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.",
"title": "Compositional differences in soybeans on the market: glyphosate accumulates in Roundup Ready GM soybeans."
},
{
"docid": "MED-4726",
"text": "The aim of these studies was to evaluate the potential of some nutritional approaches to prevent or reduce the body load of organochlorines (OC) in humans. Study 1 compared plasma OC concentrations between vegans and omnivores while study 2 verified if the dietary fat substitute olestra could prevent the increase in OC concentrations that is generally observed in response to a weight-reducing programme. In study 1, nine vegans and fifteen omnivores were recruited and the concentrations of twenty-six OC (beta-hexachlorocyclohexane (beta-HCH), p, p'-dichlorodiphenyldichloroethane (p, p'-DDE), p, p'-dichlorodiphenyltrichloroethane (p, p'-DDT), hexachlorobenzene, mirex, aldrin, alpha-chlordane, gamma-chlordane, oxychlordane, cis-nonachlor, trans-nonachlor, polychlorinated biphenyl (PCB) nos. 28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 170, 180, 183 and 187, and aroclor 1260) were determined. In study 2, the concentrations of these twenty-six OC were measured before and after weight loss over 3 months in thirty-seven obese men assigned to one of the following treatments: standard group (33 % fat diet; n 13), fat-reduced group (25 % fat diet; n 14) or fat-substituted group (1/3 of dietary lipids substituted by olestra; n 10). In study 1, plasma concentrations of five OC compounds (aroclor 1260 and PCB 99, PCB 138, PCB 153 and PCB 180) were significantly lower in vegans compared with omnivores. In study 2, beta-HCH was the only OC which decreased in the fat-substituted group while increasing in the other two groups (P = 0.045). In conclusion, there was a trend toward lesser contamination in vegans than in omnivores, and olestra had a favourable influence on beta-HCH but did not prevent plasma hyperconcentration of the other OC during ongoing weight loss.",
"title": "Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations: results from two pilot studies."
},
{
"docid": "MED-1732",
"text": "Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Glyphosate induces human breast cancer cells growth via estrogen receptors."
},
{
"docid": "MED-1728",
"text": "The United States Environmental Protection Agency and other regulatory agencies around the world have registered glyphosate as a broad-spectrum herbicide for use on multiple food and non-food use crops. Glyphosate is widely considered by regulatory authorities and scientific bodies to have no carcinogenic potential, based primarily on results of carcinogenicity studies of rats and mice. To examine potential cancer risks in humans, we reviewed the epidemiologic literature to evaluate whether exposure to glyphosate is associated causally with cancer risk in humans. We also reviewed relevant methodological and biomonitoring studies of glyphosate. Seven cohort studies and fourteen case-control studies examined the association between glyphosate and one or more cancer outcomes. Our review found no consistent pattern of positive associations indicating a causal relationship between total cancer (in adults or children) or any site-specific cancer and exposure to glyphosate. Data from biomonitoring studies underscore the importance of exposure assessment in epidemiologic studies, and indicate that studies should incorporate not only duration and frequency of pesticide use, but also type of pesticide formulation. Because generic exposure assessments likely lead to exposure misclassification, it is recommended that exposure algorithms be validated with biomonitoring data. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Epidemiologic studies of glyphosate and cancer: a review."
},
{
"docid": "MED-1741",
"text": "Roundup is a glyphosate-based herbicide used worldwide, including on most genetically modified plants that have been designed to tolerate it. Its residues may thus enter the food chain, and glyphosate is found as a contaminant in rivers. Some agricultural workers using glyphosate have pregnancy problems, but its mechanism of action in mammals is questioned. Here we show that glyphosate is toxic to human placental JEG3 cells within 18 hr with concentrations lower than those found with agricultural use, and this effect increases with concentration and time or in the presence of Roundup adjuvants. Surprisingly, Roundup is always more toxic than its active ingredient. We tested the effects of glyphosate and Roundup at lower nontoxic concentrations on aromatase, the enzyme responsible for estrogen synthesis. The glyphosate-based herbicide disrupts aromatase activity and mRNA levels and interacts with the active site of the purified enzyme, but the effects of glyphosate are facilitated by the Roundup formulation in microsomes or in cell culture. We conclude that endocrine and toxic effects of Roundup, not just glyphosate, can be observed in mammals. We suggest that the presence of Roundup adjuvants enhances glyphosate bioavailability and/or bioaccumulation.",
"title": "Differential Effects of Glyphosate and Roundup on Human Placental Cells and Aromatase"
},
{
"docid": "MED-1737",
"text": "Roundup is the major herbicide used worldwide, in particular on genetically modified plants that have been designed to tolerate it. We have tested the toxicity and endocrine disruption potential of Roundup (Bioforce on human embryonic 293 and placental-derived JEG3 cells, but also on normal human placenta and equine testis. The cell lines have proven to be suitable to estimate hormonal activity and toxicity of pollutants. The median lethal dose (LD(50)) of Roundup with embryonic cells is 0.3% within 1 h in serum-free medium, and it decreases to reach 0.06% (containing among other compounds 1.27 mM glyphosate) after 72 h in the presence of serum. In these conditions, the embryonic cells appear to be 2-4 times more sensitive than the placental ones. In all instances, Roundup (generally used in agriculture at 1-2%, i.e., with 21-42 mM glyphosate) is more efficient than its active ingredient, glyphosate, suggesting a synergistic effect provoked by the adjuvants present in Roundup. We demonstrated that serum-free cultures, even on a short-term basis (1 h), reveal the xenobiotic impacts that are visible 1-2 days later in serum. We also document at lower non-overtly toxic doses, from 0.01% (with 210 microM glyphosate) in 24 h, that Roundup is an aromatase disruptor. The direct inhibition is temperature-dependent and is confirmed in different tissues and species (cell lines from placenta or embryonic kidney, equine testicular, or human fresh placental extracts). Furthermore, glyphosate acts directly as a partial inactivator on microsomal aromatase, independently of its acidity, and in a dose-dependent manner. The cytotoxic, and potentially endocrine-disrupting effects of Roundup are thus amplified with time. Taken together, these data suggest that Roundup exposure may affect human reproduction and fetal development in case of contamination. Chemical mixtures in formulations appear to be underestimated regarding their toxic or hormonal impact.",
"title": "Time- and dose-dependent effects of roundup on human embryonic and placental cells."
},
{
"docid": "MED-1731",
"text": "Glyphosate surfactant herbicide (GlySH) toxicity is an uncommon poisoning. We report two fatalities involving suicidal ingestion of this herbicide. Both deaths occurred despite early recognition of the serious nature of the poisoning and aggressive treatment. The deaths in this series are analysed in the context of a review of existing literature. Although traditionally regarded as minimally toxic, many deaths have been reported following suicidal ingestion. Severe GlySH toxicity may be refractory even to the most intensive supportive care. The triad of pulmonary oedema, metabolic acidosis and hyperkalaemia portends poor outcome. While containing a carbon phosphorus moiety, GlySH does not exhibit organophosphate toxicity. A clinical guide to assessing severity of GlySH toxicity is proposed and treatment modalities discussed.",
"title": "Glyphosate herbicide formulation: a potentially lethal ingestion."
},
{
"docid": "MED-1725",
"text": "Methods: During the 1980s, the National Cancer Institute conducted three case-control studies of NHL in the midwestern United States. These pooled data were used to examine pesticide exposures in farming as risk factors for NHL in men. The large sample size (n = 3417) allowed analysis of 47 pesticides simultaneously, controlling for potential confounding by other pesticides in the model, and adjusting the estimates based on a prespecified variance to make them more stable. Results: Reported use of several individual pesticides was associated with increased NHL incidence, including organophosphate insecticides coumaphos, diazinon, and fonofos, insecticides chlordane, dieldrin, and copper acetoarsenite, and herbicides atrazine, glyphosate, and sodium chlorate. A subanalysis of these \"potentially carcinogenic\" pesticides suggested a positive trend of risk with exposure to increasing numbers. Conclusion: Consideration of multiple exposures is important in accurately estimating specific effects and in evaluating realistic exposure scenarios.",
"title": "Integrative assessment of multiple pesticides as risk factors for non-Hodgkin's lymphoma among men"
},
{
"docid": "MED-1745",
"text": "The composition of glyphosate-tolerant (Roundup Ready) soybean 40-3-2 was compared with that of conventional soybean grown in Romania in 2005 as part of a comparative safety assessment program. Samples were collected from replicated field trials, and compositional analyses were performed to measure proximates (moisture, fat, ash, protein, and carbohydrates by calculation), fiber, amino acids, fatty acids, isoflavones, raffinose, stachyose, phytic acid, trypsin inhibitor, and lectin in grain as well as proximates and fiber in forage. The mean values for all biochemical components assessed for Roundup Ready soybean 40-30-2 were similar to those of the conventional control and were within the published range observed for commercial soybean. The compositional profile of Roundup Ready soybean 40-3-2 was also compared to that of conventional soybean varieties grown in Romania by calculating a 99% tolerance interval to describe compositional variability in the population of traditional soybean varieties already on the marketplace. These comparisons, together with the history of the safe use of soybean as a common component of animal feed and human food, lead to the conclusion that Roundup Ready soybean 40-3-2 is compositionally equivalent to and as safe and nutritious as conventional soybean varieties grown commercially.",
"title": "Chemical composition of glyphosate-tolerant soybean 40-3-2 grown in Europe remains equivalent with that of conventional soybean (Glycine max L.)."
},
{
"docid": "MED-3938",
"text": "Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson’s disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson’s disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson’s disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson’s disease patients. When stratified by sex, the female Parkinson’s disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson’s disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson’s disease-related pathology. Furthermore, these data support epidemiological and laboratory studies reporting a link between PCB exposure and an increased risk for Parkinson’s disease, including greater susceptibility of females.",
"title": "Association between polychlorinated biphenyls and Parkinson’s disease neuropathology"
},
{
"docid": "MED-3939",
"text": "Excerpt This Statistical Brief presents data from the Healthcare Cost and Utilization Project (HCUP) on the treatment of TBI in U.S. hospitals in 2004. Hospital utilization and costs for TBI admissions are compared with hospital stays for all other injuries. Additionally, trends in hospital stays for TBI and differences in the distribution of TBI admissions by various patient characteristics are examined. Finally, common causes of TBIs resulting in hospital admission, as well as the coexisting conditions often associated with these injuries, are described. All differences between estimates noted in the text are statistically significant at the 0.05 level or better.",
"title": "Hospital Admissions for Traumatic Brain Injuries, 2004: Statistical Brief #27"
},
{
"docid": "MED-1739",
"text": "Glyphosate is the primary active constituent of the commercial pesticide Roundup. The present results show that acute Roundup exposure at low doses (36 ppm, 0.036 g/L) for 30 min induces oxidative stress and activates multiple stress-response pathways leading to Sertoli cell death in prepubertal rat testis. The pesticide increased intracellular Ca(2+) concentration by opening L-type voltage-dependent Ca(2+) channels as well as endoplasmic reticulum IP3 and ryanodine receptors, leading to Ca(2+) overload within the cells, which set off oxidative stress and necrotic cell death. Similarly, 30 min incubation of testis with glyphosate alone (36 ppm) also increased (45)Ca(2+) uptake. These events were prevented by the antioxidants Trolox and ascorbic acid. Activated protein kinase C, phosphatidylinositol 3-kinase, and the mitogen-activated protein kinases such as ERK1/2 and p38MAPK play a role in eliciting Ca(2+) influx and cell death. Roundup decreased the levels of reduced glutathione (GSH) and increased the amounts of thiobarbituric acid-reactive species (TBARS) and protein carbonyls. Also, exposure to glyphosate-Roundup stimulated the activity of glutathione peroxidase, glutathione reductase, glutathione S-transferase, γ-glutamyltransferase, catalase, superoxide dismutase, and glucose-6-phosphate dehydrogenase, supporting downregulated GSH levels. Glyphosate has been described as an endocrine disruptor affecting the male reproductive system; however, the molecular basis of its toxicity remains to be clarified. We propose that Roundup toxicity, implicated in Ca(2+) overload, cell signaling misregulation, stress response of the endoplasmic reticulum, and/or depleted antioxidant defenses, could contribute to Sertoli cell disruption in spermatogenesis that could have an impact on male fertility. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "Roundup disrupts male reproductive functions by triggering calcium-mediated cell death in rat testis and Sertoli cells."
},
{
"docid": "MED-2763",
"text": "Despite compelling statistics that show we could eliminate 80%of all heart disease and strokes, 90% of all diabetes, and 60% of all cancers with basic lifestyle changes, we have failed to motivate the public to make these changes and failed to motivate policy makers to make healthy choices the easiest choice. Dr. Katz suggests we have failed because we have focused too much on statistics and too little on passion. He implores all of us to tap into people's passion by connecting each of these statistics with a human story.",
"title": "Facing the facelessness of public health: what's the public got to do with it?"
},
{
"docid": "MED-1730",
"text": "The United States (US) Environmental Protection Agency (EPA) and other regulatory agencies around the world have registered glyphosate as a broad-spectrum herbicide for use on multiple food and non-food use crops. To examine potential health risks in humans, we searched and reviewed the literature to evaluate whether exposure to glyphosate is associated causally with non-cancer health risks in humans. We also reviewed biomonitoring studies of glyphosate to allow for a more comprehensive discussion of issues related to exposure assessment and misclassification. Cohort, case-control and cross-sectional studies on glyphosate and non-cancer outcomes evaluated a variety of endpoints, including non-cancer respiratory conditions, diabetes, myocardial infarction, reproductive and developmental outcomes, rheumatoid arthritis, thyroid disease, and Parkinson's disease. Our review found no evidence of a consistent pattern of positive associations indicating a causal relationship between any disease and exposure to glyphosate. Most reported associations were weak and not significantly different from 1.0. Because accurate exposure measurement is crucial for valid results, it is recommended that pesticide-specific exposure algorithms be developed and validated. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Epidemiologic studies of glyphosate and non-cancer health outcomes: a review."
},
{
"docid": "MED-1726",
"text": "Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone.",
"title": "Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles"
},
{
"docid": "MED-1746",
"text": "The global area covered with transgenic (genetically modified) crops has rapidly increased since their introduction in the mid-1990s. Most of these crops have been rendered herbicide resistant, for which it can be envisaged that the modification has an impact on the profile and level of herbicide residues within these crops. In this article, the four main categories of herbicide resistance, including resistance to acetolactate-synthase inhibitors, bromoxynil, glufosinate and glyphosate, are reviewed. The topics considered are the molecular mechanism underlying the herbicide resistance, the nature and levels of the residues formed and their impact on the residue definition and maximum residue limits (MRLs) defined by the Codex Alimentarius Commission and national authorities. No general conclusions can be drawn concerning the nature and level of residues, which has to be done on a case-by-case basis. International residue definitions and MRLs are still lacking for some herbicide-crop combinations, and harmonisation is therefore recommended. Copyright © 2011 Society of Chemical Industry.",
"title": "The impact of altered herbicide residues in transgenic herbicide-resistant crops on standard setting for herbicide residues."
},
{
"docid": "MED-3936",
"text": "Background Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains. Objective To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD. Design Case-control study. Setting An academic medical center. Participants Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease. Main Outcome Measures Levels of 16 organochlorine pesticides in serum samples. Results β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD. Conclusions These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD.",
"title": "Elevated Serum Pesticide Levels and Risk of Parkinson Disease"
},
{
"docid": "MED-1738",
"text": "Glyphosate is the active ingredient of several widely used herbicide formulations. Glyphosate targets the shikimate metabolic pathway, which is found in plants but not in animals. Despite the relative safety of glyphosate, various adverse developmental and reproductive problems have been alleged as a result of exposure in humans and animals. To assess the developmental and reproductive safety of glyphosate, an analysis of the available literature was conducted. Epidemiological and animal reports, as well as studies on mechanisms of action related to possible developmental and reproductive effects of glyphosate, were reviewed. An evaluation of this database found no consistent effects of glyphosate exposure on reproductive health or the developing offspring. Furthermore, no plausible mechanisms of action for such effects were elucidated. Although toxicity was observed in studies that used glyphosate-based formulations, the data strongly suggest that such effects were due to surfactants present in the formulations and not the direct result of glyphosate exposure. To estimate potential human exposure concentrations to glyphosate as a result of working directly with the herbicide, available biomonitoring data were examined. These data demonstrated extremely low human exposures as a result of normal application practices. Furthermore, the estimated exposure concentrations in humans are >500-fold less than the oral reference dose for glyphosate of 2 mg/kg/d set by the U.S. Environmental Protection Agency (U.S. EPA 1993). In conclusion, the available literature shows no solid evidence linking glyphosate exposure to adverse developmental or reproductive effects at environmentally realistic exposure concentrations.",
"title": "Developmental and reproductive outcomes in humans and animals after glyphosate exposure: a critical analysis."
}
] |
[
{
"docid": "MED-4059",
"text": "2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine formed in meat and fish during cooking and can be used as a model compound for this class of chemicals possibly involved in human carcinogenesis. Knowing the exposure to heterocyclic amines is important for establishing their role in human diseases. Serum albumin (SA) and globin (Gb) adducts were first tested as biomarkers of exposure to PhIP in male Fischer 344 rats given oral doses of 0.1, 0.5, 1 and 10 mg/kg. Blood samples were collected 24 hr after treatment and PhIP released from SA and Gb after acidic hydrolysis was analyzed by gas chromatography-mass spectrometry or liquid chromatography-tandem mass spectrometry. PhIP-SA and Gb adducts increased linearly with the dose. Studies on 35 volunteers with different dietary habits exhibited that diet was a major determinant in the formation of both adducts. PhIP-SA adducts were significantly higher in meat consumers than in vegetarians (6.7 +/- 1.6 and 0.7 +/- 0.3 fmol/mg SA; respectively, mean +/- SE; p = 0.04, Mann-Whitney U test). The Gb adduct pattern was quantitatively lower but paralleled SA (3 +/- 0.8 in meat consumers and 0.3 +/- 0.1 in vegetarians). PhIP-SA adducts were no different in smokers and in non-smokers. The results show for the first time that PhIP-blood protein adducts are present in humans not given the synthetic compound. Both biomarkers appear to be suitable for assessing dietary exposure and internal PhIP dose and may be promising tools for studying the role of heterocyclic amines in the etiology of colon cancer and other diseases. Copyright 2000 Wiley-Liss, Inc.",
"title": "Effect of diet on serum albumin and hemoglobin adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans."
},
{
"docid": "MED-760",
"text": "There is much interest in the potential of dietary antioxidants to attenuate in vivo oxidative stress, but little characterization of the time course of plasma effects exists. Culinary spices have demonstrated potent in vitro antioxidant properties. The objective of this study was to examine whether adding 14 g of a high antioxidant spice blend to a 5060-kJ (1200 kcal) meal exerted significant postprandial effects on markers of plasma antioxidant status and metabolism. Healthy overweight men (n = 6) consumed a control and spiced meal in a randomized crossover design with 1 wk between testing sessions. Blood was sampled prior to the meal and at 30-min intervals for 3.5 h (total of 8 samples). Mixed linear models demonstrated a treatment × time interaction (P < 0.05) for insulin and TG, corresponding with 21 and 31% reductions in postprandial levels with the spiced meal, respectively. Adding spices to the meal significantly increased the ferric reducing antioxidant power, such that postprandial increases following the spiced meal were 2-fold greater than after the control meal (P = 0.009). The hydrophilic oxygen radical absorbance capacity (ORAC) of plasma also was increased by spices (P = 0.02). There were no treatment differences in glucose, total thiols, lipophilic ORAC, or total ORAC. The incorporation of spices into the diet may help normalize postprandial insulin and TG and enhance antioxidant defenses.",
"title": "A High Antioxidant Spice Blend Attenuates Postprandial Insulin and Triglyceride Responses and Increases Some Plasma Measures of Antioxidant Activity in Healthy, Overweight Men"
},
{
"docid": "MED-4034",
"text": "OBJECTIVES: To determine whether foods that are good to excellent sources of fiber reduce periodontal disease progression in men. DESIGN: Prospective, observational study. SETTING: Greater Boston, Massachusetts, metropolitan area. PARTICIPANTS: Six hundred twenty-five community-dwelling men participating in the Department of Veterans Affairs Dental Longitudinal Study. MEASUREMENTS: Dental and physical examinations were conducted every 3 to 5 years. Diet was assessed using food frequency questionnaires (FFQs). Mean follow-up was 15 years (range: 2-24 years). Periodontal disease progression on each tooth was defined as alveolar bone loss (ABL) advancement of 40% or more, probing pocket depth (PPD) of 2 mm or more, or tooth loss. Good and excellent fiber sources provided 2.5 g or more of fiber per serving. Multivariate proportional hazards regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of periodontal disease progression and tooth loss in relation to fiber sources, stratified according to age younger than 65 versus 65 and older, and controlled for smoking, body mass index, calculus, baseline periodontal disease level, caries, education, exercise, carotene, thiamin and caffeine intake, and tooth brushing. RESULTS: In men aged 65 and older, each serving of good to excellent sources of total fiber was associated with lower risk of ABL progression (HR = 0.76, 95% CI = 0.60-0.95) and tooth loss (HR = 0.72, 95% CI = 0.53-0.97). Of the different food groups, only fruits that were good to excellent sources of fiber were associated with lower risk of progression of ABL (HR = 0.86 per serving, 95% CI = 0.78-0.95), PPD (HR = 0.95, 95% CI = 0.91-0.99), and tooth loss (HR = 0.88, 95% CI = 0.78-0.99). No significant associations were seen in men younger than 65. CONCLUSION: Benefits of higher intake of high-fiber foods, especially fruits, on slowing periodontal disease progression are most evident in men aged 65 and older. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.",
"title": "High-fiber foods reduce periodontal disease progression in men aged 65 and older: the Veterans Affairs normative aging study/Dental Longitudinal St..."
},
{
"docid": "MED-1793",
"text": "Most research studies in the field of dietary polyphenols or phenolic compounds use a chemical approach focusing exclusively on polyphenols extracted from plant foods with organic solvents. However, an appreciable part of polyphenols are not extracted with organic solvents and thus are ignored in biological, nutritional, and epidemiological studies. Recent studies have shown that these nonextractable polyphenols (NEPP) are a major part of total dietary polyphenols and that they exhibit a significant biological activity. A physiological approach is proposed on the basis that the bioavailability and health-related properties of polyphenols depend on their solubility in intestinal fluids, which is different from their solubility in organic solvents. This paper tries to clarify the concept of NEPP, distinguishing between chemical and physiological approaches and pointing out the main qualitative and quantitative differences between them. It is stressed that the literature and databases refer to only extractable polyphenols. Greater attention to NEPP may fill the current gap in the field of dietary polyphenols.",
"title": "Concept and health-related properties of nonextractable polyphenols: the missing dietary polyphenols."
},
{
"docid": "MED-980",
"text": "Background An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins. Objective To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159). Methods and Findings Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B6 and B12 in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans. Results A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63–0.90] in the active treatment group and 1.08% [0.94–1.22] in the placebo group (P = 0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P = 0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category. Conclusions and Significance The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease. Trial Registration Controlled-Trials.com ISRCTN94410159",
"title": "Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial"
},
{
"docid": "MED-3977",
"text": "OBJECTIVE: The aim of this study was to revisit findings from previous studies reporting that pet ownership improves outcome following an admission for acute coronary syndrome (ACS). METHOD: Four hundred and twenty-four patients admitted to a cardiac unit with an ACS completed questions regarding pet ownership in hospital. Rates of cardiac death and readmission were assessed 1 year following hospitalization. RESULTS: Pet owners were more likely to experience a death or readmission following their hospitalization, after controlling for key psychosocial and medical covariates. When dog and cat owners were considered separately, cat ownership was significantly associated with increased risk of death or readmission. CONCLUSION: In this independent study, pet ownership at baseline, and cat ownership in particular, was associated with increased cardiac morbidity and mortality in the year following an admission for an acute coronary syndrome, a finding contrary to previous reports.",
"title": "Survival following an acute coronary syndrome: a pet theory put to the test."
},
{
"docid": "MED-3734",
"text": "Cranberry products and especially cranberry juice (CJ) have been consumed for health reasons primarily due to their effect on urinary tract infections. We investigated the quantity of both free and total (after hydrolysis) phenolic antioxidants in cranberry products using the Folin assay. The order of amount of total polyphenols in cranberry foods on a fresh weight basis was as follows: dried > frozen > sauce > jellied sauce. On a serving size basis for all cranberry products, the order was as follows: frozen > 100% juice > dried > 27% juice > sauce > jellied sauce. High fructose corn syrup (HFCS) is a major source of sugar consumption in the U.S. and contains both glucose and fructose, potential mediators of oxidative stress. We investigated the effect of the consumption of HFCS and ascorbate with CJ antioxidants or without CJ (control) given to 10 normal individuals after an overnight fast. Plasma antioxidant capacity, glucose, triglycerides, and ascorbate were measured 6 times over 7 h after the consumption of a single 240 mL serving of the two different beverages. The control HFCS caused a slight decrease in plasma antioxidant capacity at all time points and thus an oxidative stress in spite of the presence of ascorbate. CJ produced an increase in plasma antioxidant capacity that was significantly greater than control HFCS at all time points. Postprandial triglycerides, due to fructose in the beverages, were mainly responsible for the oxidative stress and were significantly correlated with the oxidative stress as measured by the antioxidant capacity. Cranberries are an excellent source of high quality antioxidants and should be examined in human supplementation studies.",
"title": "Cranberries and cranberry products: powerful in vitro, ex vivo, and in vivo sources of antioxidants."
},
{
"docid": "MED-2511",
"text": "Residents of Okinawa, the southernmost prefecture of Japan, are known for their long average life expectancy, high numbers of centenarians, and accompanying low risk of age-associated diseases. Much of the longevity advantage in Okinawa is thought to be related to a healthy lifestyle, particularly the traditional diet, which is low in calories yet nutritionally dense, especially with regard to phytonutrients in the form of antioxidants and flavonoids. Research suggests that diets associated with a reduced risk of chronic diseases are similar to the traditional Okinawan diet, that is, vegetable and fruit heavy (therefore phytonutrient and antioxidant rich) but reduced in meat, refined grains, saturated fat, sugar, salt, and full-fat dairy products. Many of the characteristics of the diet in Okinawa are shared with other healthy dietary patterns, such as the traditional Mediterranean diet or the modern DASH (Dietary Approaches to Stop Hypertension) diet. Features such as the low levels of saturated fat, high antioxidant intake, and low glycemic load in these diets are likely contributing to a decreased risk for cardiovascular disease, some cancers, and other chronic diseases through multiple mechanisms, including reduced oxidative stress. A comparison of the nutrient profiles of the three dietary patterns shows that the traditional Okinawan diet is the lowest in fat intake, particularly in terms of saturated fat, and highest in carbohydrate intake, in keeping with the very high intake of antioxidant-rich yet calorie-poor orange-yellow root vegetables, such as sweet potatoes, and green leafy vegetables. Deeper analyses of the individual components of the Okinawan diet reveal that many of the traditional foods, herbs, or spices consumed on a regular basis could be labeled \"functional foods\" and, indeed, are currently being explored for their potential health-enhancing properties.",
"title": "The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load."
},
{
"docid": "MED-3022",
"text": "Methylmercury (MM) is a very potent neurotoxic agent. Its role in polluting the environment is well documented. A vast amount of study over the past several decades has finally provided insight into many aspects of its effect. Exposure to MM may be through ingestion of poisoned fish or inadvertent misuse of grain treated with the poison as a fungicide. Major epidemics have occurred in Japan (Fetal Minamata disease), Iraq, Pakistan, Guatemala, and Ghana. Sporadic incidences have occurred in the United States and Canada. There is no effective antidote to counteract the effect of MM on the central nervous system, although the information documented should provide hope for more effective therapy in acute cases.",
"title": "The many faces of methylmercury poisoning."
},
{
"docid": "MED-1890",
"text": "BACKGROUND: Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. OBJECTIVE: The objective was to review the effect of dietary cholesterol on the ratio of total to HDL cholesterol. DESIGN: Studies were identified by MEDLINE and Biological s searches (from 1974 to June 1999) and by reviewing reference lists. In addition, we included data from a more recently published study. Studies were included if they had a crossover or parallel design with a control group, if the experimental diets differed only in the amount of dietary cholesterol or number of eggs and were fed for > or =14 d, and if HDL-cholesterol concentrations were reported. Of the 222 studies identified, 17 studies involving 556 subjects met these criteria. RESULTS: The addition of 100 mg dietary cholesterol/d increased the ratio of total to HDL cholesterol by 0.020 units (95% CI: 0.010, 0.030), total cholesterol concentrations by 0.056 mmol/L (2.2 mg/dL) (95% CI: 0.046, 0.065 mmol/L; 1.8, 2.5 mg/dL), and HDL-cholesterol concentrations by 0.008 mmol/L (0.3 mg/dL) (95% CI: 0.005, 0.010 mmol/L; 0.2, 0.4 mg/dL). CONCLUSIONS: Dietary cholesterol raises the ratio of total to HDL cholesterol and, therefore, adversely affects the cholesterol profile. The advice to limit cholesterol intake by reducing consumption of eggs and other cholesterol-rich foods may therefore still be valid.",
"title": "Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans: a meta-analysis."
},
{
"docid": "MED-3024",
"text": "This experiment aimed to study the molecular toxicity of methylmercury (MeHg) in liver, brain and white muscle of Atlantic salmon fed a diet based on fish oil (FO, high dietary n-3/n-6 ratio) compared to an alternative diet mainly based on vegetable oil (VO, low dietary n-3/n-6 ratio). Juvenile salmon were fed decontaminated diets or the FO and VO diets enriched with 5 mg Hg/kg (added as MeHg) for three months. The dietary lipid composition affected the fatty acid composition in the tissues, especially in liver and white muscle. After 84 days of exposure, the liver accumulated three times as much MeHg as the brain and white muscle. Vitamin C content and heme oxygenase, tubulin alpha (TUBA) and Cpt1 transcriptional levels all showed significant effects of MeHg exposure in the liver. TBARS, α-tocopherol, γ-tocopherol, and the transcriptional levels of thioredoxin, heme oxygenase, TUBA, PPARB1, D5D and D6D showed an effect of dietary lipid composition in liver tissue. Effects of dietary lipids were observed in brain tissue for MT-A, HIF1, Bcl-X and TUBA. Interaction effects between MeHg exposure and dietary lipid composition were observed in all tissues. Our data suggest that dietary fats have modulating effects on MeHg toxicity in Atlantic salmon. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Dietary lipids modulate methylmercury toxicity in Atlantic salmon."
},
{
"docid": "MED-2090",
"text": "Taking into consideration genetic damage plays an important role in carcinogenesis, the purpose of this paper is to provide an overview on the genotoxic potential of some endodontic compounds currently used in dentistry, such as formocresol, paramonochlorophenol, calcium hydroxide, resin-based sealers, phenolic compounds, chlorhexidine, mineral trioxide aggregate, and others. Some of these compounds appear capable of exerting noxious activity on the genetic material. The action mechanisms are discussed. Therefore, this is an area that warrants investigation since the estimation of risk of these substances with respect to genotoxicity will be added to those used for regulatory purposes in improving oral health and preventing oral carcinogenesis.",
"title": "Do endodontic compounds induce genetic damage? A comprehensive review."
},
{
"docid": "MED-4593",
"text": "AIMS: The objective of the study was to determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) contamination of retail meat and to determine the level of contamination. METHODS AND RESULTS: Pork (pork chops and ground pork), ground beef and chicken (legs, wings and thighs) were purchased at retail outlets in four Canadian provinces and tested for the presence of methicillin-resistant Staph. aureus using qualitative and quantitative methods. MRSA was isolated from 9.6% of pork, 5.6% of beef and 1.2% of chicken samples (P = 0.0002). Low levels of MRSA were typically present, with 37% below the detection threshold for quantification and <100 CFU g(-1) present in most quantifiable samples. All isolates were classified as Canadian epidemic MRSA-2 (CMRSA-2) by pulsed field gel electrophoresis (PFGE), with two different PFGE subtypes, and were spa type 24/t242. CONCLUSIONS: MRSA contamination of retail meat is not uncommon. While CMRSA-2, a human epidemic clone, has been found in pigs in Canada, the lack of isolation of livestock-associated ST398 was surprising. SIGNIFICANCE AND IMPACT OF THE STUDY: The relevance of MRSA contamination of meat is unclear but investigation is required because of the potential for exposure from food handling. Sources of contamination require investigation because these results suggest that human or animal sources could be involved.",
"title": "Detection and quantification of methicillin-resistant Staphylococcus aureus (MRSA) clones in retail meat products."
},
{
"docid": "MED-2969",
"text": "OBJECTIVE: We have previously shown that 300 kcal from glucose intake induces a significant increase in reactive oxygen species (ROS) generation and nuclear factor-kappaB (NF-kappaB) binding in the circulating mononuclear cells in healthy normal subjects. We hypothesized that the intake of 300 calories as orange juice or fructose, the other major carbohydrate in orange juice, would induce a significantly smaller response than that of glucose. RESEARCH DESIGN AND METHODS: Four groups (eight subjects each) of normal-weight subjects were given a 300-cal drink of glucose (75 g), fructose (75 g), or orange juice or water sweetened with saccharin (control group) to drink, and then blood samples were collected. RESULTS: There was a significant increase in ROS generation by mononuclear cells (by 130 +/- 18%, P < 0.001), polymorph nuclear cells (by 95 +/- 22%, P < 0.01), and in NF-kappaB binding in mononuclear cells by 82 +/- 16% (P < 0.01) over the baseline after 2 h of glucose intake. These changes were absent following fructose, orange juice, or water intake. There was significantly lower ROS generation and NF-kappaB binding following orange juice, fructose, and water compared with glucose (P < 0.001 for all). Furthermore, incubation of mononuclear cells in vitro with 50 mmol/l of the flavonoids hesperetin or naringenin reduced ROS generation by 52 +/- 7% and 77 +/- 8% (P < 0.01), respectively, while fructose or ascorbic acid did not cause any change. CONCLUSIONS: Caloric intake in the form of orange juice or fructose does not induce either oxidative or inflammatory stress, possibly due to its flavonoids content and might, therefore, represent a potentially safe energy source.",
"title": "Orange juice or fructose intake does not induce oxidative and inflammatory response."
},
{
"docid": "MED-4985",
"text": "Background: Low-fat vegetarian and vegan diets are associated with weight loss, increased insulin sensitivity, and improved cardiovascular health. Objective: We compared the effects of a low-fat vegan diet and conventional diabetes diet recommendations on glycemia, weight, and plasma lipids. Design: Free-living individuals with type 2 diabetes were randomly assigned to a low-fat vegan diet (n = 49) or a diet following 2003 American Diabetes Association guidelines (conventional, n = 50) for 74 wk. Glycated hemoglobin (Hb A1c) and plasma lipids were assessed at weeks 0, 11, 22, 35, 48, 61, and 74. Weight was measured at weeks 0, 22, and 74. Results: Weight loss was significant within each diet group but not significantly different between groups (−4.4 kg in the vegan group and −3.0 kg in the conventional diet group, P = 0.25) and related significantly to Hb A1c changes (r = 0.50, P = 0.001). Hb A1c changes from baseline to 74 wk or last available values were −0.34 and −0.14 for vegan and conventional diets, respectively (P = 0.43). Hb A1c changes from baseline to last available value or last value before any medication adjustment were −0.40 and 0.01 for vegan and conventional diets, respectively (P = 0.03). In analyses before alterations in lipid-lowering medications, total cholesterol decreased by 20.4 and 6.8 mg/dL in the vegan and conventional diet groups, respectively (P = 0.01); LDL cholesterol decreased by 13.5 and 3.4 mg/dL in the vegan and conventional groups, respectively (P = 0.03). Conclusions: Both diets were associated with sustained reductions in weight and plasma lipid concentrations. In an analysis controlling for medication changes, a low-fat vegan diet appeared to improve glycemia and plasma lipids more than did conventional diabetes diet recommendations. Whether the observed differences provide clinical benefit for the macro- or microvascular complications of diabetes remains to be established. This trial was registered at clinicaltrials.gov as NCT00276939.",
"title": "A low-fat vegan diet and a conventional diabetes diet in the treatment of type 2 diabetes: a randomized, controlled, 74-wk clinical trial"
},
{
"docid": "MED-2585",
"text": "Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. A striking anticancer effect of IP6 was demonstrated in different experimental models. Inositol is also a natural constituent possessing moderate anticancer activity. The most consistent and best anticancer results were obtained from the combination of IP6 plus inositol. In addition to reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered IP6 is rapidly taken into the cells and dephosphorylated to lower-phosphate inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties can also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans.",
"title": "Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic."
},
{
"docid": "MED-2337",
"text": "Urticaria, defined by the presence of wheals and/or angio-edema, is a common condition in children, prompting parents to consult physicians. For its successful management, paediatric-specific features must be taken into account, regarding the identification of eliciting triggers and pharmacological therapy. This review systematically discusses the current best-available evidence on spontaneous acute and chronic urticaria as well as physical and other urticaria types in children. Potential underlying causes, namely infections, food and drug hypersensitivity, autoreactivity and autoimmune or other conditions, and eliciting stimuli are considered, with practical recommendations for specific diagnostic approaches. Second-generation antihistamines are the mainstay of pharmacological treatment aimed at relief of symptoms, which require dose adjustment for pae-diatric use. Other therapeutic interventions are also discussed. In addition, unmet needs are highlighted, aiming to promote research into the paediatric population, ultimately aiming at the effective management of childhood urticaria.",
"title": "Management of childhood urticaria: current knowledge and practical recommendations."
},
{
"docid": "MED-2510",
"text": "Dietary restriction (DR) extends the lifespan of a wide range of species, although the universality of this effect has never been quantitatively examined. Here, we report the first comprehensive comparative meta-analysis of DR across studies and species. Overall, DR significantly increased lifespan, but this effect is modulated by several factors. In general, DR has less effect in extending lifespan in males and also in non-model organisms. Surprisingly, the proportion of protein intake was more important for life extension via DR than the degree of caloric restriction. Furthermore, we show that reduction in both age-dependent and age-independent mortality rates drives life extension by DR among the well-studied laboratory model species (yeast, nematode worms, fruit flies and rodents). Our results suggest that convergent adaptation to laboratory conditions better explains the observed DR-longevity relationship than evolutionary conservation although alternative explanations are possible. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.",
"title": "Comparative and meta-analytic insights into life extension via dietary restriction."
},
{
"docid": "MED-4515",
"text": "BACKGROUND: Low-carbohydrate, high-animal protein diets, which are advocated for weight loss, may not promote the desired reduction in low-density lipoprotein cholesterol (LDL-C) concentration. The effect of exchanging the animal proteins and fats for those of vegetable origin has not been tested. Our objective was to determine the effect on weight loss and LDL-C concentration of a low-carbohydrate diet high in vegetable proteins from gluten, soy, nuts, fruits, vegetables, cereals, and vegetable oils compared with a high-carbohydrate diet based on low-fat dairy and whole grain products. METHODS: A total of 47 overweight hyperlipidemic men and women consumed either (1) a low-carbohydrate (26% of total calories), high-vegetable protein (31% from gluten, soy, nuts, fruit, vegetables, and cereals), and vegetable oil (43%) plant-based diet or (2) a high-carbohydrate lacto-ovo vegetarian diet (58% carbohydrate, 16% protein, and 25% fat) for 4 weeks each in a parallel study design. The study food was provided at 60% of calorie requirements. RESULTS: Of the 47 subjects, 44 (94%) (test, n = 22 [92%]; control, n = 22 [96%]) completed the study. Weight loss was similar for both diets (approximately 4.0 kg). However, reductions in LDL-C concentration and total cholesterol-HDL-C and apolipoprotein B-apolipoprotein AI ratios were greater for the low-carbohydrate compared with the high-carbohydrate diet (-8.1% [P = .002], -8.7% [P = .004], and -9.6% [P = .001], respectively). Reductions in systolic and diastolic blood pressure were also seen (-1.9% [P = .052] and -2.4% [P = .02], respectively). CONCLUSION: A low-carbohydrate plant-based diet has lipid-lowering advantages over a high-carbohydrate, low-fat weight-loss diet in improving heart disease risk factors not seen with conventional low-fat diets with animal products.",
"title": "The effect of a plant-based low-carbohydrate (\"Eco-Atkins\") diet on body weight and blood lipid concentrations in hyperlipidemic subjects."
},
{
"docid": "MED-5242",
"text": "PURPOSE: Epidemiological studies in women have revealed an association between caffeine intake and urinary incontinence, although evidence among men is limited. Therefore, we evaluated the association between caffeine intake and urinary incontinence in United States men. MATERIALS AND METHODS: Data were used from male NHANES (National Health and Nutrition Examination Surveys) 2005-2006 and 2007-2008 participants. Urinary incontinence was defined using a standard questionnaire with Incontinence Severity Index scores 3 or greater categorized as moderate to severe. Structured dietary recall was used to determine caffeine consumption (mg per day), water intake (gm per day) and total dietary moisture (gm per day). Stepwise multivariable logistic regression models were used to assess the association between caffeine intake at or above the 75th and 90th percentiles and moderate to severe urinary incontinence, controlling for potential confounders, urinary incontinence risk factors and prostate conditions in men age 40 years or older. RESULTS: Of the 5,297 men 3,960 (75%) were 20 years old or older with complete data. Among these men the prevalence of any urinary incontinence was 12.9% and moderate to severe urinary incontinence was 4.4%. Mean caffeine intake was 169 mg per day. Caffeine intake at the upper 75th percentile (234 mg or more daily) and 90th percentile (392 mg or more per day) was significantly associated with having moderate to severe urinary incontinence (1.72, 95% 1.18-2.49 and 2.08, 95% 1.15-3.77, respectively). In addition, after adjusting for prostate conditions, the effect size for the association between caffeine intake and moderate to severe urinary incontinence remained. CONCLUSIONS: Caffeine consumption equivalent to approximately 2 cups of coffee daily (250 mg) is significantly associated with moderate to severe urinary incontinence in United States men. Our findings support the further study of caffeine modification in men with urinary incontinence. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.",
"title": "Caffeine intake and its association with urinary incontinence in United States men: results from National Health and Nutrition Examination Surveys ..."
},
{
"docid": "MED-2679",
"text": "Commercial aqueous wood-smoke flavouring induced significant increases in the 6-thioguanine resistance mutation frequency of TK6 human lymphoblasts at 0.1 microliter flavouring/ml of cell suspension. This corresponds to 6 micrograms/ml of dissolved 'solids' as determined by fully drying the aqueous flavouring in a vacuum desiccator. In AHH-1 human lymphoblasts, which contain a cytochrome P-450 monooxygenase system, mutations were induced at 0.3 microliter/ml, corresponding to 18 microliters/ml of dissolved 'solids'. The flavouring did not induce 8-azaguanine resistant mutations in Salmonella typhimurium at concentrations up to 1.5 microliter/ml. At higher concentrations the flavouring was toxic to bacteria. The flavouring did not induce lung adenomas or other tumours in newborn mice when injected ip with total doses of up to 26 microliters over a 3-wk period. Toxicity to the kidney, colon and rectum was observed in some mice at 15 wk of age.",
"title": "Commercial hickory-smoke flavouring is a human lymphoblast mutagen but does not induce lung adenomas in newborn mice."
},
{
"docid": "MED-3478",
"text": "Colon cancer is one of the serious health problems in most developed countries and its incidence rate is increasing in India. Hesperetin (HN) (3',5,7-trihydroxy-4'-methoxyflavonone) and hesperetin analogue (HA) were tested for their apoptosis inducing ability. Methyl thiazolyl tetrazolium assay revealed a dose as well as duration-dependent reduction of HT-29 (colon adenocarcinoma) cellular growth in response to HN and HA treatment. At 24 h 70 μM of HN and 32 μM of HA showed 50% reduction of HT-29 cellular growth. Acridine orange/ethidium bromide staining showed apoptotic features of cell death induced by HN and HA. Rhodamine 123 staining showed significant reduction in mitochondrial membrane potential induced by HN and HA. HN and HA induced DNA damage was confirmed by comet tail formation. Lipid peroxidation markers (TBARS) and protein oxidation marker (PCC) were significantly elevated in HN and HA treated groups. Enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were slightly decreased in their activities compared to control (untreated HT-29 cells). Results of Western blot analysis of apoptosis associated genes revealed an increase in cytochrome C, Bax, cleaved caspase-3 expression and a decrease in Bcl-2 expression. These findings indicate that HN and HA induce apoptosis on HT-29 via Bax dependent mitochondrial pathway involving oxidant/antioxidant imbalance. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Role of hesperetin (a natural flavonoid) and its analogue on apoptosis in HT-29 human colon adenocarcinoma cell line--a comparative study."
},
{
"docid": "MED-4625",
"text": "Arachidonic acid (ARA) is considered to be a minor contributor to the diet. Previous reports regarding the effect of ARA supplementation on the composition of long-chain polyunsaturated fatty acids (LCPUFA) in the blood of humans are extremely limited. In the present study, we conducted a crossover double-blind, placebo-control study. Twenty-three young Japanese women consumed one capsule containing triacylglycerol enriched with 80 mg ARA, equivalent to the amount in one egg, daily for 3 weeks. Blood samples were drawn before and after treatment periods, and the compositions of the LCPUFA in blood lipid fractions were measured. The supplementation of ARA increased the composition of ARA, but did not decrease the composition of n-3LCPUFA in erythrocyte phospholipids and plasma phospholipids, esterified cholesterol, and triacylglycerol. We found that dietary ARA increased the ARA level in all lipid fractions of the blood, even at a very low dose. (c) 2010 Elsevier Ltd. All rights reserved.",
"title": "Low-dose arachidonic acid intake increases erythrocytes and plasma arachidonic acid in young women."
},
{
"docid": "MED-4506",
"text": "PURPOSE: Dietary nitrate supplementation has been shown to reduce the O2 cost of submaximal exercise and to improve high-intensity exercise tolerance. However, it is presently unknown whether it may enhance performance during simulated competition. The present study investigated the effects of acute dietary nitrate supplementation on power output (PO), VO2, and performance during 4- and 16.1-km cycling time trials (TT). METHODS: After familiarization, nine club-level competitive male cyclists were assigned in a randomized, crossover design to consume 0.5 L of beetroot juice (BR; containing ∼ 6.2 mmol of nitrate) or 0.5 L of nitrate-depleted BR (placebo, PL; containing ∼ 0.0047 mmol of nitrate), ∼ 2.5 h before the completion of a 4- and a 16.1-km TT. RESULTS: BR supplementation elevated plasma [nitrite] (PL = 241 ± 125 vs BR = 575 ± 199 nM, P < 0.05). The VO2 values during the TT were not significantly different between the BR and PL conditions at any elapsed distance (P > 0.05), but BR significantly increased mean PO during the 4-km (PL = 279 ± 51 vs BR = 292 ± 44 W, P < 0.05) and 16.1-km TT (PL = 233 ± 43 vs BR = 247 ± 44 W, P < 0.01). Consequently, BR improved 4-km performance by 2.8% (PL = 6.45 ± 0.42 vs BR = 6.27 ± 0.35 min, P < 0.05) and 16.1-km performance by 2.7% (PL = 27.7 ± 2.1 vs BR = 26.9 ± 1.8 min, P < 0.01). CONCLUSIONS: These results suggest that acute dietary nitrate supplementation with 0.5 L of BR improves cycling economy, as demonstrated by a higher PO for the same VO2 and enhances both 4- and 16.1-km cycling TT performance.",
"title": "Acute dietary nitrate supplementation improves cycling time trial performance."
},
{
"docid": "MED-5171",
"text": "The objective of this study was to determine the prevalence of enterohemorrhagic Escherichia coli (EHEC), E. coli O157, Salmonella, and Listeria monocytogenes in retail food samples from Seattle, Wash. A total of 2,050 samples of ground beef (1,750 samples), mushrooms (100 samples), and sprouts (200 samples) were collected over a 12-month period and analyzed for the presence of these pathogens. PCR assays, followed by culture confirmation were used to determine the presence or absence of each organism. Of the 1,750 ground beef samples analyzed, 61 (3.5%) were positive for EHEC, and 20 (1.1%) of these were positive for E. coli O157. Salmonella was present in 67 (3.8%) of the 1,750 ground beef samples. Of 512 ground beef samples analyzed, 18 (3.5%) were positive for L. monocytogenes. EHEC was found in 12 (6.0%) of the 200 sprout samples, and 3 (1.5%) of these yielded E. coli O157. Of the 200 total sprout samples, 14 (7.0%) were positive for Salmonella and none were positive for L. monocytogenes. Among the 100 mushroom samples, 4 (4.0%) were positive for EHEC but none of these 4 samples were positive for E. coli O157. Salmonella was detected in 5 (5.0%) of the mushroom samples, and L. monocytogenes was found in 1 (1.0%) of the samples.",
"title": "Incidence of enterohemorrhagic Escherichia coli, Escherichia coli O157, Salmonella, and Listeria monocytogenes in retail fresh ground beef, sprouts..."
},
{
"docid": "MED-744",
"text": "This paper presents a new interpretation of a unique Bronze Age (c. 3000-1100 BCE) Aegean wall painting in the building of Xeste 3 at Akrotiri,Thera. Crocus carturightianus and its active principle, saffron, are the primary subjects at Xeste 3. Several lines of evidence suggest that the meaning of these frescoes concerns saffron and healing: (1) the unusual degree of visual attention given to the crocus, including the variety of methods for display of the stigmas; (2) the painted depiction of the line of saffron production from plucking blooms to the collection of stigmas; and (3) the sheer number (ninety) of medical indications for which saffron has been used from the Bronze Age to the present. The Xeste 3 frescoes appear to portray a divinity of healing associated with her phytotherapy, saffron. Cultural and commercial interconnections between the Therans, the Aegean world, and their neighboring civilizations in the early 2nd millennium BCE indicate a close network of thematic exchange, but there is no evidence that Akrotiri borrowed any of these medicinal (or iconographic) representations. The complex production line, the monumental illustration of a goddess of medicine with her saffron attribute, and this earliest botanically accurate image of an herbal medication are all Theran innovations.",
"title": "Therapy with saffron and the goddess at Thera."
},
{
"docid": "MED-5040",
"text": "BACKGROUND: Studies suggest cardioprotective benefits of dark chocolate containing cocoa. OBJECTIVE: This study examines the acute effects of solid dark chocolate and liquid cocoa intake on endothelial function and blood pressure in overweight adults. DESIGN: Randomized, placebo-controlled, single-blind crossover trial of 45 healthy adults [mean age: 53 y; mean body mass index (in kg/m(2)): 30]. In phase 1, subjects were randomly assigned to consume a solid dark chocolate bar (containing 22 g cocoa powder) or a cocoa-free placebo bar (containing 0 g cocoa powder). In phase 2, subjects were randomly assigned to consume sugar-free cocoa (containing 22 g cocoa powder), sugared cocoa (containing 22 g cocoa powder), or a placebo (containing 0 g cocoa powder). RESULTS: Solid dark chocolate and liquid cocoa ingestion improved endothelial function (measured as flow-mediated dilatation) compared with placebo (dark chocolate: 4.3 +/- 3.4% compared with -1.8 +/- 3.3%; P < 0.001; sugar-free and sugared cocoa: 5.7 +/- 2.6% and 2.0 +/- 1.8% compared with -1.5 +/- 2.8%; P < 0.001). Blood pressure decreased after the ingestion of dark chocolate and sugar-free cocoa compared with placebo (dark chocolate: systolic, -3.2 +/- 5.8 mm Hg compared with 2.7 +/- 6.6 mm Hg; P < 0.001; and diastolic, -1.4 +/- 3.9 mm Hg compared with 2.7 +/- 6.4 mm Hg; P = 0.01; sugar-free cocoa: systolic, -2.1 +/- 7.0 mm Hg compared with 3.2 +/- 5.6 mm Hg; P < 0.001; and diastolic: -1.2 +/- 8.7 mm Hg compared with 2.8 +/- 5.6 mm Hg; P = 0.014). Endothelial function improved significantly more with sugar-free than with regular cocoa (5.7 +/- 2.6% compared with 2.0 +/- 1.8%; P < 0.001). CONCLUSIONS: The acute ingestion of both solid dark chocolate and liquid cocoa improved endothelial function and lowered blood pressure in overweight adults. Sugar content may attenuate these effects, and sugar-free preparations may augment them.",
"title": "Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial."
},
{
"docid": "MED-4826",
"text": "A role of diet and nutrition in pancreatic carcinogenesis has been suggested, but the association between selected macronutrients, fatty acids, cholesterol and pancreatic cancer remains controversial. We analysed data from a hospital-based case-control study conducted in Italy between 1991 and 2008, including 326 cases (174 men and 152 women) with incident pancreatic cancer, and 652 controls (348 men and 304 women) frequency-matched to cases by sex, age and study centre. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple logistic regression models conditioned on age, sex and study centre, and adjusted for year of interview, education, tobacco smoking, history of diabetes and energy intake. A positive association was found for animal proteins (OR=1.85 for the highest versus the lowest quintile of intake; 95% CI: 1.15-2.96; p for trend=0.039), whereas a negative association was observed for sugars (OR=0.52; 95% CI: 0.31-0.86; p for trend=0.003). Non-significant negative associations emerged for vegetable proteins (OR=0.69) and polyunsaturated fatty acids (OR=0.67). In conclusion, a diet poor in animal proteins and rich in sugars (mainly derived from fruit) appears to have a beneficial effect on pancreatic cancer risk. Copyright (c) 2009 Elsevier Ltd. All rights reserved.",
"title": "Macronutrients, fatty acids, cholesterol and pancreatic cancer."
},
{
"docid": "MED-3753",
"text": "BACKGROUND: No regulations govern placebo composition. The composition of placebos can influence trial outcomes and merits reporting. PURPOSE: To assess how often investigators specify the composition of placebos in randomized, placebo-controlled trials. DATA SOURCES: 4 English-language general and internal medicine journals with high impact factors. STUDY SELECTION: 3 reviewers screened titles and abstracts of the journals to identify randomized, placebo-controlled trials published from January 2008 to December 2009. DATA EXTRACTION: Reviewers independently abstracted data from the introduction and methods sections of identified articles, recording treatment type (pill, injection, or other) and whether placebo composition was stated. Discrepancies were resolved by consensus. DATA SYNTHESIS: Most studies did not disclose the composition of the study placebo. Disclosure was less common for pills than for injections and other treatments (8.2% vs. 26.7%; P = 0.002). LIMITATION: Journals with high impact factors may not be representative. CONCLUSION: Placebos were seldom described in randomized, controlled trials of pills or capsules. Because the nature of the placebo can influence trial outcomes, placebo formulation should be disclosed in reports of placebo-controlled trials.",
"title": "What's in placebos: who knows? Analysis of randomized, controlled trials."
},
{
"docid": "MED-2159",
"text": "AIMS: Coffee consumption has been recently linked with decreased blood gamma-glutamyltransferase (GGT) activities and protection from alcoholic liver disease. To explore the relationship and dose response, we assessed the impacts of coffee and alcohol intake on serum GGT activity in apparently healthy men and women with varying levels of coffee and alcohol consumption. METHODS: Data on coffee, alcohol consumption and serum GGT activities were collected from 18,899 individuals (8807 men and 10,092 women), mean age 48 years, range 25-74 years, who participated in a large national cross-sectional health survey. Body mass index, smoking index and age were used as covariates in all analyses. RESULTS: Among the study population, 89.8% reported varying levels of coffee consumption; 6.9% were abstainers from alcohol, 86.1% moderate drinkers, 3.7% heavy drinkers and 3.3% former drinkers. In men, the elevation of GGT induced by heavy drinking (>280 g/week) was found to be significantly reduced by coffee consumption exceeding 4 cups per day. A similar trend was also observed among women, which however, did not reach statistical significance. CONCLUSION: Coffee modulates the effect of ethanol on serum GGT activities in a dose- and gender-dependent manner. These observations should be implicated in studies on the possible hepatoprotective effects of coffee in alcohol consumers.",
"title": "Dose- and gender-dependent interactions between coffee consumption and serum GGT activity in alcohol consumers."
}
] |
287
|
Converting apoE4 to apoE3 by gene editing worsens the pathology associated with apoE4 in human iPSCderived neurons.
|
[
{
"docid": "4709641",
"text": "Efforts to develop drugs for Alzheimer's disease (AD) have shown promise in animal studies, only to fail in human trials, suggesting a pressing need to study AD in human model systems. Using human neurons derived from induced pluripotent stem cells that expressed apolipoprotein E4 (ApoE4), a variant of the APOE gene product and the major genetic risk factor for AD, we demonstrated that ApoE4-expressing neurons had higher levels of tau phosphorylation, unrelated to their increased production of amyloid-β (Aβ) peptides, and that they displayed GABAergic neuron degeneration. ApoE4 increased Aβ production in human, but not in mouse, neurons. Converting ApoE4 to ApoE3 by gene editing rescued these phenotypes, indicating the specific effects of ApoE4. Neurons that lacked APOE behaved similarly to those expressing ApoE3, and the introduction of ApoE4 expression recapitulated the pathological phenotypes, suggesting a gain of toxic effects from ApoE4. Treatment of ApoE4-expressing neurons with a small-molecule structure corrector ameliorated the detrimental effects, thus showing that correcting the pathogenic conformation of ApoE4 is a viable therapeutic approach for ApoE4-related AD.",
"title": "Gain of toxic Apolipoprotein E4 effects in Human iPSC-Derived Neurons Is Ameliorated by a Small-Molecule Structure Corrector"
}
] |
[
{
"docid": "15347087",
"text": "The amyloid cascade hypothesis posits that deposition of the amyloid β (Aβ) peptide in the brain is a key event in the initiation of Alzheimer's disease (AD). Nonetheless, it now seems increasingly unlikely that amyloid toxicity is the cause of sporadic AD, which leads to cognitive decline. Here, using accelerated-senescence nontransgenic OXYS rats, we confirmed that aggregation of Aβ is a later event in AD-like pathology. We showed that an age-dependent increase in the levels of Aβ₁₋₄₂ and extracellular Aβ deposits in the brain of OXYS rats occur later than do synaptic losses, neuronal cell death, mitochondrial structural abnormalities, and hyperphosphorylation of the tau protein. We identified the variants of the genes that are strongly associated with the risk of either late-onset or early-onset AD, including App, Apoe4, Bace1, Psen1, Psen2, and Picalm. We found that in OXYS rats nonsynonymous SNPs were located only in the genes Casp3 and Sorl1. Thus, we present proof that OXYS rats may be a model of sporadic AD. It is possible that multiple age-associated pathological processes may precede the toxic amyloid accumulation, which in turn triggers the final stage of the sporadic form of AD and becomes a hallmark event of the disease.",
"title": "Amyloid accumulation is a late event in sporadic Alzheimer's disease-like pathology in nontransgenic rats"
},
{
"docid": "13717103",
"text": "INTRODUCTION Mutations in the FUS gene have been shown to be a rare cause of amyotrophic lateral sclerosis (ALS-FUS) and whilst well documented clinically and genetically there have been relatively few neuropathological studies. Recent work suggested a possible correlation between pathological features such as frequency of basophilic inclusions in neurons and rate of clinical decline, other studies have revealed a discrepancy between the upper motor neuron features detected clinically and the associated pathology. The purpose of this study was to describe the pathological features associated with more recently discovered FUS mutations and reinvestigate those with well recognised mutations in an attempt to correlate the pathology with mutation and/or clinical phenotype. The brains and spinal cords of seven cases of ALS-FUS were examined neuropathologically, including cases with the newly described p. K510E mutation and a case with both a known p. P525L mutation in the FUS gene and a truncating p. Y374X mutation in the TARDBP gene. RESULTS The neuropathology in all cases revealed basophilic and FUS inclusions in the cord. The density and type of inclusions varied markedly between cases, but did not allow a clear correlation with clinical progression. Only one case showed significant motor cortical pathology despite the upper motor neuron clinical features being evident in 4 patients. The case with both a FUS and TARDBP mutation revealed FUS positive inclusions but no TDP-43 pathology. Instead there were unusual p62 positive, FUS negative neuronal and glial inclusions as well as dot-like neurites. CONCLUSIONS The study confirms cases of ALS-FUS to be mainly a lower motor neuron disease and to have pathology that does not appear to neatly correlate with clinical features or genetics. Furthermore, the case with both a FUS and TARDBP mutation reveals an intriguing pathological profile which at least in part involves a very unusual staining pattern for the ubiquitin-binding protein p62.",
"title": "ALS-FUS pathology revisited: singleton FUS mutations and an unusual case with both a FUS and TARDBP mutation"
},
{
"docid": "5953485",
"text": "Adenosine deaminases acting on RNA (ADARs) are involved in RNA editing that converts adenosine residues to inosine specifically in double-stranded RNAs. In this study, we investigated the interaction of the RNA editing mechanism with the RNA interference (RNAi) machinery and found that ADAR1 forms a complex with Dicer through direct protein-protein interaction. Most importantly, ADAR1 increases the maximum rate (Vmax) of pre-microRNA (miRNA) cleavage by Dicer and facilitates loading of miRNA onto RNA-induced silencing complexes, identifying a new role of ADAR1 in miRNA processing and RNAi mechanisms. ADAR1 differentiates its functions in RNA editing and RNAi by the formation of either ADAR1/ADAR1 homodimer or Dicer/ADAR1 heterodimer complexes, respectively. As expected, the expression of miRNAs is globally inhibited in ADAR1(-/-) mouse embryos, which, in turn, alters the expression of their target genes and might contribute to their embryonic lethal phenotype.",
"title": "ADAR1 Forms a Complex with Dicer to Promote MicroRNA Processing and RNA-Induced Gene Silencing"
},
{
"docid": "4405194",
"text": "Somatic cell nuclear transfer, cell fusion, or expression of lineage-specific factors have been shown to induce cell-fate changes in diverse somatic cell types. We recently observed that forced expression of a combination of three transcription factors, Brn2 (also known as Pou3f2), Ascl1 and Myt1l, can efficiently convert mouse fibroblasts into functional induced neuronal (iN) cells. Here we show that the same three factors can generate functional neurons from human pluripotent stem cells as early as 6 days after transgene activation. When combined with the basic helix-loop-helix transcription factor NeuroD1, these factors could also convert fetal and postnatal human fibroblasts into iN cells showing typical neuronal morphologies and expressing multiple neuronal markers, even after downregulation of the exogenous transcription factors. Importantly, the vast majority of human iN cells were able to generate action potentials and many matured to receive synaptic contacts when co-cultured with primary mouse cortical neurons. Our data demonstrate that non-neural human somatic cells, as well as pluripotent stem cells, can be converted directly into neurons by lineage-determining transcription factors. These methods may facilitate robust generation of patient-specific human neurons for in vitro disease modelling or future applications in regenerative medicine.",
"title": "Induction of human neuronal cells by defined transcription factors"
},
{
"docid": "4303075",
"text": "Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly induce other defined somatic cell fates, and not only an undifferentiated state. We hypothesized that combinatorial expression of neural-lineage-specific transcription factors could directly convert fibroblasts into neurons. Starting from a pool of nineteen candidate genes, we identified a combination of only three factors, Ascl1, Brn2 (also called Pou3f2) and Myt1l, that suffice to rapidly and efficiently convert mouse embryonic and postnatal fibroblasts into functional neurons in vitro. These induced neuronal (iN) cells express multiple neuron-specific proteins, generate action potentials and form functional synapses. Generation of iN cells from non-neural lineages could have important implications for studies of neural development, neurological disease modelling and regenerative medicine.",
"title": "Direct conversion of fibroblasts to functional neurons by defined factors"
},
{
"docid": "461550",
"text": "Functional elucidation of causal genetic variants and elements requires precise genome editing technologies. The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate RNA-guided site-specific DNA cleavage. We engineered two different type II CRISPR/Cas systems and demonstrate that Cas9 nucleases can be directed by short RNAs to induce precise cleavage at endogenous genomic loci in human and mouse cells. Cas9 can also be converted into a nicking enzyme to facilitate homology-directed repair with minimal mutagenic activity. Lastly, multiple guide sequences can be encoded into a single CRISPR array to enable simultaneous editing of several sites within the mammalian genome, demonstrating easy programmability and wide applicability of the RNA-guided nuclease technology.",
"title": "Multiplex genome engineering using CRISPR/Cas systems."
},
{
"docid": "4679264",
"text": "The role of DNA cytosine methylation, an epigenetic regulator of chromatin structure and function, during normal and pathological brain development and aging remains unclear. Here, we examined by MethyLight PCR the DNA methylation status at 50 loci, encompassing primarily 5′ CpG islands of genes related to CNS growth and development, in temporal neocortex of 125 subjects ranging in age from 17 weeks of gestation to 104 years old. Two psychiatric disease cohorts—defined by chronic neurodegeneration (Alzheimer's) or lack thereof (schizophrenia)—were included. A robust and progressive rise in DNA methylation levels across the lifespan was observed for 8/50 loci (GABRA2, GAD1, HOXA1, NEUROD1, NEUROD2, PGR, STK11, SYK) typically in conjunction with declining levels of the corresponding mRNAs. Another 16 loci were defined by a sharp rise in DNA methylation levels within the first few months or years after birth. Disease-associated changes were limited to 2/50 loci in the Alzheimer's cohort, which appeared to reflect an acceleration of the age-related change in normal brain. Additionally, methylation studies on sorted nuclei provided evidence for bidirectional methylation events in cortical neurons during the transition from childhood to advanced age, as reflected by significant increases at 3, and a decrease at 1 of 10 loci. Furthermore, the DNMT3a de novo DNA methyl-transferase was expressed across all ages, including a subset of neurons residing in layers III and V of the mature cortex. Therefore, DNA methylation is dynamically regulated in the human cerebral cortex throughout the lifespan, involves differentiated neurons, and affects a substantial portion of genes predominantly by an age-related increase.",
"title": "DNA Methylation in the Human Cerebral Cortex Is Dynamically Regulated throughout the Life Span and Involves Differentiated Neurons"
},
{
"docid": "4459491",
"text": "Alzheimer’s disease is the most common form of dementia, characterized by two pathological hallmarks: amyloid-β plaques and neurofibrillary tangles. The amyloid hypothesis of Alzheimer’s disease posits that the excessive accumulation of amyloid-β peptide leads to neurofibrillary tangles composed of aggregated hyperphosphorylated tau. However, to date, no single disease model has serially linked these two pathological events using human neuronal cells. Mouse models with familial Alzheimer’s disease (FAD) mutations exhibit amyloid-β-induced synaptic and memory deficits but they do not fully recapitulate other key pathological events of Alzheimer’s disease, including distinct neurofibrillary tangle pathology. Human neurons derived from Alzheimer’s disease patients have shown elevated levels of toxic amyloid-β species and phosphorylated tau but did not demonstrate amyloid-β plaques or neurofibrillary tangles. Here we report that FAD mutations in β-amyloid precursor protein and presenilin 1 are able to induce robust extracellular deposition of amyloid-β, including amyloid-β plaques, in a human neural stem-cell-derived three-dimensional (3D) culture system. More importantly, the 3D-differentiated neuronal cells expressing FAD mutations exhibited high levels of detergent-resistant, silver-positive aggregates of phosphorylated tau in the soma and neurites, as well as filamentous tau, as detected by immunoelectron microscopy. Inhibition of amyloid-β generation with β- or γ-secretase inhibitors not only decreased amyloid-β pathology, but also attenuated tauopathy. We also found that glycogen synthase kinase 3 (GSK3) regulated amyloid-β-mediated tau phosphorylation. We have successfully recapitulated amyloid-β and tau pathology in a single 3D human neural cell culture system. Our unique strategy for recapitulating Alzheimer’s disease pathology in a 3D neural cell culture model should also serve to facilitate the development of more precise human neural cell models of other neurodegenerative disorders.",
"title": "A three-dimensional human neural cell culture model of Alzheimer’s disease"
},
{
"docid": "6397191",
"text": "Endothelin-1 (ET-1) is the predominant endothelin isopeptide generated by the vascular wall and therefore appears to be the most important peptide involved in regulation of cardiovascular events. Many pathologic conditions are associated with elevations of ET-1 in the blood vessel wall. Because these conditions are often cytokine driven, we examined the effects of a mixture of cytokines on ET-1 production in human vascular smooth muscle cells (VSMCs) derived from internal mammary artery and saphenous vein (SV). Incubation of IMA and SV VSMCs with tumor necrosis factor-alpha (10 ng/ml) and interferon-gamma (1000 U/ml) in combination for up to 48 h markedly elevated the expression of mRNA for prepro-ET-1 and the release of ET-1 into the culture medium. This cytokine-stimulated release of ET-1 was inhibited by a series of dual endothelin-converting enzyme (ECE)/neutral endopeptidase inhibitors, phosphoramidon, CGS 26303, and CGS 26393, with an accompanying increase in big ET-1 release but with no effect on expression of mRNA for prepro-ET-1. These same compounds were 10 times more potent at inhibiting the conversion of exogenously applied big ET-1 to ET-1. ECE-1b/c mRNA is present in SV VSMCs, however no ECE-1a is present in these cells. Thus VSMCs most probably contain, like endothelial cells, an intracellular ECE responsible for the endogenous synthesis of ET-1. Under the influence of pro-inflammatory mediators the vascular smooth muscle can therefore become an important site of ET-1 production, as has already been established for the dilator mediators nitric oxide, prostaglandin I2, and prostaglandin E2.",
"title": "Endothelin-1 is induced by cytokines in human vascular smooth muscle cells: evidence for intracellular endothelin-converting enzyme."
},
{
"docid": "4347374",
"text": "Viral replication usually requires that innate intracellular lines of defence be overcome, a task usually accomplished by specialized viral gene products. The virion infectivity factor (Vif) protein of human immunodeficiency virus (HIV) is required during the late stages of viral production to counter the antiviral activity of APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G; also known as CEM15), a protein expressed notably in human T lymphocytes. When produced in the presence of APOBEC3G, vif-defective virus is non-infectious. APOBEC3G is closely related to APOBEC1, the central component of an RNA-editing complex that deaminates a cytosine residue in apoB messenger RNA. APOBEC family members also have potent DNA mutator activity through dC deamination; however, whether the editing potential of APOBEC3G has any relevance to HIV inhibition is unknown. Here, we demonstrate that it does, as APOBEC3G exerts its antiviral effect during reverse transcription to trigger G-to-A hypermutation in the nascent retroviral DNA. We also find that APOBEC3G can act on a broad range of retroviruses in addition to HIV, suggesting that hypermutation by editing is a general innate defence mechanism against this important group of pathogens.",
"title": "Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts"
},
{
"docid": "9217800",
"text": "The fatal adult motor neuron disease amyotrophic lateral sclerosis (ALS) shares some clinical and pathological overlap with frontotemporal dementia (FTD), an early-onset neurodegenerative disorder. The RNA/DNA-binding proteins fused in sarcoma (FUS; also known as TLS) and TAR DNA binding protein-43 (TDP-43) have recently been shown to be genetically and pathologically associated with familial forms of ALS and FTD. It is currently unknown whether perturbation of these proteins results in disease through mechanisms that are independent of normal protein function or via the pathophysiological disruption of molecular processes in which they are both critical. Here, we report that Drosophila mutants in which the homolog of FUS is disrupted exhibit decreased adult viability, diminished locomotor speed, and reduced life span compared with controls. These phenotypes were fully rescued by wild-type human FUS, but not ALS-associated mutant FUS proteins. A mutant of the Drosophila homolog of TDP-43 had similar, but more severe, deficits. Through cross-rescue analysis, we demonstrated that FUS acted together with and downstream of TDP-43 in a common genetic pathway in neurons. Furthermore, we found that these proteins associated with each other in an RNA-dependent complex. Our results establish that FUS and TDP-43 function together in vivo and suggest that molecular pathways requiring the combined activities of both of these proteins may be disrupted in ALS and FTD.",
"title": "The ALS-associated proteins FUS and TDP-43 function together to affect Drosophila locomotion and life span."
},
{
"docid": "47018050",
"text": "Here, we report that genome editing by CRISPR–Cas9 induces a p53-mediated DNA damage response and cell cycle arrest in immortalized human retinal pigment epithelial cells, leading to a selection against cells with a functional p53 pathway. Inhibition of p53 prevents the damage response and increases the rate of homologous recombination from a donor template. These results suggest that p53 inhibition may improve the efficiency of genome editing of untransformed cells and that p53 function should be monitored when developing cell-based therapies utilizing CRISPR–Cas9. CRISPR–Cas9-induced DNA damage triggers p53 to limit the efficiency of gene editing in immortalized human retinal pigment epithelial cells.",
"title": "CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response"
},
{
"docid": "7029990",
"text": "One type of RNA editing involves the conversion of adenosine residues into inosine in double-stranded RNA through the action of adenosine deaminases acting on RNA (ADAR). A-to-I RNA editing of the coding sequence could result in synthesis of proteins not directly encoded in the genome. ADAR edits also non-coding sequences of target RNAs, such as introns and 3'-untranslated regions, which may affect splicing, translation, and mRNA stability. Three mammalian ADAR gene family members (ADAR1-3) have been identified. Here we investigated phenotypes of mice homozygous for ADAR1 null mutation. Although live ADAR1-/- embryos with normal gross appearance could be recovered up to E11.5, widespread apoptosis was detected in many tissues. Fibroblasts derived from ADAR1-/- embryos were also prone to apoptosis induced by serum deprivation. Our results demonstrate an essential requirement for ADAR1 in embryogenesis and suggest that it functions to promote survival of numerous tissues by editing one or more double-stranded RNAs required for protection against stress-induced apoptosis.",
"title": "Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene."
},
{
"docid": "4462919",
"text": "The RNA-guided endonuclease Cas9 has emerged as a versatile genome-editing platform. However, the size of the commonly used Cas9 from Streptococcus pyogenes (SpCas9) limits its utility for basic research and therapeutic applications that use the highly versatile adeno-associated virus (AAV) delivery vehicle. Here, we characterize six smaller Cas9 orthologues and show that Cas9 from Staphylococcus aureus (SaCas9) can edit the genome with efficiencies similar to those of SpCas9, while being more than 1 kilobase shorter. We packaged SaCas9 and its single guide RNA expression cassette into a single AAV vector and targeted the cholesterol regulatory gene Pcsk9 in the mouse liver. Within one week of injection, we observed >40% gene modification, accompanied by significant reductions in serum Pcsk9 and total cholesterol levels. We further assess the genome-wide targeting specificity of SaCas9 and SpCas9 using BLESS, and demonstrate that SaCas9-mediated in vivo genome editing has the potential to be efficient and specific.",
"title": "In vivo genome editing using Staphylococcus aureus Cas9"
},
{
"docid": "29107180",
"text": "The structure of the human gene encoding the double-stranded RNA (dsRNA) adenosine deaminase (DRADA) was characterized. This nuclear localized enzyme is involved in the RNA editing required for the expression of certain subtypes of glutamate-gated ion channel subunits. The DRADA gene span 30 kb pairs and harbors 15 exons. The transcription of the DRADA gene driven by the putative promoter region, which contains no typical TATA or CCAAT box-like sequences, is initiated at multiple sites, 164 to 216 nucleotides upstream of the translation initiation codon. The three dsRNA binding motifs (DRBM), 70 amino acid residues long, are each encoded by two exons plus an intervening sequence that interrupts the motif at the identical amino acid position. This finding is consistent with the notion that the dsRNA binding domains may be composed of two separate functional subdomains. Fluorescent in situ hybridization localized the DRADA gene on the long arm chromosome 1, region q21. The gene structure and sequence information reported in this study will facilitate the investigation of involvement of DRADA in hereditary diseases that may be the result of malfunction of glutamate-gated ion channels.",
"title": "Genomic organization and chromosomal location of the human dsRNA adenosine deaminase gene: the enzyme for glutamate-activated ion channel RNA editing."
},
{
"docid": "13969173",
"text": "Amyotrophic lateral sclerosis (ALS) causes motor neuron degeneration, paralysis, and death. Accurate disease modeling, identifying disease mechanisms, and developing therapeutics is urgently needed. We previously reported motor neuron toxicity through postmortem ALS spinal cord-derived astrocytes. However, these cells can only be harvested after death, and their expansion is limited. We now report a rapid, highly reproducible method to convert adult human fibroblasts from living ALS patients to induced neuronal progenitor cells and subsequent differentiation into astrocytes (i-astrocytes). Non-cell autonomous toxicity to motor neurons is found following coculture of i-astrocytes from familial ALS patients with mutation in superoxide dismutase or hexanucleotide expansion in C9orf72 (ORF 72 on chromosome 9) the two most frequent causes of ALS. Remarkably, i-astrocytes from sporadic ALS patients are as toxic as those with causative mutations, suggesting a common mechanism. Easy production and expansion of i-astrocytes now enables rapid disease modeling and high-throughput drug screening to alleviate astrocyte-derived toxicity.",
"title": "Direct conversion of patient fibroblasts demonstrates non-cell autonomous toxicity of astrocytes to motor neurons in familial and sporadic ALS."
},
{
"docid": "8790729",
"text": "BACKGROUND There is a widespread interest in developing renewable sources of islet-replacement tissue for type I diabetes mellitus. Human mesenchymal cells isolated from the Wharton's jelly of the umbilical cord (HUMSCs), which can be easily obtained and processed compared with embryonic and bone marrow stem cells, possess stem cell properties. HUMSCs may be a valuable source for the generation of islets. METHODOLOGY AND PRINCIPAL FINDINGS HUMSCs were induced to transform into islet-like cell clusters in vitro through stepwise culturing in neuron-conditioned medium. To assess the functional stability of the islet-like cell clusters in vivo, these cell clusters were transplanted into the liver of streptozotocin-induced diabetic rats via laparotomy. Glucose tolerance was measured on week 12 after transplantation accompanied with immunohistochemistry and electron microscopy analysis. These islet-like cell clusters were shown to contain human C-peptide and release human insulin in response to physiological glucose levels. Real-time RT-PCR detected the expressions of insulin and other pancreatic beta-cell-related genes (Pdx1, Hlxb9, Nkx2.2, Nkx6.1, and Glut-2) in these islet-like cell clusters. The hyperglycemia and glucose intolerance in streptozotocin-induced diabetic rats was significantly alleviated after xenotransplantation of islet-like cell clusters, without the use of immunosuppressants. In addition to the existence of islet-like cell clusters in the liver, some special fused liver cells were also found, which characterized by human insulin and nuclei-positive staining and possessing secretory granules. CONCLUSIONS AND SIGNIFICANCE In this study, we successfully differentiate HUMSCs into mature islet-like cell clusters, and these islet-like cell clusters possess insulin-producing ability in vitro and in vivo. HUMSCs in Wharton's Jelly of the umbilical cord seem to be the preferential source of stem cells to convert into insulin-producing cells, because of the large potential donor pool, its rapid availability, no risk of discomfort for the donor, and low risk of rejection.",
"title": "Islet-Like Clusters Derived from Mesenchymal Stem Cells in Wharton's Jelly of the Human Umbilical Cord for Transplantation to Control Type 1 Diabetes"
},
{
"docid": "39545358",
"text": "Neuregulin 1 (NRG1) and its receptor ErbB4 are both susceptibility genes of schizophrenia. However, little is known about the underlying mechanisms of their malfunction. Although ErbB4 is enriched in GABAergic interneurons, the role of NRG1 in excitatory synapse formation in these neurons remains poorly understood. We showed that NRG1 increased both the number and size of PSD-95 puncta and the frequency and amplitude of miniature EPSCs (mEPSCs) in GABAergic interneurons, indicating that NRG1 stimulates the formation of new synapses and strengthens existing synapses. In contrast, NRG1 treatment had no effect on either the number or size of excitatory synapses in glutamatergic neurons, suggesting its synaptogenic effect is specific to GABAergic interneurons. Ecto-ErbB4 treatment diminished both the number and size of excitatory synapses, suggesting that endogenous NRG1 may be critical for basal synapse formation. NRG1 could stimulate the stability of PSD-95 in the manner that requires tyrosine kinase activity of ErbB4. Finally, deletion of ErbB4 in parvalbumin-positive interneurons led to reduced frequency and amplitude of mEPSCs, providing in vivo evidence that ErbB4 is important in excitatory synaptogenesis in interneurons. Together, our findings suggested a novel synaptogenic role of NRG1 in excitatory synapse development, possibly via stabilizing PSD-95, and this effect is specific to GABAergic interneurons. In light of the association of the genes of both NRG1 and ErbB4 with schizophrenia and dysfunction of GABAergic system in this disorder, these results provide insight into its potential pathological mechanism.",
"title": "Neuregulin 1 promotes excitatory synapse development and function in GABAergic interneurons."
},
{
"docid": "40666943",
"text": "PURPOSE To perform a systematic review on the epidemiology, the health-related quality of life (HRQoL) and economic burden of binge eating disorder (BED). METHODS A systematic literature search of English-language articles was conducted using Medline, Embase, PsycINFO, PsycARTICLES, Academic Search Complete, CINAHL Plus, Business Source Premier and Cochrane Library. Literature search on epidemiology was limited to studies published between 2009 and 2013. Cost data were inflated and converted to 2012 US$ purchasing power parities. All of the included studies were assessed for quality. RESULTS Forty-nine articles were included. Data on epidemiology were reported in 31, HRQoL burden in 16, and economic burden in 7 studies. Diagnosis of BED was made using 4th Edition of The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria in 46 studies. Lifetime prevalence of BED was 1.1-1.9% in the general population (DSM-IV). BED was associated with significant impairment in aspects of HRQoL relating to both physical and mental health; the Short Form 36 Physical and Mental Component Summary mean scores varied between 31.1 to 47.3 and 32.0 to 49.8, respectively. Compared to individuals without eating disorder, BED was related to increased healthcare utilization and costs. Annual direct healthcare costs per BED patient ranged between $2,372 and $3,731. CONCLUSIONS BED is a serious eating disorder that impairs HRQoL and is related to increased healthcare utilization and healthcare costs. The limited literature warrants further research, especially to better understand the long-term HRQoL and economic burden of BED.",
"title": "Epidemiology, health-related quality of life and economic burden of binge eating disorder: a systematic literature review"
},
{
"docid": "24652030",
"text": "Age-related degeneration of basal forebrain cholinergic neurons (BFCNs) occurs early and contributes significantly to cognitive decline in Alzheimer’s disease (AD). Proper function and morphology of BFCNs depends on the supply of nerve growth factor (NGF) from the cortex and the hippocampus. A large number of experiments have shown that decreased supply of NGF at the level of BFCN cell bodies leads to loss of neuronal markers and shrinkage, mimicking what is observed in AD. The delivery of sufficient amounts of NGF signal to BFCN cell bodies depends on the effective participation of several factors including sufficient synthesis and release of NGF, adequate synthesis and expression of NGF receptors by BFCNs, normal signaling and retrograde transport of NGF-receptor complex, and finally effective induction of gene expression by NGF. In the past few years it has become clear that decreased amounts of NGF at the level of BFCN cell bodies is largely due to failed retrograde transport rather than decreased synthesis, binding or expression of NGF receptors in the BFCN terminals. We will discuss in vivo evidence supporting decreased retrograde transport of NGF in a mouse model with BFCN degeneration, and will attempt to match these findings with our studies in postmortem human AD brain. We will speculate about the possible mechanisms of failed NGF retrograde transport and its relationship to AD pathology.",
"title": "Alzheimer’s disease and NGF signaling"
},
{
"docid": "36474",
"text": "Realizing the full potential of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) requires efficient methods for genetic modification. However, techniques to generate cell type–specific lineage reporters, as well as reliable tools to disrupt, repair or overexpress genes by gene targeting, are inefficient at best and thus are not routinely used. Here we report the highly efficient targeting of three genes in human pluripotent cells using zinc-finger nuclease (ZFN)–mediated genome editing. First, using ZFNs specific for the OCT4 (POU5F1) locus, we generated OCT4-eGFP reporter cells to monitor the pluripotent state of hESCs. Second, we inserted a transgene into the AAVS1 locus to generate a robust drug-inducible overexpression system in hESCs. Finally, we targeted the PITX3 gene, demonstrating that ZFNs can be used to generate reporter cells by targeting non-expressed genes in hESCs and hiPSCs.",
"title": "Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases"
},
{
"docid": "432261",
"text": "The generation of gene-edited animals using the CRISPRs/Cas9 system is based on microinjection into zygotes which is inefficient, time consuming and demands high technical skills. We report the optimization of an electroporation method for intact rat zygotes using sgRNAs and Cas9 protein in combination or not with ssODNs (~100 nt). This resulted in high frequency of knockouts, between 15 and 50% of analyzed animals. Importantly, using ssODNs as donor template resulted in precise knock-in mutations in 25-100% of analyzed animals, comparable to microinjection. Electroporation of long ssDNA or dsDNA donors successfully used in microinjection in the past did not allow generation of genome-edited animals despite dsDNA visualization within zygotes. Thus, simultaneous electroporation of a large number of intact rat zygotes is a rapid, simple, and efficient method for the generation of a variety of genome-edited rats.",
"title": "Generation of gene-edited rats by delivery of CRISPR/Cas9 protein and donor DNA into intact zygotes using electroporation"
},
{
"docid": "2015929",
"text": "Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease, with astrocytes implicated as contributing substantially to motor neuron death in familial (F)ALS. However, the proposed role of astrocytes in the pathology of ALS derives in part from rodent models of FALS based upon dominant mutations within the superoxide dismutase 1 (SOD1) gene, which account for <2% of all ALS cases. Their role in sporadic (S)ALS, which affects >90% of ALS patients, remains to be established. Using astrocytes generated from postmortem tissue from both FALS and SALS patients, we show that astrocytes derived from both patient groups are similarly toxic to motor neurons. We also demonstrate that SOD1 is a viable target for SALS, as its knockdown significantly attenuates astrocyte-mediated toxicity toward motor neurons. Our data highlight astrocytes as a non-cell autonomous component in SALS and provide an in vitro model system to investigate common disease mechanisms and evaluate potential therapies for SALS and FALS.",
"title": "Astrocytes from Familial and Sporadic ALS Patients are Toxic to Motor Neurons"
},
{
"docid": "27602752",
"text": "Encephalitis and dementia associated with acquired immunodeficiency syndrome (AIDS) are characterized by leukocyte infiltration into the CNS, microglia activation, aberrant chemokine expression, blood-brain barrier (BBB) disruption, and eventual loss of neurons. Little is known about whether human immunodeficiency virus 1 (HIV-1) infection of leukocytes affects their ability to transmigrate in response to chemokines and to alter BBB integrity. We now demonstrate that HIV infection of human leukocytes results in their increased transmigration across our tissue culture model of the human BBB in response to the chemokine CCL2, as well as in disruption of the BBB, as evidenced by enhanced permeability, reduction of tight junction proteins, and expression of matrix metalloproteinases (MMP)-2 and MMP-9. HIV-infected cells added to our model did not transmigrate in the absence of CCL2, nor did this condition alter BBB integrity. The chemokines CXCL10/interferon-gamma-inducible protein of 10 kDa, CCL3/macrophage inflammatory protein-1alpha, or CCL5/RANTES (regulated on activation normal T-cell expressed and secreted) did not enhance HIV-infected leukocyte transmigration or BBB permeability. The increased capacity of HIV-infected leukocytes to transmigrate in response to CCL2 correlated with their increased expression of CCR2, the chemokine receptor for CCL2. These data suggest that CCL2, but not other chemokines, plays a key role in infiltration of HIV-infected leukocytes into the CNS and the subsequent pathology characteristic of NeuroAIDS.",
"title": "CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS."
},
{
"docid": "16375102",
"text": "The simple yet powerful technique of induced pluripotency may eventually supply a wide range of differentiated cells for cell therapy and drug development. However, making the appropriate cells via induced pluripotent stem cells (iPSCs) requires reprogramming of somatic cells and subsequent redifferentiation. Given how arduous and lengthy this process can be, we sought to determine whether it might be possible to convert somatic cells into lineage-specific stem/progenitor cells of another germ layer in one step, bypassing the intermediate pluripotent stage. Here we show that transient induction of the four reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) can efficiently transdifferentiate fibroblasts into functional neural stem/progenitor cells (NPCs) with appropriate signaling inputs. Compared with induced neurons (or iN cells, which are directly converted from fibroblasts), transdifferentiated NPCs have the distinct advantage of being expandable in vitro and retaining the ability to give rise to multiple neuronal subtypes and glial cells. Our results provide a unique paradigm for iPSC-factor-based reprogramming by demonstrating that it can be readily modified to serve as a general platform for transdifferentiation.",
"title": "Direct reprogramming of mouse fibroblasts to neural progenitors."
},
{
"docid": "18104691",
"text": "AIM This review explores the molecular, neurological, and behavioural outcomes in animal models of uterine artery ligation. We analyse the relevance of this type of model to the pathological and functional phenotypes that are consistent with cerebral palsy and its developmental comorbidities in humans. METHOD A literature search of the PubMed database was conducted for research using the uterine artery ligation model published between 1990 and 2013. From the studies included, any relevant neuroanatomical and behavioural deficits were then summarized from each document and used for further analysis. RESULTS There were 25 papers that met the criteria included for review, and several outcomes were summarized from the results of these papers. Fetuses with growth restriction demonstrated a gradient of reduced body weight with a relative sparing of brain mass. There was a significant reduction in the size of the somatosensory cortex, hippocampus, and corpus callosum. The motor cortex appeared to be spared of identifiable deficits. Apoptotic proteins were upregulated, while those important to neuronal survival, growth, and differentiation were downregulated. Neuronal apoptosis and astrogliosis occurred diffusely throughout the brain regions. White matter injury involved oligodendrocyte precursor maturation arrest, hypomyelination, and an aberrant organization of existing myelin. Animals with growth restriction demonstrated deficits in gait, memory, object recognition, and spatial processing. INTERPRETATION This review concludes that neuronal death, white matter injury, motor abnormalities, and cognitive deficits are important outcomes of uterine artery ligation in animal models. Therefore, this is a clinically relevant type of model, as these findings resemble deficits in human cerebral palsy.",
"title": "Neurological outcomes of animal models of uterine artery ligation and relevance to human intrauterine growth restriction: a systematic review"
},
{
"docid": "6153754",
"text": "In patients with spinal cord injury, the primary or mechanical trauma seldom causes total transection, even though the functional loss may be complete. In addition, biochemical and pathological changes in the cord may worsen after injury. To explain these phenomena, the concept of the secondary injury has evolved for which numerous pathophysiological mechanisms have been postulated. This paper reviews the concept of secondary injury with special emphasis on vascular mechanisms. Evidence is presented to support the theory of secondary injury and the hypothesis that a key mechanism is posttraumatic ischemia with resultant infarction of the spinal cord. Evidence for the role of vascular mechanisms has been obtained from a variety of models of acute spinal cord injury in several species. Many different angiographic methods have been used for assessing microcirculation of the cord and for measuring spinal cord blood flow after trauma. With these techniques, the major systemic and local vascular effects of acute spinal cord injury have been identified and implicated in the etiology of secondary injury. The systemic effects of acute spinal cord injury include hypotension and reduced cardiac output. The local effects include loss of autoregulation in the injured segment of the spinal cord and a marked reduction of the microcirculation in both gray and white matter, especially in hemorrhagic regions and in adjacent zones. The microcirculatory loss extends for a considerable distance proximal and distal to the site of injury. Many studies have shown a dose-dependent reduction of spinal cord blood flow varying with the severity of injury, and a reduction of spinal cord blood flow which worsens with time after injury. The functional deficits due to acute spinal cord injury have been measured electrophysiologically with techniques such as motor and somatosensory evoked potentials and have been found proportional to the degree of posttraumatic ischemia. The histological effects include early hemorrhagic necrosis leading to major infarction at the injury site. These posttraumatic vascular effects can be treated. Systemic normotension can be restored with volume expansion or vasopressors, and spinal cord blood flow can be improved with dopamine, steroids, nimodipine, or volume expansion. The combination of nimodipine and volume expansion improves posttraumatic spinal cord blood flow and spinal cord function measured by evoked potentials. These results provide strong evidence that posttraumatic ischemia is an important secondary mechanism of injury, and that it can be counteracted.",
"title": "Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms."
},
{
"docid": "4399268",
"text": "Spinal muscular atrophy is one of the most common inherited forms of neurological disease leading to infant mortality. Patients have selective loss of lower motor neurons resulting in muscle weakness, paralysis and often death. Although patient fibroblasts have been used extensively to study spinal muscular atrophy, motor neurons have a unique anatomy and physiology which may underlie their vulnerability to the disease process. Here we report the generation of induced pluripotent stem cells from skin fibroblast samples taken from a child with spinal muscular atrophy. These cells expanded robustly in culture, maintained the disease genotype and generated motor neurons that showed selective deficits compared to those derived from the child’s unaffected mother. This is the first study to show that human induced pluripotent stem cells can be used to model the specific pathology seen in a genetically inherited disease. As such, it represents a promising resource to study disease mechanisms, screen new drug compounds and develop new therapies.",
"title": "Induced pluripotent stem cells from a spinal muscular atrophy patient"
},
{
"docid": "13293033",
"text": "Down syndrome (DS) is the most frequent cause of human congenital mental retardation. Cognitive deficits in DS result from perturbations of normal cellular processes both during development and in adult tissues, but the mechanisms underlying DS etiology remain poorly understood. To assess the ability of induced pluripotent stem cells (iPSCs) to model DS phenotypes, as a prototypical complex human disease, we generated bona fide DS and wild-type (WT) nonviral iPSCs by episomal reprogramming. DS iPSCs selectively overexpressed chromosome 21 genes, consistent with gene dosage, which was associated with deregulation of thousands of genes throughout the genome. DS and WT iPSCs were neurally converted at >95% efficiency and had remarkably similar lineage potency, differentiation kinetics, proliferation, and axon extension at early time points. However, at later time points DS cultures showed a twofold bias toward glial lineages. Moreover, DS neural cultures were up to two times more sensitive to oxidative stress-induced apoptosis, and this could be prevented by the antioxidant N-acetylcysteine. Our results reveal a striking complexity in the genetic alterations caused by trisomy 21 that are likely to underlie DS developmental phenotypes, and indicate a central role for defective early glial development in establishing developmental defects in DS brains. Furthermore, oxidative stress sensitivity is likely to contribute to the accelerated neurodegeneration seen in DS, and we provide proof of concept for screening corrective therapeutics using DS iPSCs and their derivatives. Nonviral DS iPSCs can therefore model features of complex human disease in vitro and provide a renewable and ethically unencumbered discovery platform.",
"title": "Integration-free induced pluripotent stem cells model genetic and neural developmental features of down syndrome etiology."
},
{
"docid": "21323758",
"text": "Tafamidis is a transthyretin (TTR) stabilizer able to prevent TTR tetramer dissociation. There have been a few encouraging studies on Tafamidis efficacy in early-onset inherited transthyretin amyloidosis (ATTR) due to Val30Met mutation. However, less is known about its efficacy in later disease stages and in non-Val30Met mutations. We performed a multi-center observational study on symptomatic ATTR patients prescribed to receive Tafamidis. We followed up patients according to a standardized protocol including general medical, cardiological and neurological assessments at baseline and every 6 months up to 3 years. Sixty-one (42 males) patients were recruited. Only 28 % of enrolled subjects had the common Val30Met mutation, mean age of onset was remarkably late (59 years) and 18 % was in advanced disease stage at study entry. Tafamidis proved safe and well-tolerated. One-third of patients did not show significant progression along 36 months, independently from mutation type and disease stage. Neurological function worsened particularly in the first 6 months but progression slowed significantly thereafter. Autonomic function remained stable in 33 %, worsened in 56 % and improved in 10 %. Fifteen percent of patients showed cardiac disease progression and 30 % new onset of cardiomyopathy. Overall, Tafamidis was not able to prevent functional progression of the disease in 23 (43 %) subjects, including 16 patients who worsened in their walking ability and 12 patients who reached a higher NYHA score during the follow-up period. A higher mBMI at baseline was associated with better preservation of neurological function. In conclusion, neuropathy and cardiomyopathy progressed in a significant proportion of patients despite treatment. However, worsening of neurological function slowed after the first 6 months and also subjects with more advanced neuropathy, as well as patients with non-Val30Met mutation, benefited from treatment. Body weight preservation is an important favorable prognostic factor.",
"title": "Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area"
}
] |
64891
|
Mel Gibson won the award for Best Actor from the Australian Film Institute.
|
[
{
"docid": "Mel_Gibson",
"text": "Mel Colmcille Gerard Gibson ( born January 3 , 1956 ) is an American actor and filmmaker . He was born in Peekskill , New York , and moved with his parents to Sydney , Australia , when he was 12 years old . Gibson is best known as an action hero , for roles such as Martin Riggs in the Lethal Weapon buddy cop film series , and Max Rockatansky in the first three films in the Mad Max post-apocalyptic action series . He studied acting at the Australian National Institute of Dramatic Art . During the 1980s , he founded Icon Entertainment , a production company which independent film director Atom Egoyan has called , `` an alternative to the studio system '' . Director Peter Weir cast him as one of the leads in the critically acclaimed World War I drama Gallipoli ( 1981 ) , which earned Gibson a Best Actor Award from the Australian Film Institute . The film also helped to earn Gibson the reputation of a serious , versatile actor . Gibson produced , directed , and starred in the epic historical drama film Braveheart ( 1995 ) , for which he won the Golden Globe Award and Academy Award for Best Director , along with the Academy Award for Best Picture . He later directed and produced the financially successful and controversial , biblical drama film The Passion of the Christ ( 2004 ) . He received further critical notice for his directorial work of the action-adventure film Apocalypto ( 2006 ) , which is set in Mesoamerica during the early 16th century . After a 10-year hiatus from directing , Gibson returned with the critically praised and financially successful Hacksaw Ridge ( 2016 ) , which won the Academy Awards for Best Sound Mixing and Best Film Editing and earned Gibson his second nomination for Best Director .",
"title": ""
}
] |
[
{
"docid": "Mel_Gibson_filmography",
"text": "Mel Gibson , AO , is an American actor , director , producer and screenwriter who made his acting debut on the Australian television drama series The Sullivans ( 19761983 ) . While a student at the National Institute of Dramatic Art in Sydney , he was given an uncredited role in I Never Promised You a Rose Garden and subsequently appeared as a leading actor in the micro budget surf drama Summer City ( both in 1977 ) . Gibson became a part of the Australian New Wave cinema movement in the early 1980s having appeared in his breakthrough role in George Miller 's dystopian action film Mad Max ( 1979 ) , portraying the eponymous hero . He reprised the role in its sequels , Mad Max 2 ( 1981 ) and Mad Max Beyond Thunderdome ( 1985 ) . He appeared in Peter Weir 's war drama Gallipoli ( 1981 ) and the romantic drama The Year of Living Dangerously ( 1982 ) . Five years later he played Martin Riggs in the buddy cop action comedy Lethal Weapon alongside Danny Glovera role he later reprised in its sequels Lethal Weapon 2 ( 1989 ) , Lethal Weapon 3 ( 1992 ) , and Lethal Weapon 4 ( 1998 ) . Gibson starred in Franco Zeffirelli 's Hamlet in 1990 , as the eponymous character of the Shakespearean tragedy of the same name . It was the first film produced by Icon Productions , a production company he co-founded with Bruce Davey . Gibson 's directorial debut was The Man Without a Face ( 1993 ) , an adaptation of Isabelle Holland 's novel of the same name . Two years later he directed and produced Braveheart , a historical epic drama in which he also portrayed Sir William Wallace , a 13th-century Scottish knight . The film earned him a Golden Globe Award and the Academy Award for Best Director , and the film won an Academy Award for Best Picture . Gibson went on to star in Ransom ( 1996 ) , Payback ( 1999 ) , What Women Want and The Patriot ( both in 2000 ) , and We Were Soldiers ( 2002 ) . Gibson directed , co-wrote and produced The Passion of the Christ in 2004 , a Biblical epic drama which chronicled the Passion of Jesus . On its release , the film garnered mixed reviews as well as notoriety for its graphic violence and alleged undertones of antisemitism from critics . Nevertheless , it grossed $ 370.3 million in the United States and $ 611.4 million worldwide , making it Gibson 's highest-grossing film to date . Two years later he directed , co-wrote and produced Apocalypto , an epic adventure set in Central America depicting the last days of Mayan civilization before Spanish arrival in the 16th century . Gibson then took a ten-year hiatus from directing during which time he landed roles in Edge of Darkness ( 2010 ) , Machete Kills ( 2013 ) , The Expendables 3 ( 2014 ) , and Blood Father ( 2016 ) . He directed Hacksaw Ridge in 2016 , a biographical war drama focusing on American World War II veteran Desmond Doss , the first conscientious objector to receive the Medal of Honor . The film received praise from critics and audiences alike , as well as various accolades .",
"title": ""
},
{
"docid": "List_of_accolades_received_by_Hacksaw_Ridge",
"text": "Hacksaw Ridge is a 2016 biographical war film , directed by Mel Gibson and written by Andrew Knight and Robert Schenkkan . Starring Andrew Garfield , the film focuses on the World War II experiences of Desmond Doss , an American pacificist combat medic who was a Seventh-day Adventist Christian , refusing to carry or use a firearm or weapons of any kind . He became the first conscientious objector to be awarded the Medal of Honor , for service above and beyond the call of duty . It was released in the United States on November 4 , 2016 . The film was released to positive reviews , with a Rotten Tomatoes approval rating of 87 % , based on 223 reviews , and an average rating of 7.2 / 10 . Metacritic lists a score of 71 out of 100 , based on 47 reviews . Hacksaw Ridge won Best Film Editing and Best Sound Mixing and was nominated for Best Picture , Best Director , Best Actor for Garfield and Best Sound Editing at the Academy Awards . The film won Best Editing and was nominated for Best Actor in a Leading Role for Garfield , Best Adapted Screenplay , Best Sound and Best Makeup and Hair at the British Academy Film Awards . The film won Best Action Movie and Best Actor in an Action Movie for Garfield and was nominated for Best Picture , Best Director , Best Actor for Garfield , Best Editing and Best Hair and Makeup at the Critics ' Choice Awards . The film received three nominations at the Golden Globe Awards , including Best Motion Picture -- Drama , Best Actor -- Motion Picture Drama for Garfield and Best Director . The film won Best Actor for Garfield , Best Film Editing and Best Sound and was nominated for Best Film , Best Director , Best Adapted Screenplay , Best Cinematography , Best Original Score and Best Art Direction and Production Design at the Satellite Awards .",
"title": ""
},
{
"docid": "Donal_Gibson",
"text": "Donal Gibson ( born May 13 , 1960 ) is an American-Australian actor , and younger brother of award-winning actor and director Mel Gibson . Gibson was born in Peekskill , New York . Donal has done voice acting in shows like ReBoot and Justice League Unlimited ( as Captain Boomerang ) . His most notable voice acting role was probably as Captain John Smith in Disney 's Pocahontas II : Journey to a New World , a role which was played by his brother Mel in the first film , Pocahontas . Aside of voice acting , Donal has also appeared for minor roles in films starring his brother Mel , such as Braveheart , Conspiracy Theory , and Maverick , as well as major motion pictures not starring his brother such as Paparazzi , Casualties of War and One Eight Seven . Donal also holds a United States patent for a type of CD packaging and is an industrial painter .",
"title": ""
},
{
"docid": "Francesco_Cabras",
"text": "Francesco Cabras ( born 1966 , in Rome ) is an Italian actor . He played the role of Gesmas on Mel Gibson 's The Passion of the Christ , played the chief of the rebels on Kurt Wimmer 's Equilibrium as Francesco Calabras , and Rasputin on Louis Nero 's Rasputin Currently he is working as a director , writer , cinematographer , cameraman and producer . His acting debut won him the 1996 Nanni Moretti 's Sacher Festival Award for best leading actor . He directed together with Alberto Molinari the The Big Question a feature documentary selected at AFI Festival in Los Angeles about the faith and the perception of the divine distributed by ThinkFilm . The film was originally produced by Mel Gibson .",
"title": ""
},
{
"docid": "List_of_winners_of_Best_Actor_AACTA_Award",
"text": "This is a list of winners of the Best Actor award from the Australian Academy of Cinema and Television Arts Awards ( AACTA Awards ) . Ray Barrett Simon Burke Russell Crowe Colin Friels Mel Gibson John Hargreaves Chris Haywood Bill Hunter Norman Kaye Leo McKern John Meillon Sam Neill Richard Roxburgh Geoffrey Rush Bruce Spence Max von Sydow Nick Tate Jack Thompson John Waters Hugo Weaving",
"title": ""
},
{
"docid": "Australian_Film_Institute_International_Award_for_Best_Actor",
"text": "The Australian Film Institute International Award for Best Actor was an award in the annual Australian Film Institute Awards ( by AFI ) . It was awarded from 2005-2010 . The award has been superseded by the AFI 's AACTA International Award for Best Actor .",
"title": ""
},
{
"docid": "Hacksaw_Ridge",
"text": "Hacksaw Ridge is a 2016 biographical war drama film about the World War II experiences of Desmond Doss , an American pacifist combat medic who was a Seventh-day Adventist Christian , refusing to carry or use a firearm or weapons of any kind . Doss became the first conscientious objector to be awarded the Medal of Honor , for service above and beyond the call of duty during the Battle of Okinawa . The film was directed by Mel Gibson and written by Andrew Knight and Robert Schenkkan , based on a 2004 documentary about Doss , and stars Andrew Garfield as Doss , with Sam Worthington , Luke Bracey , Teresa Palmer , Hugo Weaving , Rachel Griffiths and Vince Vaughn in supporting roles . It was released in the United States on November 4 , 2016 , received positive reviews and grossed $ 175.3 million worldwide . Hacksaw Ridge was chosen by the American Film Institute as one of its top ten Movies of the Year , and has received numerous awards and nominations . The film received six Oscar nominations at the 89th Academy Awards , including Best Picture , Best Director , Best Actor for Garfield and Best Sound Editing , winning the awards for Best Sound Mixing and Best Film Editing . It also received Golden Globe nominations for Best Picture , Best Director and Best Actor , and 12 AACTA Awards nominations , winning the majority , including Best Film , Best Direction , Best Original Screenplay , Best Actor for Garfield , and Best Supporting Actor for Weaving .",
"title": ""
},
{
"docid": "Heath_Ledger",
"text": "Heathcliff Andrew Ledger ( 4 April 197922 January 2008 ) was an Australian actor and director . After performing roles in several Australian television and film productions during the 1990s , Ledger left for the United States in 1998 to develop his film career . His work comprised nineteen films , including 10 Things I Hate About You ( 1999 ) , The Patriot ( 2000 ) , A Knight 's Tale ( 2001 ) , Monster 's Ball ( 2001 ) , Lords of Dogtown ( 2005 ) , Brokeback Mountain ( 2005 ) , The Dark Knight ( 2008 ) , and The Imaginarium of Doctor Parnassus ( 2009 ) , the latter two being posthumous releases . He also produced and directed music videos and aspired to be a film director . For his portrayal of Ennis Del Mar in Brokeback Mountain , Ledger won the New York Film Critics Circle Award for Best Actor and Best International Actor from the Australian Film Institute , and was nominated for the BAFTA Award for Best Actor in a Leading Role and for the Academy Award for Best Actor . Posthumously he shared the 2007 Independent Spirit Robert Altman Award with the rest of the ensemble cast , the director , and the casting director for the film I 'm Not There , which was inspired by the life and songs of American singer-songwriter Bob Dylan . In the film , Ledger portrayed a fictional actor named Robbie Clark , one of six characters embodying aspects of Dylan 's life and persona . Ledger died on 22 January 2008 from an accidental intoxication from prescription drugs . A few months before his death , Ledger had finished filming his performance as the Joker in The Dark Knight . His death occurred during editing of The Dark Knight and in the midst of filming his last role as Tony in The Imaginarium of Doctor Parnassus . His untimely death cast a shadow over the subsequent promotion of the $ 185 million Batman production . Ledger received numerous posthumous accolades for his critically acclaimed performance in the film , including the Academy Award for Best Supporting Actor , a Best Actor International Award at the 2008 Australian Film Institute Awards ( for which he became the first actor to win an award posthumously ) , the 2008 Los Angeles Film Critics Association Award for Best Supporting Actor , the 2009 Golden Globe Award for Best Supporting Actor -- Motion Picture , and the 2009 BAFTA Award for Best Supporting Actor .",
"title": ""
},
{
"docid": "Sally_McKenzie",
"text": "Sally McKenzie ( born 8 February 1955 ) is an Australian actor , director , playwright and screenwriter . She graduated from Australia 's prestigious National Institute of Dramatic Art in 1977 . As a theatre actor Sally has appeared in leading and ensemble roles for the Belvoir St Theatre , Griffin Theatre Company , La Boite Theatre Company , Malthouse Theatre , Melbourne Theatre Company , Nimrod Theatre Company , Playbox Theatre Company , Queensland Theatre Company , The Stables , State Theatre Company of South Australia , Sydney Theatre Company , Q Theatre , Queensland Performing Arts Centre and the T.N ! Theatre Company . Stage performances for the Melbourne Theatre Company include title roles in Mourning Becomes Electra by Eugene O'Neill and The Good Woman of Szechwan by Bertolt Brecht . Sally has appeared in over 20 productions for the Queensland Theatre Company including lead roles in Macbeth , Night and Day by Tom Stoppard and by David Williamson Top Silk and A Conversation . Screen performances in TV series include Mystic Marj in Mortified , Ms Cunningham in The Wayne Manifesto , Esme in Carson 's Law , Rosetta in Special Squad , Patsy Goldfisch in The Flying Doctors , Grace in A Country Practice and Roo Morgan in episodes 666 and 667 of Prisoner . Sally played Bertha Schippan in The Schippan Mystery and won Best Single Performance by an Actress in a Serial in the Penguin Awards as rape victim Lynne in a 2-hour special of Cop Shop . Feature film performances include Gail in With Love From The Person Next To Me , Carrie in We Of The Never Never , Carol in Storage , Roz in Jucy and Warden Zelda in Redheads . As a playwright plays include Martha 's War On War , i dot luv dot u ☺ , A Safer Place , episodes and Scattered Lives . As a screenwriter Sally won the highest writing accolade awarded in Australia for performance writing , an Australian Writers ' Guild AWGIE Award for Best Documentary Public Broadcast in 2014 . As a writer-director films include shorts Shopping For Baby and Death By Art , 75 minute docufiction A Woman 's Deeper Journey Into Sex , the 55 minute version A Woman 's Journey Into Sex and the 2008 documentary Acting Class of 1977 AKA actingclassof1977.com about her experiences at the National Institute of Dramatic Art and her classmates , who included Mel Gibson .",
"title": ""
},
{
"docid": "Bruce_Davey",
"text": "Bruce Davey is an Australian film producer . A partner in Icon Entertainment alongside Mel Gibson , Sydney-born Davey has produced many films including Apocalypto , The Passion of the Christ , Push , and Braveheart for which he won an Academy Award . Davey began as Gibson 's CPA after being recommended by Gibson 's running coach in Gallipoli . After becoming Gibson 's business manager , the two men founded Icon Productions in 1989 .",
"title": ""
},
{
"docid": "The_Year_of_Living_Dangerously_(film)",
"text": "The Year of Living Dangerously is a 1982 Australian romantic , drama film directed by Peter Weir and co-written by Weir and David Williamson adapted from Christopher Koch 's 1978 novel The Year of Living Dangerously . The story is about a love affair set in Indonesia during the overthrow of President Sukarno . It follows a group of foreign correspondents in Jakarta on the eve of an attempted coup by the 30 September Movement in 1965 . The film stars Mel Gibson as an Australian journalist , and Sigourney Weaver as a British Embassy officer . It also stars Linda Hunt as the male dwarf Billy Kwan , Hamilton 's local photographer contact , a role for which Hunt won the 1983 Academy Award for Best Supporting Actress . The film was shot in both Australia and the Philippines and includes Australian actors Bill Kerr as Colonel Henderson and Noel Ferrier as Wally O'Sullivan . It was banned from being shown in Indonesia until 1999 , after the forced resignation of coup-leader and political successor Suharto in 1998 . The title The Year of Living Dangerously is a quote which refers to a famous Italian phrase used by Sukarno ; vivere pericolosamente , meaning `` living dangerously '' . Sukarno used the line for the title of his Indonesian Independence Day speech of 1964 .",
"title": ""
},
{
"docid": "Braveheart",
"text": "Braveheart is a 1995 American epic war film directed by and starring Mel Gibson . Gibson portrays William Wallace , a 13th-century Scottish warrior who led the Scots in the First War of Scottish Independence against King Edward I of England . The story is inspired by Blind Harry 's epic poem The Actes and Deidis of the Illustre and Vallyeant Campioun Schir William Wallace and was adapted for the screen by Randall Wallace . The film was nominated for ten Academy Awards at the 68th Academy Awards and won five : Best Picture , Best Director , Best Cinematography , Best Makeup , and Best Sound Editing .",
"title": ""
},
{
"docid": "1977_Australian_Film_Institute_Awards",
"text": "The 1977 Australian Film Awards ceremony , presented by the Australian Film Institute ( AFI ) , honoured the best Australian films of 1976 , and took place on 21 September 1977 at Regent Theatre , in Sydney , New South Wales . The awards were televised on ABC . Actors Keir Dullea and Karen Black , and former Australian Prime Minister John Gorton hosted the show . Don 's Party won six awards including Best Direction and Best Actress . Other winners were The Picture Show Man with four awards , and Storm Boy with two awards including Best Film and the Jury Prize . Charles Chauvel was awarded the Raymond Longford Award posthumously .",
"title": ""
},
{
"docid": "AACTA_Award_for_Best_Actor_in_a_Leading_Role",
"text": "The AACTA Award for Best Actor in a Leading Role is an award presented by the Australian Academy of Cinema and Television Arts ( AACTA ) , a non-profit organisation whose aim is to `` identify , award , promote and celebrate Australia 's greatest achievements in film and television . '' The award is presented at the annual AACTA Awards , which hand out accolades for achievements in feature film , television , documentaries and short films . From 1971 -- 2010 , the category was presented by the Australian Film Institute ( AFI ) , the Academy 's parent organisation , at the annual Australian Film Institute Awards ( known as the AFI Awards ) . When the AFI launched the Academy in 2011 , it changed the annual ceremony to the AACTA Awards , with the current award being a continuum of the AFI Award for Best Actor in a Leading Role . From 1971 up until 1975 , the awards for Best Actor and Best Actress were awarded in a single category for Best Performance . In 1971 the prize was given to Monica Maughan over fellow nominee Peter Cummins , who received a special mention for his performances in the films Some Regrets , The Hot Centre of the World ( 1971 short film ) , Bonjour Balwyn and Carson 's Watermelons . From 1972-1975 , the single award was handed out to the best actor and actress of the respective award giving years , with honourable mentions made to supporting casts . From 1976 to the present , the accolade has been handed out as a separate award for Best Actor in a Leading Role . Candidates for this award must be human and male , and can not be nominated for the same role in the supporting actor category .",
"title": ""
},
{
"docid": "1993_Australian_Film_Institute_Awards",
"text": "The 35th Australian Film Institute Awards ( generally known as the AFI Awards ) were held on 5 November 1993 . Presented by the Australian Film Institute ( AFI ) , the awards celebrated the best in Australian feature film , documentary , short film and television productions of 1993 . Eighteen feature films were nominated . Jane Campion 's The Piano dominated the feature film awards with eleven awards including Best Film . Blackfellas won two awards for adapted screenplay and actor in a supporting role , and On My Own received a single award for actress in a supporting role . Television awards were shared between various productions such as miniseries The Leaving of Liverpool and drama series Phoenix and G.P. . Producer Sue Milliken received the Raymond Longford Award for lifetime achievement .",
"title": ""
},
{
"docid": "AACTA_Award_for_Best_Performance_in_a_Television_Comedy",
"text": "The AACTA Award for Best Performance in a Television Comedy is an accolade given by the Australian Academy of Cinema and Television Arts ( AACTA ) , a non-profit organisation whose aim is to `` identify , award , promote and celebrate Australia 's greatest achievements in film and television . '' The award is handed out at the annual AACTA Awards , which rewards achievements in Australian feature film , television , documentaries and short films . From 1986 -- 2010 , the category was presented by the Australian Film Institute ( AFI ) , the Academy 's parent organisation , at the annual Australian Film Institute Awards ( known as the AFI Awards ) . When the AFI launched the Academy in 2011 , it changed the annual ceremony to the AACTA Awards , with the current prize being a continuum of the AFI Award for Best Performance in a Television Comedy . From 2003-2005 , the award was given as a joint award with drama performances under the category Best Actor in a Leading Role in a Television Drama or Comedy . However , comedy performances was separated from the drama categories in 2006 , when the award for Best Performance in a Television Comedy was created . Chris Lilley and Phil Lloyd have won the award the most times with two wins each .",
"title": ""
},
{
"docid": "List_of_awards_and_nominations_received_by_Heath_Ledger",
"text": "Heath Ledger was an Australian film actor whose career lasted more than 16 years . Ledger received acclaim for his acting in the Australian crime film Two Hands ( 1999 ) , receiving nominations at the Australian Film Institute ( AFI ) and Film Critics Circle of Australia in the categories for Best Actor . After starring in the 2001 films A Knight 's Tale and Monster 's Ball , Ledger was cast as the title character in the 2003 biographical film Ned Kelly for which he received his second AFI and Film Critics Circle award nominations . Ledger 's performance as Ennis Del Mar in the 2005 film Brokeback Mountain earned him Academy Award , British Academy Film Award ( BAFTA ) , Golden Globe Award , and Screen Actors Guild Award nominations . In addition , Ledger received recognition from several North American critics ' associations , winning the 2005 Las Vegas Film Critics Society , New York Film Critics Circle , Phoenix Film Critics Society , and San Francisco Film Critics Circle awards , as Best Actor . In 2006 , he starred in the Australian romantic drama Candy , and was nominated in the category of Best Actor at the AFI , Film Critics Circle , and Inside Film awards ceremony . Following his death on 22 January 2008 , Ledger received numerous posthumous awards and honours . He shared the 2007 Independent Spirit Robert Altman Award with the rest of the ensemble cast for the 2007 biographical film I 'm Not There . In his penultimate film performance , Ledger was nominated and awarded for his portrayal of the Joker in The Dark Knight ( 2008 ) . His wins include an Academy Award , BAFTA , Golden Globe Award , and Screen Actors Guild Award for Best Supporting Actor . Ledger also won the Best Actor International Award at the 2008 AFI Awards ceremony , for which he became the first actor to win an award posthumously . In August 2008 , Ledger was posthumously honoured at the Brisbane International Film Festival with the Chauvel Award in recognition of his contribution to the Australian film industry .",
"title": ""
},
{
"docid": "Jared_Daperis",
"text": "Jared Daperis ( born 18 August 1990 ) is an Australian actor . He has received a Young Artist Award nomination . Daperis ' recent film work has been compared with that of a `` young Mel Gibson '' , whilst co-stars have likened him to Heath Ledger . He is the brother of actor and director Daniel Daperis .",
"title": ""
},
{
"docid": "AACTA_Award_for_Best_Lead_Actor_in_a_Television_Drama",
"text": "The AACTA Award for Best Lead Actor in a Television Drama is an accolade given by the Australian Academy of Cinema and Television Arts ( AACTA ) , a non-profit organisation whose aim is to `` identify , award , promote and celebrate Australia 's greatest achievements in film and television . '' The award is handed out at the annual AACTA Awards , which rewards achievements in Australian feature film , television , documentaries and short films . From 1986 -- 2010 , the category was presented by the Australian Film Institute ( AFI ) , the Academy 's parent organisation , at the annual Australian Film Institute Awards ( known as the AFI Awards ) . When the AFI launched the Academy in 2011 , it changed the annual ceremony to the AACTA Awards , with the current prize being a continuum of the AFI Award for Best Lead Actor in a Television Drama . The award was first presented in 1986 , as two separate categories for performances in a miniseries and tele feature . These were then merged in 1990 to become Best Actor in a Leading Role in a Telefeature or Mini Series , and by 1991 , the award was renamed Best Actor in a Leading Role in a Television Drama . In 2000 , the Best Performance in a Telefeature or Mini Series accolade was re-introduced as a separate prize from the drama award . All of these were then combined in 2002 , under the title Best Actor in a Leading Role in a Television Drama , and two years later , in 2004 , was renamed Best Actor in a Leading Role in a Television Drama or Comedy . A separate comedy award was established in 2006 , and the name reverted to Best Lead Actor in a Television Drama . The AACTA Award for Best Lead Actor in a Television Drama is given for performances in television drama series , miniseries , telefeature , children 's animation or children 's drama series . Candidates for this award must be human and male , and can not be nominated for best guest or supporting actor in a television drama in the same year , for the same production .",
"title": ""
},
{
"docid": "Mad_Max_2",
"text": "Mad Max 2 ( also known as The Road Warrior and Mad Max 2 : The Road Warrior ) is a 1981 Australian post-apocalyptic action film directed by George Miller . The film is the second installment in the Mad Max film series , with Mel Gibson reprising his role as `` Mad '' Max Rockatansky . The film 's tale of a community of settlers who moved to defend themselves against a roving band of marauders follows an archetypical `` Western '' frontier movie motif , as does Max 's role as a hardened man who rediscovers his humanity when he decides to help the settlers . Filming took place in locations around Broken Hill , in the outback of New South Wales . Mad Max 2 was released on 24 December 1981 , and received ample critical acclaim . Observers praised the visuals and Gibson 's role . Noteworthy elements of the film also include cinematographer Dean Semler 's widescreen photography of Australia 's vast desert landscapes ; the sparing use of dialogue throughout the film ; costume designer Norma Moriceau 's punk mohawked , leather bondage gear-wearing bikers ; and its fast-paced , tightly edited and violent battle and chase scenes . The film 's comic-book post-apocalyptic/punk style popularized the genre in film and fiction writing . It was also a box office success , winning the Best International Film from six nominations at the Saturn Award ceremony , including : Best Director for Miller ; Best Actor for Gibson ; Best Supporting Actor for Bruce Spence ; Best Writing for Miller , Hayes and Hannant ; and Best Costume for Norma Moriceau . Mad Max 2 became a cult film , with fan clubs and `` road warrior '' - themed activities continuing into the 21st century , and is now widely considered to be one of the greatest action movies ever made , as well as one of the greatest sequels ever made . The film was preceded by Mad Max in 1979 and followed by Mad Max Beyond Thunderdome in 1985 and Mad Max : Fury Road in 2015 .",
"title": ""
},
{
"docid": "AACTA_Award_for_Best_Young_Actor",
"text": "The AACTA Award for Best Young Actor is an award presented by the Australian Academy of Cinema and Television Arts ( AACTA ) , a non-profit organisation whose aim is to `` identify , award , promote and celebrate Australia 's greatest achievements in film and television . '' The award is presented at the annual AACTA Awards , which hand out accolades for achievements in feature film , television , documentaries and short films . From 1991-2010 , the category was presented by the Australian Film Institute ( AFI ) , the Academy 's parent organisation , at the annual Australian Film Institute Awards ( known as the AFI Awards ) . When the AFI launched the Academy in 2011 , it changed the annual ceremony to the AACTA Awards , with the current award being a continuum of the AFI Young Actors Award . The award was first presented in 1991 as `` Best Juvenile Performance '' , and from 1992 -- 2010 , it was known as the `` Young Actors Award '' . It was handed out as a special award from 1991-2001 , before it became a competitive award from 2002 , onwards . Additionally , a cash prize of A$ 20,000 was given to the winner from 2006 -- 2008 . The award is presented at the discretion of the Academy , and is eligible to an actor or actress who is under the age of eighteen . It is given to an individual who has performed in a lead , supporting or guest role of television , feature film and short film categories .",
"title": ""
},
{
"docid": "2005_Australian_Film_Institute_Awards",
"text": "The 47th Annual Australian Film Institute Awards ( generally known as AFI Awards ) , were a series of awards which included the AFI Craft Awards and the AFI Awards Ceremony . Presented by the Australian Film Institute ( AFI ) , the awards celebrated the best in Australian feature film , television , documentary and short film productions of 2005 . The two events were held in Melbourne , Victoria , with the former presentation at the Waterfront City Pavilion , and the latter at the Melbourne Central City Studios , on 25 November and 26 November 2005 , respectively . The AFI Awards Ceremony was televised on the Nine Network , with actor Russell Crowe hosting both this and the AFI Craft Awards . Look Both Ways received the most feature film awards with five , including Best Film and Best Direction . Little Fish and The Proposition collected four awards each . The only other winner was Three Dollars with one for Best Adapted Screenplay . In the television categories , Love My Way won five awards , including Best Drama Series , Best Direction and Best Screenplay . MDA was given two awards . Other television winners were Holly 's Heroes , John Safran vs God , The Glass House and The Incredible Journey of Mary Bryant , with one each .",
"title": ""
},
{
"docid": "Australian_Film_Institute_Global_Achievement_Award",
"text": "The Australian Film Institute Global Achievement Award was a special award presented by the Australian Film Institute ( AFI ) to `` recognise outstanding achievement by Australians working internationally '' , to an individual who has `` demonstrated outstanding excellence in their field and shows a continuing commitment to the Australian film and television industry . '' It was handed out at the Australian Film Institute Awards ( known commonly as the AFI Awards ) , which are now the AACTA Awards after the establishment of the Australian Academy of Cinema and Television Arts ( AACTA ) , by the AFI . The award was presented from 2001-2004 before it was split into two categories for International Best Actor and International Best Actress , but it was handed out again in 2007 .",
"title": ""
},
{
"docid": "2nd_AACTA_Awards",
"text": "The 2nd Australian Academy of Cinema and Television Arts Awards ( generally known as AACTA Awards ) are a series of awards which includes the 2nd AACTA Awards Luncheon , the 2nd AACTA Awards ceremony and the 2nd AACTA International Awards . The former two events were held at the The Star Event Centre , in Sydney , New South Wales on 28 January and 30 January 2013 , respectively . Presented by the Australian Academy of Cinema and Television Arts ( AACTA ) , the awards celebrated the best in Australian feature film , television , documentary and short film productions of 2012 . The AACTA Awards ceremony was televised on Network Ten . Actor Russell Crowe hosted the show . These awards are a continuum of the Australian Film Institute Awards ( known as the AFI Awards ) , established in 1958 and presented until 2010 , which was rebranded the AACTA Awards when the Australian Film Institute ( AFI ) established AACTA in 2011 . On 9 May 2012 , the Academy revealed a new category for Best Reality Television Series , due to a growth in reality programming in Australia . The recipient of the Raymond Longford Award was Al Clark , for his work as a film producer , and the Byron Kennedy Award was handed out Special : Search/posthumous to Sarah Watt . The nominees were announced during a press conference on 3 December 2012 . The Sapphires won eleven of the thirteen film awards it was nominated for , including Best Film , Best Direction , Best Actor , Best Actress and Best Supporting Actress . Other feature film winners were Wish You Were Here with two awards , and Lore , Not Suitable for Children and Iron Sky with one . In the television categories Howzat ! Kerry Packer 's War and Redfern Now won two awards , and A Moody Christmas , The Adventures of Figaro Pho , Agony Aunts , The Amazing Race Australia , Jack Irish : Bad Debts , Lowdown , Puberty Blues , Rake and Underbelly : Badness with one .",
"title": ""
},
{
"docid": "Ransom_(1996_film)",
"text": "Ransom is a 1996 American crime thriller film directed by Ron Howard and written by Richard Price and Alexander Ignon . The film stars Mel Gibson , Rene Russo , Gary Sinise , Brawley Nolte , Delroy Lindo , Liev Schreiber , Evan Handler , Donnie Wahlberg , and Lili Taylor . Gibson was nominated for a Golden Globe Award for Best Actor . The original story came from a 1954 episode of The United States Steel Hour titled `` Fearful Decision '' . In 1956 , it was adapted by Richard Maibaum and Cyril Hume into the feature film Ransom ! , starring Glenn Ford , Donna Reed , and Leslie Nielsen . The film was also influenced by Ed McBain 's police procedural novel King 's Ransom . The film received mostly positive reviews , and was a major financial success , becoming the 6th highest-grossing film of 1996 in the United States .",
"title": ""
},
{
"docid": "AACTA_Award_for_Best_Actor_in_a_Supporting_Role",
"text": "The Australian Film Institute Award for Best Actor in a Supporting Role is an award in the annual Australian Film Institute Awards . It has been awarded annually since 1974 .",
"title": ""
},
{
"docid": "A_Street_to_Die",
"text": "A Street to Die is a 1985 Australian film directed by Bill Bennett . It was nominated for three Australian Film Institute Awards ; Chris Haywood won the award for Best Actor in a Lead Role . At the Karlovy Vary International Film Festival , Bennett won a Crystal Globe . Based on a true story .",
"title": ""
},
{
"docid": "The_Last_Confession_of_Alexander_Pearce",
"text": "The Last Confession of Alexander Pearce is a 2008 Australian film directed by Michael James Rowland starring Irish actors Adrian Dunbar as Philip Conolly and Ciarán McMenamin as bushranger Alexander Pearce and an ensemble Australian cast , including Dan Wyllie , Don Hany and Chris Haywood . The film was shot on location in Tasmania and Sydney between April and May 2008 . The film was nominated for the 2010 Rose d'Or , Best Drama at the 6th Annual Irish Film and Television Awards , Best Drama at the 2009 Australian Film Institute Awards , won Best Documentary at the 2009 Inside Film Awards and the director Michael James Rowland was nominated in the Best Director ( Telemovie ) category in the 2009 Australian Directors Guild Awards .",
"title": ""
},
{
"docid": "1992_Australian_Film_Institute_Awards",
"text": "The 34th Australian Film Institute Awards ( generally known as the AFI Awards ) were held at the World Congress Centre in Melbourne on 16 October 1992 . Presented by the Australian Film Institute ( AFI ) , the awards celebrated the best in Australian feature film , documentary , short film and television productions of 1992 . Feature film Strictly Ballroom received eight awards including Best Film . Romper Stomper won three and The Last Days of Chez Nous and Black Robe each won a single award . Miniseries Brides of Christ won four awards for television including Best Television Mini Series or Telefeature . Director and producer Lee Robinson received the Raymond Longford Award for lifetime achievement .",
"title": ""
},
{
"docid": "37th_Golden_Raspberry_Awards",
"text": "The 37th Golden Raspberry Awards was an awards ceremony that honors the worst the film industry had to offer in 2016 . The Golden Raspberry Awards , also known as the Razzies , are awarded based on votes from members of the Golden Raspberry Foundation . The pre-nomination ballots were revealed on the week of January 2 , 2017 , with the nominations being revealed on January 23 , 2017 . The `` winners '' were announced on February 25 , 2017 . Hillary 's America : The Secret History of the Democratic Party became the first documentary film to be awarded Worst Picture , also winning Worst Director , Worst Actor , and Worst Actress ; Batman v Superman : Dawn of Justice also won four awards , including Worst Prequel , Remake , Rip-off or Sequel and Worst Screenplay . Misconduct and Zoolander 2 won one award each , while Mel Gibson was awarded The Razzie Redeemer Award for directing Hacksaw Ridge .",
"title": ""
}
] |
607
|
Increased diastolic blood pressure (DBP) is associated with abdominal aortic aneurysm.
|
[
{
"docid": "4506414",
"text": "BACKGROUND The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease. METHODS We used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments. We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years. This study is registered at ClinicalTrials.gov, number NCT01164371. FINDINGS During 5·2 years median follow-up, we recorded 83,098 initial cardiovascular disease presentations. In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90-114 mm Hg and diastolic blood pressure of 60-74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32-1·58]), subarachnoid haemorrhage (1·43 [1·25-1·63]), and stable angina (1·41 [1·36-1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00-1·17]). Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure. Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86-0·98]) and strongest for peripheral arterial disease (1·23 [1·20-1·27]). People with hypertension (blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3% (95% CI 62·9-63·8) compared with 46·1% (45·5-46·8) for those with normal blood pressure, and developed cardiovascular disease 5·0 years earlier (95% CI 4·8-5·2). Stable and unstable angina accounted for most (43%) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years, whereas heart failure and stable angina accounted for the largest proportion (19% each) of years of life lost from index age 80 years. INTERPRETATION The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range, and that diastolic and systolic associations are concordant, are not supported by the findings of this high-resolution study. Despite modern treatments, the lifetime burden of hypertension is substantial. These findings emphasise the need for new blood pressure-lowering strategies, and will help to inform the design of randomised trials to assess them. FUNDING Medical Research Council, National Institute for Health Research, and Wellcome Trust.",
"title": "Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people"
}
] |
[
{
"docid": "30058568",
"text": "CONTEXT Managing thoracic aortic aneurysms identified incidentally by increased use of computed tomography, echocardiography, and magnetic resonance imaging is problematic, especially in the elderly. OBJECTIVE To ascertain whether the previously reported poor prognosis for individuals with thoracic aortic aneurysms has changed with better medical therapies and improved surgical techniques that can now be applied to aneurysm management. DESIGN Population-based cohort study. SETTING AND PATIENTS All 133 patients with the diagnosis of degenerative thoracic aortic aneurysms among Olmsted County, Minnesota, residents between 1980 and 1994 compared with a previously reported cohort of similar patients between 1951 and 1980. MAIN OUTCOME MEASURES The primary clinical end points were incidence, cumulative rupture risk, rupture risk as a function of aneurysm size, and survival. RESULTS In contrast to abdominal aortic aneurysms, for which men are affected predominately, 51% of thoracic aortic aneurysms were identified in women who were considerably older at recognition than men (mean age, 75.9 vs 62.8 years, respectively; P= .01). The overall incidence rate of 10.4 per 100000 person-years (95% confidence interval [CI], 8.6-12.2) between 1980 and 1994 was more than 3-fold higher than the rate from 1951 to 1980. The cumulative risk of rupture was 20% after 5 years. Seventy-nine percent of ruptures occurred in women (P= .01). The 5-year risk of rupture as a function of aneurysm size at recognition was 0% for aneurysms less than 4 cm in diameter, 16% (95% CI, 4%-28%) for those 4 to 5.9 cm, and 31% (95% CI, 5%-56%) for aneurysms 6 cm or more. Overall 5-year survival improved to 56% (95% CI, 48%-66%) between 1980 and 1994 compared with only 19% between 1951 and 1980 (P<.01). CONCLUSIONS In this population, elderly women represent an increasing portion of all patients with clinically recognized thoracic aortic aneurysms and constitute the majority of patients whose aneurysm eventually ruptures. Overall survival for thoracic aortic aneurysms has improved significantly in the past 15 years.",
"title": "Improved prognosis of thoracic aortic aneurysms: a population-based study."
},
{
"docid": "12549585",
"text": "Pulse wave velocity (PWV) was measured in the aorta, right leg and arm of 90 control subjects (CS) and 92 hemodialysis patients (HD) of the same age and mean arterial pressure (MAP). Blood chemistry, including blood lipids, and echographic dimensions of the aorta, were measured in all subjects. Presence of aortic calcification was evaluated by abdominal X-ray and echography. Whereas femoral and brachial PWV were only slightly increased in HD (P less than 0.05), the aortic PWV was significantly elevated (1113 +/- 319 cm/sec) in comparison with CS (965 +/- 216 cm/sec; P = 0.0016). Aortic diameters were larger in HD, both at the root of aorta (32.7 +/- 4 vs. 28.2 +/- 2.8 mm; P less than 0.0001) and aortic bifurcation (16.9 +/- 3.1 vs. 14.6 +/- 2.2 mm; P less than 0.0001). Although the MAP was similar in HD (109.9 +/- 19.3 mm Hg) and CS (110.2 +/- 17.2 mm Hg), the pulse pressure was significantly increased in HD patients (76.6 +/- 23.7 vs. 63.9 +/- 22 mm Hg; P = 0.007). In the two populations, aortic PWV was found to increase with age (P less than 0.0001) and MAP (P less than 0.0001). The presence of aortic calcification showed only a borderline relationship with the increase in aortic PWV (P = 0.050 in CS and P = 0.069 in HD). As change in PWV is directly related to change in distensibility, and the aortic diameters were increased in HD, these results indicate that aortic wall compliance is decreased in HD, resulting in an increase in the pulsatile component of arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Aortic and large artery compliance in end-stage renal failure."
},
{
"docid": "30639847",
"text": "CONTEXT Vascular stiffness increases with advancing age and is a major risk factor for age-related morbidity and mortality. Vascular stiffness and blood pressure pulsatility are related; however, temporal relationships between vascular stiffening and blood pressure elevation have not been fully delineated. OBJECTIVE To examine temporal relationships among vascular stiffness, central hemodynamics, microvascular function, and blood pressure progression. DESIGN, SETTING, AND PARTICIPANTS Longitudinal community-based cohort study conducted in Framingham, Massachusetts. The present investigation is based on the 2 latest examination cycles (cycle 7: 1998-2001; cycle 8: 2005-2008 [last visit: January 25, 2008]) of the Framingham Offspring study (recruited: 1971-1975). Temporal relationships among blood pressure and 3 measures of vascular stiffness and pressure pulsatility derived from arterial tonometry (carotid-femoral pulse wave velocity [CFPWV], forward wave amplitude [FWA], and augmentation index) were examined over a 7-year period in 1759 participants (mean [SD] age: 60 [9] years; 974 women). MAIN OUTCOME MEASURES The primary outcomes were blood pressure and incident hypertension during examination cycle 8. The secondary outcomes were CFPWV, FWA, and augmentation index during examination cycle 8. RESULTS In a multivariable-adjusted regression model, higher FWA (β, 1.3 [95% CI, 0.5-2.1] mm Hg per 1 SD; P = .002) and higher CFPWV (β, 1.5 [95% CI, 0.5-2.6] mm Hg per 1 SD; P = .006) during examination cycle 7 were jointly associated with systolic blood pressure during examination cycle 8. Similarly, in a model that included systolic and diastolic blood pressure and additional risk factors during examination cycle 7, higher FWA (odds ratio [OR], 1.6 [95% CI, 1.3-2.0] per 1 SD; P < .001), augmentation index (OR, 1.7 [95% CI, 1.4-2.0] per 1 SD; P < .001), and CFPWV (OR, 1.3 [95% CI, 1.0-1.6] per 1 SD; P = .04) were associated with incident hypertension during examination cycle 8 (338 cases [32%] in 1048 participants without hypertension during examination cycle 7). Conversely, blood pressure during examination cycle 7 was not associated with CFPWV during examination cycle 8. Higher resting brachial artery flow (OR, 1.23 [95% CI, 1.04-1.46]) and lower flow-mediated dilation (OR, 0.80 [95% CI, 0.67-0.96]) during examination cycle 7 were associated with incident hypertension (in models that included blood pressure and tonometry measures collected during examination cycle 7). CONCLUSION In this cohort, higher aortic stiffness, FWA, and augmentation index were associated with higher risk of incident hypertension; however, initial blood pressure was not independently associated with risk of progressive aortic stiffening.",
"title": "Aortic stiffness, blood pressure progression, and incident hypertension."
},
{
"docid": "18997216",
"text": "Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting. We hypothesized spontaneous sympathetic baroreflex gain would be reduced in normotensive pregnant women relative to nonpregnant matched controls. Integrated muscle sympathetic burst incidence and total sympathetic activity (microneurography), blood pressure (Finometer), and R-R interval (ECG) were assessed at rest in 11 pregnant women (33 ± 1 wk gestation, 31 ± 1 yr, prepregnancy BMI: 23.5 ± 0.9 kg/m(2)) and 11 nonpregnant controls (29 ± 1 yr; BMI: 25.2 ± 1.7 kg/m(2)). Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P < 0.01) relative to controls. Both mean (88 ± 3 vs. 91 ± 2 mmHg, P = 0.4) and diastolic (DBP) (72 ± 3 vs. 73 ± 2 mmHg, P = 0.7) pressures were similar between pregnant and nonpregnant women, respectively, indicating an upward resetting of the baroreflex set point with pregnancy. Baroreflex gain, calculated as the linear relationship between sympathetic burst incidence and DBP, was reduced in pregnant women relative to controls (-3.7 ± 0.5 vs. -5.4 ± 0.5 bursts·100 heart beats(-1)·mmHg(-1), P = 0.03), as was baroreflex gain calculated with total sympathetic activity (-294 ± 24 vs. -210 ± 24 au·100 heart beats(-1)·mmHg(-1); P = 0.03). Cardiovagal baroreflex gain (sequence method) was not different between nonpregnant controls and pregnant women (49 ± 8 vs. 36 ± 8 ms/mmHg; P = 0.2). However, sympathetic (burst incidence) and cardiovagal gains were negatively correlated in pregnant women (R = -0.7; P = 0.02). Together, these data indicate that the influence of the sympathetic nervous system over arterial blood pressure is reduced in normotensive pregnancy, in terms of both long-term and beat-to-beat regulation of arterial pressure, likely through a baroreceptor-dependent mechanism.",
"title": "Sympathetic baroreflex gain in normotensive pregnant women."
},
{
"docid": "4890578",
"text": "Time for primary reveiw 27 days Atherosclerosis continues to be one of the main subjects in pathology research. The intriguing complexity of its pathogenesis as well as the importance of its clinical sequelae provide a rationale for this [1]. A large number of diseases with totally different clinical presentations are basically atherosclerosis related, and among these, myocardial infarction, stroke, abdominal aneurysms and lower limb ischemia determine to a large extent the morbidity and mortality in Western style populations. But, despite this broad spectrum of clinical disease, most of the acute manifestations of atherosclerosis share a common pathogenetic feature: rupture of an atherosclerotic plaque [2–4]. Plaque disruptions may vary greatly in extent from tiny fissures or erosions of the plaque surface to deep intimal tears which extend into the soft lipid core of lesions; in all these instances, at least some degree of thrombus formation occurs [5, 6]. The abdominal aorta is the arterial site most prominently involved in the process of plaque formation, and also of plaque complications. In this large diameter vessel the process of plaque disruption and thrombosis is not ended by luminal occlusion, and may lead to extensive surface ulcerations comprising large areas of the aortic wall, as can be observed in many autopsy cases at older age. Apart from the undisputable role of atherosclerosis in abdominal aneurysm formation [7], mural thrombosis leads to a surprisingly low rate of clinically significant complications in these patients, although cholesterol emboli can be regularly found in their kidneys and skin at autopsy. Still, it is presently unclear what impact the various biologically active mediators released from eroded aortic surfaces may have on the human body. In contrast, in small diameter vessels such as coronary arteries, occlusive thrombosis is a frequent and often fatal complication of plaque … * Corresponding author. Tel.: +31-20-5665-633; fax: +31-20-914-738; e-mail [email protected]",
"title": "Atherosclerotic plaque rupture--pathologic basis of plaque stability and instability."
},
{
"docid": "8596837",
"text": "Women with a history of hypertensive pregnancy are at greater risk for future cardiovascular events; however, the mechanisms for this increased risk are unknown. Evidence suggests that an exercise stimulus unmasks latent hypertensive tendencies, identifying individuals at the greatest risk for developing cardiovascular disease. The current study examined the hypothesis that women with a hypertensive pregnancy history exhibit an augmented exercise pressor response. Normotensive women with a history of healthy pregnancy (CON; n = 9) and hypertensive pregnancy (HP+; n = 12) were studied during the mid-luteal phase of the menstrual cycle. Heart rate (HR), systolic and diastolic blood pressure (SBP, DBP), and muscle sympathetic nerve activity (MSNA) were measured during a cold pressor test (CPT), and, following a sufficient period of recovery, during static handgrip to fatigue (SHG) and post-exercise circulatory arrest (PECA). The BP, HR, and MSNA responses to the CPT were similar between groups. The SBP response to SHG and PECA was similar between groups, but DBP and HR were significantly greater in HP+ women (both p < 0.05). MSNA burst frequency, but not burst incidence or total activity, tended to be elevated in HP+ women during the stressor (peak Δ from baseline 31 ± 13 vs. 23 ± 13 bursts/min; p for group = 0.06). Despite no clinical signs of cardiovascular disease or hypertension, women with a history of hypertensive pregnancy display an enhanced cardiovascular reactivity to an exercise stimulus compared to women with a healthy pregnancy history. This response may be indicative of impaired cardiovascular control that precedes the clinical manifestation of hypertension or cardiovascular events.",
"title": "Sympathetic neural and cardiovascular responses during static handgrip exercise in women with a history of hypertensive pregnancy"
},
{
"docid": "6525844",
"text": "BACKGROUND Damage to large arteries is a major factor in the high cardiovascular morbidity and mortality of patients with end-stage renal disease (ESRD). Increased arterial stiffness and intima-media thickness, together with increased pulse pressure, are the principal arterial alterations. Whether increased aortic pulse-wave velocity (PWV), a classic marker of increased arterial stiffness, may predict all-cause and/or cardiovascular mortality has never been investigated. METHODS AND RESULTS A cohort of 241 patients with ESRD undergoing hemodialysis was studied between April 1987 and April 1998. The mean duration of follow-up was 72+/-41 months (mean+/-SD). Mean age at entry was 51.5+/-16.3 years. Seventy-three deaths occurred, including 48 cardiovascular and 25 noncardiovascular fatal events. At entry, together with standard clinical and biochemical analyses, patients underwent echocardiography and aortic PWV measured by Doppler ultrasonography. On the basis of Cox analyses, 2 factors emerged as predictors of all-cause and cardiovascular mortality: age and aortic PWV. Hemoglobin and low diastolic pressure interfered to a smaller extent. After adjustment for all the confounding factors, an OR for PWV >12. 0 versus <9.4 m/s was 5.4 (95% CI, 2.4 to 11.9) for all-cause mortality and 5.9 (95% CI, 2.3 to 15.5) for cardiovascular mortality. For each PWV increase of 1 m/s in our study population, all-cause mortality-adjusted OR was 1.39 (95% CI, 1.19 to 1.62). CONCLUSIONS These results provide the first direct evidence that in patients with ESRD, increased aortic stiffness determined by measurement of aortic PWV is a strong independent predictor of all-cause and mainly cardiovascular mortality.",
"title": "Impact of aortic stiffness on survival in end-stage renal disease."
},
{
"docid": "202259",
"text": "BACKGROUND Patients undergoing dialysis have a substantially increased risk of cardiovascular mortality and morbidity. Although several trials have shown the cardiovascular benefits of lowering blood pressure in the general population, there is uncertainty about the efficacy and tolerability of reducing blood pressure in patients on dialysis. We did a systematic review and meta-analysis to assess the effect of blood pressure lowering in patients on dialysis. METHODS We systematically searched Medline, Embase, and the Cochrane Library database for trials reported between 1950 and November, 2008, without language restriction. We extracted a standardised dataset from randomised controlled trials of blood pressure lowering in patients on dialysis that reported cardiovascular outcomes. Meta-analysis was done with a random effects model. FINDINGS We identified eight relevant trials, which provided data for 1679 patients and 495 cardiovascular events. Weighted mean systolic blood pressure was 4.5 mm Hg lower and diastolic blood pressure 2.3 mm Hg lower in actively treated patients than in controls. Blood pressure lowering treatment was associated with lower risks of cardiovascular events (RR 0.71, 95% CI 0.55-0.92; p=0.009), all-cause mortality (RR 0.80, 0.66-0.96; p=0.014), and cardiovascular mortality (RR 0.71, 0.50-0.99; p=0.044) than control regimens. The effects seem to be consistent across a range of patient groups included in the studies. INTERPRETATION Treatment with agents that lower blood pressure should routinely be considered for individuals undergoing dialysis to reduce the very high cardiovascular morbidity and mortality rate in this population.",
"title": "Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systematic review and meta-analysis of randomised controlled trials"
},
{
"docid": "12513972",
"text": "BACKGROUND Intracranial aneurysm (IA) is significantly more prevalent in patients with coarctation of the aorta or bicuspid aortic valve than in the general population, suggesting a common pathophysiology connecting IA and aortopathy. Here, we analyzed echocardiographic aortic root dimension (ARD) in patients with IA to confirm this possibility. METHODS From January 2008 to December 2010, 260 consecutive patients with IA who were admitted to our institution for coil embolization or for acute stroke management and who also underwent echocardiography were enrolled. We hypothesized that patients with large, ruptured, or multiple IAs are more likely to harbor co-prevalent aortopathy as measured by ARD compared to patients with small, isolated, unruptured IAs. Eccentric group was defined as patients aged <55 years with at least one ruptured aneurysm, an aneurysm ≥7 mm in size, or multiple aneurysms; the remainder was classified into a non-eccentric group. Clinical, angiographic, and echocardiographic findings of the two groups were compared. RESULTS ARD was significantly larger in the eccentric group than in the non-eccentric group (P = 0.049), and the difference was confirmed by multivariable analysis (P = 0.02). Subgroup analysis of patients aged <55 years showed similar result for ARD (P = 0.03), whereas hypertension was more associated with the non-eccentric group (P = 0.01). In addition, height was inversely related to aneurysm size after adjustment for age, sex, weight, ARD, smoking status, and number of aneurysms (P = 0.004). CONCLUSIONS A certain group of IA patients share a common intrinsic wall defect with aortopathy. Shared neural crest cell origin may give rise to this phenomenon.",
"title": "Echocardiographic Evidence of Innate Aortopathy in the Human Intracranial Aneurysm"
},
{
"docid": "22730024",
"text": "OBJECTIVE To assess the antihypertensive efficacy of olmesartan medoxomil and ramipril on 24-h ambulatory blood pressure (ABP) in elderly hypertensive patients by pooled data analysis of two studies with identical designs (one Italian, one European). METHODS After a 2-week placebo wash-out 1453 elderly hypertensive patients (65-89 years; sitting office DBP 90-109 mmHg and/or sitting office SBP 140-179 mmHg) were randomized to a 12-week double-blind treatment with olmesartan medoxomil 10 mg or ramipril 2.5 mg once-daily, up-titrated (20 and 40 mg olmesartan medoxomil; 5 and 10 mg ramipril) after 2 and 6 weeks in patients without normalized office BP. 24-h ABP was recorded at randomization and after 12 weeks. RESULTS In 715 patients with valid baseline and end-of-treatment recordings baseline-adjusted 24-h SBP and DBP reductions were greater with olmesartan medoxomil (n = 356) than with ramipril (n = 359) [between-treatment differences and 95% confidence interval (CI), SBP: 2.2 (3.8, 0.6), P = 0.006; DBP: 1.3 (2.2, 0.3), P = 0.009]. Olmesartan medoxomil showed larger BP reductions in the last 6 h from the dosing interval and higher smoothness indices than ramipril. Olmesartan medoxomil reduced the SBP morning rise [-2.8 (-4.9, -0.8) mmHg], whereas ramipril did not [+1.5 (-0.6, +3.6) mmHg; P = 0.004 between-treatments]. Five hundred and eighty-two patients with sustained hypertension (office and 24-h ambulatory hypertension) showed the largest antihypertensive effect, with between-treatment differences still in favor of olmesartan medoxomil [SBP: 2.1 (3.9, 0.4), P = 0.019; DBP: 1.2 (2.3, 0.1), P = 0.032]. CONCLUSIONS Olmesartan medoxomil provides a more effective and sustained 24-h BP control than ramipril in elderly hypertensive patients, particularly in the hours farthest from last intake.",
"title": "Twenty-four hour and early morning blood pressure control of olmesartan vs. ramipril in elderly hypertensive patients: pooled individual data analysis of two randomized, double-blind, parallel-group studies."
},
{
"docid": "24998764",
"text": "Chronic kidney disease is accompanied by increased large-artery stiffness, but the relation between glomerular filtration rate within the reference range and central or peripheral arterial stiffness has been understudied. The link between renal function and arterial stiffness was assessed in 305 patients with never-treated essential hypertension (men: 58%; age: 48+/-11 years, blood pressure: 151/95+/-20/11 mm Hg), free from overt cardiovascular disease and with serum creatinine values <1.4 mg/dL (men) and <1.2 mg/dL (women), who underwent noninvasive aortic and upper-limb pulse wave velocity (PWV) determination. Aortic PWV was strongly related to age (r=0.55; P<0.001), whereas upper-limb PWV had a weaker nonlinear relation with age (beta=1.392; P<0.001 for age; beta=-1.312; P<0.001 for age squared) and a weak relation with aortic PWV (r=0.22; P<0.001). Glomerular filtration rate (GFR), estimated according to the Mayo clinic equation for healthy subjects, was inversely correlated with large-artery stiffness, as assessed by aortic PWV (r=-0.34; P<0.001), and with peripheral artery stiffness, as assessed by upper-limb PWV (r=-0.25; P<0.001). In a multivariate linear regression, aortic PWV was independently predicted by age (beta=0.48; P<0.001), mean arterial pressure (beta=0.14; P=0.013), and GFR (beta=-0.13, P=0.029). Upper-limb PWV was predicted by GFR (beta=-0.24; P<0.001) and mean arterial pressure (beta=0.20; P<0.001). We conclude that, in hypertensive patients with normal renal function, an inverse relationship exists between GFR and stiffness of both central elastic and peripheral muscular arteries. These relations are in part independent from the effect of several confounders, including age, sex, and blood pressure values.",
"title": "Relation between renal function within the normal range and central and peripheral arterial stiffness in hypertension."
},
{
"docid": "13108582",
"text": "Osteopontin (OPN), a key component of the extracellular matrix, is associated with the fibrotic process during tissue remodeling. OPN and the cytokine interleukin (IL)-18 have been shown to be overexpressed in an array of human cardiac pathologies. In the present study, we determined the role of IL-18 in the regulation of cardiac OPN expression and the subsequent interstitial fibrosis and diastolic dysfunction. We demonstrated parallel increases in IL-18, OPN expression, and interstitial fibrosis in murine models of left ventricular pressure and volume overload. Exogenous recombinant (r)IL-18 administered for 2 wk increased cardiac OPN expression, interstitial fibrosis, and diastolic dysfunction. Stimulation of the T helper (Th)1 lymphocyte phenotype with a selective toll-like receptor (TLR)9 agonist induced cardiac IL-18 and OPN expression, which was associated with increased cardiac fibrillar collagen concentrations and interstitial fibrosis resulting in diastolic dysfunction. rIL-18 induced OPN expression and protein levels in primary of cardiac fibroblast cultures. Conditioned media from TLR9-stimulated T lymphocyte cultures induced IL-18 and OPN expression in cardiac fibroblasts, while blockade of the IL-18 receptor with a neutralizing antibody abolished the increase in OPN expression. Furthermore, a mutation in the transcriptional factor interferon regulatory factor (IRF)1 or IRF1 small interfering RNA (siRNA) resulted in the decreased expression of IL-18 and OPN in cardiac fibroblasts. With pressure overload, IRF1-mutant mice showed downregulation of IL-18 and OPN expression in cardiac tissue, reduced cardiac fibrotic development, and increased left ventricular function compared with wild type. These results provide direct evidence that the induction of IL-18 regulates OPN-mediated cardiac fibrosis and diastolic dysfunction.",
"title": "IL-18 induction of osteopontin mediates cardiac fibrosis and diastolic dysfunction in mice."
},
{
"docid": "8509018",
"text": "BACKGROUND Patients with signs and symptoms of heart failure and a normal left ventricular ejection fraction are said to have diastolic heart failure. It has traditionally been thought that the pathophysiological cause of heart failure in these patients is an abnormality in the diastolic properties of the left ventricle; however, this hypothesis remains largely unproven. METHODS We prospectively identified 47 patients who met the diagnostic criteria for definite diastolic heart failure; all the patients had signs and symptoms of heart failure, a normal ejection fraction, and an increased left ventricular end-diastolic pressure. Ten patients who had no evidence of cardiovascular disease served as controls. Left ventricular diastolic function was assessed by means of cardiac catheterization and echocardiography. RESULTS The patients with diastolic heart failure had abnormal left ventricular relaxation and increased left ventricular chamber stiffness. The mean (+/-SD) time constant for the isovolumic-pressure decline (tau) was longer in the group with diastolic heart failure than in the control group (59+/-14 msec vs. 35+/-10 msec, P=0.01). The diastolic pressure-volume relation was shifted up and to the left in the patients with diastolic heart failure as compared with the controls. The corrected left ventricular passive-stiffness constant was significantly higher in the group with diastolic heart failure than in the control group (0.03+/-0.01 vs. 0.01+/-0.01, P<0.001). CONCLUSIONS Patients with heart failure and a normal ejection fraction have significant abnormalities in active relaxation and passive stiffness. In these patients, the pathophysiological cause of elevated diastolic pressures and heart failure is abnormal diastolic function.",
"title": "Diastolic heart failure--abnormalities in active relaxation and passive stiffness of the left ventricle."
},
{
"docid": "27158570",
"text": "We performed genome-wide analyses to identify genomic loci that interact with sodium to influence blood pressure (BP) using single-marker-based (1 and 2 df joint tests) and gene-based tests among 1876 Chinese participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Among GenSalt participants, the average of 3 urine samples was used to estimate sodium excretion. Nine BP measurements were taken using a random zero sphygmomanometer. A total of 2.05 million single-nucleotide polymorphisms were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing and Japanese of Tokyo HapMap reference panel. Promising findings (P<1.00×10(-4)) from GenSalt were evaluated for replication among 775 Chinese participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Single-nucleotide polymorphism and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The 1 df tests identified interactions for UST rs13211840 on diastolic BP (P=3.13×10(-9)). The 2 df tests additionally identified associations for CLGN rs2567241 (P=3.90×10(-12)) and LOC105369882 rs11104632 (P=4.51×10(-8)) with systolic BP. The CLGN variant rs2567241 was also associated with diastolic BP (P=3.11×10(-22)) and mean arterial pressure (P=2.86×10(-15)). Genome-wide gene-based analysis identified MKNK1 (P=6.70×10(-7)), C2orf80 (P<1.00×10(-12)), EPHA6 (P=2.88×10(-7)), SCOC-AS1 (P=4.35×10(-14)), SCOC (P=6.46×10(-11)), CLGN (P=3.68×10(-13)), MGAT4D (P=4.73×10(-11)), ARHGAP42 (P≤1.00×10(-12)), CASP4 (P=1.31×10(-8)), and LINC01478 (P=6.75×10(-10)) that were associated with at least 1 BP phenotype. In summary, we identified 8 novel and 1 previously reported BP loci through the examination of single-nucleotide polymorphism and gene-based interactions with sodium.",
"title": "Genome-Wide Gene-Sodium Interaction Analyses on Blood Pressure: The Genetic Epidemiology Network of Salt-Sensitivity Study."
},
{
"docid": "19804204",
"text": "BACKGROUND AND OBJECTIVES Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction, and over half have hypertension. Data on the potential contribution of hypertension to CKD-associated neurocognitive deficits in children are limited. Our objective was to determine whether children with CKD and elevated BP (EBP) had decreased performance on neurocognitive testing compared with children with CKD and normal BP. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a cross-sectional analysis of the relation between auscultatory BP and neurocognitive test performance in children 6 to 17 years enrolled in the Chronic Kidney Disease in Children (CKiD) project. RESULTS Of 383 subjects, 132 (34%) had EBP (systolic BP and/or diastolic BP ≥90(th) percentile). Subjects with EBP had lower mean (SD) scores on Wechsler Abbreviated Scales of Intelligence (WASI) Performance IQ than those with normal BP (normal BP versus EBP, 96.1 (16.7) versus 92.4 (14.9), P = 0.03) and WASI Full Scale IQ (97.0 (16.2) versus 93.4 (16.5), P = 0.04). BP index (subject's BP/95(th) percentile BP) correlated inversely with Performance IQ score (systolic, r = -0.13, P = 0.01; diastolic, r = -0.19, P < 0.001). On multivariate analysis, the association between lower Performance IQ score and increased BP remained significant after controlling for demographic and disease-related variables (EBP, β = -3.7, 95% confidence interval [CI]: -7.3 to -0.06; systolic BP index, β = -1.16 to 95% CI: -2.1, -0.21; diastolic BP index, β = -1.17, 95% CI: -1.8 to -0.55). CONCLUSIONS Higher BP was independently associated with decreased WASI Performance IQ scores in children with mild-to-moderate CKD.",
"title": "Casual blood pressure and neurocognitive function in children with chronic kidney disease: a report of the children with chronic kidney disease cohort study."
},
{
"docid": "31889025",
"text": "OBJECTIVES - To study the relative and population-attributable risks of hypertension for the development of congestive heart failure (CHF), to assess the time course of progression from hypertension to CHF, and to identify risk factors that contribute to the development of overt heart failure in hypertensive subjects. DESIGN - Inception cohort study. SETTING - General community. PARTICIPANTS - Original Framingham Heart Study and Framingham Offspring Study participants aged 40 to 89 years and free of CHF. To reflect more contemporary experience, the starting point of this study was January 1, 1970. EXPOSURE MEASURES - Hypertension (blood pressure of at least 140 mm Hg systolic or 90 mm Hg diastolic or current use of medications for treatment of high blood pressure) and other potential CHF risk factors were assessed at periodic clinic examinations. OUTCOME MEASURE - The development of CHF. RESULTS - A total of 5143 eligible subjects contributed 72422 person-years of observation. During up to 20.1 years of follow-up (mean, 14.1 years), there were 392 new cases of heart failure; in 91% (357/392), hypertension antedated the development of heart failure. Adjusting for age and heart failure risk factors in proportional hazards regression models, the hazard for developing heart failure in hypertensive compared with normotensive subjects was about 2-fold in men and 3-fold in women. Multivariable analyses revealed that hypertension had a high population-attributable risk for CHF, accounting for 39% of cases in men and 59% in women. Among hypertensive subjects, myocardial infarction, diabetes, left ventricular hypertrophy, and valvular heart disease were predictive of increased risk for CHF in both sexes. Survival following the onset of hypertensive CHF was bleak; only 24% of men and 31% of women survived 5 years. CONCLUSIONS - Hypertension was the most common risk factor for CHF, and it contributed a large proportion of heart failure cases in this population-based sample. Preventive strategies directed toward earlier and more aggressive blood pressure control are likely to offer the greatest promise for reducing the incidence of CHF and its associated mortality.",
"title": "The progression from hypertension to congestive heart failure."
},
{
"docid": "26710772",
"text": "Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min(-1), 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min(-1); main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm(-5); P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.(-1) min(-1); P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml(-1), P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml(-1), P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications.",
"title": "Sympathetic activation during early pregnancy in humans."
},
{
"docid": "4647303",
"text": "CONTEXT Exposure to cardiovascular risk factors during childhood and adolescence may be associated with the development of atherosclerosis later in life. OBJECTIVE To study the relationship between cardiovascular risk factors measured in childhood and adolescence and common carotid artery intima-media thickness (IMT), a marker of preclinical atherosclerosis, measured in adulthood. DESIGN, SETTING, AND PARTICIPANTS Population-based, prospective cohort study conducted at 5 centers in Finland among 2229 white adults aged 24 to 39 years who were examined in childhood and adolescence at ages 3 to 18 years in 1980 and reexamined 21 years later, between September 2001 and January 2002. MAIN OUTCOME MEASURES Association between cardiovascular risk variables (levels of low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides; LDL-C/HDL-C ratio; systolic and diastolic blood pressure; body mass index; smoking) measured in childhood and adulthood and common carotid artery IMT measured in adulthood. RESULTS In multivariable models adjusted for age and sex, IMT in adulthood was significantly associated with childhood LDL-C levels (P =.001), systolic blood pressure (P<.001), body mass index (P =.007), and smoking (P =.02), and with adult systolic blood pressure (P<.001), body mass index (P<.001), and smoking (P =.004). The number of risk factors measured in 12- to 18-year-old adolescents, including high levels (ie, extreme age- and sex-specific 80th percentile) of LDL-C, systolic blood pressure, body mass index, and cigarette smoking, were directly related to carotid IMT measured in young adults at ages 33 through 39 years (P<.001 for both men and women), and remained significant after adjustment for contemporaneous risk variables. The number of risk factors measured at ages 3 to 9 years demonstrated a weak direct relationship with carotid IMT at ages 24 to 30 years in men (P =.02) but not in women (P =.63). CONCLUSIONS Risk factor profile assessed in 12- to 18-year-old adolescents predicts adult common carotid artery IMT independently of contemporaneous risk factors. These findings suggest that exposure to cardiovascular risk factors early in life may induce changes in arteries that contribute to the development of atherosclerosis.",
"title": "Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study."
},
{
"docid": "13445579",
"text": "BACKGROUND AND PURPOSE IAs are found in 2.3% of adults; the mean age at detection is 52 years. Prevalence is <0.5% in young adults. Early studies suggest that 10%-50% of patients with aortic coarctation have IAs. Screening recommendations are variable. We sought to examine the prevalence of IAs through screening with MRA. MATERIALS AND METHODS Consecutive patients older than 16 years of age with coarctation undergoing brain MRA between May 1999 and October 2007 were included. MRA was performed by using a 1.5T scanner with a 3D time-of-flight protocol; simultaneous MR imaging was performed of the heart and aorta. Cerebral MRAs were double-reported by a neuroradiologist. Statistics are described as mean ± SD and median ± range. Continuous variables were compared by using Student t tests and Mann-Whitney U tests (categoric variables, by using the Fisher exact test). RESULTS One hundred seventeen MRAs were double-reported. The median age was 29 ± 11 years (range, 16-59 years). IAs were found in 12 patients (10.3%). The mean diameter of IAs was 3.9 mm (range, 2.0-8.0 mm). Patients with aneurysms were older (median, 37 years; range, 16-50 years) than those without (median, 23 years; range, 16-59 years; Z = -2.01, P = .04). Hypertension was more common in those with IAs (IA 83% versus no IA 43%, P = .01). There was no association between ascending aortopathy, bicuspid aortic valves, and IAs. CONCLUSIONS Patients with coarctation have a higher prevalence of IAs, occurring at an earlier age than in population studies. Whether routine screening is appropriate for this group of patients is unclear. Hypertension is likely to be an important pathophysiologic factor.",
"title": "Results of screening for intracranial aneurysms in patients with coarctation of the aorta."
},
{
"docid": "3552753",
"text": "BACKGROUND In the assessment of severity in community acquired pneumonia (CAP), the modified British Thoracic Society (mBTS) rule identifies patients with severe pneumonia but not patients who might be suitable for home management. A multicentre study was conducted to derive and validate a practical severity assessment model for stratifying adults hospitalised with CAP into different management groups. METHODS Data from three prospective studies of CAP conducted in the UK, New Zealand, and the Netherlands were combined. A derivation cohort comprising 80% of the data was used to develop the model. Prognostic variables were identified using multiple logistic regression with 30 day mortality as the outcome measure. The final model was tested against the validation cohort. RESULTS 1068 patients were studied (mean age 64 years, 51.5% male, 30 day mortality 9%). Age >/=65 years (OR 3.5, 95% CI 1.6 to 8.0) and albumin <30 g/dl (OR 4.7, 95% CI 2.5 to 8.7) were independently associated with mortality over and above the mBTS rule (OR 5.2, 95% CI 2.7 to 10). A six point score, one point for each of Confusion, Urea >7 mmol/l, Respiratory rate >/=30/min, low systolic(<90 mm Hg) or diastolic (</=60 mm Hg) Blood pressure), age >/=65 years (CURB-65 score) based on information available at initial hospital assessment, enabled patients to be stratified according to increasing risk of mortality: score 0, 0.7%; score 1, 3.2%; score 2, 3%; score 3, 17%; score 4, 41.5% and score 5, 57%. The validation cohort confirmed a similar pattern. CONCLUSIONS A simple six point score based on confusion, urea, respiratory rate, blood pressure, and age can be used to stratify patients with CAP into different management groups.",
"title": "Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study."
},
{
"docid": "21616324",
"text": "BACKGROUND Control of blood pressure (BP) following renal transplantation may improve allograft and patient survival. Our aims were (i) to describe the distribution of BP and the prevalence of systolic and/or diastolic hypertension in children over the first 5 years following renal transplantation and (ii) to evaluate clinical risk factors and centre-specific factors associated with hypertension in this population. METHODS We conducted a retrospective case note review of all current paediatric kidney transplant patients in the UK, with data collected at 6 months, 1, 2 and 5 years following transplantation in subjects with hypertension (systolic and/or diastolic BP > 95th > ) and non-hypertensive subjects BP ≤ 95th > . RESULTS In total, 27.3% (117/428), 27.6% (118/428), 26.0% (95/365) and 25.6% (50/195) of the patients were hypertensive (systolic and/or diastolic BP > 95th > ) at 6 months, 1, 2 and 5 years following transplantation, respectively. A total of 58.4% of the patients at 6 months, 52.8% at 1 year, 48.2% at 2 years and 48.2% at 5 years were receiving anti-hypertensive therapy, of whom 31.6-36.6% remained hypertensive. When subjects were identified as being hypertensive, on anti-hypertensive medication or had untreated hypertension (systolic and/or diastolic BP > 95th > ), 66.4, 61.0, 56.4 and 55.9% of patients were hypertensive at 6 months, 1, 2 and 5 years, respectively. In a multivariate model, odds ratios for systolic hypertension were 4.16 (deceased versus living donor), 2.65 (lowest versus highest quartile of height z-score) and 2.07 (if on anti-hypertensive; yes versus no). There was significant variation in prevalent rates of hypertension between centres (P < 0.0001) that remained significant (P = 0.003) after adjustment for all the factors in the multivariate model. CONCLUSIONS Control of BP after kidney transplantation remains sub-optimal in paediatric centres in the UK. Just over 25% of patients remain hypertensive 5 years following transplantation. Significant differences between centres remain unexplained and may reflect differences in assessment and management of hypertension.",
"title": "Systemic arterial hypertension in children following renal transplantation: prevalence and risk factors."
},
{
"docid": "14121786",
"text": "BACKGROUND Epidemiologic analysis of family data on blood pressure (BP) is often compromised by the effects of antihypertensive medications. A review of numerous clinical trials that investigated the effects of BP-lowering medications is summarized here. METHODS Published clinical trials, including 137 clinical trials with monodrug therapies and 28 clinical trials of combination drug therapies with a total of 11,739 participants, were reviewed from PubMed. Six major classes/groups of antihypertensive medications were categorized by ethnicity, including angiotensin-converting enzyme (ACE) inhibitors, alpha1-blockers, cardioselective beta-blockers (beta1-blockers), calcium channel blockers, thiazide and thiazide-like diuretics, and loop diuretics. RESULTS Using sitting or supine BP, for ethnic groups combined, monodrug therapy with ACE inhibitors showed a weighted average effect of lowering the systolic and diastolic BP by 12.5/9.5 mm Hg; alpha1-blockers by 15.5/11.7 mm Hg; beta1-blockers by 14.8/12.2 mm Hg; calcium channel blockers by 15.3/10.5 mm Hg; thiazide diuretics by 15.3/9.8 mm Hg; and loop diuretics by 15.8/8.2 mm Hg. However, ACE inhibitors, alpha1-blockers, and beta1-blockers were less effective in African Americans than in non-African Americans, whereas calcium channel blockers, thiazide diuretics, and loop diuretics were more effective in African Americans than in non-African Americans. For two-drug combination therapy with ethnic groups combined, the BP-lowering effect of the second medication, when compared to its effect as monodrug therapy, was 84% and 65% for systolic and diastolic BP, respectively. CONCLUSIONS The BP-lowering effects reported here may be used to impute the pretreatment BP levels, which can improve the information content and hence the power of epidemiologic analysis in studies where use of antihypertensive medications is a confounding factor in the BP measurements.",
"title": "A summary of the effects of antihypertensive medications on measured blood pressure."
},
{
"docid": "27449472",
"text": "The metabolic syndrome was initially described as an insulin-resistance syndrome characterized by the clustering of metabolic traits such as high triglycerides, low high-density lipoprotein cholesterol, high blood pressure, abdominal obesity and different degrees of impaired glucose regulation. Although different definitions have been developed by various consensus groups, epidemiological studies demonstrate that they all associate the metabolic syndrome with a similar cardiometabolic risk, which is high for diabetes (ranging between three- and 20-fold), depending on the number of components and the inclusion of impaired fasting glucose, impaired glucose tolerance or both. The latter appear to indicate the failure of the beta cell to produce enough insulin to compensate for the increased demand due to insulin resistance. There is a hyperbolic relationship between insulin production and insulin sensitivity, which can be calculated by the disposition index. When this is altered there is a higher risk of developing Type 2 diabetes. There have been no clinical trials in subjects selected by the diagnosis of metabolic syndrome, but structured lifestyle changes have been tested in people with impaired fasting glucose/impaired glucose tolerance and have been able to reduce incident Type 2 diabetes by almost 50%, as long as a weight loss of at least 5% is achieved. Oral antidiabetic and anti-obesity drugs have also been successful to a lesser degree. Some fibrates have reduced or delayed incident diabetes. Extended-release niacin has a neutral effect and statins are controversial. ACE inhibitors and ARBs are the antihypertensive agents least associated with incident diabetes.",
"title": "Metabolic syndrome as a risk factor for diabetes."
},
{
"docid": "25301182",
"text": "CONTEXT Limited information exists regarding the role of left ventricular function in predicting exercise capacity and impact on age- and sex-related differences. OBJECTIVES To determine the impact of measures of cardiac function assessed by echocardiography on exercise capacity and to determine if these associations are modified by sex or advancing age. DESIGN Cross-sectional study of patients undergoing exercise echocardiography with routine measurements of left ventricular systolic and diastolic function by 2-dimensional and Doppler techniques. Analyses were conducted to determine the strongest correlates of exercise capacity and the age and sex interactions of these variables with exercise capacity. SETTING Large tertiary referral center in Rochester, Minnesota, in 2006. PARTICIPANTS Patients undergoing exercise echocardiography using the Bruce protocol (N = 2867). Patients with echocardiographic evidence of exercise-induced ischemia, ejection fractions lower than 50%, or significant valvular heart disease were excluded. MAIN OUTCOME MEASURE Exercise capacity in metabolic equivalents (METs). RESULTS Diastolic dysfunction was strongly and inversely associated with exercise capacity. Compared with normal function, after multivariate adjustment, those with moderate/severe resting diastolic dysfunction (-1.30 METs; 95% confidence interval [CI], -1.52 to -0.99; P < .001) and mild resting diastolic dysfunction (-0.70 METs; 95% CI, -0.88 to -0.46; P < .001) had substantially lower exercise capacity. Variation of left ventricular systolic function within the normal range was not associated with exercise capacity. Left ventricular filling pressures measured by resting E/e' of 15 or greater (-0.41 METs; 95% CI, -0.70 to -0.11; P = .007) or postexercise E/e' of 15 or greater (-0.41 METs; 95% CI, -0.71 to -0.11; P = .007) were similarly associated with a reduction in exercise capacity, each in separate multivariate analyses. Individuals with impaired relaxation (mild dysfunction) or resting E/e' of 15 or greater had a progressive increase in the magnitude of reduction in exercise capacity with advancing age (P < .001 and P = .02, respectively). Other independent correlates of exercise capacity were age (unstandardized beta coefficient, -0.85 METs; 95% CI, -0.92 to -0.77, per 10-year increment; P < .001), female sex (-1.98 METs; 95% CI, -2.15 to -1.84; P < .001), and body mass index greater than 30 (-1.24 METs; 95% CI, -1.41 to -1.10; P < .001). CONCLUSION In this large cross-sectional study of those referred for exercise echocardiography and not limited by ischemia, abnormalities of left ventricular diastolic function were independently associated with exercise capacity.",
"title": "Left ventricular function and exercise capacity."
},
{
"docid": "3825750",
"text": "BACKGROUND Diabetic nephropathy is the leading cause of end-stage renal disease in developed countries. We evaluated the renoprotective effects of dual blockade of the renin-angiotensin-aldosterone system by adding treatment with aliskiren, an oral direct renin inhibitor, to treatment with the maximal recommended dose of losartan (100 mg daily) and optimal antihypertensive therapy in patients who had hypertension and type 2 diabetes with nephropathy. METHODS We enrolled 599 patients in this multinational, randomized, double-blind study. After a 3-month, open-label, run-in period during which patients received 100 mg of losartan daily, patients were randomly assigned to receive 6 months of treatment with aliskiren (150 mg daily for 3 months, followed by an increase in dosage to 300 mg daily for another 3 months) or placebo, in addition to losartan. The primary outcome was a reduction in the ratio of albumin to creatinine, as measured in an early-morning urine sample, at 6 months. RESULTS The baseline characteristics of the two groups were similar. Treatment with 300 mg of aliskiren daily, as compared with placebo, reduced the mean urinary albumin-to-creatinine ratio by 20% (95% confidence interval, 9 to 30; P<0.001), with a reduction of 50% or more in 24.7% of the patients who received aliskiren as compared with 12.5% of those who received placebo (P<0.001). A small difference in blood pressure was seen between the treatment groups by the end of the study period (systolic, 2 mm Hg lower [P=0.07] and diastolic, 1 mm Hg lower [P=0.08] in the aliskiren group). The total numbers of adverse and serious adverse events were similar in the groups. CONCLUSIONS Aliskiren may have renoprotective effects that are independent of its blood-pressure-lowering effect in patients with hypertension, type 2 diabetes, and nephropathy who are receiving the recommended renoprotective treatment. (ClinicalTrials.gov number, NCT00097955 [ClinicalTrials.gov].).",
"title": "Aliskiren combined with losartan in type 2 diabetes and nephropathy."
},
{
"docid": "19854543",
"text": "PURPOSE To characterize the relationship between aneurysm size and epidemiologic risk factors with growth and rupture by using computed tomographic (CT) angiography. MATERIALS AND METHODS In this HIPAA-compliant, institutional review board approved study, patients with known asymptomatic unruptured intracerebral aneurysms were followed up longitudinally with CT angiographic examinations. Growth was defined as an increase in one or more dimensions above the measurement error, and at least 5% volume by using the ABC/2 method. Associations of epidemiologic factors with aneurysm growth and rupture were analyzed by using logistic regression analysis. Intra- and interobserver agreement coefficients for dimension, volume, and growth were evaluated by using the Pearson correlation coefficient and difference of means with 95% confidence intervals, the agreement statistic, and the McNemar χ(2). RESULTS Patients (n = 165) with aneurysms (n = 258) had a mean follow-up time of 2.24 years from time of diagnosis. Forty-six of 258 (18%) aneurysms in 38 patients grew larger. Spontaneous rupture occurred in four of 228 (1.8%) intradural aneurysms of average size (6.2 mm). Risk of aneurysm rupture per patient-year was 2.4% (95% CI: 0.5%, 7.12%) with growth and 0.2% (95% CI: 0.006%, 1.22%) without growth (P = .034). There was a 12-fold higher risk of rupture for growing aneurysms (P < .002), with high intra- and interobserver correlation coefficients for size, volume, and growth. Tobacco smoking (3.806, one degree of freedom; P < .015,) and initial size (5.895, two degrees of freedom; P < .051) were independent covariates, predicting 78.4% of growing aneurysms. CONCLUSION These results support imaging follow-up of all patients with aneurysms, including those whose aneurysms are smaller than the current 7-mm treatment threshold. Aneurysm growth, size, and smoking were associated with increased rupture risk.",
"title": "Natural history of asymptomatic unruptured cerebral aneurysms evaluated at CT angiography: growth and rupture incidence and correlation with epidemiologic risk factors."
},
{
"docid": "24396137",
"text": "Older cancer survivors are a vulnerable population due to an increased risk for chronic diseases (e.g., cardiovascular disease) compounded with treatment late-effects and declines in physical functioning. Therefore, interventions that reduce chronic disease risk factors (i.e., blood pressure, chronic inflammation, and cortisol) are important in this population. Tai chi chih (TCC) is a mind-body exercise associated with reductions in chronic disease risk factors, but has not been examined with older cancer survivors. In a feasibility randomized controlled trial of TCC, we examined secondary outcomes of blood pressure, salivary cortisol, and inflammatory cytokines (interleukin (IL)-6, IL-12, tumor necrosis factor-α, IL-10, IL-4) due to their implications in chronic diseases. Sixty-three senior female cancer survivors (M age = 67 years, SD = 7.15) with physical functioning limitations (SF-12 physical functioning ≤80 or role-physical ≤72) were randomized to 12-weeks (60-min, three times a week) of TCC or Health Education control (HEC) classes. Resting blood pressure, 1-day salivary cortisol samples, and fasting plasma samples for cytokine multiplex assays were collected at baseline and 1-week post-intervention. Controlling for baseline values, the TCC group had significantly lower systolic blood pressure (SBP, p = 0.002) and cortisol area-under-curve (AUC, p = 0.02) at post-intervention than the HEC group. There was no intervention effect on inflammatory cytokines (p’s > 0.05). This TCC feasibility trial was associated with significant reductions in SBP and cortisol AUC in senior female cancer survivors. Larger, definitive trials are needed to confirm these findings. Senior survivors’ have an increased risk for chronic diseases; however, TCC interventions may help reduce associated risk factors.",
"title": "Blood pressure, salivary cortisol, and inflammatory cytokine outcomes in senior female cancer survivors enrolled in a tai chi chih randomized controlled trial"
},
{
"docid": "2774906",
"text": "Physical activity protects against cardiovascular disease, and physiological cardiac hypertrophy associated with regular exercise is usually beneficial, in marked contrast to pathological hypertrophy associated with disease. The p110alpha isoform of phosphoinositide 3-kinase (PI3K) plays a critical role in the induction of exercise-induced hypertrophy. Whether it or other genes activated in the athlete's heart might have an impact on cardiac function and survival in a setting of heart failure is unknown. To examine whether progressive exercise training and PI3K(p110alpha) activity affect survival and/or cardiac function in two models of heart disease, we subjected a transgenic mouse model of dilated cardiomyopathy (DCM) to swim training, genetically crossed cardiac-specific transgenic mice with increased or decreased PI3K(p110alpha) activity to the DCM model, and subjected PI3K(p110alpha) transgenics to acute pressure overload (ascending aortic constriction). Life-span, cardiac function, and molecular markers of pathological hypertrophy were examined. Exercise training and increased cardiac PI3K(p110alpha) activity prolonged survival in the DCM model by 15-20%. In contrast, reduced PI3K(p110alpha) activity drastically shortened lifespan by approximately 50%. Increased PI3K(p110alpha) activity had a favorable effect on cardiac function and fibrosis in the pressure-overload model and attenuated pathological growth. PI3K(p110alpha) signaling negatively regulated G protein-coupled receptor stimulated extracellular responsive kinase and Akt (via PI3K, p110gamma) activation in isolated cardiomyocytes. These findings suggest that exercise and enhanced PI3K(p110alpha) activity delay or prevent progression of heart disease, and that supraphysiologic activity can be beneficial. Identification of genes important for hypertrophy in the athlete's heart could offer new strategies for treating heart failure.",
"title": "Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy."
},
{
"docid": "597790",
"text": "Although mast cell functions have classically been related to allergic responses, recent studies indicate that these cells contribute to other common diseases such as multiple sclerosis, rheumatoid arthritis, atherosclerosis, aortic aneurysm and cancer. This study presents evidence that mast cells also contribute to diet-induced obesity and diabetes. For example, white adipose tissue (WAT) from obese humans and mice contain more mast cells than WAT from their lean counterparts. Furthermore, in the context of mice on a Western diet, genetically induced deficiency of mast cells, or their pharmacological stabilization, reduces body weight gain and levels of inflammatory cytokines, chemokines and proteases in serum and WAT, in concert with improved glucose homeostasis and energy expenditure. Mechanistic studies reveal that mast cells contribute to WAT and muscle angiogenesis and associated cell apoptosis and cathepsin activity. Adoptive transfer experiments of cytokine-deficient mast cells show that these cells, by producing interleukin-6 (IL-6) and interferon-gamma (IFN-gamma), contribute to mouse adipose tissue cysteine protease cathepsin expression, apoptosis and angiogenesis, thereby promoting diet-induced obesity and glucose intolerance. Our results showing reduced obesity and diabetes in mice treated with clinically available mast cell-stabilizing agents suggest the potential of developing new therapies for these common human metabolic disorders.",
"title": "Deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice"
},
{
"docid": "8529693",
"text": "In this paper we review the associations between maternal and child undernutrition with human capital and risk of adult diseases in low-income and middle-income countries. We analysed data from five long-standing prospective cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa and noted that indices of maternal and child undernutrition (maternal height, birthweight, intrauterine growth restriction, and weight, height, and body-mass index at 2 years according to the new WHO growth standards) were related to adult outcomes (height, schooling, income or assets, offspring birthweight, body-mass index, glucose concentrations, blood pressure). We undertook systematic reviews of studies from low-income and middle-income countries for these outcomes and for indicators related to blood lipids, cardiovascular disease, lung and immune function, cancers, osteoporosis, and mental illness. Undernutrition was strongly associated, both in the review of published work and in new analyses, with shorter adult height, less schooling, reduced economic productivity, and--for women--lower offspring birthweight. Associations with adult disease indicators were not so clear-cut. Increased size at birth and in childhood were positively associated with adult body-mass index and to a lesser extent with blood pressure values, but not with blood glucose concentrations. In our new analyses and in published work, lower birthweight and undernutrition in childhood were risk factors for high glucose concentrations, blood pressure, and harmful lipid profiles once adult body-mass index and height were adjusted for, suggesting that rapid postnatal weight gain--especially after infancy--is linked to these conditions. The review of published works indicates that there is insufficient information about long-term changes in immune function, blood lipids, or osteoporosis indicators. Birthweight is positively associated with lung function and with the incidence of some cancers, and undernutrition could be associated with mental illness. We noted that height-for-age at 2 years was the best predictor of human capital and that undernutrition is associated with lower human capital. We conclude that damage suffered in early life leads to permanent impairment, and might also affect future generations. Its prevention will probably bring about important health, educational, and economic benefits. Chronic diseases are especially common in undernourished children who experience rapid weight gain after infancy.",
"title": "Maternal and child undernutrition: consequences for adult health and human capital"
}
] |
48743
|
Little Miss Sunshine was filmed in Arizona and Southern California.
|
[
{
"docid": "Little_Miss_Sunshine",
"text": "Little Miss Sunshine is a 2006 American comedy-drama road film and the directorial debut of the husband-wife team of Jonathan Dayton and Valerie Faris . The screenplay was written by first-time writer Michael Arndt . The film stars Greg Kinnear , Steve Carell , Toni Collette , Paul Dano , Abigail Breslin and Alan Arkin , and was produced by Big Beach Films on a budget of US$ 8 million . Filming began on June 6 , 2005 and took place over 30 days in Arizona and Southern California . The film premiered at the Sundance Film Festival on January 20 , 2006 , and its distribution rights were bought by Fox Searchlight Pictures for one of the biggest deals made in the history of the festival . The film had a limited release in the United States on July 26 , 2006 , and later expanded to a wider release starting on August 18 . Little Miss Sunshine had an international box office gross of $ 100.5 million . The film was nominated for four Academy Awards , including Best Picture , and won two : Best Original Screenplay for Michael Arndt and Best Supporting Actor for Alan Arkin . It also won the Independent Spirit Award for Best Feature and received numerous other accolades .",
"title": ""
}
] |
[
{
"docid": "Little_Miss_Sunshine_(disambiguation)",
"text": "Little Miss Sunshine may mean : Little Miss Sunshine , a 2006 black comedy road film . Little Miss Sunshine ( musical ) , the 2006 musical of the film Little Miss Sunshine ( soundtrack ) , the soundtrack Little Miss Sunshine ( character ) , a character in the Mr. Men children 's books Little Miss Sunshine and the Wicked Witch , a series `` special ''",
"title": ""
},
{
"docid": "Little_Miss_Sunshine_(musical)",
"text": "Little Miss Sunshine is a musical adapted from the 2006 film of the same name , with music and lyrics by William Finn and book and direction by James Lapine . The musical premiered in San Diego , California at the Mandell Weiss Theater , La Jolla Playhouse on February 15 , 2011 . and began performances Off-Broadway at the Second Stage Theatre in October 2013 .",
"title": ""
},
{
"docid": "List_of_accolades_received_by_Little_Miss_Sunshine",
"text": "Little Miss Sunshine received numerous awards and honors from film organizations , film festivals , and critics groups . The 2006 film was commended for its ensemble cast , individual roles , screenplay , and other aspects of the film .",
"title": ""
},
{
"docid": "Ron_Yerxa",
"text": "Ron Yerxa ( born May 18 , 1947 ) is an American film producer . He is known for the films Little Miss Sunshine , Hamlet 2 and Cold Mountain . Yerxa and fellow producer Albert Berger were nominated for an Academy Award for Best Picture for the 2013 film Nebraska . Ron Yerxa attended the University of California Santa Cruz and Stanford University",
"title": ""
},
{
"docid": "Michael_Arndt",
"text": "Michael Arndt is an American screenwriter . He is best known as the writer of the films Little Miss Sunshine ( 2006 ) , Toy Story 3 ( 2010 ) and Star Wars : The Force Awakens ( 2015 ) . Arndt won the Academy Award for Best Original Screenplay for Little Miss Sunshine and was nominated for Best Adapted Screenplay for Toy Story 3 . This made Arndt the first screenwriter ever to be nominated for both the Academy Award for Best Original Screenplay and Best Adapted Screenplay for his first two screenplays . He has also been credited under the pseudonyms Michael deBruyn and Rick Kerb , which are mainly used for script revisions .",
"title": ""
},
{
"docid": "Alan_Arkin",
"text": "Alan Wolf Arkin ( born March 26 , 1934 ) is an American actor , director , screenwriter , musician , and singer . With a film career spanning more than 55 years , Arkin is known for his performances in Popi , Wait Until Dark , The Russians Are Coming , the Russians Are Coming , The Heart Is a Lonely Hunter , Catch-22 , The In-Laws , Edward Scissorhands , Glengarry Glen Ross , Thirteen Conversations About One Thing , Little Miss Sunshine , and Argo . He has been nominated for the Academy Award for Best Actor twice for his performances in The Russians Are Coming , the Russians Are Coming and The Heart Is a Lonely Hunter . He won an Academy Award for Best Supporting Actor for his performance in Little Miss Sunshine and received a Best Supporting Actor nomination for his performance in Argo .",
"title": ""
},
{
"docid": "Albert_Berger",
"text": "Albert Berger is a film producer of such films as King of the Hill , Election , Cold Mountain , Little Children , Little Miss Sunshine , Ruby Sparks , and Nebraska . He is also a co-executive producer on the HBO series The Leftovers ( TV series ) . Berger and fellow producer Ron Yerxa were nominated for an Academy Award for Best Picture for the 2013 film Nebraska .",
"title": ""
},
{
"docid": "David_T._Friendly",
"text": "David T. Friendly ( born May 1 , 1956 ) is an American film producer best known for co-producing the 2006 film Little Miss Sunshine , for which he was nominated for an Academy Award for Best Picture .",
"title": ""
},
{
"docid": "Big_Beach_(company)",
"text": "Big Beach is an American independent production company founded in 2004 by Marc Turtletaub and Peter Saraf , based in New York City . It is best known for their lower-budget comedy-drama films , including the 2006 film Little Miss Sunshine .",
"title": ""
},
{
"docid": "Little_Miss_Sunshine_(soundtrack)",
"text": "The soundtrack for Little Miss Sunshine is a mix of indie rock and folk music . DeVotchKa provides the majority of the music on the soundtrack , and also the score , which they did with Mychael Danna . There are also selections from Sufjan Stevens , Rick James , and Tony Tisdale featured on the album . The song heard on the trailer featured on TV was `` Coming Home '' by The 88 . The internet trailer was accompanied by the `` The Yeah Yeah Yeah Song ( With All Your Power ) '' by The Flaming Lips .",
"title": ""
},
{
"docid": "On_the_Trail_with_Miss_Snail_Pail",
"text": "On the Trail with Miss Snail Pail is a 2009 short documentary film that follows Colleen Flanigan , aka Miss Snail Pail , as she provides a snail removal service that recycles the garden pests into food . On the Trail 's first festival screening was at the 2009 Tucson Slow Food & Film Festival in Arizona . The film was also selected for screening by the 2009 Modesto Reel Food Film Festival in California , the 2009 Colorado Environmental Film Festival in Golden , Colorado , and the 2011 9th Annual Wild and Scenic Film Festival in Nevada City , California .",
"title": ""
},
{
"docid": "Coreocarpus_arizonicus",
"text": "Coreocarpus arizonicus ( little lemonhead ) is a North American species of flowering plants in the daisy family native to northwestern Mexico and the southwestern United States . It has been found in southern Arizona ( Pima , Santa Cruz , Cochise Counties ) , and in the adjacent Mexican States of Sonora , Chihuahua , Sinaloa , and Baja California Sur . Coreocarpus arizonicus is a branching perennial subshrub up to 120 cm ( 48 inches ) tall . The plant usually produces several flower heads , each head having yellow disc florets and white , purplish , yellow , or orange ray florets . Sometimes the ray florets are missing . The species grows in open sites along streams and in mountain canyons . Varieties Coreocarpus arizonicus var . arizonicus - Arizona , Sonora , Chihuahua , Baja California Sur Coreocarpus arizonicus var . filiformis ( Greenm . ) S.F.Blake - Sinaloa Coreocarpus arizonicus var . macrophyllus Sherff - Chihuahua Coreocarpus arizonicus var . pubescens ( B.L.Rob . & Fernald ) S.F.Blake - Sonora Coreocarpus arizonicus var . sanpedroensis ( E.B.Sm . ) B.L.Turner - Sonora",
"title": ""
},
{
"docid": "List_of_Little_Picacho_Wilderness_flora",
"text": "The flora of the Little Picacho Wilderness located in southeastern Imperial County , Southern California . It is within the Colorado Desert subregion , of the Sonoran Desert ecoregion The Little Picacho Wilderness is located in the southern portion of the Lower Colorado River Valley , with its eastern side along the Colorado River ( Little Picacho Wash runs ~ 1.5 mi downstream ) ; and is 10 mi north of Yuma , Arizona and Winterhaven , California . The wilderness area protects a region of the southeastern Chocolate Mountains .",
"title": ""
},
{
"docid": "Danielle_Demski",
"text": "Danielle Demski ( born 1981 ) is a television presenter and beauty queen from Chandler , Arizona , who has competed in the Miss Teen USA and Miss USA pageants . Demski won her first pageant title in 1998 , when she was crowned Miss Arizona Teen USA 1999 . She competed in the Miss Teen USA 1999 pageant held in Shreveport , Louisiana , in August 1999 , where she became the third delegate from Arizona to make the semi-finals . Demski placed sixth in the interview competition with a score of 9.22 , sixth in swimsuit ( 9.45 ) and third in evening gown ( 9.68 ) , entering the top six in fourth place with an average combined score of 9.45 . She retained fourth position following the final question , and placed third runner-up overall . In 2003 Demski won the Miss Arizona USA 2004 pageant in her first attempt at the title , becoming the third Miss Arizona Teen USA to win the Miss Arizona USA title . She represented Arizona in the Miss USA 2004 pageant broadcast live from the Kodak Theatre in Hollywood , California , on April 11 , 2004 , and again made the first cut , the first Arizonan to do so since 1998 . She competed in the evening gown competition , but did not advance to the top ten . Demski is one of only seventeen women who have placed in both the Miss Teen USA and Miss USA pageants . Demski is a graduate in of the Walter Cronkite School at Arizona State University , with a degree in broadcast journalism and a minor in theater . She was a cheerleader for the Arizona Cardinals during college . After graduating she has worked as the main presenter for Destination TV , as a correspondent for the Phoenix Suns and as co-host for an NFL programme on ESPN Radio . Currently , Demski is working for the World Series of Poker held at the Rio in Las Vegas , NV as a correspondent . She has appeared in several short online videos highlighting tournament play as well as various `` featurettes '' concerning the tournament and the players on the tournament 's Web Site , World Series of Poker Web Site . Demski is also the host of The Vegas Minute , a weekly video segment which airs on KTLA in Los Angeles , California , several other American television stations , and the website Vegas.com . Demski joined Let 's Make a Deal during Season 5 of the Wayne Brady-hosted version in 2013 when Tiffany Coyne left early in the season to take maternity leave . In 2014 she appeared on an episode of The Young and the Restless . Demski has also had a few roles in film , such as the role of Alicia in The Pit and the Pendulum ( 2009 film ) and that of Reporter # 2 in Blue Lagoon : The Awakening .",
"title": ""
},
{
"docid": "Jo_Wyatt",
"text": "Joanna Louise `` Jo '' Wyatt ( born 28 September 1970 in London , England ) is an English actress and voice actress known for her voice as Little Miss Helpful , Little Miss Naughty , Little Miss Scary and Little Miss Sunshine in The Mr. Men Show . She also voiced Daisy Kribotnik in Love Soup , a woman in a bar in Extras , Natella in Bromwell High and a character in Guess with Jess . Including additional voices in Perfect Dark Zero and Dragon Quest VIII as well as narrating To Leo with Love .",
"title": ""
},
{
"docid": "De_Dhakka",
"text": "De Dhakka ( Marathi : दे धक्का ) is a Marathi film released in India in 2008 inspired by the Hollywood film Little Miss Sunshine ( 2006 ) . It was remade in Kannada as Crazy Kutumba . Arati Ankalikar-Tikekar , the play back singer of this film , received Maharashtra State Award , V Shantaram Award and Maharashtra Times award in the category of ` Best Play back singer ' .",
"title": ""
},
{
"docid": "Little_League_World_Series_1957–2000_(West_Region)",
"text": "The original West Region was a region that competed in the Little League World Series between and until it was split into a Northwest Region and a new West Region in 2001 . The West Region was inaugurated in 1957 . The Region consisted of teams from Alaska , Arizona , Northern California , Southern California , Colorado , Hawaii ( since 1962 ) , Idaho , Montana , Nevada , New Mexico , Oregon , Utah , Washington , and Wyoming . Before 1962 , Hawaiian teams competed in the Pacific Region ( see below ) . Prior to 1966 , teams from Western Canada also competed in the West Region . Little League Baseball expanded the LLWS to sixteen teams for the 2001 Little League World Series . At the same time , the original West Region was split into a new West Region ( Arizona , Northern California , Southern California , Hawaii , Nevada , New Mexico , and Utah ) and a Northwest Region ( Alaska , Colorado , Idaho , Montana , Oregon , Washington , and Wyoming ) . Colorado and New Mexico moved to the Southwest Region for the 2002 tournament . Between 2002 and 2005 , Hawaii competed in the Northwest Region and Wyoming competed in the West Region , before switching back to the original configuration in 2006 .",
"title": ""
},
{
"docid": "Steven_Christopher_Parker",
"text": "Steven Christopher Parker ( born January 8 , 1989 ) is an American actor who is best known for his role as `` Sledgehammer '' Big Wes in the 2005 film Rebound . Parker has appeared in more than a dozen feature films , including Rebound , Juno and Little Miss Sunshine . He can also be seen as a pizza delivery impostor in a late-2008 television advertisement for DiGiorno . He also had an uncredited scene on `` Blades of Glory '' for less than 5 seconds . Parker was a contestant on The Price Is Right '' on his birthday in January 2010 . He ended up getting on stage with Drew Carey . However , he did not win his game and ended up with 55 cents while spinning the Big Wheel , not good enough to make it into the Showcase . The show was broadcast on CBS on March 2 , 2010 . Parker is a 2006 graduate of Gorman High School in Gorman , California .",
"title": ""
},
{
"docid": "Crazy_Kutumba",
"text": "Crazy Kutumba is a 2010 Kannada comedy film directed by B. Ramamurthy and produced by Ravi Joshi for Luv Kush Productions banner . The story is a remake of Marathi film De Dhakka ( 2008 ) which was inspired from the Hollywood film , Little Miss Sunshine ( 2006 ) . The film features Ramesh Aravind and Ananth Nag in leading roles with Sanathini , Dhanya Rao , Jai Jagadish , Bank Janardhan and other theater artistes from North Karnataka region playing supporting roles .",
"title": ""
},
{
"docid": "Peter_Saraf",
"text": "Peter Saraf is an American film producer whose feature film credits include Adaptation ( 2002 ) , Little Miss Sunshine ( 2006 ) , Our Idiot Brother ( 2011 ) and The Kings of Summer ( 2013 ) . In 2004 , he co-founded the film production company Big Beach with Marc Turtletaub ; the two still run the company , and produce most of their films through it . Saraf is the son of the late film producer and director , Irving Saraf . Irving Saraf , who was born in Poland and raised in Israel , won an Academy Award for the documentary film , In the Shadow of the Stars , in 1991 .",
"title": ""
},
{
"docid": "Pamela_Martin_(film_editor)",
"text": "Pamela Martin is an American film and television editor with more than fifteen feature film credits commencing in 1994 . Martin was nominated for an American Cinema Editors `` Eddie '' Award for Little Miss Sunshine ( directed by Jonathan Dayton and Valerie Faris-2005 ) . For her work on The Fighter ( directed by David O. Russell-2010 ) , Martin was nominated for an Academy Award for Best Film Editing and an `` Eddie '' . Martin was also a member of the dramatic jury at the Sundance Film Festival in 2007 , and has been selected as a member of the American Cinema Editors .",
"title": ""
},
{
"docid": "Southern_Pacific_Depot",
"text": "The names Southern Pacific Depot , Southern Pacific Railroad Station , Southern Pacific Railroad Depot , and variations , apply to a number of train stations operated by the Southern Pacific Railroad . Many of these are historic and are listed on the U.S. National Register of Historic Places ( NRHP ) . Arizona : Southern Pacific Railroad Depot ( Casa Grande , Arizona ) , listed on the NRHP in Arizona Southern Pacific Railroad Depot ( Safford , Arizona ) , listed on the NRHP in Arizona Southern Pacific Freight Depot ( Yuma , Arizona ) , listed on the NRHP in Arizona Southern Pacific Railroad Depot ( Yuma , Arizona ) , listed on the NRHP in Arizona Yuma ( Amtrak station ) , at site of a former Southern Pacific Railroad Depot , in Yuma , Arizona California : 16th Street Station ( Oakland , California ) Southern Pacific Depot ( Chico , California ) , listed on the NRHP Colfax Depot , Colfax , California Danville Southern Pacific Depot , Danville , California , listed on the NRHP in California Davis ( Amtrak station ) , Davis , California , listed on the NRHP as Southern Pacific Railroad Station Southern Pacific Depot , Fillmore , California Southern Pacific Depot , Folsom , California Southern Pacific Depot ( Fresno , California ) , listed on the NRHP in California Glendale Southern Pacific Railroad Depot ( Glendale , California ) , now the Glendale Amtrak station , listed on the NRHP Goleta Depot , Goleta , California Lodi Depot , Lodi , California Southern Pacific Depot in Los Angeles , also known as Central Station Southern Pacific Depot ( Millbrae , California ) , listed on the NRHP in California Niles Depot , Fremont , California , now the Niles Depot Museum North Hollywood Depot , Los Angeles , California Palo Alto Southern Pacific Railroad Depot , now Palo Alto Station , listed on the NRHP Sacramento Valley Rail Station , Sacramento , California , listed on the NRHP as Southern Pacific Railroad Company 's Sacramento Depot Saint Helena Southern Pacific Railroad Depot , Saint Helena , California , listed on the NRHP in California Santa Susana Depot ( Simi Valley , California ) Southern Pacific Depot ( San Carlos , California ) , now San Carlos ( Caltrain station ) , listed on the NRHP Southern Pacific Depot ( San Jose , California ) , now known as Diridon Station , listed on the NRHP Southern Pacific Depot , Sanger , California Southern Pacific Train Depot ( Santa Barbara , California ) , listed on the NRHP in California Suisun-Fairfield Depot , Suisun-Fairfield , California Southern Pacific Depot , Sunol , California Southern Pacific Railroad Depot , Whittier , California , listed on the NRHP Louisiana : Southern Pacific Railroad Depot ( New Iberia , Louisiana ) , listed on the NRHP in Louisiana Oregon : Canby Depot , Canby , Oregon Eugene -- Springfield station , listed as `` Southern Pacific Passenger Depot '' , in Eugene , Oregon Lebanon Southern Pacific Railroad Depot , Lebanon , Oregon , listed on the NRHP in Oregon Medford Southern Pacific Railroad Passenger Depot , Medford , Oregon , listed on the NRHP in Oregon Southern Pacific Railroad Passenger Station and Freight House , Springfield , Oregon , listed on the NRHP in Oregon Texas : Southern Pacific Railroad Freight Depot ( Brenham , Texas ) , listed on the NRHP in Texas Southern Pacific Railroad Passenger Depot ( Brownsville , Texas ) , listed on the NRHP in Texas Southern Pacific Railroad Depot ( Nacogdoches , Texas ) , listed on the NRHP in Texas Southern Pacific Depot Historic District , San Antonio , Texas , listed on the NRHP in Texas Southern Pacific Railroad Passenger Station ( San Antonio , Texas ) , now San Antonio Station , listed on the NRHP",
"title": ""
},
{
"docid": "Writers_Guild_of_America_Awards_2006",
"text": "59th WGA Awards Presented by the Writers Guild of America , East and the Writers Guild of America , west 2007 Best Adapted Screenplay : The Departed Best Original Screenplay : Little Miss Sunshine The 59th Writers Guild of America Awards honored the best film and television writers of 2006 .",
"title": ""
},
{
"docid": "Jonathan_Dayton_and_Valerie_Faris",
"text": "Jonathan Dayton ( born July 7 , 1957 ) and Valerie Faris ( born October 20 , 1958 ) are a team of American film directors and music video directors , also husband and wife , that received critical acclaim for their feature film directorial debut , Little Miss Sunshine . Later the couple went on to direct the 2012 romantic comedy-drama Ruby Sparks , which was also met with a positive critical consensus .",
"title": ""
},
{
"docid": "Fox_Searchlight_Pictures",
"text": "Fox Searchlight Pictures is an American film distribution company within the Fox Entertainment Group , a sister company of the larger Fox studio 20th Century Fox , all owned by Rupert Murdoch 's 21st Century Fox . It specializes in North American distribution of independent and British films alongside dramedy and horror films as well as art-house and foreign films and is sometimes also involved in the financing of these films . As is the case with Fox 's television unit , all copyright notices of programming produced by a Fox-related company ( with some exceptions ) bear the copyright of the overall film studio , i.e. '' © ( respective year ) Twentieth Century Fox Film Corporation '' . Fox Searchlight 's Slumdog Millionaire , 12 Years a Slave , and Birdman have all won the Academy Award for Best Picture at the 81st Academy Awards , 86th Academy Awards , and 87th Academy Awards respectively , as well as a further 12 Academy Awards combined . Other Fox Searchlight films receiving Best Picture nominations include The Full Monty , Sideways , Little Miss Sunshine , Juno , Black Swan , 127 Hours , The Tree of Life , The Descendants , Beasts of the Southern Wild , The Grand Budapest Hotel and Brooklyn . Slumdog Millionaire is also Searchlight 's largest commercial success , with over $ 377 million ( US ) of box office receipts , against a production budget of only $ 15 million .",
"title": ""
},
{
"docid": "California_Sunshine",
"text": "The California Sunshine was an American soccer club based in Fountain Valley , California that was a member of the American Soccer League . The team was owned by Dr. Robert Everakes and his wife Alexandra , who was the general manager . Their home games were held at Chapman University in Orange , California and Eddie West Field at Santa Ana Stadium ( aka Santa Ana Bowl ) in Santa Ana , California but had exhibition games at the University of California in Riverside , California and Palm Springs Stadium in Palm Springs , California . Their first season was 1977 , but the team folded in 1981 after four seasons . The head coach was Derek Lawther . The California Sunshine Soccer Team was founded in 1977 by Warren Hoffnung ( a nuclear physicist , aerospace executive and entrepreneur -- currently CEO of MyWrapper , a software company that sells software for creating personalized candy wrappers ) and Lee Andrews ( a financial advisor ) . They acquired the Orange County , California territorial rights in the American Soccer League , the oldest U.S. professional soccer league . The commissioner of the ASL at the time was basketball great Bob Cousy and there were teams spread across the U.S. . A little known fact is that the California Sunshine approved the move of the Quicksilver to Anaheim Stadium where it was renamed the California Surf . The California Sunshine was founded with two major philosophies : To field as many American players as possible and to keep profanity off the playing field . The goal was to encourage American youth to be able to attend the matches and see how soccer could be an important part of their sports participation . In fact , all but one of the players were American .",
"title": ""
},
{
"docid": "Little_Mary_Sunshine_(1916_film)",
"text": "Little Mary Sunshine is a 1916 silent movie directed by Henry King .",
"title": ""
},
{
"docid": "Greg_Kinnear",
"text": "Gregory Buck `` Greg '' Kinnear ( born June 17 , 1963 ) is an American actor and television personality . He was nominated for an Academy Award for his role in As Good as It Gets . Kinnear has appeared in many popular films , including Sabrina , You 've Got Mail , Nurse Betty , We Were Soldiers , Little Miss Sunshine , Robots , Invincible and Green Zone , and television roles , such as Friends , Talk Soup , The Kennedys , Modern Family and Rake .",
"title": ""
},
{
"docid": "Alicyn_Packard",
"text": "Alicyn Packard ( born September 27 , 1979 ; Hanson , Massachusetts ) is an American voice actress , writer and singer nominated for a 2014 Voice Arts Award . She voices the characters Little Miss Sunshine , Little Miss Naughty , and Little Miss Whoops on the Cartoon Network animated series the The Mr. Men Show . She also stars as Alma on the Sprout network show Poppy Cat and wrote an episode of the show 's second season . She plays Toodles on The Tom and Jerry Show , and Connor and Caitlin on Olivia , and Jibanyan on Yo-kai Watch . Ms. Packard is the voice of the female blood elf in the video game World of Warcraft . She has also voiced Pericci in Star Ocean : The First Departure and the characters of Luce Valenci and Altyria Jono in Vandal Hearts : Flames of Judgment .",
"title": ""
},
{
"docid": "Save_a_Little_Sunshine",
"text": "Save a Little Sunshine is a 1938 British comedy film directed by Norman Lee and starring Dave Willis , Pat Kirkwood and Tommy Trinder .",
"title": ""
}
] |
PLAIN-1423
|
intelligence
|
[
{
"docid": "MED-4949",
"text": "Methyl mercury is a developmental neurotoxicant. Exposure results principally from consumption by pregnant women of seafood contaminated by mercury from anthropogenic (70%) and natural (30%) sources. Throughout the 1990s, the U.S. Environmental Protection Agency (EPA) made steady progress in reducing mercury emissions from anthropogenic sources, especially from power plants, which account for 41% of anthropogenic emissions. However, the U.S. EPA recently proposed to slow this progress, citing high costs of pollution abatement. To put into perspective the costs of controlling emissions from American power plants, we have estimated the economic costs of methyl mercury toxicity attributable to mercury from these plants. We used an environmentally attributable fraction model and limited our analysis to the neurodevelopmental impacts—specifically loss of intelligence. Using national blood mercury prevalence data from the Centers for Disease Control and Prevention, we found that between 316,588 and 637,233 children each year have cord blood mercury levels > 5.8 μg/L, a level associated with loss of IQ. The resulting loss of intelligence causes diminished economic productivity that persists over the entire lifetime of these children. This lost productivity is the major cost of methyl mercury toxicity, and it amounts to $8.7 billion annually (range, $2.2–43.8 billion; all costs are in 2000 US$). Of this total, $1.3 billion (range, $0.1–6.5 billion) each year is attributable to mercury emissions from American power plants. This significant toll threatens the economic health and security of the United States and should be considered in the debate on mercury pollution controls.",
"title": "Public Health and Economic Consequences of Methyl Mercury Toxicity to the Developing Brain"
},
{
"docid": "MED-5141",
"text": "Objective To examine the relation between IQ in childhood and vegetarianism in adulthood. Design Prospective cohort study in which IQ was assessed by tests of mental ability at age 10 years and vegetarianism by self-report at age 30 years. Setting Great Britain. Participants 8170 men and women aged 30 years participating in the 1970 British cohort study, a national birth cohort. Main outcome measures Self-reported vegetarianism and type of diet followed. Results 366 (4.5%) participants said they were vegetarian, although 123 (33.6%) admitted eating fish or chicken. Vegetarians were more likely to be female, to be of higher social class (both in childhood and currently), and to have attained higher academic or vocational qualifications, although these socioeconomic advantages were not reflected in their income. Higher IQ at age 10 years was associated with an increased likelihood of being vegetarian at age 30 (odds ratio for one standard deviation increase in childhood IQ score 1.38, 95% confidence interval 1.24 to 1.53). IQ remained a statistically significant predictor of being vegetarian as an adult after adjustment for social class (both in childhood and currently), academic or vocational qualifications, and sex (1.20, 1.06 to 1.36). Exclusion of those who said they were vegetarian but ate fish or chicken had little effect on the strength of this association. Conclusion Higher scores for IQ in childhood are associated with an increased likelihood of being a vegetarian as an adult.",
"title": "IQ in childhood and vegetarianism in adulthood: 1970 British cohort study"
},
{
"docid": "MED-4939",
"text": "Parkinson's disease (PD) is increasingly recognized as a neurodegenerative disorder strongly associated with environmental chemical exposures. Recent epidemiological data demonstrate that environmental risk factors may play a dominant role as compared to genetic factors in the etiopathogenesis of idiopathic Parkinson's disease. Identification of key genetic defects such as alpha-synuclein and parkin mutations in PD also underscores the important role of genetic factors in the disease. Thus, understanding the interplay between genes and environment in PD may be critical to unlocking the mysteries of this 200-year-old neurodegenerative disease. Pesticides and metals are the most common classes of environmental chemicals that promote dopaminergic degeneration. The organochlorine pesticide dieldrin has been found in human PD postmortem brain tissues, suggesting that this pesticide has potential to promote nigral cell death. Though dieldrin has been banned, humans continue to be exposed to the pesticide through contaminated dairy products and meats due to the persistent accumulation of the pesticide in the environment. This review summarizes various neurotoxic studies conducted in both cell culture and animals models following dieldrin exposure and discusses their relevance to key pathological mechanisms associated with nigral dopaminergic degeneration including oxidative stress, mitochondrial dysfunction, protein aggregation, and apoptosis.",
"title": "Dieldrin-induced neurotoxicity: relevance to Parkinson's disease pathogenesis."
},
{
"docid": "MED-4941",
"text": "Laboratory and population-based studies suggest that exposure to environmental toxicants may be one of several triggers for the development of endometriosis. We discuss evidence that modulation of the endometrial endocrine-immune interface could mechanistically link toxicant exposure to the development of this disease. Capsule Summary: Environmental toxicant exposure induces an inflammatory-like endometrial response that may promote the development of endometriosis.",
"title": "Dioxin May Promote Inflammation-Related Development of Endometriosis"
},
{
"docid": "MED-5092",
"text": "BACKGROUND: While there is a large body of data on the effects of long-chain polyunsaturated fatty acid supplementation of infant formula on visual and cognitive maturation during infancy, longterm visual and cognitive outcome data from randomized trials are scarce. AIM: To evaluate docosahexaenoic acid (DHA) and arachidonic acid (ARA)-supplementation of infant formula on visual and cognitive outcomes at 4 years of age. METHODS: Fifty-two of 79 healthy term infants who were enrolled in a single-center, double-blind, randomized clinical trial of DHA and ARA supplementation of infant formula were available for follow-up at 4 years of age. In addition, 32 breast-fed infants served as a \"gold standard\". Outcome measures were visual acuity and the Wechsler Preschool and Primary Scale of Intelligence--Revised. RESULTS: At 4 years, the control formula group had poorer visual acuity than the breast-fed group; the DHA- and DHA+ARA-supplemented groups did not differ significantly from the breast-fed group. The control formula and DHA-supplemented groups had Verbal IQ scores poorer than the breast-fed group. CONCLUSION: DHA and ARA-supplementation of infant formula supports visual acuity and IQ maturation similar to that of breast-fed infants.",
"title": "Visual acuity and cognitive outcomes at 4 years of age in a double-blind, randomized trial of long-chain polyunsaturated fatty acid-supplemented in..."
},
{
"docid": "MED-4938",
"text": "Objective To test the effect of four polychlorinated biphenyl congeners (PCB-77, PCB-105, PCB 153 and PCB 180) on expression of three adhesion markers, TGF-β1, VEGF, and type I collagen in normal human peritoneal and adhesion fibroblasts Design Cell culture study Settings University Research Laboratory Patients Primary cultures of normal peritoneal and adhesion fibroblasts were established from three patients. Interventions Fibroblasts were treated with PCB-77, PCB-105, PCB-153 or PCB-180, 20 ppm for 24 hours. Total RNA was extracted from each treatment and subjected to real-time RT/PCR. Main Outcome and Measures mRNA levels of type I collagen, VEGF and TGF-β1. Results Normal human peritoneal fibroblasts expressed type I collagen, VEGF and TGF-β1. Exposure of normal human fibroblasts to PCB-77, PCB-105, PCB-153 or PCB-180 did not affect mRNA levels of β-actin, the house keeping gene used to normalized RNA levels for the real-time RT/PCR, nor did it affect cell viability as assessed by trypan blue exclusion. PCB treatments, compared to control, resulted in no significant change for TGF-β1 or VEGF mRNA levels, in normal peritoneal and adhesion fibroblasts. In marked contrast, type I collagen mRNA levels were markedly increased in response to the brief 24 hrs exposure to each PCB, treatment each (P<0.0001) in both cell types. Conclusion The finding that PCB-77, PCB-105, PCB-153 or PCB-180 increased the expression of type I collagen in human normal peritoneal and adhesion fibroblasts is the first demonstration of involvement of organochlorines in the pathogenesis of tissue fibrosis. This may implicate organochlorine exposure as an etiologic factor in a wide variety of previously unlinked human ailments characterized by fibrosis.",
"title": "PCBs Enhance Collagen I Expression from Human Peritoneal Fibroblasts"
},
{
"docid": "MED-5093",
"text": "BACKGROUND: There are few studies reporting on docosahexaenoic acid (DHA, 22:6n-3) supplementation during pregnancy and infant cognitive function. DHA supplementation in pregnancy and infant problem solving in the first year have not been investigated. OBJECTIVE: We tested the hypothesis that infants born to women who consumed a DHA-containing functional food during pregnancy would demonstrate better problem-solving abilities and recognition memory than would infants born to women who consumed the placebo during pregnancy. DESIGN: In a double-blind, placebo-controlled, randomized trial, pregnant women consumed a DHA-containing functional food or a placebo from gestation week 24 until delivery. Study groups received DHA-containing cereal-based bars (300 mg DHA/92-kcal bar; average consumption: 5 bars/wk; n = 14) or cereal-based placebo bars (n = 15). The Infant Planning Test and Fagan Test of Infant Intelligence were administered to infants at age 9 mo. The problem-solving trial included a support step and a search step. The procedure was scored on the basis of the infant's performance on each step and on the entire problem (intention score and total intentional solutions). Scores were generated on the basis of the cumulative performance of the infant on 5 trials. RESULTS: Treatment had significant effects on the performance of problem-solving tasks: total intention score (P = 0.017), total intentional solutions (P = 0.011), and number of intentional solutions on both cloth (P = 0.008) and cover (P = 0.004) steps. There were no significant differences between groups in any measure of Fagan Test of Infant Intelligence. CONCLUSION: These data point to a benefit for problem solving but not for recognition memory at age 9 mo in infants of mothers who consumed a DHA-containing functional food during pregnancy.",
"title": "Maternal consumption of a docosahexaenoic acid-containing functional food during pregnancy: benefit for infant performance on problem-solving but n..."
},
{
"docid": "MED-5091",
"text": "BACKGROUND: Docosahexaenoic acid (DHA) is important to neural development. Whether DHA intakes are low enough in some pregnant women to impair infant development is uncertain. OBJECTIVE: We sought to determine whether DHA deficiency occurs in pregnant women and contributes to poor infant development. DESIGN: Biochemical cutoffs, dietary intakes, or developmental scores indicative of DHA deficiency are not defined. Infant development has a distribution in which an individual's potential development is unknown. This was a randomized intervention to establish a distribution of developmental scores for infants of women with DHA intakes considered to be above requirements against which to compare the development of infants of mothers consuming their usual diet. DHA (400 mg/d; n = 67) or a placebo (n = 68) was consumed by the women from 16 wk gestation until delivery. We determined maternal red blood cell ethanolamine phosphoglyceride fatty acids, dietary intakes at 16 and 36 wk gestation, and infant visual acuity at 60 d of age. RESULTS: We described an approach to identify DHA deficiency when biochemical and functional markers of deficiency are unknown. In multivariate analyses, infant visual acuity was related to sex (beta = 0.660, SE = 0.93, and odds ratio = 1.93) and maternal DHA intervention (beta = 1.215, SE = 1.64, and odds ratio = 3.37). More infant girls in the placebo than in the DHA intervention group had a visual acuity below average (P = 0.048). Maternal red blood cell ethanolamine phosphoglyceride docosatetraenoic acid was inversely related to visual acuity in boys (rho = -0.37, P < 0.05) and girls (rho = -0.48, P < 0.01). CONCLUSIONS: These studies suggest that some pregnant women in our study population were DHA-deficient.",
"title": "Essential n-3 fatty acids in pregnant women and early visual acuity maturation in term infants."
},
{
"docid": "MED-4942",
"text": "The association of 11 polychlorinated biphenyls (PCBs) with hypertension was investigated using the National Health and Nutrition Examination Survey (NHANES), 1999-2002. The unweighted number of participants assessed for hypertension ranged from 2074 to 2556 depending on the chemical(s) being analyzed. In unadjusted logistic regressions all 11 PCBs were associated with hypertension. After adjustment for age, gender, race, smoking status, body mass index, exercise, total cholesterol, and family history of coronary heart disease, seven of the 11 PCBs (PCBs 126, 74, 118, 99, 138/158, 170, and 187) were significantly associated with hypertension. The strongest adjusted associations with hypertension were found for dioxin-like PCBs 126 and 118. PCB 126>59.1 pg/g lipid adjusted had an odds ratio of 2.45 (95% CI 1.48-4.04) compared to PCB 126<or=26.1 pg/g lipid adjusted. PCB 118>27.5 ng/g lipid adjusted had an odds ratio of 2.30 (95% CI 1.29-4.08) compared to PCB 118<or=12.5 ng/g lipid adjusted. Moreover, participants with one or more elevated PCBs had an odds ratio of 1.84 (95% CI 1.25-2.70) compared to no PCBs elevated in an adjusted logistic regression. The prevalence of one or more elevated PCBs was 22.76% or 32 million of 142 million persons >or=20 years old in the non-institutionalized US population. We hypothesize that association of seven PCBs with hypertension indicates elevated PCBs are a risk factor for hypertension. What clinicians can do, given the results of this study, is limited unless the appropriate laboratory methods can be made more widely available for testing patients.",
"title": "Association of polychlorinated biphenyls with hypertension in the 1999-2002 National Health and Nutrition Examination Survey."
},
{
"docid": "MED-4948",
"text": "The southeastern United States, and in particular the coastal areas along the Gulf of Mexico (Gulf Coast) in Florida, experience some of the highest levels of mercury deposition in the country. Although the State of Florida's coastal border is among the longest in the United States, and the State has issued fish consumption advisories due to mercury on multiple fish species, few data have been systematically collected to assess mercury levels in the human population of the state or to assess the efficacy of the consumption advisories. Because of the generally high rate of seafood consumption among coastal populations, the human population in the Florida Panhandle, near Pensacola, FL is potentially exposed to elevated levels of mercury. In the present study, we analyzed hair mercury levels in women of child-bearing age (16-49 years) who had resided near Pensacola, FL for at least 1 year. We also surveyed the fish consumption practices of the cohort and evaluated awareness of the Florida Fish Consumption Advisory. Hair mercury levels were significantly higher in women who consumed fish within the 30 days prior to sampling (p<0.05) and in those women who were unaware of the consumption advisory (p<0.05). Only 31% of the women reported knowledge of the consumption advisory and pregnant women exhibited lower awareness of the advisory than non-pregnant women. The data suggest that public health interventions such as education and fish advisories have not reached the majority of women in the counties surrounding Pensacola who are most at risk from consumption of fish with high levels of mercury.",
"title": "Mercury levels and fish consumption practices in women of child-bearing age in the Florida Panhandle."
},
{
"docid": "MED-4622",
"text": "We developed a probabilistic model to characterize the plausible distribution of health and economic benefits that would accrue to the U.S. population following reduction of methyl mercury (MeHg) exposure. MeHg, a known human developmental neurotoxicant, may increase fatal heart attack risks. Model parameters reflect current understanding of the relationships between MeHg intake, health risks, and societal valuation of these risks. The expected monetary value of the annual health benefits generated by a 10% reduction in U.S. population exposure to MeHg for one year is $860 million; 80% of this is associated with reductions in fatal heart attacks and the remainder with IQ gains. The plausible distribution of the benefits is quite broad with 5th and 95th percentile estimates of approximately $50 million and $3.5 billion, respectively. The largest source of uncertainty is whether epidemiological associations between MeHg exposure and fatal heart attacks reflect causality. The next largest sources of uncertainty concern the slope of the relationship between maternal MeHg exposure and reduced intelligence among children and whether this relationship exhibits a threshold. Our analysis suggests that the possible causal relationship between MeHg exposure and fatal heart attacks should be better characterized, using additional epidemiological studies and formally elicited expert judgment.",
"title": "A probabilistic characterization of the health benefits of reducing methyl mercury intake in the United States."
},
{
"docid": "MED-4940",
"text": "Dioxins are known to affect infant growth and neurodevelopment in both humans and animals. In this study, we examined the relationship between neonatal head circumference, which is related to fetal brain development, and the concentration of dioxins in breast milk as an indicator of maternal exposure. A total of 42 milk samples were obtained on the fifth to eighth postpartum day from mothers in Japan exposed to dioxins in the environment. The levels of seven dioxins and 10 furan isomers were measured in each milk sample using an HR-GC/MS system. The relationships between the concentration of each dioxin isomer and newborn size, including head circumference, were then investigated after adjustment for confounding factors. The concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic dioxin isomer, negatively correlated with newborn head circumference, even after adjustment for gestational age, infant sex, parity and other confounding factors. However, there were no significant relationships between the concentration of other dioxin and furan isomers in maternal breast milk and infant height, weight and chest circumference at birth. These facts suggested that fetal brain development might be influenced by maternal exposure to TCDD in the environment.",
"title": "2,3,7,8-Tetrachlorodibenzo-p-dioxin in maternal breast milk and newborn head circumference."
},
{
"docid": "MED-4947",
"text": "The focus of the present study was on the relationship between Hong Kong male subfertility and fish consumption. Mercury concentrations found in the hair of 159 Hong Kong males aged 25-72 (mean age = 37 years) was positively correlated with age and was significantly higher in Hong Kong subjects than in European and Finnish subjects (1.2 and 2.1 ppm, respectively). Mercury in the hair of 117 subfertile Hong Kong males (4.5 ppm, P < 0.05) was significantly higher than mercury levels found in hair collected from 42 fertile Hong Kong males (3.9 ppm). Subfertile males had approx. 40% more mercury in their hair than fertile males of similar age. Although there were only 35 female subjects, they had significantly lower levels of hair mercury than males in similar age groups. Overall, males had mercury levels that were 60% higher than females. Hair samples collected from 16 vegetarians living in Hong Kong (vegans that had consumed no fish, shellfish or meat for at least the last 5 years) had very low levels of mercury. Their mean hair mercury concentration was only 0.38 ppm.",
"title": "Hong Kong male subfertility links to mercury in human hair and fish."
}
] |
[
{
"docid": "MED-1166",
"text": "Context: Organophosphate (OP) pesticides are neurotoxic at high doses. Few studies have examined whether chronic exposure at lower levels could adversely affect children’s cognitive development. Objective: We examined associations between prenatal and postnatal exposure to OP pesticides and cognitive abilities in school-age children. Methods: We conducted a birth cohort study (Center for the Health Assessment of Mothers and Children of Salinas study) among predominantly Latino farmworker families from an agricultural community in California. We assessed exposure to OP pesticides by measuring dialkyl phosphate (DAP) metabolites in urine collected during pregnancy and from children at 6 months and 1, 2, 3.5, and 5 years of age. We administered the Wechsler Intelligence Scale for Children, 4th edition, to 329 children 7 years of age. Analyses were adjusted for maternal education and intelligence, Home Observation for Measurement of the Environment score, and language of cognitive assessment. Results: Urinary DAP concentrations measured during the first and second half of pregnancy had similar relations to cognitive scores, so we used the average of concentrations measured during pregnancy in further analyses. Averaged maternal DAP concentrations were associated with poorer scores for Working Memory, Processing Speed, Verbal Comprehension, Perceptual Reasoning, and Full-Scale intelligence quotient (IQ). Children in the highest quintile of maternal DAP concentrations had an average deficit of 7.0 IQ points compared with those in the lowest quintile. However, children’s urinary DAP concentrations were not consistently associated with cognitive scores. Conclusions: Prenatal but not postnatal urinary DAP concentrations were associated with poorer intellectual development in 7-year-old children. Maternal urinary DAP concentrations in the present study were higher but nonetheless within the range of levels measured in the general U.S. population.",
"title": "Prenatal Exposure to Organophosphate Pesticides and IQ in 7-Year-Old Children"
},
{
"docid": "MED-2904",
"text": "Background Prenatal exposure to mercury has been associated with adverse childhood neurologic outcomes in epidemiologic studies. Dose–response information for this relationship is useful for estimating benefits of reduced mercury exposure. Objectives We estimated a dose–response relationship between maternal mercury body burden and subsequent childhood decrements in intelligence quotient (IQ), using a Bayesian hierarchical model to integrate data from three epidemiologic studies. Methods Inputs to the model consist of dose–response coefficients from studies conducted in the Faroe Islands, New Zealand, and the Seychelles Islands. IQ coefficients were available from previous work for the latter two studies, and a coefficient for the Faroe Islands study was estimated from three IQ subtests. Other tests of cognition/achievement were included in the hierarchical model to obtain more accurate estimates of study-to-study and end point–to–end point variability. Results We find a central estimate of −0.18 IQ points (95% confidence interval, −0.378 to −0.009) for each parts per million increase of maternal hair mercury, similar to the estimates for both the Faroe Islands and Seychelles studies, and lower in magnitude than the estimate for the New Zealand study. Sensitivity analyses produce similar results, with the IQ coefficient central estimate ranging from −0.13 to −0.25. Conclusions IQ is a useful end point for estimating neurodevelopmental effects, but may not fully represent cognitive deficits associated with mercury exposure, and does not represent deficits related to attention and motor skills. Nevertheless, the integrated IQ coefficient provides a more robust description of the dose–response relationship for prenatal mercury exposure and cognitive functioning than results of any single study.",
"title": "Dose–Response Relationship of Prenatal Mercury Exposure and IQ: An Integrative Analysis of Epidemiologic Data"
},
{
"docid": "MED-3026",
"text": "Background Prenatal exposure to mercury has been associated with adverse childhood neurologic outcomes in epidemiologic studies. Dose–response information for this relationship is useful for estimating benefits of reduced mercury exposure. Objectives We estimated a dose–response relationship between maternal mercury body burden and subsequent childhood decrements in intelligence quotient (IQ), using a Bayesian hierarchical model to integrate data from three epidemiologic studies. Methods Inputs to the model consist of dose–response coefficients from studies conducted in the Faroe Islands, New Zealand, and the Seychelles Islands. IQ coefficients were available from previous work for the latter two studies, and a coefficient for the Faroe Islands study was estimated from three IQ subtests. Other tests of cognition/achievement were included in the hierarchical model to obtain more accurate estimates of study-to-study and end point–to–end point variability. Results We find a central estimate of −0.18 IQ points (95% confidence interval, −0.378 to −0.009) for each parts per million increase of maternal hair mercury, similar to the estimates for both the Faroe Islands and Seychelles studies, and lower in magnitude than the estimate for the New Zealand study. Sensitivity analyses produce similar results, with the IQ coefficient central estimate ranging from −0.13 to −0.25. Conclusions IQ is a useful end point for estimating neurodevelopmental effects, but may not fully represent cognitive deficits associated with mercury exposure, and does not represent deficits related to attention and motor skills. Nevertheless, the integrated IQ coefficient provides a more robust description of the dose–response relationship for prenatal mercury exposure and cognitive functioning than results of any single study.",
"title": "Dose–Response Relationship of Prenatal Mercury Exposure and IQ: An Integrative Analysis of Epidemiologic Data"
},
{
"docid": "MED-1681",
"text": "BACKGROUND: Previous studies have examined individual dietary and lifestyle factors in relation to type 2 diabetes, but the combined effects of these factors are largely unknown. METHODS: We followed 84,941 female nurses from 1980 to 1996; these women were free of diagnosed cardiovascular disease, diabetes, and cancer at base line. Information about their diet and lifestyle was updated periodically. A low-risk group was defined according to a combination of five variables: a bodymass index (the weight in kilograms divided by the square of the height in meters) of less than 25; a diet high in cereal fiber and polyunsaturated fat and low in trans fat and glycemic load (which reflects the effect of diet on the blood glucose level); engagement in moderate-to-vigorous physical activity for at least half an hour per day; no current smoking; and the consumption of an average of at least half a drink of an alcoholic beverage per day. RESULTS: During 16 years of follow-up, we documented 3300 new cases of type 2 diabetes. Overweight or obesity was the single most important predictor of diabetes. Lack of exercise, a poor diet, current smoking, and abstinence from alcohol use were all associated with a significantly increased risk of diabetes, even after adjustment for the body-mass index. As compared with the rest of the cohort, women in the low-risk group (3.4 percent of the women) had a relative risk of diabetes of 0.09 (95 percent confidence interval, 0.05 to 0.17). A total of 91 percent of the cases of diabetes in this cohort (95 percent confidence interval, 83 to 95) could be attributed to habits and forms of behavior that did not conform to the low-risk pattern. CONCLUSIONS: Our findings support the hypothesis that the vast majority of cases of type 2 diabetes could be prevented by the adoption of a healthier lifestyle.",
"title": "Diet, lifestyle, and the risk of type 2 diabetes mellitus in women."
},
{
"docid": "MED-5325",
"text": "Objective Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores. Design Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Setting Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire. Subjects Five hundred white subjects representing the AHS-2 cohort. Results Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β =−6·8, P<0·05 and β = −6·9, P<0·001). Findings for lacto-ovo vegetarians (β = −9·1, P<0·001 and β = −5·8, P<0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI. Conclusions We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.",
"title": "Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2)"
},
{
"docid": "MED-2723",
"text": "Rising prevalence of obesity is a worldwide health concern because excess weight gain within populations forecasts an increased burden from several diseases, most notably cardiovascular diseases, diabetes, and cancers. In this report, we used a simulation model to project the probable health and economic consequences in the next two decades from a continued rise in obesity in two ageing populations--the USA and the UK. These trends project 65 million more obese adults in the USA and 11 million more obese adults in the UK by 2030, consequently accruing an additional 6-8·5 million cases of diabetes, 5·7-7·3 million cases of heart disease and stroke, 492,000-669,000 additional cases of cancer, and 26-55 million quality-adjusted life years forgone for USA and UK combined. The combined medical costs associated with treatment of these preventable diseases are estimated to increase by $48-66 billion/year in the USA and by £1·9-2 billion/year in the UK by 2030. Hence, effective policies to promote healthier weight also have economic benefits. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Health and economic burden of the projected obesity trends in the USA and the UK."
},
{
"docid": "MED-4436",
"text": "The consumption of meat and other foods of animal origin is a risk factor for several types of cancer, but the results for lymphomas are inconclusive. Therefore, we examined these associations among 411,097 participants of the European Prospective Investigation into Cancer and Nutrition. During a median follow-up of 8.5 years, 1,334 lymphomas (1,267 non-Hodgkin lymphoma (NHL) and 67 Hodgkin lymphomas) were identified. Consumption of red and processed meat, poultry, milk and dairy products was assessed by dietary questionnaires. Cox proportional hazard regression was used to evaluate the association of the consumption of these food groups with lymphoma risk. Overall, the consumption of foods of animal origin was not associated with an increased risk of NHLS or HL, but the associations with specific subgroups of NHL entities were noted. A high intake of processed meat was associated with an increased risk of B-cell chronic lymphocytic leukemia (BCLL) [relative risk (RR) per 50 g intake = 1.31, 95% confidence interval (CI) 1.06-1.63], but a decreased risk of follicular lymphomas (FL) (RR = 0.58; CI 0.38-0.89). A high intake of poultry was related to an increased risk of B-cell lymphomas (RR = 1.22; CI 1.05-1.42 per 10 g intake), FL (RR = 1.65; CI 1.18-2.32) and BCLL (RR = 1.54; CI 1.18-2.01) in the continuous models. In conclusion, no consistent associations between red and processed meat consumption and lymphoma risk were observed, but we found that the consumption of poultry was related to an increased risk of B-cell lymphomas. Chance is a plausible explanation of the observed associations, which need to be confirmed in further studies.",
"title": "Consumption of meat and dairy and lymphoma risk in the European Prospective Investigation into Cancer and Nutrition."
},
{
"docid": "MED-2844",
"text": "OBJECTIVE It is important to identify modifiable factors that may lower gestational diabetes mellitus (GDM) risk. Dietary iron is of particular interest given that iron is a strong prooxidant, and high body iron levels can damage pancreatic β-cell function and impair glucose metabolism. The current study is to determine if prepregnancy dietary and supplemental iron intakes are associated with the risk of GDM. RESEARCH DESIGN AND METHODS A prospective study was conducted among 13,475 women who reported a singleton pregnancy between 1991 and 2001 in the Nurses’ Health Study II. A total of 867 incident GDM cases were reported. Pooled logistic regression was used to estimate the relative risk (RR) of GDM by quintiles of iron intake controlling for dietary and nondietary risk factors. RESULTS Dietary heme iron intake was positively and significantly associated with GDM risk. After adjusting for age, BMI, and other risk factors, RRs (95% CIs) across increasing quintiles of heme iron were 1.0 (reference), 1.11 (0.87–1.43), 1.31 (1.03–1.68), 1.51 (1.17–1.93), and 1.58 (1.21–2.08), respectively (P for linear trend 0.0001). The multivariate adjusted RR for GDM associated with every 0.5-mg per day of increase in intake was 1.22 (1.10–1.36). No significant associations were observed between total dietary, nonheme, or supplemental iron intake and GDM risk. CONCLUSIONS These findings suggest that higher prepregnancy intake of dietary heme iron is associated with an increased GDM risk.",
"title": "A Prospective Study of Prepregnancy Dietary Iron Intake and Risk for Gestational Diabetes Mellitus"
},
{
"docid": "MED-5006",
"text": "We projected future prevalence and BMI distribution based on national survey data (National Health and Nutrition Examination Study) collected between 1970s and 2004. Future obesity-related health-care costs for adults were estimated using projected prevalence, Census population projections, and published national estimates of per capita excess health-care costs of obesity/overweight. The objective was to illustrate potential burden of obesity prevalence and health-care costs of obesity and overweight in the United States that would occur if current trends continue. Overweight and obesity prevalence have increased steadily among all US population groups, but with notable differences between groups in annual increase rates. The increase (percentage points) in obesity and overweight in adults was faster than in children (0.77 vs. 0.46-0.49), and in women than in men (0.91 vs. 0.65). If these trends continue, by 2030, 86.3% adults will be overweight or obese; and 51.1%, obese. Black women (96.9%) and Mexican-American men (91.1%) would be the most affected. By 2048, all American adults would become overweight or obese, while black women will reach that state by 2034. In children, the prevalence of overweight (BMI >/= 95th percentile, 30%) will nearly double by 2030. Total health-care costs attributable to obesity/overweight would double every decade to 860.7-956.9 billion US dollars by 2030, accounting for 16-18% of total US health-care costs. We continue to move away from the Healthy People 2010 objectives. Timely, dramatic, and effective development and implementation of corrective programs/policies are needed to avoid the otherwise inevitable health and societal consequences implied by our projections .",
"title": "Will all Americans become overweight or obese? estimating the progression and cost of the US obesity epidemic."
},
{
"docid": "MED-4051",
"text": "The food mutagens IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) are heterocyclic amines (HCA), generated when heating proteinaceous food. This study investigates the protective potential of the flavonoids quercetin (Q) and rutin (R) against oxidative stress induced in vitro by IQ and PhIP in lymphocytes from healthy individuals and untreated, newly diagnosed colon cancer patients using the Comet assay. In the presence of up to 500μM Q and R, the DNA damage resulting from a high dose of PhIP (75μM) or IQ (150μM) was significantly reduced (P<0.001) to levels comparable to six times lower IQ or 7.5 times lower PhIP doses. Lymphocytes from colon cancer patients had greater baseline DNA damage than those from healthy individuals (P<0.01) and this higher level of damage was also observed throughout in vitro treatment. Except for the >50years of age group and male gender, confounding factors such as smoking, drinking and/or dietary habits were not found to be significant. In conclusion, flavonoids reduced oxidative stress caused by food mutagens in vitro in lymphocytes of healthy individuals and colon cancer patients. Thus, dietary supplementation with flavonoid-rich vegetables and fruits may prove very effective in protecting against oxidative stress. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "The protective effect of the flavonoids on food-mutagen-induced DNA damage in peripheral blood lymphocytes from colon cancer patients."
},
{
"docid": "MED-1331",
"text": "Many changes in diet and in physical activity are occurring simultaneously in the developing world. These diet shifts include large increases in energy density, in the proportion of the population consuming a high fat diet and in animal product intake. Animal source foods (ASF) play a major role in these diet shifts. This article documents the large shifts in the composition of diets and obesity across the developing world and notes that these changes are accelerating. Using China as a case study, evidence of the speeding up of this process is presented in descriptive and more rigorous dynamic longitudinal analysis. The implications of these changes for dietary and obesity patterns and cardiovascular disease are great. Indeed, developing countries are at a point where the prevalence of obesity is greater than that of undernutrition and concerns related to intake of saturated fat and energy imbalance must be considered more seriously by the agriculture sector. Current agriculture development policy in many developing countries focuses on livestock promotion and does not consider the potential adverse health consequences of this strategy. Although linkages between ASF intake and obesity cannot be established as clearly as they are for high ASF intakes, heart disease and cancer, the potential adverse health effects linked with an increased ASF intake should no longer be ignored.",
"title": "Dynamics of the nutrition transition toward the animal foods sector in China and its implications: a worried perspective."
},
{
"docid": "MED-2673",
"text": "Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.",
"title": "Determination of microbial transglutaminase in meat and meat products."
},
{
"docid": "MED-4239",
"text": "BACKGROUND: Prostate cancer is the most common solid-tumor cancer in US males but is rare in Asian males. When Asian men adopt the US lifestyle, clinical prostate cancer increases greatly. Epidemiological data from men in the US indicate that regular activity may reduce the risk for prostate cancer. METHODS: Serum was obtained from three groups of similar-aged men, Control, Diet and Exercise, and Exercise alone were used to stimulate LNCaP cells in culture. Growth and apoptosis of tumor cells were measured. Serum samples were also used to measure insulin, IGF-1, IGFBP-1. RESULTS: The Diet and Exercise and the Exercise alone groups had lower serum insulin and IGF-1 but higher IGFBP-1 compared to Controls. LNCaP cell growth was reduced in both groups compared to Control and there was a major increase in apoptosis of tumor cells. CONCLUSIONS: A low-fat diet and/or intensive exercise results in change in serum hormones and growth factors in vivo that can reduce growth and induce apoptosis of LNCaP prostate tumor cells in vitro. Copyright 2003 Wiley-Liss, Inc.",
"title": "A low-fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro."
},
{
"docid": "MED-2248",
"text": "The consequences of a change from a mixed to a lactovegetarian diet for 12 mo on trace element concentrations in plasma, hair, urine, and feces were studied in 16 women and 4 men. After the diet shift, intakes of zinc and magnesium did not change but that of selenium decreased by 40%. Three months after the diet shift, plasma and hair concentrations of zinc, copper, and selenium had decreased but those of magnesium had increased and the concentrations of mercury, lead, and cadmium in hair were lower. Also, the excretion of zinc, copper, and magnesium in urine, and that of selenium in urine and feces had decreased. Only small changes occurred during the remaining lactovegetarian-diet period. Three years later trace element concentrations had reverted towards baseline concentrations; copper values were similar to baseline concentrations but data for magnesium were slightly higher, and more complex patterns were observed for zinc and selenium. It is concluded that a shift to a lactovegetarian diet changes trace element status.",
"title": "Trace element status in healthy subjects switching from a mixed to a lactovegetarian diet for 12 mo."
},
{
"docid": "MED-4073",
"text": "The cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces tumours of the breast, colon and prostate in rats. Here we show that in addition to its well-established genotoxicity, which can be detected at concentrations >10(-6) M, PhIP is also oestrogenic. In COS-1 cells transiently transfected with an oestrogen-responsive reporter gene, PhIP (10(-10)-10(-6) M) mediated transcription through oestrogen receptor (ER) alpha, but not ER-beta, and inhibition by the pure ER antagonist ICI 182 780 demonstrated a requirement for a functional ER. In contrast, the structurally related food-derived carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) failed to induce reporter gene transcription. Additionally, we show that in a hormonally responsive breast cancer cell line (MCF-7 cells), PhIP induced transcriptional activation using endogenously expressed ER. Examination of the genotoxic potential of PhIP using a model mammalian cell mutation assay (hprt(-) locus) demonstrated that the genetic toxicology of PhIP was readily detectable, but separate, in terms of effective concentration, from its oestrogenic activity. To determine whether the oestrogenicity of PhIP could mediate oestrogen-dependent responses such as cell growth, we examined the growth of hormonally responsive cells (MCF-7 cells). We show that PhIP can stimulate cell proliferation and, again, this was dependent upon a functional ER. Using ligand blotting, we further show that PhIP can stimulate the expression of progesterone receptor (PR-A and PR-B) and c-MYC and activate the MAPK signal transduction pathway. These responses were similar to that produced by oestradiol, in terms of temporal aspects, potency and a requirement for a functional ER. Each of these dose-dependent mitogenic responses occurred at concentrations of PhIP ( approximately 10(-9)-10(-11)M) that are likely to be equivalent to systemic human exposure via consumption of cooked meat. Thus PhIP can induce cellular responses that encompass altered gene expression and mitogenesis. We suggest that the combination of genetic toxicology and oestrogen-like promotion of genomic and cellular events provide a mechanism for the tissue-specific tumorigenicity of this compound.",
"title": "The cooked food derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine is a potent oestrogen: a mechanistic basis for its tissue-speci..."
},
{
"docid": "MED-4197",
"text": "Human diet may contain many mutagenic or carcinogenic aromatic compounds as well as some beneficial physiologically active dietary components, especially plant food phytochemicals, which act as mutagenesis or carcinogenesis inhibitors. This study compared the binding properties of natural compounds in the human diet (caffeine, theophylline, theobromine, and resveratrol) with a water-soluble derivative of chlorophyll to bind to acridine orange, a known mutagen. An analysis was conducted to determine which substances were effective binding agents and may thus be useful in prevention of chemical-induced mutagenesis and carcinogenesis. Data indicated that in order to bind 50% of the mutagen in a complex, less than twice the concentration of chlorophyllin was needed, the resveratrol concentration was 20-fold higher, while a 1000-fold or even 10,000-fold excess of xanthines were required to bind acridine orange.",
"title": "Natural compounds in the human diet and their ability to bind mutagens prevents DNA-mutagen intercalation."
},
{
"docid": "MED-4000",
"text": "Coconut oil is a common edible oil in many countries, and there is mixed evidence for its effects on lipid profiles and cardiovascular disease risk. Here we examine the association between coconut oil consumption and lipid profiles in a cohort of 1,839 Filipino women (age 35–69 years) participating in the Cebu Longitudinal Health and Nutrition Survey, a community based study in Metropolitan Cebu City. Coconut oil intake was measured as individual coconut oil intake calculated using two 24-hour dietary recalls (9.54 ± 8.92 grams). Cholesterol profiles were measured in plasma samples collected after an overnight fast. Mean lipid values in this sample were total cholesterol (TC) (186.52 ± 38.86 mg/dL), high density lipoprotein cholesterol (HDL-c) (40.85 ± 10.30 mg/dL), low density lipoprotein cholesterol (LDL-c) (119.42 ± 33.21 mg/dL), triglycerides (130.75 ± 85.29 mg/dL) and the TC/HDL ratio (4.80 ± 1.41). Linear regression models were used to estimate the association between coconut oil intake and each plasma lipid outcome after adjusting for total energy intake, age, body mass index (BMI), number of pregnancies, education, menopausal status, household assets and urban residency. Dietary coconut oil intake was positively associated with HDL-c levels.",
"title": "Coconut oil predicts a beneficial lipid profile in pre-menopausal women in the Philippines"
},
{
"docid": "MED-1621",
"text": "Except for conflicting evidence about coffee and risk of coronary disease, coffee and tea are not linked to major causes of death. Because of widespread use of both beverages and limitations of prior studies, concern persists. Using Cox models (ten covariates) we studied relations in 128,934 persons to 4501 subsequent deaths. Except for slightly increased risk from acute myocardial infarction among heavier (> or = 4 cups/d) coffee users (relative risk versus nondrinkers = 1.4, 95% confidence interval = 1.0 to 1.9, P = 0.07), there was no increased risk of mortality for all deaths (relative risk per cup of coffee per day = 0.99, 95% confidence interval = 0.97 to 1.01; relative risk per cup of tea per day = 0.98, 95% confidence interval = 0.96 to 1.00) or major causes in adjusted analyses. Coffee was related to lower risk of liver cirrhosis death (relative risk per cup of coffee per day = 0.77, 95% confidence interval = 0.67 to 0.89). Use of both beverages was related to a lower risk of suicide, progressively lower at higher coffee intake (relative risk per cup of coffee per day = 0.87, 95% confidence interval = 0.77 to 0.98). We conclude that coffee and tea have no overall relation to mortality risk. If coffee increases coronary risk, this is balanced by an unexplained lower risk of other conditions, notably cirrhosis and suicide.",
"title": "Coffee, tea, and mortality."
},
{
"docid": "MED-3138",
"text": "Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.",
"title": "Perceptions of flatulence from bean consumption among adults in 3 feeding studies"
},
{
"docid": "MED-3563",
"text": "In developing countries like India, occurrence of Human papillomavirus (HPV) in cervical cancer as well as in the asymptomatic population was observed to be very high. Studies on HPV prevalence have been conducted in different parts of the country but no data were available from the eastern region of Uttar Pradesh (UP). The present study aimed to determine the status of HPV prevalence and its association with different socio-demographic factors in this population. Prevalence of HPV was investigated in a total of 2424 cervical scrape samples of asymptomatic women. Primer sets from L1 consensus region of viral genome were used to detect the presence of HPV, and the positive samples were genotyped by sequencing. Univariate binary logistic regression analysis was used to evaluate association of socio-demographic factors with HPV. 9.9% of the clinically asymptomatic women were found to be infected with HPV comprising 26 different genotypes. Among HPV-positive women, 80.8% showed single infection, while 15.4% harboured multiple infections. HPV-16 (63.7%) was the most prevalent, followed by HPV-31 (6.7%), HPV-6 (5.4%), HPV-81 (4.6%) and HPV-33 (4.2%). Significant association of HPV with non-vegetarian diet (P less than 0.05) and rural residential areas (P less than 0.01) were observed. High prevalence of HPV-16 in asymptomatic women of this population, a frequency comparable to invasive cervical cancers, highlights an urgent need for a therapeutic HPV vaccine covering HPV-16 and other high-risk types to provide protection against the disease.",
"title": "High prevalence of oncogenic HPV-16 in cervical smears of asymptomatic women of eastern Uttar Pradesh, India: a population-based study."
},
{
"docid": "MED-5064",
"text": "To find out if the cancer protective effects of Brussels sprouts seen in epidemiological studies are due to protection against DNA-damage, an intervention trial was conducted in which the impact of vegetable consumption on DNA-stability was monitored in lymphocytes with the comet assay. After consumption of the sprouts (300 g/p/d, n = 8), a reduction of DNA-migration (97%) induced by the heterocyclic aromatic amine 2-amino-1-methyl-6-phenyl-imidazo-[4,5-b]pyridine (PhIP) was observed whereas no effect was seen with 3-amino-1-methyl-5H-pyrido[4,3-b]-indole (Trp-P-2). This effect protection may be due to inhibition of sulfotransferase 1A1, which plays a key role in the activation of PhIP. In addition, a decrease of the endogenous formation of oxidized bases was observed and DNA-damage caused by hydrogen peroxide was significantly (39%) lower after the intervention. These effects could not be explained by induction of antioxidant enzymes glutathione peroxidase and superoxide dismutase, but in vitro experiments indicate that sprouts contain compounds, which act as direct scavengers of reactive oxygen species. Serum vitamin C levels were increased by 37% after sprout consumption but no correlations were seen between prevention of DNA-damage and individual alterations of the vitamin levels. Our study shows for the first time that sprout consumption leads to inhibition of sulfotransferases in humans and to protection against PhIP and oxidative DNA-damage.",
"title": "Consumption of Brussels sprouts protects peripheral human lymphocytes against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and oxidative ..."
},
{
"docid": "MED-4412",
"text": "BACKGROUND & AIMS: The aim of this study was to investigate whether nutritional risk factors, especially black tea consumptions, are inversely associated with the development of chronic obstructive pulmonary disease (COPD) in male smokers. METHODS: Forty male smokers with clinical diagnosis of COPD (Group-I (GI)) and 36 healthy smokers without COPD (Group-II (GII)) were included in this study. We compared the dietary habits and food intakes of the two groups using an adaptation of the Arizona Food Frequency Questionnaire (AFFQ). Question form included a list of 65 food items formed from five main food groups (grain, meat and alternatives, dairy products, vegetables-fruits and fat) and 25 dietary habits. The data were evaluated by binary logistic regression analysis, receiver operating characteristic (ROC) curve, Kolmogorov-Smirnov, Student's t, Mann-Whitney, and Chi-square tests. RESULTS: When both groups compared, black tea consumptions (GI-700ml; GII-1600ml (OR: 0.635, P<0.001)), vegetable fruits scores (GI-54.30; GII-63.81 (OR: 0.863, P<0.001)), regularly breakfast habit (GI-24 patients; GII-36 cases (OR: 0.549, P<0.001)) and eating salty (GI-22 patients; GII-5 cases (P<0.001)) made significant differences. In ROC curves, the area under the curve of black tea (0.898 (95% CI: 0.819-0.977) and vegetables-fruits (0.833 (95% CI: 0.727-0.938) provided high accuracy to distinguish between COPD group and controls (P<0.001). CONCLUSIONS: High intakes of black tea and vegetables-fruits consumptions may be protecting male smokers from developing COPD.",
"title": "Nutritional risk factors for the development of chronic obstructive pulmonary disease (COPD) in male smokers."
},
{
"docid": "MED-857",
"text": "Individual-based studies that investigated the relation between dietary alpha-linolenic acid (ALA) intake and prostate cancer risk have shown inconsistent results. We carried out a meta-analysis of prospective studies to examine this association. We systematically searched studies published up to December 2008. Log relative risks (RRs) were weighted by the inverse of their variances to obtain a pooled estimate with its 95% confidence interval (CI). We identified five prospective studies that met our inclusion criteria and reported risk estimates by categories of ALA intake. Comparing the highest to the lowest ALA intake category, the pooled RR was 0.97 (95% CI:0.86-1.10) but the association was heterogeneous. Using the reported numbers of cases and non-cases in each category of ALA intake, we found that subjects who consumed more than 1.5 g/day of ALA compared with subjects who consumed less than 1.5 g/day had a significant decreased risk of prostate cancer: RR = 0.95 (95% CI:0.91-0.99). Divergences in results could partly be explained by differences in sample sizes and adjustment but they also highlight limits in dietary ALA assessment in such prospective studies. Our findings support a weak protective association between dietary ALA intake and prostate cancer risk but further research is needed to conclude on this question.",
"title": "Prospective studies of dietary alpha-linolenic acid intake and prostate cancer risk: a meta-analysis."
},
{
"docid": "MED-1042",
"text": "The human colon is still a relatively unknown viscus, especially concerning its motor activity. However, in recent years, techniques have been perfected that allow a better understanding of colonic motility, especially through prolonged recording periods. In this way, it has been demonstrated that the viscus contracts according to a circadian trend, is responsive to physiological stimuli (meals, sleep), and features high amplitude, propulsive contractions that are part of the complex dynamic of the defecatory process. These physiological properties and their alterations in patients with chronic idiopathic constipation are reviewed in this article.",
"title": "Colonic motility in man: features in normal subjects and in patients with chronic idiopathic constipation."
},
{
"docid": "MED-5224",
"text": "Dry-eye syndrome (DES) is a multifactorial disease affecting millions of individuals worldwide. Various factors, including age, hormonal status, genetics, sex, immune status, innervation status, nutrition, pathogens, and environmental stress, can alter the cellular and molecular structure or function of components of the ocular surface system. The resulting imbalance increases susceptibility to desiccation and epithelial damage, leading to a vicious circle in which inflammation amplifies and sustains further damage by chronic deregulation of the system. Lubricating agents and steroids have been used as treatment options. However, as the causes of the disease become better elucidated, the more chemically complex cyclosporine A has become an increasingly useful treatment option and in the United States is currently the only Food and Drug Administration (FDA)-approved prescription drug for the treatment of dry eye. The safety and efficacy of cyclosporine have been shown in numerous studies.",
"title": "Safety and Efficacy of Cyclosporine in the Treatment of Chronic Dry Eye"
},
{
"docid": "MED-3129",
"text": "BRCA1 mutations have been associated with hereditary breast cancer only. Recent studies indicate that a subgroup of sporadic breast cancer might also be associated with reduction in BRCA1 mRNA levels and protein expression. However, the mechanism of reduced mRNA and protein expression is yet not fully elucidated. This study aims to assess BRCA1 protein expression and the role of BRCA1 promoter methylation in sporadic breast cancer in North Indian population and to correlate these with known prognostic factors and molecular profiles of breast cancer. BRCA1 protein expression was normal (>50 % tumour cells) in 41 (43 %) cases, reduced (20-50 % tumour cells) in 33 (35 %) cases and absent/markedly reduced (<20 % tumour cells) in 21 (22.1 %) cases. Cases which were negative for BRCA1 protein were more frequently positive for basal markers (29 versus 5 %) and were more often ER-negative (62 versus 39 %) than BRCA1-positive tumours. Methylation of BRCA1 promoter region was seen in 11/45 cases (24 %). All 11 cases showing BRCA1 methylation had absent (eight cases) or reduced (three cases) BRCA1 protein expression. BRCA1 protein-negative tumours were more frequently basal marker-positive and ER-negative, highlighting the 'BRCAness' of sporadic breast cancer with loss of BRCA1 protein expression through promoter hypermethylation similar to hereditary breast cancer with BRCA1 mutations. Loss of BRCA1 in sporadic breast cancer suggests that therapeutics targeting BRCA1 pathway in hereditary breast cancer like PARP inhibitors might be used as therapeutic targets for sporadic breast tumours.",
"title": "BRCA1-methylated sporadic breast cancers are BRCA-like in showing a basal phenotype and absence of ER expression."
},
{
"docid": "MED-4482",
"text": "Consumption of red meat, particularly well done meat, has been associated with increased prostate cancer risk. High temperature cooking methods such as grilling and barbequeing may produce heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) which are known carcinogens. We assessed the association with meat consumption and estimated HCA and PAH exposure in a population-based case-control study of prostate cancer. Newly diagnosed cases aged 40–79 years (531 advanced cases, 195 localized cases) and 527 controls were asked about dietary intake, including usual meat cooking methods and doneness levels. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression. For advanced prostate cancer, but not localized disease, increased risks were associated with higher consumption of hamburgers (OR=1.79. CI=1.10–2.92), processed meat (OR=1.57, CI=1.04, 2.36), grilled red meat (OR=1.63, CI=0.99–2.68), and well done red meat (OR=1.52, CI=0.93–2.46), and intermediate intake of 2-amino-1-methyl1-6-phenylimidazo[4,5-b]pyridine (PhIP) (quartile 2 vs. 1: OR=1.41, CI=0.98–2.01; quartile 3 vs. 1: OR=1.42, CI=0.98–2.04), but not for higher intake. White meat consumption was not associated with prostate cancer. These findings provide further evidence that consumption of processed meat and red meat cooked at high temperature is associated with increased risk of advanced, but not localized prostate cancer.",
"title": "Meat consumption, Cooking Practices, Meat Mutagens and Risk of Prostate Cancer"
},
{
"docid": "MED-3809",
"text": "Mutagenicity and liver toxicity of the herb tarragon (Artemisia dracunculus) were evaluated using single cell gel (comet) electrophoresis. Ten microlitres aliquots of peripheral venous human blood were incubated with tarragon extract, saline, or the mutagen sodium dichromate. Cell suspensions dispersed in low-melting agarose were electrophoresed in ethidium bromide. The resulting DNA migration trails were obtained using fluorescent microscopy at 400× magnification, and graded according to the mutagenicity index (MI) for each cell incubation condition. The in vivo liver toxicity of Artemisia dracunculus was assessed in the blood of mice treated orally with the extract of the herb, using alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as liver function indicators. Liver morphology was assessed using hematoxylin and eosin (HE) staining of liver tissue. The present study demonstrated a direct correlation between tarragon extract dosage and three major outcome variables: MI; serum liver enzyme activity; and liver histopathology. These outcomes are possibly due to the presence in tarragon of methylchavicol and other genotoxic compounds. These findings provide a preliminary guide for risk assessment of tarragon in diet and in possible therapeutic applications. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Toxicological and mutagenic analysis of Artemisia dracunculus (tarragon) extract."
},
{
"docid": "MED-3052",
"text": "Drug addiction and obesity appear to share several properties. Both can be defined as disorders in which the saliency of a specific type of reward (food or drug) becomes exaggerated relative to, and at the expense of others rewards. Both drugs and food have powerful reinforcing effects, which are in part mediated by abrupt dopamine increases in the brain reward centres. The abrupt dopamine increases, in vulnerable individuals, can override the brain's homeostatic control mechanisms. These parallels have generated interest in understanding the shared vulnerabilities between addiction and obesity. Predictably, they also engendered a heated debate. Specifically, brain imaging studies are beginning to uncover common features between these two conditions and delineate some of the overlapping brain circuits whose dysfunctions may underlie the observed deficits. The combined results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning, self-control, stress reactivity and interoceptive awareness. In parallel, studies are also delineating differences between them that centre on the key role that peripheral signals involved with homeostatic control exert on food intake. Here, we focus on the shared neurobiological substrates of obesity and addiction. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.",
"title": "Obesity and addiction: neurobiological overlaps."
},
{
"docid": "MED-1705",
"text": "Despite an archive of over 73,000 research papers published in the last two decades on the subject of Alzheimer's disease (AD), little clinical progress has been made relative to how people get sporadic AD and what can be done to help them avoid it. This review spotlights strategic steps that could be a turning point in the dramatic lowering of Alzheimer prevalence. The main strategy includes application of four pillars of prevention: 1) early identification of AD vascular risk factors; 2) early detection of AD vascular risk factors; 3) early intervention of AD vascular risk factors based on evidence-based medical decisions; 4) patient follow-up to assess and modify interventions as needed. Tandem to these four pillars of prevention, a proactive lifestyle consisting of a healthy diet coupled to physical and mental activity should be applied as part of any therapeutic intervention. We are persuaded by mounting and compelling evidence that AD is a multifactorial disorder kindled by vascular risk factors that generate chronic brain hypoperfusion (CBH) during advanced aging. A pathobiological cascade of biochemical events in the presence of CBH that leads to oxidative stress and neurodegeneration appears to involve multiple biofactors including micronutrients, trace metals, lipids, and pro-oxidants, as reviewed in this special issue of BioFactors. Modulation of these biofactors may help prevent or control incipient AD. © 2012 International Union of Biochemistry and Molecular Biology, Inc. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "A turning point for Alzheimer's disease?"
}
] |
PLAIN-253
|
Diet vs. Exercise: What’s More Important?
|
[
{
"docid": "MED-4286",
"text": "Nuts are rich sources of multiple nutrients and phytochemicals associated with health benefits, including reduced cardiovascular disease risk. This has prompted recommendations to increase their consumption. However, they are also high in fat and are energy dense. The associations between these properties, positive energy balance and body weight raise questions about such recommendations. Numerous epidemiological and clinical studies show that nuts are not associated with weight gain. Mechanistic studies indicate this is largely attributable to the high satiety and low metabolizable energy (poor bioaccessibility leading to inefficient energy absorption) properties of nuts. Compensatory dietary responses account for 55-75% of the energy provided by nuts. Limited data suggest that routine nut consumption is associated with elevated resting energy expenditure and the thermogenic effect of feeding, resulting in dissipation of another portion of the energy they provide. Additionally, trials contrasting weight loss through regimens that include or exclude nuts indicate improved compliance and greater weight loss when nuts are permitted. Nuts may be included in the diet, in moderation, to enhance palatability, nutrient quality, and chronic disease risk reduction without compromising weight loss or maintenance.",
"title": "Nuts and healthy body weight maintenance mechanisms."
},
{
"docid": "MED-5327",
"text": "OBJECTIVE: To investigate the associations between dietary patterns and mental health in early adolescence. METHOD: The Western Australian Pregnancy Cohort (Raine) Study is a prospective study of 2900 pregnancies recruited from 1989-1992. At 14 years of age (2003-2006; n=1324), the Child Behaviour Checklist (CBCL) was used to assess behaviour (characterising mental health status), with higher scores representing poorer behaviour. Two dietary patterns (Western and Healthy) were identified using factor analysis and food group intakes estimated by a 212-item food frequency questionnaire. Relationships between dietary patterns, food group intakes and behaviour were examined using general linear modelling following adjustment for potential confounding factors at age 14: total energy intake, body mass index, physical activity, screen use, family structure, income and functioning, gender and maternal education at pregnancy. RESULTS: Higher total (b=2.20, 95% CI=1.06, 3.35), internalizing (withdrawn/depressed) (b=1.25, 95% CI=0.15, 2.35) and externalizing (delinquent/aggressive) (b=2.60, 95% CI=1.51, 3.68) CBCL scores were significantly associated with the Western dietary pattern, with increased intakes of takeaway foods, confectionary and red meat. Improved behavioural scores were significantly associated with higher intakes of leafy green vegetables and fresh fruit (components of the Healthy pattern). CONCLUSION: These findings implicate a Western dietary pattern in poorer behavioural outcomes for adolescents. Better behavioural outcomes were associated with a higher intake of fresh fruit and leafy green vegetables.",
"title": "The association between dietary patterns and mental health in early adolescence."
},
{
"docid": "MED-4257",
"text": "We conducted a systematic review investigating body fat distribution in older adults and its association with morbidity and mortality. Our search yielded 2,702 citations. Following three levels of screening, 25 studies were selected to evaluate the association between body fat distribution and comorbidity, and 17 studies were used in the mortality analysis. Most of the selected studies in our analyses used anthropometric measures, e.g., body mass index (BMI), waist circumference, and waist-hip ratio; relatively few studies used direct measures, such as body fat/lean mass, and percentage body fat. Studies reported inconsistent findings regarding the strongest predictor(s) of morbidity and mortality. However, the majority of studies suggested that BMI per se was not the most appropriate predictor of morbidity and mortality in the elderly because of its inability to discern or detect age-related body fat redistribution. In addition, studies using BMI found that the optimal BMI range for the lowest mortality in the elderly was overweight (25 kg/m2 ≤ BMI < 30 kg/m2) or mildly obese (30 kg/m2 ≤ BMI < 35 kg/m2). Our findings suggest that the current clinical guidelines, recommending that overweight and obesity are major risk factors for increased morbidity and mortality are not applicable to this population. Therefore, the central message of this review is to admonish the government to establish new guidelines specifically for this population, using a combination of body fat distribution measurements, and to certify that these guidelines will not be applied to inappropriate populations.",
"title": "A Systematic Review of Body Fat Distribution and Mortality in Older People"
},
{
"docid": "MED-5341",
"text": "The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.",
"title": "Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro."
},
{
"docid": "MED-5339",
"text": "Recently, it has been suggested that the Escherichia coli causing urinary tract infection (UTI) may come from meat and animals. The purpose was to investigate if a clonal link existed between E. coli from animals, meat and UTI patients. Twenty-two geographically and temporally matched B2 E. coli from UTI patients, community-dwelling humans, broiler chicken meat, pork, and broiler chicken, previously identified to exhibit eight virulence genotypes by microarray-detection of approximately 300 genes, were investigated for clonal relatedness by PFGE. Nine isolates were selected and tested for in vivo virulence in the mouse model of ascending UTI. UTI and community-dwelling human strains were closely clonally related to meat strains. Several human derived strains were also clonally interrelated. All nine isolates regardless of origin were virulent in the UTI model with positive urine, bladder and kidney cultures. Further, isolates with the same gene profile also yielded similar bacterial counts in urine, bladder and kidneys. This study showed a clonal link between E. coli from meat and humans, providing solid evidence that UTI is zoonosis. The close relationship between community-dwelling human and UTI isolates may indicate a point source spread, e.g. through contaminated meat.",
"title": "Is Escherichia coli urinary tract infection a zoonosis? Proof of direct link with production animals and meat."
},
{
"docid": "MED-4256",
"text": "This systematic review collated seventy-eight studies exploring waist-to-height ratio (WHtR) and waist circumference (WC) or BMI as predictors of diabetes and CVD, published in English between 1950 and 2008. Twenty-two prospective analyses showed that WHtR and WC were significant predictors of these cardiometabolic outcomes more often than BMI, with similar OR, sometimes being significant predictors after adjustment for BMI. Observations from cross-sectional analyses, forty-four in adults, thirteen in children, supported these predictions. Receiver operator characteristic (ROC) analysis revealed mean area under ROC (AUROC) values of 0·704, 0·693 and 0·671 for WHtR, WC and BMI, respectively. Mean boundary values for WHtR, covering all cardiometabolic outcomes, from studies in fourteen different countries and including Caucasian, Asian and Central American subjects, were 0·50 for men and 0·50 for women. WHtR and WC are therefore similar predictors of diabetes and CVD, both being stronger than, and independent of, BMI. To make firmer statistical comparison, a meta-analysis is required. The AUROC analyses indicate that WHtR may be a more useful global clinical screening tool than WC, with a weighted mean boundary value of 0·5, supporting the simple public health message 'keep your waist circumference to less than half your height'.",
"title": "A systematic review of waist-to-height ratio as a screening tool for the prediction of cardiovascular disease and diabetes: 0·5 could be a suitable..."
},
{
"docid": "MED-5335",
"text": "Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Does a vegan diet reduce risk for Parkinson's disease?"
},
{
"docid": "MED-5322",
"text": "BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%) and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks. Copyright 2009 S. Karger AG, Basel.",
"title": "Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting."
},
{
"docid": "MED-5324",
"text": "Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.",
"title": "Effects of a high-fat meal on pulmonary function in healthy subjects."
},
{
"docid": "MED-4686",
"text": "There is ample reason to believe that diets rich in phytochemicals provide protection from vascular diseases and many cancers; direct antioxidant activity as well as modulation of enzyme expression or hormone activity contribute to this effect. Phytochemicals derived from diverse foods presumably can interact additively and (possibly) synergistically; thus, the total dietary load of phytochemicals may have important implications for health. As a means of very roughly quantifying this load, a \"phytochemical index\" (PI) is proposed, defined as the percent of dietary calories derived from foods rich in phytochemicals. Calories derived from fruits, vegetables (excluding potatoes), legumes, whole grains, nuts, seeds, fruit/vegetable juices, soy products, wine, beer, and cider - and foods compounded therefrom - would be counted in this index. Partial credit could be given for antioxidant-rich extra virgin olive oil. Other added oils, refined sugars, refined grains, potato products, hard liquors, and animal products - regrettably, the chief sources of calories in typical Western diets - would be excluded. Although the PI would provide only a very rough approximation of the quantity or quality of phytochemical nutrition, it nonetheless could aid epidemiologists in exploring the health consequences of diets high in phytochemical-rich plant foods, and could also help clinical nutritionists in their efforts to improve the phytochemical nutrition of their clients.",
"title": "Proposal for a dietary \"phytochemical index\"."
},
{
"docid": "MED-5342",
"text": "Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.",
"title": "Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults"
},
{
"docid": "MED-4261",
"text": "BACKGROUND: Meat intake may be related to weight gain because of its high energy and fat content. Some observational studies have shown that meat consumption is positively associated with weight gain, but intervention studies have shown mixed results. OBJECTIVE: Our objective was to assess the association between consumption of total meat, red meat, poultry, and processed meat and weight gain after 5 y of follow-up, on average, in the large European population who participated in the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (EPIC-PANACEA) project. DESIGN: A total of 103,455 men and 270,348 women aged 25-70 y were recruited between 1992 and 2000 in 10 European countries. Diet was assessed at baseline with the use of country-specific validated questionnaires. A dietary calibration study was conducted in a representative subsample of the cohort. Weight and height were measured at baseline and self-reported at follow-up in most centers. Associations between energy from meat (kcal/d) and annual weight change (g/y) were assessed with the use of linear mixed models, controlled for age, sex, total energy intake, physical activity, dietary patterns, and other potential confounders. RESULTS: Total meat consumption was positively associated with weight gain in men and women, in normal-weight and overweight subjects, and in smokers and nonsmokers. With adjustment for estimated energy intake, an increase in meat intake of 250 g/d (eg, one steak at approximately 450 kcal) would lead to a 2-kg higher weight gain after 5 y (95% CI: 1.5, 2.7 kg). Positive associations were observed for red meat, poultry, and processed meat. CONCLUSION: Our results suggest that a decrease in meat consumption may improve weight management.",
"title": "Meat consumption and prospective weight change in participants of the EPIC-PANACEA study."
},
{
"docid": "MED-5337",
"text": "PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.",
"title": "Intensive lifestyle changes may affect the progression of prostate cancer."
},
{
"docid": "MED-5330",
"text": "Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05 compared with low-fat meal data). No changes in lipoproteins or flow-mediated vasoactivity were observed after the low-fat meal. Fasting low-density lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results demonstrate that a single high-fat meal transiently impairs endothelial function. These findings identify a potential process by which a high-fat diet may be atherogenic independent of induced changes in cholesterol.",
"title": "Effect of a single high-fat meal on endothelial function in healthy subjects."
},
{
"docid": "MED-5363",
"text": "OBJECTIVE: Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. METHODS: Subjects were 521 municipal employees (309 men and 212 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D >or=16) with adjustment for potential confounding variables. RESULTS: We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62-1.59) and 0.44 (0.25-0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms. CONCLUSIONS: Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status.",
"title": "Dietary patterns and depressive symptoms among Japanese men and women."
},
{
"docid": "MED-5325",
"text": "Objective Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores. Design Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Setting Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire. Subjects Five hundred white subjects representing the AHS-2 cohort. Results Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β =−6·8, P<0·05 and β = −6·9, P<0·001). Findings for lacto-ovo vegetarians (β = −9·1, P<0·001 and β = −5·8, P<0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI. Conclusions We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.",
"title": "Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2)"
},
{
"docid": "MED-5328",
"text": "Aim To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. Methods and Results Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses. Conclusion Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.",
"title": "Vegetarian diets and incidence of diabetes in the Adventist Health Study-2"
},
{
"docid": "MED-5323",
"text": "This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta-hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.",
"title": "Endocrine-disrupting chemicals and obesity development in humans: a review."
},
{
"docid": "MED-5331",
"text": "A global health transition is currently underway. The burden of non-communicable diseases (NCDs) is increasing rapidly in the developing world, very much as a result of changes in lifestyles. In addition to changes in tobacco use and physical activity, major changes are taking place in diets, contributing greatly to the growing epidemic of NCD. Thus, a huge global public health challenge is how to influence the trends in diet and nutrition for effective global NCD prevention. The health transition took place rapidly in Finland after World War II and mortality from cardiovascular disease (CVD) was exceptionally high. The North Karelia Project was launched in 1972 as a community-based, and later as a national, programme to influence diet and other lifestyles that are crucial in the prevention of CVD. The intervention had a strong theory base and it employed comprehensive strategies. Broad community organisation and the strong participation of people were the key elements. Evaluation has shown how the diet (particularly fat consumption) has changed and how these changes have led to a major reduction in population serum cholesterol and blood pressure levels. It has also shown how ischaemic heart disease mortality in a working-age population has declined by 73% in North Karelia and by 65% in the whole country from 1971 to 1995. Although Finland is an industrialised country, North Karelia was rural, of rather low socio-economic level and with many social problems in the 1970s and 1980s. The project was based on low-cost intervention activities, where people's participation and community organisations played a key role. Comprehensive interventions in the community were eventually supported by national activities--from expert guidelines and media activities to industry collaboration and policy. Similar principles for nutrition intervention programmes could be used in developing countries, obviously tailored to the local conditions. This paper discusses the experiences of the North Karelia Project in the light of needs from the less-industrialised countries and makes some general recommendations.",
"title": "Influencing public nutrition for non-communicable disease prevention: from community intervention to national programme--experiences from Finland."
},
{
"docid": "MED-5340",
"text": "In Asia, vegetarianism is a well-established eating behavior. It appears that the adoption of a vegan diet leads to a lessening of several health risk factors. Although vegetarianism has some notable effects on the hematological system, the effect on the nephrological system has not been well clarified. The pattern of renal function parameters was studied in 25 Thai vegans compared with 25 non-vegetarians. Of the studied parameters, it was found that urine protein was significantly different (p < 0.05) in vegans and controls. Vegans had significantly lower urine protein level.",
"title": "Renal function parameters of Thai vegans compared with non-vegans."
},
{
"docid": "MED-5333",
"text": "BACKGROUND/AIM: A vegetarian diet is known to prevent a series of diseases but may influence the balance of carbohydrate and fat metabolism as well as collagen synthesis. This study compares expression patterns of relevant genes in oral mucosa of omnivores and vegetarians. METHODS: Quantitative reverse transcriptase polymerase chain reaction was applied for analysis of mRNA levels from carnitine transporter OCTN2, hepatic CPT1A and nonhepatic CPT1B isoforms of carnitine palmitoyltransferase and collagen (CCOL2A1) in oral mucosa. RESULTS: Compared with volunteers with traditional eating habits, carbohydrate consumption was significantly higher (+22%) in vegetarians. This was associated with a significant stimulation of CPT1A (+50%) and OCTN2 (+10%) and a lowered collagen synthesis (-10%). CONCLUSION: These novel findings provide further insight into the association of a changed fat metabolism and reduced collagen synthesis in vegetarians, which could also play a role in the aging process. Copyright 2008 S. Karger AG, Basel.",
"title": "Vegetarian diet affects genes of oxidative metabolism and collagen synthesis."
},
{
"docid": "MED-5332",
"text": "The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.",
"title": "Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age."
},
{
"docid": "MED-5334",
"text": "Until recently, intact protein that is rich in tryptophan was not seen as an alternative to pharmaceutical-grade tryptophan because protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a rich source of tryptophan with approximately 22 mg/g protein) is combined with glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective and subjective measures of anxiety in those suffering from social phobia (also known as social anxiety disorder) were employed to measure changes in anxiety in response to a stimulus as part of a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between study sessions. Subjects were randomly assigned to start with either (i) protein-source tryptophan (deoiled gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week after the initial session, subjects returned for a follow-up session and received the opposite treatment of that received at the first session. All 7 subjects who began the study completed the 2-week protocol. Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement on an objective measure of anxiety. Protein-source tryptophan combined with a high glycemic carbohydrate is a potential anxiolytic to those suffering from social phobia.",
"title": "Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study."
},
{
"docid": "MED-5326",
"text": "The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Red meat and colon cancer: should we become vegetarians, or can we make meat safer?"
},
{
"docid": "MED-5338",
"text": "Summary Background and objectives Patients with advanced chronic kidney disease (CKD) are in positive phosphorus balance, but phosphorus levels are maintained in the normal range through phosphaturia induced by increases in fibroblast growth factor-23 (FGF23) and parathyroid hormone (PTH). This provides the rationale for recommendations to restrict dietary phosphate intake to 800 mg/d. However, the protein source of the phosphate may also be important. Design, setting, participants, & measurements We conducted a crossover trial in nine patients with a mean estimated GFR of 32 ml/min to directly compare vegetarian and meat diets with equivalent nutrients prepared by clinical research staff. During the last 24 hours of each 7-day diet period, subjects were hospitalized in a research center and urine and blood were frequently monitored. Results The results indicated that 1 week of a vegetarian diet led to lower serum phosphorus levels and decreased FGF23 levels. The inpatient stay demonstrated similar diurnal variation for blood phosphorus, calcium, PTH, and urine fractional excretion of phosphorus but significant differences between the vegetarian and meat diets. Finally, the 24-hour fractional excretion of phosphorus was highly correlated to a 2-hour fasting urine collection for the vegetarian diet but not the meat diet. Conclusions In summary, this study demonstrates that the source of protein has a significant effect on phosphorus homeostasis in patients with CKD. Therefore, dietary counseling of patients with CKD must include information on not only the amount of phosphate but also the source of protein from which the phosphate derives.",
"title": "Original Articles: Vegetarian Compared with Meat Dietary Protein Source and Phosphorus Homeostasis in Chronic Kidney Disease"
},
{
"docid": "MED-5329",
"text": "OBJECTIVE: This study was conducted to demonstrate the effectiveness of a strictly vegetarian, very low-fat diet on cardiac risk factor modification. METHODS: Five hundred men and women, participants in an intensive 12-day live-in program, were studied. The program focused on dietary modification, moderate exercise, and stress management at a hospital-based health-center. RESULTS: During this short time period, cardiac risk factors improved: there was an average reduction of total serum cholesterol of 11% (p < 0.001), of blood pressure of 6% (p < 0.001) and a weight loss of 2.5 kg for men and 1 kg for women. Serum triglycerides did not increase except for two subgroups: females age > or = 65 years with serum cholesterol < 6.5 mmol/L and for females 50 to 64 years with baseline serum cholesterol between 5.2-6.5 mmol/L. High-density lipoprotein cholesterol measured on 66 subjects decreased by 19%. CONCLUSION: A strict, very low-fat vegetarian diet free from all animal products combined with lifestyle changes that include exercise and weight loss is an effective way to lower serum cholesterol and blood pressure.",
"title": "Rapid reduction of serum cholesterol and blood pressure by a twelve-day, very low fat, strictly vegetarian diet."
}
] |
[
{
"docid": "MED-1543",
"text": "The goal of this research was to evaluate the personal health behaviors of physicians in training and attending physicians in association with patient-related lifestyle counseling. Physicians at a major teaching hospital were surveyed regarding their personal lifestyle behavior, perceived confidence, and frequency of counseling patients regarding lifestyle behaviors. One hundred eighty-three total responses were received. Trainees were more likely to consume fast food and less likely to consume fruits and vegetables than attendings. Attending physicians were more likely to exercise 4 or more days per week and more than 150 minutes per week. Attending physicians were more likely to counsel their patients regarding a healthy diet (70.7% vs 36.3%, P<.0001) and regular exercise (69.1% vs 38.2%, P<.0001) compared with trainees. Few trainees or attendings were confident in their ability to change patients' behaviors. Predictors of confidence in counseling for exercise included the provider's own exercise time of > 150 minutes per week, being overweight, and reported adequate training in counseling. Only adequate training in counseling was a predictor of strong self-efficacy for counseling in diet. Many physicians lack confidence in their ability to counsel patients regarding lifestyle. Personal behaviors including regular exercise and better training in counseling techniques may improve patient counseling. © 2010 Wiley Periodicals, Inc.",
"title": "Patient-related diet and exercise counseling: do providers' own lifestyle habits matter?"
},
{
"docid": "MED-1053",
"text": "CONTEXT: While some studies have shown that physicians with healthy personal habits are especially likely to discuss prevention with their patients, to our knowledge no one has published information testing whether physician credibility and patient motivation to adopt healthier habits are enhanced by physician's disclosures of their own healthy behaviors. DESIGN: Two brief health education videos about improving diet and exercise were produced and shown to subjects (n1 = 66, n2 = 65) in an Emory University general medical clinic waiting room in Atlanta, Ga. In one video, the physician revealed an additional half minute of information about her personal healthy dietary and exercise practices and had a bike helmet and an apple visible on her desk (physician-disclosure video). In the other video, discussion of personal practices and the apple and bike helmet were not included (control video). RESULTS: Viewers of the physician-disclosure video considered the physician to be generally healthier, some-what more believable, and more motivating than did viewers of the control video. They also rated this physician to be specifically more believable and motivating regarding exercise and diet (P < or = .001). CONCLUSION: Physicians' abilities to motivate patients to adopt healthy habits can be enhanced by conveying their own healthy habits. Educational institutions should consider encouraging health professionals-in-training to practice and demonstrate healthy personal lifestyles.",
"title": "Physician disclosure of healthy personal behaviors improves credibility and ability to motivate."
},
{
"docid": "MED-3815",
"text": "Aims The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. Methods A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. Results Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [–6.2 kg (95% CI –6.6 to –5.3) vs. –3.2 kg (95% CI –3.7 to –2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5–39) vs. 20% (95% CI 14–25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. Conclusions A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.",
"title": "Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes"
},
{
"docid": "MED-5225",
"text": "Aims The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. Methods A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. Results Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [–6.2 kg (95% CI –6.6 to –5.3) vs. –3.2 kg (95% CI –3.7 to –2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5–39) vs. 20% (95% CI 14–25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. Conclusions A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.",
"title": "Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes"
},
{
"docid": "MED-1488",
"text": "Aims To discover whether patients have the same expectations of benefit from taking the first and any additional drugs for the treatment of hypertension and to investigate any patient characteristics which predict willingness to take treatment. Methods This was an anonymous questionnaire survey carried out in a single primary care group. A random sample of patients from the practice list stratified by age and gender were surveyed to determine what benefit they required before deciding to receive first and subsequent drugs to treat hypertension. They were asked to indicate the largest number needing treatment for 5 years (NNT5) to prevent myocardial infarction in 1 (smallest benefit) that would persuade them of the need for treatment. Demographic information which might explain variability in enthusiasm for treatment was also collected. Results Participants required far higher benefit to consider drug treatment than expected with a mean NNT5 for the first treatment of 15.0 (95% CI 12.3, 17.8). Marginal benefit demanded for the addition of second and third treatments was at least as great with an NNT5 of 13.2 (95% CI 10.8, 15.7) and NNT5 of 11.0 (95% CI 8.6, 13.4). Additional factors influencing willingness to take treatment were gender with a difference in NNT5 between men and women of 7.1 (95% CI 1.7, 12.5), difficulty in making the decision (very easy vs very difficult) of 14.9 (95% CI 6.0, 23.8), and years in full time education 2.0 (95% CI 0.9, 3.0) for each additional year of education. Any slope of NNT5 with increasing number of tablets disappeared when gender, years in education, and difficulty in reaching a decision were taken into account simultaneously. Conclusions People may have greater expectation of benefit from antihypertensive drug treatment than it provides. They certainly do not view the addition of subsequent drugs as any lesser step than starting the first in terms of the benefit expected. Full understanding of both the risks and benefits may be of critical importance with those spending longer in full time education and those expending more effort in making the decision accepting more treatment. The discrepancy between benefit expected and that available demands further research into methods of determining patients’ expectations and informing individual patient decisions.",
"title": "What benefit do patients expect from adding second and third antihypertensive drugs?"
},
{
"docid": "MED-944",
"text": "Many products used in everyday life are made with the assistance of nanotechnologies. Cosmetic, pharmaceuticals, sunscreen, powdered food are only few examples of end products containing nano-sized particles (NPs), generally added to improve the product quality. To evaluate correctly benefits vs. risks of engineered nanomaterials and consequently to legislate in favor of consumer's protection, it is necessary to know the hazards connected with the exposure levels. This information implies transversal studies and a number of different competences. On analytical point of view the identification, quantification and characterization of NPs in food matrices and in cosmetic or personal care products pose significant challenges, because NPs are usually present at low concentration levels and the matrices, in which they are dispersed, are complexes and often incompatible with analytical instruments that would be required for their detection and characterization. This paper focused on some analytical techniques suitable for the detection, characterization and quantification of NPs in food and cosmetics products, reports their recent application in characterizing specific metal and metal-oxide NPs in these two important industrial and market sectors. The need of a characterization of the NPs as much as possible complete, matching complementary information about different metrics, possible achieved through validate procedures, is what clearly emerges from this research. More work should be done to produce standardized materials and to set-up methodologies to determine number-based size distributions and to get quantitative date about the NPs in such a complex matrices.",
"title": "Nanomaterials in consumer products: a challenging analytical problem."
},
{
"docid": "MED-2300",
"text": "Aging is a natural and complex physiological process influenced by many factors, some of which are modifiable. As the number of older individuals continues to increase, it is important to develop interventions that can be easily implemented and contribute to \"successful aging\". In addition to a healthy diet and psychosocial well-being, the benefits of regular exercise on mortality, and the prevention and control of chronic disease affecting both life expectancy and quality of life are well established. We summarize the benefits of regular exercise on longevity, present the current knowledge regarding potential mechanisms, and outline the main recommendations. Exercise can partially reverse the effects of the aging process on physiological functions and preserve functional reserve in the elderly. Numerous studies have shown that maintaining a minimum quantity and quality of exercise decreases the risk of death, prevents the development of certain cancers, lowers the risk of osteoporosis and increases longevity. Training programs should include exercises aimed at improving cardiorespiratory fitness and muscle function, as well as flexibility and balance. Though the benefits of physical activity appear to be directly linked to the notion of training volume and intensity, further research is required in the elderly, in order to develop more precise recommendations, bearing in mind that the main aim is to foster long-term adherence to physical activity in this growing population. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.",
"title": "Exercise and longevity."
},
{
"docid": "MED-3156",
"text": "Exercise-induced oxidative stress is instrumental in achieving the health benefits from regular exercise. Therefore, inappropriate use of fruit-derived products (commonly applied as prophalytic antioxidants) may counteract the positive effects of exercise. Using human exercise and cellular models we found that 1) blackcurrant supplementation suppressed exercise-induced oxidative stress, e.g., plasma carbonyls (0.9 +/- 0.1 vs. 0.6 +/- 0.1 nmol/mg protein, placebo vs. blackcurrant), and 2) preincubation of THP-1 cells with an anthocyanin-rich blackcurrant extract inhibited LPS-stimulated cytokine secretion [TNF-alpha (16,453 +/- 322 vs. 10,941 +/- 82 pg/ml, control vs. extract, P < 0.05) and IL-6 (476 +/- 14 vs. 326 +/- 32 pg/ml, control vs. extract, P < 0.05)] and NF-kappaB activation. In addition to its antioxidant and anti-inflammatory properties, we found that postexercise plasma collected after blackcurrant supplementation enhanced the differential temporal LPS-stimulated inflammatory response in THP-1 cells, resulting in an early suppression of TNF-alpha (1,741 +/- 32 vs. 1,312 +/- 42 pg/ml, placebo vs. blackcurrant, P < 0.05) and IL-6 (44 +/- 5 vs. 36 +/- 3 pg/ml, placebo vs. blackcurrant, P < 0.05) secretion after 24 h. Furthermore, by using an oxidative stress cell model, we found that preincubation of THP-1 cells with hydrogen peroxide (H(2)O(2)) prior to extract exposure caused a greater suppression of LPS-stimulated cytokine secretion after 24 h, which was not evident when cells were simultaneously incubated with H(2)O(2) and the extract. In summary, our findings support the concept that consumption of blackcurrant anthocyanins alleviate oxidative stress, and may, if given at the appropriate amount and time, complement the ability of exercise to enhance immune responsiveness to potential pathogens.",
"title": "Short-term blackcurrant extract consumption modulates exercise-induced oxidative stress and lipopolysaccharide-stimulated inflammatory responses."
},
{
"docid": "MED-748",
"text": "Questions of medical ethics are often treated as especially difficult casuistical problems or as difficult cases illustrative of paradoxes or advantages in global moral theories. I argue here, in opposition to such approaches, for the inseparability of questions of social history and social theory from any normative assessment of medical practices. The focus of the discussion is the question of the legitimacy of the social authority exercised by physicians, and the insufficiency of traditional defences of such authority in liberal societies (voluntarist, informed consent approaches), as well as traditional attacks on such strategies (ideology critique). Seeing such authority as institution bound and role based, it is argued, can help reframe, more broadly and more adequately, what is an \"ethical problem\" in medical practice and why.",
"title": "Medical practice and social authority."
},
{
"docid": "MED-1467",
"text": "Human adiposity has long been associated with insulin resistance and increased cardiovascular risk, and abdominal adiposity is considered particularly adverse. Intra-abdominal fat is associated with insulin resistance, possibly mediated by greater lipolytic activity, lower adiponectin levels, resistance to leptin, and increased inflammatory cytokines, although the latter contribution is less clear. Liver lipid is also closely associated with, and likely to be an important contributor to, insulin resistance, but it may also be in part the consequence of the lipogenic pathway of insulin action being up-regulated by hyperinsulinemia and unimpaired signaling. Again, intramyocellular triglyceride is associated with muscle insulin resistance, but anomalies include higher intramyocellular triglyceride in insulin-sensitive athletes and women (vs men). Such issues could be explained if the \"culprits\" were active lipid moieties such as diacylglycerol and ceramide species, dependent more on lipid metabolism and partitioning than triglyceride amount. Subcutaneous fat, especially gluteofemoral, appears metabolically protective, illustrated by insulin resistance and dyslipidemia in patients with lipodystrophy. However, some studies suggest that deep sc abdominal fat may have adverse properties. Pericardial and perivascular fat relate to atheromatous disease, but not clearly to insulin resistance. There has been recent interest in recognizable brown adipose tissue in adult humans and its possible augmentation by a hormone, irisin, from exercising muscle. Brown adipose tissue is metabolically active, oxidizes fatty acids, and generates heat but, because of its small and variable quantities, its metabolic importance in humans under usual living conditions is still unclear. Further understanding of specific roles of different lipid depots may help new approaches to control obesity and its metabolic sequelae.",
"title": "Adiposity and insulin resistance in humans: the role of the different tissue and cellular lipid depots."
},
{
"docid": "MED-1520",
"text": "Background Enhancing athletic performance is a great desire among the athletes, coaches and researchers. Mint is one of the most famous natural herbs used for its analgesic, anti-inflammatory, antispasmodic, antioxidant, and vasoconstrictor effects. Even though inhaling mint aroma in athletes has been investigated, there were no significant effects on the exercise performance. Methods Twelve healthy male students every day consumed one 500 ml bottle of mineral water, containing 0.05 ml peppermint essential oil for ten days. Blood pressure, heart rate, and spirometry parameters including forced vital capacity (FVC), peak expiratory flow rate (PEF), and peak inspiratory flow (PIF) were determined one day before, and after the supplementation period. Participants underwent a treadmill-based exercise test with metabolic gas analysis and ventilation measurement using the Bruce protocol. Results The FVC (4.57 ± 0.90 vs. 4.79 ± 0.84; p < 0.001), PEF (8.50 ± 0.94 vs. 8.87 ± 0.92; p < 0.01), and PIF (5.71 ± 1.16 vs. 6.58 ±1.08; p < 0.005) significantly changed after ten days of supplementation. Exercise performance evaluated by time to exhaustion (664.5 ± 114.2 vs. 830.2 ± 129.8 s), work (78.34 ±32.84 vs. 118.7 ± 47.38 KJ), and power (114.3 ± 24.24 vs. 139.4 ± 27.80 KW) significantly increased (p < 0.001). In addition, the results of respiratory gas analysis exhibited significant differences in VO2 (2.74 ± 0.40 vs. 3.03 ± 0.351 L/min; p < 0.001), and VCO2 (3.08 ± 0.47 vs. 3.73 ± 0.518 L/min; p < 0.001). Conclusions The results of the experiment support the effectiveness of peppermint essential oil on the exercise performance, gas analysis, spirometry parameters, blood pressure, and respiratory rate in the young male students. Relaxation of bronchial smooth muscles, increase in the ventilation and brain oxygen concentration, and decrease in the blood lactate level are the most plausible explanations.",
"title": "The effects of peppermint on exercise performance"
},
{
"docid": "MED-4640",
"text": "BACKGROUND: The gut and immune system form a complex integrated structure that has evolved to provide effective digestion and defence against ingested toxins and pathogenic bacteria. However, great variation exists in what is considered normal healthy gut and immune function. Thus, whilst it is possible to measure many aspects of digestion and immunity, it is more difficult to interpret the benefits to individuals of variation within what is considered to be a normal range. Nevertheless, it is important to set standards for optimal function for use both by the consumer, industry and those concerned with the public health. The digestive tract is most frequently the object of functional and health claims and a large market already exists for gut-functional foods worldwide. AIM: To define normal function of the gut and immune system and describe available methods of measuring it. RESULTS: We have defined normal bowel habit and transit time, identified their role as risk factors for disease and how they may be measured. Similarly, we have tried to define what is a healthy gut flora in terms of the dominant genera and their metabolism and listed the many, varied and novel methods for determining these parameters. It has proved less easy to provide boundaries for what constitutes optimal or improved gastric emptying, gut motility, nutrient and water absorption and the function of organs such as the liver, gallbladder and pancreas. The many tests of these functions are described. We have discussed gastrointestinal well being. Sensations arising from the gut can be both pleasant and unpleasant. However, the characteristics of well being are ill defined and merge imperceptibly from acceptable to unacceptable, a state that is subjective. Nevertheless, we feel this is an important area for future work and method development. The immune system is even more difficult to make quantitative judgements about. When it is defective, then clinical problems ensure, but this is an uncommon state. The innate and adaptive immune systems work synergistically together and comprise many cellular and humoral factors. The adaptive system is extremely sophisticated and between the two arms of immunity there is great redundancy, which provides robust defences. New aspects of immune function are discovered regularly. It is not clear whether immune function can be \"improved\". Measuring aspects of immune function is possible but there is no one test that will define either the status or functional capacity of the immune system. Human studies are often limited by the ability to sample only blood or secretions such as saliva but it should be remembered that only 2% of lymphocytes circulate at any given time, which limits interpretation of data. We recommend assessing the functional capacity of the immune system by: measuring specific cell functions ex vivo. measuring in vivo responses to challenge, e. g. change in antibody in blood or response to antigens. determining the incidence and severity of infection in target populations during naturally occurring episodes or in response to attenuated pathogens.",
"title": "PASSCLAIM--gut health and immunity."
},
{
"docid": "MED-4452",
"text": "Background: Evidence for the role of diet and physical activity in cancer incidence is well documented, but owing to increased cancer survivorship, an understanding of these lifestyle factors after a cancer diagnosis is of crucial importance. The purpose of this review was to update the literature in a review undertaken for the National Cancer Survivorship Initiative and to include observational studies that were not included in the WCRF survivorship systematic review. Methods: Evidence was initially gathered from pre-defined searches of the Cochrane Library Database and PubMed from March 2006 to February 2010. After a comprehensive review regarding lifestyle and cancer, for the purpose of this article, any studies not related to diet and physical activity, prognostic outcomes, and breast, colorectal or prostate cancers were excluded. Another search of 2011 literature was conducted to update the evidence. Results: A total of 43 records were included in this review. Evidence from observational studies suggests that a low-fat, high-fibre diet might be protective against cancer recurrence and progression. However, there is a paucity of RCTs substantiating this. There is more support for physical activity, with a dose response for better outcomes. When synthesized with findings from the World Cancer Research Fund review of RCTs investigating the effect of diet and physical activity interventions on cancer survival, evidence suggests that the mechanism of benefit from diet and physical activity pertains to body weight, with excess body weight being a risk factor, which is modifiable through lifestyle. Implications: Cancer survivors would like to have a more active role in their health care and to know how to look after themselves after diagnosis, including what diet and lifestyle changes they should make. The challenge is in integrating lifestyle support into standardised models of aftercare.",
"title": "The role of diet and physical activity in breast, colorectal, and prostate cancer survivorship: a review of the literature"
},
{
"docid": "MED-834",
"text": "Polycystic ovarian syndrome (PCOS) affects 18–22% of women at reproductive age. We conducted a systematic review and meta-analysis evaluating the expected benefits of lifestyle (exercise plus diet) interventions on the reproductive endocrine profile in women with PCOS. Potential studies were identified by systematically searching PubMed, CINAHL and the Cochrane Controlled Trials Registry (1966–April 30, 2013) systematically using key concepts of PCOS. Significant improvements were seen in women receiving lifestyle intervention vs usual care in follicle-stimulating hormone (FSH) levels, mean difference (MD) 0.39 IU/l (95% CI 0.09 to 0.70, P=0.01), sex hormone-binding globulin (SHBG) levels, MD 2.37 nmol/l (95% CI 1.27 to 3.47, P<0.0001), total testosterone levels, MD −0.13 nmol/l (95% CI −0.22 to −0.03, P=0.008), androstenedione levels, MD −0.09 ng/dl (95% CI −0.15 to −0.03, P=0.005), free androgen index (FAI) levels, MD −1.64 (95% CI −2.94 to −0.35, P=0.01) and Ferriman–Gallwey (FG) score, MD −1.01 (95% CI −1.54 to −0.48, P=0.0002). Significant improvements were also observed in women who received exercise-alone intervention vs usual care in FSH levels, MD 0.42 IU/l (95% CI 0.11 to 0.73, P=0.009), SHBG levels, MD 3.42 nmol/l (95% CI 0.11 to 6.73, P=0.04), total testosterone levels, MD −0.16 nmol/l (95% CI −0.29 to −0.04, P=0.01), androstenedione levels, MD −0.09 ng/dl (95% CI −0.16 to −0.03, P=0.004) and FG score, MD −1.13 (95% CI −1.88 to −0.38, P=0.003). Our analyses suggest that lifestyle (diet and exercise) intervention improves levels of FSH, SHBG, total testosterone, androstenedione and FAI, and FG score in women with PCOS.",
"title": "Effect of lifestyle intervention on the reproductive endocrine profile in women with polycystic ovarian syndrome: a systematic review and meta-analysis"
},
{
"docid": "MED-1641",
"text": "Background Caffeine is one of the most widely consumed pharmacologically active substances. Its acute effect on myocardial blood flow is widely unknown. Our aim was to assess the acute effect of caffeine in a dose corresponding to two cups of coffee on myocardial blood flow (MBF) in coronary artery disease (CAD). Methodology/Principal Findings MBF was measured with 15O-labelled H2O and Positron Emission Tomography (PET) at rest and after supine bicycle exercise in controls (n = 15, mean age 58±13 years) and in CAD patients (n = 15, mean age 61±9 years). In the latter, regional MBF was assessed in segments subtended by stenotic and remote coronary arteries. All measurements were repeated fifty minutes after oral caffeine ingestion (200 mg). Myocardial perfusion reserve (MPR) was calculated as ratio of MBF during bicycle stress divided by MBF at rest. Resting MBF was not affected by caffeine in both groups. Exercise-induced MBF response decreased significantly after caffeine in controls (2.26±0.56 vs. 2.02±0.56, P<0.005), remote (2.40±0.70 vs. 1.78±0.46, P<0.001) and in stenotic segments (1.90±0.41 vs. 1.38±0.30, P<0.001). Caffeine decreased MPR significantly by 14% in controls (P<0.05 vs. baseline). In CAD patients MPR decreased by 18% (P<0.05 vs. baseline) in remote and by 25% in stenotic segments (P<0.01 vs. baseline). Conclusions We conclude that caffeine impairs exercise-induced hyperaemic MBF response in patients with CAD to a greater degree than age-matched controls.",
"title": "Caffeine Impairs Myocardial Blood Flow Response to Physical Exercise in Patients with Coronary Artery Disease as well as in Age-Matched Controls"
},
{
"docid": "MED-4269",
"text": "PURPOSE OF REVIEW: High-fiber diets have been shown to reduce plasma concentrations of inflammation markers. Increased production of fermentation-derived short-chain fatty acids (SCFAs) is one of the factors that could exert these positive effects. This review examines the effects of SCFAs on immune cells and discusses the relevance of their effects on systemic inflammation, as frequently seen in obesity. RECENT FINDINGS: SCFAs have been shown to reduce chemotaxis and cell adhesion; this effect is dependent on type and concentration of SCFA. In spite of conflicting results, especially butyrate seems to have an anti-inflammatory effect, mediated by signaling pathways like nuclear factor-κB and inhibition of histone deacetylase. The discrepancies in the results could be explained by differences in cell types used and their proliferative and differentiation status. SUMMARY: SCFAs show anti-inflammatory effects and seem to have the potency to prevent infiltration of immune cells from the bloodstream in, for example, the adipose tissue. In addition, their ability to inhibit the proliferation and activation of T cells and to prevent adhesion of antigen-presenting cells could be important as it recently has been shown that obesity-associated inflammation might be antigen-dependent. More studies with concentrations in micromolar range are needed to approach more physiological concentrations.",
"title": "Butyrate and other short-chain fatty acids as modulators of immunity: what relevance for health?"
},
{
"docid": "MED-3894",
"text": "The purpose of this study was to examine the effects of a natural carbohydrate (CHO) source in the form of sun-dried raisins (SDRs) vs. Sports Jelly Beans™ (SJBs) on endurance performance in trained cyclists and triathletes. Ten healthy men (18-33 years) completed 1 water-only acclimatization exercise trial and 2 randomized exercise trials administered in a crossover fashion. Each trial consisted of a 120-minute constant-intensity glycogen depletion period followed by a 10-km time trial (TT). During each experimental trial, participants consumed isocaloric amounts of SDRs or SJBs in 20-minute intervals. Measurements included time to complete 10-km TT, power output during 10-km TT, blood glucose levels and respiratory exchange ratio during glycogen depletion period, rate of perceived exertion (RPE), 'flow' questionnaire responses, and a hedonic (i.e., pleasantness) sensory acceptance test. There were no significant differences in endurance performance for TT time (SDRs vs. SJBs, 17.3 ± 0.4 vs. 17.3 ± 0.4 seconds) or power (229.3 ± 13.0 vs. 232.0 ± 13.6 W), resting blood glucose levels (5.8 ± 04 mmol·L(-1) for SDRs and 5.4 ± 0.2 mmol·L(-1) for SJBs), RPE, or flow experiences between SDR and SJB trials. However, the mean sensory acceptance scores were significantly higher for the SDRs compared to the SJBs (50.7 ± 1.7 vs. 44.3 ± 2.7). Consuming SDRs or SJBs during 120 minutes of intense cycling results in similar subsequent TT performances and are equally effective in maintaining blood glucose levels during exercise. Therefore, SDRs are a natural, pleasant, cost-effective CHO alternative to commercial SJBs that can be used during moderate- to high-intensity endurance exercise.",
"title": "Sun-dried raisins are a cost-effective alternative to Sports Jelly Beans in prolonged cycling."
},
{
"docid": "MED-2584",
"text": "In a 6-year prospective study, the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study (California, 1976-1982) who, at baseline, had no documented or reported history of cancer. The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates. The authors found a positive association with total meat intake (risk ratio (RR) for > or =1 time/week vs. no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87; p for trend = 0.01) and, among subjects who favored specific types of meat, positive associations with red meat intake (RR for > or =1 time/week vs. no red meat intake = 1.90, 95% CI 1.16-3.11; p for trend = 0.02) and white meat intake (RR for > or =1 time/week vs. no white meat intake = 3.29, 95% CI 1.60-6.75; p for trend = 0.006). An inverse association with legume intake (RR for >2 times/week vs. <1 time/week = 0.53, 95% CI 0.33-0.86; p for trend = 0.03) was observed. Among men, a positive association with body mass index was observed (relative to the RR for tertile III (>25.6 kg/m2) vs. tertile I (<22.5 kg/m2) = 2.63, 95% CI 1.12-6.13; p for trend = 0.05). A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables. This pattern of putative risk factors would likely contribute to increases in both insulin resistance (high body mass, high red meat intake) and glycemic load (low legume intake), a synergism that, if causal, implicates hyperinsulinemic exposure in colon carcinogenesis. The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology.",
"title": "Dietary risk factors for colon cancer in a low-risk population."
},
{
"docid": "MED-4890",
"text": "Epidemiological studies suggest a positive association between nutrient intake, hyperinsulinemia and risk of Benign prostatic hyperplasis (BPH). This study tests the hypothesis that a low-fat, high-fiber diet and daily exercise would lower serum insulin and reduce the growth of serum-stimulated primary prostate epithelial cells in culture. Serum samples were obtained from eight overweight men before and after the Pritikin residential, 2-week diet and exercise intervention and from seven men who were long-term followers of the low-fat, high-fiber diet and regular exercise lifestyle. The serum was used to stimulate primary prostate epithelial cells in culture. Growth was measured after 48 and 96 h and apoptosis after 96 h. At 48 h there was no significant difference in growth within the Pre, 2-week or Long-Term groups. At 96 h growth was significantly reduced in the 2-week (13%) and in the Long-Term (14%) groups compared to the Pre data. At 96 h, apoptosis was not significantly different among the three groups. Fasting insulin was reduced by 30% in the 2-week group and by 52% in the Long-Term group compared to the Pre data. Testosterone was unchanged in the 2-week group. The results of this study indicate that a low-fat, high-fiber diet and daily exercise lowers insulin and reduces growth of prostate primary epithelial cells and suggests that lifestyle may be an important factor in the development or progression of BPH. Future prospective trials should address the effects of this lifestyle modification on BPH symptomatology and progression.",
"title": "Effect of diet and exercise intervention on the growth of prostate epithelial cells."
},
{
"docid": "MED-2166",
"text": "Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors are likely to play important etiological roles. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. Previously, elevated blood harmane concentrations were demonstrated in ET cases compared to controls, but these observations were all been cross-sectional, assessing each subject at only one time point. Thus, no one has ever repeat-assayed blood harmane in the same subjects twice. Whether the observed case-control difference persists at a second time point, years later, is unknown. The current goal was to re-assess a sample of our ET cases and controls to determine whether blood harmane concentration remained elevated in ET at a second time point. Blood harmane concentrations were quantified by a well-established high performance liquid chromatography method in 63 ET cases and 70 controls. A mean of approximately 6 years elapsed between the initial and this subsequent blood harmane determination. The mean log blood harmane concentration was significantly higher in cases than controls (0.30 ± 0.61 g−10/ml vs. 0.08 ± 0.55 g−10/ml), and the median value in cases was double that of controls: 0.22 g−10/ml vs. 0.11 g−10/ml. The log blood harmane concentration was highest in cases with a family history of ET. Blood harmane concentration was elevated in ET cases compared to controls when re-assessed at a second time point several years later, indicating what seems to be a stable association between this environmental toxin and ET.",
"title": "Blood Harmane (1-methyl-9h-pyrido[3,4-b]indole) Concentrations in Essential Tremor: Repeat Observation in Cases and Controls in New York"
},
{
"docid": "MED-4505",
"text": "The anion nitrate-abundant in our diet-has recently emerged as a major pool of nitric oxide (NO) synthase-independent NO production. Nitrate is reduced stepwise in vivo to nitrite and then NO and possibly other bioactive nitrogen oxides. This reductive pathway is enhanced during low oxygen tension and acidosis. A recent study shows a reduction in oxygen consumption during submaximal exercise attributable to dietary nitrate. We went on to study the effects of dietary nitrate on various physiological and biochemical parameters during maximal exercise. Nine healthy, nonsmoking volunteers (age 30+/-2.3 years, VO(2max) 3.72+/-0.33 L/min) participated in this study, which had a randomized, double-blind crossover design. Subjects received dietary supplementation with sodium nitrate (0.1 mmol/kg/day) or placebo (NaCl) for 2 days before the test. This dose corresponds to the amount found in 100-300 g of a nitrate-rich vegetable such as spinach or beetroot. The maximal exercise tests consisted of an incremental exercise to exhaustion with combined arm and leg cranking on two separate ergometers. Dietary nitrate reduced VO(2max) from 3.72+/-0.33 to 3.62+/-0.31 L/min, P<0.05. Despite the reduction in VO(2max) the time to exhaustion trended to an increase after nitrate supplementation (524+/-31 vs 563+/-30 s, P=0.13). There was a correlation between the change in time to exhaustion and the change in VO(2max) (R(2)=0.47, P=0.04). A moderate dietary dose of nitrate significantly reduces VO(2max) during maximal exercise using a large active muscle mass. This reduction occurred with a trend toward increased time to exhaustion implying that two separate mechanisms are involved: one that reduces VO(2max) and another that improves the energetic function of the working muscles. Copyright 2009 Elsevier Inc. All rights reserved.",
"title": "Dietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exercise."
},
{
"docid": "MED-3895",
"text": "Research suggests that pre-exercise sources of dietary carbohydrate with varying glycemic indexes may differentially affect metabolism and endurance. This study was designed to examine potential differences in metabolism and cycling performance after consumption of moderate glycemic raisins vs. a high glycemic commercial sports gel. Eight endurance-trained male (n = 4) and female (n = 4) cyclists 30 +/- 5 years of age completed 2 trials in random order. Subjects were fed 1 g carbohydrate per kilogram body weight from either raisins or sports gel 45 minutes prior to exercise on a cycle ergometer at 70% V(.-)O2max. After 45 minutes of submaximal exercise, subjects completed a 15-minute performance trial. Blood was collected prior to the exercise bout, as well as after the 45th minute of exercise, to determine serum concentrations of glucose, insulin, lactate, free fatty acids (FFAs), triglycerides, and beta-hydroxybutyrate. Performance was not different (p > 0.05) between the raisin (189.5 +/- 69.9 kJ) and gel (188.0 +/- 64.8 kJ) trials. Prior to exercise, serum concentrations of glucose and other fuel substrates did not differ between trials; however, insulin was higher (p < 0.05) for the gel (110.0 +/- 70.4 microU x ml(-1)) vs. raisin trial (61.4 +/- 37.4 microU x ml(-1)). After 45 minutes of exercise, insulin decreased to 14.2 +/- 6.2 microU x ml(-1) and 13.3 +/- 18.9 microU x ml(-1) for gel and raisin trials, respectively. The FFA concentration increased (+0.2 +/- 0.1 mmol x L(-1)) significantly (p < 0.05) during the raisin trial. Overall, minor differences in metabolism and no difference in performance were detected between the trials. Raisins appear to be a cost-effective source of carbohydrate for pre-exercise feeding in comparison to sports gel for short-term exercise bouts.",
"title": "Metabolic and performance effects of raisins versus sports gel as pre-exercise feedings in cyclists."
},
{
"docid": "MED-4942",
"text": "The association of 11 polychlorinated biphenyls (PCBs) with hypertension was investigated using the National Health and Nutrition Examination Survey (NHANES), 1999-2002. The unweighted number of participants assessed for hypertension ranged from 2074 to 2556 depending on the chemical(s) being analyzed. In unadjusted logistic regressions all 11 PCBs were associated with hypertension. After adjustment for age, gender, race, smoking status, body mass index, exercise, total cholesterol, and family history of coronary heart disease, seven of the 11 PCBs (PCBs 126, 74, 118, 99, 138/158, 170, and 187) were significantly associated with hypertension. The strongest adjusted associations with hypertension were found for dioxin-like PCBs 126 and 118. PCB 126>59.1 pg/g lipid adjusted had an odds ratio of 2.45 (95% CI 1.48-4.04) compared to PCB 126<or=26.1 pg/g lipid adjusted. PCB 118>27.5 ng/g lipid adjusted had an odds ratio of 2.30 (95% CI 1.29-4.08) compared to PCB 118<or=12.5 ng/g lipid adjusted. Moreover, participants with one or more elevated PCBs had an odds ratio of 1.84 (95% CI 1.25-2.70) compared to no PCBs elevated in an adjusted logistic regression. The prevalence of one or more elevated PCBs was 22.76% or 32 million of 142 million persons >or=20 years old in the non-institutionalized US population. We hypothesize that association of seven PCBs with hypertension indicates elevated PCBs are a risk factor for hypertension. What clinicians can do, given the results of this study, is limited unless the appropriate laboratory methods can be made more widely available for testing patients.",
"title": "Association of polychlorinated biphenyls with hypertension in the 1999-2002 National Health and Nutrition Examination Survey."
},
{
"docid": "MED-973",
"text": "There is no recognized definition of what constitutes a high fiber diet. Intakes of dietary fiber in different populations internationally vary widely from less than 20 g to more than 80 g per day. The types of foods contributing fiber also vary; in some countries cereals contribute the most fiber, in others leafy or root vegetables predominate. Vegetables have the highest fiber content per Kcal, and in most populations with fiber intakes over 50 g, vegetables contribute over 50% of total fiber intake. In rural Uganda, where the fiber hypothesis was first developed by Burkitt and Trowell, vegetables contribute over 90% of fiber intake. An experimental diet, the \"Simian\" diet, has been developed to mimic as closely as possible using human foods, the diet consumed by our simian ancestors the great apes. It is also similar to the Ugandan diet in containing large amounts of vegetables and 50 g fiber/1000 Kcal. Though nutritionally adequate, this diet is very bulky and not a suitable model for general recommendations. Dietary guidelines are that fat intake should be < 30% of energy, with a fiber intake of 20-35 g/d. These recommendations are inconsistent with a high fiber diet because, for people consuming more than about 2400 Kcal, low fiber choices for fruits and grains must be selected to keep dietary fiber intake within the range of 20-35 g. In a 30% fat, 1800 Kcal omnivorous diet, selection of wholemeal bread and whole fruit, results in a fiber intake over 35 g/d, and for and 1800 Kcal vegetarian diet, with substitution of modest amounts of peanut butter and beans for meats, dietary fiber intake goes up to 45 g/d. Thus, if it is desirable to promote the use of unrefined foods, the recommended dietary fiber intake should be a minimum of 15-20 g/1000 Kcal.",
"title": "What is a high fiber diet?"
},
{
"docid": "MED-3524",
"text": "Sleep, much like eating, is an essential part of life. The mechanisms of sleep are only partially clear and are the subject of intense research. There is increasing evidence showing that sleep has an influence on dietary choices. Both cross-sectional and epidemiologic studies have demonstrated that those who sleep less are more likely to consume energy-rich foods (such as fats or refined carbohydrates), to consume fewer portions of vegetables, and to have more irregular meal patterns. In this narrative review, we pose the opposite question: can ingested food affect sleep? The purpose of this review is to discuss the evidence linking diet and sleep and to determine whether what we eat and what kind of nutrients we obtain from the food consumed before bedtime matter. In addition, scientific evidence behind traditional sleep-promoting foods such as milk and some herbal products is briefly described. These are reviewed using data from clinical trials, mostly in healthy subjects. In addition, we discuss the possible mechanisms behind these observations. Lastly, we summarize our findings that emerging evidence confirms a link between diet and sleep. Overall, foods impacting the availability of tryptophan, as well as the synthesis of serotonin and melatonin, may be the most helpful in promoting sleep. Although there are clear physiological connections behind these effects, the clinical relevance needs to be studied further. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Diet promotes sleep duration and quality."
},
{
"docid": "MED-4087",
"text": "Many people suffer from fibromyalgia (FM) without an effective treatment. They do not have a good quality of life and cannot maintain normal daily activity. Among the different hypotheses for its ethiopathophysiology, oxidative stress is one of the possibilities. Non-scientific information addressed to patients regarding the benefits of nutrition is widely available, and they are used to trying non-evidenced strategies. The aim of this paper is to find out what we know right now from scientific studies regarding fibromyalgia disease and nutritional status, diets and food supplements. A systematic search has been performed on Medline with a wide range of terms about these nutritional issues. The search has been made during 2009, for articles published between 1998 and 2008. TARGET POPULATION: people suffering from FM. Vegetarian diets could have some beneficial effects probably due to the increase in antioxidant intake. There is a high prevalence of obesity and overweight in patients, and weight control seems to be an effective tool to improve the symptoms. Some nutritional deficiencies have been described, it is not clear whether they are directly related to this disease or not. About the usefulness of some food supplements we found very little data, and it seems that more studies are needed to prove which ones could be of help. Dietary advice is necessary to these patients to improve their diets and maintain normal weight. It would be interesting to investigate more in the field of nutrition and FM to reveal any possible relationships.",
"title": "Fibromyalgia and nutrition, what do we know?"
},
{
"docid": "MED-2970",
"text": "There is increasing evidence that the postprandial state is an important contributing factor to chronic disease. The role of fruit phenolic compounds to protect health and lower disease risk through their actions in mitigating fed-state metabolic and oxidative stressors is of interest and the topic of the present paper. Two main questions are posed: first, what is the role of plant foods, specifically fruits rich in complex and simple phenolic compounds in postprandial metabolic management; and second, does the evidence support consuming these fruits with meals as a practical strategy to preserve health and lower risk for disease? This review provides an overview of the postprandial literature, specifically on the effect of fruits and their inherent phenolic compounds in human subjects on postprandial lipaemia, glycaemia/insulinaemia and associated events, such as oxidative stress and inflammation. Among the identified well-controlled human trials using a postprandial paradigm, >50 % of the trials used wine or wine components and the remaining used various berries. Notwithstanding the need for more research, the collected data suggest that consuming phenolic-rich fruits increases the antioxidant capacity of the blood, and when they are consumed with high fat and carbohydrate 'pro-oxidant and pro-inflammatory' meals, they may counterbalance their negative effects. Given the content and availability of fat and carbohydrate in the Western diet, regular consumption of phenolic-rich foods, particularly in conjunction with meals, appears to be a prudent strategy to maintain oxidative balance and health.",
"title": "Postprandial metabolic events and fruit-derived phenolics: a review of the science."
},
{
"docid": "MED-2304",
"text": "Background There is overwhelming evidence that behavioural factors influence health, but their combined impact on the general population is less well documented. We aimed to quantify the potential combined impact of four health behaviours on mortality in men and women living in the general community. Methods and Findings We examined the prospective relationship between lifestyle and mortality in a prospective population study of 20,244 men and women aged 45–79 y with no known cardiovascular disease or cancer at baseline survey in 1993–1997, living in the general community in the United Kingdom, and followed up to 2006. Participants scored one point for each health behaviour: current non-smoking, not physically inactive, moderate alcohol intake (1–14 units a week) and plasma vitamin C >50 mmol/l indicating fruit and vegetable intake of at least five servings a day, for a total score ranging from zero to four. After an average 11 y follow-up, the age-, sex-, body mass–, and social class–adjusted relative risks (95% confidence intervals) for all-cause mortality(1,987 deaths) for men and women who had three, two, one, and zero compared to four health behaviours were respectively, 1.39 (1.21–1.60), 1.95 (1.70–-2.25), 2.52 (2.13–3.00), and 4.04 (2.95–5.54) p < 0.001 trend. The relationships were consistent in subgroups stratified by sex, age, body mass index, and social class, and after excluding deaths within 2 y. The trends were strongest for cardiovascular causes. The mortality risk for those with four compared to zero health behaviours was equivalent to being 14 y younger in chronological age. Conclusions Four health behaviours combined predict a 4-fold difference in total mortality in men and women, with an estimated impact equivalent to 14 y in chronological age. Editors' Summary Background. Every day, or so it seems, new research shows that some aspect of lifestyle—physical activity, diet, alcohol consumption, and so on—affects health and longevity. For the person in the street, all this information is confusing. What is a healthy diet, for example? Although there are some common themes such as the benefit of eating plenty of fruit and vegetables, the details often differ between studies. And exactly how much physical activity is needed to improve health? Is a gentle daily walk sufficient or simply a stepping stone to doing enough exercise to make a real difference? The situation with alcohol consumption is equally confusing. Small amounts of alcohol apparently improve health but large amounts are harmful. As a result, it can be hard for public-health officials to find effective ways to encourage the behavioral changes that the scientific evidence suggests might influence the health of populations. Why Was This Study Done? There is another factor that is hindering official attempts to provide healthy lifestyle advice to the public. Although there is overwhelming evidence that individual behavioral factors influence health, there is very little information about their combined impact. If the combination of several small differences in lifestyle could be shown to have a marked effect on the health of populations, it might be easier to persuade people to make behavioral changes to improve their health, particularly if those changes were simple and relatively easy to achieve. In this study, which forms part of the European Prospective Investigation into Cancer and Nutrition (EPIC), the researchers have examined the relationship between lifestyle and the risk of dying using a health behavior score based on four simply defined behaviors—smoking, physical activity, alcohol drinking, and fruit and vegetable intake. What Did the Researchers Do and Find? Between 1993 and 1997, about 20,000 men and women aged 45–79 living in Norfolk UK, none of whom had cancer or cardiovascular disease (heart or circulation problems), completed a health and lifestyle questionnaire, had a health examination, and had their blood vitamin C level measured as part of the EPIC-Norfolk study. A health behavior score of between 0 and 4 was calculated for each participant by giving one point for each of the following healthy behaviors: current non-smoking, not physically inactive (physical inactivity was defined as having a sedentary job and doing no recreational exercise), moderate alcohol intake (1–14 units a week; a unit of alcohol is half a pint of beer, a glass of wine, or a shot of spirit), and a blood vitamin C level consistent with a fruit and vegetable intake of at least five servings a day. Deaths among the participants were then recorded until 2006. After allowing for other factors that might have affected their likelihood of dying (for example, age), people with a health behavior score of 0 were four times as likely to have died (in particular, from cardiovascular disease) than those with a score of 4. People with a score of 2 were twice as likely to have died. What Do These Findings Mean? These findings indicate that the combination of four simply defined health behaviors predicts a 4-fold difference in the risk of dying over an average period of 11 years for middle-aged and older people. They also show that the risk of death (particularly from cardiovascular disease) decreases as the number of positive health behaviors increase. Finally, they can be used to calculate that a person with a health score of 0 has the same risk of dying as a person with a health score of 4 who is 14 years older. These findings need to be confirmed in other populations and extended to an analysis of how these combined health behaviors affect the quality of life as well as the risk of death. Nevertheless, they strongly suggest that modest and achievable lifestyle changes could have a marked effect on the health of populations. Armed with this information, public-health officials should now be in a better position to encourage behavior changes likely to improve the health of middle-aged and older people. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050012.",
"title": "Combined Impact of Health Behaviours and Mortality in Men and Women: The EPIC-Norfolk Prospective Population Study"
},
{
"docid": "MED-2655",
"text": "Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.",
"title": "Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial"
},
{
"docid": "MED-1527",
"text": "Importance Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality, but the relationship is not well established. Objective To evaluate the association between vegetarian dietary patterns and mortality. Design Prospective cohort study; mortality analysis by Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. Setting Adventist Health Study 2 (AHS-2), a large North American cohort. Participants A total of 96 469 Seventh-day Adventist men and women recruited between 2002 and 2007, from which an analytic sample of 73 308 participants remained after exclusions. Exposures Diet was assessed at baseline by a quantitative food frequency questionnaire and categorized into 5 dietary patterns: nonvegetarian, semi-vegetarian, pesco-vegetarian, lacto-ovo–vegetarian, and vegan. Main Outcome and Measure The relationship between vegetarian dietary patterns and all-cause and cause-specific mortality; deaths through 2009 were identified from the National Death Index. Results There were 2570 deaths among 73 308 participants during a mean follow-up time of 5.79 years. The mortality rate was 6.05 (95% CI, 5.82–6.29) deaths per 1000 person-years. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs non-vegetarians was 0.88 (95% CI, 0.80–0.97). The adjusted HR for all-cause mortality in vegans was 0.85 (95% CI, 0.73–1.01); in lacto-ovo–vegetarians, 0.91 (95% CI, 0.82–1.00); in pesco-vegetarians, 0.81 (95% CI, 0.69–0.94); and in semi-vegetarians, 0.92 (95% CI, 0.75–1.13) compared with nonvegetarians. Significant associations with vegetarian diets were detected for cardiovascular mortality, noncardiovascular noncancer mortality, renal mortality, and endocrine mortality. Associations in men were larger and more often significant than were those in women. Conclusions and Relevance Vegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality. Results appeared to be more robust in males. These favorable associations should be considered carefully by those offering dietary guidance.",
"title": "Vegetarian Dietary Patterns and Mortality in Adventist Health Study 2"
}
] |
7040
|
Want to buy above market price?
|
[
{
"docid": "331521",
"text": "Buy and sell orders always include the price at which you buy/sell. That's how the market prices for stocks are determines. So if you want to place a buy order at 106, you can do that. When that order was fulfilled and you have the stock, you can place a sell order at 107. It will be processed as soon as someone places a buy order at 107. Theoretically you can even place sell orders for stocks you haven't even bought yet. That's called short selling. You do that when you expect a stock to go down in the future. But this is a very risky operation, because when you mispredict the market you might end up owing more money than you invested. No responsible banker will even discuss this with you when you can not prove you know what you are doing.",
"title": ""
},
{
"docid": "184390",
"text": "Yes, you can do this buy placing a conditional order to buy at market if the price moves to 106 or above. Once the price hits 106 your market order will hit the market and you will purchase the stock at 106 or above. You can also place a tack profit order at 107 linked to your initial conditional buy order, so that once you buy order is executed and you buy at 106, a take profit order will be executed only if the price reaches 107 or above. If the price never reaches 106, neither your market buy order or take profit order will hit the market and you won't buy or sell anything.",
"title": ""
}
] |
[
{
"docid": "126885",
"text": "\"Yes it is possible, as long as the broker you use allows conditional orders. I use CMC Markets in Australia, and they allow free conditional orders either when initially placing a buy order or after already buying a stock. See the Place New Order box below: Once you have selected a stock to buy, the number of shares you want to buy and at what price you can place up to 3 conditional orders. The first condition is a \"\"Place order if...\"\" conditional order. Here you can place a condition that your buy order will only be placed onto the market if that condition is met first. Say the stock last traded at $9.80 and you only want to place your order the next day if the stock price moves above the current resistance at $10.00. So you would Place order if Price is at or above $10.00. So if the next day the price moves up to $10 or above your order will be placed onto the market. The second condition is a \"\"Stop loss\"\" conditional order. Here you place the price you want to sell at if the price drops to or past your stop loss price. It will only be placed on to the market if your buy order gets traded. So if you wanted to place your stop loss at $9.00, you would type in 9.00 in the box after \"\"If at or below ?\"\" and select if you want a limit or market order. The third condition is a \"\"Take profit\"\" conditional order. This allows you to take profits if the stock reaches a certain price. Say you wanted to take profits at 50%, that is if the price reached $15.00. So you would type in 15.00 in the box after \"\"If at or above ?\"\" and again select if you want a limit or market order. These conditional orders can all be placed at the time you enter your buy order and can be edited or deleted at any time. The broker you use may have a different process for entering conditional orders, and some brokers may have many more conditional orders than these three, so investigate what is out there and if you are confused in how to use the orders with your broker, simply ask them for a demonstration in how to use them.\"",
"title": ""
},
{
"docid": "254542",
"text": "If you want to buy once the price goes up to $101 or above you can place a conditional order to be triggered at $101 or above and for a limit order to entered to buy at $102. This will mean that as soon as the price reaches $101 or above, your limit order will enter the market and you will buy at any price from $102 or below. So if the price just trickles over $101 you will end up buying at around $101 or just over $101. However, if the price gaps above $101, say it gaps up to $101.50, then you will end up buying at around $101.50. If the price gaps up above $102, say $102.50, then your limit order at $102 will hit the market but it will not trade until the price drops back to $102 or below.",
"title": ""
},
{
"docid": "59638",
"text": "\"Yes there is, it is called a One-Cancels-the-Other Order (OCO). Investopedia defines a OCO order as: Definition of 'One-Cancels-the-Other Order - OCO' A pair of orders stipulating that if one order is executed, then the other order is automatically canceled. A one-cancels-the-other order (OCO) combines a stop order with a limit order on an automated trading platform. When either the stop or limit level is reached and the order executed, the other order will be automatically canceled. Seasoned traders use OCO orders to mitigate risk. I use CMC Markets in Australia, and they allow free conditional and OCO orders either when initially placing a buy order or after already buying a stock. See the Place New Order box below: Once you have selected a stock to buy, the number of shares you want to buy and at what price you can place up to 3 conditional orders. The first condition is a \"\"Place order if...\"\" conditional order. Here you can place a condition that your buy order will only be placed onto the market if that condition is met first. Say the stock last traded at $9.80 and you only want to place your order the next day if the stock price moves above the current resistance at $10.00. So you would Place order if Price is at or above $10.00. So if the next day the price moves up to $10 or above your order will be placed onto the market. The next two conditional orders form part of the OCO Orders. The second condition is a \"\"Stop loss\"\" conditional order. Here you place the price you want to sell at if the price drops to or past your stop loss price. It will only be placed on to the market if your buy order gets traded. So if you wanted to place your stop loss at $9.00, you would type in 9.00 in the box after \"\"If at or below ?\"\" and select if you want a limit or market order. The third condition is a \"\"Take profit\"\" conditional order. This allows you to take profits if the stock reaches a certain price. Say you wanted to take profits at 30%, that is if the price reached $13.00. So you would type in 13.00 in the box after \"\"If at or above ?\"\" and again select if you want a limit or market order. Once you have bought the stock if the stop order gets triggered then the take profit order gets cancelled automatically. If on the other hand the take profit order gets triggered then the stop loss order gets cancelled automatically. These OCO conditional orders can be placed either at the time you enter your buy order or after you have already bought the stock, and they can be edited or deleted at any time. The broker you use may have a different process for entering conditional and OCO orders such as these.\"",
"title": ""
},
{
"docid": "278630",
"text": "Firstly what are you trading that you could lose more than you put in? If you are simply trading stocks you will not lose more than you put in, unless you are trading on margin. A limit order is basically that, a limit on the maximum price you want your buy order bought at or the minimum price you want your sell order sold at. If you can't be glued to the screen all day when you place a limit order, and the market moves the opposite way, you may miss out on your order being executed. Even if you can be in front of the screen all day, you then have to decide if you want to chase the market of miss out on your purchase or sale. For example, if a stock is trading at $10.10 and you put a limit buy order to buy 1000 shares at or below $10.00 and the price keeps moving up to $10.20, then $10.30 and then $10.50, until it closes the day at $11.00. You then have the choice during the day to miss out on buying the shares or to increase your limit order in order to buy at a higher price. Sometime if the stock is not very liquid, i.e. it does not trade very often and has low volume, the price may hit $10.00 and you may only have part of your order executed, say 500 out of your 1000 shares were bought. This may mean that you may have to increase the price of your remaining order or be happy with only buying 500 shares instead of 1000. The same can happen when you are selling (but in reverse obviously). With market order, however, you are placing a buy order to buy at the next bid price in the depth or a sell order to sell at the next offer price in the depth. See the market depth table below: Note that this price depth table is taken before market open so it seems that the stock is somewhat illiquid with a large gap between the first and second prices in the buyers (bid) prices. When the market opened this gap is closed, as WBC is a major Australian bank and is quite liquid. (the table is for demonstration purposes only). If we pretend that the market was currently open and saw the current market depth for WBC as above, you could decide to place a limit sell order to sell 1000 shares at say $29.91. You would sell 100 shares straight away but your remaining 900 sell order will remain at the top of the Sellers list. If other Buyers come in at $29.91 you may get your whole sale completed, however, if no other Buyers place orders above $29.80 and other Sellers come into the market with sell orders below $29.91, your remaining order may never be executed. If instead you placed a market sell order you would immediately sell 100 shares at $29.91 and the remaining 900 shares at $29.80. (so you would be $99 or just over 0.3% worse off than if you were able to sell the full 1000 shares at $29.91). The question is how low would you have had to lower your limit order price if the price for WBC kept on falling and you had to sell that day? There are risks with whichever type of order you use. You need to determine what the purpose of your order is. Is it to get in or out of the market as soon as possible with the possibility of giving a little bit back to the market? Or is it to get the price you want no matter how long it takes you? That is you are willing to miss out on buying the shares (can miss out on a good buy if the price keeps rising for weeks or months or even years) or you are willing to miss out on selling them right now and can wait for the price to come back up to the price you were willing to sell at (where you may miss out on selling the shares at a good price and they keep on falling and you give back all your profits and more). Just before the onset of the GFC I sold some shares (which I had bought a few years earlier at $3.40) through a market order for $5.96. It had traded just above $6 a few days earlier, but if instead of a market order I had placed a limit order to sell at $6.00 or more I would have missed out on the sale. The price never went back up to $6 or above, and the following week it started dropping very quickly. It is now trading at about $1.30 and has never gone back above $2.00 (5.5 years later). So to me placing a limit order in this case was very risky.",
"title": ""
},
{
"docid": "389329",
"text": "Consider the mechanic which actually drives the 'price' of a stock. In simplest terms, the 'price' of a stock is the price at which the most recent trade occurred. ie: if the price of IBM is $100/share, that means the last time someone bought IBM stock, they paid $100. Above and below the 'spot price', are dozens/hundreds/thousands of buyers and sellers who have placed orders that no one is yet willing to match. ie: if IBM's spot price is at $100, there could still be 10,000 people willing to sell for $101 (called the 'ask' price, for the lowest price someone is currently willing to sell at), and 15,000 willing to buy for $99 (called the 'bid' price, for the highest price someone is currently willing to buy for). Until someone is willing to buy for $101, then no one will be able to sell at $101. Until someone is willing to sell for $99, no one will be able to buy for $99. Typically orders are placed in the market at a particular limit. Meaning that those orders to buy at $99/sell at $101 are already in the 'system', and will be matched immediately as soon as someone is willing to meet the price on the other side. Now consider general market economics: high demand drives up price, and high supply drives down price. If the details above for IBM were yesterday, and today some news came out that IBM was laying off employees, imagine that another 10,000 people who held shares wanted to sell. Now there would be 20,000 sellers and only 15,000 buyers. If those new sellers were aggressive about wanting to sell, they would have to drop their price to $99, to match the highest buyers in the market. Put together, this means that as more sellers enter the market, supply of shares increases, driving down price. Conversely, as more buyers enter the market, demand for shares increases, driving up share price. As a result of the above, you can say that (all else being equal) if price for a stock goes up, there were more buyers that day, and if price goes down, there were more sellers that day. On the face of it, that is not necessarily true, because you could have the same number of buyers and sellers, one side could have simply decreased/increased their acceptable price to match the other side.",
"title": ""
},
{
"docid": "494295",
"text": "There are a couple of things you could do, but it may depend partly on the type of orders your broker has available to you. Firstly, if you are putting your limit order the night before after close of market at the top of the bids, you may be risking missing out if bid & offer prices increase by the time the market opens the next day. On the other hand, if bid & offer prices fall at the open of the next day you should get your order filled at or below your limit price. Secondly, you could be available at the market open to see if prices are going up or down and then work out the price you want to buy at then and work out the quantity you can buy at that price. I personally don't like this method because you usually get too emotional, start chasing the market if prices start rising, or start regretting buying at a price and prices fall straight afterwards. My preferred method is this third option. If your broker provides stop orders you can use these to both get into and out of the market. How they work when trying to get into the market is that once you have done your analysis and picked a price that you would want to purchase at, you put a stop buy order in. For example, the price closed at $9.90 the previous day and there has been resistance at $10.00, so you would put a stop buy trigger if the price goes over $10, say $10.01. If your stop buy order gets triggered you can have either a buy market order or a limit order above $10.01 (say $10.02). The market order would go through immediately whilst the limit order would only go through if the price continues going to $10.02 or above. The advantage of this is that you don't get emotional trying to buy your securities whilst sitting in front of the screen, you do your analysis and set your prices whilst the market is closed, you only buy when the security is rising (not falling). As your aim is to be in long term you shouldn't be concerned about buying a little bit higher than the previous days close. On the other hand if you try and buy when the price is falling you don't know when it will stop falling. It is better to buy when the price shows signs of rising rather than falling (always follow the trend).",
"title": ""
},
{
"docid": "259178",
"text": "You bought the right – but not the obligation – to buy a certain number of shares at $15 from whomsoever sold you the option, and you paid a premium for it. You can choose whether you want to buy the shares at $15 during the period agreed upon. If you call for the shares, the other guy has to sell the shares to you for $15 each, even if the market price is higher. You can then turn around and promptly resell the purchased shares at the higher market price. If the market price never rises above $15 at any time while the option is open, you still have the right to buy the shares for $15 if you choose to do so. Most rational people would let the option expire without exercising it, but this is not a legal requirement. Doing things like buying shares at $15 when the market price is below $15 is perfectly legal; just not very savvy. You cannot cancel the option in the sense of going to the seller of the option and demanding your premium money back because you don't intend to exercise the option because the market price is below $15. Of course, if the market price is above $15 and you tell the seller to cancel the contract, they will be happy to do so, since it lets them off the hook. They may or may not give you the premium back in this case.",
"title": ""
},
{
"docid": "362212",
"text": "Buying stocks is like an auction. Put in the price you want to pay and see if someone is willing to sell at that price. Thing to remember about after hours trading; There is a lot less supply so there's always a larger bid/ask price spread. That's the price brokers charge to handle the stocks they broker over and above the fee. That means you will always pay more after the market closes. Unless it is bad news, but I don't think you want to buy when that happens. I think a lot of the after market trading is to manipulate the market. Traders drive up the price overnight with small purchases then sell their large holdings when the market opens.",
"title": ""
},
{
"docid": "212685",
"text": "At any point of time, buyer wants to purchase a stock at lesser price and seller wants to sell the stock at a higher price. Let's consider this scenario Company XYZ is trading at 100$, as stated above buyer wants to purchase at lower price and seller at higher price, this information will be available in Market depth, let's consider there are 5 buyers and 5 sellers, below are the details of their orders Buyers List Sellers List Highest order in buyers list will contain the bid price and bid quantity, Lowest order in Sellers list will contain the offer price and offer quantity. Now, if I want to buy 50 Stocks of company XYZ, need to place an order first, it can be either limit or Market. Limit Order : In this order, I will mention the price(buy price) at which I wish to buy, if there is any seller selling the stock less than or equal to price I have mentioned, then the order will be executed else it will be added to buyers list Market Order : In this order, I will not mention the price, if I wish to purchase 50 Stocks, then it will find the lowest offer price and buy stocks, in our case it will be 101. if I wish to purchase 200 Stocks, then it will find the lowest offer price and buy stocks, in our case it will be 2 transactions, since entire request cannot be accommodated in single order Usually the volume(Ask Volume and Offer Volume) being displayed are all Limit orders and not Market orders, Market orders are executed immediately. This is just an example, However several transactions are executed within a second, hence we will get to know the exact value only after the order is completed(executed)",
"title": ""
},
{
"docid": "178446",
"text": "\"Correcting Keith's answer (you should have read about these details in the terms and conditions of your bank/broker): Entrustment orders are like a \"\"soft\"\" limit order and meaningless without a validity (which is typically between 1 and 5 days). If you buy silver at an entrustment price above market price, say x when the market offer is m, then parts of your order will likely be filled at the market price. For the remaining quantity there is now a limit, the bank/broker might fill your order over the next 5 days (or however long the validity is) at various prices, such that the overall average price does not exceed x. This is different to a limit order, as it allows the bank/broker to (partially) buy silver at higher prices than x as long as the overall averages is x or less. In a limit set-up you might be (partially) filled at market prices first, but if the market moves above x the bank/broker will not fill any remaining quantities of your order, so you might end up (after a day or 5 days) with a partially filled order. Also note that an entrustment price below the market price and with a short enough validity behaves like a limit price. The 4th order type is sort of an opposite-side limit price: A stop-buy means buy when the market offer quote goes above a certain price, a stop-sell means sell when the market bid quote goes below a certain price. Paired with the entrusment principle, this might mean that you buy/sell on average above/below the price you give. I don't know how big your orders are or will be but always keep in mind that not all of your order might be filled immediately, a so-called partial fill. This is particularly noteworthy when you're in a pro-rata market.\"",
"title": ""
},
{
"docid": "169062",
"text": "\"It's good to ask this question, because this is one of the fundamental dichotomies in market microstructure. At any time T for each product on a (typical) exchange there are two well-defined prices: At time T there is literally no person in the market who wants to sell below the ask, so all the people who are waiting to buy at the bid (or below) could very well be waiting there forever. There's simply no guarantee that any seller will ever want to part with their product for a lesser price than they think it's worth. So if you want to buy the product at time T you have a tough choice to make: you get in line at the bid price, where there's no guarantee that your request will ever be filled, and you might never get your hands on the product you decide that owning the product right now is more valuable to you than (ask - bid) * quantity, so you tell the exchange that you're willing to buy at the ask price, and the exchange matches you with whichever seller is first in line Now, if you're in the market for the long term, the above choice is completely immaterial to you. Who cares if you pay $10.00 * 1000 shares or $10.01 * 1000 shares when you plan to sell 30 years from now at $200 (or $200.01)? But if you're a day trader or anyone else with a very short time horizon, then this choice is extremely important: if the price is about to go up several cents and you got in line at the bid (and never got filled) then you missed out on some profit if you \"\"cross the spread\"\" to buy at the ask and then the price doesn't go up (or worse, goes down), you're screwed. In order to get out of the position you'll have to cross the spread again and sell at at most the bid, meaning you've now paid the spread twice (plus transaction fees and regulatory fees) for nothing. (All of the above also applies in reverse for selling at the ask versus selling at the bid, but most people like to learn in terms of buying rather than selling.)\"",
"title": ""
},
{
"docid": "377186",
"text": "If you want to invest in the stock market, whether over a shorter period of 1 to 2 years or over a longer period of 10 or 20 years or longer you need to take some precautions and have a written investment plan with a risk management strategy incorporated in your plan. Others have said that 1 to 2 years is too short to invest in the stock market as the stock market can have a correction and fall by 50%. But it doesn't matter if you invest for 1 year or if you invest for 50 years, the stock market can still fall by 50% just before you plan to withdraw your funds. What you need to figure out is a way to get out before the market falls by 40% to 50%. A simple way to do this is to use technical indicators to warn you when a market trend is starting to change and that it is time to get out of the market. Two simple indicators you can use on a market index are the Rate of Change (ROC) indicator and the 100 week Moving Average (MA). Below is a 10 year weekly chart of the S&P500 with these two indicators charted. They show good times to get into the market and good times to get out. If you are using the 100 week MA you would buy in when the price crosses above the MA line and sell when the price crosses below the MA line. If you are using the ROC indicator you would buy in when the ROC indicator crosses above the zero line and sell when the ROC indicator crosses below the zero line. So your investment plan could be to buy an Index ETF representing the S&P500 when the ROC moves above zero and sell when it crosses below zero. You can also place a trailing stop loss of 10% to protect you in case of a sudden fall over a couple of days. You can manage your investments in as little as 10 minutes per week by checking the chart once per week and adjusting your stop loss order. If you want to progressively add to your investment each month you could check the charts and only add any new funds if both the ROC is above zero and sloping upwards. Another option for adding new funds could be if the price is above the MA and moving further away from the MA. All these rules should be incorporated into your investment plan so that you are not basing your decisions based on emotions. There are many other Technical Analysis Indicators you could also learn about to make better educated decisions about your stock market investments. However, what I have provided here is enough for anyone to test over different indexes and time frames and do their own paper trading on to gain some confidence before placing any real money on the table.",
"title": ""
},
{
"docid": "447886",
"text": "\"After learning about things that happened in the \"\"flash crash\"\" I always use limit orders. In an extremely rare instance if you place a market order when there is a some glitch, for example some large trader adds a zero at the end of their volume, you could get an awful price. If I want to buy at the market price, I just set the limit about 1% above the market price. If I want to sell, I set the limit 1% below the market price. I should point out that your trade is not executed at the limit price. If your limit price on a buy order is higher than the lowest offer, you still get filled at the lowest offer. If before your order is submitted someone fills all offers up to your limit price, you will get your limit price. If someone, perhaps by accident, fills all orders up to twice your limit price, you won't end up making the purchase. I have executed many purchases this way and never been filled at my limit price.\"",
"title": ""
},
{
"docid": "28604",
"text": "\"The current stock price you're referring to is actually the price of the last trade. It is a historical price – but during market hours, that's usually mere seconds ago for very liquid stocks. Whereas, the bid and ask are the best potential prices that buyers and sellers are willing to transact at: the bid for the buying side, and the ask for the selling side. But, think of the bid and ask prices you see as \"\"tip of the iceberg\"\" prices. That is: The \"\"Bid: 13.20 x200\"\" is an indication that there are potential buyers bidding $13.20 for up to 200 shares. Their bids are the highest currently bid; and there are others in line behind with lower bid prices. So the \"\"bid\"\" you're seeing is actually the best bid price at that moment. If you entered a \"\"market\"\" order to sell more than 200 shares, part of your order would likely be filled at a lower price. The \"\"Ask: 13.27 x1,000\"\" is an indication that there are potential sellers asking $13.27 for up to 1000 shares. Their ask prices are the lowest currently asked; and there are others in line behind with higher ask prices. So the \"\"ask\"\" you're seeing is the best asking price at that moment. If you entered a \"\"market\"\" order to buy more than 1000 shares, part of your order would likely be filled at a higher price. A transaction takes place when either a potential buyer is willing to pay the asking price, or a potential seller is willing to accept the bid price, or else they meet in the middle if both buyers and sellers change their orders. Note: There are primarily two kinds of stock exchanges. The one I just described is a typical order-driven matched bargain market, and perhaps the kind you're referring to. The other kind is a quote-driven over-the-counter market where there is a market-maker, as JohnFx already mentioned. In those cases, the spread between the bid & ask goes to the market maker as compensation for making a market in a stock. For a liquid stock that is easy for the market maker to turn around and buy/sell to somebody else, the spread is small (narrow). For illiquid stocks that are harder to deal in, the spread is larger (wide) to compensate the market-maker having to potentially carry the stock in inventory for some period of time, during which there's a risk to him if it moves in the wrong direction. Finally ... if you wanted to buy 1000 shares, you could enter a market order, in which case as described above you'll pay $13.27. If you wanted to buy your shares at no more than $13.22 instead, i.e. the so-called \"\"current\"\" price, then you would enter a limit order for 1000 shares at $13.22. And more to the point, your order would become the new highest-bid price (until somebody else accepts your bid for their shares.) Of course, there's no guarantee that with a limit order that you will get filled; your order could expire at the end of the day if nobody accepts your bid.\"",
"title": ""
},
{
"docid": "550643",
"text": "If you can afford the cost and risk of 100 shares of stock, then just sell a put option. If you can only afford a few shares, you can still use the information the options market is trying to give you -- see below. A standing limit order to buy a stock is essentially a synthetic short put option position. [1] So deciding on a stock limit order price is the same as valuing an option on that stock. Options (and standing limit orders) are hard to value, and the generally accepted math for doing so -- the Black-Scholes-Merton framework -- is also generally accepted to be wrong, because of black swans. So rather than calculate a stock buy limit price yourself, it's simpler to just sell a put at the put's own midpoint price, accepting the market's best estimate. Options market makers' whole job (and the purpose of the open market) is price discovery, so it's easier to let them fight it out over what price options should really be trading at. The result of that fight is valuable information -- use it. Sell a 1-month ATM put option every month until you get exercised, after which time you'll own 100 shares of stock, purchased at: This will typically give you a much better cost basis (several dollars better) versus buying the stock at spot, and it offloads the valuation math onto the options market. Meanwhile you get to keep the cash from the options premiums as well. Disclaimer: Markets do make mistakes. You will lose money when the stock drops more than the option market's own estimate. If you can't afford 100 shares, or for some reason still want to be in the business of creating synthetic options from pure stock limit orders, then you could maybe play around with setting your stock purchase bid price to (approximately): See your statistics book for how to set ndev -- 1 standard deviation gives you a 30% chance of a fill, 2 gives you a 5% chance, etc. Disclaimer: The above math probably has mistakes; do your own work. It's somewhat invalid anyway, because stock prices don't follow a normal curve, so standard deviations don't really mean a whole lot. This is where market makers earn their keep (or not). If you still want to create synthetic options using stock limit orders, you might be able to get the options market to do more of the math for you. Try setting your stock limit order bid equal to something like this: Where put_strike is the strike price of a put option for the equity you're trading. Which option expiration and strike you use for put_strike depends on your desired time horizon and desired fill probability. To get probability, you can look at the delta for a given option. The relationship between option delta and equity limit order probability of fill is approximately: Disclaimer: There may be math errors here. Again, do your own work. Also, while this method assumes option markets provide good estimates, see above disclaimer about the markets making mistakes.",
"title": ""
},
{
"docid": "561997",
"text": "I think your premise is slightly flawed. Every investment can add or reduce risk, depending on how it's used. If your ordering above is intended to represent the probability you will lose your principal, then it's roughly right, with caveats. If you buy a long-term government bond and interest rates increase while you're holding it, its value will decrease on the secondary markets. If you need/want to sell it before maturity, you may not recover your principal, and if you hold it, you will probably be subject to erosion of value due to inflation (inflation and interest rates are correlated). Over the short-term, the stock market can be very volatile, and you can suffer large paper losses. But over the long-term (decades), the stock market has beaten inflation. But this is true in aggregate, so, if you want to decrease equity risk, you need to invest in a very diversified portfolio (index mutual funds) and hold the portfolio for a long time. With a strategy like this, the stock market is not that risky over time. Derivatives, if used for their original purpose, can actually reduce volatility (and therefore risk) by reducing both the upside and downside of your other investments. For example, if you sell covered calls on your equity investments, you get an income stream as long as the underlying equities have a value that stays below the strike price. The cost to you is that you are forced to sell the equity at the strike price if its value increases above that. The person on the other side of that transaction loses the price of the call if the equity price doesn't go up, but gets a benefit if it does. In the commodity markets, Southwest Airlines used derivatives (options to buy at a fixed price in the future) on fuel to hedge against increases in fuel prices for years. This way, they added predictability to their cost structure and were able to beat the competition when fuel prices rose. Even had fuel prices dropped to zero, their exposure was limited to the pre-negotiated price of the fuel, which they'd already planned for. On the other hand, if you start doing things like selling uncovered calls, you expose yourself to potentially infinite losses, since there are no caps on how high the price of a stock can go. So it's not possible to say that derivatives as a class of investment are risky per se, because they can be used to reduce risk. I would take hedge funds, as a class, out of your list. You can't generally invest in those unless you have quite a lot of money, and they use strategies that vary widely, many of which are quite risky.",
"title": ""
},
{
"docid": "498075",
"text": "\"The response to this question will be different depending which of the investment philosophies you are using. Value investors look at the situation the company is in and try to determine what the company is worth and what it will be worth in the future. Then they look at the current stock price and decide whether or not the stock is priced at a good deal or not. If the stock price is priced lower than they believe the company is worth, they would want to buy stock, and if the price rises above what they believe to be the true value, they would sell. These types of investors are not looking at the history or trend of what the price has done in the past, only what the current price is and where they believe the price should be in the future. Technical analysis investors do something different. It is their belief that as stock prices go up and down, they generally follow patterns. By looking at a chart of what a stock price has been in the past, they try to predict where it is headed, and buy or sell based on that prediction. In general, value investors are longer-term investors, and technical analysis investors are short-term investors. The advice you are considering makes a lot of sense if you are using technical analysis. If you have a stock that is trending down, your strategy probably tells you to sell; buying more in the hopes of turning things around would be seen as a mistake. It is like the gambler in Vegas who keeps playing a game he is losing, hoping that his luck changes. However, for the value investor, the historical price of a stock, and even the amount you currently have gained or lost in the stock, are essentially ignored. All that matters is whether or not the stock price is above or below the true value determined by the investor. For him, if the stock price falls and he believes the company still has a high value, it could be a signal to buy more. The above advice doesn't really apply for them. Many investors don't follow either of these strategies. They believe that it is too difficult and risky to try to predict the future price of an individual stock. Instead, they invest in many companies all at once using index mutual funds, believing that the stock market as a whole always heads up over a long time frame. Those investors don't care at all if the prices of stock are going up or down. They simply keep investing each month, and hold until they have another use for the money. The above advice isn't useful for them at all. No matter which kind of investing you are doing, the most important thing is to pick a strategy you believe in and follow the plan without emotion. Emotions can cause investors to make mistakes and start buying when their strategy tells them to sell. Instead of trying to follow fortune cookie advice like \"\"Don't throw good money after bad,\"\" choose an investment strategy, make a plan, test it, and follow it, cautiously (after all, it may be a bad plan). For what it is worth, I am the third type of investor listed above. I don't buy individual stocks, and I don't look at the stock prices when investing more each month. Your description of your own strategy as \"\"buy and hold\"\" suggests you might prefer the same approach.\"",
"title": ""
},
{
"docid": "514841",
"text": "A limit order is simply an order to buy at a maximum price or sell at a minimum price. For example, if the price is $100 and you want to sell if the price rises to $110, then you can simply put a limit order to sell at $110. The order will be placed in the market and when the price reaches $110 your order will be executed. If the price gaps at the open to $111, then you would end up selling for $111. In other words you will get a minimum of $110 per share. A stop limit order is where you put a stop loss order, which when it gets triggered, will place a limit order in the market for you. For example, you want to limit your losses by placing a stop loss order if the price drops to $90. If you chose a market order with your stop loss as soon as the price hits $90 your stop loss would be triggered and the shares would sell at the next available price, usually at $90, but could be less if the market gaps down past $90. If on the other hand you placed a limit order at $89.50 with your stop loss, when the stop loss order gets triggered at $90 your limit order will be placed into the market to sell at $89.50. So you would get a minimum of $89.50 per share, however, if the market gaps down below $89.50 your order will be placed onto the market but it won't sell, unless the price goes back to or above $89.50. Hope this helps.",
"title": ""
},
{
"docid": "581579",
"text": "\"For any large company, there's a lot of activity, and if you sell at \"\"market\"\" your buy or sell will execute in seconds within a penny or two of the real-time \"\"market\"\" price. I often sell at \"\"limit\"\" a few cents above market, and those sell within 20 minutes usually. For much smaller companies, obviously you are beholden to a buyer also wanting that stock, but those are not on major exchanges. You never see whose buy order you're selling into, that all happens behind the curtain so to speak.\"",
"title": ""
},
{
"docid": "475019",
"text": "\"The short version of JB King's excellent answer is that the company will typically buy back shares from the open market at market price. Sometimes, it will specifically target larger stakeholders, even controlling interests, who are making noise that they want to divest; if such an investor were to just dump their stock on the open market, neither the investor nor the company would be very happy with the resulting price collapse. In those cases, the company may offer an incentive price above market rates. In recent times, the investor looking to divest has often been the U.S. Government, who received stock in return for bailouts, and (with notable exceptions) turned a modest profit on many of them. Not enough to break even on the entire bailout, but the Government didn't just throw $700 billion in taxpayer money down a hole as conservative pundits would have you believe. In the '80s, a specific type of buy-back was made famous, called the \"\"leveraged buyout\"\". Basically, the company took out a huge loan against itself, and used that money to buy up all the company's publicly-traded shares, essentially becoming a private company. This became a popular tool among private equity groups, for better and worse.\"",
"title": ""
},
{
"docid": "251002",
"text": "When using the Stochastic Indicator your basic aim is to buy (go long) when the stochastic becomes oversold (goes below 20%) and then the %K line crosses above the %D line at a market low, and to sell (go short) when the stochastic becomes overbought (goes above 80%) and then the %K line crosses below the %D line at a market high. Other indicators or candlestick patters can also be used to further confirm the trade. Below is a chart of a trade I recently took on GUD.AX using the Slow Stochastic in combination with support and resistance levels as well as a candlestick pattern. When I conducted my stock search on the evening of 28th July 2015, GUD was one of the results from the search that I particularly liked. The Slow Stochastic had just made a crossover in the oversold area just as the price was bouncing off its recent lows at the support line. But what I really like about this opportunity was that there was also a bullish reversal candle (a Hammer) at this short term market bottom. The high for the day was $8.34, so I placed a stop buy order to buy the stock tomorrow if the price opened or moved above this high of today. So I would only buy if the stock hit or moved above $8.35 during the next days trading. So if the stock opened and stayed below the previous day's high I would not buy the stock and my order would be canceled at the end of the day. This is very important because it stops you from getting into trades that don't go in the direction you want. If this happens then you could check the chart again after market close to see if it is still worthwhile to place a new order for the next day. On the 29th July 2015 the stock did open higher at $8.42 (which is where my order got executed) and closed at $8.46. So I ended up buying slightly above my target price but it did move higher on the day, so a successful entry overall. I had placed my initial stop loss at $8.09 (just below the low of the previous day of $8.10). If the trade had gone against me in the following days the most I would have lost was 1% of my total account capital. My target for this trade was $9.86 (just below the resistance line near $10), which would represent a 5% gain against my total account capital (or approx. 16.7% gain on the trade). So my win to loss ratio was 5:1. As you can see from the chart, the next day gapped up at the open and prices continued moving up strongly during the day. The next day was a slightly negative day, and then a few days later, on the 5th August 2015 my target price of $9.86 was reached (with a high of $9.88 for that day), so my order was closed for a total profit of 16.7% on the face value of the trade. However, as I bought on margin (using CFDs) my actual profit on the initial margin I had invested was 167%. My total time in the trade was 7 days, and I spent about an hour in the evening doing my searches and placing my orders, then less than 10 minutes managing the trade each evening after market close. The stock did go up a bit further after my profit target was reached, but the day after that the price started to fall as the price hit the resistance line and the Slow Stochastic did a crossover in the overbought area. Overall, this was a very ideal trade and I was very happy with it. Not all my trades reach my profit targets and I may get stopped out at a smaller profit or I might make a small loss (as I move my stops up as the price moves up). The key to successful trading over the long term is to keep you losses small and let your profits run (with my longer term trend trading I don't have profit targets and let my profits run until I get stopped out, but with my shorter term trading I do use a profit target usually 5 or 6 times the size of my initial stop). If you have an average win to average loss ratio of 3:1 or higher and have a success rate of 50% winners you will make money over the long term.",
"title": ""
},
{
"docid": "536788",
"text": "The safest real estate investment is to underpay. In most areas the market is very public. Flippers are abundant, because most people want a move-in ready home, and as it is leveraged, they will overpay for that luxury. Buy an under market, and you are safer. The people who lose their shirts buy new condos at market rates at the peak of the market. At the same time, people are purchasing starter homes that need a little work, and stay well above water. Always remember you can't change the location of a home, but you can change almost everything else. Find a well located but beat up home priced well under market, and financially you will generally do very well.",
"title": ""
},
{
"docid": "538979",
"text": "On June 30 2015, the value of a key should be exactly the expected revenue from selling the chest contents, owing to the fact that the next day the keys become worthless. Looking at the steam community market, it seems like the value of a key is higher than this, but lower than 2.50? If that's true, then since the price of a key is higher than the expected revenue from selling the chest contents as you say, then you can see that at some point the value of a key will have to go down. And as you get closer to the cutoff date, the price will fall faster. It's not quite the same, but this pattern is usually what you see in the ticket resale market on say, StubHub. If there's something about keys that keeps their worth above the expected value of selling chest contents (some value to the flexibility that keys offer over other tradable items maybe?), then in the short run that won't change due to this distant deadline, just because it's so far off. People will still want the flexibility keys offer. Orthodox economics might suggest sell sooner rather than later, but certainly don't wait too long. Different people react differently though. If there are a lot of panicky people who sell their keys after hearing this news, it might be a good time to buy. Of course it's a gamble, but if you trust in whatever force keeps keys priced above the expected value of the loot they can buy, then that force should win out in the medium term and you could turn a profit.",
"title": ""
},
{
"docid": "168080",
"text": "\"The reason for this is arbitrage. In an free and open market, investments that are certain to generate above-average profits would do so by being sold cheaply, while having a high return on investment after that. But in a free market, prices are set by supply and demand. There is a high demand and little supply for investments that would certainly outperform the market. The demand is in fact so high, that the purchase price rises to the point of eliminating that excess return. And with high-frequency automated trading, that price hike is instant. But who would even want to sell such guaranteed outperformers in the first place? Of course, there are uncertainties associated with stocks, and individual stocks therefore move independently. As \"\"the market\"\" is an average, some stocks will therefore beat the market over certain time periods. That's random statistical variation. The only realistic path to above-average returns is to accept higher risks. As discussed above, nobody wants to sell you safe bets. But risky bets are another matter. Different actors will price risk differently. If you aren't worried much about risk, you can pick up stocks that are cheap by your standards. That is possible only because such stocks aren't cheap by risk-averse standards. Looking a bit deeper, we see that arbitrage works in a free market because there's essentially perfect information. But risk is precisely the absence of such information, and that can lead to price variations. Yet, as the lack of information means a lack of certainty, you can't use this to reliably beat the market.\"",
"title": ""
},
{
"docid": "494727",
"text": "\"Re: A trader when buying needs to buy at the ask price and when selling needs to sell at the bid price. So how can a trade happen 'in between' the bid and ask? Saying the trade can happen \"\"in between\"\" the bid & ask is simplistic. There is a time dimension to the market. It's more accurate to say that an order can be placed \"\"in between\"\" the current best bid & ask (observed at time T=0), thus establishing a new level for one or the other of those quoted prices (observed at time T>0). If you enter a market order to buy (or sell), then yes, you'll generally be accepting the current best ask (or best bid) with your order, because that's what a market order says to do: Accept the current best market price being offered for your kind of transaction. Of course, prices may move much faster than your observation of the price and the time it takes to process your order – you're far from being the only participant. Market orders aside, you are free to name your own price above or below the current best bid & ask, respectively. ... then one could say that you are placing an order \"\"in between\"\" the bid and ask at the time your order is placed. However – and this is key – you are also moving one or the other of those quoted prices in the process of placing your above-bid buy order or your below-ask sell order. Then, only if somebody else in the market chooses to accept your new ask (or bid) does your intended transaction take place. And that transaction takes place at the new ask (or bid) price, not the old one that was current when you entered your order. Read more about bid & ask prices at this other question: (p.s. FWIW, I don't necessarily agree with the assertion from the article you quoted, i.e.: \"\"By looking for trades that take place in between the bid and ask, you can tell when a strong trend is about to come to an end.\"\" I would say: Maybe, perhaps, but maybe not.)\"",
"title": ""
},
{
"docid": "31933",
"text": "The Limit Order are matched based on amount and time. The orders are listed Highest to Lowest on the Buy Side. The orders are listed Lowest to Highest on the Sell Side. If there are 2 Sell orders for same amount the order which is first in time [fractions of milliseconds] is first. The about is the example as to how the orders would look like on any exchange. Now the highest price the buyer is ready to pay is 20.21 and the lowest price a seller is ready to sell for is 20.25. Hence there is no trade. Now if a new Buy order comes in at 20.25, it matches with the sell and the deal is made. If a new Buy order comes in at 20.30, it still matches at 20.25. Similarly if a Sell order come in at 20.21, it matches and a deal is made. If a Sell order come in at 20.11, it still matches 20.21. Incase of market order, with the above example if there is a Buy order, it would match with the lowest sell order at 20.25, if there is not enough quantity , it would match the remaining quantity to the next highest at 20.31 and continue down. Similarly if there is a Sell market order, the it would match to the maximum a seller is ready to buy, ie 20.21, if there is not sufficient buy quantity at 20.21, it will match with next for 20.19 If say there are new buy order at 20.22 and sell orders at 20.24, these will sit first the the above queue to be matched. In your above example the Lowest Sell order was at 20.10 at time t1 and hence any buy order after time t1 for amount 20.10 or greater would match to this and the price would be 20.10. However if the Buy order was first ie at t1 there was a buy order for 20.21 and then at time later than t1, there is a sell order for say 20.10 [amount less than or equal to 20.21] it would match for 20.21. Essentially the market looks at who was the first to sell at lower price or who was the first to buy at higher price and then decide the trade. Edit [To Clarify xyz]: Say if there is an Sell order at $10 Qty 100. There is a buyer who is willing to pay Max $20 and is looking for Qty 500. Your key assumption that the Buyer does not know the current SELL price of $10 is incorrect. Now there are multiple things, the Buyer knows the lowest Sell order is at $10, he can put a matching Buy order at $10 Qty 100, and say $11 Qty 100 etc. This is painful. Second, lets say he puts a Buy order at $10 Qty 100, by the time the order hits the system someone else has put the trade at $10 and his order is fulfilled. So this buyer has to keep looking at booking and keep making adjustments, if its a large order, it would be extremely difficult and frustrating for this Buyer. Hence the logic of giving preference. The later Buy order says ... The Max I can pay is $20, match eveything at the current price and get the required shares.",
"title": ""
},
{
"docid": "371205",
"text": "\"Alrighty. So your question is, how confident are people that FB stock will close above a certain price at a certain time. A \"\"call\"\" option contract allows you to buy shares in the future at a certain price. FB calls are available for March of 2013. The number in the \"\"strike\"\" column is the price you can buy FB stock at on the given date. Let's take the \"\"33.00\"\" strike. This allows you to buy FB shares at $33 each next March. If at that time it turns out they're worth $50 each, you can buy them at $33, then immediately sell them on the open market for $50, making money. The person selling you the option knows that there's a chance the price will be above $33 in March, so he's going to charge you a few bucks to cover that possibility. In this case, he's charging you $5.30 (as of me writing this). So, you can have the option to buy FB shares at $33 each for $5.30. This means the guy selling you the option is reasonably confident that in March, FB stock will be at or under $38.50, otherwise he'd lose money when you exercised the option. Therefore, $38.50 is the option market's best guess as to the highest FB stock will be going for in March.\"",
"title": ""
},
{
"docid": "376399",
"text": "He can buy at 69.95 or 69.70 or whatever because he already has all the shares. The HFT bought at a cheaper price earlier. The HFT has all the shares. Now he's testing the guy who won't go above 70.00 with small orders. When he sees that this guy is willing to buy 10 at 70.00 the HFT makes a limit order of all the shares in the market at 70.00 when he got them all already at 69.95. Whatever doesn't get bought up goes back into the market at the price the HFT originally bought at. The HFT was in line ahead of the guy who won't go above 70.00 as soon as he saw him buying. Like at the horse race, remember?",
"title": ""
},
{
"docid": "53041",
"text": "\"A \"\"market maker\"\" is someone that is contractually bound, by the exchange, to provide both bid and ask prices for a given volume (e.g. 5000 shares). A single market maker usually covers many stocks, and a single stock is usually covered by many market makers. The NYSE has \"\"specialists\"\" that are market makers that also performed a few other roles in the management of trading for a stock, and usually a single issue on the NYSE is covered by only one market maker. Market makers are often middlemen between brokers (ignoring stuff like dark pools, and the fact that brokers will often trade stocks internally among their own clients before going to the exchange). Historically, the market makers gave up buy/sell discretion in exchange for being the \"\"go-to guys\"\" for anyone wanting to trade in that stock. When you told your broker to buy a stock for you, he didn't hook you up with another retail investor; he went to the market maker. Market makers would also sometimes find investors willing to step in when more liquidity was needed for a security. They were like other floor traders; they hung out on the exchange floors and interacted with traders to buy and sell stocks. Traders came to them when they wanted to buy one of the specialist's issues. There was no public order book; just ticker tape and a quote. It was up to the market maker to maintain that order book. Since they are effectively forbidden from being one-sided traders in a security, their profit comes from the bid-ask spread. Being the counter-party to almost every trade, they'd make profit from always selling above where they were buying. (Except when the price moved quickly -- the downside to this arrangement.) \"\"The spread goes to the market maker\"\" is just stating that the profit implicit in the spread gets consumed by the market maker. With the switch to ECNs, the role of the market maker has changed. For example, ForEx trading firms tend to act as market makers to their customers. On ECNs, the invisible, anonymous guy at the other end of most trades is often a market maker, still performing his traditional role. Yet brokers can interact directly with each other now, rather than relying on the market maker's book. With modern online investing and public order books, retail investors might even be trading directly with each other. Market makers are still out there; in part, they perform a service sold by an Exchange to the companies that choose to be listed on that exchange. That service has changed to helping tamp volatility during normal high-volatility periods (such as at open and close).\"",
"title": ""
},
{
"docid": "149420",
"text": "The shift to trading at the close began in 2008. Traders did not want to be caught off guard by surprise news and there was a lot of volatility during the financial crisis, so they would close their position in the evening. Thats how it began. There are two reasons why it sticks around. First, there has been an increase usage of index funds or passive funds. These funds tend to update their positions at the end of the day. From the WSJ: Another factor behind the shift has been the proliferation of passively managed investments, such as index funds. These funds aim to mimic an index, like the S&P 500, by owning the shares that comprise it. Index funds don’t trade as often as active investors, but when they do, it is typically near the market close, traders say. That is because buying or selling a stock at its closing price better aligns their performance with the index they are trying to emulate. The second reason is simply that volume attracts volume. As a result of whats mentioned above, you have a shift to end of day trading, and the corrolary to that is that there is a liquidity shortage from 10am to 3pm. Thus, if you want to buy or sell a stock, but there are few buyers or sellers around, you will significant move the price when you enter your order. Obviously this does not affect retail traders, but imagine hedge funds entering or closing a billion dollar position. It can make a huge impact on price. And one way to mitigate that is to wait until there are more market participants to take the other end of your trade, just as at the end of the day. So this is a self-reinforcing trend that has begun in the markets and will likely stick around. http://www.wsj.com/articles/traders-pile-in-at-the-close-1432768080",
"title": ""
}
] |
6457
|
Kate Nash only released 2 albums.
|
[
{
"docid": "Kate_Nash",
"text": "Kate Marie Nash ( born 6 July 1987 ) is an English singer , songwriter , musician and actress . Nash rose to prominence in the UK with the sleeper hit `` Foundations '' ( 2007 ) . Her debut album , Made of Bricks , peaked at number 1 in the UK and number 36 in the US . Nash won the award for Best British Female Artist at the 2008 Brit Awards . Her second studio album , My Best Friend Is You , was released in 2010 and reached the top 10 in both the UK and Germany . The album 's lead single , `` Do-Wah-Doo '' , peaked at number 15 in the UK , becoming her fourth UK Top 40 single . After being dropped by her record label , Nash self-released her third studio album , Girl Talk , on 4 March 2013 . The album failed to match the commercial success of Nash 's previous albums , though it charted inside the top 100 in the UK , Ireland , Germany and Austria . In April 2017 , Nash launched a Kickstarter to finance a fourth studio album . On 21 April 2017 , Nash released a four-track EP , Agenda .",
"title": ""
}
] |
[
{
"docid": "Kate_Nash_discography",
"text": "The discography of British singer-songwriter and musician Kate Nash consists of three studio albums , eight singles and seven music videos . Her debut album , Made of Bricks charted at number one in the United Kingdom and achieved Platinum status . The album garnered success across Europe and achieved Gold status in Germany , as well as moderate success in the United States and Australia . It spawned four singles , UK number 2 `` Foundations '' , `` Mouthwash '' , `` Pumpkin Soup '' and `` Merry Happy '' . Nash released her riot grrrl and doo-wop inspired second studio album , My Best Friend Is You , in 2010 . It charted at number eight in the UK and received success in both Europe and the United States , however not to the same extent as her previous album . The record spawned three singles and two promotional singles , including Nash 's second highest charting song `` Do Wah Doo '' , and `` Kiss That Grrrl '' .",
"title": ""
},
{
"docid": "Do-Wah-Doo",
"text": "`` Do-Wah-Doo '' is a song by English indie pop singer-songwriter Kate Nash , featured on her 2010 second album My Best Friend Is You ( 2010 ) . Written by Nash and produced by Bernard Butler , it was released as the lead single from the album on 12 April 2010 , one week before the release of the album . `` Do-Wah-Doo '' was a moderate commercial success , reaching number 15 on the UK Singles Chart -- a position exceeded only by her hit song `` Foundations '' in 2007 .",
"title": ""
},
{
"docid": "Girl_Talk_(Kate_Nash_album)",
"text": "Girl Talk is the third studio album by English singer-songwriter Kate Nash . Nash self-released the album under Have 10p Records along with Fontana in March 2013 after she raised money for the album on PledgeMusic . Girl Talk has received mixed to positive reviews from critics . Featuring a heavier rock-influenced sound , the album is a noticeable departure from her first two indie pop albums . Lyrically , it draws a lot of influence from the riot grrrl movement . Girl Talk did not achieve the chart success of its predecessors , and the three singles released failed to chart . The vinyl LP version of the record was pressed by United Record Pressing in Nashville , TN .",
"title": ""
},
{
"docid": "List_of_awards_and_nominations_received_by_Kate_Nash",
"text": "Kate Nash is an English singer-songwriter from London , England . She debuted in 2005 , uploading several demos to the social networking service Myspace . Nash released her debut single `` Caroline 's a Victim '' through independent record label Moshi Moshi Records in February 2007 . The release brought her to the attention of Fiction Records , which signed her two months later . She has released three studio albums : Made of Bricks ( 2007 ) , My Best Friend Is You ( 2010 ) and Girl Talk ( 2013 ) . Made of Bricks reached number one in the United Kingdom and was certified platinum by the British Phonographic Industry ( BPI ) . My Best Friend Is You charted at number eight in the UK , while Girl Talk peaked at number eighty-five . Nash 's debut studio album earned her several recognitions , including the BRIT Award for British Female Solo Artist , the ASCAP Vanguard Award and the Q Award for Breakthrough Artist . The album 's lead single , `` Foundations '' , received three nominations and won a UK Music Video Award for Best Pop Video . She has also been recognized by the Elle Style Awards , the NME Awards and the Vodafone Live Music Awards . As of 2013 , Nash has received eight awards from fifteen nominations .",
"title": ""
},
{
"docid": "Kiss_That_Grrrl",
"text": "`` Kiss That Grrrl '' is a song by English indie pop singer-songwriter Kate Nash , featured on her 2010 second album My Best Friend Is You . Written by Nash and produced by Bernard Butler , it was released as the second single from the album on 12 July 2010 .",
"title": ""
},
{
"docid": "Caroline's_a_Victim",
"text": "`` Caroline 's a Victim '' is the debut single by English singer-songwriter Kate Nash , released digitally and on 7 '' vinyl 5 February 2007 . `` Caroline 's a Victim '' was a popular track on Kate Nash 's MySpace profile . It is also featured on the CD Moshi Moshi Singles Compilation , and appears on the CD single for her song `` Foundations '' . The B-side , `` Birds '' , later featured on her début album , Made of Bricks . It has sold a total of 2,000 copies in the U.K. The music video for `` Caroline 's a Victim '' consists of Nash playing various instruments while singing . The Teenagers Myspace page is visible in the video . It was directed by Kinga Burza .",
"title": ""
},
{
"docid": "Mouthwash_(song)",
"text": "`` Mouthwash '' is a song by Kate Nash , featured her third single , and the second to be lifted from her debut album Made of Bricks . It was released on 1 October 2007 . The track was described by Nash as a protest song .",
"title": ""
},
{
"docid": "Pumpkin_Soup",
"text": "`` Pumpkin Soup '' is a song by Kate Nash that is featured on her fourth single , the third to be lifted from her debut album Made of Bricks . It was released on 17 December 2007 , making it a contender for the Christmas number one and entered the charts at number 58 on the UK Top 75 based on downloads only , then reached number 40 with a physical release the following week . It reached a peak of number 23 on 6 January , equalling the peak of previous single `` Mouthwash '' .",
"title": ""
},
{
"docid": "Real_Girl_(song)",
"text": "`` Real Girl '' is a song written by Lenny Kravitz , Niara Scarlett , Matt Ward and Dean Gillard . It was produced by Matt Ward and Dean Gillard for Mutya Buena 's debut album , Real Girl , and was released as the first single from the album . It charted at # 2 on the UK singles chart . It was released on 28 May 2007 . The song includes a sample of Lenny Kravitz ' `` It Ai n't Over 'Til It 's Over '' . It was shortlisted at the 2008 BRIT Awards for Best British Single . The track was up against her former bandmembers , Sugababes , as well as Leona Lewis , Kate Nash and Take That . `` Real Girl '' is played in a scene in Sex and the City : The Movie , which was released in May 2008 .",
"title": ""
},
{
"docid": "My_Best_Friend_Is_You",
"text": "My Best Friend Is You is the second studio album by English singer-songwriter Kate Nash , released in the United Kingdom on 19 April 2010 and elsewhere on 20 April . The album was originally entitled Crayon Full Of Colour but the name was changed due to Paolo Nutini 's similar song title at that time , `` Pencil Full Of Lead '' . On 13 April 2010 , Kate appeared on John Kennedy 's XFM show Xposure , where they did a track-by-track interview playing the whole of the album . The album spawned three official singles : the lead single `` Do-Wah-Doo '' achieved the most commercial success , charting respectively in European countries . `` I 've Got A Secret '' was released as a promotional single and the fourth single overall .",
"title": ""
},
{
"docid": "Best_of_Bizzle",
"text": "`` Best of Bizzle '' is a compilation album by Grime MC , Lethal Bizzle . It was released on February 27 , 2011 for digital download . The album features artists such as Mr Hudson , Donae'o , Dizzee Rascal , Tawiah , Kate Nash and Mark Ronson - along with Lethal Bizzle 's fellow grime artists . The first single off the album , `` Pow 2011 '' , was released on February 6 , 2011 . The album consists of 27 songs .",
"title": ""
},
{
"docid": "Made_of_Bricks",
"text": "Made of Bricks is the debut studio album by English singer-songwriter Kate Nash , released in the United Kingdom on 6 August 2007 by Fiction Records , Cherrytree Records , and the Universal Music Group . The album was a commercial success , topping the UK Albums Chart and spawning a number-two single in the form of the lead single `` Foundations '' . The album was later released in Europe on 10 September and in the United States on 18 September 2007 .",
"title": ""
},
{
"docid": "London_Town_(Kano_album)",
"text": "London Town is the second studio album by British rapper Kano , released on 10 September 2007 by 679 Artists . The first single , featuring Craig David , `` This Is the Girl '' , was released on 27 August 2007 , the second being `` Feel Free '' , featuring Damon Albarn . Guests include , other than David and Albarn , Vybz Kartel , Kate Nash and Leo the Lion . The album debuted at number 14 on the UK Albums Chart .",
"title": ""
},
{
"docid": "Foundations_(song)",
"text": "`` Foundations '' is a song co-written by British singer-songwriter Kate Nash for her debut album , Made of Bricks ( 2007 ) . It was released as the album 's lead single in June 2007 , her first single since signing with Fiction Records after the success of her debut single `` Caroline 's a Victim '' .",
"title": ""
},
{
"docid": "Britannia_Row_Studios",
"text": "Britannia Row Studios is a recording studio in Fulham , London SW6 , England . Pink Floyd built the original Britannia Row Studios . It was built in a three-story block at 35 Britannia Row , Islington , London N1 , after their 1975 album Wish You Were Here was released . They then went on to use the studio to record their next album , Animals , and parts of The Wall including the famous school chorus on `` Another Brick in the Wall '' . Nick Mason eventually assumed full ownership of the studio , but in the early 1990s he decided to sell the studio to its current owner , Kate Koumi , who has been managing it since the mid-1980s . In the mid-1990s the studio relocated to its present location , while the space in Britannia Row is currently used as a training facility for the London School of Sound . The studio has been used by many high-profile artists over the years , including : Richard Ashcroft Atomic Kitten Bijelo Dugme Björk James Blunt Kate Bush Coil The Cult Pete Doherty Joy Division Ronan Keating Liberty X Manic Street Preachers Dannii Minogue Kylie Minogue Kate Nash Nash the Slash New Order Page and Plant The Pillows Pink Floyd Pulp Section 25 Skindred Snow Patrol Sugababes Supergrass Westlife",
"title": ""
},
{
"docid": "Merry_Happy",
"text": "`` Merry Happy '' is the fifth single by British singer-songwriter Kate Nash . It is the fourth single from her album , Made of Bricks . It was released on CD and two 7 '' singles on 24 March 2008 , limited to 1000 of each format .",
"title": ""
},
{
"docid": "CSN_(album)",
"text": "CSN is the fifth studio album by Crosby , Stills & Nash released in 1977 . It is the second release by the trio configuration and the first without Neil Young since his entry into the band . It peaked at # 2 on the Billboard Top Pop Albums chart ; two singles taken from the album , Nash 's `` Just a Song Before I Go '' and Stills ' `` Fair Game '' peaked at # 7 and # 43 respectively on the Billboard Hot 100 . It is currently the trio configuration 's best selling record , outselling their debut Crosby , Stills & Nash by 200,000 copies . It has been certified for quadruple platinum sales by the RIAA .",
"title": ""
},
{
"docid": "There_Goes_a_Tenner",
"text": "`` There Goes a Tenner '' is a song by the English singer Kate Bush . It was released as a single on 2 November 1982 , the third to be taken from her album The Dreaming . It was released as a 7 '' single in the UK and Ireland only .",
"title": ""
},
{
"docid": "Hollies'_Greatest",
"text": "Hollies ' Greatest is the only number one album in the UK by British band The Hollies . It was released after Graham Nash 's departure from the Hollies and was intended to include all of their British hit singles with Nash . Only 3 of the 14 songs on the album -- `` Stay '' , `` I Ca n't Let Go '' and `` Stop ! Stop ! Stop ! '' had previously been released on U.K. albums . It spent seven weeks at the top of the chart in 1968 . In total , it spent 27 weeks in the British LP chart , and is the most successful album by The Hollies . The version of `` Yes I Will '' that appears on the mono version of this album is not the 1965 hit single version , but an earlier and previously unreleased recording from 1964 -- the result of an administrative error at EMI which was not noticed until after the album had been released . It features a completely different guitar break with Tony Hicks .",
"title": ""
},
{
"docid": "Hollies_Sing_Dylan",
"text": "Hollies Sing Dylan is a 1969 cover album where the Hollies sing Bob Dylan songs . It was also released in the US as Words and Music by Bob Dylan with a different cover but using the same band image and track order . First released on compact disc in West Germany in the late 1980s , it was not released in that format in the rest of Europe until 1993 . For this issue , two bonus tracks , the single version of `` Blowin ' in the Wind '' and a live version of `` The Times They Are a-Changin ' '' . A later remastered issue in 1999 added a third bonus track , a live version of `` Blowin ' in the Wind '' . This album was recorded and released following Graham Nash 's departure from the band to join David Crosby and Stephen Stills in December 1968 after early sessions for a follow-up to the psychedelic concept album , Butterfly broke down . Nash became frustrated when the other band members showed opposition to lyrics in his latest compositions . By that time , Nash was the only member of the band using LSD and marijuana and a rift was forming between him and his beer drinking bandmates : Nash quickly became disillusioned with the direction that the band was moving artistically and especially derided their decision to record an entire album of covers : There have been claims that the album was hated by fans and critics alike . However it peaked at no. 3 in the UK , their third highest showing for any LP and second-highest charting for one with newly recorded material . Nevertheless , the group 's next album was titled Hollies Sing Hollies in an apparent move to placate critics . In an interview for Billboard magazine in 1974 , Clarke reflected on the album : This is the first album with new member Terry Sylvester , who replaced Nash .",
"title": ""
},
{
"docid": "Stephen_Stills_2",
"text": "Stephen Stills 2 is the second solo album by Stephen Stills and was released in 1971 . He had already performed `` Bluebird Revisited '' on tour with Crosby , Stills , Nash , & Young in 1969 . The album was not as well received as its predecessor peaking at # 8 on the Billboard album chart and with most reviews labeling it as indulgent , or as Rolling Stone put it , `` fifth-rate self-indulgence '' . About the only thing the reviewers complimented were the songs `` Change Partners '' and `` Marianne '' , which were the album 's singles but only hit # 43 and # 42 , respectively , on the Billboard singles chart.Stills later re-recorded two songs from this collection : `` Singin ' Call '' for his 1991 CD Stills Alone , and `` Word Game '' for his 2013 CD with blues supergroup The Rides .",
"title": ""
},
{
"docid": "Stronger_(Kate_Ryan_album)",
"text": "Stronger is the second album by Belgian singer Kate Ryan , released on 2004 in Europe and released in the U.S. on 2005 . Stronger includes the hits singles `` Only If I '' , `` The Promise You Made '' and `` Goodbye '' .",
"title": ""
},
{
"docid": "Just_a_Song_Before_I_Go",
"text": "`` Just a Song Before I Go '' is a song from Crosby , Stills and Nash that appeared on the 1977 album CSN . It was also released as a single and made it to number seven on the Billboard singles charts , becoming the band 's highest charting hit . It is also one of the band 's shortest songs , with a running time of only 2:14 . In Canada , it peaked at number 10 . The song was written by Graham Nash about leaving loved ones behind before going on a concert tour . It was written in Hawaii in about 20 minutes at the piano while Nash and Leslie Morris were staying with a friend , waiting for the rain to stop before leaving the house . The opening line came from the question : `` You 've got half an hour , why do n't you just write a song before you go ? '' In a February 25 , 2016 interview on The Late Show with Stephen Colbert , Nash stated that the homeowner bet him $ 500 that he could n't write a song before he left . Nash said he still has that $ 500 . `` Just a Song Before I Go '' is lyrically straightforward about the situation Nash was in at the moment he wrote it , and there is also an undercurrent of regret towards rootlessness , a feeling that Nash -- born and raised in England , a resident of the United States who had lived in California and was now living in Hawaii -- might very well have had at the time . Crosby , Stills and Nash arranged `` Just a Song Before I Go '' as a straight ballad , with mostly acoustic textures anchored by two electric guitar solos from Stephen Stills . In 2008 , drummer Russ Kunkel and the group Chateau Beach covered the song on their album `` Rivage . ''",
"title": ""
},
{
"docid": "ITunes_Originals_–_Something_for_Kate",
"text": "iTunes Originals -- Something for Kate is an iTunes Originals album recorded by Something for Kate , released May 22 , 2007 . It has a variety of live tracks , and tracks from existing albums , as well as short discussions and comments from the band . The album is only available for download through iTunes ; no physical copies are available .",
"title": ""
},
{
"docid": "Immigration_Man",
"text": "`` Immigration Man '' is a song written by Graham Nash and recorded by David Crosby and Graham Nash , released as a single in March 1972 . It was the lead single for the duo 's debut album , Graham Nash David Crosby . It peaked at # 36 on the Billboard Hot 100 , and is their only Top 40 hit as a duo .",
"title": ""
},
{
"docid": "Greatest_Hits_(Crosby,_Stills_&_Nash_album)",
"text": "Greatest Hits is the fifteenth Crosby , Stills & Nash album , and their fifth compilation , released by Rhino Records in 2005 . It peaked at # 24 on the Billboard 200 , debuting at that position on April 2 , 2005 with first week sales of 33,000 copies , and spending eight weeks on the chart . Its current sales sit at over 640,000 . The album was dedicated to Cass Elliot with great thanks to Neil Young .",
"title": ""
},
{
"docid": "Complainte_pour_Ste._Catherine",
"text": "Complainte pour Ste. Catherine is a song written by Canadians Philippe Tatartcheff & Anna McGarrigle , first featured on Kate & Anna McGarrigle 's eponymous debut album , Kate & Anna McGarrigle , released in 1976 . With lyrics in Swedish by Ola Magnell as `` Ingen kommer undan politiken '' ( `` No-one escapes politics '' ) , the song was recorded by Marie Bergman on the 1977 album Närma mej , and by Marie Fredriksson in 2006 on the album Min bäste vän . The Marie Fredriksson version was also released as a digital single on 25 July 2006 . It was the second single released from Marie Fredriksson 's cover album Min bäste vän , in digital format only . A promotional single ( 0946 3707622 4 ) was also released . `` I owned the record by Kate and Anna McGarrigle and I was blown away by the way they sang it '' , Marie says . The Marie Fredriksson version was also released as a digital single on 25 July 2006 .",
"title": ""
},
{
"docid": "Good_Monsters",
"text": "Good Monsters is the seventh full-length studio album from Jars of Clay , released by Essential Records on September 5 , 2006 . This is their last album of new material from Essential Records and it is said to be lyrically their most aggressive album to date . It features eleven original songs , and a remake of `` All My Tears '' by Julie Miller . It also features guest appearances by singer/songwriter Kate York ( on `` Even Angels Cry '' ) , Leigh Nash , of Sixpence None the Richer ( on `` Mirrors & Smoke '' ) , and the African Children 's Choir ( on `` Light Gives Heat '' ) . `` Dead Man ( Carry Me ) '' , the first single from the album , was released to radio stations on June 23 , 2006 . `` Work '' was released as the second single , along with its music video , in late August . The band also released a music video for the album track `` Good Monsters '' . In the September 2006 edition of CCM Magazine , the band credited fellow artist Ashley Cleveland with inspiring the improvisational sound of the album . In an editor 's fall albums overview in CCM Magazine , Good Monsters was called , `` the album that Jars of Clay will be remembered for . '' It ended up taking the award for the CCM Magazine staff picks as album of the year , winning four out of the five spaces .",
"title": ""
},
{
"docid": "Wild_Tales_(album)",
"text": "Wild Tales is the second solo studio album by British singer-songwriter Graham Nash , released on Atlantic Records in 1974 . It peaked at # 34 on the Billboard 200 . Nash blamed its failure to chart higher in the United States on a supposed lack of support and promotion from Atlantic Records . Following the protracted breakup of Crosby , Stills , Nash & Young in late 1974 and early 1975 , Nash left the label and signed a four-album contract with ABC Records as a duo with his CSNY partner David Crosby . Contrary to later reports , the darker tone of this album was not inspired by the murder of Nash 's then-girlfriend , Amy Gossage , by her brother ; that tragedy happened more than a year after the release of this LP . Rather , Nash was in a somber mood in the wake of the failures of his relationships with Joni Mitchell and Rita Coolidge , and the unwillingness at the time of the other members of Crosby , Stills , Nash & Young to reunite for a new album .",
"title": ""
},
{
"docid": "Metronomy",
"text": "Metronomy are an electronic music group formed in 1999 . The current band consists of Joseph Mount ( vocals , keyboards and guitar ) , Oscar Cash ( saxophone , backing vocals , guitars and keyboards ) , Anna Prior ( drums and vocals ) and Gbenga Adelekan ( bass guitar and vocals ) . Their music consists of instrumental electronic music and more recently , with the release of Nights Out , vocal electronic pop music . Mount also releases remixes under the name Metronomy , and has remixed many artists including Gorillaz , Sebastien Tellier , Roots Manuva , Franz Ferdinand , Klaxons , Goldfrapp , Young Knives , Zero 7 , Ladytron , Kate Nash , Lady Gaga and Lykke Li . Metronomy have released five albums of original material , Pip Paine ( Pay The # 5000 You Owe ) , Nights Out , The English Riviera , and Love Letters - their fifth studio album titled Summer 08 was released on 1 July 2016 .",
"title": ""
}
] |
81
|
Acute ablation of Snail in the embryonic cortex affects the proliferation and number of embryonic cortical precursors.
|
[
{
"docid": "1797622",
"text": "Asymmetric cell division and apoptosis (programmed cell death) are two fundamental processes that are important for the development and function of multicellular organisms. We have found that the processes of asymmetric cell division and apoptosis can be functionally linked. Specifically, we show that asymmetric cell division in the nematode Caenorhabditis elegans is mediated by a pathway involving three genes, dnj-11 MIDA1, ces-2 HLF, and ces-1 Snail, that directly control the enzymatic machinery responsible for apoptosis. Interestingly, the MIDA1-like protein GlsA of the alga Volvox carteri, as well as the Snail-related proteins Snail, Escargot, and Worniu of Drosophila melanogaster, have previously been implicated in asymmetric cell division. Therefore, C. elegans dnj-11 MIDA1, ces-2 HLF, and ces-1 Snail may be components of a pathway involved in asymmetric cell division that is conserved throughout the plant and animal kingdoms. Furthermore, based on our results, we propose that this pathway directly controls the apoptotic fate in C. elegans, and possibly other animals as well.",
"title": "Control of Apoptosis by Asymmetric Cell Division"
}
] |
[
{
"docid": "38919140",
"text": "The Snail transcription factor plays a key role in regulating diverse developmental processes but is not thought to play a role in mammalian neural precursors. Here, we have examined radial glial precursor cells of the embryonic murine cortex and demonstrate that Snail regulates their survival, self-renewal, and differentiation into intermediate progenitors and neurons via two distinct and separable target pathways. First, Snail promotes cell survival by antagonizing a p53-dependent death pathway because coincident p53 knockdown rescues survival deficits caused by Snail knockdown. Second, we show that the cell cycle phosphatase Cdc25b is regulated by Snail in radial precursors and that Cdc25b coexpression is sufficient to rescue the decreased radial precursor proliferation and differentiation observed upon Snail knockdown. Thus, Snail acts via p53 and Cdc25b to coordinately regulate multiple aspects of mammalian embryonic neural precursor biology.",
"title": "Snail coordinately regulates downstream pathways to control multiple aspects of mammalian neural precursor development."
},
{
"docid": "16964262",
"text": "Precursor cells of the embryonic cortex sequentially generate neurons and then glial cells, but the mechanisms regulating this neurogenic-to-gliogenic transition are unclear. Using cortical precursor cultures, which temporally mimic this in vivo differentiation pattern, we demonstrate that cortical neurons synthesize and secrete the neurotrophic cytokine cardiotrophin-1, which activates the gp130-JAK-STAT pathway and is essential for the timed genesis of astrocytes in vitro. Our data indicate that a similar phenomenon also occurs in vivo. In utero electroporation of neurotrophic cytokines in the environment of embryonic cortical precursors causes premature gliogenesis, while acute perturbation of gp130 in cortical precursors delays the normal timed appearance of astrocytes. Moreover, the neonatal cardiotrophin-1-/- cortex contains fewer astrocytes. Together, these results describe a neural feedback mechanism; newly born neurons produce cardiotrophin-1, which instructs multipotent cortical precursors to generate astrocytes, thereby ensuring that gliogenesis does not occur until neurogenesis is largely complete.",
"title": "Evidence that Embryonic Neurons Regulate the Onset of Cortical Gliogenesis via Cardiotrophin-1"
},
{
"docid": "18038250",
"text": "Within the developing mammalian CNS, growth factors direct multipotent precursors to generate neurons versus glia, a process that if perturbed might lead to neural dysfunction. In this regard, genetic mutations resulting in constitutive activation of the protein tyrosine phosphatase SHP-2 cause Noonan Syndrome (NS), which is associated with learning disabilities and mental retardation. Here, we demonstrate that genetic knockdown of SHP-2 in cultured cortical precursors or in the embryonic cortex inhibited basal neurogenesis and caused enhanced and precocious astrocyte formation. Conversely, expression of an NS SHP-2 mutant promoted neurogenesis and inhibited astrogenesis. Neural cell-fate decisions were similarly perturbed in a mouse knockin model that phenocopies human NS. Thus, SHP-2 instructs precursors to make neurons and not astrocytes during the neurogenic period, and perturbations in the relative ratios of these two cell types upon constitutive SHP-2 activation may contribute to the cognitive impairments in NS patients.",
"title": "Control of CNS Cell-Fate Decisions by SHP-2 and Its Dysregulation in Noonan Syndrome"
},
{
"docid": "33796570",
"text": "Neurofibromatosis type 1 (NF1) is a prevalent genetic disorder that affects growth properties of neural-crest-derived cell populations. In addition, approximately one-half of NF1 patients exhibit learning disabilities. To characterize NF1 function both in vitro and in vivo, we circumvent the embryonic lethality of NF1 null mouse embryos by generating a conditional mutation in the NF1 gene using Cre/loxP technology. Introduction of a Synapsin I promoter driven Cre transgenic mouse strain into the conditional NF1 background has ablated NF1 function in most differentiated neuronal populations. These mice have abnormal development of the cerebral cortex, which suggests that NF1 has an indispensable role in this aspect of CNS development. Furthermore, although they are tumor free, these mice display extensive astrogliosis in the absence of conspicuous neurodegeneration or microgliosis. These results indicate that NF1-deficient neurons are capable of inducing reactive astrogliosis via a non-cell autonomous mechanism.",
"title": "Ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain."
},
{
"docid": "15833835",
"text": "Adult neural stem/progenitor (B1) cells within the walls of the lateral ventricles generate different types of neurons for the olfactory bulb (OB). The location of B1 cells determines the types of OB neurons they generate. Here we show that the majority of mouse B1 cell precursors are produced between embryonic days (E) 13.5 and 15.5 and remain largely quiescent until they become reactivated postnatally. Using a retroviral library carrying over 100,000 genetic tags, we found that B1 cells share a common progenitor with embryonic cells of the cortex, striatum, and septum, but this lineage relationship is lost before E15.5. The regional specification of B1 cells is evident as early as E11.5 and is spatially linked to the production of neurons that populate different areas of the forebrain. This study reveals an early embryonic regional specification of postnatal neural stem cells and the lineage relationship between them and embryonic progenitor cells.",
"title": "Embryonic Origin of Postnatal Neural Stem Cells"
},
{
"docid": "16939583",
"text": "Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output.",
"title": "2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size."
},
{
"docid": "23901235",
"text": "Neurogenesis occurs in the hippocampus of the developing and adult brain due to the presence of multipotent stem cells and restricted precursor cells at different stages of differentiation. It has been proposed that they may be of potential benefit for use in cell transplantation approaches for neurodegenerative disorders and trauma. Prolonged release of interleukin-1β (IL-1β) from activated microglia has a deleterious effect on hippocampal neurons and is implicated in the impaired neurogenesis and cognitive dysfunction associated with aging, Alzheimer's disease and depression. This study assessed the effect of IL-1β on the proliferation and differentiation of embryonic rat hippocampal NPCs in vitro. We show that IL-1R1 is expressed on proliferating NPCs and that IL-1β treatment decreases cell proliferation and neurosphere growth. When NPCs were differentiated in the presence of IL-1β, a significant reduction in the percentages of newly-born neurons and post-mitotic neurons and a significant increase in the percentage of astrocytes was observed in these cultures. These effects were attenuated by IL-1 receptor antagonist. These data reveal that IL-1β exerts an anti-proliferative, anti-neurogenic and pro-gliogenic effect on embryonic hippocampal NPCs, which is mediated by IL-1R1. The present results emphasise the consequences of an inflammatory environment during NPC development, and indicate that strategies to inhibit IL-1β signalling may be necessary to facilitate effective cell transplantation approaches or in conditions where endogenous hippocampal neurogenesis is impaired.",
"title": "A role for interleukin-1β in determining the lineage fate of embryonic rat hippocampal neural precursor cells."
},
{
"docid": "16090672",
"text": "Dynein at the cortex contributes to microtubule-based positioning processes such as spindle positioning during embryonic cell division and centrosome positioning during fibroblast migration. To investigate how cortical dynein interacts with microtubule ends to generate force and how this functional association impacts positioning, we have reconstituted the 'cortical' interaction between dynein and dynamic microtubule ends in an in vitro system using microfabricated barriers. We show that barrier-attached dynein captures microtubule ends, inhibits growth, and triggers microtubule catastrophes, thereby controlling microtubule length. The subsequent interaction with shrinking microtubule ends generates pulling forces up to several pN. By combining experiments in microchambers with a theoretical description of aster mechanics, we show that dynein-mediated pulling forces lead to the reliable centering of microtubule asters in simple confining geometries. Our results demonstrate the intrinsic ability of cortical microtubule-dynein interactions to regulate microtubule dynamics and drive positioning processes in living cells.",
"title": "Cortical Dynein Controls Microtubule Dynamics to Generate Pulling Forces that Position Microtubule Asters"
},
{
"docid": "3095620",
"text": "The homologues of the two distinct architectonic areas 44 and 45 that constitute the anterior language zone (Broca's region) in the human ventrolateral frontal lobe were recently established in the macaque monkey. Although we know that the inferior parietal lobule and the lateral temporal cortical region project to the ventrolateral frontal cortex, we do not know which of the several cortical areas found in those regions project to the homologues of Broca's region in the macaque monkey and by means of which white matter pathways. We have used the autoradiographic method, which permits the establishment of the cortical area from which axons originate (i.e., the site of injection), the precise course of the axons in the white matter, and their termination within particular cortical areas, to examine the parietal and temporal connections to area 44 and the two subdivisions of area 45 (i.e., areas 45A and 45B). The results demonstrated a ventral temporo-frontal stream of fibers that originate from various auditory, multisensory, and visual association cortical areas in the intermediate superolateral temporal region. These axons course via the extreme capsule and target most strongly area 45 with a more modest termination in area 44. By contrast, a dorsal stream of axons that originate from various cortical areas in the inferior parietal lobule and the adjacent caudal superior temporal sulcus was found to target both areas 44 and 45. These axons course in the superior longitudinal fasciculus, with some axons originating from the ventral inferior parietal lobule and the adjacent superior temporal sulcus arching and forming a simple arcuate fasciculus. The cortex of the most rostral part of the inferior parietal lobule is preferentially linked with the ventral premotor cortex (ventral area 6) that controls the orofacial musculature. The cortex of the intermediate part of the inferior parietal lobule is linked with both areas 44 and 45. These findings demonstrate the posterior parietal and temporal connections of the ventrolateral frontal areas, which, in the left hemisphere of the human brain, were adapted for various aspects of language production. These precursor circuits that are found in the nonlinguistic, nonhuman, primate brain also exist in the human brain. The possible reasons why these areas were adapted for language use in the human brain are discussed. The results throw new light on the prelinguistic precursor circuitry of Broca's region and help understand functional interactions between Broca's ventrolateral frontal region and posterior parietal and temporal association areas.",
"title": "Distinct Parietal and Temporal Pathways to the Homologues of Broca's Area in the Monkey"
},
{
"docid": "2437807",
"text": "The remarkable developmental potential and replicative capacity of human embryonic stem (ES) cells promise an almost unlimited supply of specific cell types for transplantation therapies. Here we describe the in vitro differentiation, enrichment, and transplantation of neural precursor cells from human ES cells. Upon aggregation to embryoid bodies, differentiating ES cells formed large numbers of neural tube–like structures in the presence of fibroblast growth factor 2 (FGF-2). Neural precursors within these formations were isolated by selective enzymatic digestion and further purified on the basis of differential adhesion. Following withdrawal of FGF-2, they differentiated into neurons, astrocytes, and oligodendrocytes. After transplantation into the neonatal mouse brain, human ES cell–derived neural precursors were incorporated into a variety of brain regions, where they differentiated into both neurons and astrocytes. No teratoma formation was observed in the transplant recipients. These results depict human ES cells as a source of transplantable neural precursors for possible nervous system repair.",
"title": "In vitro differentiation of transplantable neural precursors from human embryonic stem cells"
},
{
"docid": "3090454",
"text": "In 93 allograft recipients, the numbers of marrow B-cell precursors on days 80 and 365 correlated with the counts of circulating B cells, suggesting that the posttransplantation B-cell deficiency is at least in part due to insufficient B lymphopoiesis. Factors that could affect B lymphopoiesis were evaluated. The number of marrow B-cell precursors on days 30 and 80 was at least 4-fold lower in patients with grade 2 to 4 acute graft-versus-host disease (GVHD) compared with patients with grade 0 to 1 acute GVHD. The number of B-cell precursors on day 365 was 18-fold lower in patients with extensive chronic GVHD compared with patients with no or limited chronic GVHD. The number of B-cell precursors was not related to CD34 cell dose, type of transplant (marrow versus blood stem cells), donor age, or patient age. It was concluded that posttransplantation B-cell deficiency results in part from inhibition of B lymphopoiesis by GVHD and/or its treatment.",
"title": "Factors influencing B lymphopoiesis after allogeneic hematopoietic cell transplantation."
},
{
"docid": "4457834",
"text": "The transfer of somatic cell nuclei into oocytes can give rise to pluripotent stem cells that are consistently equivalent to embryonic stem cells, holding promise for autologous cell replacement therapy. Although methods to induce pluripotent stem cells from somatic cells by transcription factors are widely used in basic research, numerous differences between induced pluripotent stem cells and embryonic stem cells have been reported, potentially affecting their clinical use. Because of the therapeutic potential of diploid embryonic stem-cell lines derived from adult cells of diseased human subjects, we have systematically investigated the parameters affecting efficiency of blastocyst development and stem-cell derivation. Here we show that improvements to the oocyte activation protocol, including the use of both kinase and translation inhibitors, and cell culture in the presence of histone deacetylase inhibitors, promote development to the blastocyst stage. Developmental efficiency varied between oocyte donors, and was inversely related to the number of days of hormonal stimulation required for oocyte maturation, whereas the daily dose of gonadotropin or the total number of metaphase II oocytes retrieved did not affect developmental outcome. Because the use of concentrated Sendai virus for cell fusion induced an increase in intracellular calcium concentration, causing premature oocyte activation, we used diluted Sendai virus in calcium-free medium. Using this modified nuclear transfer protocol, we derived diploid pluripotent stem-cell lines from somatic cells of a newborn and, for the first time, an adult, a female with type 1 diabetes.",
"title": "Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells"
},
{
"docid": "12903921",
"text": "It has been proved that oxidative stress increases when leukemia is accompanied by depression. This fact may indicate the role of oxidative stress in the development of depression in cancer patients. The aim of this study was to determine whether the acute myeloid leukemia of Brown Norway rats, which is accompanied by oxidative stress, evoked behavioral and receptor changes resembling alterations characteristic of rat models of depression. The rats were divided into two groups: leukemic rats and healthy control. Leukemia was induced through intraperitoneal injection of 10(7) promyelocytic leukemia cells to the Brown Norway rats. Depression-like behavior was evaluated in the forced swim test at 30 or 34 days after leukemic cells injection. The rats were killed after the evaluation and the spleen, brain cortex and hippocampus were excised. The red-ox state was assessed in homogenates of tissues by measuring total glutathione (GSH) content, the ferric ion reducing ability of plasma (FRAP) level, expression of heme oxygenase-1 (HO-1), biliverdin reductase (BvR) and ferritin mRNA, superoxide dismutase (SOD) activity, as well as malondialdehyde (MDA) concentration. Radioligand binding assay was used to assess of the effect of leukemia on cortical receptors. Leukemic cells were identified using RM-124 antibody by FACS Calibur flow cytometry. Leukemia influenced locomotory activity as well as forced swim test behavior in a 34-day series of experiments. Signs of oxidative stress in leukemic rats were observed in each examined stage of leukemia development. The FRAP values and glutathione contents, were significantly lowered whereas HO-1 mRNA expression, and malonodialdehyde concentrations were significantly increased in the spleen and brain structures of leukemic rats in comparison with the healthy controls. A significant increase in the potency of glycine to displace [(3)H]L-689,560 from the strychnine-insensitive glycine site of the N-methyl-D-aspartic (NMDA) receptors receptor complex in cortical homogenates of the leukemic rats in 30- and 34-day experimental series was observed in comparison with the control. Upregulation of 5-HT(2A) receptors was observed in rat cortex after 30 days of leukemia development but not in 34-days series compared with the control. It is concluded that disturbances in antioxidant system in brain cortex were accompanied by an activation of glycine sites of the NMDA receptor complex, regardless of stage of leukemia development, which are characteristic of model of depression. Findings of our study demonstrate the link between glutamatergic activity, oxidative stress and leukemia.",
"title": "Evaluation of oxidative status and depression-like responses in Brown Norway rats with acute myeloid leukemia"
},
{
"docid": "17119869",
"text": "The pancreas emerges independently from dorsal and ventral domains of embryonic gut endoderm. Gene inactivation experiments in mice have identified factors required for dorsal pancreas development, but factors that initiate the ventral pancreas have remained elusive. In this study, we investigated the hypothesis that the emergence of the ventral pancreas is related to the emergence of the liver. We find that the liver and ventral pancreas are specified at the same time and in the same general domain of cells. Using embryo tissue explantation experiments, we find that the default fate of the ventral foregut endoderm is to activate the pancreas gene program. FGF signalling from the cardiac mesoderm diverts this endoderm to express genes for liver instead of those for pancreas. No evidence was found to indicate that the cell type choice for pancreas or liver involves a selection for growth or viability. Cardiac mesoderm or FGF induces the local expression of sonic hedgehog, which in turn is inhibitory to pancreas but not to liver. The bipotential precursor cell population for pancreas and liver in embryonic development and its fate selection by FGF has features that appear to be recapitulated in the adult pancreas and are reflected in the evolution of these organs.",
"title": "A bipotential precursor population for pancreas and liver within the embryonic endoderm."
},
{
"docid": "5002665",
"text": "The embryonic cell lineage of Caenorhabditis elegans has been traced from zygote to newly hatched larva, with the result that the entire cell lineage of this organism is now known. During embryogenesis 671 cells are generated; in the hermaphrodite 113 of these (in the male 111) undergo programmed death and the remainder either differentiate terminally or become postembryonic blast cells. The embryonic lineage is highly invariant, as are the fates of the cells to which it gives rise. In spite of the fixed relationship between cell ancestry and cell fate, the correlation between them lacks much obvious pattern. Thus, although most neurons arise from the embryonic ectoderm, some are produced by the mesoderm and a few are sisters to muscles; again, lineal boundaries do not necessarily coincide with functional boundaries. Nevertheless, cell ablation experiments (as well as previous cell isolation experiments) demonstrate substantial cell autonomy in at least some sections of embryogenesis. We conclude that the cell lineage itself, complex as it is, plays an important role in determining cell fate. We discuss the origin of the repeat units (partial segments) in the body wall, the generation of the various orders of symmetry, the analysis of the lineage in terms of sublineages, and evolutionary implications.",
"title": "The embryonic cell lineage of the nematode Caenorhabditis elegans."
},
{
"docid": "40254495",
"text": "Transcript regulation is essential for cell function, and misregulation can lead to disease. Despite technologies to survey the transcriptome, we lack a comprehensive understanding of transcript kinetics, which limits quantitative biology. This is an acute challenge in embryonic development, where rapid changes in gene expression dictate cell fate decisions. By ultra-high-frequency sampling of Xenopus embryos and absolute normalization of sequence reads, we present smooth gene expression trajectories in absolute transcript numbers. During a developmental period approximating the first 8 weeks of human gestation, transcript kinetics vary by eight orders of magnitude. Ordering genes by expression dynamics, we find that \"temporal synexpression\" predicts common gene function. Remarkably, a single parameter, the characteristic timescale, can classify transcript kinetics globally and distinguish genes regulating development from those involved in cellular metabolism. Overall, our analysis provides unprecedented insight into the reorganization of maternal and embryonic transcripts and redefines our ability to perform quantitative biology.",
"title": "Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development."
},
{
"docid": "4412772",
"text": "Unicellular organisms such as yeasts require a single cyclin-dependent kinase, Cdk1, to drive cell division. In contrast, mammalian cells are thought to require the sequential activation of at least four different cyclin-dependent kinases, Cdk2, Cdk3, Cdk4 and Cdk6, to drive cells through interphase, as well as Cdk1 to proceed through mitosis. This model has been challenged by recent genetic evidence that mice survive in the absence of individual interphase Cdks. Moreover, most mouse cell types proliferate in the absence of two or even three interphase Cdks. Similar results have been obtained on ablation of some of the activating subunits of Cdks, such as the D-type and E-type cyclins. Here we show that mouse embryos lacking all interphase Cdks (Cdk2, Cdk3, Cdk4 and Cdk6) undergo organogenesis and develop to midgestation. In these embryos, Cdk1 binds to all cyclins, resulting in the phosphorylation of the retinoblastoma protein pRb and the expression of genes that are regulated by E2F transcription factors. Mouse embryonic fibroblasts derived from these embryos proliferate in vitro, albeit with an extended cell cycle due to inefficient inactivation of Rb proteins. However, they become immortal on continuous passage. We also report that embryos fail to develop to the morula and blastocyst stages in the absence of Cdk1. These results indicate that Cdk1 is the only essential cell cycle Cdk. Moreover, they show that in the absence of interphase Cdks, Cdk1 can execute all the events that are required to drive cell division.",
"title": "Cdk1 is sufficient to drive the mammalian cell cycle"
},
{
"docid": "19204979",
"text": "Cells derived from blood vessels of human skeletal muscle can regenerate skeletal muscle, similarly to embryonic mesoangioblasts. However, adult cells do not express endothelial markers, but instead express markers of pericytes, such as NG2 proteoglycan and alkaline phosphatase (ALP), and can be prospectively isolated from freshly dissociated ALP+ cells. Unlike canonical myogenic precursors (satellite cells), pericyte-derived cells express myogenic markers only in differentiated myotubes, which they form spontaneously with high efficiency. When transplanted into severe combined immune deficient–X-linked, mouse muscular dystrophy (scid–mdx) mice, pericyte-derived cells colonize host muscle and generate numerous fibres expressing human dystrophin. Similar cells isolated from Duchenne patients, and engineered to express human mini-dystrophin, also give rise to many dystrophin-positive fibres in vivo. These data show that myogenic precursors, distinct from satellite cells, are associated with microvascular walls in the human skeletal muscle, may represent a correlate of embryonic 'mesoangioblasts' present after birth and may be a promising candidate for future cell-therapy protocols in patients.",
"title": "Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells"
},
{
"docid": "26612216",
"text": "ATP-dependent chromatin remodeling complexes are a notable group of epigenetic modifiers that use the energy of ATP hydrolysis to change the structure of chromatin, thereby altering its accessibility to nuclear factors. BAF250a (ARID1a) is a unique and defining subunit of the BAF chromatin remodeling complex with the potential to facilitate chromosome alterations critical during development. Our studies show that ablation of BAF250a in early mouse embryos results in developmental arrest (about embryonic day 6.5) and absence of the mesodermal layer, indicating its critical role in early germ-layer formation. Moreover, BAF250a deficiency compromises ES cell pluripotency, severely inhibits self-renewal, and promotes differentiation into primitive endoderm-like cells under normal feeder-free culture conditions. Interestingly, this phenotype can be partially rescued by the presence of embryonic fibroblast cells. DNA microarray, immunostaining, and RNA analyses revealed that BAF250a-mediated chromatin remodeling contributes to the proper expression of numerous genes involved in ES cell self-renewal, including Sox2, Utf1, and Oct4. Furthermore, the pluripotency defects in BAF250a mutant ES cells appear to be cell lineage-specific. For example, embryoid body-based analyses demonstrated that BAF250a-ablated stem cells are defective in differentiating into fully functional mesoderm-derived cardiomyocytes and adipocytes but are capable of differentiating into ectoderm-derived neurons. Our results suggest that BAF250a is a key component of the gene regulatory machinery in ES cells controlling self-renewal, differentiation, and cell lineage decisions.",
"title": "ES cell pluripotency and germ-layer formation require the SWI/SNF chromatin remodeling component BAF250a."
},
{
"docid": "24523573",
"text": "Previous studies have shown that synchronized beta frequency (14-30 Hz) oscillations in the primary motor cortex are involved in maintaining steady contractions of contralateral arm and hand muscles. However, little is known about the role of postcentral cortical areas in motor maintenance and their patterns of interaction with motor cortex. We investigated the functional relations of beta-synchronized neuronal assemblies in pre- and postcentral areas of two monkeys as they pressed a hand lever during the wait period of a visual discrimination task. By using power and coherence spectral analysis, we identified a beta-synchronized large-scale network linking pre- and postcentral areas. We then used Granger causality spectra to measure directional influences among recording sites. In both monkeys, strong Granger causal influences were observed from primary somatosensory cortex to both motor cortex and inferior posterior parietal cortex, with the latter area also exerting Granger causal influences on motor cortex. Granger causal influences from motor cortex to postcentral sites, however, were weak in one monkey and not observed in the other. These results are the first, to our knowledge, to demonstrate in awake monkeys that synchronized beta oscillations bind multiple sensorimotor areas into a large-scale network during motor maintenance behavior and carry Granger causal influences from primary somatosensory and inferior posterior parietal cortices to motor cortex.",
"title": "Beta oscillations in a large-scale sensorimotor cortical network: directional influences revealed by Granger causality."
},
{
"docid": "12887068",
"text": "Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail of histone H3.3. The role of the H3.3K27M mutation in tumorigenesis is not fully understood. Here, we use a human embryonic stem cell system to model this tumor. We show that H3.3K27M expression synergizes with p53 loss and PDGFRA activation in neural progenitor cells derived from human embryonic stem cells, resulting in neoplastic transformation. Genome-wide analyses indicate a resetting of the transformed precursors to a developmentally more primitive stem cell state, with evidence of major modifications of histone marks at several master regulator genes. Drug screening assays identified a compound targeting the protein menin as an inhibitor of tumor cell growth in vitro and in mice.",
"title": "Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation"
},
{
"docid": "13878124",
"text": "Radial glial cells (RGCs) in the developing cerebral cortex are progenitors for neurons and glia, and their processes serve as guideposts for migrating neurons. So far, it has remained unclear whether RGC processes also control the function of RGCs more directly. Here, we show that RGC numbers and cortical size are reduced in mice lacking beta1 integrins in RGCs. TUNEL stainings and time-lapse video recordings demonstrate that beta1-deficient RGCs processes detach from the meningeal basement membrane (BM) followed by apoptotic death of RGCs. Apoptosis is also induced by surgical removal of the meninges. Finally, mice lacking the BM components laminin alpha2 and alpha4 show defects in the attachment of RGC processes at the meninges, a reduction in cortical size, and enhanced apoptosis of RGC cells. Our findings demonstrate that attachment of RGC processes at the meninges is important for RGC survival and the control of cortical size.",
"title": "Regulation of radial glial survival by signals from the meninges."
},
{
"docid": "10846815",
"text": "The actin cortex both facilitates and hinders the exocytosis of secretory granules. How cells consolidate these two opposing roles was not well understood. Here we show that antigen activation of mast cells induces oscillations in Ca(2+) and PtdIns(4,5)P(2) lipid levels that in turn drive cyclic recruitment of N-WASP and cortical actin level oscillations. Experimental and computational analysis argues that vesicle fusion correlates with the observed actin and Ca(2+) level oscillations. A vesicle secretion cycle starts with the capture of vesicles by actin when cortical F-actin levels are high, followed by vesicle passage through the cortex when F-actin levels are low, and vesicle fusion with the plasma membrane when Ca(2+) levels subsequently increase. Thus, cells employ oscillating levels of Ca(2+), PtdIns(4,5)P(2) and cortical F-actin to increase secretion efficiency, explaining how the actin cortex can function as a carrier as well as barrier for vesicle secretion.",
"title": "Coordinated oscillations in cortical actin and Ca2+ correlate with cycles of vesicle secretion"
},
{
"docid": "36651210",
"text": "Embryonic stem cells have the ability to remain undifferentiated and proliferate indefinitely in vitro while maintaining the potential to differentiate into derivatives of all three embryonic germ layers. These cells have, therefore, potential for in vitro differentiation studies, gene function, and so on. The aim of this study was to produce a human embryonic stem cell line. An inner cell mass of a human blastocyst was separated and cultured on mouse embryonic fibroblasts in embryonic stem cell medium with related additives. The established line was evaluated by morphology; passaging; freezing and thawing; alkaline phosphatase; Oct-4 expression; anti-surface markers including Tra-1-60 and Tra-1-81; and karyotype and spontaneous differentiation. Differentiated cardiomyocytes and neurons were evaluated by transmission electron microscopy and immunocytochemistry. Here, we report the derivation of a new embryonic stem cell line (Royan H1) from a human blastocyst that remains undifferentiated in morphology during continuous passaging for more than 30 passages, maintains a normal XX karyotype, is viable after freezing and thawing, and expresses alkaline phosphatase, Oct-4, Tra-1-60, and Tra-1-81. These cells remain undifferentiated when grown on mouse embryonic fibroblast feeder layers in the presence or absence of recombinant human leukemia inhibitory factor. Royan H1 cells can differentiate in vitro in the absence of feeder cells and can produce embryoid bodies that can further differentiate into beating cardiomyocytes as well as neurons. These results define Royan H1 cells as a new human embryonic stem cell line.",
"title": "Establishment and in vitro differentiation of a new embryonic stem cell line from human blastocyst."
},
{
"docid": "4335423",
"text": "Despite decades of research, the identity of the cells generating the first haematopoietic cells in mammalian embryos is unknown. Indeed, whether blood cells arise from mesodermal cells, mesenchymal progenitors, bipotent endothelial–haematopoietic precursors or haemogenic endothelial cells remains controversial. Proximity of endothelial and blood cells at sites of embryonic haematopoiesis, as well as their similar gene expression, led to the hypothesis of the endothelium generating blood. However, owing to lacking technology it has been impossible to observe blood cell emergence continuously at the single-cell level, and the postulated existence of haemogenic endothelial cells remains disputed. Here, using new imaging and cell-tracking methods, we show that embryonic endothelial cells can be haemogenic. By continuous long-term single-cell observation of mouse mesodermal cells generating endothelial cell and blood colonies, it was possible to detect haemogenic endothelial cells giving rise to blood cells. Living endothelial and haematopoietic cells were identified by simultaneous detection of morphology and multiple molecular and functional markers. Detachment of nascent blood cells from endothelium is not directly linked to asymmetric cell division, and haemogenic endothelial cells are specified from cells already expressing endothelial markers. These results improve our understanding of the developmental origin of mammalian blood and the potential generation of haematopoietic stem cells from embryonic stem cells.",
"title": "Continuous single-cell imaging of blood generation from haemogenic endothelium"
},
{
"docid": "4311206",
"text": "Pancreatic insulin-producing beta-cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime. Nevertheless, they show increased self-duplication after increased metabolic demand or after injury (that is, beta-cell loss). It is not known whether adult mammals can differentiate (regenerate) new beta-cells after extreme, total beta-cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-beta-cell) source. Here we show beta-cell regeneration in a transgenic model of diphtheria-toxin-induced acute selective near-total beta-cell ablation. If given insulin, the mice survived and showed beta-cell mass augmentation with time. Lineage-tracing to label the glucagon-producing alpha-cells before beta-cell ablation tracked large fractions of regenerated beta-cells as deriving from alpha-cells, revealing a previously disregarded degree of pancreatic cell plasticity. Such inter-endocrine spontaneous adult cell conversion could be harnessed towards methods of producing beta-cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration.",
"title": "Conversion of Adult Pancreatic α-cells to β-cells After Extreme β-cell Loss"
},
{
"docid": "92499",
"text": "Hematopoietic stem cells (HSCs) develop during embryogenesis in a complex process that involves multiple anatomical sites. Once HSC precursors have been specified from mesoderm, they have to mature into functional HSCs and undergo self-renewing divisions to generate a pool of HSCs. During this process, developing HSCs migrate through various embryonic niches, which provide signals for their establishment and the conservation of their self-renewal ability. These processes have to be recapitulated to generate HSCs from embryonic stem cells. Elucidating the interactions between developing HSCs and their niches should facilitate the generation and expansion of HSCs in vitro to exploit their clinical potential.",
"title": "The journey of developing hematopoietic stem cells."
},
{
"docid": "14460402",
"text": "The molecular mechanisms that regulate adult neural precursor cell (NPC) survival, and thus maintain adult neurogenesis, are not well defined. Here, we investigate the role of p63, a p53 family member, in adult NPC function in mice. Conditional ablation of p63 in adult NPCs or p63 haploinsufficiency led to reduced numbers of NPCs and newborn neurons in the neurogenic zones of the hippocampus and lateral ventricles and in the olfactory bulb. These reductions were attributable to enhanced apoptosis of NPCs and newborn neurons and were rescued by inhibition of caspase activity, p53, or the p53 apoptotic effector PUMA (p53-upregulated modulator of apoptosis). Moreover, these cellular deficits were functionally important because they led to perturbations in hippocampus-dependent memory formation. These results indicate that p63 regulates the numbers of adult NPCs and adult-born neurons as well as neural stem cell-dependent cognitive functions, and that it does so, at least in part, by inhibiting p53-dependent cell death.",
"title": "p63 Regulates adult neural precursor and newly born neuron survival to control hippocampal-dependent Behavior."
},
{
"docid": "19770974",
"text": "Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages. After undifferentiated proliferation in vitro for 4 to 5 months, these cells still maintained the developmental potential to form trophoblast and derivatives of all three embryonic germ layers, including gut epithelium (endoderm); cartilage, bone, smooth muscle, and striated muscle (mesoderm); and neural epithelium, embryonic ganglia, and stratified squamous epithelium (ectoderm). These cell lines should be useful in human developmental biology, drug discovery, and transplantation medicine.",
"title": "Prev | Table of Contents Reports Embryonic Stem Cell Lines Derived from Human"
},
{
"docid": "19522248",
"text": "We targeted the locus encoding the cyclin-dependent kinase 2 (CDK2) by homologous recombination in mouse embryonic stem (ES) cells. Embryonic fibroblasts lacking CDK2 proliferate normally and become immortal after continuous passage in culture. Elimination of a conditional Cdk2 allele in immortal cells does not have a significant effect on proliferation. Cdk2−/− mice are viable and survive for up to two years, indicating that CDK2 is also dispensable for proliferation and survival of most cell types. But CDK2 is essential for completion of prophase I during meiotic cell division in male and female germ cells, an unforeseen role for this cell cycle kinase.",
"title": "Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice"
}
] |
5876
|
Investment in mutual fund in India for long term goals
|
[
{
"docid": "281865",
"text": "On reading couple of articles & some research over internet, I got to know about diversified investment where one should invest 70% in equity related & rest 30% in debt related funds Yes that is about right. Although the recommendation keeps varying a bit. However your first investment should not aim for diversification. Putting small amounts in multiple mutual funds may create paper work and tracking issues. My suggestion would be to start with an Index EFT or Large cap. Then move to balanced funds and mid caps etc. On this site we don't advise on specific funds. You can refer to moneycontrol.com or economictimes or quite a few other personal finance advisory sites to understand the top funds in the segments and decide on funds accordingly. PS: Rather than buying paper, buy it electronic, better you can now buy it as Demat. If you already have an Demat account it would be best to buy through it.",
"title": ""
},
{
"docid": "183497",
"text": "Buy only 'Direct' Plans, not regular. - Demat providers won't sell Direct plans, that you can do it through https://www.mfuindia.com Make sure expense ratio < 2.5% (With direct plans it will be much lesser) I hope these points will help you to take a better decision.",
"title": ""
}
] |
[
{
"docid": "386173",
"text": "It isn't just ETFs, you have normal mutual funds in India which invest internationally. This could be convenient if you don't already have a depository account and a stockbroker. Here's a list of such funds, along with some performance data: Value Research - Equity: International: Long-term Performance. However, you should also be aware that in India, domestic equity and equity fund investing is tax-free in the long-term (longer than one year), but this exemption doesn't apply to international investments. Ref: Invest Around the World.",
"title": ""
},
{
"docid": "88575",
"text": "\"A mutual fund's return or yield has nothing to do with what you receive from the mutual fund. The annual percentage return is simply the percentage increase (or decrease!) of the value of one share of the mutual fund from January 1 till December 31. The cash value of any distributions (dividend income, short-term capital gains, long-term capital gains) might be reported separately or might be included in the annual return. What you receive from the mutual fund is the distributions which you have the option of taking in cash (and spending on whatever you like, or investing elsewhere) or of re-investing into the fund without ever actually touching the money. Regardless of whether you take a distribution as cash or re-invest it in the mutual fund, that amount is taxable income in most jurisdictions. In the US, long-term capital gains are taxed at different (lower) rates than ordinary income, and I believe that long-term capital gains from mutual funds are not taxed at all in India. You are not taxed on the increase in the value of your investment caused by an increase in the share price over the year nor do you get deduct the \"\"loss\"\" if the share price declined over the year. It is only when you sell the mutual fund shares (back to the mutual fund company) that you have to pay taxes on the capital gains (if you sold for a higher price) or deduct the capital loss (if you sold for a lower price) than the purchase price of the shares. Be aware that different shares in the sale might have different purchase prices because they were bought at different times, and thus have different gains and losses. So, how do you calculate your personal return from the mutual fund investment? If you have a money management program or a spreadsheet program, it can calculate your return for you. If you have online access to your mutual fund account on its website, it will most likely have a tool called something like \"\"Personal rate of return\"\" and this will provide you with the same calculations without your having to type in all the data by hand. Finally, If you want to do it personally by hand, I am sure that someone will soon post an answer writing out the gory details.\"",
"title": ""
},
{
"docid": "393009",
"text": "Waiting for the next economic downturn probably isn't the best plan at this point. While it could happen tomorrow, you may end up waiting a long time. If you would prefer not to think much about your investment and just let them grow then mutual funds are a really good option. Make sure you research them before you buy into any and make sure to diversify, as in buy into a lot of different mutual funds that cover different parts of the market. If you want to be more active in investing then start researching the market and stick to industries you have very good understanding of. It's tough to invest in a market you know nothing about. I'd suggest putting at least some of that into a retirement savings account for long term growth. Make sure you look at both your short term and long term goals. Letting an investment mature from age 20 through to retirement will net you plenty of compound interest but don't forget about your short term goals like possible cars, houses and families. Do as much research as you can and you will be fine!",
"title": ""
},
{
"docid": "135596",
"text": "This might be better suited to r/personalfinance but if you're looking to invest I'd say start with an index fund. The MER's (fees) for most other mutual funds take too heavy a chunk of returns to be worth it in a market where actively managed funds are either underperforming of performing at par with passive funds. Additionally if these are your first investments, make sure you're doing it with investment goals in mind. Is this money you're saving for short, medium, or long term? For medium and long term investing make sure you're doing it through a tax efficient instrument like an IRA or 401k.",
"title": ""
},
{
"docid": "315741",
"text": "It's not so much pros and cons as much as it is what are your savings goals? While it's best to start early to save money for retirement, you may have numerous short- to medium-term savings goals (school, down payment, etc). Here's a template you can consider. I would suggest that you open up an RRSP mutual fund or brokerage account and invest a certain amount that you feel free locking up for the next few decades and investing it in some sort of growth product (perhaps look at portfolios using the Couch Potato strategy). Then, also open up a TFSA mutual fund or brokerage account and use it to invest for medium-term goals (i.e. 5-10 years). Invest in products that will allow for some growth but with low chance of losing principle in that time frame. What I wouldn't do is open up a TFSA savings account and use it for day-to-day savings. The tax you save is negligible and you would need to keep track of deposits and withdrawals to ensure that you don't overcontribute for the tax year. Similarly, an RRSP savings account or GIC is far too conservative at your age, IMHO. Think of RRSP and TFSA as investment vehicles rather than accounts per se. Either type allows for you to invest in a vast array of products, including mutual funds, equities, some derivatives, gold, bonds, GICs, etc. To conclude, my view is to use RRSP to invest for conventional retirement goals, and use the TFSA to invest for medium-term and early retirement goals.",
"title": ""
},
{
"docid": "240351",
"text": "Just to clarify Short Team Goals & Long Term Goals... Long Term goals are for something in future, your retirement fund, Children’s education etc. Short Term goals are something in the near future, your down payment for car, house, and holiday being planned. First have both the long and short terms goals defined. Of Couse you would need to review both these goals on a ongoing basis... To meet the short term goals you would need to make short term investments. Having arrived at a short term goal value, you would now need to make a decision as to how much risk you are willing [also how much is required to take] to take in order to meet your goal. For example if you goal is to save Rs 100,000 by yearend for the car, and you can easily set aside Rs 8,000 every month, you don't really need to take a risk. A simple Term / Fixed Deposit would suffice you to meet your goal. On the other hand if you can only save Rs 6,000 a year, then you would need to invest this into something that would return you around 35%. You would now need to take a risk. Stocks market is one option, there are multiple types of trades [day trades, shorts, options, regular trades] that one can do ... however the risk can wipe out even your capital. As you don't know these types of investments, suggest you start with dummy investing using quite a few free websites, MoneyControl is one such site, you get pseudo money and can buy sell and see how things actually move. This should teach you something about making quick gains or losses without actually gaining or loosing real money. Once you reach some confidence level, you can start trading using real money by opening a trading account almost every other bank in India offers online trading linked to bank account. Never lose sight of risk appetite, and revise if every now and then. When you don't have dependents, you can easily risk money for potential bumper, however after you have other commitments, you may want to tone down... Edit: http://moneybhai.moneycontrol.com/moneybhai-rules.html is one such site, there are quite a few others as well that offer you to trade on virtual money. Try this for few months and you will understand whether you are making right decissions or not.",
"title": ""
},
{
"docid": "385600",
"text": "For some ideas on investing priority guidelines, see Oversimplify it for me: the correct order of investing. Congratulations on being debt free! My advice to you is to do what you can to remain debt free. You could certainly invest the money; it will earn much more over the long-term in a stock mutual fund than it would left in a savings account. However, if you need any of this money in the next few years, it would be a shame if it lost money in the short-term. How much do you need to finish grad school? Don't invest that money in the stock market, because you will need it over the next few years. Likewise, think about other expenses that are coming up. Will your car need to be replaced in the next couple of years? Will you have enough income to meet your living expenses while you are in grad school, or will you need some of this to money to help with that? Finally, it would be good to keep some extra as an emergency fund, so you can easily pay for any unexpected expenses that come up. If you can make it through grad school debt free, you will be much better off than if you invest all the money but take out student loans in the process. After you've accounted for all of that, whatever is left of the money could definitely be invested. If your goal is to start a retirement fund, an index mutual fund invested inside a Roth IRA is a great place to start.",
"title": ""
},
{
"docid": "594257",
"text": "\"My original plan was to wait for the next economic downturn and invest in index funds. These funds have historically yielded 6-7% annually when entered at any given time, but maybe around 8-9% annually when entered during a recession. These numbers have been adjusted for inflation. Questions or comments on this strategy? Educate yourself as index funds are merely a strategy that could be applied to various asset classes such as US Large-cap value stocks, Emerging Market stocks, Real Estate Investment Trusts, US Health Care stocks, Short-term bonds, and many other possibilities. Could you be more specific about which funds you meant as there is some great work by Fama and French on the returns of various asset classes over time. What about a Roth IRA? Mutual fund? Roth IRA is a type of account and not an investment in itself, so while I think it is a good idea to have Roth IRA, I would highly advise researching the ins and outs of this before assuming you can invest in one. You do realize that index funds are just a special type of mutual fund, right? It is also worth noting that there are a few kinds of mutual funds: Open-end, exchange-traded and closed-end. Which kind did you mean? What should I do with my money until the market hits another recession? Economies have recessions, markets have ups and downs. I'd highly consider forming a real strategy rather than think, \"\"Oh let's toss it into an index fund until I need the money,\"\" as that seems like a recipe for disaster. Figure out what long-term financial goals do you have in mind, how OK are you with risk as if the market goes down for more than a few years straight, are you OK with seeing those savings be cut in half or worse?\"",
"title": ""
},
{
"docid": "518487",
"text": "One estimate is to sell today, estimate the taxes, and determine how much cash you need to set aside over the next 12 months. The is no way to calculate what impact dividends and capital gains the funds will have, because unlike interest they aren't guaranteed. The other complexity is that the funds themselves could drop in value. In that case the dividends and capital gains may not even be enough to get you back to even. I use mutual funds to invest over the long term, with the idea of spending the funds over decades. When needing to save for a short term goal, I use banking products. They are guaranteed not to lose value, and the interest changes are slowerand thus easier to predict.",
"title": ""
},
{
"docid": "473647",
"text": "Other answers are already very good, but I'd like to add one step before taking the advice of the other answers... If you still can, switch to a 15 year mortgage, and figure out what percentage of your take-home pay the new payment is. This is the position taken by Dave Ramsey*, and I believe this will give you a better base from which to launch your other goals for two reasons: Since you are then paying it off faster at a base payment, you may then want to take MrChrister's advice but put all extra income toward investments, feeling secure that your house will be paid off much sooner anyway (and at a lower interest rate). * Dave's advice isn't for everyone, because he takes a very long-term view. However, in the long-term, it is great advice. See here for more. JoeTaxpayer is right, you will not see anything near guaranteed yearly rates in mutual funds, so make sure they are part of a long-term investing plan. You are not investing your time in learning the short-term stock game, so stay away from it. As long as you are continuing to learn in your own career, you should see very good short-term gains there anyway.",
"title": ""
},
{
"docid": "87722",
"text": "In my opinion, if you are doing long-term investing, this is a non-issue. The difference of hours in being able to trade an ETF during the day vs. only being able to trade a traditional mutual fund at day-end is irrelevant if you are holding the investment for a long time. If you are engaging in day trading, market timing, or other advanced/controversial trading practices, then I suppose it could make a difference. For the way I invest (index funds, long-term, set-it-and-forget-it), ETFs have no advantage over traditional mutual funds.",
"title": ""
},
{
"docid": "333004",
"text": "First of all kudos to you for seeing the value in saving at a young age. There are several different things you can mean by this and I'm not sure which is accurate so I am going to address the first two that I thought of. If you are selling your investments because you need the money (emergency expenses, saved enough for a short term goal, whatever the reason) then this may not be the best solution for your savings. Investing in mutual funds, ETFs, stocks, 401k, IRA, etc are typically for longer term goals such as a goal that is 10+ years away (maybe buying a home, paying for college for your children, retirement, etc). If you are selling your investments because you believe that another investment is performing better and you want to get in on that one instead what I would suggest is leaving the money you have invested where it is and starting future investments in the new fund/ETF you are interested in. For example if you have $2000 invested in fund X and now you do some research and fund Q looks more appealing that is great, start investing in fund Q with your next deposit. Any research you do will be based on past results, there is nothing that guarantees that fund Q will continue doing better than the fund X you already have. Trying to time the market rarely ends well for the investor. I would encourage you to continue saving money a bit at a time just like you have been doing. Avoid selling your investments until it is time to sell them for whatever goal you intended them for. Set aside some cash to cover any unexpected expenses so you won't have to sell your investments to cover the costs, even at 18 unplanned things happen.",
"title": ""
},
{
"docid": "45190",
"text": "\"A mutual fund could make two different kinds of distributions to you: Capital gains: When the fund liquidates positions that it holds, it may realize a gain if it sells the assets for a greater price than the fund purchased them for. As an example, for an index fund, assets may get liquidated if the underlying index changes in composition, thus requiring the manager to sell some stocks and purchase others. Mutual funds are required to distribute most of their income that they generate in this way back to its shareholders; many often do this near the end of the calendar year. When you receive the distribution, the gains will be categorized as either short-term (the asset was held for less than one year) or long-term (vice versa). Based upon the holding period, the gain is taxed differently. Currently in the United States, long-term capital gains are only taxed at 15%, regardless of your income tax bracket (you only pay the capital gains tax, not the income tax). Short-term capital gains are treated as ordinary income, so you will pay your (probably higher) tax rate on any cash that you are given by your mutual fund. You may also be subject to capital gains taxes when you decide to sell your holdings in the fund. Any profit that you made based on the difference between your purchase and sale price is treated as a capital gain. Based upon the period of time that you held the mutual fund shares, it is categorized as a short- or long-term gain and is taxed accordingly in the tax year that you sell the shares. Dividends: Many companies pay dividends to their stockholders as a way of returning a portion of their profits to their collective owners. When you invest in a mutual fund that owns dividend-paying stocks, the fund is the \"\"owner\"\" that receives the dividend payments. As with capital gains, mutual funds will redistribute these dividends to you periodically, often quarterly or annually. The main difference with dividends is that they are always taxed as ordinary income, no matter how long you (or the fund) have held the asset. I'm not aware of Texas state tax laws, so I can't comment on your other question.\"",
"title": ""
},
{
"docid": "94040",
"text": "Short-term to intermediate-term corporate bond funds are available. The bond fund vehicle helps manage the credit risk, while the short terms help manage inflation and interest rate risk. Corporate bond funds will have fewer Treasuries bonds than a general-purpose short-term bond fund: it sounds like you're interested in things further out along the risk curve than a 0.48% return on a 5-year bond, and thus don't care for the Treasuries. Corporate bonds are generally safer than stocks because, in bankruptcy, all your bondholders have to be paid in full before any equity-holders get a penny. Stocks are much more volatile, since they're essentially worth the value of their profits after paying all their debt, taxes, and other expenses. As far as stocks are concerned, they're not very good for the short term at all. One of the stabler stock funds would be something like the Vanguard Equity Income Fund, and it cautions: This fund is designed to provide investors with an above-average level of current income while offering exposure to the stock market. Since the fund typically invests in companies that are dedicated to consistently paying dividends, it may have a higher yield than other Vanguard stock mutual funds. The fund’s emphasis on slower-growing, higher-yielding companies can also mean that its total return may not be as strong in a significant bull market. This income-focused fund may be appropriate for investors who have a long-term investment goal and a tolerance for stock market volatility. Even the large-cap stable companies can have their value fall dramatically in the short term. Look at its price chart; 2008 was brutal. Avoid stocks if you need to spend your money within a couple of years. Whatever you choose, read the prospectus to understand the risks.",
"title": ""
},
{
"docid": "500486",
"text": "First, it's not always the case that ETFs have lower expenses than the equivalent mutual funds. For example, in the Vanguard family of funds the expense ratio for the ETF version is the same as it is for the Admiral share class in the mutual fund version. With that in mind, the main advantages of a mutual fund over an equivalent ETF are: From a long-term investor's point of view, the main disadvantage of mutual funds relative to ETFs is the minimum account sizes. Especially if the fund has multiple share classes (i.e., where better classes get lower expense ratios), you might have to have quite a lot of money invested in the fund in order to get the same expense ratio as the ETF. There are some other differences that matter to more active investors (e.g., intraday trading, options, etc.), but for a passive investor the ones above are the major ones. Apart from those mutual funds and ETFs are pretty similar. Personally, I prefer mutual funds because I'm at a point where the fund minimums aren't really an issue, and I don't want to deal with the more fiddly aspects of ETFs. For investors just starting out the lower minimum investment for an ETF is a big win, as long as you can get commission-free trades (which is what I've assumed above.)",
"title": ""
},
{
"docid": "81304",
"text": "You can look the Vanguard funds up on their website and view a risk factor provided by Vanguard on a scale of 1 to 5. Short term bond funds tend to get their lowest risk factor, long term bond funds and blended investments go up to about 3, some stock mutual funds are 4 and some are 5. Note that in 2008 Swenson himself had slightly different target percentages out here that break out the international stocks into emerging versus developed markets. So the average risk of this portfolio is 3.65 out of 5. My guess would be that a typical twenty-something who expects to retire no earlier than 60 could take more risk, but I don't know your personal goals or circumstances. If you are looking to maximize return for a level of risk, look into Modern Portfolio Theory and the work of economist Harry Markowitz, who did extensive work on the topic of maximizing the return given a set risk tolerance. More info on my question here. This question provides some great book resources for learning as well. You can also check out a great comparison and contrast of different portfolio allocations here.",
"title": ""
},
{
"docid": "537394",
"text": "If you are concerned about FDIC coverage, then yes, you can spread your money across multiple banks. The limit is $250k, so after you invest in property, 4 banks should do it. That having been said, in my opinion, it would be a waste to keep all this money in a bank's savings account. You will slowly lose value over time due to inflation. I suggest you spend a little money on an independent fee-based investment advisor. Choose someone who will teach you about investing in mutual funds, so you can feel comfortable with it. He or she should take into account your tolerance for risk, look at your goals, and help you come up with a low cost plan for investing your money. It's certainly okay to keep the money in a bank short-term, but don't wait too long; take steps toward putting that money to work for you.",
"title": ""
},
{
"docid": "114054",
"text": "\"I'm not following what's the meaning of \"\"open a mutual fund\"\". You don't open a mutual fund, you invest in it. There's a minimum required investment ($2000? Could be, some funds have lower limits, you don't have to go with the Fidelity one necessarily), but in general it has nothing to do with your Roth IRA account. You can invest in mutual funds with any trading account, not just Roth IRA (or any other specific kind). If you invest in ETF's - you can invest in funds just as well (subject to the minimums set). As to the plan itself - buying and selling ETF's will cost you commission, ~2-3% of your investment. Over several months, you may get positive returns, and may get negative returns, but keep in mind that you start with the 2-3% loss on day 1. Within a short period of time, especially in the current economic climate (which is very unstable - just out of recession, election year, etc etc), I would think that keeping the cash in a savings account would be a better choice. While with ETF you don't have any guarantees other than -3%, then with savings accounts you can at least have a guaranteed return of ~1% APY (i.e.: won't earn much over the course of your internship, but you'll keep your money safe for your long term investment). For the long term - the fluctuations of month to month don't matter much, so investing now for the next 50 years - you shouldn't care about the stock market going 10% in April. So, keep your 1000 in savings account, and if you want to invest 5000 in your Roth IRA - invest it then. Assuming of course that you're completely positive about not needing this money in the next several decades.\"",
"title": ""
},
{
"docid": "282375",
"text": "My suggestion is that you speak with a financial adviser that specializes in Islamic investing. For the long term there are Islam approved mutual funds that only invest in non-banking organizations, and I would assume there are more conservative options for the short term as well (3-4 years). Although you may not feel the effects of inflation all that much in just a few years, it would still be beneficial to utilize programs that allow you to earn a return on your money. (I may not have said that for $2,500 but for $25,000 I think it's worth looking into.) Also, some scholars suggest that it is even allowed to invest in mutual funds that deal with banks, as long as you calculate the portion of your return that came from the bank charging interest, and donate that amount to charity.",
"title": ""
},
{
"docid": "549364",
"text": "\"As you alluded to in your question, there is not one answer that will be true for all mutual funds. In fact, I would argue the question is not specific to mutual funds but can be applied to almost anyone who must make an investment decision: a mutual fund manager, hedge fund manager, or an individual investor. Even though money going into a company 401(k) retirement savings plan is typically automatically allocated to different funds as we have specified, this is generally not the case for other investment accounts. For example, I also have a Roth IRA in which I have some money from each paycheck direct deposited and it's up to me to decide whether to leave that money in cash or to invest it somewhere else. Every time you invest more money into a mutual fund, the fund manager has the same decision to make. There are two commonly used mutual fund figures that relate to your question: turnover rate, and cash reserves. Turnover rate measures the percent of a fund's portfolio that changes every year. For example, a turnover rate of 100% indicates that a fund replaces every asset it held at the beginning of the year with something else at the end of the year – funds with turnover rates greater than 100% average a holding period for a given asset of less than one year, and funds with turnover rates less than 100% average a holding period for a given asset of more than one year. Cash reserves simply measure the amount of money funds choose to keep as cash instead of investing in other assets. Another important distinction to make is between actively managed funds and passively managed funds. Passively managed funds are often referred to as \"\"index funds\"\" and have as their goal only to match the returns of a given index or some other benchmark. Actively managed funds on the other hand try to beat the market by exploiting so-called market inefficiencies; e.g. buying undervalued assets, selling overvalued assets, \"\"timing\"\" the market, etc. To answer your question for a specific fund, I would encourage you to look at the fund's prospectus. I take as one example of a passively managed fund the Vanguard 500 Index Fund (VFINX), a mutual fund that was created to track the S&P 500. In its prospectus, the fund states that, \"\"to track its target index as closely as possible, the Fund attempts to remain fully invested in stocks\"\". Furthermore, the prospectus states that \"\"the fund's daily cash balance may be invested in one or more Vanguard CMT Funds, which are very low-cost money market funds.\"\" Therefore, we would expect both this fund's turnover rate and cash reserves to be extremely low. When we look at its portfolio composition, we see this is true – it is currently at a 4.8% turnover rate and holds 0.0% in short term reserves. Therefore, we can assume this fund is regularly purchasing shares (similar to a dollar cost averaging strategy) instead of holding on to cash and purchasing shares together at a specific time. For actively managed funds, the picture will tend to look a little different. For example, if we look at the Magellan Fund's portfolio composition, we can see it has a turnover rate of 42%, and holds around .95% in cash/short term reserves. In this case, we can safely guess that trading activity may not be as regular as a passively managed fund, as an active manager attempts to time the market. You may find mutual funds that have much higher cash reserves – perhaps 10% or even more. Granted, it is impossible to know the exact trading strategy of a mutual fund, and for good reason – if we knew for example, that a fund purchases shares every day at 2:30PM in order to realign with the S&P 500, then sellers of S&P components could up the prices at that time to exploit the mutual fund's trade strategy. Large traders are constantly trying to find ways to conceal their actual trading activity in order to avoid these exact problems. Finally, I feel obligated to note that it is important to keep in mind that trade frequency is linked to transactions costs – in general, the more frequently an investment manager (whether it be you or a mutual fund manager) executes trades, the more that manager will lose in transactions costs.\"",
"title": ""
},
{
"docid": "264820",
"text": "\"An investment is sold when you sell that particular stock or fund. It doesn't wait until you withdraw cash from the brokerage account. Whether an investment is subject to long term or short term taxes depends on how long you held that particular stock. Sorry, you can't get around the higher short term tax by leaving the money in a brokerage account or re-investing in something else. If you are invested in a mutual fund, whether it's long or short term depends on when you buy and sell the fund. The fact that the fund managers are buying and selling behind your back doesn't affect this. (I don't know what taxes they have to pay, maybe you really are paying for it in the form of management fees or lower returns, but you don't explicitly pay the tax on these \"\"inner\"\" transactions.) Your broker should send you a tax statement every year giving the numbers that you need to fill in to the various boxes of your income tax form. You don't have to figure it out. Of course it helps to know the rules. If you've held a stock for 11 1/2 months and are planning to sell, you might want to consider waiting a couple of weeks so it becomes a long term capital gain rather than short term and thus subject to lower tax.\"",
"title": ""
},
{
"docid": "157414",
"text": "Let's look at some of your options: In a savings account, your $40,000 might be earning maybe 0.5%, if you are lucky. In a year, you'll have earned $200. On the plus side, you'll have your $40,000 easily accessible to you to pay for moving, closing costs on your new house, etc. If you apply it to your mortgage, you are effectively saving the interest on the amount for the life of the loan. Let's say that the interest rate on your mortgage is 4%. If you were staying in the house long-term, this interest would be compounded, but since you are only going to be there for 1 year, this move will save you $1600 in interest this year, which means that when you sell the house and pay off this mortgage, you'll have $1600 extra in your pocket. You said that you don't like to dabble in stocks. I wouldn't recommend investing in individual stocks anyway. A stock mutual fund, however, is a great option for investing, but only as a long-term investment. You should be able to beat your 4% mortgage, but only over the long term. If you want to have the $40,000 available to you in a year, don't invest in a mutual fund now. I would lean toward option #2, applying the money to the mortgage. However, there are some other considerations: Do you have any other debts, maybe a car loan, student loan, or a credit card balance? If so, I would forget everything else and put everything toward one or more of these loans first. Do you have an emergency fund in place, or is this $40,000 all of the cash that you have available to you? One rule of thumb is that you have 3 to 6 months of expenses set aside in a safe, easily accessible account ready to go if something comes up. Are you saving for retirement? If you don't already have retirement savings in place and are adding to it regularly, some of this cash would be a great start to a Roth IRA or something like that, invested in a stock mutual fund. If you are already debt free except for this mortgage, you might want to do some of each: Keep $10,000 in a savings account for an emergency fund (if you don't already have an emergency fund), put $5,000 in a Roth IRA (if you aren't already contributing a satisfactory amount to a retirement account), and apply the rest toward your mortgage.",
"title": ""
},
{
"docid": "403701",
"text": "This is really an extended comment on the last paragraph of @BenMiller's answer. When (the manager of) a mutual fund sells securities that the fund holds for a profit, or receives dividends (stock dividends, bond interest, etc.), the fund has the option of paying taxes on that money (at corporate rates) and distributing the rest to shareholders in the fund, or passing on the entire amount (categorized as dividends, qualified dividends, net short-term capital gains, and net long-term capital gains) to the shareholders who then pay taxes on the money that they receive at their own respective tax rates. (If the net gains are negative, i.e. losses, they are not passed on to the shareholders. See the last paragraph below). A shareholder doesn't have to reinvest the distribution amount into the mutual fund: the option of receiving the money as cash always exists, as does the option of investing the distribution into a different mutual fund in the same family, e.g. invest the distributions from Vanguard's S&P 500 Index Fund into Vanguard's Total Bond Index Fund (and/or vice versa). This last can be done without needing a brokerage account, but doing it across fund families will require the money to transit through a brokerage account or a personal account. Such cross-transfers can be helpful in reducing the amounts of money being transferred in re-balancing asset allocations as is recommended be done once or twice a year. Those investing in load funds instead of no-load funds should keep in mind that several load funds waive the load for re-investment of distributions but some funds don't: the sales charge for the reinvestment is pure profit for the fund if the fund was purchased directly or passed on to the brokerage if the fund was purchased through a brokerage account. As Ben points out, a shareholder in a mutual fund must pay taxes (in the appropriate categories) on the distributions from the fund even though no actual cash has been received because the entire distribution has been reinvested. It is worth keeping in mind that when the mutual fund declares a distribution (say $1.22 a share), the Net Asset Value per share drops by the same amount (assuming no change in the prices of the securities that the fund holds) and the new shares issued are at this lower price. That is, there is no change in the value of the investment: if you had $10,000 in the fund the day before the distribution was declared, you still have $10,000 after the distribution is declared but you own more shares in the fund than you had previously. (In actuality, the new shares appear in your account a couple of days later, not immediately when the distribution is declared). In short, a distribution from a mutual fund that is re-invested leads to no change in your net assets, but does increase your tax liability. Ditto for a distribution that is taken as cash or re-invested elsewhere. As a final remark, net capital losses inside a mutual fund are not distributed to shareholders but are retained within the fund to be written off against future capital gains. See also this previous answer or this one.",
"title": ""
},
{
"docid": "269671",
"text": "At your age (heck, at MY age :-)) I would not think about doing any of those types of investments (not savings) on your own, unless you are really interested in the investment process for its own sake, and are willing to devote a lot of time to investigating companies in order to try to pick good investments. Instead, find a good mutual fund from say Vanguard or TRP, put your money in there, and relax. Depending on your short-term goals (e.g. will you expect to need the money for college?) you could pick either an index fund, or a low-risk, mostly bond fund.",
"title": ""
},
{
"docid": "43781",
"text": "@Victor above has provided a very good answer, I shall try and highlight some differences. The differences are specific to a country, however, it does offer some insight regarding the difference between investing in retirement fund vis-a-vis investing in stock directly: In many countries the retirement fund is mandated by the govt. and has to be invested in (in form of direct deduction from salary) ~ Investing in stock is up to the individual In many cases (if not most) capital gain/interest accrual in retirement funds are not taxable ~ Depending upon current laws capital gain (long term/short term) from stocks are taxable Retirement funds are managed and are (in general) more stable in their returns ~ Returns from direct stock investments are dependent on investment decisions of the investor Retirement funds tend to, (though this is very country specific) return somewhat less than market, as an example, in India Public Provident Fund (PPF)/Employee Provident Fund (EPF) return 8.68% tax free ~ As for direct investment on stocks, Nifty has returned approx. 17% CAGR over 15-20 years. Given the above, if you can invest in stock by taking informed calls and you have a good understanding of the financial markets and their underpinning and (probably) looking at long term investment, then investing directly in stock could fetch returns that might not be paralled by retirement funds. If on the other hand, if you feel investing in stock is not for you, then it probably is better to stick with retirement funds and other low risk investments. Either way, you probably have to (and may be you should) carry some portion of your portfolio as retirement funds.",
"title": ""
},
{
"docid": "405178",
"text": "\"I would refer you to this question and answers. Here in the US we have two basic types of life insurance: term and whole life. Universal life is a marketing response to whole life being such a bad deal, and is whole life just not quite as bad. I am not familiar with the products in India, but given the acronym (ULIP), it is probably universal life, and as you describe is variable universal life. Likely Description \"\"Under the hood\"\", or in effect, you are purchasing a term life policy and investing excess premiums in a collection of stock mutual funds. This is a bad deal for a few reasons: A much better option is to buy \"\"level term insurance\"\" and invest on your own. You won't necessarily lose money, but you can make better financial decisions. It is good to invest, it is good to have life. A better decision would not to combine the two into a single product.\"",
"title": ""
},
{
"docid": "524612",
"text": "ETFs are a type of investment, not a specific choice. In other words, there are good ETFs and bad. What you see is the general statement that ETFs are preferable to most mutual funds, if only for the fact that they are low cost. An index ETF such as SPY (which reflects the S&P 500 index) has a .09% annual expense, vs a mutual fund which average a full percent or more. sheegaon isn't wrong, I just have a different spin to offer you. Given a long term return of say even 8% (note - this question is not a debate of the long term return, and I purposely chose a low number compared to the long term average, closer to 10%) and the current CD rate of <1%, a 1% hit for the commission on the buy side doesn't bother me. The sell won't occur for a long time, and $8 on a $10K sale is no big deal. I'd not expect you to save $1K/yr in cash/CDs for the years it would take to make that $8 fee look tiny. Not when over time the growth will overshaddow this. One day you will be in a position where the swings in the market will produce the random increase or decrease to your net worth in the $10s of thousands. Do you know why you won't lose a night's sleep over this? Because when you invested your first $1K, and started to pay attention to the market, you saw how some days had swings of 3 or 4%, and you built up an immunity to the day to day noise. You stayed invested and as you gained wealth, you stuck to the right rebalancing each year, so a market crash which took others down by 30%, only impacted you by 15-20, and you were ready for the next move to the upside. And you also saw that since mutual funds with their 1% fees never beat the index over time, you were happy to say you lagged the S&P by .09%, or 1% over 11 year's time vs those whose funds had some great years, but lost it all in the bad years. And by the way, right until you are in the 25% bracket, Roth is the way to go. When you are at 25%, that's the time to use pre-tax accounts to get just below the cuttoff. Last, welcome to SE. Edit - see sheegaon's answer below. I agree, I missed the cost of the bid/ask spread. Going with the lowest cost (index) funds may make better sense for you. To clarify, Sheehan points out that ETFs trade like a stock, a commission, and a bid/ask, both add to transaction cost. So, agreeing this is the case, an indexed-based mutual fund can provide the best of possible options. Reflecting the S&P (for example) less a small anual expense, .1% or less.",
"title": ""
},
{
"docid": "161445",
"text": "The S&P 500 is a stock market index, which is a list of 500 stocks from the largest companies in America. You could open a brokerage account with a broker and buy shares in each of these companies, but the easiest, least expensive way to invest in all these stocks is to invest in an S&P 500 index mutual fund. Inside an index mutual fund, your money will be pooled together with everyone else in the fund to purchase all the stocks in the index. These types of funds are very low expense compared to managed mutual funds. Most mutual fund companies have an S&P 500 index fund; two examples are Vanguard and Fidelity. The minimum investment in most of these mutual funds is low enough that you will be able to open an account with your $4000. Something you need to keep in mind, however: investing in any stock mutual fund is not non-risk. It's not even low-risk, really. It is very possible to lose money by investing in the stock market. An S&P 500 index fund is diversified in the sense that you have money in lots of different stocks, but it is also not diversified, in a sense, because it is all in large cap American stocks. Before investing in the stock market, you should have a goal for the money you are investing. If you are investing for something several years away, an index fund can be a good place to invest, but if you will need this money within the next few years, the stock market might be too risky for you.",
"title": ""
},
{
"docid": "354136",
"text": "\"This answer is applicable to the US. Similar rules may hold in some other countries as well. The shares in an open-ended (non-exchange-traded) mutual fund are not traded on stock exchanges and the \"\"market\"\" does not determine the share price the way it does for shares in companies as brokers make offers to buy and sell stock shares. The price of one share of the mutual fund (usually called Net Asset Value (NAV) per share) is usually calculated at the close of business, and is, as the name implies, the net worth of all the shares in companies that the fund owns plus cash on hand etc divided by the number of mutual fund shares outstanding. The NAV per share of a mutual fund might or might not increase in anticipation of the distribution to occur, but the NAV per share very definitely falls on the day that the distribution is declared. If you choose to re-invest your distribution in the same fund, then you will own more shares at a lower NAV per share but the total value of your investment will not change at all. If you had 100 shares currently priced at $10 and the fund declares a distribution of $2 per share, you will be reinvesting $200 to buy more shares but the fund will be selling you additional shares at $8 per share (and of course, the 100 shares you hold will be priced at $8 per share too. So, you will have 100 previous shares worth only $800 now + 25 new shares worth $200 for a total of 125 shares at $8 = $1000 total investment, just as before. If you take the distribution in cash, then you still hold the 100 shares but they are worth only $800 now, and the fund will send you the $200 as cash. Either way, there is no change in your net worth. However, (assuming that the fund is is not in a tax-advantaged account), that $200 is taxable income to you regardless of whether you reinvest it or take it as cash. The fund will tell you what part of that $200 is dividend income (as well as what part is Qualified Dividend income), what part is short-term capital gains, and what part is long-term capital gains; you declare the income in the appropriate categories on your tax return, and are taxed accordingly. So, what advantage is there in re-investing? Well, your basis in those shares has increased and so if and when you sell the shares, you will owe less tax. If you had bought the original 100 shares at $10 and sell the 125 shares a few years later at $11 and collect $1375, you owe (long-term capital gains) tax on just $1375-$1200 =$175 (which can also be calculated as $1 gain on each of the original 100 shares = $100 plus $3 gain on the 25 new shares = $175). In the past, some people would forget the intermediate transactions and think that they had invested $1000 initially and gotten $1375 back for a gain of $375 and pay taxes on $375 instead. This is less likely to occur now since mutual funds are now required to report more information on the sale to the shareseller than they used to in the past. So, should you buy shares in a mutual fund right now? Most mutual fund companies publish preliminary estimates in November and December of what distributions each fund will be making by the end of the year. They also usually advise against purchasing new shares during this period because one ends up \"\"buying a dividend\"\". If, for example, you bought those 100 shares at $10 on the Friday after Thanksgiving and the fund distributes that $2 per share on December 15, you still have $1000 on December 15, but now owe taxes on $200 that you would not have had to pay if you had postponed buying those shares till after the distribution was paid. Nitpickers: for simplicity of exposition, I have not gone into the detailed chronology of when the fund goes ex-dividend, when the distribution is recorded, and when cash is paid out, etc., but merely treated all these events as happening simultaneously.\"",
"title": ""
},
{
"docid": "388252",
"text": "\"(Congrats on earning/saving $3K and not wanting to blow it all on immediate gratification!) I currently have it invested in sector mutual funds but with the rise and fall of the stock market, is this really the best way to prepare long-term? Long-term? Yes! However... four years is not long term. It is, in fact, borderline short term. (When I was your age, that was incomprehensible too, but trust me: it's true.) The problem is that there's an inverse relationship between reward and risk: the higher the possible reward, the greater the risk that you'll lose a big chunk of it. I invest that middle-term money in a mix of junk high yield bond funds and \"\"high\"\" yield savings accounts at an online bank. My preferences are HYG purchased at Fidelity (EDIT: because it's commission-free and I buy a few hundred dollars worth every month), and Ally Bank.\"",
"title": ""
}
] |
828
|
NAC inhibits the generation of angiotensin-converting enzyme.
|
[
{
"docid": "4678846",
"text": "CONTEXT The antioxidant acetylcysteine prevents acute contrast nephrotoxicity in patients with impaired renal function who undergo computed tomography scanning. However, its role in coronary angiography is unclear. OBJECTIVE To determine whether oral acetylcysteine prevents acute deterioration in renal function in patients with moderate renal insufficiency who undergo elective coronary angiography. DESIGN AND SETTING Prospective, randomized, double-blind, placebo-controlled trial conducted from May 2000 to December 2001 at the Grantham Hospital at the University of Hong Kong. PARTICIPANTS Two hundred Chinese patients aged mean (SD) 68 (6.5) years with stable moderate renal insufficiency (creatinine clearance <60 mL/min [1.00 mL/s]) who were undergoing elective coronary angiography with or without intervention. INTERVENTION Participants were randomly assigned to receive oral acetylcysteine(600 mg twice per day; n = 102) or matching placebo tablets (n = 98) on the day before and the day of angiography. All patients received low-osmolality contrast agent. MAIN OUTCOME MEASURES Occurrence of more than a 25% increase in serum creatinine level within 48 hours after contrast administration; change in creatinine clearance and serum creatinine level. RESULTS Twelve control patients (12%) and 4 acetylcysteine patients (4%) developed a more than 25% increase in serum creatinine level within 48 hours after contrast administration (relative risk, 0.32; 95% confidence interval [CI], 0.10-0.96; P =.03). Serum creatinine was lower in the acetylcysteine group (1.22 mg/dL [107.8 micromol/L]; 95% CI, 1.11-1.33 mg/dL vs 1.38 mg/dL [122.9 micromol/L]; 95% CI, 1.27-1.49 mg/dL; P =.006) during the first 48 hours after angiography. Acetylcysteine treatment significantly increased creatinine clearance from 44.8 mL/min (0.75 mL/s) (95% CI, 42.7-47.6 mL/min) to 58.9 mL/min (0.98 mL/s) (95% CI, 55.6-62.3 mL/min) 2 days after the contrast administration (P<.001). The increase was not significant in the control group (from 42.1 to 44.1 mL/min [0.70 to 0.74 mL/s]; P =.15). The benefit of acetylcysteine was consistent among various patient subgroups and persistent for at least 7 days. There were no major treatment-related adverse events. CONCLUSION Acetylcysteine protects patients with moderate chronic renal insufficiency from contrast-induced deterioration in renal function after coronary angiographic procedures, with minimal adverse effects and at a low cost.",
"title": "Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: a randomized controlled trial."
}
] |
[
{
"docid": "1759213",
"text": "OBJECTIVE To examine the safety of using aliskiren combined with agents used to block the renin-angiotensin system. DESIGN Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES Medline, Embase, the Cochrane Library, and two trial registries, published up to 7 May 2011. STUDY SELECTION Published and unpublished randomised controlled trials that compared combined treatment using aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers with monotherapy using these agents for at least four weeks and that provided numerical data on the adverse event outcomes of hyperkalaemia and acute kidney injury. A random effects model was used to calculate pooled risk ratios and 95% confidence intervals for these outcomes. RESULTS 10 randomised controlled studies (4814 participants) were included in the analysis. Combination therapy with aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers significantly increased the risk of hyperkalaemia compared with monotherapy using angiotensin converting enzymes or angiotensin receptor blockers (relative risk 1.58, 95% confidence interval 1.24 to 2.02) or aliskiren alone (1.67, 1.01 to 2.79). The risk of acute kidney injury did not differ significantly between the combined therapy and monotherapy groups (1.14, 0.68 to 1.89). CONCLUSION Use of aliskerin in combination with angiotensin converting enzyme inhibitors or angiotensin receptor blockers is associated with an increased risk for hyperkalaemia. The combined use of these agents warrants careful monitoring of serum potassium levels.",
"title": "The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis"
},
{
"docid": "26199970",
"text": "Objective: It is unclear whether blockade of the angiotensin system has effects on mental health. Our objective was to determine the impact of angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor (AT1R) blockers on mental health domain of quality of life. Study design: Meta-analysis of published literature. Data sources: PubMed and clinicaltrials.gov databases. The last search was conducted in January 2017. Study selection: Randomized controlled trials comparing any angiotensin converting enzyme inhibitor or AT1R blocker versus placebo or non-angiotensin converting enzyme inhibitor or non-AT1R blocker were selected. Study participants were adults without any major physical symptoms. We adhered to meta-analysis reporting methods as per PRISMA and the Cochrane Collaboration. Data synthesis: Eleven studies were included in the analysis. When compared with placebo or other antihypertensive medications, AT1R blockers and angiotensin converting enzyme inhibitors were associated with improved overall quality of life (standard mean difference = 0.11, 95% confidence interval = [0.08, 0.14], p < 0.0001), positive wellbeing (standard mean difference = 0.11, 95% confidence interval = [0.05, 0.17], p < 0.0001), mental (standard mean difference = 0.15, 95% confidence interval = [0.06, 0.25], p < 0.0001), and anxiety (standard mean difference = 0.08, 95% confidence interval = [0.01, 0.16], p < 0.0001) domains of QoL. No significant difference was found for the depression domain (standard mean difference = 0.05, 95% confidence interval = [0.02, 0.12], p = 0.15). Conclusions: Use of angiotensin blockers and inhibitors for the treatment of hypertension in otherwise healthy adults is associated with improved mental health domains of quality of life. Mental health quality of life was a secondary outcome in the included studies. Research specifically designed to analyse the usefulness of drugs that block the angiotensin system is necessary to properly evaluate this novel psychiatric target.",
"title": "Blockade of the angiotensin system improves mental health domain of quality of life: A meta-analysis of randomized clinical trials"
},
{
"docid": "14584755",
"text": "The renin-angiotensin-aldosterone system plays a major role in the pathophysiology of hypertension and closely related cardio- and cerebrovascular events. Although both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists (angiotensin receptor blockers; ARBs) are equally important in the treatment of hypertension, according to the results of recent years, there might be substantial differences in their cardiovascular protective effects, and these differences might be explained by our increasing knowledge of their non-overlapping mechanisms of action. The number of studies investigating how ACE inhibitors and ARB agents differ will certainly be increasing in the future. ACE inhibitors are the safe therapeutic opportunity for hypertensive patients at high risk, with a cardiological comorbidity.",
"title": "Differences in the Clinical Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: A Critical Review of the Evidence"
},
{
"docid": "6157837",
"text": "Angiotensin converting enzyme (ACE) inhibitors are now one of the most frequently used classes of antihypertensive drugs. Beyond their utility in the management of hypertension, their use has been extended to the long-term management of patients with congestive heart failure (CHF), as well as diabetic and nondiabetic nephropathies. Although ACE inhibitor therapy usually improves renal blood flow (RBF) and sodium excretion rates in CHF and reduces the rate of progressive renal injury in chronic renal disease, its use can also be associated with a syndrome of “functional renal insufficiency” and/or hyperkalemia. This form of acute renal failure (ARF) most commonly develops shortly after initiation of ACE inhibitor therapy but can be observed after months or years of therapy, even in the absence of prior ill effects. ARF is most likely to occur when renal perfusion pressure cannot be sustained because of substantial decreases in mean arterial pressure (MAP) or when glomerular filtration rate (GFR) is highly angiotensin II (Ang II) dependent. Conditions that predict an adverse hemodynamic effect of ACE inhibitors in patients with CHF are preexisting hypotension and low cardiac filling pressures. The GFR is especially dependent on Ang II during extracellular fluid (ECF) volume depletion, high-grade bilateral renal artery stenosis, or stenosis of a dominant or single kidney, as in a renal transplant recipient. Understanding the pathophysiological mechanisms and the common risk factors for ACE inhibitor–induced functional ARF is critical, because preventive strategies for ARF exist, and if effectively used, they may permit use of these compounds in a less restricted fashion. Under normal physiological conditions, renal autoregulation adjusts renal vascular resistance, so that RBF and GFR remain constant over a wide range of MAPs.1 The intrinsic renal autoregulation mechanism is adjusted by Ang II and the sympathetic nervous system. When renal perfusion pressure falls (as in …",
"title": "Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association."
},
{
"docid": "43417006",
"text": "New-onset diabetes mellitus (NOD) refers to forms of diabetes mellitus that develop during the therapeutic processes of other diseases such as hypertension. This study has been conducted in a network meta-analysis to compare antihypertensive drugs by identifying both the advantages and disadvantages on NOD by focusing on their respective effect rates. Odd ratios and corresponding 95% confidence intervals or credible intervals were calculated within pairwise and network meta-analysis. A total of 38 articles with 224 140 patients were included to evaluate the preventive effect of hypertension drugs on NOD. From the network meta-analysis it was evident that both angiotensin-converting enzyme inhibitor as well as angiotensin receptor blocker treatments are associated with a lower risk of developing NOD compared with placebo, with ranking probabilities of 79.81% and 72.77%, respectively, while β-blockers and calcium channel blockers may significantly increase the probability of developing NOD (β-blockers: odds ratio, 2.18 [95% credible intervals: 1.36-3.50]; calcium channel blockers: odds ratio, 1.16 [95% credible intervals, 1.05-1.29]). In conclusion, angiotensin receptor blockers have an advantage over the other treatments regarding the NOD.",
"title": "Comparative risk of new-onset diabetes mellitus for antihypertensive drugs: A network meta-analysis."
},
{
"docid": "4700428",
"text": "BACKGROUND Relapse to cocaine seeking has been linked with low glutamate in the nucleus accumbens core (NAcore) causing potentiation of synaptic glutamate transmission from prefrontal cortex (PFC) afferents. Systemic N-acetylcysteine (NAC) has been shown to restore glutamate homeostasis, reduce relapse to cocaine seeking, and depotentiate PFC-NAcore synapses. Here, we examine the effects of NAC applied directly to the NAcore on relapse and neurotransmission in PFC-NAcore synapses, as well as the involvement of the metabotropic glutamate receptors 2/3 (mGluR2/3) and 5 (mGluR5). METHODS Rats were trained to self-administer cocaine for 2 weeks and following extinction received either intra-accumbens NAC or systemic NAC 30 or 120 minutes, respectively, before inducing reinstatement with a conditioned cue or a combined cue and cocaine injection. We also recorded postsynaptic currents using in vitro whole cell recordings in acute slices and measured cystine and glutamate uptake in primary glial cultures. RESULTS NAC microinjection into the NAcore inhibited the reinstatement of cocaine seeking. In slices, a low concentration of NAC reduced the amplitude of evoked glutamatergic synaptic currents in the NAcore in an mGluR2/3-dependent manner, while high doses of NAC increased amplitude in an mGluR5-dependent manner. Both effects depended on NAC uptake through cysteine transporters and activity of the cysteine/glutamate exchanger. Finally, we showed that by blocking mGluR5 the inhibition of cocaine seeking by NAC was potentiated. CONCLUSIONS The effect of NAC on relapse to cocaine seeking depends on the balance between stimulating mGluR2/3 and mGluR5 in the NAcore, and the efficacy of NAC can be improved by simultaneously inhibiting mGluR5.",
"title": "The effect of N-acetylcysteine in the nucleus accumbens on neurotransmission and relapse to cocaine."
},
{
"docid": "35724562",
"text": "In adult patients with CKD, hypertension is linked to the development of left ventricular hypertrophy, but whether this association exists in children with CKD has not been determined conclusively. To assess the relationship between BP and left ventricular hypertrophy, we prospectively analyzed data from the Chronic Kidney Disease in Children cohort. In total, 478 subjects were enrolled, and 435, 321, and 142 subjects remained enrolled at years 1, 3, and 5, respectively. Echocardiograms were obtained 1 year after study entry and then every 2 years; BP was measured annually. A linear mixed model was used to assess the effect of BP on left ventricular mass index, which was measured at three different visits, and a mixed logistic model was used to assess left ventricular hypertrophy. These models were part of a joint longitudinal and survival model to adjust for informative dropout. Predictors of left ventricular mass index included systolic BP, anemia, and use of antihypertensive medications other than angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Predictors of left ventricular hypertrophy included systolic BP, female sex, anemia, and use of other antihypertensive medications. Over 4 years, the adjusted prevalence of left ventricular hypertrophy decreased from 15.3% to 12.6% in a systolic BP model and from 15.1% to 12.6% in a diastolic BP model. These results indicate that a decline in BP may predict a decline in left ventricular hypertrophy in children with CKD and suggest additional factors that warrant additional investigation as predictors of left ventricular hypertrophy in these patients.",
"title": "BP control and left ventricular hypertrophy regression in children with CKD."
},
{
"docid": "32463364",
"text": "OBJECTIVES Prevention of cognitive decline and dementia with blood pressure lowering treatments has shown inconsistent results. We compared the effects of different classes of antihypertensive drugs on the incidence of dementia, and on cognitive function. METHODS We conducted a systematic review and included 19 randomized trials (18 515 individuals) and 11 studies (831 674 individuals) analysing the effects of antihypertensive treatment on cognition and on the incidence of dementia, respectively, in hypertensive patients without prior cerebrovascular disorders. Network meta-analysis was used for the comparison of antihypertensive classes. RESULTS Antihypertensive treatment, regardless of the drug class, had benefits on overall cognition [effect size 0.05, 95% confidence interval (CI) 0.02-0.07] and all cognitive functions except language. Antihypertensive treatment reduced the risk of all-cause dementia by 9%, with reference to the control group (hazard ratio 0.91, 95% CI 0.89-0.94), when randomized trials and observationnal studies were combined (n = 15). Result was not significant with randomized trials alone (n = 4). Angiotensin II receptor blockers (ARBs) had larger benefits than placebo on overall cognition (adjusted effect size 0.60 ± 0.18, P = 0.02). ARBs were more effective than β-blockers (0.67 ± 0.18, P = 0.01), diuretics (0.54 ± 0.19, P = 0.04) and angiotensin-converting enzyme inhibitors (0.47 ± 0.17, P = 0.04) in rank. The mean change in blood pressure did not differ significantly between the different antihypertensive drug classes. CONCLUSION Our results support the notion that antihypertensive treatment has beneficial effects on cognitive decline and prevention of dementia, and indicate that these effects may differ between drug classes with ARBs possibly being the most effective.",
"title": "Antihypertensive classes, cognitive decline and incidence of dementia: a network meta-analysis."
},
{
"docid": "26025370",
"text": "Background: Vasoconstriction and reactive oxygen species (ROS) accumulation following contrast media (CM) injection are the key factors triggering CM-induced nephropathy. We compared the effects of N-acetylcysteine (NAC), theophylline or sodium bicarbonate on intrarenal vasoconstriction and ROS generation in a rat model of CM-induced nephropathy. Methods: Following a 3-day dehydration, Sprague-Dawley rats received CM (Telebrix) or sham ‘CM’ injection of 0.9% saline. Part of them received NAC, theophylline or bicarbonate prior to CM. Medullar renal blood flow was estimated by laser Doppler. The animals were sacrificed 1, 15 or 30 min after the respective treatments, their kidneys allocated and intrarenal STAT-8 isoprostane, PGE2 and NO assessed. Results: Vasoconstriction was significantly attenuated by NAC. Theophylline only mildly attenuated the perfusion drop at 15 min, and was ineffective following 30 min. Unlike theophylline or bicarbonate, NAC significantly augmented intrarenal PGE2. NAC, theophylline but not bicarbonate, gradually increased intrarenal NO. In all experimental variables, CM-induced ROS accumulation, represented by STAT-8 isoprostane estimation, progressed undisturbed. Conclusions: (1) CM-induced intrarenal vasoconstriction was efficiently prohibited by NAC but not bicarbonate or theophylline; (2) the vasodilatory effect of NAC was mediated via increased PGE2 synthesis, and (3) ROS accumulation was a primary renal response to CM-induced injury, not affected by any pharmacologic manipulations.",
"title": "Differential Effects of N-Acetylcysteine, Theophylline or Bicarbonate on Contrast-Induced Rat Renal Vasoconstriction"
},
{
"docid": "6397191",
"text": "Endothelin-1 (ET-1) is the predominant endothelin isopeptide generated by the vascular wall and therefore appears to be the most important peptide involved in regulation of cardiovascular events. Many pathologic conditions are associated with elevations of ET-1 in the blood vessel wall. Because these conditions are often cytokine driven, we examined the effects of a mixture of cytokines on ET-1 production in human vascular smooth muscle cells (VSMCs) derived from internal mammary artery and saphenous vein (SV). Incubation of IMA and SV VSMCs with tumor necrosis factor-alpha (10 ng/ml) and interferon-gamma (1000 U/ml) in combination for up to 48 h markedly elevated the expression of mRNA for prepro-ET-1 and the release of ET-1 into the culture medium. This cytokine-stimulated release of ET-1 was inhibited by a series of dual endothelin-converting enzyme (ECE)/neutral endopeptidase inhibitors, phosphoramidon, CGS 26303, and CGS 26393, with an accompanying increase in big ET-1 release but with no effect on expression of mRNA for prepro-ET-1. These same compounds were 10 times more potent at inhibiting the conversion of exogenously applied big ET-1 to ET-1. ECE-1b/c mRNA is present in SV VSMCs, however no ECE-1a is present in these cells. Thus VSMCs most probably contain, like endothelial cells, an intracellular ECE responsible for the endogenous synthesis of ET-1. Under the influence of pro-inflammatory mediators the vascular smooth muscle can therefore become an important site of ET-1 production, as has already been established for the dilator mediators nitric oxide, prostaglandin I2, and prostaglandin E2.",
"title": "Endothelin-1 is induced by cytokines in human vascular smooth muscle cells: evidence for intracellular endothelin-converting enzyme."
},
{
"docid": "7821634",
"text": "Neoadjuvant chemotherapy (NAC) induces a pathological complete response (pCR) in ∼30% of patients with breast cancer. However, many patients have residual cancer after chemotherapy, which correlates with a higher risk of metastatic recurrence and poorer outcome than those who achieve a pCR. We hypothesized that molecular profiling of tumors after NAC would identify genes associated with drug resistance. Digital transcript counting was used to profile surgically resected breast cancers after NAC. Low concentrations of dual specificity protein phosphatase 4 (DUSP4), an ERK phosphatase, correlated with high post-NAC tumor cell proliferation and with basal-like breast cancer (BLBC) status. BLBC had higher DUSP4 promoter methylation and gene expression patterns of Ras-ERK pathway activation relative to other breast cancer subtypes. DUSP4 overexpression increased chemotherapy-induced apoptosis, whereas DUSP4 depletion dampened the response to chemotherapy. Reduced DUSP4 expression in primary tumors after NAC was associated with treatment-refractory high Ki-67 scores and shorter recurrence-free survival. Finally, inhibition of mitogen-activated protein kinase kinase (MEK) synergized with docetaxel treatment in BLBC xenografts. Thus, DUSP4 downregulation activates the Ras-ERK pathway in BLBC, resulting in an attenuated response to anti-cancer chemotherapy.",
"title": "Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance"
},
{
"docid": "25816994",
"text": "BACKGROUND Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage. METHODS The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101. FINDINGS 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 [13.4%]) and ramipril (1150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1233 [14.5%]; HR 1.09, 1.01-1.18, p=0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%]; HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24, 1.01-1.51, p=0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m(2)vs -4.12 [17.4], p<0.0001) or combination therapy (-6.11 [17.9], p<0.0001). The increase in urinary albumin excretion was less with telmisartan (p=0.004) or with combination therapy (p=0.001) than with ramipril. INTERPRETATION In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.",
"title": "Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial."
},
{
"docid": "38944245",
"text": "Lung Krüppel-like factor (LKLF/KLF2) is an endothelial transcription factor that is crucially involved in murine vasculogenesis and is specifically regulated by flow in vitro. We now show a relation to local flow variations in the adult human vasculature: decreased LKLF expression was noted at the aorta bifurcations to the iliac and carotid arteries, coinciding with neointima formation. The direct involvement of shear stress in the in vivo expression of LKLF was determined independently by in situ hybridization and laser microbeam microdissection/reverse transcriptase-polymerase chain reaction in a murine carotid artery collar model, in which a 4- to 30-fold induction of LKLF occurred at the high-shear sites. Dissection of the biomechanics of LKLF regulation in vitro demonstrated that steady flow and pulsatile flow induced basal LKLF expression 15- and 36-fold at shear stresses greater than approximately 5 dyne/cm2, whereas cyclic stretch had no effect. Prolonged LKLF induction in the absence of flow changed the expression of angiotensin-converting enzyme, endothelin-1, adrenomedullin, and endothelial nitric oxide synthase to levels similar to those observed under prolonged flow. LKLF repression by siRNA suppressed the flow response of endothelin-1, adrenomedullin, and endothelial nitric oxide synthase (P < 0.05). Thus, we demonstrate that endothelial LKLF is regulated by flow in vivo and is a transcriptional regulator of several endothelial genes that control vascular tone in response to flow.",
"title": "Endothelial KLF2 links local arterial shear stress levels to the expression of vascular tone-regulating genes."
},
{
"docid": "5573975",
"text": "Molecules associated with the transforming growth factor β (TGF-β) superfamily, such as bone morphogenic proteins (BMPs) and TGF-β, are key regulators of inflammation, apoptosis and cellular transitions. Here we show that the BMP receptor activin-like kinase 3 (Alk3) is elevated early in diseased kidneys after injury. We also found that its deletion in the tubular epithelium leads to enhanced TGF-β1-Smad family member 3 (Smad3) signaling, epithelial damage and fibrosis, suggesting a protective role for Alk3-mediated signaling in the kidney. A structure-function analysis of the BMP-Alk3-BMP receptor, type 2 (BMPR2) ligand-receptor complex, along with synthetic organic chemistry, led us to construct a library of small peptide agonists of BMP signaling that function through the Alk3 receptor. One such peptide agonist, THR-123, suppressed inflammation, apoptosis and the epithelial-to-mesenchymal transition program and reversed established fibrosis in five mouse models of acute and chronic renal injury. THR-123 acts specifically through Alk3 signaling, as mice with a targeted deletion for Alk3 in their tubular epithelium did not respond to therapy with THR-123. Combining THR-123 and the angiotensin-converting enzyme inhibitor captopril had an additive therapeutic benefit in controlling renal fibrosis. Our studies show that BMP signaling agonists constitute a new line of therapeutic agents with potential utility in the clinic to induce regeneration, repair and reverse established fibrosis.",
"title": "Activin–like kinase–3 activity is important for kidney regeneration and reversal of fibrosis"
},
{
"docid": "3831884",
"text": "Cancer cells have metabolic dependencies that distinguish them from their normal counterparts. Among these dependencies is an increased use of the amino acid glutamine to fuel anabolic processes. Indeed, the spectrum of glutamine-dependent tumours and the mechanisms whereby glutamine supports cancer metabolism remain areas of active investigation. Here we report the identification of a non-canonical pathway of glutamine use in human pancreatic ductal adenocarcinoma (PDAC) cells that is required for tumour growth. Whereas most cells use glutamate dehydrogenase (GLUD1) to convert glutamine-derived glutamate into α-ketoglutarate in the mitochondria to fuel the tricarboxylic acid cycle, PDAC relies on a distinct pathway in which glutamine-derived aspartate is transported into the cytoplasm where it can be converted into oxaloacetate by aspartate transaminase (GOT1). Subsequently, this oxaloacetate is converted into malate and then pyruvate, ostensibly increasing the NADPH/NADP(+) ratio which can potentially maintain the cellular redox state. Importantly, PDAC cells are strongly dependent on this series of reactions, as glutamine deprivation or genetic inhibition of any enzyme in this pathway leads to an increase in reactive oxygen species and a reduction in reduced glutathione. Moreover, knockdown of any component enzyme in this series of reactions also results in a pronounced suppression of PDAC growth in vitro and in vivo. Furthermore, we establish that the reprogramming of glutamine metabolism is mediated by oncogenic KRAS, the signature genetic alteration in PDAC, through the transcriptional upregulation and repression of key metabolic enzymes in this pathway. The essentiality of this pathway in PDAC and the fact that it is dispensable in normal cells may provide novel therapeutic approaches to treat these refractory tumours.",
"title": "Glutamine supports pancreatic cancer growth through a Kras-regulated metabolic pathway"
},
{
"docid": "14121786",
"text": "BACKGROUND Epidemiologic analysis of family data on blood pressure (BP) is often compromised by the effects of antihypertensive medications. A review of numerous clinical trials that investigated the effects of BP-lowering medications is summarized here. METHODS Published clinical trials, including 137 clinical trials with monodrug therapies and 28 clinical trials of combination drug therapies with a total of 11,739 participants, were reviewed from PubMed. Six major classes/groups of antihypertensive medications were categorized by ethnicity, including angiotensin-converting enzyme (ACE) inhibitors, alpha1-blockers, cardioselective beta-blockers (beta1-blockers), calcium channel blockers, thiazide and thiazide-like diuretics, and loop diuretics. RESULTS Using sitting or supine BP, for ethnic groups combined, monodrug therapy with ACE inhibitors showed a weighted average effect of lowering the systolic and diastolic BP by 12.5/9.5 mm Hg; alpha1-blockers by 15.5/11.7 mm Hg; beta1-blockers by 14.8/12.2 mm Hg; calcium channel blockers by 15.3/10.5 mm Hg; thiazide diuretics by 15.3/9.8 mm Hg; and loop diuretics by 15.8/8.2 mm Hg. However, ACE inhibitors, alpha1-blockers, and beta1-blockers were less effective in African Americans than in non-African Americans, whereas calcium channel blockers, thiazide diuretics, and loop diuretics were more effective in African Americans than in non-African Americans. For two-drug combination therapy with ethnic groups combined, the BP-lowering effect of the second medication, when compared to its effect as monodrug therapy, was 84% and 65% for systolic and diastolic BP, respectively. CONCLUSIONS The BP-lowering effects reported here may be used to impute the pretreatment BP levels, which can improve the information content and hence the power of epidemiologic analysis in studies where use of antihypertensive medications is a confounding factor in the BP measurements.",
"title": "A summary of the effects of antihypertensive medications on measured blood pressure."
},
{
"docid": "35345807",
"text": "Sirtuins are an evolutionarily conserved family of NAD(+)-dependent protein deacetylases that function in the regulation of gene transcription, cellular metabolism, and aging. Their activity requires the maintenance of an adequate intracellular NAD(+) concentration through the combined action of NAD(+) biosynthesis and salvage pathways. Nicotinamide (NAM) is a key NAD(+) precursor that is also a byproduct and feedback inhibitor of the deacetylation reaction. In Saccharomyces cerevisiae, the nicotinamidase Pnc1 converts NAM to nicotinic acid (NA), which is then used as a substrate by the NAD(+) salvage pathway enzyme NA phosphoribosyltransferase (Npt1). Isonicotinamide (INAM) is an isostere of NAM that stimulates yeast Sir2 deacetylase activity in vitro by alleviating the NAM inhibition. In this study, we determined that INAM stimulates Sir2 through an additional mechanism in vivo, which involves elevation of the intracellular NAD(+) concentration. INAM enhanced normal silencing at the rDNA locus but only partially suppressed the silencing defects of an npt1Δ mutant. Yeast cells grown in media lacking NA had a short replicative life span, which was extended by INAM in a SIR2-dependent manner and correlated with increased NAD(+). The INAM-induced increase in NAD(+) was strongly dependent on Pnc1 and Npt1, suggesting that INAM increases flux through the NAD(+) salvage pathway. Part of this effect was mediated by the NR salvage pathways, which generate NAM as a product and require Pnc1 to produce NAD(+). We also provide evidence suggesting that INAM influences the expression of multiple NAD(+) biosynthesis and salvage pathways to promote homeostasis during stationary phase.",
"title": "Isonicotinamide enhances Sir2 protein-mediated silencing and longevity in yeast by raising intracellular NAD+ concentration."
},
{
"docid": "3669694",
"text": "Generation of induced pluripotent stem cells (iPSCs) by somatic cell reprogramming involves global epigenetic remodelling. Whereas several proteins are known to regulate chromatin marks associated with the distinct epigenetic states of cells before and after reprogramming, the role of specific chromatin-modifying enzymes in reprogramming remains to be determined. To address how chromatin-modifying proteins influence reprogramming, we used short hairpin RNAs (shRNAs) to target genes in DNA and histone methylation pathways, and identified positive and negative modulators of iPSC generation. Whereas inhibition of the core components of the polycomb repressive complex 1 and 2, including the histone 3 lysine 27 methyltransferase EZH2, reduced reprogramming efficiency, suppression of SUV39H1, YY1 and DOT1L enhanced reprogramming. Specifically, inhibition of the H3K79 histone methyltransferase DOT1L by shRNA or a small molecule accelerated reprogramming, significantly increased the yield of iPSC colonies, and substituted for KLF4 and c-Myc (also known as MYC). Inhibition of DOT1L early in the reprogramming process is associated with a marked increase in two alternative factors, NANOG and LIN28, which play essential functional roles in the enhancement of reprogramming. Genome-wide analysis of H3K79me2 distribution revealed that fibroblast-specific genes associated with the epithelial to mesenchymal transition lose H3K79me2 in the initial phases of reprogramming. DOT1L inhibition facilitates the loss of this mark from genes that are fated to be repressed in the pluripotent state. These findings implicate specific chromatin-modifying enzymes as barriers to or facilitators of reprogramming, and demonstrate how modulation of chromatin-modifying enzymes can be exploited to more efficiently generate iPSCs with fewer exogenous transcription factors.",
"title": "Chromatin modifying enzymes as modulators of reprogramming"
},
{
"docid": "45770026",
"text": "Eicosapentaenoic acid (EPA) has beneficial effects in many inflammatory disorders. In this study, dietary EPA was converted to 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) by ω-3 epoxygenation in the mouse peritoneal cavity. Mediator lipidomics revealed a series of novel oxygenated metabolites of 17,18-EpETE, and one of the major metabolites, 12-hydroxy-17,18-epoxyeicosatetraenoic acid (12-OH-17,18-EpETE), displayed a potent anti-inflammatory action by limiting neutrophil infiltration in murine zymosan-induced peritonitis. 12-OH-17,18-EpETE inhibited leukotriene B4-induced neutrophil chemotaxis and polarization in vitro in a low nanomolar range (EC50 0.6 nM). The complete structures of two natural isomers were assigned as 12S-OH-17R,18S-EpETE and 12S-OH-17S,18R-EpETE, using chemically synthesized stereoisomers. These natural isomers displayed potent anti-inflammatory action, whereas the unnatural stereoisomers were essentially devoid of activity. These results demonstrate that 17,18-EpETE derived from dietary EPA is converted to a potent bioactive metabolite 12-OH-17,18-EpETE, which may generate an endogenous anti-inflammatory metabolic pathway.",
"title": "Eicosapentaenoic acid is converted via ω-3 epoxygenation to the anti-inflammatory metabolite 12-hydroxy-17,18-epoxyeicosatetraenoic acid."
},
{
"docid": "2086909",
"text": "The Tet family of enzymes (Tet1/2/3) converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Mouse embryonic stem cells (mESCs) highly express Tet1 and have an elevated level of 5hmC. Tet1 has been implicated in ESC maintenance and lineage specification in vitro but its precise function in development is not well defined. To establish the role of Tet1 in pluripotency and development, we have generated Tet1 mutant mESCs and mice. Tet1(-/-) ESCs have reduced levels of 5hmC and subtle changes in global gene expression, and are pluripotent and support development of live-born mice in tetraploid complementation assay, but display skewed differentiation toward trophectoderm in vitro. Tet1 mutant mice are viable, fertile, and grossly normal, though some mutant mice have a slightly smaller body size at birth. Our data suggest that Tet1 loss leading to a partial reduction in 5hmC levels does not affect pluripotency in ESCs and is compatible with embryonic and postnatal development.",
"title": "Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development."
},
{
"docid": "27428509",
"text": "Type 2 diabetes mellitus is becoming a major health problem associated with excess morbidity and mortality. As the prevalence of type 2 diabetes is rapidly increasing, prevention of the disease should be considered as a key objective in the near future. Besides lifestyle changes, various pharmacological treatments have proven their efficacy in placebo-controlled clinical trials, including antidiabetic drugs such as metformin, acarbose and troglitazone, or antiobesity agents such as orlistat. Arterial hypertension, a clinical entity in which insulin resistance is common, is strongly associated with type 2 diabetes and may precede the disease by several years. While antihypertensive agents such as diuretics or β-adrenoceptor antagonists may worsen insulin resistance and impair glucose tolerance, newer antihypertensive agents exert neutral or even slightly positive metabolic effects. Numerous clinical trials have investigated the effects of ACE inhibitors or angiotensin II receptor antagonists (ARAs) on insulin sensitivity in hypertensive patients, with or without diabetes, with no consistent results. Almost half of the studies with ACE inhibitors in hypertensive nondiabetic individuals demonstrated a slight but significant increase in insulin sensitivity as assessed by insulin-stimulated glucose disposal during a euglycaemic hyperinsulinaemic clamp, while the other half failed to reveal any significant change. The effects of ARAs on insulin sensitivity are neutral in most studies. Mechanisms of improvement of glucose tolerance and insulin sensitivity through the inhibition of the renin-angiotensin system (RAS) are complex. They may include improvement of blood flow and microcirculation in skeletal muscles and, thereby, enhancement of insulin and glucose delivery to the insulin-sensitive tissues, facilitating insulin signalling at the cellular level and improvement of insulin secretion by the β cells. Six recent large-scale clinical studies reported a remarkably consistent reduction in the incidence of type 2 diabetes in hypertensive patients treated with either ACE inhibitors or ARAs for 3–6 years, compared with a thiazide diuretic, β-adrenoceptor antagonist, the calcium channel antagonist amlodipine or even placebo. The relative risk reduction averaged 14% (p = 0.034) in the CAPPP (Captopril Prevention Project) with captopril compared with a thiazide or β1-adrenoceptor antagonist, 34% (p < 0.001) in the HOPE (Heart Outcomes Prevention Evaluation) study with ramipril compared with placebo, 30% (p < 0.001) in the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) with lisinopril compared with chlortalidone, 25% (p < 0.001) in the LIFE (Losartan Intervention For Endpoint reduction in hypertension study) with losartan compared with atenolol, and 25% (p = 0.09) in the SCOPE (Study on Cognition and Prognosis in the Elderly) with candesartan cilexetil compared with placebo, and 23% (p < 0.0001) in the VALUE (Valsartan Antihypertensive Long-term Use Evaluation) trial with valsartan compared with amlodipine. All these studies considered the development of diabetes as a secondary endpoint, except the HOPE trial where it was a post hoc analysis. These encouraging observations led to the initiation of two large, prospective, placebo-controlled randomised clinical trials whose primary outcome is the prevention of type 2 diabetes: the DREAM (Diabetes REduction Approaches with ramipril and rosiglitazone Medications) trial with the ACE inhibitor ramipril and the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) trial with the ARA valsartan. Finally, ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) will also investigate as a secondary endpoint whether it is possible to prevent the development of type 2 diabetes by blocking the RAS with either an ACE inhibitor or an ARA or a combination of both. Thus, the recent consistent observations of a 14–34% reduction of the development of diabetes in hypertensive patients receiving ACE inhibitors or ARAs are exciting. From a theoretical point of view, they emphasise that there are many aspects of the pathogenesis, prevention and treatment of type 2 diabetes that still need to be uncovered. From a practical point of view, they may offer a new strategy to reduce the ongoing epidemic and burden of type 2 diabetes.",
"title": "Prevention of Type 2 Diabetes Mellitus Through Inhibition of the Renin-Angiotensin System"
},
{
"docid": "3866315",
"text": "Aspirin therapy inhibits prostaglandin biosynthesis without directly acting on lipoxygenases, yet via acetylation of cyclooxygenase 2 (COX-2) it leads to bioactive lipoxins (LXs) epimeric at carbon 15 (15-epi-LX, also termed aspirin-triggered LX [ATL]). Here, we report that inflammatory exudates from mice treated with ω-3 polyunsaturated fatty acid and aspirin (ASA) generate a novel array of bioactive lipid signals. Human endothelial cells with upregulated COX-2 treated with ASA converted C20:5 ω-3 to 18R-hydroxyeicosapentaenoic acid (HEPE) and 15R-HEPE. Each was used by polymorphonuclear leukocytes to generate separate classes of novel trihydroxy-containing mediators, including 5-series 15R-LX5 and 5,12,18R-triHEPE. These new compounds proved to be potent inhibitors of human polymorphonuclear leukocyte transendothelial migration and infiltration in vivo (ATL analogue > 5,12,18R-triHEPE > 18R-HEPE). Acetaminophen and indomethacin also permitted 18R-HEPE and 15R-HEPE generation with recombinant COX-2 as well as ω-5 and ω-9 oxygenations of other fatty acids that act on hematologic cells. These findings establish new transcellular routes for producing arrays of bioactive lipid mediators via COX-2–nonsteroidal antiinflammatory drug–dependent oxygenations and cell–cell interactions that impact microinflammation. The generation of these and related compounds provides a novel mechanism(s) for the therapeutic benefits of ω-3 dietary supplementation, which may be important in inflammation, neoplasia, and vascular diseases.",
"title": "Novel Functional Sets of Lipid-Derived Mediators with Antiinflammatory Actions Generated from Omega-3 Fatty Acids via Cyclooxygenase 2–Nonsteroidal Antiinflammatory Drugs and Transcellular Processing"
},
{
"docid": "4447055",
"text": "Contusive spinal cord injury leads to a variety of disabilities owing to limited neuronal regeneration and functional plasticity. It is well established that an upregulation of glial-derived chondroitin sulphate proteoglycans (CSPGs) within the glial scar and perineuronal net creates a barrier to axonal regrowth and sprouting. Protein tyrosine phosphatase σ (PTPσ), along with its sister phosphatase leukocyte common antigen-related (LAR) and the nogo receptors 1 and 3 (NgR), have recently been identified as receptors for the inhibitory glycosylated side chains of CSPGs. Here we find in rats that PTPσ has a critical role in converting growth cones into a dystrophic state by tightly stabilizing them within CSPG-rich substrates. We generated a membrane-permeable peptide mimetic of the PTPσ wedge domain that binds to PTPσ and relieves CSPG-mediated inhibition. Systemic delivery of this peptide over weeks restored substantial serotonergic innervation to the spinal cord below the level of injury and facilitated functional recovery of both locomotor and urinary systems. Our results add a new layer of understanding to the critical role of PTPσ in mediating the growth-inhibited state of neurons due to CSPGs within the injured adult spinal cord.",
"title": "Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury"
},
{
"docid": "4405194",
"text": "Somatic cell nuclear transfer, cell fusion, or expression of lineage-specific factors have been shown to induce cell-fate changes in diverse somatic cell types. We recently observed that forced expression of a combination of three transcription factors, Brn2 (also known as Pou3f2), Ascl1 and Myt1l, can efficiently convert mouse fibroblasts into functional induced neuronal (iN) cells. Here we show that the same three factors can generate functional neurons from human pluripotent stem cells as early as 6 days after transgene activation. When combined with the basic helix-loop-helix transcription factor NeuroD1, these factors could also convert fetal and postnatal human fibroblasts into iN cells showing typical neuronal morphologies and expressing multiple neuronal markers, even after downregulation of the exogenous transcription factors. Importantly, the vast majority of human iN cells were able to generate action potentials and many matured to receive synaptic contacts when co-cultured with primary mouse cortical neurons. Our data demonstrate that non-neural human somatic cells, as well as pluripotent stem cells, can be converted directly into neurons by lineage-determining transcription factors. These methods may facilitate robust generation of patient-specific human neurons for in vitro disease modelling or future applications in regenerative medicine.",
"title": "Induction of human neuronal cells by defined transcription factors"
},
{
"docid": "18348376",
"text": "BACKGROUND Multiple mechanisms have been advanced to account for CD4+FOXP3+ regulatory T cell (Treg)-mediated suppression of CD4+ effector T cells (Teffs) but none appear to completely explain suppression. Previous data indicates that Tregs may affect the microenvironment redox state. Given the inherent redox sensitivity of T cells, we tested the hypothesis that oxidants may mediate the direct suppression of Teffs by Tregs. METHODOLOGY/PRINCIPAL FINDINGS Tregs and Teffs were isolated from the spleens of wild type (WT) C57BL/6 mice or Ncf1(p47phox)-deficient C57BL/6 mice which lack NADPH oxidase function. Teffs were labeled with CFSE and co-cultured with unlabeled Tregs at varying Treg:Teff ratios in the presence of anti-CD3/CD28 coated beads for 3 days in suppression assays. Treg-mediated suppression was quantified by flow cytometric analysis of CFSE dilution in Teffs. The presence of the antioxidants n-acetylcysteine (NAC) or 2-mercaptoethanol or inhibitors of NADPH oxidase (diphenyleneiodonium and VAS-2870) resulted in reduced WT Treg-mediated suppression. The observed suppression was in part dependent upon TGFβ as it was partially blocked with neutralizing antibodies. The suppression of Teff proliferation induced by exogenous TGFβ treatment could be overcome with NAC. Ncf1-deficient Teff were slightly but significantly less sensitive than WT Teff to suppression by exogenous TGFβ. Ncf1-deficient Tregs suppressed Ncf1-deficient Teff very poorly compared to wild type controls. There was partial but incomplete reconstitution of suppression in assays with WT Tregs and Ncf1-deficient Teff. CONCLUSIONS/SIGNIFICANCE We present evidence that NADPH oxidase derived ROS plays a role in the direct Treg mediated suppression of CD4+ effector T cells in a process that is blocked by thiol-containing antioxidants, NADPH oxidase inhibitors or a lack of Ncf1 expression in Tregs and Teffs. Oxidants may represent a potential new target for therapeutic modulation of Treg function.",
"title": "Ncf1 (p47phox) Is Essential for Direct Regulatory T Cell Mediated Suppression of CD4+ Effector T Cells"
},
{
"docid": "44030361",
"text": "Accumulated evidence suggests that an altered ambulatory blood pressure (BP) profile, particularly elevated nighttime BP, reflects target organ injury and is a better predictor of further cardiorenal risk than the clinic BP or daytime BP in hypertensive patients complicated by chronic kidney disease (CKD). In this study, we examined the beneficial effects of olmesartan, an angiotensin II type 1 receptor blocker (ARB), on ambulatory BP profiles and renal function in hypertensive CKD patients. Forty-six patients were randomly assigned to the olmesartan add-on group (n=23) or the non-ARB group (n=23). At baseline and after the 16-week treatment period, ambulatory BP monitoring was performed and renal function parameter measurements were collected. Although the baseline clinic BP levels and the after-treatment/baseline (A/B) ratios of clinic BP levels were similar in the olmesartan add-on and non-ARB groups, the A/B ratios of ambulatory 24-h and nighttime BP levels in the olmesartan add-on group were significantly lower. Furthermore, the A/B ratios of urinary protein, albumin and type IV collagen excretion in the olmesartan add-on group were significantly lower than those in the non-ARB group (urinary protein excretion, 0.72±0.41 vs. 1.45±1.48, P=0.030; urinary albumin excretion, 0.73±0.37 vs. 1.50±1.37, P=0.005; urinary type IV collagen excretion, 0.87±0.42 vs. 1.48±0.87, P=0.014) despite comparable A/B ratios for the estimated glomerular filtration rate in the two groups. These results indicate that in hypertensive patients with CKD, olmesartan add-on therapy improves the ambulatory BP profile via a preferential reduction in nighttime BP with concomitant renal injury inhibition.",
"title": "The angiotensin II type 1 receptor blocker olmesartan preferentially improves nocturnal hypertension and proteinuria in chronic kidney disease"
},
{
"docid": "5849439",
"text": "Microsporogenesis has been examined in wild-type Arabidopsis thaliana and the nuclear male-sterile mutant BM3 by cytochemical staining. The mutant lacks adenine phosphoribosyltransferase, an enzyme of the purine salvage pathway that converts adenine to AMP. Pollen development in the mutant began to diverge from wild type just after meiosis, as the tetrads of microspores were released from their callose walls. The first indication of abnormal pollen development in the mutant was a darker staining of the microspore wall due to an incomplete synthesis of the intine. Vacuole formation was delayed and irregular in the mutant, and the majority of the mutant microspores failed to undergo mitotic divisions. Enzyme activities of alcohol dehydrogenase and esterases decreased in the mutant soon after meiosis and were undetectable in mature pollen grains of the mutant. RNA accumulation was also diminished. These results are discussed in relation to the possible role(s) of adenine salvage in pollen development.",
"title": "Cytochemical Analysis of Pollen Development in Wild-Type Arabidopsis and a Male-Sterile Mutant."
},
{
"docid": "10284593",
"text": "Observational clinical and ex vivo studies have established a strong association between atrial fibrillation and inflammation. However, whether inflammation is the cause or the consequence of atrial fibrillation and which specific inflammatory mediators may increase the atria's susceptibility to fibrillation remain elusive. Here we provide experimental and clinical evidence for the mechanistic involvement of myeloperoxidase (MPO), a heme enzyme abundantly expressed by neutrophils, in the pathophysiology of atrial fibrillation. MPO-deficient mice pretreated with angiotensin II (AngII) to provoke leukocyte activation showed lower atrial tissue abundance of the MPO product 3-chlorotyrosine, reduced activity of matrix metalloproteinases and blunted atrial fibrosis as compared to wild-type mice. Upon right atrial electrophysiological stimulation, MPO-deficient mice were protected from atrial fibrillation, which was reversed when MPO was restored. Humans with atrial fibrillation had higher plasma concentrations of MPO and a larger MPO burden in right atrial tissue as compared to individuals devoid of atrial fibrillation. In the atria, MPO colocalized with markedly increased formation of 3-chlorotyrosine. Our data demonstrate that MPO is a crucial prerequisite for structural remodeling of the myocardium, leading to an increased vulnerability to atrial fibrillation.",
"title": "Myeloperoxidase acts as a profibrotic mediator of atrial fibrillation"
},
{
"docid": "13777138",
"text": "TET family enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. Here, we show that Tet1 and Tet2 are Oct4-regulated enzymes that together sustain 5hmC in mouse embryonic stem cells (ESCs) and are induced concomitantly with 5hmC during reprogramming of fibroblasts to induced pluripotent stem cells. ESCs depleted of Tet1 by RNAi show diminished expression of the Nodal antagonist Lefty1 and display hyperactive Nodal signaling and skewed differentiation into the endoderm-mesoderm lineage in embryoid bodies in vitro. In Fgf4- and heparin-supplemented culture conditions, Tet1-depleted ESCs activate the trophoblast stem cell lineage determinant Elf5 and can colonize the placenta in midgestation embryo chimeras. Consistent with these findings, Tet1-depleted ESCs form aggressive hemorrhagic teratomas with increased endoderm, reduced neuroectoderm, and ectopic appearance of trophoblastic giant cells. Thus, 5hmC is an epigenetic modification associated with the pluripotent state, and Tet1 functions to regulate the lineage differentiation potential of ESCs.",
"title": "Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells."
},
{
"docid": "17546486",
"text": "Skeletal muscle overload induces the expression of angiogenic factors such as vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-2, leading to new capillary growth. We found that the overload-induced increase in angiogenesis, as well as increases in VEGF, MMP-2 and MT1-MMP transcripts were abrogated in muscle VEGF KO mice, highlighting the critical role of myocyte-derived VEGF in controlling this process. The upstream mediators that contribute to overload-induced expression of VEGF have yet to be ascertained. We found that muscle overload increased angiotensinogen expression, a precursor of angiotensin (Ang) II, and that Ang II signaling played an important role in basal VEGF production in C2C12 cells. Furthermore, matrix-bound VEGF released from myoblasts induced the activation of endothelial cells, as evidenced by elevated endothelial cell phospho-p38 levels. We also found that exogenous Ang II elevates VEGF expression, as well as MMP-2 transcript levels in C2C12 myotubes. Interestingly, these responses also were observed in skeletal muscle endothelial cells in response to Ang II treatment, indicating that these cells also can respond directly to the stimulus. The involvement of Ang II in muscle overload-induced angiogenesis was assessed. We found that blockade of AT1R-dependent Ang II signaling using losartan did not attenuate capillary growth. Surprisingly, increased levels of VEGF protein were detected in overloaded muscle from losartan-treated rats. Similarly, we observed elevated VEGF production in cultured endothelial cells treated with losartan alone or in combination with Ang II. These studies conclusively establish the requirement for muscle derived VEGF in overload-induced angiogenesis and highlight a role for Ang II in basal VEGF production in skeletal muscle. However, while Ang II signaling is activated following overload and plays a role in muscle VEGF production, inhibition of this pathway is not sufficient to halt overload-induced angiogenesis, indicating that AT1-independent signals maintain VEGF production in losartan-treated muscle.",
"title": "Angiotensin II Evokes Angiogenic Signals within Skeletal Muscle through Co-ordinated Effects on Skeletal Myocytes and Endothelial Cells"
}
] |
647
|
Integrated care is ineffective at tackling multiple comorbidities.
|
[
{
"docid": "15041758",
"text": "OBJECTIVE To evaluate the effectiveness of integrated care for chronic physical diseases and depression in reducing disability and improving quality of life. DESIGN A randomised controlled trial of multi-condition collaborative care for depression and poorly controlled diabetes and/or risk factors for coronary heart disease compared with usual care among middle aged and elderly people SETTING Fourteen primary care clinics in Seattle, Washington. PARTICIPANTS Patients with diabetes or coronary heart disease, or both, and blood pressure above 140/90 mm Hg, low density lipoprotein concentration >3.37 mmol/L, or glycated haemoglobin 8.5% or higher, and PHQ-9 depression scores of ≥ 10. INTERVENTION A 12 month intervention to improve depression, glycaemic control, blood pressure, and lipid control by integrating a \"treat to target\" programme for diabetes and risk factors for coronary heart disease with collaborative care for depression. The intervention combined self management support, monitoring of disease control, and pharmacotherapy to control depression, hyperglycaemia, hypertension, and hyperlipidaemia. MAIN OUTCOME MEASURES Social role disability (Sheehan disability scale), global quality of life rating, and World Health Organization disability assessment schedule (WHODAS-2) scales to measure disabilities in activities of daily living (mobility, self care, household maintenance). RESULTS Of 214 patients enrolled (106 intervention and 108 usual care), disability and quality of life measures were obtained for 97 intervention patients at six months (92%) and 92 at 12 months (87%), and for 96 usual care patients at six months (89%) and 92 at 12 months (85%). Improvements from baseline on the Sheehan disability scale (-0.9, 95% confidence interval -1.5 to -0.2; P = 0.006) and global quality of life rating (0.7, 0.2 to 1.2; P = 0.005) were significantly greater at six and 12 months in patients in the intervention group. There was a trend toward greater improvement in disabilities in activities of daily living (-1.5, -3.3 to 0.4; P = 0.10). CONCLUSIONS Integrated care that covers chronic physical disease and comorbid depression can reduce social role disability and enhance global quality of life. Trial registration Clinical Trials NCT00468676.",
"title": "Functional outcomes of multi-condition collaborative care and successful ageing: results of randomised trial"
}
] |
[
{
"docid": "19945096",
"text": "OBJECTIVES To describe and explain the primary care experiences of people with multiple long-term conditions in England. DESIGN AND METHODS Using questionnaire data from 906,578 responders to the English 2012 General Practice Patient Survey, we describe the primary care experiences of patients with long-term conditions, including 583,143 patients who reported one or more long-term conditions. We employed mixed effect logistic regressions to analyse data on six items covering three care domains (access, continuity and communication) and a single item on overall primary care experience. We controlled for sociodemographic characteristics, and for general practice using a random effect, and further, controlled for, and explored the importance of, health-related quality of life measured using the EuroQoL (EQ-5D) scale. RESULTS Most patients with long-term conditions report a positive experience of care at their general practice (after adjusting for sociodemographic characteristics and general practice, range 74.0-93.1% reporting positive experience of care across seven questions) with only modest variation by type of condition. For all three domains of patient experience, an increasing number of comorbid conditions is associated with a reducing percentage of patients reporting a positive experience of care. For example, compared with respondents with no long-term condition, the OR for reporting a positive experience is 0.83 (95% CI 0.80 to 0.87) for respondents with four or more long-term conditions. However, this relationship is no longer observed after adjusting for health-related quality of life (OR (95% CI) single condition=1.23 (1.21 to 1.26); four or more conditions=1.31 (1.25 to 1.37)), with pain making the greatest difference among five quality of life variables included in the analysis. CONCLUSIONS Patients with multiple long-term conditions more frequently report worse experiences in primary care. However, patient-centred measures of health-related quality of life, especially pain, are more important than the number of conditions in explaining why patients with multiple long-term conditions report worse experiences of care.",
"title": "Why do patients with multimorbidity in England report worse experiences in primary care? Evidence from the General Practice Patient Survey"
},
{
"docid": "6767133",
"text": "STUDY DESIGN Prospective observational cohort. OBJECTIVE To describe the baseline characteristics of patients with a diagnosis of intervertebral disc herniation who had different treatment preferences and the relationship of specific expectations with those preferences. SUMMARY OF BACKGROUND DATA Data were gathered from the observational cohort of the Spine Patient Outcomes Research Trial (SPORT). Patients in the observational cohort met eligibility requirements identical to those of the randomized cohort, but declined randomization, receiving instead the treatment of their choice. METHODS Baseline preference and expectation data were acquired at the time of enrollment of the patient, before exposure to the informed consent process. Univariate analyses were performed using a t test for continuous variables and chi for categorical variables. Multivariate analyses were also performed with ANCOVA for continuous variables and logistic regression for categorical variables. Multiple logistic regression models were developed in a forward stepwise fashion using blocks of variables. RESULTS More patients preferred operative care: 67% preferred surgery, 28% preferred nonoperative treatment, and 6% were unsure; 53% of those preferring surgery stated a definite preference, whereas only 18% of those preferring nonoperative care had a definite preference. Patients preferring surgery were younger, had lower levels of education, and higher levels of unemployment/disability. This group also reported higher pain, worse physical and mental functioning, more back pain related disability, a longer duration of symptoms, and more opiate use. Gender, race, comorbidities, and use of other therapies did not differ significantly across preference groups. Patients' expectations regarding improvement with nonoperative care was the strongest predictor of preference. CONCLUSION Patient expectations, particularly regarding the benefit of nonoperative treatment, are the primary determinant of surgery preference among patients with lumbar intervertebral disc herniation. Demographic, functional status, and prior treatment experience had significant associations with patients' expectations and preferences.",
"title": "Patient preferences and expectations for care: determinants in patients with lumbar intervertebral disc herniation."
},
{
"docid": "44409062",
"text": "In recent years, a new paradigm for genome annotation has emerged, termed \"proteogenomics,\" that leverages peptide MS to annotate a genome. This is achieved by mapping peptides to a six-frame translation of a genome, including available splice databases, which may suggest refinements to gene models. Using this approach, it is possible to refine gene regions such as exon boundaries, novel genes, gene boundaries, frame shifts, reverse strands, translated UTRs, and novel splice junctions. One of the challenges of proteogenomics is how best to (1) tackle assigning confidence to any resulting annotation and (2) apply these gene model refinements, either through manual annotation or through an automated process via training gene prediction tools. This is not a straightforward process, as many gene prediction tools have their defined suitability for niche genomes (either eukaryotic or prokaryotic) trained on and refined with model organisms such as Arabidopsis thaliana and Escherichia coli, and varying degrees of features that can leverage the use of external evidence. In this study, we outline a suitable approach toward preprocessing mass spectra and optimizing the MS/MS search for a given dataset. We also discuss future challenges, which continue to pose a problem in the field of proteogenomics, and better strategies to successfully tackle them with, using existing tools. We use Bradyrhizobium diazoefficiens (Nitrogen-fixing bacteria), with a 9.1 Mb genome as a case study, utilizing the latest in second-generation proteogenomics tools with multiple gene models for cross-validation of proteogenomics annotations.",
"title": "High-throughput parallel proteogenomics: a bacterial case study."
},
{
"docid": "6334188",
"text": "BACKGROUND Chemotherapy-induced febrile neutropenia (FN) is a clinically important complication that affects patient outcome by delaying chemotherapy doses or reducing dose intensity. Risk of FN depends on chemotherapy- and patient-level factors. We sought to determine the effects of chronic comorbidities on risk of FN. DESIGN We conducted a cohort study to examine the association between a variety of chronic comorbidities and risk of FN in patients diagnosed with six types of cancer (non-Hodgkin lymphoma and breast, colorectal, lung, ovary, and gastric cancer) from 2000 to 2009 who were treated with chemotherapy at Kaiser Permanente Southern California, a large managed care organization. We excluded those patients who received primary prophylactic granulocyte colony-stimulating factor. History of comorbidities and FN events were identified using electronic medical records. Cox models adjusting for propensity score, stratified by cancer type, were used to determine the association between comorbid conditions and FN. Models that additionally adjusted for cancer stage, baseline neutrophil count, chemotherapy regimen, and dose reduction were also evaluated. RESULTS A total of 19 160 patients with mean age of 60 years were included; 963 (5.0%) developed FN in the first chemotherapy cycle. Chronic obstructive pulmonary disease [hazard ratio (HR) = 1.30 (1.07-1.57)], congestive heart failure [HR = 1.43 (1.00-1.98)], HIV infection [HR = 3.40 (1.90-5.63)], autoimmune disease [HR = 2.01 (1.10-3.33)], peptic ulcer disease [HR = 1.57 (1.05-2.26)], renal disease [HR = 1.60 (1.21-2.09)], and thyroid disorder [HR = 1.32 (1.06-1.64)] were all associated with a significantly increased FN risk. CONCLUSIONS These results provide evidence that history of several chronic comorbidities increases risk of FN, which should be considered when managing patients during chemotherapy.",
"title": "History of chronic comorbidity and risk of chemotherapy-induced febrile neutropenia in cancer patients not receiving G-CSF prophylaxis."
},
{
"docid": "7595742",
"text": "Frailty has long been considered synonymous with disability and comorbidity, to be highly prevalent in old age and to confer a high risk for falls, hospitalization and mortality. However, it is becoming recognized that frailty may be a distinct clinical syndrome with a biological basis. The frailty process appears to be a transitional state in the dynamic progression from robustness to functional decline. During this process, total physiological reserves decrease and become less likely to be sufficient for the maintenance and repair of the ageing body. Central to the clinical concept of frailty is that no single altered system alone defines it, but that multiple systems are involved. Clinical consensus regarding the phenotype which constitutes frailty, drawing upon the opinions of numerous authors, shows the characteristics to include wasting (loss of both muscle mass and strength and weight loss), loss of endurance, decreased balance and mobility, slowed performance, relative inactivity and, potentially, decreased cognitive function. Frailty is a distinct entity easily recognized by clinicians, with multiple manifestations and with no single symptom being sufficient or essential in its presentation. Manifestations include appearance (consistent or not with age), nutritional status (thin, weight loss), subjective health rating (health perception), performance (cognition, fatigue), sensory/physical impairments (vision, hearing, strength) and current care (medication, hospital). Although the early stages of the frailty process may be clinically silent, when depleted reserves reach an aggregate threshold leading to serious vulnerability, the syndrome may become detectable by looking at clinical, functional, behavioral and biological markers. Thus, a better understanding of these clinical changes and their underlying mechanisms, beginning in the pre-frail state, may confirm the impression held by many geriatricians that increasing frailty is distinguishable from ageing and in consequence is potentially reversible. We therefore provide an update of the physiopathology and clinical and biological characteristics of the frailty process and speculate on possible preventative approaches.",
"title": "Frailty Syndrome: A Transitional State in a Dynamic Process"
},
{
"docid": "5836",
"text": "Myelodysplastic syndromes (MDS) are age-dependent stem cell malignancies that share biological features of activated adaptive immune response and ineffective hematopoiesis. Here we report that myeloid-derived suppressor cells (MDSC), which are classically linked to immunosuppression, inflammation, and cancer, were markedly expanded in the bone marrow of MDS patients and played a pathogenetic role in the development of ineffective hematopoiesis. These clonally distinct MDSC overproduce hematopoietic suppressive cytokines and function as potent apoptotic effectors targeting autologous hematopoietic progenitors. Using multiple transfected cell models, we found that MDSC expansion is driven by the interaction of the proinflammatory molecule S100A9 with CD33. These 2 proteins formed a functional ligand/receptor pair that recruited components to CD33’s immunoreceptor tyrosine-based inhibition motif (ITIM), inducing secretion of the suppressive cytokines IL-10 and TGF-β by immature myeloid cells. S100A9 transgenic mice displayed bone marrow accumulation of MDSC accompanied by development of progressive multilineage cytopenias and cytological dysplasia. Importantly, early forced maturation of MDSC by either all-trans-retinoic acid treatment or active immunoreceptor tyrosine-based activation motif–bearing (ITAM-bearing) adapter protein (DAP12) interruption of CD33 signaling rescued the hematologic phenotype. These findings indicate that primary bone marrow expansion of MDSC driven by the S100A9/CD33 pathway perturbs hematopoiesis and contributes to the development of MDS.",
"title": "Induction of myelodysplasia by myeloid-derived suppressor cells."
},
{
"docid": "9274291",
"text": "PURPOSE To compare expectations for cancer survivorship care between patients and their physicians and between primary care providers (PCPs) and oncologists. METHODS Survivors and their physicians were surveyed to evaluate for expectations regarding physician participation in primary cancer follow-up, screening for other cancers, general preventive health, and management of comorbidities. RESULTS Of 992 eligible survivors and 607 physicians surveyed, 535 (54%) and 378 (62%) were assessable, respectively. Among physician respondents, 255 (67%) were PCPs and 123 (33%) were oncologists. Comparing patients with their oncologists, expectations were highly discrepant for screening for cancers other than the index one (agreement rate, 29%), with patients anticipating significantly more oncologist involvement. Between patients and their PCPs, expectations were most incongruent for primary cancer follow-up (agreement rate, 35%), with PCPs indicating they should contribute a much greater part to this aspect of care. Expectations between patients and their PCPs were generally more concordant than between patients and their oncologists. PCPs and oncologists showed high discordances in perceptions of their own roles for primary cancer follow-up, cancer screening, and general preventive health (agreement rates of 3%, 44%, and 51%, respectively). In the case of primary cancer follow-up, both PCPs and oncologists indicated they should carry substantial responsibility for this task. CONCLUSION Patients and physicians have discordant expectations with respect to the roles of PCPs and oncologists in cancer survivorship care. Uncertainties around physician roles and responsibilities can lead to deficiencies in care, supporting the need to make survivorship care planning a standard component in cancer management.",
"title": "Comparisons of patient and physician expectations for cancer survivorship care."
},
{
"docid": "46353045",
"text": "Late presentation remains a major concern despite the dramatically improved prognosis realized by ART. We define a first presentation for HIV care during the course of HIV infection as 'late' if an AIDS-defining opportunistic disease is apparent, or if CD4+ T-cells are <200/microl. In the Western world, approximately 10 and 30% of HIV-infected individuals still present with CD4+ T-cells <50 and <200/microl, respectively; estimates are substantially higher for developing countries. Diagnosis and treatment of opportunistic diseases and intense supportive in-hospital care take precedence over ART. Benefits of starting ART without delay, that is, when opportunistic diseases are still active, include faster resolution of opportunistic diseases and a decreased risk of recurrence. The downside of starting ART without delay could include toxicity, drug interactions and immune reconstitution inflammatory syndrome (IRIS). Among asymptomatic or oligosymptomatic individuals presenting late, where ART and primary prophylaxis are initiated, approximately 10-20% will become symptomatic from drug toxicity or undiagnosed opportunistic complications, including IRIS, which require appropriate therapies. In this review we describe late presentation to HIV care, the scale of the problem, the evaluation of a late-presenting patient and challenges associated with initiation of potent antiretroviral therapy (ART) in the setting of acute opportunistic infections and other comorbidities.",
"title": "Late presentation of HIV-infected individuals."
},
{
"docid": "24276304",
"text": "CONTEXT Uncertainties exist about prevalence and correlates of major depressive disorder (MDD). OBJECTIVE To present nationally representative data on prevalence and correlates of MDD by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and on study patterns and correlates of treatment and treatment adequacy from the recently completed National Comorbidity Survey Replication (NCS-R). DESIGN Face-to-face household survey conducted from February 2001 to December 2002. SETTING The 48 contiguous United States. PARTICIPANTS Household residents ages 18 years or older (N = 9090) who responded to the NCS-R survey. MAIN OUTCOME MEASURES Prevalence and correlates of MDD using the World Health Organization's (WHO) Composite International Diagnostic Interview (CIDI), 12-month severity with the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR), the Sheehan Disability Scale (SDS), and the WHO disability assessment scale (WHO-DAS). Clinical reinterviews used the Structured Clinical Interview for DSM-IV. RESULTS The prevalence of CIDI MDD for lifetime was 16.2% (95% confidence interval [CI], 15.1-17.3) (32.6-35.1 million US adults) and for 12-month was 6.6% (95% CI, 5.9-7.3) (13.1-14.2 million US adults). Virtually all CIDI 12-month cases were independently classified as clinically significant using the QIDS-SR, with 10.4% mild, 38.6% moderate, 38.0% severe, and 12.9% very severe. Mean episode duration was 16 weeks (95% CI, 15.1-17.3). Role impairment as measured by SDS was substantial as indicated by 59.3% of 12-month cases with severe or very severe role impairment. Most lifetime (72.1%) and 12-month (78.5%) cases had comorbid CIDI/DSM-IV disorders, with MDD only rarely primary. Although 51.6% (95% CI, 46.1-57.2) of 12-month cases received health care treatment for MDD, treatment was adequate in only 41.9% (95% CI, 35.9-47.9) of these cases, resulting in 21.7% (95% CI, 18.1-25.2) of 12-month MDD being adequately treated. Sociodemographic correlates of treatment were far less numerous than those of prevalence. CONCLUSIONS Major depressive disorder is a common disorder, widely distributed in the population, and usually associated with substantial symptom severity and role impairment. While the recent increase in treatment is encouraging, inadequate treatment is a serious concern. Emphasis on screening and expansion of treatment needs to be accompanied by a parallel emphasis on treatment quality improvement.",
"title": "The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R)."
},
{
"docid": "22688699",
"text": "OBJECT Awake craniotomy was performed as the standard surgical approach to supratentorial intraaxial tumors, regardless of the involvement of eloquent cortex, in a prospective trial of 200 patients surgically treated by the same surgeon at a single institution. METHODS Patient presentations, comorbid conditions, tumor locations, and the histological characteristics of lesions were recorded. Brain mapping was possible in 195 (97.5%) of 200 patients. The total number of patients sustaining complications was 33 for an overall complication rate of 16.5%. There were two deaths in this series, for a mortality rate of 1%. New postoperative neurological deficits were seen in 13% of the patients, but these were permanent in only 4.5% of them. Complication rates were higher in patients who had gliomas or preoperative neurological deficits and in those who had undergone prior radiation therapy or surgery. No patient who entered the operating room neurologically intact sustained a permanent neurological deficit postoperatively. Of the most recent 50 patients treated, three (6%) required a stay in the intensive care unit, and the median total hospital stay was 1 day. CONCLUSIONS Use of awake craniotomy can result in a considerable reduction in resource utilization without compromising patient care by minimizing intensive care time and total hospital stay. Awake craniotomy is a practical and effective standard surgical approach to supratentorial tumors with a low complication rate, and provides an excellent alternative to craniotomy performed with the patient in the state of general anesthesia because it allows the opportunity for brain mapping and avoids general anesthesia.",
"title": "Awake craniotomy with brain mapping as the routine surgical approach to treating patients with supratentorial intraaxial tumors: a prospective trial of 200 cases."
},
{
"docid": "24318630",
"text": "Since 2008 the World Health Organization (WHO), through its mental health Gap Action Programme, has attempted to revitalize efforts to integrate mental health into non-specialized (e.g. primary) healthcare. While this has led to renewed interest in this potential method of mental health service delivery, it has also prompted criticism. Some concerns raised are that it would contribute to the medicalization of social and psychological problems, and narrowly focus on primary care without sufficient attention given to strengthening other levels of the healthcare system, notably community-based care and care on district levels. This paper discusses seven elements that may be critical to preventing inadvertently contributing to increasing a narrow biomedical approach to mental healthcare when integrating mental health into non-specialized healthcare: (1) using task shifting approaches within a system of stepped care, (2) ensuring primary mental healthcare also includes brief psychotherapeutic interventions, (3) promote community-based recovery-oriented interventions for people with disabling chronic mental disorders, (4) conceptualizing training as a continuous process of strengthening clinical competencies through supervision, (5) engaging communities as partners in psychosocial interventions, (6) embedding shifts to primary mental healthcare within wider health policy reforms, and (7) promoting inter-sectoral approaches to address social determinants of mental health.",
"title": "Integration of mental health into primary healthcare in low-income countries: avoiding medicalization."
},
{
"docid": "17693849",
"text": "BACKGROUND Appropriate understanding of health information by patients with cardiovascular disease (CVD) is fundamental for better management of risk factors and improved morbidity, which can also benefit their quality of life. OBJECTIVES To assess the relationship between health literacy and health-related quality of life (HRQoL) in patients with ischaemic heart disease (IHD), and to investigate the role of sociodemographic and clinical variables as possible confounders. METHODS Cross-sectional study of patients with IHD recruited from a stratified sample of general practices in two Australian states (Queensland and South Australia) between 2007 and 2009. Health literacy was measured using a validated questionnaire and classified as inadequate, marginal, or adequate. Physical and mental components of HRQoL were assessed using the Medical Outcomes Study Short Form (SF12) questionnaire. Analyses were adjusted for confounders (sociodemographic variables, clinical history of IHD, number of CVD comorbidities, and CVD risk factors) using multiple linear regression. RESULTS A total sample of 587 patients with IHD (mean age 72.0±8.4 years) was evaluated: 76.8% males, 84.2% retired or pensioner, and 51.4% with up to secondary educational level. Health literacy showed a mean of 39.6±6.7 points, with 14.3% (95%CI 11.8-17.3) classified as inadequate. Scores of the physical component of HRQoL were 39.6 (95%CI 37.1-42.1), 42.1 (95%CI 40.8-43.3) and 44.8 (95%CI 43.3-46.2) for inadequate, marginal, and adequate health literacy, respectively (p-value for trend = 0.001). This association persisted after adjustment for confounders. Health literacy was not associated with the mental component of HRQoL (p-value = 0.482). Advanced age, lower educational level, disadvantaged socioeconomic position, and a larger number of CVD comorbidities adversely affected both, health literacy and HRQoL. CONCLUSION Inadequate health literacy is a contributing factor to poor physical functioning in patients with IHD. Increasing health literacy may improve HRQoL and reduce the impact of IHD among patients with this chronic CVD.",
"title": "Effect of Health Literacy on Quality of Life amongst Patients with Ischaemic Heart Disease in Australian General Practice"
},
{
"docid": "20187433",
"text": "Family members are an integral part of a patient's cancer care from the moment the diagnosis is delivered to the conclusion of treatment. Family members bring with them a range of emotional reactions, interpersonal dynamics and expectations for the care the patient receives. This study is part of a multi-institutional project to continue to improve the process of cancer care. In this study, 19 focus groups (11 patient and 8 provider) were conducted concerning issues related to doctor-patient communication in eight cancer centers in the United States. The content of the conversations was analyzed and thematic categories emerged that highlight the various strengths and difficulties associated with family involvement. The focus groups' comments support the need for explicit conversations between professional caregivers, patients and their loved ones, in order to negotiate the expectations and needs of each team member. Implications for clinical practice and strategies for working with family members are offered.",
"title": "Involving family members in cancer care: focus group considerations of patients and oncological providers."
},
{
"docid": "6517267",
"text": "BACKGROUND The Dutch multidisciplinary sciatica guideline recommends that the team of professionals involved in sciatica care and the patient together decide on surgical or prolonged conservative treatment (shared decision making [SDM]). Despite this recommendation, SDM is not yet integrated in sciatica care. Existing literature concerning barriers and facilitators to SDM implementation mainly focuses on one discipline only, whereas multidisciplinary care may involve other barriers and facilitators, or make these more complex for both professionals and patients. Therefore, this qualitative study aims to identify barriers and facilitators perceived by patients and professionals for SDM implementation in multidisciplinary sciatica care. METHODS We conducted 40 semi-structured interviews with professionals involved in sciatica care (general practitioners, physical therapists, neurologists, neurosurgeons, and orthopedic surgeons) and three focus groups among patients (six to eight per group). The interviews and focus groups were audiotaped and transcribed in full. Reported barriers and facilitators were classified according to the framework of Grol and Wensing. The software package Atlas.ti 7.0 was used for analysis. RESULTS Professionals reported 53 barriers and 5 facilitators, and patients 35 barriers and 18 facilitators for SDM in sciatica care. Professionals perceived most barriers at the level of the organizational context, and facilitators at the level of the individual professional. Patients reported most barriers and facilitators at the level of the individual professional. Several barriers and facilitators correspond with barriers and facilitators found in the literature (e.g., lack of time, motivation) but also new barriers and facilitators were identified. Many of these new barriers mentioned by both professionals and patients were related to the multidisciplinary setting, such as lack of visibility, lack of trust in expertise of other disciplines, and lack of communication between disciplines. CONCLUSIONS This study identified barriers and facilitators for SDM in the multidisciplinary sciatica setting, by both professionals and patients. It is clear that more barriers than facilitators are perceived for implementation of SDM in sciatica care. Newly identified barriers and facilitators are related to the multidisciplinary care setting. Therefore, an effective implementation strategy of SDM in a multidisciplinary setting such as in sciatica care should focus on these barriers and facilitators.",
"title": "Barriers and facilitators to implement shared decision making in multidisciplinary sciatica care: a qualitative study"
},
{
"docid": "44830890",
"text": "OBJECTIVE To investigate the frequency of depressive and anxiety disorders in patients with chronic daily headache. BACKGROUND There is a lack of data in the literature on the extent of psychiatric comorbidity in patients with different subtypes of chronic daily headache. METHODS We recruited consecutive patients with chronic daily headache seen in a headache clinic from November 1998 to December 1999. The subtypes of chronic daily headache were classified according to the criteria proposed by Silberstein et al. A psychiatrist evaluated the patients according to the structured Mini-International Neuropsychiatric Interview to assess the comorbidity of depressive and anxiety disorders. RESULTS Two hundred sixty-one patients with chronic daily headache were recruited. The mean age was 46 years, and 80% were women. Transformed migraine was diagnosed in 152 patients (58%) and chronic tension-type headache in 92 patients (35%). Seventy-eight percent of patients with transformed migraine had psychiatric comorbidity, including major depression (57%), dysthymia (11%), panic disorder (30%), and generalized anxiety disorder (8%). Sixty-four percent of patients with chronic tension-type headache had psychiatric diagnoses, including major depression (51%), dysthymia (8%), panic disorder (22%), and generalized anxiety disorder (1%). The frequency of anxiety disorders was significantly higher in patients with transformed migraine after controlling for age and sex (P =.02). Both depressive and anxiety disorders were significantly more frequent in women. CONCLUSION Psychiatric comorbidity, especially major depression and panic disorders, was highly prevalent in patients with chronic daily headache seen in a headache clinic. These results demonstrate that women and patients with transformed migraine are at higher risk of psychiatric comorbidity.",
"title": "Comorbidity of depressive and anxiety disorders in chronic daily headache and its subtypes."
},
{
"docid": "15968271",
"text": "OBJECTIVE Our objective is to estimate and compare the prevalence of selected adverse consequences associated with unmet need for assistance among a socioeconomically and medically vulnerable subgroup of the older adult population, those who are dually eligible for Medicare and Medicaid, with those eligible for Medicare only. METHOD Using data from the National Health and Aging Trends Study (NHATS), a representative survey of the older Medicare population, we calculated the prevalence of disability-related need for assistance with self-care, household tasks, and mobility activities and the prevalence of adverse consequences of unmet need by dually eligible and Medicare only status. RESULTS Over 2 million community-dwelling older persons experienced an adverse consequence due to unmet need for assistance with self-care (e.g., soiled their clothes), over 2 million experienced adverse consequences due to unmet need for assistance with household tasks (e.g., went without groceries), and over 3 million persons experienced at least one adverse consequence of unmet need for assistance with mobility-related activities (e.g., had to stay in bed) in the month prior to the NHATS interview. Dually eligible persons experienced higher rates of 6 of the 11 adverse consequences studied and were more likely to have at least one adverse consequence in all 3 domains than others. DISCUSSION Several care models are emerging with the goal of integrating medical care, behavioral health, and long-term services for the dual eligible population. Indicators of adverse consequences of unmet need could be used to monitor the quality and adequacy of such care systems.",
"title": "The adverse consequences of unmet need among older persons living in the community: dual-eligible versus Medicare-only beneficiaries."
},
{
"docid": "474325",
"text": "The helmet is a new interface with the potential of increasing the success rate of non-invasive ventilation by improving tolerance. To perform a physiological comparison between the helmet and the conventional facial mask in delivering non-invasive ventilation in hypercapnic patients with chronic obstructive pulmonary disease. Prospective, controlled, randomized study with cross-over design. In 10 patients we evaluated gas exchange, inspiratory effort, patient–ventilator synchrony and patient tolerance after 30 min of non-invasive ventilation delivered either by helmet or facial mask; both trials were preceded by periods of spontaneous unassisted breathing. Arterial blood gases, inspiratory effort, duration of diaphragm contraction and ventilator assistance, effort-to-support delays (at the beginning and at the end of inspiration), number of ineffective efforts, and patient comfort. Non-invasive ventilation improved gas exchange (p< 0.05) and inspiratory effort (p< 0.01) with both interfaces. The helmet, however, was less efficient than the mask in reducing inspiratory effort (p< 0.05) and worsened the patient–ventilator synchrony, as indicated by the longer delays to trigger on (p< 0.05) and cycle off (p< 0.05) the mechanical assistance and by the number of ineffective efforts (p< 0.005). Patient comfort was no different with the two interfaces. Helmet and facial mask were equally tolerated and both were effective in ameliorating gas exchange and decreasing inspiratory effort. The helmet, however, was less efficient in decreasing inspiratory effort and worsened the patient–ventilator interaction.",
"title": "Non-invasive ventilation in chronic obstructive pulmonary disease patients: helmet versus facial mask"
},
{
"docid": "42095718",
"text": "Clinical evidence suggests that chronic daily headache (CDH) occurs in association with psychopathologies: previous studies have focused particularly on migraine. To evaluate this association, we studied, using the DSM-IIIR criteria, a population of 88 patients (18M, 70F) affected by CDH (mean duration 7.4 +/- 8.7 years). We documented the presence of a psychiatric disorder in 90% of this population. The most frequent diagnosis was a comorbidity of anxiety and mood disorders. The comorbidity of psychiatric disorders and headache has important implications as far as treatment is concerned.",
"title": "Psychiatric comorbidity in chronic daily headache."
},
{
"docid": "20109325",
"text": "Chronic obstructive pulmonary disease (COPD) is a global health problem, and since 2001, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) has published its strategy document for the diagnosis and management of COPD. This executive summary presents the main contents of the second 5-year revision of the GOLD document that has implemented some of the vast knowledge about COPD accumulated over the last years. Today, GOLD recommends that spirometry is required for the clinical diagnosis of COPD to avoid misdiagnosis and to ensure proper evaluation of severity of airflow limitation. The document highlights that the assessment of the patient with COPD should always include assessment of (1) symptoms, (2) severity of airflow limitation, (3) history of exacerbations, and (4) comorbidities. The first three points can be used to evaluate level of symptoms and risk of future exacerbations, and this is done in a way that splits patients with COPD into four categories-A, B, C, and D. Nonpharmacologic and pharmacologic management of COPD match this assessment in an evidence-based attempt to relieve symptoms and reduce risk of exacerbations. Identification and treatment of comorbidities must have high priority, and a separate section in the document addresses management of comorbidities as well as COPD in the presence of comorbidities. The revised document also contains a new section on exacerbations of COPD. The GOLD initiative will continue to bring COPD to the attention of all relevant shareholders and will hopefully inspire future national and local guidelines on the management of COPD.",
"title": "Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary."
},
{
"docid": "6171953",
"text": "Inflammation accompanies obesity and its comorbidities-type 2 diabetes, non-alcoholic fatty liver disease and atherosclerosis, among others-and may contribute to their pathogenesis. Yet the cellular machinery that links nutrient sensing to inflammation remains incompletely characterized. The protein deacetylase sirtuin-1 (SirT1) is activated by energy depletion and plays a critical role in the mammalian response to fasting. More recently it has been implicated in the repression of inflammation. SirT1 mRNA and protein expression are suppressed in obese rodent and human white adipose tissue, while experimental reduction of SirT1 in adipocytes and macrophages causes low-grade inflammation that mimics that observed in obesity. Thus suppression of SirT1 during overnutrition may be critical to the development of obesity-associated inflammation. This effect is attributable to multiple actions of SirT1, including direct deacetylation of NFκB and chromatin remodeling at inflammatory gene promoters. In this work, we report that SirT1 is also suppressed by diet-induced obesity in macrophages, which are key contributors to the ontogeny of metabolic inflammation. Thus, SirT1 may be a common mechanism by which cells sense nutrient status and modulate inflammatory signaling networks in accordance with organismal energy availability.",
"title": "Sirtuin-1 is a nutrient-dependent modulator of inflammation"
},
{
"docid": "13906581",
"text": "Background Extensive debate exists in the healthcare community over whether outcomes of medical care at teaching hospitals and other healthcare units are better or worse than those at the respective nonteaching ones. Thus, our goal was to systematically evaluate the evidence pertaining to this question. Methods and Findings We reviewed all studies that compared teaching versus nonteaching healthcare structures for mortality or any other patient outcome, regardless of health condition. Studies were retrieved from PubMed, contact with experts, and literature cross-referencing. Data were extracted on setting, patients, data sources, author affiliations, definition of compared groups, types of diagnoses considered, adjusting covariates, and estimates of effect for mortality and for each other outcome. Overall, 132 eligible studies were identified, including 93 on mortality and 61 on other eligible outcomes (22 addressed both). Synthesis of the available adjusted estimates on mortality yielded a summary relative risk of 0.96 (95% confidence interval [CI], 0.93–1.00) for teaching versus nonteaching healthcare structures and 1.04 (95% CI, 0.99–1.10) for minor teaching versus nonteaching ones. There was considerable heterogeneity between studies (I2 = 72% for the main analysis). Results were similar in studies using clinical and those using administrative databases. No differences were seen in the 14 studies fully adjusting for volume/experience, severity, and comorbidity (relative risk 1.01). Smaller studies did not differ in their results from larger studies. Differences were seen for some diagnoses (e.g., significantly better survival for breast cancer and cerebrovascular accidents in teaching hospitals and significantly better survival from cholecystectomy in nonteaching hospitals), but these were small in magnitude. Other outcomes were diverse, but typically teaching healthcare structures did not do better than nonteaching ones. Conclusions The available data are limited by their nonrandomized design, but overall they do not suggest that a healthcare facility's teaching status on its own markedly improves or worsens patient outcomes. Differences for specific diseases cannot be excluded, but are likely to be small.",
"title": "Patient Outcomes with Teaching Versus Nonteaching Healthcare: A Systematic Review"
},
{
"docid": "2048139",
"text": "BackgroundIndividuals with substance use disorders (SUDs) are at increased risk for hepatitis C viral infection (HCV), and few studies have explored their treatment responses empirically. The objective of this study was to assess interferon alpha therapy (IFN) completion and response rates among patients with HCV who had a history of comorbid SUDs. More data is needed to inform treatment strategies and guidelines for these patients. Using a medical record database, information was retrospectively collected on 307,437 veterans seen in the Veterans Integrated Service Network 20 (VISN 20) of the Veterans Healthcare Administration (VHA) between 1998 and 2003. For patients treated with any type of IFN (including regular or pegylated IFN) or combination therapy (IFN and ribavirin) who had a known HCV genotype, IFN completion and response rates were compared among patients with a history of SUD (SUD+ Group) and patients without a history of SUD (SUD- Group).ResultsOdds ratio analyses revealed that compared with the SUD- Group, the SUD+ Group was equally likely to complete IFN therapy if they had genotypes 2 and 3 (73.1% vs. 68.0%), and if they had genotypes 1 and 4 (39.5% vs. 39.9%). Within the sample of all patients who began IFN therapy, the SUD- and SUD+ groups were similarly likely to achieve an end of treatment response (genotypes 2 and 3, 52.8% vs. 54.3%; genotypes 1 and 4, 24.5% vs. 24.8%) and a sustained viral response (genotypes 2 and 3, 42.6% vs. 41.1%; genotypes 1 and 4: 16.0% vs. 22.3%).ConclusionIndividuals with and without a history of SUD responded to antiviral therapy for HCV at similar rates. Collectively, these findings suggest that patients who have co-morbid SUD and HCV diagnoses can successfully complete a course of antiviral therapy.",
"title": "Interferon alpha therapy for hepatitis C: treatment completion and response rates among patients with substance use disorders"
},
{
"docid": "45457778",
"text": "The change in the world's age demographics and the predicted rise in the incidence of age-related diseases, including dementia, is a source of major public health concern. Major research effort in both the United States and Europe has been targeted toward understanding the pathogenesis and epidemiology of dementia. This article presents a general overview of the history of dementia research in Europe and how it compares with that in the United States. The review highlights the common issues which both U.S. and European researchers have identified and attempted to tackle. To maximize information gained from studies across the world, better harmonization of methodology is needed, as informed from current research practice.",
"title": "A European perspective on population studies of dementia."
},
{
"docid": "26067999",
"text": "The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms. It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment. The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms. Summary of Recommendation and Evidence The USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) See the Clinical Considerations section for suggestions for implementation in practice. See the Figure for a summary of the recommendation and suggestions for clinical practice. Figure. Screening for lung cancer: clinical summary of U.S. Preventive Services Task Force recommendation. Appendix Table 1 describes the USPSTF grades, and Appendix Table 2 describes the USPSTF classification of levels of certainty about net benefit. Appendix Table 1. What the USPSTF Grades Mean and Suggestions for Practice Appendix Table 2. USPSTF Levels of Certainty Regarding Net Benefit Supplement. Consumer Fact Sheet. Rationale Importance Lung cancer is the third most common cancer and the leading cause of cancer-related death in the United States (1). The most important risk factor for lung cancer is smoking, which results in approximately 85% of all U.S. lung cancer cases (2). Although the prevalence of smoking has decreased, approximately 37% of U.S. adults are current or former smokers (2). The incidence of lung cancer increases with age and occurs most commonly in persons aged 55 years or older. Increasing age and cumulative exposure to tobacco smoke are the 2 most common risk factors for lung cancer. Lung cancer has a poor prognosis, and nearly 90% of persons with lung cancer die of the disease. However, early-stage nonsmall cell lung cancer (NSCLC) has a better prognosis and can be treated with surgical resection. Detection Most lung cancer cases are NSCLC, and most screening programs focus on the detection and treatment of early-stage NSCLC. Although chest radiography and sputum cytologic evaluation have been used to screen for lung cancer, LDCT has greater sensitivity for detecting early-stage cancer (3). Benefits of Detection and Early Treatment Although lung cancer screening is not an alternative to smoking cessation, the USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancerrelated deaths. Direct evidence from a large, well-conducted, randomized, controlled trial (RCT) provides moderate certainty of the benefit of lung cancer screening with LDCT in this population (4). The magnitude of benefit to the person depends on that person's risk for lung cancer because those who are at highest risk are most likely to benefit. Screening cannot prevent most lung cancerrelated deaths, and smoking cessation remains essential. Harms of Detection and Early Intervention and Treatment The harms associated with LDCT screening include false-negative and false-positive results, incidental findings, overdiagnosis, and radiation exposure. False-positive LDCT results occur in a substantial proportion of screened persons; 95% of all positive results do not lead to a diagnosis of cancer. In a high-quality screening program, further imaging can resolve most false-positive results; however, some patients may require invasive procedures. The USPSTF found insufficient evidence on the harms associated with incidental findings. Overdiagnosis of lung cancer occurs, but its precise magnitude is uncertain. A modeling study performed for the USPSTF estimated that 10% to 12% of screen-detected cancer cases are overdiagnosedthat is, they would not have been detected in the patient's lifetime without screening. Radiation harms, including cancer resulting from cumulative exposure to radiation, vary depending on the age at the start of screening; the number of scans received; and the person's exposure to other sources of radiation, particularly other medical imaging. USPSTF Assessment The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT is of moderate net benefit in asymptomatic persons who are at high risk for lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. The moderate net benefit of screening depends on limiting screening to persons who are at high risk, the accuracy of image interpretation being similar to that found in the NLST (National Lung Screening Trial), and the resolution of most false-positive results without invasive procedures (4). Clinical Considerations Patient Population Under Consideration The risk for lung cancer increases with age and cumulative exposure to tobacco smoke and decreases with time since quitting smoking. The best evidence for the benefit of screening comes from the NLST, which enrolled adults aged 55 to 74 years who had at least a 30 pack-year smoking history and were current smokers or had quit within the past 15 years. As with all screening trials, the NLST tested a specific intervention over a finite period. Because initial eligibility extended through age 74 years and participants received 3 annual screening computed tomographic scans, the oldest participants in the trial were aged 77 years. The USPSTF used modeling studies to predict the benefits and harms of screening programs that use different screening intervals, age ranges, smoking histories, and times since quitting. A program that annually screens adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years is projected to have a reasonable balance of benefits and harms. The model assumes that persons who achieve 15 years of smoking cessation during the screening program discontinue screening. This model predicts the outcomes of continuing the screening program used in the NLST through age 80 years. Screening may not be appropriate for patients with substantial comorbid conditions, particularly those at the upper end of the screening age range. The NLST excluded persons who were unlikely to complete curative lung cancer surgery and those with medical conditions that posed a substantial risk for death during the 8-year trial. The baseline characteristics of the NLST showed a relatively healthy sample, and fewer than 10% of enrolled participants were older than 70 years (5). Persons with serious comorbid conditions may experience net harm, no net benefit, or at least substantially less net benefit. Similarly, persons who are unwilling to have curative lung surgery are unlikely to benefit from a screening program. Assessment of Risk Age, total exposure to tobacco smoke, and years since quitting smoking are important risk factors for lung cancer and were used to determine eligibility in the NLST. Other risk factors include specific occupational exposures, radon exposure, family history, and history of pulmonary fibrosis or chronic obstructive lung disease. The incidence of lung cancer is relatively low in persons younger than 50 years but increases with age, especially after age 60 years. In current and former smokers, age-specific incidence rates increase with age and cumulative exposure to tobacco smoke. Smoking cessation substantially reduces a person's risk for developing and dying of lung cancer. Among persons enrolled in the NLST, those who were at highest risk because of additional risk factors or a greater cumulative exposure to tobacco smoke experienced most of the benefit (6). A validated multivariate model showed that persons in the highest 60% of risk accounted for 88% of all deaths preventable by screening. Screening Tests Low-dose computed tomography has shown high sensitivity and acceptable specificity for the detection of lung cancer in high-risk persons. Chest radiography and sputum cytologic evaluation have not shown adequate sensitivity or specificity as screening tests. Therefore, LDCT is currently the only recommended screening test for lung cancer. Treatment Surgical resection is the current standard of care for localized NSCLC. This type of cancer is treated with surgical resection when possible and also with radiation and chemotherapy. Annual LDCT screening may not be useful for patients with life-limiting comorbid conditions or poor functional status who may not be candidates for surgery. Other Approaches to Prevention Smoking cessation is the most important intervention to prevent NSCLC. Advising smokers to stop smoking and preventing nonsmokers from being exposed to tobacco smoke are the most effective ways to decrease the morbidity and mortality associated with lung cancer. Current smokers should be informed of their continuing risk for lung cancer and offered cessation treatments. Screening with LDCT should be viewed as an adjunct to tobacco cessation interventions. Useful Resources Clinicians have many resources to help patients stop smoking. The Centers for Disease Control and Prevention has developed a Web site with many such resources, including information on tobacco quit lines, available in several languages (www.cdc.gov/tobacco/campaign/tips). Quit l",
"title": "Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation Statement"
},
{
"docid": "13282296",
"text": "CONTEXT Although acute hypoglycemia may be associated with cognitive impairment in children with type 1 diabetes, no studies to date have evaluated whether hypoglycemia is a risk factor for dementia in older patients with type 2 diabetes. OBJECTIVE To determine if hypoglycemic episodes severe enough to require hospitalization are associated with an increased risk of dementia in a population of older patients with type 2 diabetes followed up for 27 years. DESIGN, SETTING, AND PATIENTS A longitudinal cohort study from 1980-2007 of 16,667 patients with a mean age of 65 years and type 2 diabetes who are members of an integrated health care delivery system in northern California. MAIN OUTCOME MEASURE Hypoglycemic events from 1980-2002 were collected and reviewed using hospital discharge and emergency department diagnoses. Cohort members with no prior diagnoses of dementia, mild cognitive impairment, or general memory complaints as of January 1, 2003, were followed up for a dementia diagnosis through January 15, 2007. Dementia risk was examined using Cox proportional hazard regression models, adjusted for age, sex, race/ethnicity, education, body mass index, duration of diabetes, 7-year mean glycated hemoglobin, diabetes treatment, duration of insulin use, hyperlipidemia, hypertension, cardiovascular disease, stroke, transient cerebral ischemia, and end-stage renal disease. RESULTS At least 1 episode of hypoglycemia was diagnosed in 1465 patients (8.8%) and dementia was diagnosed in 1822 patients (11%) during follow-up; 250 patients had both dementia and at least 1 episode of hypoglycemia (16.95%). Compared with patients with no hypoglycemia, patients with single or multiple episodes had a graded increase in risk with fully adjusted hazard ratios (HRs): for 1 episode (HR, 1.26; 95% confidence interval [CI], 1.10-1.49); 2 episodes (HR, 1.80; 95% CI, 1.37-2.36); and 3 or more episodes (HR, 1.94; 95% CI, 1.42-2.64). The attributable risk of dementia between individuals with and without a history of hypoglycemia was 2.39% per year (95% CI, 1.72%-3.01%). Results were not attenuated when medical utilization rates, length of health plan membership, or time since initial diabetes diagnosis were added to the model. When examining emergency department admissions for hypoglycemia for association with risk of dementia (535 episodes), results were similar (compared with patients with 0 episodes) with fully adjusted HRs: for 1 episode (HR, 1.42; 95% CI, 1.12-1.78) and for 2 or more episodes (HR, 2.36; 95% CI, 1.57-3.55). CONCLUSIONS Among older patients with type 2 diabetes, a history of severe hypoglycemic episodes was associated with a greater risk of dementia. Whether minor hypoglycemic episodes increase risk of dementia is unknown.",
"title": "Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus."
},
{
"docid": "25837950",
"text": "Obesity is associated with higher mortality in the general population, but this association is reversed in patients on dialysis. The nature of the relationship of obesity with adverse clinical outcomes in nondialysis-dependent CKD and the putative interaction of the severity of disease with this association are unclear. We analyzed data from a nationally representative cohort of 453,946 United States veterans with eGFR<60 ml/min per 1.73 m(2). The associations of body mass index categories (<20, 20 to <25, 25 to <30, 30 to <35, 35 to <40, 40 to <45, 45 to <50, and ≥50 kg/m(2)) with all-cause mortality and disease progression (using multiple definitions, including incidence of ESRD, doubling of serum creatinine, and the slopes of eGFR) were examined in Cox proportional hazards models and logistic regression models. Multivariable adjustments were made for age, race, comorbidities and medications, and baseline eGFR. Body mass index showed a relatively consistent U-shaped association with clinical outcomes, with the best outcomes observed in overweight and mildly obese patients. Body mass index levels <25 kg/m(2) were associated with worse outcomes in all patients, independent of severity of CKD. Body mass index levels ≥35 kg/m(2) were associated with worse outcomes in patients with earlier stages of CKD, but this association was attenuated in those patients with eGFR<30 ml/min per 1.73 m(2). Thus, until clinical trials establish the ideal body mass index, a cautious approach to weight management is warranted in this patient population.",
"title": "Association of body mass index with outcomes in patients with CKD."
},
{
"docid": "24323695",
"text": "RATIONALE Up to 80% of patients with lung cancer have comorbid chronic obstructive pulmonary disease (COPD). Many of them are poor candidates for stage-specific lung cancer treatment due to diminished lung function and poor functional status, and many forego treatment. The negative effect of COPD may be moderated by pulmonologist-guided management. OBJECTIVES This study examined the association between pulmonologist management and the probability of receiving the recommended stage-specific treatment modality and overall survival among patients with non-small cell lung cancer (NSCLC) with preexisting COPD. METHODS Early- and advanced-stage NSCLC cases diagnosed between 2002 and 2005 with a prior COPD diagnosis (3-24 months before NSCLC diagnosis) were identified in Surveillance, Epidemiology, and End Results tumor registry data linked to Medicare claims. Study outcomes included receipt of recommended stage-specific treatment (surgical resection for early-stage NSCLC and chemotherapy for advanced-stage NSCLC [advNSCLC]) and overall survival. Pulmonologist management was considered present if one or more Evaluation and Management visit claims with pulmonologist specialty were observed within 6 months after NSCLC diagnosis. Stage-specific multivariate logistic regression tested association between pulmonologist management and treatment received. Cox proportional hazard models examined the independent association between pulmonologist care and mortality. Two-stage residual inclusion instrumental variable (2SRI-IV) analyses tested and adjusted for potential confounding based on unobserved factors or measurement error. MEASUREMENTS AND MAIN RESULTS The cohorts included 5,488 patients with early-stage NSCLC and 6,426 patients with advNSCLC disease with preexisting COPD. Pulmonologist management was recorded for 54.9% of patients with early stage NSCLC and 35.7% of patients with advNSCLC. Of those patients with pulmonologist involvement, 58.5% of patients with early NSCLC received surgical resection, and 43.6% of patients with advNSCLC received chemotherapy. Pulmonologist management post NSCLC diagnosis was associated with increased surgical resection rates (odds ratio, 1.26; 95% confidence interval, 1.11-1.45) for early NSCLC and increased chemotherapy rates (odds ratio, 1.88; 95% confidence interval, 1.67-2.10) for advNSCLC. Pulmonologist management was also associated with reduced mortality risk for patients with early-stage NSCLC but not AdvNSCLC. CONCLUSIONS Pulmonologist management had a positive association with rates of stage-specific treatment in both groups and overall survival in early-stage NSCLC. These results provide preliminary support for the recently published guidelines emphasizing the role of pulmonologists in lung cancer management.",
"title": "Pulmonologist involvement, stage-specific treatment, and survival in adults with non-small cell lung cancer and chronic obstructive pulmonary disease."
},
{
"docid": "21274919",
"text": "OBJECTIVE Chronic physical comorbidity is common in dementia. However, there is an absence of evidence to support good practice guidelines for attention to these problems. We aimed to study the extent of this comorbidity and its impact on cognitive function and disability in population-based studies in low and middle income countries, where chronic diseases and impairments are likely to be both common and undertreated. METHODS A multicentre cross-sectional survey of all over 65 year old residents (n = 15 022) in 11 catchment areas in China, India, Cuba, Dominican Republic, Venezuela, Mexico and Peru. We estimated the prevalence of pain, incontinence, hearing and visual impairments, mobility impairment and undernutrition according to the presence of dementia and its severity, and, among those with dementia, the independent contribution of these impairments to cognitive function and disability, adjusting for age, gender, education and dementia severity. RESULTS Incontinence, hearing impairment, mobility impairment and undernutrition were consistently linearly associated with the presence of dementia and its severity across regions. Among people with dementia, incontinence, hearing impairment and mobility impairment were independently associated with disability in all regions while the contributions of pain, visual impairment and undernutrition were inconsistent. Only hearing impairment made a notable independent contribution to cognitive impairment. CONCLUSIONS There is an urgent need for clinical trials of the feasibility, efficacy and cost-effectiveness of regular physical health checks and remediation of identified pathologies, given the considerable comorbidity identified in our population based studies, and the strong evidence for independent impact upon functioning.",
"title": "The association between common physical impairments and dementia in low and middle income countries, and, among people with dementia, their association with cognitive function and disability. A 10/66 Dementia Research Group population-based study."
},
{
"docid": "1412089",
"text": "BACKGROUND Traditional T2 weighted MR imaging results are non-specific for the extent of underlying white matter structural abnormalities present in late life depression (LLD). Diffusion tensor imaging provides a unique opportunity to investigate the extent and nature of structural injury, but has been limited by examining only a subset of regions of interest (ROI) and by confounds common to the study of an elderly population, including comorbid vascular pathology. Furthermore, comprehensive correlation of diffusion tensor imaging (DTI) measurements, including axial and radial diffusivity measurements, has not been demonstrated in the late life depression population. METHODS 51 depressed and 16 non-depressed, age- and cerebrovascular risk factor-matched elderly subjects underwent traditional anatomic T1 and T2 weight imaging, as well as DTI. The DTI data were skeletonized using tract based spatial statistics (TBSS), and both regional and global analyses were performed. RESULTS Widespread structural abnormalities within white matter were detected in the LLD group, accounting for age, gender and education and matched for cerebrovascular risk factors and global T2 white matter hyperintensities (T2WMH). Regional differences were most prominent in uncinate and cingulate white matter and were generally characterized by an increase in radial diffusivity. Age-related changes particularly in the cingulate bundle were more advanced in individuals with LLD relative to controls. Regression analysis demonstrated significant correlations of regional fractional anisotropy and radial diffusivity with five different neuropsychological factor scores. TBSS analysis demonstrated a greater extent of white matter abnormalities in LLD not responsive to treatment, as compared to controls. CONCLUSIONS White matter integrity is compromised in late life depression, largely manifested by increased radial diffusivity in specific regions, suggesting underlying myelin injury. A possible mechanism for underlying myelin injury is chronic white matter ischemia related to intrinsic cerebrovascular disease. In some regions such as the cingulate bundle, the white matter injury related to late life depression appears to be independent of and compounded by age-related changes. The correlations with neuropsychological testing indicate the essential effects of white matter injury on functional status. Lastly, response to treatment may depend on the extent of white matter injury, suggesting a need for intact functional networks.",
"title": "Diminished performance on neuropsychological testing in late life depression is correlated with microstructural white matter abnormalities."
},
{
"docid": "32777637",
"text": "BACKGROUND Concurrent use of multiple standing antipsychotics (antipsychotic polypharmacy) is increasingly common among both inpatients and outpatients. Although this has often been cited as a potential quality-of-care problem, reviews of research evidence on antipsychotic polypharmacy have not distinguished between appropriate versus inappropriate use. METHODS A MEDLINE search from 1966 to December 2007 was completed to identify studies comparing changes in symptoms, functioning, and/or side effects between patients treated with multiple antipsychotics and patients treated with a single antipsychotic. The studies were reviewed in two groups on the basis of whether prescribing was concordant with guideline recommendations for multiple-antipsychotic use. RESULTS A review of the literature, including three randomized controlled trials, found no support for the use of antipsychotic polypharmacy in patients without an established history of treatment resistance to multiple trials of monotherapy. In patients with a history of treatment resistance to multiple monotherapy trials, limited data support antipsychotic polypharmacy, but positive outcomes were primarily found in studies of clozapine augmented with a second-generation antipsychotic. DISCUSSION Research evidence is consistent with the goal of avoiding antipsychotic polypharmacy in patients who lack guideline-recommended indications for its use. The Joint Commission is implementing a core measure set for Hospital-Based Inpatient Psychiatric Services. Two of the measures address antipsychotic polypharmacy. The first measure assesses the overall rate. The second measure determines whether clinically appropriate justification has been documented supporting the use of more than one antipsychotic medication.",
"title": "When is antipsychotic polypharmacy supported by research evidence? Implications for QI."
}
] |
773
|
Transfering money from NRE account in India to family member
|
[
{
"docid": "157712",
"text": "I am a US citizen and I want to transfer some amount 10 lakhs+ to my brother from my NRE account in India to his account. My brother is going to purchase something for his business. He is going to return my amount after 3-4 Months From the description it looks like you would like to loan to your brother on repatriation basis. Yes this is allowed. See the RBI Guide here and here for more details. There are some conditions; (iv) Scheme for raising loans from NRIs on repatriation basis Borrowings not exceeding US$ 2,50,000 or its equivalent in foreign exchange by an individual resident in India from his close relatives resident outside India, subject to the conditions that - a) the loan is free of interest; b) the minimum maturity period of the loan is seven years; c) The amount of loan is received by inward remittance in free foreign exchange through normal banking channels or by debit to the NRE/FCNR account of the non-resident lender; d) The loan is utilised for the borrower's personal purposes or for carrying on his normal business activity but not for carrying on agricultural/plantation activities, purchase of immovable property or shares/debentures/bonds issued by companies in India or for re-lending. Although it is mentioned as Seven years, this is revised to one year. Since he cannot deposit into my NRE account I guess he has to deposit it into my NRO account. A repatriate-able loan as above can be deposited into NRE Account. Is there any illegality here doing such transaction? No. Please ensure proper paper work to show this as loan and document the money trail. Also once I get my money in NRO account do I need to pay taxes in India on the money he deposited? This question does not arise.",
"title": ""
}
] |
[
{
"docid": "516260",
"text": "I have read from lot of places that transferring funds from NRO to NRE is possible given correct documents are provided. Yes this is correct. The key document 15CB establishes that you have paid taxes that were due before money is transferred from the NRO account to the NRE account and/or are repatriated. Here is what I am simply doing- Steps 3 & 4 more so the step 4 can be seen as new income. So the source of the funds is originally from NRE account. However, the CA feels that since my withdrawal and deposit mechanism in NRO is cash, I might be subject to questioning. Is there any issues in doing the above? The CA is right. The Cash Withdrawal and Cash Deposit has broken the link between the money withdrawn and the money deposited. It could easily be the case that the Cash Withdrawals were spent on expenses and the Cash Deposit is new (taxable) income to you. This new income needs to be declared and the taxes paid. If you Uncle is a close relative (the exact relationships that are called close relatives are defined by law), the return of the money can be declared to be a gift from your Uncle to you and no taxes are due from you on the money. If the funds are large, it is advised to have a gift deed. It is not a simple matter of creating a gift deed stating that your Uncle has given you a gift; your Uncle has to show how he acquired so many assets that he gave you some money as a gift and whether appropriate taxes were paid by him. If your Uncle is not a close relative, he can still gift you up to Rs 50,000 per year without you having to pay any income tax on the money received, but again, a gift deed would be needed to account for the cash deposits. In short, keep speaking to your CA. He will advise you on the best course of action. Related Question Transfering money from NRE account in India to family member",
"title": ""
},
{
"docid": "16068",
"text": "I have not opened any NRE/NRO account before coming to Finland. This is in violation of Foreign Exchange Management Act. Please get this regularized ASAP. All your savings account need to be converted to NRO. Shall I transfer funds from abroad to both NRE and NRO account or I can transfer only to NRE account in India? You can transfer to NRE or NRO. It is advisable to transfer into NRE as funds from here can be repatriated out of India without any paperwork. Funds from NRO account need paperwork to move out of India. I am a regular tax payer in abroad. The Funds which i'll transfer in future will attract any additional tax in India? As your status is Non Resident and the income is during that period, there is no tax applicable in India on this. Few Mutual Fund SIPs (monthly basis) are linked with my existing saving account in india. Do these SIPs will stop when the savings account will turn into NRO account? Shall I need to submit any documents for KYC compliance? If yes, to whom I should submit these? is there any possibility to submit it Online? Check your Bank / Mutual Fund company. Couple of FDs are also opened online and linked with this existing saving account. Do the maturity amount(s) subject to TDS or any tax implication such as 30.9% as this account will be turned into NRO account till that time and NRO account attracts this higher tax percentage. These are subject to taxes in India. This will be as per standard tax brackets. Which account (NRE/NRO) is better for paying EMIs for Home Loan, SIPs of Mutual Funds, utility bills in India, transfer money to relative's account etc Home Loan would be better from NRE account as if you sell the house, the EMI paid can be credited into NRE account and you can transfer this out of India without much paperwork. Same for SIP's. For other it doesn't really matter as it is an expense. Is there any charge to transfer fund from NRE to NRO account if both account maintain in same Bank same branch. Generally No. Check with your bank. Which Bank account's (NRE/NRO) debit/ATM card should be used in Abroad in case of emergency. Check with your bank. NRE funds are more easy. NRO there will be limits and reporting. Do my other savings accounts, maintained in different Banks, also need to be converted into NRO account? If yes, how can it be done from Abroad? Yes. ASAP. Quite a few leading banks allow you to do this if you are not present. Check you bank for guidance.",
"title": ""
},
{
"docid": "448981",
"text": "am I allowed to transfer into NRE account from paypal? Credits into NRE accounts are restricted. It has to be established that the funds being credited are income outside of India. In case of paypal, paypal uses local clearing to credit funds into Bank Accounts. So essentially one cannot credit NRE account by domestic clearing network like NEFT. It is best that you withdraw the funds into Bank Account outside India and use SWIFT or remittance service to credit your NRE account. I do not want to transfer to an NRO account since the money credited into it will become taxable. This is not the right assumption. Credits into NRO are not taxable by default; if you establish that the funds are from outside India, there is no tax on the income money transferred from abroad into the NRO account. However, the interest that will be paid by the bank on the balance of the NRO account is taxable income in India and is subject to TDS. In contrast, interest paid on the balance in an NRE account is not taxable in India and is not subject to TDS as long as you maintain NRI status. However it does make sense to keep accounts segregated, i.e. income generated in India, credit the NRO account and income generated outside India credit to NRE.",
"title": ""
},
{
"docid": "263648",
"text": "On my recent visit to the bank, I was told that money coming into the NRE account can only be foreign currency and for NRO accounts, the money can come in local currency but has to be a valid source of income (e.g. rent or investments in India). Yes this is correct as per FMEA regulation in India. Now if we use 3rd party remittances like Remitly or Transferwise etc, they usually covert the foreign currency into local currency like INR and then deposit it. The remittance services are better suited for transferring funds to Normal Savings accounts of your loved ones. Most remittance services would transfer funds using a domestic clearing network [NEFT] and hence the trace that funds originated outside of India is lost. There could be some generic remittance that may have direct tie-up with some banks to do direct transfers. How can we achieve this in either NRE/NRO accounts? If not, what are the other options ? You can do a Wire Transfer [SWIFT] from US to Indian NRE account. You can also use the remittance services [if available] from Banks where you hold NRE Account. For example RemittoIndia from HDFC for an NRE account in HDFC, or Money2India from ICICI for an NRE account in ICICI or QuickRemit from SBI etc. These would preserve the history that funds originated from outside India. Similarly you can also deposit a Foreign Currency Check into Indian Bank Account. The funds would take around month or so to get credited. All other funds can be deposited in NRO account.",
"title": ""
},
{
"docid": "521753",
"text": "I am on employment based visa in USA and want to send dollars from USA to India from my savings (after paying Tax). How much maximum dollars I can send in a day? month? or in a year regularly? There is no such limit. You can transfer as money you like to yourself anywhere. To pay the Bank Loan-student Loan how much maximum dollars I can send in a day, in a month or in a year? to pay that I have to pay directly to that Bank Account or in any account I can send money? You can transfer to your NRE account in India and move it further. You can also send it directly to the Loan Account [Check with the Bank, they may not be able to receive funds from outside for a Loan Account] My mother is having Green Card. She is not working. She has a NRE account in India. Can I send dollars from my USA Bank account to her NRE account in India? what are the rules for that? any Tax or limit for that? Or I have to get any permission before sending it? If you are sending money to your mother, it would come under Gift Tax act in US. There is no issue in India. Suggest you transfer to your own NRE account.",
"title": ""
},
{
"docid": "495315",
"text": "Is it possible to move money from NRE to NRO account Yes you can move money from NRE to NRO without any issue. You can't do the other way round. i.e. Move money from NRO to NRE. I would like to move USD earning to NRE Yes you can further move money in NRE to NRO account Yes you can I am planning to give NRO account to HDFC Home loan for EMI processing Yes you can. Depending on your long term plan it may not be a good idea. For example if you were to sell the house you cannot move the funds into NRE and outside of India without some amount of paperwork. However if you pay the EMI via NRE account, on the sale of house, you can transfer the funds into NRE account to the extent of the loan paid and the Original downpayment [if made from NRE account]. also I can deposit money from other savings account to NRO; As an NRI, you can't hold ordinary savings account in India. This is violation of norms. Please have any/all savings account in India converted to NRO at the earliest.",
"title": ""
},
{
"docid": "307404",
"text": "I am a non-resident alien transferring a limited amount ( in dollars post tax) to India every couple of months. Assuming you are transferring this into an NRE account in India or atleast NRO account in India. As a NRI, by regulations one should not hold normal Savings account. This has to be converted into NRO. I put that money as a fixed deposit in a bank (which gives 6-7 percent annual return) Assuming you have FCNR deposits. Also assuming that you are declaring the taxes in your US Tax returns and paying tax accordingly. There is no tax in India on FCNR. If this was in ordinary FD or in NRO account, you are declaring and paying taxes in India as well as in US. What is the max limit on transferring money back from India to USA? If you have transferred this into NRE account, there is no limit. Other account there is a limit. Read more at Liberalized Remittance Scheme and here. What are the legitimate ways to transfer the money? From India point of view, this has to be Bank to Bank transfers. You can't carry cash [Indian Rupees] outside of India beyond Rs 25000 [or 15000?]. You can't hold excess of USD 250 without valid purpose. Western Union is not authorized to transfer funds out of India. Will there be any tax levied? No assuming you are already paying taxes on the Interest in US and depending on the type of account in India.",
"title": ""
},
{
"docid": "446647",
"text": "I want to send some money to Indian in my saving account but I haven't any NRO/NRE account. It is advisable to Open an NRE account. As an NRI you cannot hold a savings account. Please have this converted into NRO account ASAP. Process or Transaction charges or Tax (levied by Indian bank) on money what I'll send to my saving account in India. I know the process or transaction charges (applied by UK banks) from UK to India. There will be a nominal charge levied by banks in India. If you use dedicated Remittance services [Most Leading Indian Banks offer this], these are mostly free. Is there any limit to get rid off tax? Nope there isn't any limit. This depends on service provider. What types of paper work I'll need to do for showing that income is sent from UK after paying tax. If you transfer to NRE account. There is no paperwork required. It is implicit. If not you have to establish that the funds are received from outside India, keep copies of the transfer request initiated, debits to the Bank Account in UK, your salary slips, Passport stamps etc.",
"title": ""
},
{
"docid": "450925",
"text": "How to send the full loan amount from Saudi Arabia (money exchange), because I have a money transfer limit? There is no limit for sending money into India. Just use the right banking channel and transfer the funds. If I sent to India, what about tax and all that in India? In a financial year if you are outside of India for more than 182 days, you are Non-Resident for tax purposes. Any money you earn outside of India is tax free in India. i.e. there is no tax for this funds in India. If it is possible to send the money, to whom do I have to send it (my account, or my parents account) Whatever is convenient, preferably to your own NRE/NRO account. Any documents I have to show for tax issues (in case tax) You have to establish that you are NRI and hence this funds are not taxable. Hence its best you transfer into NRE/NRO account. If you transfer to your parents account, you would need a gift deed to make this non-taxable to your parents. I have savings account my self in Axis Bank, for the past 3 years I am paying taxes, if I send to my Axis Bank account how can I withdraw the full amount (10 lakhs (1,000,000)) on single day Withdrawal is possible by cash or cheque You can write a check, do a NEFT/RTGS transfer to your loan account, you can withdraw cash by giving some notice time to the Branch Manager of your Branch.",
"title": ""
},
{
"docid": "286825",
"text": "There is no difference in taxation in India if you transfer every month or bulk. If you use specialized remittance services from leading Indian Banks, there would be little difference in fees. Assuming you are keeping the funds in NRE account in India and hold it in GBP, you get a slight better rate of interest that what you would get in UK. The interest would not be taxable in India, however it would be in UK. If you convert the funds at hold it in NRE, Rupee account, you would get still better rate of interest. However you are taking the Fx risk when you try and convert this back to GBP incase you decide to stay on. There are no right or wrong answers Edit: There is no limit on the amount of funds earned as NRE that can be got into India tax free. There is a time limit of 7 Years to get the funds back to India tax free. From a tax point of view if you transfer into NRE account its easy. If you transfer into Normal Savings account you would need some paperwork.",
"title": ""
},
{
"docid": "354255",
"text": "Will I able to put the Rs amount back in the NRE account the same amount which I have paid against that house? If you have purchased the property by debiting an NRE account [you should have the paper trail], the same amount of funds can be transferred back to NRE Account. For example the house was for 50 lacs, and you paid Rs 30 lacs from NRE account, when you sell the house, you can transfer back only 30 lacs into the NRE account. Will I need to pay TAX on NRE account money before transferring out of India? You need not pay tax on the funds in NRE account. However if you have made gains by buying and selling a house [irrespective of the source of funds], you have to pay capital gains tax.",
"title": ""
},
{
"docid": "147197",
"text": "Assuming that the NRE (NonResident External) account is in good standing, that is, you are still eligible to have an NRE account because your status as a NonResident of India has not changed in the interim, you can transfer money back from your NRE account to your US accounts without any problems. But be aware that you bear the risk of getting back a much smaller amount than you invested in the NRE account because of devaluation of the Indian Rupee (INR). NRE accounts are held in INR, and whatever amounts (in INR) that you choose to withdraw will be converted to US$ at the exchange rate then applicable. Depending on whether it is the Indian bank that is doing the conversion and sending money by wire to your US bank, or you are depositing a cheque in INR in your US bank, you may be charged miscellaneous service fees also. To answer a question that you have not asked as yet, there is no US tax on the transfer of the money. The interest paid on your deposits into the NRE account are not taxable income to you in India, but are taxable income to you in the US, and so I hope that you have been declaring this income each year on Schedule B of your income tax return, and also reporting that you have accounts held abroad, as required by US law. See for example, this question and its answer and also this question and its answer.",
"title": ""
},
{
"docid": "78813",
"text": "The simplest way is you transfer the funds into your NRE account in India. From the NRE account transfer the funds to your brother-in-law and show the purpose as Loan. From 2012 onwards RBI has simplified things under FMEA and your brother-in-law can deposit/repay the loan back into the NRE account. Once the funds are in NRE account you can repatriate then whenever you like. This entire process requires less paperwork. The option you have suggested is also fine, however your brother-in-law needs to engage the services of a CA and he will authenticate the purpose of remittance to the Bank. Based on this certificate the Bank will transfer the funds outside of India.",
"title": ""
},
{
"docid": "586772",
"text": "Citizens of India who are not residents to India (have NRI status) are not entitled to have ordinary savings accounts in India. If you have such accounts (e.g. left them behind to support your family while you are abroad), they need to be converted to NRO (NonResident Ordinary) accounts as soon as possible. Your bank will have forms for completion of this process. Any interest that these accounts earn will be taxable income to you in India, and possibly in the U.K. too, though tax treaties (or Double Taxation Avoidance Agreements) generally allow you to claim credit for taxes paid to other countries. Now, with regard to your question, NRIs are entitled to make deposits into NRO accounts as well as NRE (NonResident External) accounts. The differences are that money deposited into an NRE account, though converted to Indian Rupees, can be converted back very easily to foreign currency if need be. However, the re-conversion is at the exchange rate then in effect, and you may well lose that 10% interest earned because of a change in exchange rate. Devaluation of the Indian Rupee as occurred several times in the past 70 years. Once upon a time, it was essentially impossible to take money in an NRO account and convert it to foreign currency, but under the new recently introduced schemes, money in an NRO account can also be converted to foreign currencies, but it needs certification by a CA, and various forms to be filled out, and thus is more hassle. interest earned by the money in an NRE account is not taxable income in India, but is taxable income in the U.K. There is no taxable event (neither in U.K. nor in India) when you change an ordinary savings account held in India into an NRO account, or when you deposit money from abroad into an NRE or NRO account in an Indian bank. What is taxable is the interest that you receive from the Indian bank. In the case of an NRO account, what is deposited into your NRO account is the interest earned less the (Indian) income tax (usually 20%) deducted at the source (TDS) and sent to the Income Tax Authority on your behalf. In the case of an NRE account, the full amount of interest earned is deposited into the NRE account -- no TDS whatsoever. It is your responsibility to declare these amounts to the U.K. income tax authority (HM Revenue?) and pay any taxes due. Finally, you say that you recently moved to the U.K. for a job. If this is a temporary job and you might be back in India very soon, all the above might not be applicable to you since you would not be classified as an NRI at all.",
"title": ""
},
{
"docid": "153528",
"text": "For the financial year 1 April 2014 to 31 March 2015 as you have / will be spending more than 182 days outside of India, you are Non-Resident from tax point of view. For the period 1 April 2014 to Aug 2014, any salary / income you have earned in India is taxable and tax need to be paid. For the period Aug 2014 to 31 March 2015 the income you have earned in Saudi is not taxable in India. You can transfer money to India or keep in Saudi, it has no effect on the taxes. Any interest income you earn, or rental income you earn, or any other source of income in India is taxable. You would need to file returns accordingly. An NRE Accounts allows you to transfer funds out of India without any questions. So if you intend at some point in time in future to move funds out of India [say settling down in Saudi or UK or US etc] it is advisable to have NRE account. If you are sure you don't want to transfer funds out of India, you should open an NRO account.",
"title": ""
},
{
"docid": "344290",
"text": "foreign income, transfer it to my savings account in India Yes you can transfer to India. The right account would be NRO/NRE. As an NRI one should not hold a regular savings account. forum that foreign income is not taxable unless used to buy stocks, fds etc If you are an NRI, income earned outside of India is not taxable in India. However any income you generate in India is taxable, i.e. interest income, gains from shares etc. Do we need to pay taxes for the money transferred No tax if you are an NRI even if you transfer funds to India. Taxation does not depend on whether or not you transfer the money, it depends on your status used to pay home EMIs or principle amount? You can use the money for what ever you like.",
"title": ""
},
{
"docid": "210853",
"text": "Check with Lawyer and CA who deals with international laws. It maybe illegal in Saudi Arabia. From India tax point of view, any credits into NRE account is not taxable. However credits to friends/family will be treated as GIFT and friends/family will be liable to pay a gift tax if such transfer are more than Rs 50,000/- per year. Although FEMA does not prohibit explicitly such arrangement, these look like round about way of moving money and can be investigated.",
"title": ""
},
{
"docid": "570639",
"text": "\"Transferring the money or keeping it in US does has no effect on taxes. Your residency status has. Assuming you are Resident Alien in US for tax purpose and have paid the taxes to IRS and you are \"\"Non-Resident\"\" Indian for tax purposes in India as you are more than 182 outside India. How would it effect my Tax in US and India If you are \"\"Non-Resident\"\" in India for tax purposes, there is no tax liability of this in India. I have transferred an amount of approx 15-20k$ to Indian Account (not NRE) By RBI regulation, if you are \"\"Non-Resident\"\" then you should get your savings account converted to \"\"NRO\"\". You may not may not choose to open an NRE account. To keep the paper work clear it helps that you open an NRE account in India. Any investment needed ? Where do i need to declare if any ? These are not relevant. Note any income generated in India, i.e. interest in Savings account / FDs / Rent etc; taxes need to be paid in India and declared in US and taxes paid in US as well. There is some relief under DTAA. There are quite a few question on this site that will help you clarify what needs to be done.\"",
"title": ""
},
{
"docid": "429271",
"text": "What is the best and most economical way for me to pay the loan EMIs directly? (whether from a Singapore account or a NRE/NRO account) It is advisable to have it via the NRE account as this would be easier. If you already have funds in NRO account, you can use that before you use the funds from NRE account. For all expenses I make in India (e.g shopping, general expenses in India visits) what account should I be using, ideally? Is the route to transfer into NRE then NRO and then withdraw from NRO? Whatever is convenient. Both are fine. If I plan to make any investments in SIPs/Stock markets, should I link my NRE account with a demat account and directly use that? If I sell the shares will the earnings come back into NRO or NRE? You need to open a DEMAT PINS Account and link it to NRE account. You are sell and repatriate the funds without any issue from PINS account. Related question Indian Demat account",
"title": ""
},
{
"docid": "260889",
"text": "As NRI/PIO (Non-Resident Indian/Person of Indian Origin), the overseas income and transfers in foreign currency are exempt from Indian income taxes. However, the account in India has to be designated NRE or FCNR. There are three kind of accounts that an NRI can maintain Interest earned in NRE and FCNR accounts is exempt from income taxes. Interest earned in NRO accounts is not exempt from income taxes, in fact banks would withhold about 30% of interest (TDS). The exact tax liability would depend upon income generated in India and TDS could be applied towards that liability when the tax returns are filed. There are other implications also of designating the account as NRE or NRO. NRE accounts can only be funded via inward remittance of permitted foreign currency e.g. deposit USD/GBP. So proceeds like rental income, pension etc. that are generated in INR within India can't be deposited in this account. The money deposited in NRE account can grow tax free and can be converted back in any foreign currency freely. On the other hand NRO accounts can be funded through both inward remittance of permitted foreign currency or local income e.g. rental, pension etc. All the amount in this account is treated as Indian originated INR (even if remitted in foreign currency) and thus is taxed as any other bank account. The amount in this account is subject to the annual cap of convertibility of USD 1 million. Both NRE and NRO accounts are maintained in INR and can be Saving and Term Deposit. Any remittance made to these accounts in any foreign currency is converted to INR at the time of deposit and is maintained in INR. FCNR account are held in foreign currency and can only be Term Deposit. Official definitions: Accounts for Non Resident Indians (NRIs) and Persons of Indian Origin (PIOs)",
"title": ""
},
{
"docid": "468462",
"text": "Your bank will gladly help you convert your Indian savings accounts into NRO savings accounts. You cannot change these accounts into NRE accounts directly; NRE accounts are supposed to be funded via deposits made from foreign currency accounts. Under the liberalized schemes available now, you can transfer the money in your regular savings account into your account abroad, converting it into foreign currency, if you (and your CA) provide proof to your bank (and the Reserve Bank of India) that you have paid all applicable taxes on the money in your savings account. And then you can transfer it all back into your NRE account. Perhaps you can combine these two steps into a single one, thereby putting the money in your regular savings account into an NRE account in one step, but I am sure that there will be lots of fees involved (e.g. you might get whacked by commissions, as well as the exchange rate differential as if you converted Indian rupees to US dollars, say, and then converted the dollars back to rupees) just as if you did the two-step conversion. There are no taxes involved in moving your own money into different accounts but there can be lots of fees and service charges.",
"title": ""
},
{
"docid": "271415",
"text": "As an NRI, you can't hold a regular savings account. It should have been converted to NRO. Option 1: Open NRE account : Since I am relocating permanently this might not be good option for me as converting This is the best Option as funds into NRE are not taxable in India. The provides a clean paper trail so that if there are any tax queries, you can answer them easily. You can open a Rupee NRE account, move the funds. On return move the funds into Normal Savings account and close the NRE account. This is not much of hassle. Option 2: Create NRO account: There would be taxes on the interest earned of the funds. But I am not sure of this, since I will have been moved to India permanently would I need to still pay taxes on the interest earned while I am in India? Any interest in NRO or normal savings account is taxable in India. There is no exemption. Option 3: I can transfer my funds directly to my account in India but I believe I would have to pay tax on the the funds that I transfer and that would be double taxation. Which I think would be the worst option for me. Please correct me if I am wrong. This is incorrect. Any earnings outside of India when your status is NRI, is not taxable in India. Opening an NRE account provides proper paper trail of funds. As an NRI one cannot hold normal savings account. This should have been converted into an NRO account. Although there is no penalty prescribed, its violation of FEMA regulation. I also hope you were declaring any income in India, i.e. interest etc on savings and filing returns accordingly. Option 4: I can transfer the funds to my direct relatives account. I still believe there would be tax to be paid on the interest earned of the amount. You can transfer it to your parents / siblings / etc. This would come under gift tax purview and would not be taxable. They can then gift this back to you. However such transactions would appear to be evading regulations and may come under scrutiny. Interest on Savings account is taxable. So best is go with Option 1. No hassle. Else go with Option 3, but ensure that you have all the paperwork kept handy for next 7 years.",
"title": ""
},
{
"docid": "232043",
"text": "Is it liable for taxation in India? Taxation does not depend on whether to transfer money to India or keep it in GCC. It depends on your tax status. In a given Financial year; 1st April to 31st March, if you are outside of India for more than 182 days, your are Non-Resident Indian, NRI for tax purposes. If you are NRI, income earned outside of India is not taxable in India [even if you transfer the funds to India]. If you are not an NRI, you income in GCC will be taxable in India [Even if you keep the money in GCC]. We both send our salary into a friends account in India and then transfer an amount to our own accounts This is an incorrect practise, If you are NRI, you should not be holding a Savings account, it should be converted into NRO and you can if you want open an NRE account. For your friend where you are transferring money, if there is an income tax audit, there would be quite a few questions asked and your friend has to establish and keep records that this is not GIFT, but more of a convenience agreement.",
"title": ""
},
{
"docid": "483081",
"text": "1.What are the tax implications - income tax, gift tax, wealth tax etc. for the money credited in the NRO Account? As the funds are transferred by your wife to you, there is NO Income. Hence Income Tax rules don't apply. It would be treated as GIFT and come uder Gift Act. As per gift Act, one can transfer unlimited amount between close releatives. The defination of close relative as per Income Tax includes parents, spouse, siblings etc. The interest you earn in NRO account is taxable in India. 2.Can I transfer this money to my parents and would that attract any tax?. I understand my parents will have bear any tax based on income they earn on my transfer... Are there any tax implications for me? You can transfer this money to your parents. This will not be taxable to you. It will not be taxable to your parents as its Gift. Any income earned by your parents on this will ofcourse be taxable. 3.Can I move this money to NRE account and what is the process for that and how easy it is? Its best if you had your wife send funds into NRE account. Direct transfer as much as know is not allowed. Having said that, it is possible to transfer funds out of India via proper paperwork, there is also a limit [quite large] on the amount that can be transferred a year. Get a CA to help you with the paperwork.",
"title": ""
},
{
"docid": "193842",
"text": "You would need to pay tax on the 10% gain. Was this money loaned from your NRE account? Is there paperwork to show that there was this loan given? If yes then it would be easy to get this back into NRE account. Once in NRE account you can move this back to US without any issue. If not, then you can get this into NRO account. From NRO account you would need to consult a CA to do some paperwork [essentially certifying that you have paid all taxes due] so that funds can be remitted outside. Edit: Looks like you have completed all formalities. A credit to NRE Account can only happen from funds outside of India. However a credit from India into NRE account can happen under some circumstances, like Loan give and received back. You would need a CA in India to help you complete the formalities. The tax is due in India as this was due to gain in India. As you are US resident for tax purposes, and US taxes global income, this is taxable in US as well. You can claim relief in US to the extent of taxes paid in India. India and US have DTAA.",
"title": ""
},
{
"docid": "355796",
"text": "Can we wire transfer money from my NRE account to USA checking account? Yes you can Is there any restrictions for transferring money? Nothing in India Hopefully someone else will answer the US side of questions.",
"title": ""
},
{
"docid": "452384",
"text": "Can she send money to me in India through their NRI account? She can transfer the money to her NRE account and then to your Savings Account. Alternatively she can also transfer money directly to your savings account. There is no tax for this transaction in India as it is gift and exempt under gift tax act. If the amounts are large [run in quite a few tens of lacs], have some paperwork showing this as Gift. You can transfer this to son or doing anything you like with it.",
"title": ""
},
{
"docid": "585947",
"text": "Legally if you are NRI for tax purposes, then you are required to convert all your Savings Account into NRO accounts. For tax purposes it be advisable to open an NRE account. Depending on the Banks policy you can convert the account into NRO by submitted a scanned copy of passport along with the Visa page. You can transfer money from US to any Account in India [Savings/Current/NRO/NRE] using xoom or any other remittance services remit2india, money2india etc.",
"title": ""
},
{
"docid": "9084",
"text": "You can open a NRE account or a NRO account online before you leave the US and transfer the bulk of your money into it. After returning to India, your tax status will be RNOR (Resident but Not Ordinarily Resident) and you can keep the NRE and NRO accounts for several years (three?) and can do whatever you like with the money in them: transfer the money to ordinary (resident) savings accounts, or reconvert back to US dollars for payment of any outstanding bills (e.g. credit card bills) or US taxes for 2017 etc. Don't forget to close your US bank account before you leave. Many banks allow opening of NRE and NRO accounts on-line, though some paperwork needs to be sent in (e.g. copies of passport pages, signature cards etc). In most cases, one month is more than enough time to complete these formalities.",
"title": ""
},
{
"docid": "448689",
"text": "\"For the financial year 1 April 2014 to 31 March 2015, as you have [or will be] spent more than 182 days outside India, you would be treated as \"\"Non-Resident\"\" [NRI] for tax purposes. If you are NRI Show my Kuwaiti Income in my Income Tax Return? Pay any tax on the money that I am sending to savings bank accounts in India You need not Pay Tax on your income outside India. i.e. there is no tax obligation created. It cannot be declared in Tax Returns. However any interest you earn on the money deposited in India would be subject to taxes. Will my wife have to show the income and/or pay the income tax on the money that I am sending to her savings bank accounts? There is no Income to you wife [Income is something you earn] and hence its out of scope from Income Tax act. It would fall under gift tax rules. As per Gift Tax one can transfer unlimited funds between close relatives. Hence there is No tax. It would be better if you open an NRO/NRE account and transfer funds into that account\"",
"title": ""
}
] |
157906
|
Ruth Negga has been nominated for an Academy Award for Best Actress.
|
[
{
"docid": "Ruth_Negga",
"text": "Ruth Negga ( -LSB- ˈneɪgə -RSB- born 7 January 1982 ) is an Ethiopian born Irish actress , who has appeared in the films Capital Letters ( 2004 ) ( also released as Trafficked in some countries ) , Isolation ( 2005 ) , Breakfast on Pluto ( 2005 ) and Warcraft ( 2016 ) . She has also played roles in television , such as in the BBC 's mini-series Criminal Justice , RTÉ 's Love/Hate , E4 's Misfits , and ABC 's Marvel 's Agents of S.H.I.E.L.D. . In 2016 , she began a starring role as Tulip O'Hare in AMC 's Preacher . For her portrayal of Mildred Loving in Loving ( 2016 ) , Negga was nominated for an Academy Award for Best Actress , Golden Globe Award for Best Actress in a Motion Picture - Drama , Independent Spirit Award for Best Female Lead and Critics ' Choice Movie Award for Best Actress , as well as the BAFTA Rising Star Award .",
"title": ""
}
] |
[
{
"docid": "Iona_(film)",
"text": "Iona is a 2015 drama film directed by Scott Graham and starring Ruth Negga . It is set on the Scottish island of Iona . The film earned Ruth Negga a nomination for Best Actress at the 2016 British Academy Scotland Awards .",
"title": ""
},
{
"docid": "Loving_(2016_film)",
"text": "Loving is a 2016 American historical drama film which tells the story of Richard and Mildred Loving , the plaintiffs in the 1967 U.S. Supreme Court decision Loving v. Virginia , which invalidated state laws prohibiting interracial marriage . The film was produced by Big Beach and Raindog Films , and distributed by Focus Features . The film takes inspiration from The Loving Story ( 2011 ) by Nancy Buirski , a documentary which follows the Lovings and their landmark case . The film was directed by Jeff Nichols , who also wrote the screenplay . Joel Edgerton stars as Richard Loving , with Ruth Negga co-starring as Mildred Loving . Marton Csokas , Nick Kroll , and Michael Shannon are all featured in supporting roles . Principal photography began in Richmond , Virginia on September 16 , 2015 and ended on November 19 . The locations used for Loving were mainly based in Richmond , also in King and Queen County , Caroline County , Central Point , and Bowling Green . Loving began a limited release in the United States on November 4 , 2016 , before a wide release on November 11 , 2016 . The film received positive reviews , and was named one of the best films of 2016 by several media outlets . The film was selected to compete for the Palme d'Or at the 2016 Cannes Film Festival , and was nominated for numerous awards , including a Golden Globe nomination for Best Actor for Edgerton and Academy Award and Golden Globe nominations for Negga .",
"title": ""
},
{
"docid": "List_of_actors_nominated_for_Academy_Awards_for_foreign_language_performances",
"text": "The Academy of Motion Picture Arts and Sciences has given Academy Awards to actors and actresses for foreign language ( non-English ) performances in films , with the first award given in 1961 . For an actor or actress to be eligible for any of the Academy Awards for Best Actor , Best Actress , Best Supporting Actor , or Best Supporting Actress for a foreign language performance in a film produced outside the United States , the film must have been commercially released in Los Angeles County and have English subtitles with the theatrical release . In 1962 , Sophia Loren became the first actor to win an Oscar for a foreign-language performance . , 33 actors and actresses have been nominated for Academy Awards for foreign language performances . Eight of these actors and actresses have received Academy Awards for their performances . Five actors have won for a performance that was mostly or solely spoken in a foreign language : Sophia Loren for Two Women ( Italian ) , Robert De Niro for The Godfather Part II ( Italian ) , Roberto Benigni for Life Is Beautiful ( Italian ) , Benicio del Toro for Traffic ( Spanish ) , and Marion Cotillard for La Vie en Rose ( French ) . Two actors have won for performances mostly spoken in English ( Penélope Cruz for her English and Spanish-language performance in Vicky Cristina Barcelona and Christoph Waltz for Inglourious Basterds ( English , German and French ) . Six actors have had multiple Academy Award nominations for foreign-language performances : Marcello Mastroianni ( three Best Actor nominations for Italian-language performances ) , Sophia Loren ( one Academy Award for Best Actress for Two Women and another Best Actress nomination for Marriage Italian-Style , both for Italian-language performances ) , Liv Ullmann ( two Best Actress nominations for Swedish-language performances ) , Isabelle Adjani ( two Best Actress nominations for French-language performances ) , Javier Bardem ( two Best Actor nominations for Spanish-language performances ) and Marion Cotillard ( one Academy Award for Best Actress for La Vie en Rose and another Best Actress nomination for Two Days , One Night , both for French-language performances ) . Sophia Loren and Marion Cotillard are the only actresses to win an Academy Award for Best Actress for foreign language performances , Italian and French , respectively . Cotillard is the only actor to receive two Oscar nominations for foreign films without having her films nominated for an Academy Award for Best Foreign Language Film . She is also the only actor to be nominated for a Belgian film ( `` Two Days , One Night '' ) . Roberto Benigni is the only actor to win an Academy Award for Best Actor for a foreign language performance .",
"title": ""
},
{
"docid": "List_of_actors_nominated_for_two_Academy_Awards_in_the_same_year",
"text": "The Academy of Motion Picture Arts and Sciences has had occurrences of actors and actresses nominated for two different Academy Awards in acting categories in a single year , with the first instance in 1938 . Provided that they receive enough votes from the Academy in both categories to earn a nomination , there are no restrictions on actors being nominated for the Academy Award for Best Actor and Best Supporting Actor or actresses being nominated for the Academy Award for Best Actress and Best Supporting Actress in any given year . The sole rule with regard to multiple nominations is that an actor or actress can not receive multiple nominations for the same performance . This rule was introduced in 1944 after Barry Fitzgerald received a Best Actor nomination and a Best Supporting Actor nomination for his performance in Going My Way . As of 2015 , 11 actors and actresses have been nominated for two different Academy Awards in the same year . The first of these actors and actresses was Fay Bainter , who received nominations for her performances in White Banners and Jezebel at the 11th Academy Awards . The most recent occurrence was during the 80th Academy Awards , in which Cate Blanchett received nominations for Elizabeth : The Golden Age and I 'm Not There . Seven of these actors and actresses received an Academy Award in one of the categories they were nominated in , and none have won two Academy Awards in the same year . Four did not receive an Academy Award in either category : Sigourney Weaver ( nominations for Gorillas in the Mist and Working Girl ) , Emma Thompson ( nominations for The Remains of the Day and In the Name of the Father ) , Julianne Moore ( nominations for Far from Heaven and The Hours ) , and Cate Blanchett ( nominations for Elizabeth : The Golden Age and I 'm Not There ) .",
"title": ""
},
{
"docid": "List_of_Australian_Academy_Award_winners_and_nominees",
"text": "This list details Australian people working in the film industry who have been nominated for , or won , Academy Awards ( also known as Oscars ) . These awards honour outstanding achievements in theatrically released motion pictures and were first presented by the United States Academy of Motion Picture Arts and Sciences ( AMPAS ) in 1929 . As of 2016 , a total of 43 awards from 154 nominations have been won by Australians . Additionally , awards for Scientific and Engineering achievements have been given to Australians four times . Art director and costume designer Catherine Martin has received more awards than any other Australian with four wins from six nominations in the Best Costume Design and Best Production Design categories . Cate Blanchett is the most nominated individual in this list with seven nominations , which resulted in a win for Best Leading Actress and Best Supporting Actress . Peter Weir has received five nominations in the Best Picture , Best Director and Best Original Screenplay categories without a win . May Robson was the first Australian-born person to receive an Oscar nomination for Best Actress in 1933 for Lady for a Day . In 1942 , Ken G. Hall became the first Australian to win an Academy Award for his documentary Kokoda Front Line ! in the Best Documentary category . Suzanne Baker was the first Australian woman to win an Oscar , which was given to her in 1977 for Best Animated Short for Leisure . Cate Blanchett was the first Australian actor to win more than one award in the acting categories . Peter Finch was the first actor to be awarded an Oscar posthumously , winning the Academy Award for Best Actor for his performance in Network in 1976 . The only other acting Oscar awarded posthumously was to fellow Australian Heath Ledger 32 years later when his performance in The Dark Knight earned him the Academy Award for Best Supporting Actor in 2008 . Australians have been nominated at least once in all categories except Best Live Action Short Film . The Oscar for Best Costume Design has been the most successful category for Australians with seven wins from 17 nominations . The Academy Awards for Best Director and Best Documentary ( Short Subject ) are the only categories in this list where Australians have been nominated without winning .",
"title": ""
},
{
"docid": "Academy_Award_for_Best_Actress",
"text": "The Academy Award for Best Actress is an award presented annually by the Academy of Motion Picture Arts and Sciences ( AMPAS ) . It is given in honor of an actress who has delivered an outstanding performance in a leading role while working within the film industry . The 1st Academy Awards ceremony was held in 1929 with Janet Gaynor receiving the award for her roles in 7th Heaven , Street Angel , and Sunrise . Currently , nominees are determined by single transferable vote within the actors branch of AMPAS ; winners are selected by a plurality vote from the entire eligible voting members of the Academy . In the first three years of the awards , actresses were nominated as the best in their categories . At that time , all of their work during the qualifying period ( as many as three films , in some cases ) was listed after the award . However , during the 3rd ceremony held in 1930 , only one of those films was cited in each winner 's final award , even though each of the acting winners had two films following their names on the ballots . The following year , this unwieldy and confusing system was replaced by the current system in which an actress is nominated for a specific performance in a single film . Starting with the 9th ceremony held in 1937 , the category was officially limited to five nominations per year . One actress has been nominated posthumously , Jeanne Eagels . Only three film characters have been nominated more than once in this category . Elizabeth I of England ( two times by Cate Blanchett ) , Leslie Crosbie in The Letter , and Esther Blodgett in A Star is Born . Six women on the list have received an Honorary Academy Award for their acting ; they are Greta Garbo , Barbara Stanwyck , Mary Pickford , Deborah Kerr , Gena Rowlands , and Sophia Loren . Since its inception , the award has been given to 74 actresses . Katharine Hepburn has won the most awards in this category , with four Oscars . Meryl Streep , who has a total of 20 Oscar nominations ( three wins ) , has been nominated in this category on 16 occasions , resulting in two awards . As of the 2017 ceremony , Emma Stone is the most recent winner in this category for her role as Mia Dolan in La La Land .",
"title": ""
},
{
"docid": "Ruth_Wilson",
"text": "Ruth Wilson ( born 13 January 1982 ) is an English actress . She is known for her performances in Suburban Shootout ( 2005 ) , Jane Eyre ( 2006 ) , and as Alice Morgan in the BBC TV psychological crime drama Luther since 2010 . She has also appeared in Anna Karenina ( 2012 ) , The Lone Ranger ( 2013 ) , Saving Mr. Banks ( 2013 ) and Suite Française ( 2015 ) . In 2014 , she had a voice role in the film Locke and has a starring role in the Showtime series The Affair . Wilson is a two-time Olivier Award winner . She has won a Golden Globe for her role in The Affair and received nominations for a British Academy Television Award for Best Actress and a Golden Globe Award for Best Actress -- Television Series Drama for her role in Jane Eyre .",
"title": ""
},
{
"docid": "List_of_awards_and_nominations_received_by_Amy_Adams",
"text": "Amy Adams is an American actress who has received various awards and nominations , including two Golden Globe Awards , four Critics ' Choice Awards and a Screen Actors Guild Award . Additionally , she has been nominated for five Academy Awards and six BAFTA Awards . In 2017 , Adams received a star on the Hollywood Walk of Fame for her contributions to the motion picture industry . Adams ' breakthrough role in the 2005 acclaimed independent comedy-drama Junebug earned her an Academy Award nomination for Best Supporting Actress and won her the Critics ' Choice Movie Award for Best Supporting Actress and the Independent Spirit Award for Best Supporting Actress . In 2007 , she starred in Walt Disney Pictures ' romantic musical Enchanted , for which she won the Saturn Award for Best Actress and was nominated for the Golden Globe Award for Best Actress -- Motion Picture Comedy or Musical , the Critics ' Choice Award for Best Actress and three MTV Movie Awards . Adams ' performances in the critically acclaimed dramas Doubt , ( 2008 ) , The Fighter ( 2010 ) and The Master ( 2012 ) garnered her several accolades , including nominations from the Oscar , Hollywood Foreign Press , BAFTA , SAG and Critics ' Choice award ceremonies . Since 2013 , Adams has received two People 's Choice and four Teen Choice Awards nominations for playing the DC Comics character Lois Lane in the DC Extended Universe . For her performance as a con artist in the 2013 crime comedy-drama American Hustle , Adams won the Golden Globe Award for Best Actress -- Motion Picture Comedy or Musical and the Critics ' Choice Movie Award for Best Actress in a Comedy and received her first Academy Award for Best Actress nomination . The following year , she starred as Margaret Keane in the autobiographical drama Big Eyes , which won her a second consecutive Golden Globe Award for Best Actress -- Motion Picture Comedy or Musical , making her the fourth actress to achieve this feat . She also received her second nomination for the BAFTA Award for Best Actress in a Leading Role for her portrayal . In 2016 , Adams won the National Board of Review Award for Best Actress and was nominated for the Golden Globe Award , the SAG Award , the BAFTA Award and the Critic 's Choice Award for Best Actress for playing a linguist in the science fiction film Arrival .",
"title": ""
},
{
"docid": "List_of_awards_and_nominations_received_by_Saoirse_Ronan",
"text": "Irish-American actress Saoirse Ronan has been honored with numerous awards and nominations . She came to international prominence in 2007 with her co-starring role in Atonement , for which she received nominations for the Academy Award for Best Supporting Actress , the BAFTA Award for Best Actress in a Supporting Role and the Golden Globe Award for Best Supporting Actress , making her one of the youngest actresses to receive an Oscar nomination in this category . In 2015 , Ronan starred in the romantic-drama film Brooklyn , for which she received nominations for the Academy Award for Best Actress , the BAFTA Award for Best Actress in a Leading Role , the Golden Globe Award for Best Actress -- Motion Picture Drama and the Screen Actors Guild Award for Outstanding Performance by a Female Actor in a Leading Role . Ronan also is noted for being the second-youngest actress to ever get two Oscar nominations , getting her second at 21 , behind Angela Lansbury , who got her second at age 20 .",
"title": ""
},
{
"docid": "List_of_awards_and_nominations_received_by_Marion_Cotillard",
"text": "The following a list of awards and nominations received by French actress Marion Cotillard . For her portrayal of the title role in the French film Lisa ( 2001 ) , Cotillard was the winner of Verona Love Screens Film Festival award for Best Actress . She was the winner of Newport Beach Film Festival jury award for Best Actress Drama for Love Me If You Dare in 2004 . She has been nominated for numerous awards , including César Award for Most Promising Actress for Taxi ( 1998 ) and Pretty Things ( 2001 ) , and a nod for European Film Award for Best Actress for La Vie en Rose ( 2007 ) . Cotillard won a César Award for Best Supporting Actress for A Very Long Engagement ( 2004 ) . She also won an Academy Award for Best Actress , a Golden Globe Award for Best Actress -- Motion Picture Musical or Comedy , a BAFTA Award for Best Actress in a Leading Role , a Satellite Award for Best Actress -- Motion Picture Drama and a César Award for Best Actress for her portrayal of Édith Piaf in La Vie en Rose ( 2007 ) . Cotillard and her co-stars of Nine won a Satellite Award for Best Cast -- Motion Picture for their performances in the film . In 2007 , Cotillard received the Academy Award for Best Actress , becoming only the second French cinema actress , after Simone Signoret in 1959 British film Room at the Top , to win this award and the third overall to receive an Academy Award ( Juliette Binoche won the Academy Award for Best Supporting Actress in 1997 for her role in American film The English Patient ) . Cotillard is the first Best Actress winner in a non-English language performance since Sophia Loren 's win in 1961 for Italian film Two Women and also became the first -- and so far only -- winner of an Academy Award for a performance primarily in the French language . In 2010 , Cotillard was nominated for an Golden Globe Award for Best Actress -- Motion Picture Musical or Comedy for Nine ( 2009 ) . Furthermore , in 2012 , Cotillard found herself nominated for her first Drama Golden Globe Award for Best Actress , a second leading actress Screen Actors Guild Award nomination , a second leading actress César Award nomination , a Lumières Award nomination and a Globe de Cristal Award , and Étoile d'Or award for her performance as Stéphanie in Rust and Bone . In 2013 , she was named Hasty Pudding Theatricals ' Woman of the Year by Harvard 's students . She has also won a Los Angeles Film Critics Association Award for La Vie en Rose and a New York Film Critics Circle Award and a National Society of Film Critics Award for Best Actress for The Immigrant and Two Days , One Night , achieving the critics ' awards trifecta . Cotillard and Isabelle Adjani are the only French actresses to win the New York Film Critics Circle Award for Best Actress . Adjani won in 1975 for The Story of Adele H. , while Cotillard was awarded for her performances in The Immigrant and Two Days , One Night in 2014 . In 2015 , Cotillard was nominated for her second Academy Award for Best Actress for her performance in the Belgian film Two Days , One Night , becoming the second French actress to receive two Oscar nominations for French-language films after Isabelle Adjani in 1990 , and the fourth actress overall to receive two Academy Award nominations for Best Actress for foreign language films , following Sophia Loren , Liv Ullmann and Adjani . On July 14 , 2016 , Cotillard received France 's highest honour - she was named a Chevalier ( Knight ) of the Légion d'Honneur ( Legion of Honor ) .",
"title": ""
},
{
"docid": "List_of_actors_with_two_or_more_Academy_Award_nominations_in_acting_categories",
"text": "The Academy of Motion Picture Arts and Sciences ( AMPAS ) have presented their annual Academy Awards , commonly known as the Oscars , since 1929 . The Academy Awards for Best Actor and Best Actress have been presented since the 1st ceremony , while the awards for Best Supporting Actor and Best Supporting Actress have been presented since the 9th ceremony . Of the 908 Academy Award nominees in an acting category , a total of 332 have received two or more acting nominations ( 162 men , 170 women ) . Meryl Streep is the most nominated performer in the acting categories , with 20 nominations between 1978 and 2016 . As well as the record for total number of acting nominations , Streep holds the record for most Best Actress nominations with 16 , ahead of Katharine Hepburn with 12 and Bette Davis with 10 . Jack Nicholson is the most nominated male performer in the acting categories with 12 nominations . The most Best Actor nominations is nine , for both Spencer Tracy and Laurence Olivier ( Nicholson has eight ) . Thelma Ritter is the most nominated in the Best Supporting Actress category with six , while in the Best Supporting Actor category six actors have each received four nominations , they are Walter Brennan , Claude Rains , Arthur Kennedy , Jack Nicholson , Robert Duvall and Jeff Bridges . The record for most nominations in the acting categories without a win , is eight by Peter O'Toole , followed by Richard Burton with seven , and Deborah Kerr , Thelma Ritter and Glenn Close all with six . Both O'Toole and Kerr did receive the Academy 's Honorary Oscar .",
"title": ""
},
{
"docid": "List_of_actors_with_two_or_more_Academy_Awards_in_acting_categories",
"text": "The Academy of Motion Picture Arts and Sciences has given Academy Awards to actors and actresses for their performances in films since its inception . Throughout the history of the Academy Awards , there have been actors and actresses who have received multiple Academy Awards for Best Actor , Best Actress , Best Supporting Actor , or Best Supporting Actress . The only restriction is that actors can not receive multiple nominations for the same performance . This rule was implemented after Barry Fitzgerald received a Best Actor and a Best Supporting Actor nomination for his performance in Going My Way . , 40 actors and actresses have received two or more Academy Awards in acting categories . Six of these actors and actresses have received three or more acting Academy Awards : Katharine Hepburn ( four Best Actress awards ) , Ingrid Bergman ( two Best Actress awards and one Best Supporting Actress award ) , Walter Brennan ( three Best Supporting Actor awards ) , Jack Nicholson ( two Best Actor awards and one Best Supporting Actor award ) , Meryl Streep ( two Best Actress awards and one Best Supporting Actress award ) , and Daniel Day-Lewis ( three Best Actor awards ) . Brennan was the first to receive three or more Academy Awards in 1940 , followed by Hepburn in 1968 , Bergman in 1974 , Nicholson in 1997 , Streep in 2011 , and most recently Day-Lewis in 2012 . Of the six , only Nicholson , Streep , and Day-Lewis are still living .",
"title": ""
},
{
"docid": "List_of_awards_and_nominations_received_by_Isabelle_Huppert",
"text": "The following is a list of awards and nominations received by actress Isabelle Huppert . For her work in cinema , she has won two César Awards , a BAFTA Award , a Golden Globe Award , and been nominated for the Academy Award for Best Actress . She is the most nominated actress for the César Award with 16 nominations . She has also twice won the Cannes Film Festival Award for Best Actress , twice won the Volpi Cup for Best Actress at Venice , and is a two-time winner of the European Film Award for Best Actress . Huppert is the most nominated actress for the Molière Award , with 7 nominations . In 2017 , she was awarded the Honorary Molière . Huppert was made Chevalier of the Ordre national du Mérite in 1994 and was promoted to Officier in 2005 . She was made a Chevalier of the Legion of Honour in 1999 and was promoted to Officer in 2009 .",
"title": ""
},
{
"docid": "List_of_awards_and_nominations_received_by_Emma_Stone",
"text": "As of 2017 , American actress Emma Stone has won 31 awards from 93 nominations and was named runner-up for five of those nominations . She has been nominated for an AACTA International Award , two Academy Awards , and three British Academy Film Awards , winning one from the last of these . She has also won a Golden Globe Award , two MTV Movie & TV Awards , a People 's Choice Award , three Screen Actors Guild Awards , and three Teen Choice Awards . Stone began her acting career with a role in a theater production of The Wind in the Willows in 2000 . She won the Young Hollywood Award for Exciting New Face for her debut film -- the teen comedy Superbad ( 2007 ) , which had her play a high school student . For the role of a zombie apocalypse survivor and a con-artist in the horror comedy film Zombieland , she received a nomination for the Teen Choice Award for Choice Movie Actress -- Comedy . At the 2010 Scream Awards , she garnered Best Ensemble award and Best Horror Actress nomination . She had her breakthrough with her first leading role in Easy A ( 2010 ) , a teen comedy which saw her play a high school student perceived to be sexually promiscuous . She was nominated for BAFTA Rising Star Award and Golden Globe Award for Best Actress in a Musical or Comedy , and won the MTV Movie Award for Best Comedic Performance . Her role was also included in TIME list of `` Top 10 Everything of 2010 '' . Stone played a supporting role in the 2011 romantic comedy-drama Crazy , Stupid , Love , for which she was awarded the Teen Choice Award for Choice Movie Actress -- Comedy . Further success came with the critically acclaimed drama The Help ( 2011 ) , in which she played an aspiring writer learning about the lives of the African-American maids . The film won Best Ensemble Cast from Women Film Critics Circle , Broadcast Film Critics Association and Screen Actors Guild Awards ; she was nominated for the Teen Choice Awards for Choice Movie Actress -- Drama . For portraying Gwen Stacy in The Amazing Spider-Man ( 2012 ) , she was nominated for the People 's Choice Award for Favorite Movie Actress and the Teen Choice Award for Choice Female Movie Star of the Summer . The role of a recovering drug addict in the black comedy-drama Birdman ( 2014 ) earned her nominations for the Academy Award , BAFTA Award , Golden Globe Award and Screen Actors Guild Award for Best Supporting Actress , and MTV Movie Award for Best Performance . She also won the Boston Society of Film Critics Award for Best Supporting Actress for the film . Stone won the Academy Award for Best Actress , BAFTA Award , Golden Globe Award and Volpi Cup for Best Actress for playing an aspiring actress in the musical La La Land ( 2016 ) .",
"title": ""
},
{
"docid": "The_Actress",
"text": "The Actress is an 1953 American comedy-drama film based on Ruth Gordon 's autobiographical play Years Ago . Gordon herself wrote the screenplay . The film was directed by George Cukor and stars Jean Simmons , Spencer Tracy , Teresa Wright , and Anthony Perkins in his film debut . The film basically is a series of vignettes involving Ruth , her parents , her best friends , and the college boy romantically pursuing her . Although Gordon did in fact become an accomplished Academy Award-winning actress and a successful writer , the film ends without the audience seeing Gordon achieve her goals . The film was nominated for an Oscar for Best Black-and-White Costume Design . Tracy won the Golden Globe Award for Best Motion Picture Actor in a Drama and was nominated for a BAFTA as Best Foreign Actor . Simmons was named Best Actress by the National Board of Review , and Gordon 's screenplay was nominated Best Written American Comedy by the Writers Guild of America , despite being far more dramatic than comedic .",
"title": ""
},
{
"docid": "30th_Academy_Awards",
"text": "The 30th Academy Awards ceremony was held on March 26 , 1958 , to honor the best films of 1957 . The Oscar for Writing Based on Material From Another Medium was awarded to Pierre Boulle for The Bridge on the River Kwai , despite the fact that he did not know English . The actual writers , Carl Foreman and Michael Wilson were blacklisted at the time and did not receive screen credit for their work . Foreman and Wilson have since been acknowledged by the Academy for their contributions . Joanne Woodward 's win for Best Actress for her triple role as Eve White , Eve Black , and Jane in The Three Faces of Eve made the film the last to win Best Actress without being nominated for other awards until 31 years later , when Jodie Foster won Best Actress for her role in The Accused , the film 's only nomination . Peyton Place tied the record for the most nominations without a win ( 9 ) set by The Little Foxes ( 1941 ) . This record would stand until 1977 when The Turning Point received 11 nominations without a win , which is the record to date ( The Color Purple tied the record in 1985 ) . Peyton Place also set the record for most unsuccessful acting nominations with five ; this record has been tied once , by Tom Jones at the 36th Academy Awards . This was the first time all five Best Picture nominations were nominated for Best Director as well .",
"title": ""
},
{
"docid": "BAFTA_Award_for_Best_Actress_in_a_Supporting_Role",
"text": "Best Actress in a Supporting Role is a British Academy Film Award presented annually by the British Academy of Film and Television Arts ( BAFTA ) to recognize an actress who has delivered an outstanding supporting performance in a film . This award began in 1968 and had four nominees until 1999 when expanded to five nominees . There has been one tie in this category . No award was given for the years 1980 or 1981 . † -- indicates the performance also won the Academy Award ‡ -- indicates the performance was also nominated for the Academy Award",
"title": ""
},
{
"docid": "Ruth_Hussey",
"text": "Ruth Carol Hussey ( October 30 , 1911 -- April 19 , 2005 ) was an American actress best known for her Academy Award-nominated role as photographer Elizabeth Imbrie in The Philadelphia Story .",
"title": ""
},
{
"docid": "BET_Award_for_Best_Actor_&_Actress",
"text": "The BET Awards for Best Actor & Actress is a are awarded to actors and actresses from both television and film . Some nominees have been nominated based on their performances in multiple bodies of work within the eligibility period . 8 Academy Award-Winning Actors/Actress ( Jennifer Hudson , Cuba Gooding Jr. , Forest Whitaker , Denzel Washington , Morgan Freeman , Mo'Nique , Jamie Foxx & Halle Berry ) , and 11 Academy Award nominated Actors/Actress ( Gabourey Sidibe , Queen Latifah , Taraji P. Henson , Samuel L. Jackson , Terrence Howard , Alfre Woodard , Angela Bassett , Don Cheadle , Will Smith , Viola Davis & Eddie Murphy ) have earned BET Best Actor & Actress nominations and/or wins . This list also has 10 singer/rappers-turned-actors ( Beyoncé , Aaliyah , Common , Queen Latifah , Jennifer Hudson , Will Smith , Ludacris , Jill Scott , Jamal Woolard , Mos Def , Janelle Monae & Yazz the Greatest ) nominated in these categories .",
"title": ""
},
{
"docid": "List_of_films_with_all_four_Academy_Award_acting_nominations",
"text": "This is a list of films with performances that have been nominated in all of the Academy Award acting categories . The Academy of Motion Picture Arts and Sciences annually bestows Academy Awards for acting performances in the following four categories : Best Actor , Best Actress , Best Supporting Actor , and Best Supporting Actress .",
"title": ""
},
{
"docid": "Glenn_Close",
"text": "Glenn Close ( born March 19 , 1947 ) is an American actress , singer and film producer . With an acting career spanning over 40 years , she has been consistently acclaimed for her versatility and is widely regarded as one of the finest actresses of her generation . She has won three Emmy Awards , three Tony Awards , four Golden Globe Awards , and has received six Academy Award nominations . Close began her professional stage career in 1974 in Love for Love , and was mostly a New York stage actress through the rest of the 1970s and early 1980s , appearing in both plays and musicals , including the Broadway productions of Barnum in 1980 and The Real Thing in 1983 , for which she won the Tony Award for Best Actress in a Play . Her film debut was in The World According to Garp ( 1982 ) , which she followed up with supporting roles in The Big Chill ( 1983 ) and The Natural ( 1984 ) ; all three earned her nominations for the Academy Award for Best Supporting Actress . She would later receive nominations for the Academy Award for Best Actress for her performances in Fatal Attraction ( 1987 ) , Dangerous Liaisons ( 1988 ) and Albert Nobbs ( 2011 ) . She won two more Tony Awards in the 1990s , for Death and the Maiden in 1992 and Sunset Boulevard in 1995 , while she won her first Emmy Award for the 1995 TV film Serving in Silence : The Margarethe Cammermeyer Story . She starred as Eleanor of Aquitaine in the 2003 TV film The Lion in Winter , winning a Golden Globe Award . In 2005 , she starred in the drama series The Shield . Then , from 2007 to 2012 , she starred as Patty Hewes in the FX drama series Damages , a role that won her a Golden Globe and two Emmys . She has voiced the character of Mona Simpson in the animated sitcom The Simpsons since 1995 . She returned to Broadway in November 2014 , in a revival of Edward Albee 's A Delicate Balance . Her other films include Jagged Edge ( 1985 ) , Hamlet ( 1990 ) , Reversal of Fortune ( 1990 ) , 101 Dalmatians ( 1996 ) , Paradise Road ( 1997 ) , Air Force One ( 1997 ) , Cookie 's Fortune ( 1999 ) , Heights ( 2005 ) , Guardians of the Galaxy ( 2014 ) and The Girl With All The Gifts ( 2016 ) . Close is a six-time Academy Award nominee , tying the record for being the actress with the most nominations never to have won ( along with Deborah Kerr and Thelma Ritter ) . As of 2016 , Close has more Oscar nominations without a win than any other living actor . In addition , she has been nominated for four Tonys ( three wins ) , fourteen Emmys ( three wins ) , thirteen Golden Globes ( two wins ) , two Drama Desk Awards ( one win ) and eight Screen Actors Guild Awards ( one win ) . She has also won an Obie award and has been nominated for three Grammy Awards and a BAFTA . Close has received a star on the Hollywood Walk of Fame and has been inducted into the American Theater Hall of Fame .",
"title": ""
},
{
"docid": "List_of_awards_and_nominations_received_by_Barbara_Hershey",
"text": "The following is a list of awards and nominations received by Barbara Hershey . Throughout Hershey 's acting career , she has been nominated for an Academy Award for Best Supporting Actress for the 1996 film The Portrait of a Lady , received three Golden Globe nominations and two Primetime Emmy Award nominations . She won a Golden Globe for Best Actress in a Miniseries or TV Film and a Primetime Emmy Award for Outstanding Lead Actress in a Miniseries or Movie for the 1990 TV film A Killing in a Small Town . At the Cannes Film Festival , Hershey became the first actress to receive back-to-back Best Actress awards , winning for Shy People in 1987 and A World Apart in 1988 . In 2010 , a resurgence in her career took place when she co-starred as The Queen in Black Swan . Hershey was nominated for her second BAFTA Award for Best Actress in a Supporting Role ; and along with the cast of the film , was nominated for her first Screen Actors Guild Award for Outstanding Performance by a Cast in a Motion Picture .",
"title": ""
},
{
"docid": "Golden_Globe_Award_for_Best_Supporting_Actress_–_Motion_Picture",
"text": "The Golden Globe Award for Best Supporting Actress -- Motion Picture was first awarded by the Hollywood Foreign Press Association in 1944 for a performance in a motion picture released in the previous year . The formal title has varied since its inception ; since 2005 , the award has officially been called `` Best Performance by an Actress in a Supporting Role in a Motion Picture '' . Notes : '' † '' indicates the winner of the Academy Award . '' ‡ '' indicates a Golden Globe Award-nominee who was nominated for an Academy Award .",
"title": ""
},
{
"docid": "Golden_Globe_Award_for_Best_Actress_in_a_Motion_Picture_–_Drama",
"text": "The Golden Globe Award for Best Actress in a Motion Picture -- Drama was first awarded by the Hollywood Foreign Press Association as a separate category in 1951 . Previously , there was a single award for `` Best Actress in a Motion Picture '' but the splitting allowed for recognition of it and the Best Actress -- Comedy or Musical . The formal title has varied since its inception . In 2005 , it was officially called : `` Best Performance by an Actress in a Motion Picture -- Drama '' . As of 2013 , the wording is `` Best Actress in a Motion Picture -- Drama '' . Notes : '' † '' indicates an Academy Award-winning performance . '' ‡ '' indicates an Academy Award-nomination . '' § '' indicates a Golden Globe Award-winning performance that was not nominated for an Academy Award .",
"title": ""
},
{
"docid": "Nicole_Kidman",
"text": "Nicole Mary Kidman , AC ( born June 20 , 1967 ) is an Australian actress and film producer . Kidman 's breakthrough roles were in the 1989 feature film thriller Dead Calm and television thriller miniseries Bangkok Hilton . Appearing in several films in the early 1990s , she came to worldwide recognition for her performances in the stock-car racing film Days of Thunder ( 1990 ) , the romance-drama Far and Away ( 1992 ) , and the superhero film Batman Forever ( 1995 ) . Other successful films followed in the late 1990s . Her performance in the musical Moulin Rouge ! ( 2001 ) earned her a second Golden Globe Award for Best Actress -- Motion Picture Comedy or Musical and her first nomination for the Academy Award for Best Actress . Kidman 's performance as Virginia Woolf in the drama film The Hours ( 2002 ) received critical acclaim and earned her the Academy Award for Best Actress , the BAFTA Award for Best Actress in a Leading Role , the Golden Globe Award for Best Actress in a Motion Picture -- Drama and the Silver Bear for Best Actress at the Berlin International Film Festival . Kidman 's other notable films include the crime comedy-drama To Die For ( 1995 ) , for which she won her first Golden Globe Award for Best Actress -- Motion Picture Comedy or Musical , the erotic thriller Eyes Wide Shut ( 1999 ) , the horror-thriller The Others ( 2001 ) , the epic war drama film Cold Mountain ( 2003 ) , the drama Dogville ( 2003 ) , the political thriller The Interpreter ( 2005 ) , and the epic historical romantic drama Australia ( 2008 ) . Her performances in the drama Birth ( 2004 ) and the thriller The Paperboy ( 2012 ) earned her Golden Globe nominations for Best Actress and Supporting Actress respectively . Her performance in the 2010 drama Rabbit Hole ( 2010 ) , which she also produced , earned Kidman further accolades , including a third nomination for the Academy Award for Best Actress . In 2012 , she earned her first Primetime Emmy Award nomination for Outstanding Lead Actress in a Miniseries or a Movie for her role in the biopic Hemingway & Gellhorn ( 2012 ) . Kidman 's performance in Lion ( 2016 ) earned her a fourth Academy Award nomination , her first for the Academy Award for Best Supporting Actress . In 2017 , Kidman returned to television , starring in the HBO miniseries Big Little Lies . Kidman has been a Goodwill Ambassador for UNICEF since 1994 and for UNIFEM since 2006 . In 2006 , Kidman was made a Companion in the Order of Australia , and was the highest-paid actress in the motion picture industry for that year . As a result of being born to Australian parents in Hawaii , Kidman has dual citizenship in Australia and the United States . Kidman founded and owns the production company Blossom Films .",
"title": ""
},
{
"docid": "Golden_Globe_Award_for_Best_Actress_–_Motion_Picture_Comedy_or_Musical",
"text": "The Golden Globe Award for Best Actress in a Motion Picture -- Comedy or Musical was first awarded by the Hollywood Foreign Press Association as a separate category in 1951 . Previously , there was a single award for `` Best Actress in a Motion Picture '' but the splitting allowed for recognition of it and the Best Actress -- Drama . The formal title has varied since its inception . In 2005 , it was officially called : `` Best Performance by an Actress in a Motion Picture -- Comedy or Musical '' . As of 2014 , the wording is `` Best Actress in a Motion Picture -- Comedy or Musical '' . Notes : '' † '' indicates an Academy Award-winning performance . '' ‡ '' indicates an Academy Award nomination . '' § '' indicates a Golden Globe Award-winning performance that was not nominated for an Academy Award .",
"title": ""
},
{
"docid": "Laura_Dern",
"text": "Laura Elizabeth Dern ( born February 10 , 1967 ) is an American actress . For her performance in the 1991 film Rambling Rose , she was nominated for the Academy Award for Best Actress , while for her performance in the 2014 film Wild , she was nominated for the Academy Award for Best Supporting Actress . Her other film roles include Mask ( 1985 ) , Smooth Talk ( 1985 ) , Blue Velvet ( 1986 ) , Wild at Heart ( 1990 ) , Jurassic Park ( 1993 ) , Citizen Ruth ( 1996 ) , October Sky ( 1999 ) , I Am Sam ( 2001 ) , Inland Empire ( 2006 ) , The Master ( 2012 ) , The Fault in Our Stars ( 2014 ) , and Star Wars : The Last Jedi ( 2017 ) . Dern won the Golden Globe Award for Best Actress -- Miniseries or Television Film for the 1992 film Afterburn , and guest starred in the 1997 `` Puppy Episode '' of the sitcom Ellen . She went on to win the Golden Globe Award for Best Supporting Actress on Television for her portrayal of Florida Secretary of State Katherine Harris in the 2008 TV film Recount , and the 2012 Golden Globe Award for Best Actress in a Musical or Comedy Series for her role as Amy Jellicoe in HBO 's Enlightened ( 2011 -- 13 ) . She is known for her collaborations with filmmaker David Lynch , having appeared in three of his films and the revival of Twin Peaks .",
"title": ""
},
{
"docid": "Jackie_Appiah",
"text": "Jackie Aygemang Appiah ( born ; 5 December 1983 ) is a Ghanaian actress . For her work as an actress , she has received several awards and nominations , including the awards for Best Actress in a Leading Role at the 2010 Africa Movie Academy Awards ; and Best Actress in a Supporting Role at the Africa Movie Academy Awards in 2007 . She received two nominations for Best Actress in a Leading Role and Best Upcoming Actress at the Africa Movie Academy Awards in 2008 . Queen Jeddy ( south Eastern Kenya university student also Jedidah wanjiku ) is a Kenyan aspiring actress who want to be like Jackie appiah .",
"title": ""
},
{
"docid": "List_of_awards_and_nominations_received_by_Liza_Minnelli",
"text": "American actress and singer Liza Minnelli has been honored with numerous awards and nominations for her work in film , television , and theatre . Among the awards she has received is an Academy Award for Best Actress for Cabaret .",
"title": ""
},
{
"docid": "Imelda_Staunton",
"text": "Imelda Mary Philomena Bernadette Staunton , CBE ( born 9 January 1956 ) is an English stage and screen actress . After training at the Royal Academy of Dramatic Art , Staunton began her career in repertory theatre in the 1970s before appearing in seasons at various theatres in the UK . Staunton has since performed in a variety of plays and musicals in London , winning four Olivier Awards ; three for Best Actress in a Musical for her roles as the Baker 's Wife in Into the Woods ( 1991 ) , Mrs. Lovett in Sweeney Todd ( 2013 ) and Mama Rose in Gypsy ( 2016 ) , and one for Best Supporting Performance for her work in both A Chorus of Disapproval ( 1985 ) and The Corn is Green ( 1985 ) . Her appearances on stage in The Beggar 's Opera ( 1982 ) , The Wizard of Oz ( 1987 ) , Uncle Vanya ( 1988 ) , Guys and Dolls ( 1996 ) , Entertaining Mr Sloane ( 2009 ) and Good People ( 2014 ) also earned her Olivier nominations . Staunton has been nominated for a total of 11 Olivier Awards . Staunton drew critical acclaim for the title role in the 2004 film Vera Drake , for which she won the BAFTA Award for Best Actress in a Leading Role and the Venice Film Festival Volpi Cup for Best Actress in addition to being nominated for the Academy Award , the Golden Globe and the Screen Actors Guild Award for Best Actress . Her other film roles include Mrs. Blatherwick in Nanny McPhee ( 2005 ) , Dolores Jane Umbridge in two of the Harry Potter films ( 2007 -- 2010 ) and Hefina Headon in Pride ( 2014 ) , for which she received a nomination for the BAFTA Award for Best Actress in a Supporting Role . On television , she starred in the sitcoms Up the Garden Path ( 1990 -- 1993 ) and Is it Legal ? ( 1995 -- 1998 ) . Her performance in My Family and Other Animals ( 2005 ) earned her a nomination for the International Emmy Award for Best Actress , while her roles in Return to Cranford ( 2009 ) and The Girl ( 2012 ) earned her BAFTA TV Award nominations for Best Supporting Actress . For the latter , she was also nominated for the Primetime Emmy Award for Outstanding Supporting Actress in a Miniseries or a Movie .",
"title": ""
}
] |
153687
|
Robert F. Kennedy died on June 6th 1968.
|
[
{
"docid": "Robert_F._Kennedy",
"text": "Robert Francis `` Bobby '' Kennedy ( November 20 , 1925 -- June 6 , 1968 ) , commonly known by his initials RFK , was an American politician from Massachusetts . He served as the United States junior senator from New York from January 1965 until his assassination in June 1968 . He was previously the 64th U.S. Attorney General from January 1961 to September 1964 , serving under his older brother President John F. Kennedy and his successor , President Lyndon B. Johnson . Kennedy was a member of the Democratic Party , and is seen as an icon of modern American liberalism . After serving in the United States Naval Reserve as a Seaman Apprentice from 1944 to 1946 , Kennedy graduated from Harvard University and the University of Virginia . He began his political career in Massachusetts as the manager for his brother John 's successful campaign for the U.S. Senate in 1952 . Prior to entering public office himself , he worked as a correspondent for The Boston Post and as an assistant counsel to the Senate committee chaired by Joe McCarthy . He gained national attention as the chief counsel of the Senate Labor Rackets Committee from 1957 to 1959 , where he publicly challenged Teamsters President Jimmy Hoffa over the corrupt practices of its union and authored The Enemy Within , a book about corruption in organized labor . Kennedy resigned from the committee to conduct his brother John 's campaign in the 1960 presidential election . He was appointed Attorney General after the successful election and served as the closest adviser to the president from 1961 to 1963 . His tenure is best known for its advocacy for the Civil Rights Movement , the fight against organized crime and the Mafia , and involvement in U.S. foreign policy related to Cuba . After his brother 's assassination , he remained in office in the Johnson administration for several months . He left to run for the United States Senate from New York in 1964 and defeated Republican incumbent Kenneth Keating . In 1968 , Kennedy was a leading candidate for the Democratic nomination for the presidency ; he appealed especially to poor , African-American , Hispanic , Catholic and young voters . Shortly after midnight on June 5 , 1968 , after defeating Senator Eugene McCarthy in the California and South Dakota presidential primaries , he was mortally wounded by Sirhan Sirhan , a 24-year-old enraged Palestinian , and died the following day .",
"title": ""
}
] |
[
{
"docid": "Abraham,_Martin_and_John",
"text": "`` Abraham , Martin and John '' is a 1968 song written by Dick Holler and first recorded by Dion . It is a tribute to the memory of four assassinated Americans , all icons of social change , Abraham Lincoln , Martin Luther King , Jr. , John F. Kennedy and Robert F. Kennedy . It was written in response to the assassination of King and that of Robert Kennedy in April and June 1968 , respectively .",
"title": ""
},
{
"docid": "Grave_of_Robert_F._Kennedy",
"text": "The grave of Robert F. Kennedy is a historic grave site and memorial to assassinated U.S. Senator and 1968 Democratic presidential candidate Robert F. Kennedy located in section 45 of Arlington National Cemetery in Arlington County , Virginia , in the United States . It was dedicated on December 6 , 1971 , and replaced a temporary grave in which Kennedy was originally buried on June 8 , 1968 . It is adjacent to the John F. Kennedy Eternal Flame . The grave is aligned along an east -- west axis , roughly along the line of sight between Arlington House and the Jefferson Memorial . The grave consists of an unadorned , white wooden cross at the head of the grave and a simple grey granite marker set flush with the earth at the foot of it . The memorial consists of a small semicircular granite plaza , which provides viewing for the grave . At the back ( straight ) axis of the plaza is a low rectangular grey granite wall inscribed with quotations from two of Kennedy 's speeches . A small , rectangular reflecting pool is at the base of the wall .",
"title": ""
},
{
"docid": "Assassination_of_Robert_F._Kennedy",
"text": "On June 5 , 1968 , presidential candidate Robert F. Kennedy was fatally shot at the Ambassador Hotel in Los Angeles , shortly after winning the California presidential primaries in the 1968 election , and died the next day while hospitalized . After winning the California and South Dakota primary elections for the Democratic nomination for President of the United States , Kennedy was fatally shot while exiting through the hotel kitchen immediately after leaving the podium in the Ambassador Hotel and died in the Good Samaritan Hospital twenty-six hours later . Sirhan Sirhan , a 24-year-old Palestinian/Jordanian immigrant , was convicted of Kennedy 's murder and sentenced to death in 1969 , although his sentence was commuted to life in prison in 1972 . On November 22 , 2013 , Sirhan was transferred from Corcoran to the Richard J. Donovan Correctional Facility in San Diego County . The shooting was recorded on audio tape by a freelance newspaper reporter , and the aftermath was captured on film . Kennedy 's body lay in repose at St. Patrick 's Cathedral in New York for two days before a funeral Mass was held on June 8 . His body was interred near his brother John at Arlington National Cemetery . His death prompted the protection of presidential candidates by the United States Secret Service . Hubert Humphrey later went on to win the Democratic nomination for the presidency , but ultimately lost the election to Republican Richard Nixon . As with his brother John 's death , Kennedy 's assassination and the circumstances surrounding it have spawned a variety of conspiracy theories . Kennedy and Huey Long ( in 1935 ) are the only two sitting United States Senators to be assassinated .",
"title": ""
},
{
"docid": "Robert_F._Kennedy_presidential_campaign,_1968",
"text": "The Robert F. Kennedy presidential campaign began on March 16 , 1968 . Robert Francis Kennedy , a U.S. Senator from New York who won a Senate seat in 1964 , faced what was widely considered an unrealistic race against an incumbent , President Lyndon B. Johnson . After Johnson 's announcement on March 31 that he would not seek re-election , Kennedy still faced Johnson 's leading challenger , Eugene McCarthy , a U.S. Senator from Minnesota , and Vice President Hubert Humphrey , who entered the race following Johnson 's withdrawal , for the Democratic Party 's presidential nomination . Kennedy and McCarthy remained the main challengers to Humphrey and the policies of the Johnson administration . Throughout the spring of 1968 , Kennedy campaigned in presidential primary elections , especially those in Indiana , Nebraska , Oregon , South Dakota , California , and Washington , D.C. . He had made progress in achieving Democratic support for the nomination until his assassination on June 5 , 1968 , in Los Angeles , California .",
"title": ""
},
{
"docid": "RFK_(disambiguation)",
"text": "Robert F. Kennedy ( 1925-1968 ) was an American politician who is often referred to by his initials RFK RFK may also refer to : RFK ( film ) , a 2002 television movie about Robert F. Kennedy RFK ( 2004 ) , a television documentary directed by David Grubin Robert F. Kennedy , Jr. ( born 1954 ) , lawyer , journalist , author , and son of Robert F. Kennedy Robert F. Kennedy Memorial Stadium , Washington DC",
"title": ""
},
{
"docid": "Donald_Dowd",
"text": "Donald Dowd ( 1923 -- 2010 ) was a long-time campaign aide to the Kennedy family , including Senator Ted Kennedy . He was a member of the John F. Kennedy Library Foundation , and worked there for almost 25 years . Richard Neal described Donald as a legendary figure , and recalled him as a great friend and mentor . Dowd was the retired vice president of public affairs for Coca-Cola in Boston . In 1968 , Donald Dowd worked on the Presidential campaign of Robert F. Kennedy , and was on the campaign trail with Kennedy when Kennedy was shot dead at the Ambassador Hotel in Los Angeles on June 6 , 1968 . Dowd previously worked in President Kennedy 's administration , in the Post Office Department .",
"title": ""
},
{
"docid": "Robert_F._Kennedy_assassination_conspiracy_theories",
"text": "The conspiracy theories relating to the assassination of Robert F. Kennedy , a United States Senator and brother of assassinated President John F. Kennedy , relate to non-standard accounts of the assassination that took place shortly after midnight on June 5 , 1968 , in Los Angeles , California . Robert F. Kennedy was assassinated during celebrations of his successful campaign in the Californian primary elections while seeking the Democratic nomination for U.S. president . The perpetrator was a 24-year-old Palestinian immigrant named Sirhan Sirhan , who remains incarcerated for the crime . However , as with his brother 's death , Robert Kennedy 's assassination and the circumstances surrounding it have spawned various conspiracy theories , particularly regarding the existence of a supposed second gunman . Such theories have also centered on the alleged presence of a woman wearing a polka dot dress claiming responsibility for the crime and the purported involvement of the Central Intelligence Agency . Many of these theories were examined during an investigation ordered by the United States Senate , and were judged to be erroneous by the Federal Bureau of Investigation , which investigated on the Senate 's behalf .",
"title": ""
},
{
"docid": "Robert_F._Kennedy's_speech_on_the_assassination_of_Martin_Luther_King_Jr.",
"text": "Robert F. Kennedy 's speech on the assassination of Martin Luther King Jr. was given on April 4 , 1968 , in Indianapolis , Indiana . Kennedy , the United States senator from New York , was campaigning to earn the 1968 Democratic presidential nomination when he learned that King had been assassinated in Memphis , Tennessee . Earlier that day Kennedy had spoken at the University of Notre Dame in South Bend and at Ball State University in Muncie , Indiana . Before boarding a plane to attend campaign rallies in Indianapolis , Kennedy learned that King had been shot . When he arrived , Kennedy was informed that King had died . Despite fears of riots and concerns for his safety , Kennedy went ahead with plans to attend a rally at 17th and Broadway in the heart of Indianapolis 's African-American ghetto . That evening Kennedy addressed the crowd , many of whom had not heard about King 's assassination . Instead of the rousing campaign speech they expected , Kennedy offered brief , impassioned remarks for peace that is considered to be one of the great public addresses of the modern era .",
"title": ""
},
{
"docid": "Hoover_vs._The_Kennedys",
"text": "Hoover vs. The Kennedys : The Second Civil War is a four-hour 1987 made-for-television mini-series depicting the political struggles between FBI Director J. Edgar Hoover and President John F. Kennedy and Attorney-General Robert F. Kennedy . The film takes place between the 1960 Democratic National Convention in July 1960 and the Assassination of Robert F. Kennedy in June 1968 , with the majority of the mini-series focusing on the Kennedy Administration ( 1961 -- 1963 ) . Other sub-plots include Bobby Kennedy 's frustration with his elder brother 's politically risky womanizing and his often turbulent relationship with Hoover and the Civil Rights leadership of the era . The mini-series also touches on the alleged bargains Joseph P. Kennedy Sr. made with Mafia figures in order to get his son elected to the U.S. Presidency . Hoover vs. The Kennedys was primarily filmed on location in and around Toronto , Ontario . Produced by : Paul Saltzman Daniel Selznick and Joe Glickman Written by : Lionel E. Siegel and Michael O'Herlihy",
"title": ""
},
{
"docid": "Robert_F._Kennedy_Journalism_Award",
"text": "The Robert F. Kennedy Awards for Excellence in Journalism is a journalism award named after Robert F. Kennedy and awarded by the Robert F. Kennedy Center for Justice and Human Rights . The annual awards are issued in several categories and were established in December 1968 by a group of reporters who covered Kennedy 's campaigns . Winners are judged by more than 50 journalists each year , led by a committee of six independent journalists . The awards honor reporting `` on issues that reflect Robert F. Kennedy 's concerns , including human rights , social justice and the power of individual action in the United States and around the world . Entries include insights into the causes , conditions and remedies of injustice and critical analysis of relevant public policies , programs , attitudes and private endeavors . '' The awards are known as the `` poor people 's Pulitzers '' in media circles .",
"title": ""
},
{
"docid": "Robert_F._Kennedy's_1948_visit_to_Palestine",
"text": "Robert F. Kennedy visited the British Mandate of Palestine in 1948 , one month before Israel declared its independence . Twenty-two years old at the time , he was reporting on the tense situation in the region for The Boston Post . During his stay , he grew to admire the Jewish inhabitants of the area . He later became a strong supporter of Israel ; this was later cited as Sirhan Sirhan 's motivation for assassinating him on the first anniversary of the start of the Six-Day War on June 5 , 1968 . Sirhan happened to see a documentary about Kennedy in Palestine in 1948 . Later in his murder trial , Sirhan Sirhan testified : `` I hoped he will win Presidency until that moment . But when I saw , heard , he was supporting Israel , sir , not in 1968 , but he was supporting , it from all the way from its inception in 1948 , sir ... '' Author Robert Blair Kaiser points out a discrepancy in the timing of Sirhan 's decision . In Sirhan 's diary , the entry in which he decided to kill Robert Kennedy was made on May 18 . The documentary in question was first shown on TV in the Los Angeles area on May 20 . When asked to explain , Sirhan said that he did not recall writing the journal .",
"title": ""
},
{
"docid": "Robert_F._Kennedy's_speech_at_Ball_State_University",
"text": "Robert F. Kennedy 's speech at Ball State University was given on April 4 , 1968 , in Muncie , Indiana .",
"title": ""
},
{
"docid": "Robert_F._Kennedy's_remarks_at_the_University_of_Kansas",
"text": "Robert F. Kennedy 's remarks at the University of Kansas were given on March 18 , 1968 . He spoke about student protests , the Vietnam War , and the gross national product . At the time , Kennedy 's words on the latter subject went relatively unnoticed , but they have since become famous .",
"title": ""
},
{
"docid": "Robert_Kennedy_(disambiguation)",
"text": "Robert Kennedy ( 1925 -- 1968 ) was an American politician . Robert Kennedy may also refer to : Robert Kennedy ( cricketer ) ( born 1972 ) , cricketer from New Zealand Robert Kennedy ( field hockey ) ( 1880 -- 1963 ) , Irish field hockey player Robert Kennedy ( Jesuit ) ( born 1933 ) , Zen priest , Jesuit , psychotherapist , professor and author Robert Kennedy ( publisher ) ( 1938 -- 2012 ) , magazine publisher Robert B. Kennedy ( born 1940 ) , American politician from Lowell , Massachusetts Robert D. Kennedy , American businessman Robert E. Kennedy ( Ivey Business School ) , university administrator Robert E. Kennedy ( University president ) ( 1915 -- 2010 ) , president emeritus of California Polytechnic State University Robert F. Kennedy , Jr. ( born 1954 ) , American environmental lawyer and son of Robert F. Kennedy Robert Foster Kennedy ( 1884 -- 1952 ) , Irish-American neurologist Robert H. Kennedy ( 1869 -- 1951 ) , farmer , merchant and political figure in Nova Scotia , Canada Robert P. Kennedy ( 1840 -- 1918 ) , American politician , U.S. Representative from Ohio Bob or Bobby Kennedy Bob Kennedy ( 1920 -- 2005 ) , American baseball player and manager Bob Kennedy ( American football , born 1921 ) ( 1921 -- 2010 ) , American football running back Bob Kennedy ( American football , born 1928 ) ( 1928 -- 1991 ) , American football player Bob Kennedy ( athlete ) ( born 1970 ) , American distance runner Bob Kennedy ( ice hockey ) ( 1930 -- 1998 ) , Canadian ice hockey player Bobby Kennedy ( footballer ) ( born 1937 ) , Scottish footballer",
"title": ""
},
{
"docid": "Bill_Eppridge",
"text": "William E. `` Bill '' Eppridge ( March 20 , 1938 − October 3 , 2013 ) was an American photographer and photojournalist for Life magazine , known for his photography of the dying Robert F. Kennedy , taken in June 1968 . Eppridge was born in Buenos Aires , Argentina on March 20 , 1938 and grew up in Richmond , Virginia , Nashville , Tennessee , and Wilmington , Delaware . Eppridge died of pneumonia caused by a sepsis infection on October 3 , 2013 , aged 75 , at the Danbury Hospital in Danbury , Connecticut .",
"title": ""
},
{
"docid": "Kenneth_O'Donnell",
"text": "Kenneth Patrick `` Kenny '' O'Donnell ( March 4 , 1924 -- September 9 , 1977 ) was an American political consultant who served as the special assistant and appointments secretary to President John F. Kennedy from 1961 until President Kennedy 's assassination in November 1963 . O'Donnell was a close friend of President Kennedy and his younger brother , politician Robert F. Kennedy , and was part of the group of Kennedy 's close advisors called the `` Irish Mafia . '' O'Donnell served as President Lyndon B. Johnson 's aide from 1963 to 1965 , and was a key campaign advisor for Robert Kennedy 's 1968 presidential campaign .",
"title": ""
},
{
"docid": "Senator_Kennedy",
"text": "Senator Kennedy may refer to the following : Joe Kennedy ( Georgia politician ) , Georgia State Senator ( 1966 -- 1990 ) John F. Kennedy , United States Senator from Massachusetts ( 1953 -- 1960 ) and subsequently President of the United States John Neely Kennedy , United States Senator from Louisiana ( 2017 -- ) Robert F. Kennedy , United States Senator from New York ( 1965 -- 1968 ) Ted Kennedy , United States Senator from Massachusetts ( 1962 -- 2009 )",
"title": ""
},
{
"docid": "Arthur_M._Schlesinger_Jr.",
"text": "Arthur Meier Schlesinger Jr. ( -LSB- ˈʃlɛsɪndʒər -RSB- born Arthur Bancroft Schlesinger ; October 15 , 1917 -- February 28 , 2007 ) was an American historian , social critic , and public intellectual . The son of the influential historian Arthur M. Schlesinger Sr. and a specialist in American history , much of Schlesinger 's work explored the history of 20th-century American liberalism . In particular , his work focused on leaders such as Harry S. Truman , Franklin D. Roosevelt , John F. Kennedy , and Robert F. Kennedy . In the 1952 and 1956 presidential campaigns , he was a primary speechwriter and adviser to the Democratic presidential nominee both times , Adlai Stevenson II . Schlesinger served as special assistant and `` court historian '' to President Kennedy from 1961 to 1963 . He wrote a detailed account of the Kennedy administration , from the 1960 presidential campaign to the president 's state funeral , titled A Thousand Days : John F. Kennedy in the White House , which won the 1966 Pulitzer Prize for Biography or Autobiography . In 1968 , Schlesinger actively supported the presidential campaign of Senator Robert F. Kennedy , which ended with Kennedy 's assassination in Los Angeles . Schlesinger wrote a popular biography , Robert Kennedy and His Times , several years later . He later popularized the term `` imperial presidency '' during the Nixon administration book of the same name .",
"title": ""
},
{
"docid": "Pierre_Salinger",
"text": "Pierre Emil George Salinger ( June 14 , 1925 -- October 16 , 2004 ) was an American politician , author and journalist . He served as the White House Press Secretary to U.S. Presidents John F. Kennedy and Lyndon B. Johnson . Salinger served as a United States Senator in 1964 and was campaign manager for the 1968 Robert F. Kennedy presidential campaign . He later became known for his work as an ABC News correspondent , and in particular for his coverage of the American hostage crisis in Iran , the bombing of Pan Am Flight 103 over Lockerbie , Scotland , and his claims as to the cause of the explosion of TWA flight 800 .",
"title": ""
},
{
"docid": "Ethel_Kennedy",
"text": "Ethel Skakel Kennedy ( born April 11 , 1928 ) is an American human-rights campaigner and widow of Senator Robert F. Kennedy , who was assassinated while running for nomination as Democratic presidential candidate in 1968 . As Ethel Skakel , she was a classmate of Kennedy 's sister Jean at Manhattanville College of the Sacred Heart . She and Kennedy married in 1950 and had seven sons and four daughters . Their house , Hickory Hill at McLean , Virginia , was the scene of exclusive parties . Soon after her husband 's death , she founded the Robert F. Kennedy Center for Justice and Human Rights , a nonprofit charity working to realize RFK 's dream of a just and peaceful world . In 2009 , Ethel Kennedy was among the chief mourners at the funeral of her brother-in-law Ted Kennedy . In 2014 , President Barack Obama awarded her a Presidential Medal of Freedom .",
"title": ""
},
{
"docid": "Eunice_Kennedy_Shriver",
"text": "Dame Eunice Mary Kennedy Shriver , DSG ( July 10 , 1921 -- August 11 , 2009 ) was a member of the Kennedy family ; she was the sister of President John F. Kennedy and senators Robert F. Kennedy and Ted Kennedy . Her husband , Sargent Shriver , was the United States Ambassador to France during the Lyndon Johnson presidency and the Democratic vice presidential candidate in the 1972 U.S. presidential election . In 1962 , she founded Camp Shriver , which started on her Maryland farm known as Timberlawn , and evolved into the Special Olympics in 1968 .",
"title": ""
},
{
"docid": "U.S._National_Commission_on_the_Causes_and_Prevention_of_Violence",
"text": "The U.S. National Commission on the Causes and Prevention of Violence ( National Violence Commission ) was formed by President Lyndon B. Johnson in on June 10 , 1968 , after the assassinations of Reverend Martin Luther King , Jr. and Senator Robert F. Kennedy .",
"title": ""
},
{
"docid": "The_Snow_Papers",
"text": "The Snow Papers , by Richard Smart , is a book whose central theme is the author 's period of addiction to cocaine . A portion of the book covers Smart 's role as an insider in Robert F Kennedy 's 1968 Democratic nomination campaign , and his assassination at a victory celebration ( RFK had essentially won the nomination ) on June 4 , 1968 . Category : American non-fiction books Category : Politics of the United States Category :1985 books Category : Little , Brown and Company books Category : Memoirs about drugs",
"title": ""
},
{
"docid": "Bob_Clark_(television_reporter)",
"text": "Bob Clark was a television reporter and White House Correspondent for ABC News from the 1960s until the 1970s . He is most remembered for reporting the assassinations of John F. Kennedy in 1963 and Robert F. Kennedy in 1968 . Clark was the only person to see both Kennedy brothers after each was shot in Dallas , Texas and Los Angeles , California , respectively . He was also a contributing host to the ABC Sunday interview program , then entitled Issues and Answers , now known as This Week .",
"title": ""
},
{
"docid": "Ken_Jones_(news_reporter)",
"text": "Kenneth Leon `` Ken '' Jones ( June 9 , 1938 -- May 13 , 1993 ) was an American television journalist , actor , reporter and news anchor . He was Los Angeles television 's first black weeknight news anchor , working for Los Angeles television station KTTV-TV channel 11 and KNXT channel 2 ( now known as KCBS-TV ) . Jones was known for his reports on the 1965 Watts riots and the assassination of Sen. Robert F. Kennedy in 1968 . Ken Jones also conceived and published , along with his wife Regina Jones , SOUL , a black entertainment newsmagazine , from 1966-82 . In 1992 , Ken was diagnosed with bladder cancer and after a short battle with the disease , died in May 1993 .",
"title": ""
},
{
"docid": "Ambassador_Hotel_(Los_Angeles)",
"text": "The Ambassador Hotel was a hotel in Los Angeles , California , and location of the Cocoanut Grove nightclub until it was demolished in 2005 . The hotel began operation formally on January 1 , 1921 , and subsequently was the site of the 2nd Academy Awards , the 12th Academy Awards , and the June 1968 assassination of presidential candidate , United States Senator , and former U.S. Attorney General Robert F. Kennedy .",
"title": ""
},
{
"docid": "RFK_(film)",
"text": "RFK is a 2002 American television film directed by Robert Dornhelm . It takes place through the eyes of Robert F. Kennedy after his brother John F. Kennedy 's assassination in 1963 . As he lives through the loss , he starts to identify himself as a political figure , not just the former President 's brother . He makes it official with a Presidential bid in 1968 to what he says was to `` save the Democratic Party . '' During his campaign , in which the American people showed great support for him , RFK was shot and killed by Sirhan Sirhan . The film was shot in Hamilton , Ontario , Canada .",
"title": ""
},
{
"docid": "PT_109_(film)",
"text": "PT 109 is a 1963 biographical war film which depicts the actions of John F. Kennedy ( JFK ) as an officer of the United States Navy in command of Motor Torpedo Boat PT-109 during the Pacific War of World War II . The film was adapted by Vincent Flaherty and Howard Sheehan from the book PT 109 : John F. Kennedy in World War II by Robert J. Donovan , and the screenplay was written by Robert L. Breen . Cliff Robertson stars as Kennedy , with featured performances by Ty Hardin , James Gregory , Robert Culp , and Grant Williams . PT 109 was the first commercial theatrical film about a sitting United States President released while he was still in office and still alive . It was released in the United States on June 19 , 1963 , five months before Kennedy was assassinated .",
"title": ""
},
{
"docid": "Mark_Shaw_(photographer)",
"text": "Mark Shaw ( June 25 , 1921 -- January 26 , 1969 ) was an American fashion and celebrity photographer in the 1950s and 1960s . He worked for Life magazine from 1952 to 1968 , during which time 27 issues of Life carried cover photos by Shaw . Shaw 's work also appeared in Esquire , Harper 's Bazaar , Mademoiselle , and many other publications . He is best known for his photographs of John F. Kennedy , his wife Jacqueline Kennedy , and their children , Caroline and John F. Kennedy , Jr. . In 1964 , many of these images were published in the book The John F. Kennedys : A Family Album , which became a bestseller .",
"title": ""
},
{
"docid": "David_A._Kennedy",
"text": "David Anthony Kennedy ( June 15 , 1955 -- April 25 , 1984 ) was the fourth of eleven children of Robert F. Kennedy and Ethel Skakel .",
"title": ""
}
] |
PLAIN-104
|
A Low Methionine Diet May Help Starve Cancer Cells
|
[
{
"docid": "MED-3715",
"text": "INTRODUCTION: Questions have recently arisen in the popular press about the association between specific sexual behaviors, namely, fellatio and cunnilingus, with head and neck cancers. Although there has been an overall decline in the incidence of head and neck cancers over the past 25 years, there has been a shift in the distribution of these cancers toward a particular type known as oral squamous cell carcinomas (OSCCs), and a younger demographic. These particular cancers, OSCCs, have been shown to be associated with the human papillomavirus (HPV). Several researchers have suggested that this shift in the epidemiology of head and neck cancers might be attributable to changing sexual practices. While this speculation has caught on in the popular press, there are several interesting contradictions in the existing evidence that suggest this conclusion might be premature and overreached. AIM: The intent of this article is to help clarify the issues so that sexual medicine professionals can give accurate and up-to-date information to their patients. MAIN OUTCOME MEASURES: This is a review article; no outcome data are reported. This is a review article; no measures were collected. METHODS: Pubmed search on HPV, oral sex, oral cancers, and OSCCs. RESULTS: One hundred ninety-six articles on HPV were found; 63 articles on oral sex, 55 on oral cancer, and 5 articles on OSCCs were identified as relevant. CONCLUSIONS: HPV infections occur commonly and are usually cleared within 18 months, thus HPV infection should not be a cause for concern among monogamous couples with a rich and varied sex life as long as the sexual system remains closed and other immune compromising factors are not present. HPV becomes a concern in the context of immune system compromise and infection persistence. Factors contributing to immune system compromise, HPV persistence, and oncogenesis are reviewed. © 2012 International Society for Sexual Medicine.",
"title": "Is oral sex really a dangerous carcinogen? Let's take a closer look."
},
{
"docid": "MED-5327",
"text": "OBJECTIVE: To investigate the associations between dietary patterns and mental health in early adolescence. METHOD: The Western Australian Pregnancy Cohort (Raine) Study is a prospective study of 2900 pregnancies recruited from 1989-1992. At 14 years of age (2003-2006; n=1324), the Child Behaviour Checklist (CBCL) was used to assess behaviour (characterising mental health status), with higher scores representing poorer behaviour. Two dietary patterns (Western and Healthy) were identified using factor analysis and food group intakes estimated by a 212-item food frequency questionnaire. Relationships between dietary patterns, food group intakes and behaviour were examined using general linear modelling following adjustment for potential confounding factors at age 14: total energy intake, body mass index, physical activity, screen use, family structure, income and functioning, gender and maternal education at pregnancy. RESULTS: Higher total (b=2.20, 95% CI=1.06, 3.35), internalizing (withdrawn/depressed) (b=1.25, 95% CI=0.15, 2.35) and externalizing (delinquent/aggressive) (b=2.60, 95% CI=1.51, 3.68) CBCL scores were significantly associated with the Western dietary pattern, with increased intakes of takeaway foods, confectionary and red meat. Improved behavioural scores were significantly associated with higher intakes of leafy green vegetables and fresh fruit (components of the Healthy pattern). CONCLUSION: These findings implicate a Western dietary pattern in poorer behavioural outcomes for adolescents. Better behavioural outcomes were associated with a higher intake of fresh fruit and leafy green vegetables.",
"title": "The association between dietary patterns and mental health in early adolescence."
},
{
"docid": "MED-3282",
"text": "BACKGROUND AND AIMS: The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation. METHODS: Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells. RESULTS: Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect. CONCLUSIONS: Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.",
"title": "Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment."
},
{
"docid": "MED-3732",
"text": "Background Endoscopic submucosal dissection (ESD) is an advanced technique of therapeutic endoscopy alternative to endoscopic mucosal resection (EMR) for superficial gastrointestinal neoplasms >2 cm. ESD allows for the direct dissection of the submucosa and large lesions can be resected en bloc. ESD is not limited by resection size, increases histologically complete resection rates and may reduce the local recurrence. Nevertheless, the technique is time-consuming, technically demanding and associated with a high complication rate. To reduce the risk of complications, different devices and technical advances have been proposed with conflicting results and, still, ESD en bloc resections of huge lesions are associated with increased complications. Case Presentation We successfully used a combined ESD/EMR technique for huge rectal laterally spreading tumors (LSTs). ESD was used for circumferential resection of 2/3 of the lesion followed by piecemeal resection (2-3 pieces) of the central part of the tumour. In all three patients we obtained the complete dissection of the polyp and the complete histological evaluation in absence of complications and recurrence at 6 months' follow up. Conclusions In the treatment of rectal LSTs, the combined treatment - ESD/EMR resection may be considered a suitable therapeutic option, indicated in selected cases as an alternative to surgery, in which the two techniques are neither reliable nor safe separately. However, to confirm our results, larger trials with longer follow up are required together with improvement of the technique and of the technical devices.",
"title": "Rectal laterally spreading tumors successfully treated in two steps by endoscopic submucosal dissection and endoscopic mucosal resection"
},
{
"docid": "MED-3549",
"text": "Studies have shown that fisetin, a small phytochemical molecule, has antitumor activity; however, its antiangiogenic activity has not yet been examined. Accordingly, herein, we investigated the antiangiogenic efficacy and associated mechanisms of fisetin in human umbilical vein endothelial cells (HUVECs). Fisetin (10-50 μM) strongly inhibited the regular serum plus growth supplement- and vascular endothelial growth factor (VEGF)-induced growth (up to 92%, P < 0.001) and survival (up to 16%, P < 0.001) of HUVEC in a dose- and time-dependent manner. Fisetin also caused cell cycle arrest at G(1) (strong) and G(2)/M (moderate) phases together with a decrease in cyclin D1 and an increase in p53 levels. Fisetin-caused cell death was accompanied by decreased expression of survivin and an increase in cleaved levels of caspases-3 and -7 and poly-(ADP-ribose) polymerase along with an increased ratio of Bax to Bcl-2. Furthermore, fisetin inhibited capillary-like tube formation on Matrigel (up to 85%, P < 0.001) as well as migration (up to 66%, P < 0.001), which were associated with decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF in HUVEC. It also decreased the expression of eNOS, VEGF, inducible nitric oxide synthase, matrix metalloproteinase-2 and -9 in A549 and DU145 human cancer cells. In vivo matrigel plug assay in mice showed significant decrease in size (up to 43%, P < 0.001), vascularization and hemoglobin content (up to 94%, P < 0.001) in the plugs from fisetin-treated, compared with control mice. Overall, these results suggest that fisetin inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects, and therefore, fisetin warrants further investigation for its angiopreventive potential toward cancer control.",
"title": "Fisetin inhibits various attributes of angiogenesis in vitro and in vivo--implications for angioprevention."
},
{
"docid": "MED-4116",
"text": "The growths of many and perhaps all tumors may be stimulated rather than inhibited by a quantitatively low level of immunity. The reason tumors have antigens may be that tumors do not develop in vivo in the absence of at least a minimal immune reaction; in this sense, cancer may be considered an autoimmune disease. This review, based largely on the work of our own laboratory, outlines the data showing that the titration of anti-tumor immunity exhibits the phenomenon of hormesis, i.e. the dose-response curve is non-linear such that low levels of immunity are generally stimulatory but larger quantities of the same immune reactants may inhibit tumor growth. Evidence is also reviewed that suggests that the immune response may vary qualitatively and quantitatively during progression, such that there seems to be, during oncogenesis, a very low level of immune reaction that aids initial tumor growth, followed by a larger reaction that may cause remission of early neoplasms, followed, if the neoplasm survives, by a relative immunologic tolerance to the tumor that may be dependent, at least in part, on suppressor cells. This knowledge may help to explain some clinical observations concerning the relationships among tumor types and the organ distribution of metastases.",
"title": "The flip side of immune surveillance: immune dependency."
},
{
"docid": "MED-5341",
"text": "The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.",
"title": "Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro."
},
{
"docid": "MED-3731",
"text": "Esophageal cancer is highly aggressive and is a common cancer both worldwide and in the US. In the past two decades, the incidence and mortality of esophageal cancer in the US have both increased, where as the incidence and mortality of other cancers have decreased. Although esophageal squamous cell carcinoma and esophageal adenocarcinoma differ in their histology and epidemiologic distribution, some of their risk factors (e.g. dietary deficiencies and tobacco) and underlying mechanisms of carcinogenesis are the same. Intensive research into risk factors combined with the ability to identify precursor lesions (e.g.squamous dysplasia in esophageal squamous cell carcinoma and Barrett's esophagus in esophageal adenocarcinoma) has paved the way for studies of chemoprevention for esophageal cancer, some of which have shown promising results.",
"title": "Esophageal cancer: epidemiology, pathogenesis and prevention."
},
{
"docid": "MED-3274",
"text": "Objective To determine whether dogs can be trained to identify people with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. Design Experimental, “proof of principle” study in which six dogs were trained to discriminate between urine from patients with bladder cancer and urine from diseased and healthy controls and then evaluated in tests requiring the selection of one bladder cancer urine sample from six controls. Participants 36 male and female patients (age range 48-90 years) presenting with new or recurrent transitional cell carcinoma of the bladder (27 samples used for training; 9 used for formal testing); 108 male and female controls (diseased and healthy, age range 18-85 years—54 samples used in training; 54 used for testing). Main outcome measure Mean proportion of successes per dog achieved during evaluation, compared with an expected value of 1 in 7 (14%). Results Taken as a group, the dogs correctly selected urine from patients with bladder cancer on 22 out of 54 occasions. This gave a mean success rate of 41% (95% confidence intervals 23% to 58% under assumptions of normality, 26% to 52% using bootstrap methods), compared with 14% expected by chance alone. Multivariate analysis suggested that the dogs' capacity to recognise a characteristic bladder cancer odour was independent of other chemical aspects of the urine detectable by urinalysis. Conclusions Dogs can be trained to distinguish patients with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. This suggests that tumour related volatile compounds are present in urine, imparting a characteristic odour signature distinct from those associated with secondary effects of the tumour, such as bleeding, inflammation, and infection.",
"title": "Olfactory detection of human bladder cancer by dogs: proof of principle study"
},
{
"docid": "MED-4891",
"text": "The current annual incidence of sudden cardiac death in the US is likely to be in the range of 180–250,000 per year. Coinciding with the decreased mortality from coronary artery disease, there is evidence pointing toward a significant decrease in rates of sudden cardiac death in the US during the second half of the twentieth century. However the alarming rise in prevalence of obesity and diabetes in the first decade of the new millennium both in the US and worldwide, would indicate that this favorable trend is unlikely to persist. We are likely to witness a resurgence of coronary artery disease and heart failure, as a result of which sudden cardiac death will have to be confronted as a shared and indiscriminate, worldwide public health problem. There is also increasing recognition of the fact that discovery of meaningful and relevant risk stratification and prevention methodologies will require careful prospective community-wide analyses, with access to large archives of DNA, serum and tissue that link with well-phenotyped databases. The purpose of this review is to summarize current knowledge of sudden cardiac death epidemiology. We will discuss the significance and strengths of community-wide evaluations of sudden cardiac death, summarize recent observations from such studies, and finally highlight specific potential predictors that warrant further evaluation as determinants of sudden cardiac death in the general population.",
"title": "Epidemiology of Sudden Cardiac Death: Clinical and Research Implications"
},
{
"docid": "MED-3728",
"text": "On the basis of copious preclinical data supporting the preventive efficacy of small fruits such as berries and grapes, Chen and colleagues conducted a randomized (noncomparative) phase II trial evaluating two doses of strawberry powder (60 g/d or 30 g/d for six months) to prevent esophageal cancer in China (reported in this issue of the journal, beginning on page 41); 60 g/d reduced the histologic grade of dysplastic lesions and reduced localized biomarkers, whereas 30 g/d was not effective. Fundamental questions remain such as the best formulation of strawberry powder, the active components associated with powder, and the actual mechanism of action, and standardized preparations will be required to permit the widespread use of strawberry powder with a predicable outcome. Clearly, however, this work is a good example of proof-of-principle and highlights the important role of diet, nutrition, and natural products in cancer prevention. ©2012 AACR.",
"title": "Strawberry fields forever?"
},
{
"docid": "MED-3276",
"text": "Methionine is an essential amino acid with many key roles in mammalian metabolism such as protein synthesis, methylation of DNA and polyamine synthesis. Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. Methionine dependence in cancer may be due to one or a combination of deletions, polymorphisms or alterations in expression of genes in the methionine de novo and salvage pathways. Cancer cells with these defects are unable to regenerate methionine via these pathways. Defects in the metabolism of folate may also contribute to the methionine dependence phenotype in cancer. Selective killing of methionine dependent cancer cells in co-culture with normal cells has been demonstrated using culture media deficient in methionine. Several animal studies utilizing a methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span. In humans, vegan diets, which can be low in methionine, may prove to be a useful nutritional strategy in cancer growth control. The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth. The application of nutritional methionine restriction and methioninase in combination with chemotherapeutic regimens is the current focus of clinical studies. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension."
},
{
"docid": "MED-3726",
"text": "Cancer is the second leading cause of death worldwide. Therefore, the fight against cancer is one of the most important areas of research in medicine, and one that possibly contributes to the increased interest in chemoprevention as an alternative approach to the control of cancer. Cancer prevention by nutraceuticals present in fruits and vegetables has received considerable attention because of their low cost and wide safety margin. A substantial amount of evidence from human, animal, and cell culture studies has shown cancer chemopreventive effects from these natural products. However, single-agent intervention has failed to produce the expected outcome in clinical trials; therefore, combinations of nutraceuticals are gaining increasing popularity. Thus, combinations of nutraceuticals that mimic real-life situations and are competent in targeting multiple targets with very little or virtually no toxicity are needed. In this review, we summarize the results of those studies that report combinatorial cancer chemopreventive action of various nutraceuticals and their combinations with anticancer drugs. © 2011 New York Academy of Sciences.",
"title": "Combinatorial strategies employing nutraceuticals for cancer development."
},
{
"docid": "MED-5339",
"text": "Recently, it has been suggested that the Escherichia coli causing urinary tract infection (UTI) may come from meat and animals. The purpose was to investigate if a clonal link existed between E. coli from animals, meat and UTI patients. Twenty-two geographically and temporally matched B2 E. coli from UTI patients, community-dwelling humans, broiler chicken meat, pork, and broiler chicken, previously identified to exhibit eight virulence genotypes by microarray-detection of approximately 300 genes, were investigated for clonal relatedness by PFGE. Nine isolates were selected and tested for in vivo virulence in the mouse model of ascending UTI. UTI and community-dwelling human strains were closely clonally related to meat strains. Several human derived strains were also clonally interrelated. All nine isolates regardless of origin were virulent in the UTI model with positive urine, bladder and kidney cultures. Further, isolates with the same gene profile also yielded similar bacterial counts in urine, bladder and kidneys. This study showed a clonal link between E. coli from meat and humans, providing solid evidence that UTI is zoonosis. The close relationship between community-dwelling human and UTI isolates may indicate a point source spread, e.g. through contaminated meat.",
"title": "Is Escherichia coli urinary tract infection a zoonosis? Proof of direct link with production animals and meat."
},
{
"docid": "MED-3729",
"text": "Oxidative stress is a key component in linking environmental toxicity to the multistage carcinogenic process. Reactive oxygen species (ROS) are generated in response to both endogenous and exogenous stimuli. To counterbalance ROS-mediated injury, an endogenous antioxidants defense system exists; however, when oxidation exceeds the control mechanisms, oxidative stress arises. Chronic and cumulative oxidative stress induces deleterious modifications to a variety of macromolecular components, such as DNA, lipids, and proteins. A primary mechanism of many chemotherapy drugs against cancer cells is the formation of ROS, or free radicals. Radiotherapy is based on the fact that ionizing radiation destroys tumor cells. Radiotherapy induces direct lesions in the DNA or biological molecules, which eventually affect DNA. Free radicals produced by oncology therapy are often a source of serious side effects as well. The objective of this review is to provide information about the effects of antioxidants during oncology treatments and to discuss the possible events and efficacy. Much debate has arisen about whether antioxidant supplementation alters the efficacy of cancer chemotherapy. There is still limited evidence in both quality and sample size, suggesting that certain antioxidant supplements may reduce adverse reactions and toxicities. Significant reductions in toxicity may alleviate dose-limiting toxicities so that more patients are able to complete prescribed chemotherapy regimens and thus, in turn, improve the potential for success in terms of tumor response and survival. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "Role of antioxidants in cancer therapy."
},
{
"docid": "MED-3724",
"text": "Drug resistance remains an on-going challenge in ovarian cancer chemotherapy. The objective of this study was to determine the effect on synergism in activity from the sequenced combinations of cisplatin (Cis) with curcumin (Cur) and epigallocatechin-3-gallate (EGCG) in the human ovarian cancer cell lines. The drugs were added in binary combinations: Cis combined with Cur, and Cis combined with EGCG to the human ovarian A2780 and A2780(cisR) cancer cell lines, using five different sequences of administration: 0/0 h, 4/0 h, 0/4 h, 24/0 h and 0/24 h. The combination index (CI) was used to assess the combined action of the drugs. CIs <1, =1 and >1 indicated synergism, additiveness and antagonism respectively. Cellular accumulation of platinum and platinum-DNA binding levels from Cis and its combination with the phytochemicals were determined using graphite furnace atomic absorption spectrometry. Addition of Cis 4 h before Cur and EGCG (0/4 h combination) produced the most synergistic outcomes in both the A2780 and A2780(cisR) cell lines. The cellular accumulations of platinum and platinum-DNA binding resulting from the 0/4 h combinations were greater as compared to the values using Cis alone, thus providing an explanation for the synergistic action. When sequenced combinations of Cis with Cur and with EGCG are applied to human ovarian A2780 and A2780(cisR) cancer cell lines, lower concentrations and shorter time gap between the two additions seem to produce a higher cytotoxic effect.",
"title": "Synergism from sequenced combinations of curcumin and epigallocatechin-3-gallate with cisplatin in the killing of human ovarian cancer cells."
},
{
"docid": "MED-4609",
"text": "Two pandemics of heart attack deaths have plagued the world's population during the past 130 years. The first pandemic, induced by beriberi, was caused by the industrial revolution altering the nutritional composition of rice. By 1892 a simple working knowledge, then at hand, could have terminated the beriberi plague; however, orthodox medicine being then enchanted with the false concept that all disease was caused by germs, permitted millions of Asians to die needlessly of beriberi by refusing to tell them to eat rice bran or to drink rice bran tea. A second pandemic of heart attack deaths, called myocardial infarction (MI), struck the developed nations of the Western World in full force after 1930. As a hypothesis, it is suggested that this MI pandemic, still raging today, was caused by a change in food processing that occurred after 1920, when the new oil seed industry introduced into our food three greatly harmful lipid substances. The unnatural trans-trans isomer of linoleic acid, which had never been in human food prior to 1920 and which entered our food in margarines and refined oils, blocked the conversion of natural cis-cis linoleic acid to prostaglandin E1, which tends to prevent MI, both by acting as a vasodilator and by minimizing platelet aggregation. Harmful lactones were also introduced into our food, increasing the risk of MI by decreasing the fibrinolytic activity of our blood. The oil seed industry also introduced into our diet free radical lipid peroxides that make the myocardium more vulnerable to infarction. It is suggested that except for the one in 500 of us who is afflicted by familial hypercholesterolemia, the cholesterol concept of MI is as false today as was the concept in 1900 that germs caused beriberi. It is further suggested that a working knowledge is at hand today that can make death from MI just as rare as death is now from a beriberi-induced heart attack.",
"title": "The beriberi analogy to myocardial infarction."
},
{
"docid": "MED-4886",
"text": "OBJECTIVES: Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen (PSA) levels, inhibition of LNCaP cell growth, and fewer prostate cancer-related clinical events at the end of 1 year compared with controls. The aim of this study was to examine the clinical events in this trial during a 2-year period. METHODS: The Prostate Cancer Lifestyle Trial was a 1-year randomized controlled clinical trial of 93 patients with early-stage prostate cancer (Gleason score <7, PSA 4-10 ng/mL) undergoing active surveillance. The patients in the experimental arm were encouraged to adopt a low-fat, plant-based diet, to exercise and practice stress management, and to attend group support sessions. The control patients received the usual care. RESULTS: By 2 years of follow-up, 13 of 49 (27%) control patients and 2 of 43 (5%) experimental patients had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation, P < .05). No differences were found between the groups in other clinical events (eg, cardiac), and no deaths occurred. Three of the treated control patients but none of the treated experimental patients had a PSA level of >or=10 ng/mL, and 1 treated control patient but no treated experimental patients had a PSA velocity of >2 ng/mL/y before treatment. No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years. CONCLUSIONS: Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle.",
"title": "Clinical events in prostate cancer lifestyle trial: results from two years of follow-up."
},
{
"docid": "MED-4890",
"text": "Epidemiological studies suggest a positive association between nutrient intake, hyperinsulinemia and risk of Benign prostatic hyperplasis (BPH). This study tests the hypothesis that a low-fat, high-fiber diet and daily exercise would lower serum insulin and reduce the growth of serum-stimulated primary prostate epithelial cells in culture. Serum samples were obtained from eight overweight men before and after the Pritikin residential, 2-week diet and exercise intervention and from seven men who were long-term followers of the low-fat, high-fiber diet and regular exercise lifestyle. The serum was used to stimulate primary prostate epithelial cells in culture. Growth was measured after 48 and 96 h and apoptosis after 96 h. At 48 h there was no significant difference in growth within the Pre, 2-week or Long-Term groups. At 96 h growth was significantly reduced in the 2-week (13%) and in the Long-Term (14%) groups compared to the Pre data. At 96 h, apoptosis was not significantly different among the three groups. Fasting insulin was reduced by 30% in the 2-week group and by 52% in the Long-Term group compared to the Pre data. Testosterone was unchanged in the 2-week group. The results of this study indicate that a low-fat, high-fiber diet and daily exercise lowers insulin and reduces growth of prostate primary epithelial cells and suggests that lifestyle may be an important factor in the development or progression of BPH. Future prospective trials should address the effects of this lifestyle modification on BPH symptomatology and progression.",
"title": "Effect of diet and exercise intervention on the growth of prostate epithelial cells."
},
{
"docid": "MED-3555",
"text": "A number of epidemiological studies have investigated associations between various phytochemicals and cancer risk. Phytoestrogens and carotenoids are the two most commonly studied classes of phytochemicals; phytosterols, isothiocyanates, and chlorophyll also have been investigated, although to a much lesser extent. Because there have been no systematic reviews of the literature on all phytochemicals and cancer risk to date, this article systematically reviews 96 published epidemiological studies that examined associations between phytochemicals and cancer risk. Most studies found null associations between individual phytochemicals and cancer risk at various sites. In addition, results from past studies have been largely inconsistent, and observed associations have been of relatively modest magnitude. The most consistent protective effects were observed for higher levels--dietary intake, serum, plasma, or urinary metabolites--of β-carotene and renal cell cancer, β-cryptoxanthin and lung cancer, isothiocyanates and lung cancer, isothiocyanates and gastrointestinal cancer, lignans and postmenopausal breast cancer, and flavonoids and lung cancer. Although elevated risk of certain cancers with higher levels of certain phytochemicals was observed, an insufficient pool of studies examining the same associations or inconsistent findings across studies limit the ability to conclude that any one phytochemical increases cancer risk. Additional research is needed to support previously identified associations in cases where only one study has examined a particular relationship. Importantly, continued research efforts are needed to evaluate the cumulative and interactive effects of numerous phytochemicals and phytochemical-rich foods on cancer risk.",
"title": "Phytochemicals and cancer risk: a review of the epidemiological evidence."
},
{
"docid": "MED-3714",
"text": "The present study was conducted to determine differences in antioxidant levels of fresh, frozen, and freeze-dried strawberries, and strawberry jam. Hydrophilic antioxidant activity (HAA) and lipophilic antioxidant activity (LAA) were measured using the ABTS/H₂O₂/HRP decoloration method. HAA and LAA were then summed to calculate the total antioxidant activity (TAA). Mean differences in HAA and LAA were analyzed using one-way analysis of variance and Dunnett's T3 pairwise comparisons. The mean TAA for freeze-dried strawberries based on an 'as consumed' weight (95% confidence interval [CI]: 29.58, 30.58) was significantly higher than for fresh (95% CI: 3.18, 3.66), frozen (95% CI: 2.58, 2.79), and jam (95% CI: 1.10, 1.22). The mean TAA based on dry weight for fresh strawberries (95% CI: 40.48, 46.67) was significantly higher than for freeze-dried (95% CI: 29.58, 30.58), frozen (95% CI: 24.62, 26.59), and jam (95% CI: 1.48, 1.64). Results agree with previous studies reporting that strawberries are a valuable source of antioxidants for consumers.",
"title": "Differences in antioxidant levels of fresh, frozen and freeze-dried strawberries and strawberry jam."
},
{
"docid": "MED-3552",
"text": "The study evaluated the protective effects of purple rice (Oryza sativa L.) bran extract (PRE) and its constituents, cyanidin and peonidin, against angiogenesis induced by vascular endothelial growth factor (VEGF). The effects of VEGF and PRE were examined by in vitro tube formation assays and following 14-day co-culture of human umbilical vein endothelial cells (HUVECs) and fibroblasts. The antiangiogenic mechanism of PRE was evaluated by VEGF-induced proliferation and migration of HUVECs and/or human retinal microvascular endothelial cells (HRMECs) and phosphorylation of extracellular signal-regulated kinase (ERK) and p38. The PRE significantly suppressed VEGF-induced tube formation, proliferation and migration in HUVECs and HRMECs as well as phosphorylation of ERK and p38. Cyanidin and peonidin also suppressed the proliferation and migration induced by VEGF. These findings indicate that PRE and anthocyanidins suppress VEGF-induced angiogenesis by inhibiting proliferation and migration and suggest that the inhibition of phosphorylated-ERK and -p38 may be involved in the underlying mechanism. Copyright © 2011 John Wiley & Sons, Ltd.",
"title": "Purple rice (Oryza sativa L.) extract and its constituents inhibit VEGF-induced angiogenesis."
},
{
"docid": "MED-3722",
"text": "BACKGROUND: The role of dietary habits on esophageal cancer risk has been rarely considered in terms of dietary patterns. PATIENTS AND METHODS: We analyzed data from an Italian case-control study, including 304 cases with squamous cell carcinoma of the esophagus and 743 hospital controls. Dietary habits were evaluated using a food frequency questionnaire. A posteriori dietary patterns were identified through principal component factor analysis performed on 28 selected nutrients. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained from multiple logistic regression models applied on quartiles of factor scores, adjusting for potential confounding variables. RESULTS: We identified five major dietary patterns, named 'animal products and related components', 'vitamins and fiber', 'starch-rich', 'other polyunsaturated fatty acids and vitamin D', and 'other fats'. The 'animal products and related components' pattern was positively related to esophageal cancer (OR = 1.64, 95% CI:1.06-2.55, for the highest versus the lowest quartile of factor scores category). The 'vitamins and fiber' (OR = 0.50, 95% CI: 0.32-0.78) and the 'other polyunsaturated fatty acids and vitamin D' (OR = 0.48, 95% CI: 0.31-0.74) were inversely related to esophageal cancer. No significant association was observed for the other patterns. CONCLUSION: Our findings suggest that a diet rich in foods from animal origin and poor in foods containing vitamins and fiber increase esophageal cancer risk.",
"title": "Dietary patterns and the risk of esophageal cancer."
},
{
"docid": "MED-3271",
"text": "Most metastatic tumors, such as those originating in the prostate, lung, and gastrointestinal tract, respond poorly to conventional chemotherapy. Novel treatment strategies for advanced cancer are therefore desperately needed. Dietary restriction of the essential amino acid methionine offers promise as such a strategy, either alone or in combination with chemotherapy or other treatments. Numerous in vitro and animal studies demonstrate the effectiveness of dietary methionine restriction in inhibiting growth and eventually causing death of cancer cells. In contrast, normal host tissues are relatively resistant to methionine restriction. These preclinical observations led to a phase I clinical trial of dietary methionine restriction for adults with advanced cancer. Preliminary findings from this trial indicate that dietary methionine restriction is safe and feasible for the treatment of patients with advanced cancer. In addition, the trial has yielded some preliminary evidence of antitumor activity. One patient with hormone-independent prostate cancer experienced a 25% reduction in serum prostate-specific antigen (PSA) after 12 weeks on the diet, and a second patient with renal cell cancer experienced an objective radiographic response. The possibility that methionine restriction may act synergistically with other cancer treatments such as chemotherapy is being explored. Findings to date support further investigation of dietary methionine restriction as a novel treatment strategy for advanced cancer.",
"title": "Can dietary methionine restriction increase the effectiveness of chemotherapy in treatment of advanced cancer?"
},
{
"docid": "MED-3275",
"text": "In tissue cultures of normal adult and malignant mammalian cells, homocystine has been substituted for methionine in a medium rich in folic acid and cyanocobalamin. Normal adult cells thrive. Three highly malignant cell types from three different species, including man, die.",
"title": "The Effect of Replacement of Methionine by Homocystine on Survival of Malignant and Normal Adult Mammalian Cells in Culture"
},
{
"docid": "MED-3281",
"text": "INTRODUCTION: Amino acid auxotrophy or the metabolic defect which renders cancer incapable of surviving under amino acid depleted conditions is being exploited and explored as a therapeutic against cancer. Early clinical data on asparagine- and arginine-depleting drugs have demonstrated low toxicity and efficacy in melanoma, hepatocellular carcinoma and acute lymphoblastic leukemia. Methionine auxotrophy is a novel niche currently under exploration for targeting certain cancers. AREAS COVERED: In this review we explore the discovery of methionine auxotrophy followed by in vitro, in vivo and patient data on targeting cancer with methionine depletion. We end with a small discussion on bioengineering, pegylation and red blood cell encapsulation as mechanisms for decreasing immunogenicity of methionine-depleting drugs. We hope to provide a platform for future pharmacology, toxicology and cytotoxicity studies with methionine depletion therapy and drugs. EXPERT OPINION: Although methionine auxotrophy seems as a viable target, extensive research addressing normal versus cancer cell toxicity needs to be conducted. Further research also needs to be conducted into the molecular mechanism associated with methionine depletion therapy. Finally, novel methods need to be developed to decrease the immunogenicity of methionine-depleting drugs, a current issue with protein therapeutics.",
"title": "Targeting methionine auxotrophy in cancer: discovery & exploration."
},
{
"docid": "MED-5322",
"text": "BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%) and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks. Copyright 2009 S. Karger AG, Basel.",
"title": "Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting."
},
{
"docid": "MED-5324",
"text": "Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.",
"title": "Effects of a high-fat meal on pulmonary function in healthy subjects."
},
{
"docid": "MED-5335",
"text": "Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Does a vegan diet reduce risk for Parkinson's disease?"
},
{
"docid": "MED-4612",
"text": "Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.",
"title": "Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity."
},
{
"docid": "MED-3721",
"text": "Reduced expression of proapoptotic and terminal differentiation genes in conjunction with increased levels of the proinflammatory and angiogenesis-inducing enzymes, cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), correlate with malignant transformation of oral intraepithelial neoplasia (IEN). Accordingly, this study investigated the effects of a 10% (w/w) freeze-dried black raspberry gel on oral IEN histopathology, gene expression profiles, intraepithelial COX-2 and iNOS proteins, and microvascular densities. Our laboratories have shown that freeze-dried black raspberries possess antioxidant properties and also induce keratinocyte apoptosis and terminal differentiation. Oral IEN tissues were hemisected to provide samples for pretreatment diagnoses and establish baseline biochemical and molecular variables. Treatment of the remaining lesional tissue (0.5 g gel applied four times daily for 6 weeks) began 1 week after the initial biopsy. RNA was isolated from snap-frozen IEN lesions for microarray analyses, followed by quantitative reverse transcription-PCR validation. Additional epithelial gene-specific quantitative reverse transcription-PCR analyses facilitated the assessment of target tissue treatment effects. Surface epithelial COX-2 and iNOS protein levels and microvascular densities were determined by image analysis quantified immunohistochemistry. Topical berry gel application uniformly suppressed genes associated with RNA processing, growth factor recycling, and inhibition of apoptosis. Although the majority of participants showed posttreatment decreases in epithelial iNOS and COX-2 proteins, only COX-2 reductions were statistically significant. These data show that berry gel application modulated oral IEN gene expression profiles, ultimately reducing epithelial COX-2 protein. In a patient subset, berry gel application also reduced vascular densities in the superficial connective tissues and induced genes associated with keratinocyte terminal differentiation.",
"title": "Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions"
},
{
"docid": "MED-4888",
"text": "Epidemiological and prospective studies indicate that comprehensive lifestyle changes may modify the progression of prostate cancer. However, the molecular mechanisms by which improvements in diet and lifestyle might affect the prostate microenvironment are poorly understood. We conducted a pilot study to examine changes in prostate gene expression in a unique population of men with low-risk prostate cancer who declined immediate surgery, hormonal therapy, or radiation and participated in an intensive nutrition and lifestyle intervention while undergoing careful surveillance for tumor progression. Consistent with previous studies, significant improvements in weight, abdominal obesity, blood pressure, and lipid profile were observed (all P < 0.05), and surveillance of low-risk patients was safe. Gene expression profiles were obtained from 30 participants, pairing RNA samples from control prostate needle biopsy taken before intervention to RNA from the same patient's 3-month postintervention biopsy. Quantitative real-time PCR was used to validate array observations for selected transcripts. Two-class paired analysis of global gene expression using significance analysis of microarrays detected 48 up-regulated and 453 down-regulated transcripts after the intervention. Pathway analysis identified significant modulation of biological processes that have critical roles in tumorigenesis, including protein metabolism and modification, intracellular protein traffic, and protein phosphorylation (all P < 0.05). Intensive nutrition and lifestyle changes may modulate gene expression in the prostate. Understanding the prostate molecular response to comprehensive lifestyle changes may strengthen efforts to develop effective prevention and treatment. Larger clinical trials are warranted to confirm the results of this pilot study.",
"title": "Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention"
},
{
"docid": "MED-4117",
"text": "Breast cancer is a complex disease. Its aetiology is multifactorial, its period of development can span decades, and its clinical course is highly variable. Evaluation of the role of the immune response in either the development or control of breast cancer is also complex. Nevertheless, there is substantial information that in this disease, the immune response is not a host defence reaction and may even serve to facilitate cancer development. This evidence comes from a variety of sources including clinical-pathological investigations in women that show a correlation between the intensity of lymphocytic infiltration into the tumour mass with poor prognosis, studies in breast cancer patients that demonstrate a similar correlation between delayed hypersensitivity reactivity or in vitro assays of immune reactivity to tumour cell membranes or non-specific antigens and poor prognosis, and analyses of cancer incidence in chronically immunosuppressed, kidney transplant recipients who develop an unexpectedly low incidence of breast cancer. The overall conclusions from these human studies are corroborated by observations in mouse mammary tumour models that also demonstrate immune enhancement of breast cell proliferation in vitro and of breast cancer development in vivo. Potential mechanisms for these effects include production, by inflammatory cell infiltrates, of direct or indirect modulators of breast cell growth, e.g. cytokines, peptide or steroid hormones, enzymes involved in steroid metabolism, as well as of antibodies to growth factors or their receptors. These immune facilitatory mechanisms must be overcome if immune-based therapies are to be applied successfully in breast cancer.",
"title": "Immunological enhancement of breast cancer."
},
{
"docid": "MED-5342",
"text": "Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.",
"title": "Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults"
},
{
"docid": "MED-3717",
"text": "We briefly highlight the growing body of recent evidence linking unprotected oral sex with the development of some types of head and neck cancer in younger patients. These tumours appear to be increasing in incidence although the development of more sensitive methods of HPV detection may be a confounding factor.",
"title": "Oral sex, cancer and death: sexually transmitted cancers"
},
{
"docid": "MED-5337",
"text": "PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.",
"title": "Intensive lifestyle changes may affect the progression of prostate cancer."
},
{
"docid": "MED-3280",
"text": "Conventional chemotherapies have showed their limits, notably for patients with advanced cancer. New therapeutic strategies must be identified, and the metabolic abnormalities of cancer cells offer such opportunities. Many human cancer cell lines and primary tumors have absolute requirements for methionine, an essential amino acid. In contrast, normal cells are relatively resistant to exogenous methionine restriction. The biochemical mechanism for methionine dependency has been studied extensively, but the fundamental mechanism remains unclear. A number of investigators have attempted to exploit the methionine dependence of tumors for therapeutic effects in vivo. To reduce in vivo methionine in plasma and tumours, dietary and pharmacological treatments have been used. Methionine-free diet or methionine-deprived total parenteral nutrition causes regression of a variety of animal tumours. Alternatively, methionine depletion was achieved by the use of methioninase. This enzyme specifically degrades methionine and inhibits tumour growth in preclinical models. Because of potential toxicity and quality of life problems, prolonged methionine restriction with diet or with methioninase is not suitable for clinical use. Methionine restriction may find greater application in association with various chemotherapeutic agents. Several preclinical studies have demonstrated synergy between methionine restriction and various cytotoxic chemotherapy drugs. The experimental results accumulated during the last three decades suggest that methionine restriction can become an additional cancer therapeutic strategy, notably in association with chemotherapy.",
"title": "Methionine dependency and cancer treatment."
},
{
"docid": "MED-3548",
"text": "Cancer metastasis refers to the spread of cancer cells from the primary neoplasm to distant sites, where secondary tumors are formed, and is the major cause of death from cancer. Natural phytochemicals containing phenolic compounds have been widely demonstrated to have the capability to prevent cancer metastasis. Among phenolic compounds, flavonoids are a very large subclass, and they are abundant in food and nutraceuticals. The number of reports demonstrating that flavonoids are an effective natural inhibitor of cancer invasion and metastasis is increasing in the scientific literature. Catechin derivatives, (−)-epigallocatechin-3-gallate, (−)-epigallocatechin, (−)-epicatechin-3-gallate,and (−)-epicatechin, are the most studied compounds in this topic so far; genistein/genistin, silibinin, quercetin, and anthocyanin have also been widely investigated for their inhibitory activities on invasion/metastasis. Other flavonoids in dietary vegetable foods that are responsible for anti-invasive and anti-metastatic activities of tumors include luteolin,apigenin, myricetin, tangeretin, kaempferol, glycitein, licoricidin,daidzein, and naringenin. To effectively overcome the metastatic cascade, including cell-cell attachment, tissue barrier degradation, migration, invasion, cell-matrix adhesion,and angiogenesis, it is essential that a bioactive compound prevent tumor cells from metastasizing. This review summarizes the effects of flavonoids on the metastatic cascade and the related proteins, the in vitro anti-invasive activity of flavonoids against cancer cells, and the effects of flavonoids on antiangiogenic and in vivo anti-metastatic models. The available scientific evidence indicates that flavonoids are a ubiquitous dietary phenolics subclass and exert extensive in vitro anti-invasive and in vivo anti-metastatic activities.",
"title": "Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities."
},
{
"docid": "MED-3553",
"text": "Several epidemiological studies have indicated that abundant consumption of foods from plant origin is associated with a reduced risk of developing several types of cancers. This chemopreventive effect is related to the high content of these foods in phytochemicals, such as polyphenols, that interfere with several processes involved in cancer progression including tumor cell growth, survival and angiogenesis. In addition to the low intake of plant-based foods, increased body mass and physical inactivity have recently emerged as other important lifestyle factors influencing cancer risk, leading to the generation of low-grade chronic inflammatory conditions which are a key process involved in tumor progression. The objectives of the current study are to investigate the inhibitory effects of these polyphenols on angiogenesis triggered by an inflammatory cytokine (IL-6) and to determine the mechanisms underlying this action. We found that, among the tested polyphenols, apigenin and luteolin were the most potent angiogenesis inhibitors through their inhibitory effect on the inflammatory cytokine IL-6/STAT3 pathway. These effects resulted in modulation of the activation of extracellular signal-regulated kinase-1/2 signaling triggered by IL-6, as well as in a marked reduction in the proliferation, migration and morphogenic differentiation of endothelial cells. Interestingly, these polyphenols also modulated the expression of IL-6 signal transducing receptor (IL-6Rα) and the secretion of the extracellular matrix degrading enzyme MMP-2 as well as the expression of suppressor of cytokine signaling (SOCS3) protein. Overall, these results may provide important new information on the role of diet in cancer prevention. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Diet-derived polyphenols inhibit angiogenesis by modulating the interleukin-6/STAT3 pathway."
},
{
"docid": "MED-5330",
"text": "Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05 compared with low-fat meal data). No changes in lipoproteins or flow-mediated vasoactivity were observed after the low-fat meal. Fasting low-density lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results demonstrate that a single high-fat meal transiently impairs endothelial function. These findings identify a potential process by which a high-fat diet may be atherogenic independent of induced changes in cholesterol.",
"title": "Effect of a single high-fat meal on endothelial function in healthy subjects."
},
{
"docid": "MED-3730",
"text": "Dysplasia is a histologic precursor of esophageal squamous cell carcinoma (SCC). We previously showed that dietary freeze-dried, or lyophilized, strawberry powder inhibits N-nitrosomethylbenzylamine-induced SCC in the rat esophagus. On the basis of this observation, we conducted a randomized (noncomparative) phase II trial in China to investigate the effects of two doses of freeze-dried strawberries in patients with esophageal dysplastic lesions in a high-risk area for esophageal cancer. We randomly assigned 75 patients identified by endoscopy to have dysplastic esophageal premalignant lesions to receive freeze-dried strawberry powder at either 30 g/d (37 patients) or 60 g/d (38 patients) for six months; the powder was mixed with water and drunk. After six months, we assessed the changes in histologic grade of these lesions (primary endpoint) in a blinded fashion. The dose of 30 g/d, did not significantly affect histology or any other measured parameter. The dose of 60 g/d, however, reduced the histologic grade of dysplastic premalignant lesions in 29 (80.6%) of the 36 patients at this dose who were evaluated for histology (P < 0.0001). The strawberry powder was well tolerated, with no toxic effects or serious adverse events. Strawberries (60 g/d) also reduced protein expression levels of inducible nitric oxide synthase (iNOS) by 79.5% (P < 0.001), cyclooxygenase-2 (COX-2) by 62.9% (P < 0.001), phospho-nuclear factor kappa B (NFκB)-p65 (pNFκB-p65) by 62.6% (P < 0.001), and phospho-S6 (pS6) by 73.2% (P < 0.001). Freeze-dried strawberries (60 g/d) also significantly inhibited the Ki-67 labeling index by 37.9% (P = 0.023). Our present results indicate the potential of freeze-dried strawberry powder for preventing human esophageal cancer, supporting further clinical testing of this natural agent in this setting. ©2011 AACR.",
"title": "Randomized phase II trial of lyophilized strawberries in patients with dysplastic precancerous lesions of the esophagus."
},
{
"docid": "MED-5363",
"text": "OBJECTIVE: Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. METHODS: Subjects were 521 municipal employees (309 men and 212 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D >or=16) with adjustment for potential confounding variables. RESULTS: We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62-1.59) and 0.44 (0.25-0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms. CONCLUSIONS: Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status.",
"title": "Dietary patterns and depressive symptoms among Japanese men and women."
},
{
"docid": "MED-5325",
"text": "Objective Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores. Design Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Setting Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire. Subjects Five hundred white subjects representing the AHS-2 cohort. Results Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β =−6·8, P<0·05 and β = −6·9, P<0·001). Findings for lacto-ovo vegetarians (β = −9·1, P<0·001 and β = −5·8, P<0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI. Conclusions We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.",
"title": "Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2)"
},
{
"docid": "MED-5328",
"text": "Aim To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. Methods and Results Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses. Conclusion Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.",
"title": "Vegetarian diets and incidence of diabetes in the Adventist Health Study-2"
},
{
"docid": "MED-3719",
"text": "Purpose The objective of this study was to formulate and evaluate freeze-dried black raspberry (FBR) ethanol extract (RE) loaded poly(DL-lactic-co-glycolic acid) (PLGA) and poly(DL-lactic acid) (PLA) injectable millicylindrical implants for sustained delivery of chemopreventive FBR anthocyanins (cyanidin-3-sambubioside (CS), cyanidin-3-glucoside (CG) and cyanidin-3-rutinoside (CR)). Methods Identification and quantitation of CS, CG, and CR in RE was performed by mass spectroscopy and HPLC. RE:triacetyl-β-cyclodextrin (TA-β-CD) inclusion complex (IC) was prepared by a kneading method and characterized by X-ray diffraction (XRD), nuclear magnetic resonance spectroscopy (NMR) and UV-visible spectroscopy. RE or RE:TA-β-CD IC-loaded PLGA or PLA implants were prepared by a solvent extrusion method. In vitro and in vivo controlled release studies were conducted in phosphate-buffered saline Tween-80 (pH 7.4, 37°C) and after subcutaneous administration in male Sprague-Dawley rats, respectively. Anthocyanins were quantified by HPLC at 520 nm. Results The content of CS, CG, and CR in RE was 0.2, 1.5, and 3.5 wt%, respectively. The chemical stability of anthocyanins in solution was determined to be pH-dependent, and their degradation rate increased with an increase in pH from 2.4 to 7.4. PLGA/PLA millicylindrical implants loaded with 5 or 10 wt% RE exhibited a high initial burst and short release duration of anthocyanins (35–52 and 80–100% CG + CR release after 1 and 14 days, respectively). The cause for rapid anthocyanins release was linked to higher polymer water uptake and porosity associated with the high osmolytic components of large non-anthocyanin fraction of RE. XRD, 1H NMR and UV-visible spectroscopy indicated that the non-anthocyanin fraction molecules of RE formed an IC with TA-β-CD, decreasing the hydrophilicity of RE. Formation of an IC with hydrophobic carrier, TA-β-CD, provided better in vitro/in vivo sustained release of FBR anthocyanins (16–24 and 97–99% CG + CR release, respectively, after 1 and 28 days from 20 wt% RE:TA-β-CD IC/PLA implants) over 1 month, owing to reduced polymer water uptake and porosity. Conclusion PLA injectable millicylindrical implants loaded with RE:TA-β-CD IC are optimal dosage forms for 1-month slow and continuous delivery of chemopreventive FBR anthocyanins.",
"title": "Formulation and In Vitro-In Vivo Evaluation of Black Raspberry Extract-Loaded PLGA/PLA Injectable Millicylindrical Implants for Sustained Delivery of Chemopreventive Anthocyanins"
},
{
"docid": "MED-5323",
"text": "This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta-hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.",
"title": "Endocrine-disrupting chemicals and obesity development in humans: a review."
},
{
"docid": "MED-5331",
"text": "A global health transition is currently underway. The burden of non-communicable diseases (NCDs) is increasing rapidly in the developing world, very much as a result of changes in lifestyles. In addition to changes in tobacco use and physical activity, major changes are taking place in diets, contributing greatly to the growing epidemic of NCD. Thus, a huge global public health challenge is how to influence the trends in diet and nutrition for effective global NCD prevention. The health transition took place rapidly in Finland after World War II and mortality from cardiovascular disease (CVD) was exceptionally high. The North Karelia Project was launched in 1972 as a community-based, and later as a national, programme to influence diet and other lifestyles that are crucial in the prevention of CVD. The intervention had a strong theory base and it employed comprehensive strategies. Broad community organisation and the strong participation of people were the key elements. Evaluation has shown how the diet (particularly fat consumption) has changed and how these changes have led to a major reduction in population serum cholesterol and blood pressure levels. It has also shown how ischaemic heart disease mortality in a working-age population has declined by 73% in North Karelia and by 65% in the whole country from 1971 to 1995. Although Finland is an industrialised country, North Karelia was rural, of rather low socio-economic level and with many social problems in the 1970s and 1980s. The project was based on low-cost intervention activities, where people's participation and community organisations played a key role. Comprehensive interventions in the community were eventually supported by national activities--from expert guidelines and media activities to industry collaboration and policy. Similar principles for nutrition intervention programmes could be used in developing countries, obviously tailored to the local conditions. This paper discusses the experiences of the North Karelia Project in the light of needs from the less-industrialised countries and makes some general recommendations.",
"title": "Influencing public nutrition for non-communicable disease prevention: from community intervention to national programme--experiences from Finland."
},
{
"docid": "MED-5340",
"text": "In Asia, vegetarianism is a well-established eating behavior. It appears that the adoption of a vegan diet leads to a lessening of several health risk factors. Although vegetarianism has some notable effects on the hematological system, the effect on the nephrological system has not been well clarified. The pattern of renal function parameters was studied in 25 Thai vegans compared with 25 non-vegetarians. Of the studied parameters, it was found that urine protein was significantly different (p < 0.05) in vegans and controls. Vegans had significantly lower urine protein level.",
"title": "Renal function parameters of Thai vegans compared with non-vegans."
},
{
"docid": "MED-3270",
"text": "Aging affects all organisms and its basic mechanisms are expected to be conserved across species. Oxidation of proteins has been proposed to be one of the basic mechanisms linking oxygen radicals with the basic aging process. If oxidative damage to proteins is involved in aging, long-lived animals (which age slowly) should show lower levels of markers of this kind of damage than short-lived ones. However, this possibility has not been investigated yet. In this study, steady-state levels of markers of different kinds of protein damage--oxidation (glutamic and aminoadipic semialdehydes), mixed glyco- and lipoxidation (carboxymethyl- and carboxyethyllysine), lipoxidation (malondialdehydelysine) and amino acid composition--were measured in the heart of eight mammalian species ranging in maximum life span (MLSP) from 3.5 to 46 years. Oxidation markers were directly correlated with MLSP across species. Mixed glyco- and lipoxidation markers did not correlate with MLSP. However, the lipoxidation marker malondialdehydelysine was inversely correlated with MLSP (r2=0.85; P<0.001). The amino acid compositional analysis revealed that methionine is the only amino acid strongly correlated MLSP and that such correlation is negative (r2=0.93; P<0.001). This trait may contribute to lower steady-state levels of oxidized methionine residues in cellular proteins. These results reinforce the notion that high longevity in homeothermic vertebrates is achieved in part by constitutively decreasing the sensitivity of both tissue proteins and lipids to oxidative damage. This is obtained by modifying the constituent structural components of proteins and lipids, selecting those less sensitive to oxidative modifications.",
"title": "Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals."
},
{
"docid": "MED-3272",
"text": "Objective Early detection and early treatment are of vital importance to the successful treatment of various cancers. The development of a novel screening method that is as economical and non-invasive as the faecal occult blood test (FOBT) for early detection of colorectal cancer (CRC) is needed. A study was undertaken using canine scent detection to determine whether odour material can become an effective tool in CRC screening. Design Exhaled breath and watery stool samples were obtained from patients with CRC and from healthy controls prior to colonoscopy. Each test group consisted of one sample from a patient with CRC and four control samples from volunteers without cancer. These five samples were randomly and separately placed into five boxes. A Labrador retriever specially trained in scent detection of cancer and a handler cooperated in the tests. The dog first smelled a standard breath sample from a patient with CRC, then smelled each sample station and sat down in front of the station in which a cancer scent was detected. Results 33 and 37 groups of breath and watery stool samples, respectively, were tested. Among patients with CRC and controls, the sensitivity of canine scent detection of breath samples compared with conventional diagnosis by colonoscopy was 0.91 and the specificity was 0.99. The sensitivity of canine scent detection of stool samples was 0.97 and the specificity was 0.99. The accuracy of canine scent detection was high even for early cancer. Canine scent detection was not confounded by current smoking, benign colorectal disease or inflammatory disease. Conclusions This study shows that a specific cancer scent does indeed exist and that cancer-specific chemical compounds may be circulating throughout the body. These odour materials may become effective tools in CRC screening. In the future, studies designed to identify cancer-specific volatile organic compounds will be important for the development of new methods for early detection of CRC.",
"title": "Colorectal cancer screening with odour material by canine scent detection"
},
{
"docid": "MED-3277",
"text": "Methionine dependence is a metabolic defect that occurs in many human tumor cell lines but not normal in unestablished cell strains. Methionine-dependent tumor cell lines are unable to proliferate and arrest in the late S/G2 phase of the cell cycle when methionine is replaced by its immediate precursor homocysteine in the culture medium (MET-HCY+ medium). However, it is not known whether methionine dependence occurs in fresh patient tumors as it does in cell lines. In order to determine whether methionine dependence occurs in fresh patient tumors as well as whether methionine dependence occurs in fresh patient tumors as well as in cell lines we took advantage of the technique of sponge-gel-supported histoculture to grow tumors directly from surgery. We then measured nuclear DNA content by image analysis to determine the cell cycle position in MET-HCY+ compared to MET+HCY- medium in 21 human patient tumors. Human tumor cell lines found to be methionine dependent by cell count were used as positive controls and were found to have marked reduction of cells in G1 compared to total cells in the cell cycle in MET-HCY+ medium with respect to the G1: total cell ratio in MET+HCY- medium. Therefore late cell cycle arrest was used as a marker of methionine dependence for histocultured patient tumors. We found that 5 human tumors of 21, including tumors of the colon, breast, ovary, prostate, and a melanoma, were methionine dependent based on cell cycle analysis. These data on fresh human tumors indicate that methionine dependence may frequently occur in the cancer patient population. Implications for potential therapy based on methionine dependence are discussed.",
"title": "Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture."
},
{
"docid": "MED-3278",
"text": "Lung cancer (LC) continues to represent a heavy burden for health care systems worldwide. Epidemiological studies predict that its role will increase in the near future. While patient prognosis is strongly associated with tumour stage and early detection of disease, no screening test exists so far. It has been suggested that electronic sensor devices, commonly referred to as ‘electronic noses’, may be applicable to identify cancer-specific volatile organic compounds in the breath of patients and therefore may represent promising screening technologies. However, three decades of research did not bring forward a clinically applicable device. Here, we propose a new research approach by involving specially trained sniffer dogs into research strategies by making use of their ability to identify LC in the breath sample of patients.",
"title": "Sniffer dogs as part of a bimodal bionic research approach to develop a lung cancer screening"
},
{
"docid": "MED-3716",
"text": "Purpose The aim of this study was to assess the effects of topical application of a 10% (w/w) freeze-dried black raspberry (FBR) gel on oral intraepithelial neoplasia (IEN) variables that included histologic diagnoses and loss of heterozygosity (LOH) indices. Microsatellite instability and/or LOH at tumor suppressor gene – associated chromosomal loci have been associated with a higher risk for oral IEN progression to oral squamous cell carcinoma. Previously, our laboratories have shown that FBRs are well tolerated and possess potent antioxidant, apoptotic, and differentiation-inducing properties. Experimental Design Each participant with IEN served as their own internal control. Before treatment, all lesions were photographed, and lesional tissue was hemisected to obtain a pretreatment diagnosis and baseline biochemical and molecular variables. Gel dosing (0.5 g applied four times daily for 6 weeks) was initiated 1 week after the initial biopsy. Genomic DNA was isolated from laser-captured basilar and suprabasilar surface epithelial cells followed by PCR amplification using primer sets that targeted known and presumed tumor suppressor gene loci associated with INK4a/ARF, p53, and FHIT. Allelic imbalance was determined by sequence analysis using normal participant tissues to establish microsatellite marker peak patterns and allele sizes. Results Confirming earlier phase I data, none of the 27 participants developed FBR gel – associated toxicities. Furthermore, our results show histologic regression in a subset of patients as well as statistically significant reduction in LOH at tumor suppressor gene – associated loci. Conclusions These preliminary data suggest that further evaluation of berry gels for oral IEN chemoprevention is warranted.",
"title": "Effects of a Topically Applied Bioadhesive Berry Gel on Loss of Heterozygosity Indices in Premalignant Oral Lesions"
},
{
"docid": "MED-5333",
"text": "BACKGROUND/AIM: A vegetarian diet is known to prevent a series of diseases but may influence the balance of carbohydrate and fat metabolism as well as collagen synthesis. This study compares expression patterns of relevant genes in oral mucosa of omnivores and vegetarians. METHODS: Quantitative reverse transcriptase polymerase chain reaction was applied for analysis of mRNA levels from carnitine transporter OCTN2, hepatic CPT1A and nonhepatic CPT1B isoforms of carnitine palmitoyltransferase and collagen (CCOL2A1) in oral mucosa. RESULTS: Compared with volunteers with traditional eating habits, carbohydrate consumption was significantly higher (+22%) in vegetarians. This was associated with a significant stimulation of CPT1A (+50%) and OCTN2 (+10%) and a lowered collagen synthesis (-10%). CONCLUSION: These novel findings provide further insight into the association of a changed fat metabolism and reduced collagen synthesis in vegetarians, which could also play a role in the aging process. Copyright 2008 S. Karger AG, Basel.",
"title": "Vegetarian diet affects genes of oxidative metabolism and collagen synthesis."
},
{
"docid": "MED-4617",
"text": "The need for consistent and current data describing the true incidence of SCA and/or SCD was highlighted during the most recent Sudden Cardiac Arrest Thought Leadership Alliance’s (SCATLA) Think Tank meeting of national experts with broad representation of key stakeholders including thought leaders and representatives from the American College of Cardiology, American Heart Association, and the Heart Rhythm Society. As such, to evaluate the true magnitude of this public health problem, we performed a systematic literature search in MEDLINE using the MeSH headings, “death, sudden” OR the terms “sudden cardiac death” OR “sudden cardiac arrest” OR “cardiac arrest” OR “cardiac death” OR “sudden death” OR “arrhythmic death.” Study selection criteria included peer-reviewed publications of primary data used to estimate SCD incidence in the U.S. We used Web of Science®’s Cited Reference Search to evaluate the impact of each primary estimate on the medical literature by determining the number of times each “primary source” has been cited. The estimated U.S. annual incidence of SCD varied widely from 180,000 to > 450,000 among 6 included studies. These different estimates were in part due to different data sources (with data age ranging from 1980 to 2007), definitions of SCD, case ascertainment criteria, methods of estimation/extrapolation, and sources of case ascertainment. The true incidence of SCA and/or SCD in the U.S. remains unclear with a wide range in the available estimates, which are badly dated. As reliable estimates of SCD incidence are important for improving risk stratification and prevention, future efforts are clearly needed to establish uniform definitions of SCA and SCD and then to prospectively and precisely capture cases of SCA and SCD in the overall U.S. population.",
"title": "Systematic Review of the Incidence of Sudden Cardiac Death in the United States"
},
{
"docid": "MED-3720",
"text": "Black raspberries are a rich natural source of chemopreventive phytochemicals. Recent studies have shown that freeze-dried black raspberries inhibit the development of oral, esophageal, and colon cancer in rodents, and extracts of black raspberries inhibit benzo(a)pyrene-induced cell transformation of hamster embryo fibroblasts. However, the molecular mechanisms and the active components responsible for black raspberry chemoprevention are unclear. In this study, we found that 2 major chemopreventive components of black raspberries, ferulic acid and beta-sitosterol, and a fraction eluted with ethanol (RO-ET) during silica column chromatography of the organic extract of freeze-dried black raspberries inhibit the growth of premalignant and malignant but not normal human oral epithelial cell lines. Another fraction eluted with CH2Cl2/ethanol (DM:ET) and ellagic acid inhibited the growth of normal as well as premalignant and malignant human oral cell lines. We investigated the molecular mechanisms by which ferulic acid and beta-sitosterol and the RO-ET fraction selectively inhibited the growth of premalignant and malignant oral cells using flow cytometry and Western blotting of cell cycle regulatory proteins. There was no discernable change in the cell cycle distribution following treatment of cells with the RO-ET fraction. Premalignant and malignant cells redistributed to the G2/M phase of the cell cycle following incubation with ferulic acid. beta-sitosterol treated premalignant and malignant cells accumulated in the G0/G1 and G2/M phases, respectively. The RO-ET fraction reduced the levels of cyclin A and cell division cycle gene 2 (cdc2) in premalignant cells and cyclin B1, cyclin D1, and cdc2 in the malignant cell lines. This fraction also elevated the levels of p21waf1/cip1 in the malignant cell line. Ferulic acid treatment led to increased levels of cyclin B1 and cdc2 in both cell lines, and p21waf1/cip1 was induced in the malignant cell line. beta-sitosterol reduced the levels of cyclin B1 and cdc2 while increasing p21waf1/cip1 in both the premalignant and malignant cell lines. These results show for the first time that the growth inhibitory effects of black raspberries on premalignant and malignant human oral cells may reside in specific components that target aberrant signaling pathways regulating cell cycle progression.",
"title": "Inhibition of the growth of premalignant and malignant human oral cell lines by extracts and components of black raspberries."
},
{
"docid": "MED-3744",
"text": "Consumption of fruits and vegetables has been associated with reduced risk of chronic diseases such as cardiovascular disease and cancer. Phytochemicals, especially phenolics, in fruits and vegetables are suggested to be the major bioactive compounds for the health benefits. However, the phenolic contents and their antioxidant activities in fruits and vegetables were underestimated in the literature, because bound phenolics were not included. This study was designed to investigate the profiles of total phenolics, including both soluble free and bound forms in common fruits, by applying solvent extraction, base digestion, and solid-phase extraction methods. Cranberry had the highest total phenolic content, followed by apple, red grape, strawberry, pineapple, banana, peach, lemon, orange, pear, and grapefruit. Total antioxidant activity was measured using the TOSC assay. Cranberry had the highest total antioxidant activity (177.0 +/- 4.3 micromol of vitamin C equiv/g of fruit), followed by apple, red grape, strawberry, peach, lemon, pear, banana, orange, grapefruit, and pineapple. Antiproliferation activities were also studied in vitro using HepG(2) human liver-cancer cells, and cranberry showed the highest inhibitory effect with an EC(50) of 14.5 +/- 0.5 mg/mL, followed by lemon, apple, strawberry, red grape, banana, grapefruit, and peach. A bioactivity index (BI) for dietary cancer prevention is proposed to provide a new alternative biomarker for future epidemiological studies in dietary cancer prevention and health promotion.",
"title": "Antioxidant and antiproliferative activities of common fruits."
},
{
"docid": "MED-4887",
"text": "Cardiovascular symptom relief is a major indicator for revascularization procedures. To examine the effects of intensive lifestyle modification on symptom relief, we investigated changes in angina pectoris, coronary risk factors, quality of life, and lifestyle behaviors in patients with stable coronary artery disease enrolled in the multisite cardiac lifestyle intervention program, an ongoing health insurance-covered lifestyle intervention conducted at 22 sites in the united states. Patients with coronary artery disease (nonsmokers; 757 men, 395 women; mean age 61 years) were asked to make changes in diet (10% calories from fat, plant based), engage in moderate exercise (3 hours/week), and practice stress management (1 hour/day). At baseline, 108 patients (43% women) reported mild angina and 174 patients (37% women) reported limiting angina. By 12 weeks, 74% of these patients were angina free, and an additional 9% moved from limiting to mild angina. This improvement in angina was significant for patients with mild and limiting angina at baseline regardless of gender (p <0.01). Significant improvements in cardiac risk factors, quality of life, and lifestyle behaviors were observed, and patients with angina who became angina free by 12 weeks showed the greatest improvements in exercise capacity, depression, and health-related quality of life (p <0.05). In conclusion, the observed improvements in angina in patients making intensive lifestyle changes could drastically reduce their need for revascularization procedures.",
"title": "Angina pectoris and atherosclerotic risk factors in the multisite cardiac lifestyle intervention program."
},
{
"docid": "MED-5332",
"text": "The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.",
"title": "Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age."
},
{
"docid": "MED-5334",
"text": "Until recently, intact protein that is rich in tryptophan was not seen as an alternative to pharmaceutical-grade tryptophan because protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a rich source of tryptophan with approximately 22 mg/g protein) is combined with glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective and subjective measures of anxiety in those suffering from social phobia (also known as social anxiety disorder) were employed to measure changes in anxiety in response to a stimulus as part of a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between study sessions. Subjects were randomly assigned to start with either (i) protein-source tryptophan (deoiled gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week after the initial session, subjects returned for a follow-up session and received the opposite treatment of that received at the first session. All 7 subjects who began the study completed the 2-week protocol. Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement on an objective measure of anxiety. Protein-source tryptophan combined with a high glycemic carbohydrate is a potential anxiolytic to those suffering from social phobia.",
"title": "Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study."
},
{
"docid": "MED-3554",
"text": "A great deal of effort is now being devoted to the development of new drugs that hopefully will control the spread of inoperable cancer by safely inhibiting tumor-evoked angiogenesis. However, there is growing evidence that certain practical nutritional measures have the potential to slow tumor angiogenesis, and it is reasonable to anticipate that, by combining several measures that work in distinct but complementary ways to impede the angiogenic process, a clinically useful 'multifocal angiostatic therapy' (MAT) might be devised. Several measures which might reasonably be included in such a protocol are discussed below, and include: a low-fat, low-glycemic index vegan diet, which may down-regulate the systemic IGF-I activity that supports angiogenesis; supplemental omega-3-rich fish oil, which has been shown to inhibit endothelial expression of Flk-1, a functionally crucial receptor for VEGF, and also can suppress tumor production of pro-angiogenic eicosanoids; high-dose selenium, which has recently been shown to inhibit tumor production of VEGF; green tea polyphenols, which can suppress endothelial responsiveness to both VEGF and fibroblast growth factor; and high-dose glycine, whose recently reported angiostatic activity may reflect inhibition of endothelial cell mitosis, possibly mediated by activation of glycine-gated chloride channels. In light of evidence that tumor-evoked angiogenesis has a high requirement for copper, copper depletion may have exceptional potential as an angiostatic measure, and is most efficiently achieved with the copper-chelating drug tetrathiomolybdate. If logistical difficulties make it difficult to acquire this experimental drug, high-dose zinc supplementation can achieve a slower depletion of the body's copper pool, and in any case can be used as maintenance therapy to maintain an adequate level of copper depletion. A provisional protocol is offered for a nutritionally based MAT entailing a vegan diet and supplemental intakes of fish oil, selenium, green tea polyphenols, glycine, and zinc. Inasmuch as cox-2 is overexpressed in many cancers, and cAMP can boost tumor production of various angiogenic factors as well as autogenous growth factors, adjunctive use of cox-2-specific NSAIDS may be warranted in some cases.",
"title": "A wholly nutritional 'multifocal angiostatic therapy' for control of disseminated cancer."
},
{
"docid": "MED-5326",
"text": "The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Red meat and colon cancer: should we become vegetarians, or can we make meat safer?"
},
{
"docid": "MED-3279",
"text": "Various pesticides are being used to destabilize, perturb, or inhibit crucial biochemical and physiological targets related to metabolism, growth, development, nervous communication, or behavior in pestiferous organisms. Chitin is an eukaryotic extracellular aminosugar biopolymer, massively produced by most fungal systems and by invertebrates, notably arthropods. Being an integral supportive component in fungal cell wall, insect cuticle, and nematode egg shell, chitin has been considered as a selective target for pesticide action. Throughout the elaborate processes of chitin formation and deposition, only the polymerization events associated with the cell membrane compartment are so far available for chemical interference. Currently, the actinomycetes-derived nucleoside peptide fungicides such as the polyoxins and the insecticidal benzoylaryl ureas have reached commercial pesticide status. The polyoxins and other structurally-related antibiotics like nikkomycins are strong competitive inhibitors of the polymerizing enzyme chitin synthase. The exact biochemical lesion inflicted by the benzoylaryl ureas is still elusive, but a post-polymerization event, such as translocation of chitin chains across the cell membrane, is suggested. Hydrolytic degradation of the chitin polymer is essential for hyphal growth, branching, and septum formation in fungal systems as well as for the normal molting of arthropods. Recently, insect chitinase activity was strongly and specifically suppressed by allosamidin, an actimomycetes-derived metabolite. In part, the defense mechanism in plants against invasion of pathogens is associated with induced chitinases. Chitin, chitosan, and their oligomers are able to act as elicitors which induce enhanced levels of chitinases in various plants. Lectins which bind to N-acetyl-D-glucosamine strongly interfere with fungal and insect chitin synthases. Plant lectins with similar properties may be involved in plant-pathogen interaction inter alia by suppressing fungal invasion.",
"title": "Chitin synthesis and degradation as targets for pesticide action."
},
{
"docid": "MED-3283",
"text": "Available information indicates that long-lived mammals have low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, many studies have consistently shown that dietary restriction (DR) in rodents also decreases mitochondrial ROS (mtROS) production and oxidative damage to mitochondrial DNA and proteins. It has been observed that protein restriction also decreases mtROS generation and oxidative stress in rat liver, whereas neither carbohydrate nor lipid restriction change these parameters. This is interesting because protein restriction also increases maximum longevity in rodents (although to a lower extent than DR) and is a much more practicable intervention for humans than DR, whereas neither carbohydrate nor lipid restriction seem to change rodent longevity. Moreover, it has been found that isocaloric methionine restriction also decreases mtROS generation and oxidative stress in rodent tissues, and this manipulation also increases maximum longevity in rats and mice. In addition, excessive dietary methionine also increases mtROS generation in rat liver. These studies suggest that the reduced intake of dietary methionine can be responsible for the decrease in mitochondrial ROS generation and the ensuing oxidative damage that occurs during DR, as well as for part of the increase in maximum longevity induced by this dietary manipulation. In addition, the mean intake of proteins (and thus methionine) of Western human populations is much higher than needed. Therefore, decreasing such levels to the recommended ones has a great potential to lower tissue oxidative stress and to increase healthy life span in humans while avoiding the possible undesirable effects of DR diets.",
"title": "Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible i..."
},
{
"docid": "MED-3550",
"text": "Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic drugs are now available for many advanced malignancies (colorectal, lung, breast, kidney, liver, brain, thyroid, neuroendocrine, multiple myeloma, myelodysplastic syndrome), cost and toxicity considerations preclude their broad use for cancer prevention. Potent antiangiogenic molecules have now been identified in dietary sources, suggesting that a rationally designed antiangiogenic diet could provide a safe, widely available, and novel strategy for preventing cancer. This paper presents the scientific, epidemiologic, and clinical evidence supporting the role of an antiangiogenic diet for cancer prevention.",
"title": "Tumor Angiogenesis as a Target for Dietary Cancer Prevention"
},
{
"docid": "MED-4220",
"text": "OBJECTIVE: Accumulating evidence indicates that prostate cancer is associated with high levels of serum IGF-I. This study was conducted to determine whether a low-fat diet and exercise (DE) intervention may modulate the IGF axis and reduce prostate cancer cell growth in vitro. METHODS: Fasting serum was obtained from 14 men (age 60 +/- 3 years) participating in an 11-day DE program and from eight similarly aged men who had followed the DE program for 14.2 +/- 1.7 years (long-term). Insulin, IGF-I, IGFBP-1, and IGFBP-3 were measured by ELISA, and serum was used to stimulate LNCaP cell growth in vitro. RESULTS: Serum IGF-I levels decreased by 20% while IGFBP-1 increased by 53% after 11-day DE. In the long-term group, IGF-I was 55% lower, while IGFBP-1 was 150% higher relative to baseline. Serum insulin decreased by 25% after 11-day DE and was 68% lower in the long-term group, relative to baseline. No changes in serum IGFBP-3 were observed. Serum-stimulated LNCaP cell growth was reduced by 30% in post-11-day serum and by 44% in long-term serum relative to baseline. LNCaP cells incubated with post-DE serum showed increased apoptosis/ necrosis, compared to baseline. CONCLUSIONS: A low-fat diet and exercise intervention induces in-vivo changes in the circulating IGF axis and is associated with reduced growth and enhanced apoptosis/necrosis of LNCaP tumor cells in vitro.",
"title": "Effect of diet and exercise on serum insulin, IGF-I, and IGFBP-1 levels and growth of LNCaP cells in vitro (United States)."
},
{
"docid": "MED-5338",
"text": "Summary Background and objectives Patients with advanced chronic kidney disease (CKD) are in positive phosphorus balance, but phosphorus levels are maintained in the normal range through phosphaturia induced by increases in fibroblast growth factor-23 (FGF23) and parathyroid hormone (PTH). This provides the rationale for recommendations to restrict dietary phosphate intake to 800 mg/d. However, the protein source of the phosphate may also be important. Design, setting, participants, & measurements We conducted a crossover trial in nine patients with a mean estimated GFR of 32 ml/min to directly compare vegetarian and meat diets with equivalent nutrients prepared by clinical research staff. During the last 24 hours of each 7-day diet period, subjects were hospitalized in a research center and urine and blood were frequently monitored. Results The results indicated that 1 week of a vegetarian diet led to lower serum phosphorus levels and decreased FGF23 levels. The inpatient stay demonstrated similar diurnal variation for blood phosphorus, calcium, PTH, and urine fractional excretion of phosphorus but significant differences between the vegetarian and meat diets. Finally, the 24-hour fractional excretion of phosphorus was highly correlated to a 2-hour fasting urine collection for the vegetarian diet but not the meat diet. Conclusions In summary, this study demonstrates that the source of protein has a significant effect on phosphorus homeostasis in patients with CKD. Therefore, dietary counseling of patients with CKD must include information on not only the amount of phosphate but also the source of protein from which the phosphate derives.",
"title": "Original Articles: Vegetarian Compared with Meat Dietary Protein Source and Phosphorus Homeostasis in Chronic Kidney Disease"
},
{
"docid": "MED-4613",
"text": "The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations. (c)2001 CHF, Inc.",
"title": "Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition."
},
{
"docid": "MED-3551",
"text": "Breast cancer is the leading cause of cancer-related deaths for women in the United States and the rest of the world. About 8% of women develop breast cancer during the course of their lives. Dietary habits are closely associated with both the risk and progression of breast cancer. Dietary agents have accumulated increasing importance with regards to the prevention and treatment of breast cancer. One such manner by which these compounds can target breast cancer development and progression is through interference with the angiogenic pathways. Angiogenesis is an intricate process that involves the development of new capillaries from previously existing blood vessels. Disruption of this pathway, therefore, provides a novel and effective avenue for therapeutic intervention of breast cancer. Various phytochemicals found in the diet kill breast cancer cells in vitro and prevent as well as suppress breast cancer progression in various preclinical animal models. This review examines the value of dietary phytoconstituents in the prevention and treatment of breast cancer through modulation of the intricate and complex process of angiogenesis. In addition, the potential benefits, challenges, and future directions of research on anti-angiogenic dietary phytochemicals in the prevention and intervention of breast cancer are also addressed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Modulation of angiogenesis by dietary phytoconstituents in the prevention and intervention of breast cancer."
},
{
"docid": "MED-3718",
"text": "The American Cancer Society (ACS) publishes Nutrition and Physical Activity Guidelines to serve as a foundation for its communication, policy, and community strategies and ultimately, to affect dietary and physical activity patterns among Americans. These Guidelines, published every 5 years, are developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and as such, they represent the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS Guidelines include recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or interferes with healthy behaviors. Community efforts are essential to create a social environment that promotes healthy food choices and physical activity. Therefore, this committee presents one key recommendation for community action to accompany the four recommendations for individual choices to reduce cancer risk. This recommendation for community action recognizes that a supportive social environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. The ACS Guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion, as defined by the Department of Health and Human Services' 2005 Dietary Guidelines for Americans.",
"title": "American Cancer Society Guidelines on Nutrition and Physical Activity for cancer prevention: reducing the risk of cancer with healthy food choices ..."
},
{
"docid": "MED-3723",
"text": "Epidemiological studies investigating the association between dietary intake and oesophageal cancer have mostly focused on nutrients and food groups instead of dietary patterns. We conducted a population-based case-control study, which included 365 oesophageal adenocarcinoma (OAC), 426 oesophagogastric junction adenocarcinoma (OGJAC) and 303 oesophageal squamous cell carcinoma (OSCC) cases, with frequency matched on age, sex and geographical location to 1580 controls. Data on demographic, lifestyle and dietary factors were collected using self-administered questionnaires. We used principal component analysis to derive three dietary patterns: 'meat and fat', 'pasta and pizza' and 'fruit and vegetable', and unconditional logistic regression models to estimate risks of OAC, OGJAC and OSCC associated with quartiles (Q) of dietary pattern scores. A high score on the meat-and-fat pattern was associated with increased risk of all three cancers: multivariable-adjusted OR 2·12 (95 % CI 1·30, 3·46) for OAC; 1·88 (95% CI 1·21, 2·94) for OGJAC; 2·84 (95% CI 1·67, 4·83) for OSCC (P-trend <0·01 for all three cancers). A high score on the pasta-and-pizza pattern was inversely associated with OSCC risk (OR 0·58, 95 % CI 0·36, 0·96, P for trend=0·009); and a high score on the fruit-and-vegetable pattern was associated with a borderline significant decreased risk of OGJAC (OR for Q4 v. Q1 0·66, 95% CI 0·42, 1·04, P=0·07) and significantly decreased risk of OSCC (OR 0·41, 95% CI 0·24, 0·70, P for trend=0·002). High-fat dairy foods appeared to play a dominant role in the association between the meat-and-fat pattern and risk of OAC and OGJAC. Further investigation in prospective studies is needed to confirm these findings.",
"title": "Dietary patterns and risk of oesophageal cancers: a population-based case-control study."
},
{
"docid": "MED-5329",
"text": "OBJECTIVE: This study was conducted to demonstrate the effectiveness of a strictly vegetarian, very low-fat diet on cardiac risk factor modification. METHODS: Five hundred men and women, participants in an intensive 12-day live-in program, were studied. The program focused on dietary modification, moderate exercise, and stress management at a hospital-based health-center. RESULTS: During this short time period, cardiac risk factors improved: there was an average reduction of total serum cholesterol of 11% (p < 0.001), of blood pressure of 6% (p < 0.001) and a weight loss of 2.5 kg for men and 1 kg for women. Serum triglycerides did not increase except for two subgroups: females age > or = 65 years with serum cholesterol < 6.5 mmol/L and for females 50 to 64 years with baseline serum cholesterol between 5.2-6.5 mmol/L. High-density lipoprotein cholesterol measured on 66 subjects decreased by 19%. CONCLUSION: A strict, very low-fat vegetarian diet free from all animal products combined with lifestyle changes that include exercise and weight loss is an effective way to lower serum cholesterol and blood pressure.",
"title": "Rapid reduction of serum cholesterol and blood pressure by a twelve-day, very low fat, strictly vegetarian diet."
},
{
"docid": "MED-4481",
"text": "The aim of this study was to investigate whether dietary fat and meat intakes are associated with reflux esophagitis (RE), Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). In this all-Ireland case-control study, dietary intake data was collected using a food frequency questionnaire in 219 RE patients, 220 BE patients, 224 EAC patients, and 256 frequency-matched controls between 2002 and 2005. Unconditional multiple logistic regression analysis was used to examine the association between dietary variables and disease risk using quartiles of intake, to attain odds ratios (OR) and 95% confidence intervals (95%CI), while adjusting for potential confounders. Patients in the highest quartile of total fat intake had a higher risk of RE (OR=3.54; 95%CI=1.32–9.46) and EAC (OR=5.44; 95%CI=2.08–14.27). A higher risk of RE and EAC was also reported for patients in the highest quartile of saturated fat intake (OR=2.79; 95%CI=1.11–7.04; OR=2.41; 95%CI=1.14–5.08, respectively) and monounsaturated fat intake (OR=2.63; 95%CI=1.01–6.86; OR=5.35; 95%CI=2.14–13.34, respectively). Patients in the highest quartile of fresh red meat intake had a higher risk of EAC (OR=3.15; 95%CI=1.38–7.20). Patients in the highest category of processed meat intake had a higher risk of RE (OR=4.67; 95%CI=1.71–12.74). No consistent associations were seen for BE with either fat or meat intakes. Further studies, investigating the association between dietary fat and food sources of fat are needed to confirm these results.",
"title": "Dietary fat and meat intakes and risk of reflux esophagitis, Barrett’s esophagus and esophageal adenocarcinoma"
},
{
"docid": "MED-3273",
"text": "Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving \"aging retardant\" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins - especially those derived from legumes or nuts - tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction - though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents.",
"title": "The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy."
}
] |
[
{
"docid": "MED-1333",
"text": "New epidemiology confirms that glucose intolerance is a risk factor for pancreatic cancer, and that this association cannot be accounted for by an adverse impact of early pancreatic cancer on beta cell function. Previous reports indicate that risk for pancreatic cancer is increased in adult-onset diabetics. Since streptozotocin diabetes inhibits carcinogen-mediated induction of pancreatic cancer in hamsters, the most reasonable interpretation of these findings is that insulin (or some other beta cell product) acts as a promoter for pancreatic carcinogenesis. This view is consistent with a report that human pancreatic adenocarcinomas express insulin receptors that can stimulate mitosis; an additional possibility is that high insulin levels indirectly promote pancreatic carcinogenesis by boosting effective IGF-I activity via hepatic actions. In international ecologic epidemiology, pancreatic cancer rates correlate tightly with dietary intake of animal products; this may reflect the fact that vegan diets are associated with low diurnal insulin secretion. There is also suggestive evidence that macrobiotic vegan diets, which are low in glycemic index, may increase mean survival time in pancreatic cancer. However, other types of diets associated with decreased postprandial insulin response, such as high-protein diets or 'Mediterranean' diets high in oleic acid, may also have the potential for pancreatic cancer prevention. The huge increases of age-adjusted pancreatic cancer mortality in Japan and among African-Americans during the last century imply that pancreatic cancer is substantially preventable; a low-insulin-response diet coupled with exercise training, weight control, and smoking avoidance, commendable for a great many other reasons, may slash pancreatic cancer mortality dramatically. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Insulin secretion as a determinant of pancreatic cancer risk."
},
{
"docid": "MED-2578",
"text": "The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high-fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber-rich diets. The authors have found that phytic acid is a potent inhibitor of iron-mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.",
"title": "Dietary suppression of colonic cancer. Fiber or phytate?"
},
{
"docid": "MED-1305",
"text": "This viewpoint aims to 1) review the available scientific literature on the relationship between whole grain consumption and body weight regulation; 2) evaluate the potential mechanisms whereby whole grain intake may help reduce overweight and 3) try to understand why epidemiological studies and clinical trials provide diverging results on this topic. All the prospective epidemiological studies demonstrate that a higher intake of whole grains is associated with lower BMI and body weight gain. However, these results do not clarify whether whole grain consumption is simply a marker of a healthier lifestyle or a factor favoring \"per se\" lower body weight. Habitual whole grain consumption seems to cause lower body weight by multiple mechanisms such as lower energy density of whole grain based products, lower glycemic index, fermentation of non digestible carbohydrates (satiety signals) and finally by modulating intestinal microflora. In contrast with epidemiological evidence, the results of few clinical trials do not confirm that a whole grain low-calorie diet is more effective in reducing body weight than a refined cereal diet, but their results may have been affected by small sample size or short duration of the intervention. Therefore, further intervention studies with adequate methodology are needed to clarify this question. For the time being, whole grain consumption can be recommended as one of the features of the diet that may help control body weight but also because is associated with a lower risk to develop type 2 diabetes, cardiovascular diseases and cancer. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Whole grain intake in relation to body weight: from epidemiological evidence to clinical trials."
},
{
"docid": "MED-2044",
"text": "Cancer incidence increases with advancing age. Over 60% of new cancers and 70% of cancer deaths occur in individuals aged 65 years or older. One factor that may contribute to this is immunosenescence - a canopy term that is used to describe age-related declines in the normal functioning of the immune system. There are multiple age-related deficits in both the innate and adaptive systems that may play a role in the increased incidence of cancer. These include decreased NK-cell function, impaired antigen uptake and presentation by monocytes and dendritic cells, an increase in 'inflammaging', a decline in the number of naïve T-cells able to respond to evolving tumor cells, and an increase in functionally exhausted senescent cells. There is consensus that habitual physical exercise can offer protection against certain types of cancer; however the evidence linking immunological mechanisms, exercise, and reduced cancer risk remain tentative. Multiple studies published over the last two decades suggest that exercise can mitigate the deleterious effects of age on immune function, thus increasing anti-cancer immunity. The potential ameliorative effect of exercise on these mechanisms include evidence that physical activity is able to stimulate greater NK-cell activity, enhance antigen-presentation, reduce inflammation, and prevent senescent cell accumulation in the elderly. Here we discuss the role played by the immune system in preventing and controlling cancer and how aging may retard these anti-cancer mechanisms. We also propose a pathway by which exercise-induced alterations in immunosenescence may decrease the incidence of cancer and help improve prognosis in cancer patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.",
"title": "Can exercise-related improvements in immunity influence cancer prevention and prognosis in the elderly?"
},
{
"docid": "MED-4239",
"text": "BACKGROUND: Prostate cancer is the most common solid-tumor cancer in US males but is rare in Asian males. When Asian men adopt the US lifestyle, clinical prostate cancer increases greatly. Epidemiological data from men in the US indicate that regular activity may reduce the risk for prostate cancer. METHODS: Serum was obtained from three groups of similar-aged men, Control, Diet and Exercise, and Exercise alone were used to stimulate LNCaP cells in culture. Growth and apoptosis of tumor cells were measured. Serum samples were also used to measure insulin, IGF-1, IGFBP-1. RESULTS: The Diet and Exercise and the Exercise alone groups had lower serum insulin and IGF-1 but higher IGFBP-1 compared to Controls. LNCaP cell growth was reduced in both groups compared to Control and there was a major increase in apoptosis of tumor cells. CONCLUSIONS: A low-fat diet and/or intensive exercise results in change in serum hormones and growth factors in vivo that can reduce growth and induce apoptosis of LNCaP prostate tumor cells in vitro. Copyright 2003 Wiley-Liss, Inc.",
"title": "A low-fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro."
},
{
"docid": "MED-3785",
"text": "PURPOSE: Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before. MATERIALS AND METHODS: We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression. RESULTS: Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; P(trend) = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; P(trend) = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; P(trend) = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk. CONCLUSION: The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation.",
"title": "One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites."
},
{
"docid": "MED-2434",
"text": "The specific role of dietary fat in breast cancer progression is unclear, although a low-fat diet was associated with decreased recurrence of estrogen receptor alpha negative (ER(-)) breast cancer. ER(-) basal-like MDA-MB-231 and MDA-MB-436 breast cancer cell lines contained a greater number of cytoplasmic lipid droplets compared to luminal ER(+) MCF-7 cells. Therefore, we studied lipid storage functions in these cells. Both triacylglycerol and cholesteryl ester (CE) concentrations were higher in the ER(-) cells, but the ability to synthesize CE distinguished the two types of breast cancer cells. Higher baseline, oleic acid- and LDL-stimulated CE concentrations were found in ER(-) compared to ER(+) cells. The differences corresponded to greater mRNA and protein levels of acyl-CoA:cholesterol acyltransferase 1 (ACAT1), higher ACAT activity, higher caveolin-1 protein levels, greater LDL uptake, and lower de novo cholesterol synthesis in ER(-) cells. Human LDL stimulated proliferation of ER(-) MDA-MB-231 cells, but had little effect on proliferation of ER(+) MCF-7 cells. The functional significance of these findings was demonstrated by the observation that the ACAT inhibitor CP-113,818 reduced proliferation of breast cancer cells, and specifically reduced LDL-induced proliferation of ER(-) cells. Taken together, our studies show that a greater ability to take up, store and utilize exogenous cholesterol confers a proliferative advantage to basal-like ER(-) breast cancer cells. Differences in lipid uptake and storage capability may at least partially explain the differential effect of a low-fat diet on human breast cancer recurrence.",
"title": "High ACAT1 expression in estrogen receptor negative basal-like breast cancer cells is associated with LDL-induced proliferation."
},
{
"docid": "MED-2117",
"text": "Recent evidence underlines the role of Western diet in the pathogenesis of acne. Acne is absent in populations consuming Palaeolithic diets with low glycaemic load and no consumption of milk or dairy products. Two randomized controlled studies, one of which is presented in this issue of Acta Dermato-Venereologica, have provided evidence for the beneficial therapeutic effects of low glycaemic load diets in acne. Epidemiological evidence confirms that milk consumption has an acne-promoting or acne-aggravating effect. Recent progress in understanding the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1) allows a new view of nutrient signalling in acne by both high glycaemic load and increased insulin-, IGF-1-, and leucine signalling due to milk protein consumption. Acne should be regarded as an mTORC1-driven disease of civilization, like obesity, type 2 diabetes and cancer induced by Western diet. Early dietary counselling of teenage acne patients is thus a great opportunity for dermatology, which will not only help to improve acne but may reduce the long-term adverse effects of Western diet on more serious mTORC1-driven diseases of civilization.",
"title": "Diet in acne: further evidence for the role of nutrient signalling in acne pathogenesis."
},
{
"docid": "MED-4299",
"text": "The evolution of the human diet over the past 10,000 years from a Paleolithic diet to our current modern pattern of intake has resulted in profound changes in feeding behavior. Shifts have occurred from diets high in fruits, vegetables, lean meats, and seafood to processed foods high in sodium and hydrogenated fats and low in fiber. These dietary changes have adversely affected dietary parameters known to be related to health, resulting in an increase in obesity and chronic disease, including cardiovascular disease (CVD), diabetes, and cancer. Some intervention trials using Paleolithic dietary patterns have shown promising results with favorable changes in CVD and diabetes risk factors. However, such benefits may be offset by disadvantages of the Paleolithic diet, which is low in vitamin D and calcium and high in fish potentially containing environmental toxins. More advantageous would be promotion of foods and food ingredients from our ancestral era that have been shown to possess health benefits in the form of functional foods. Many studies have investigated the health benefits of various functional food ingredients, including omega-3 fatty acids, polyphenols, fiber, and plant sterols. These bioactive compounds may help to prevent and reduce incidence of chronic diseases, which in turn could lead to health cost savings ranging from $2 to $3 billion per year as estimated by case studies using omega-3 and plant sterols as examples. Thus, public health benefits should result from promotion of the positive components of Paleolithic diets as functional foods.",
"title": "Evolution of the human diet: linking our ancestral diet to modern functional foods as a means of chronic disease prevention."
},
{
"docid": "MED-3874",
"text": "Background Prostate cancer affects one-out-of-six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods We undertook a multi-site, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n=161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: 1) control (usual diet); 2) flaxseed-supplemented diet (30 g/day); 2) low-fat diet (<20% total energy); or 4) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin, testosterone, insulin-like growth factor-1 and binding protein-3, c-reactive protein, and total and low density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. Results Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67 positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) vs. 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serological endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P=0.048). Conclusions Findings suggest that flaxseed is safe, and associated with biologic alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol.",
"title": "Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery"
},
{
"docid": "MED-4885",
"text": "Background Prostate cancer affects one-out-of-six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods We undertook a multi-site, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n=161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: 1) control (usual diet); 2) flaxseed-supplemented diet (30 g/day); 2) low-fat diet (<20% total energy); or 4) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin, testosterone, insulin-like growth factor-1 and binding protein-3, c-reactive protein, and total and low density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. Results Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67 positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) vs. 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serological endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P=0.048). Conclusions Findings suggest that flaxseed is safe, and associated with biologic alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol.",
"title": "Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery"
},
{
"docid": "MED-1293",
"text": "In the domain of nutrition, exploring the diet-health linkages is major area of research. The outcomes of such interventions led to widespread acceptance of functional and nutraceutical foods; however, augmenting immunity is a major concern of dietary regimens. Indeed, the immune system is incredible arrangement of specific organs and cells that enabled humans to carry out defense against undesired responses. Its proper functionality is essential to maintain the body homeostasis. Array of plants and their components hold immunomodulating properties. Their possible inclusion in diets could explore new therapeutic avenues to enhanced immunity against diseases. The review intended to highlight the importance of garlic (Allium sativum), green tea (Camellia sinensis), ginger (Zingiber officinale), purple coneflower (Echinacea), black cumin (Nigella sativa), licorice (Glycyrrhiza glabra), Astragalus and St. John's wort (Hypericum perforatum) as natural immune boosters. These plants are bestowed with functional ingredients that may provide protection against various menaces. Modes of their actions include boosting and functioning of immune system, activation and suppression of immune specialized cells, interfering in several pathways that eventually led to improvement in immune responses and defense system. In addition, some of these plants carry free radical scavenging and anti-inflammatory activities that are helpful against cancer insurgence. Nevertheless, interaction between drugs and herbs/botanicals should be well investigated before recommended for their safe use, and such information must be disseminated to the allied stakeholders.",
"title": "Immunity: plants as effective mediators."
},
{
"docid": "MED-2808",
"text": "Chemotherapy remains the core of anticancer treatment. However, despite the tremendous strides made in the development of targeted anticancer therapies, emergence of resistance to chemotherapeutic drugs is still a major obstacle in the successful management of resistant tumours. Therefore, profound investigation into the in-depth molecular mechanisms of drug resistance is essential and may hopefully translate into effective therapies that can flip the switch from drug resistance to susceptibility. Mechanistically, resistance phenomena may be explained by (i) overexpression of drug efflux pumps, (ii) enhanced drug detoxification, (iii) rapid DNA repair efficiency, (iv) defects in apoptosis regulation, and (v) active cell survival signals. Several adverse effects associated with multidrug resistance and the need for safe multi-targeted anticancer drugs instigated the use of the phytochemical, curcumin, the yellow pigment of the spice turmeric, which has pleotropic activities. We performed a structured literature review using PubMed and Medline searches with secondary review of cited publications, identifying studies on the role of curcumin in conquering drug resistance in cancer. This review describes how curcumin sensitizes cancer cells through regulation of multiple multidrug resistance pathways, thus employing one drug for multiple targets. Curcumin helps the cancer cells to regain their 'forgotten' apoptosis, modulates drug-target interaction at different levels, restrains survival pathways when their proteins are overexpressed, and finds an alternate way to carry forward the process of sensitization of different resistant tumours. Additionally, the review dissects the role of curcumin, if any, in targeting the major culprit of drug resistance, cancer stem cells (CSC), thereby circumventing resistance. Taken together, this review strongly suggests that curcumin is a promising chemosensitizing agent and that the unique properties of curcumin may be exploited for successful management of resistant tumours.",
"title": "Death by design: where curcumin sensitizes drug-resistant tumours."
},
{
"docid": "MED-3878",
"text": "Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30–31 days. Among the individual arms, the largest number of significant changes (baseline vs pre-operative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (p<.05). Compared to the control arm, 6 CAFs—including pro-angiogenic factors (stromal-cell derived-1α and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor — all decreased in the LF arm compared to controls; 3 and 4 CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P <0.001). The CAFs that changed in the LF arm are all known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm, but not in the FS-containing arms. These results suggest that a low-fat diet without flaxseed may reduce levels of specific inflammatory cytokines and angiogenic factors and suggests that the NF-κB pathway may be a mediator of these changes.",
"title": "Effect of Low-fat Diets on Plasma Levels of NFκB-regulated Inflammatory Cytokines and Angiogenic Factors in Men with Prostate Cancer"
},
{
"docid": "MED-1419",
"text": "To determine the effects of different diets on the genotoxicity of human faecal water, a diet rich in fat, meat and sugar but poor in vegetables and free of wholemeal products (diet 1) was consumed by seven healthy volunteers over a period of 12 days. One week after the end of this period, the volunteers started to consume a diet enriched with vegetables and wholemeal products but poor in fat and meat (diet 2) over a second period of 12 days. The genotoxic effect of faecal waters obtained after both diets was assessed with the single cell gel electrophoresis (Comet assay) using the human colon adenocarcinoma cell line HT29 clone 19a as a target. The fluorescence and length of the tails of the comet images reflects the degree of DNA damage in single cells. The mean DNA damage, expressed as the ratio of tail intensity (fluorescence in the tail) to total intensity of the comet after incubation with faecal water from volunteers consuming diet 1 was about twice as high as for diet 2. The susceptibility of the cells incubated with faecal water to DNA damage caused by additional hydrogen peroxide treatment showed no significant differences between the two diets. Generation of oxidized pyrimidine and purine bases revealed no differences after pretreatment with both types of faecal water. The results indicate that diets high in fat and meat but low in dietary fibre increase the genotoxicity of faecal water to colonic cells and may contribute to an enhanced risk of colorectal cancer.",
"title": "A diet high in fat and meat but low in dietary fibre increases the genotoxic potential of 'faecal water'."
},
{
"docid": "MED-1607",
"text": "Background: As sodium, potassium and fluid intake are related to hypertension, an established risk factor for renal cell cancer (RCC), they may be independent risk factors for RCC. Methods: The Netherlands Cohort Study (NLCS) with case-cohort design included 120 852 participants aged 55–69 years. At baseline, diet and lifestyle were assessed with questionnaires. After 17.3 years of follow-up, 485 RCC cases and 4438 subcohort members were available for analyses. Results: Sodium intake increased RCC risk (P-trend=0.03), whereas fluid and potassium intake did not. For high sodium and low fluid intake, the RCC risk additionally increased (P-interaction=0.02). Conclusion: Sodium intake is a potential risk factor for RCC, particularly if fluid consumption is low.",
"title": "Long-term dietary sodium, potassium and fluid intake; exploring potential novel risk factors for renal cell cancer in the Netherlands Cohort Study on diet and cancer"
},
{
"docid": "MED-3106",
"text": "PURPOSE OF REVIEW: The aryl hydrocarbon receptor (AhR), a transcription factor activated by a large number of environmental agents, modulates the activity of immune and nonimmune cells in the gut, and may represent an important link between the environment and the immune perturbations which underlie the pathogenesis of inflammatory bowel disease. This review will summarize the current knowledge of the role of AhR in regulation of intestinal immune homeostasis and inflammation. RECENT FINDINGS: Activation of AhR by dietary ligands is necessary for the maintenance or expansion of innate immune cells in the gut, such as intraepithelial lymphocytes (IELs) and interleukin (IL)-22-producing lymphoid cells (ILC22). AhR-deficient mice lack IELs, have reduced number of ILC22 cells, and are more susceptible to bacterial infections and experimental colitis. In animal models, AhR activators inhibit proinflammatory cytokine synthesis and attenuate colitis by a pathway that involves IL-22. Analysis of AhR in the human gut reveals that intestinal T cells and natural killer cells isolated from Crohn's disease patients express low levels of AhR and respond to AhR ligands by downregulating inflammatory cytokines and upregulating IL-22. SUMMARY: These novel findings may help explain how environmental factors may regulate mucosal immune responses.",
"title": "The aryl hydrocarbon receptor in inflammatory bowel disease: linking the environment to disease pathogenesis."
},
{
"docid": "MED-5185",
"text": "There is some evidence that dietary factors may modify the risk of squamous cell carcinoma (SCC) of the skin, but the association between food intake and SCC has not been evaluated prospectively. We examined the association between food intake and SCC incidence among 1,056 randomly selected adults living in an Australian sub-tropical community. Measurement-error corrected estimates of intake in 15 food groups were defined from a validated food frequency questionnaire in 1992. Associations with SCC risk were assessed using Poisson and negative binomial regression to the persons affected and tumour counts, respectively, based on incident, histologically confirmed tumours occurring between 1992 and 2002. After multivariable adjustment, none of the food groups was significantly associated with SCC risk. Stratified analysis in participants with a past history of skin cancer showed a decreased risk of SCC tumours for high intakes of green leafy vegetables (RR = 0.45, 95% CI = 0.22-0.91; p for trend = 0.02) and an increased risk for high intake of unmodified dairy products (RR = 2.53, 95% CI: 1.15-5.54; p for trend = 0.03). Food intake was not associated with SCC risk in persons who had no past history of skin cancer. These findings suggest that consumption of green leafy vegetables may help prevent development of subsequent SCCs of the skin among people with previous skin cancer and that consumption of unmodified dairy products, such as whole milk, cheese and yoghurt, may increase SCC risk in susceptible persons. Copyright 2006 Wiley-Liss, Inc.",
"title": "Food intake and risk of squamous cell carcinoma of the skin in a community: the Nambour skin cancer cohort study."
},
{
"docid": "MED-5048",
"text": "Despite the continuing reports supporting the hepatoprotective effects of green tea against ethanol intoxication, there remain controversies regarding the active compound(s) and molecular mechanism. These issues were addressed in the present study using cultured HepG2 cells exposed to a lethal dose of ethanol. Gamma-glutamyl transferase (GGT) was chosen as a marker of ethanol toxicity because it is widely used in clinics. When the cells were treated with ethanol at various concentrations, there was a dose-dependent increase of GGT activity in the culture media and loss of cell viability. Pretreatment of the cells with green tea extract attenuated the changes significantly. Among the green tea constituents, (-)-epigallocatechin gallate (EGCG) attenuated the ethanol cytotoxicity effectively, whereas L-theanine and caffeine had no effects. The ethanol cytotoxicity was also attenuated by alcohol dehydrogenase inhibitor 4-methyl pyrazol and GGT inhibitor acivicin as well as by thiol modulators such as S-adenosyl-L-methionine, N-acetyl-L-cysteine and glutathione. EGCG failed to prevent the intracellular glutathione loss caused by ethanol, but it appeared to be a strong GGT inhibitor. Therefore the cytoprotective effects of green tea could be attributed to the inhibition of GGT activity by EGCG. This study suggests that GGT inhibitors including EGCG may provide a novel strategy for attenuating ethanol-induced liver damage.",
"title": "Effect of green tea and (-)-epigallocatechin gallate on ethanol-induced toxicity in HepG2 cells."
},
{
"docid": "MED-984",
"text": "We investigated total, free and protein-bound plasma homocysteine, cysteine and cysteinylglycine in 13 subjects aged 24-29 y after a breakfast at 0900 h containing 15-18 g of protein and a dinner at 1500 h containing approximately 50 g of protein. Twelve subjects had normal fasting homocysteine (mean +/- SD, 7.6 +/- 1.1 mumol/L) and methionine concentrations (22.7 +/- 3.5 mumol/L) and were included in the statistical analyses. Breakfast caused a small but significant increase in plasma methionine (22.2 +/- 20.6%) and a brief, nonsignificant increase followed by a significant decline in free homocysteine. However, changes in total and bound homocysteine were small. After dinner, there was a marked increase in plasma methionine by 16.7 +/- 8.9 mumol/L (87.9 +/- 49%), which was associated with a rapid and marked increase in free homocysteine (33.7 +/- 19.6%, 4 h after dinner) and a moderate and slow increase in total (13.5 +/- 7.5%, 8 h) and protein-bound (12.6 +/- 9.4%, 8 h) homocysteine. After both meals, cysteine and cysteinylglycine concentrations seemed related to changes in homocysteine, because there were parallel fluctuations in the free:bound ratios of all three thiols. Dietary changes in plasma homocysteine will probably not affect the evaluation of vitamin deficiency states associated with moderate to severe hyperhomocysteinemia but may be of concern in the risk assessment of cardiovascular disease in patients with mild hyperhomocysteinemia. Synchronous fluctuations in the free:bound ratio of the plasma aminothiol compounds indicate that biological effects of homocysteine may be difficult to separate from effects due to associated changes in other aminothiol compounds.",
"title": "Plasma concentrations of homocysteine and other aminothiol compounds are related to food intake in healthy human subjects."
},
{
"docid": "MED-1618",
"text": "To study the effect of a moderate increase in insulin secretion produced by an increased daily protein intake on dehydroepiandrosterone sulfate (DHEAS), a balanced randomized crossover trial consisting of three strictly controlled dietary regimens was performed in six healthy male volunteers. The basic diet (B) contained 50 g protein/d; diets P and M (also basic diets) were enriched with either 32 g protein/d (P) or 10 mmol L-methionine/d (M). Methionine was given (as a specific nonprotein source of endogenously derived sulfate) to control for possible confounding effects on DHEAS due to an increased sulfate supply. At the end of each 4-day diet period, blood and 24-hour urine samples were collected. Fasting plasma levels of testosterone, cortisol, insulin-like growth factor-I (IGF-I), and insulin, as well as urinary output of total (hot acid-cleaved) testosterone conjugates and 3alpha-androstanediol glucuronide, did not show significant changes in response to dietary manipulations. Endogenous sulfate availability (as reflected by renal sulfate output per 24 hours) approximately doubled with diets P and M. However, plasma levels (6.3 +/- 1.5, 6.8 +/- 1.8, and 6.9 +/- 2.1 micromol/L for B, P, and M, respectively) and urinary excretion (8.8 +/- 9.8, 9.4 +/- 11.2, 8.0 +/- 8.3 micromol/d) of DHEAS remained unaffected. Considering the clear increments (P < .01) in urinary C-peptide excretion with diet P (20.4 +/- 10.3 nmol/d) versus diets B and M (12.6 +/- 5.1 and 13.2 +/- 3.6 nmol/d), respectively, our results suggest that a moderately strong diet-induced increase in daily insulin secretion does not alter urinary and plasma levels of DHEAS.",
"title": "A moderate increase in daily protein intake causing an enhanced endogenous insulin secretion does not alter circulating levels or urinary excretion..."
},
{
"docid": "MED-2250",
"text": "Chronic low-level cadmium (Cd) exposure is linked to kidney and cardiovascular disease, fractures, and cancer. Diet and smoking are primary sources of exposure in the general population. We analyzed urinary Cd in NHANES 1999-2008 to determine whether levels declined significantly over the decade for U.S. children, teens, and adults (nonsmokers and smokers) and, if so, factors influencing the decline(s). For each subpopulation, we modeled log urinary Cd using variable-threshold censored multiple regression. Models included individual-level covariates (age, gender, BMI, income, race/ethnicity/country of origin, education, survey period), smoking, housing (home age, water source, filter use), and diet (supplement use; 24-h calorie, fat, protein, micronutrient, and Cd-containing food intakes), creatinine, and survey year variables. Geometric mean urinary Cd (ng/mL) declined 20-25% in these subpopulations, and the regressions showed statistically significant declines in later years for teens and adults. While certain covariates were significantly associated with Cd by subpopulation (creatinine; age; BMI; race/ethnicity/origin; education; smokers in the home; serum cotinine; 24-h fat, Mg, Fe intakes; use of dietary supplements), they did not help explain the declines. Instead, unidentified time-related factors appeared responsible. Despite the declines, millions of Americans remain potentially at risk of adverse outcomes associated with low-level Cd exposure.",
"title": "Urinary cadmium in the 1999-2008 U.S. National Health and Nutrition Examination Survey (NHANES)."
},
{
"docid": "MED-2848",
"text": "Type 1 diabetes is increasing rapidly in many parts of the Western world, most evidently in Scandinavia. A low concordance rate of insulin-dependent diabetes mellitus among monozygotic twins clearly indicates that genetic risk factors may be necessary, but are not sufficient for the disease to occur. The strongest genetic risk markers are located in the HLA region of chromosome 6, but these DNA specificities differ in different populations. Risk genes are indicated in other chromosomes of the human genome, suggesting a complex interaction between genes and environment as the cause of the disease. The pathogenesis of the disease is proposed to be autoimmune in nature and environmental risk factors may either initiate autoimmunity or accelerate an already ongoing beta-cell destruction. Risk factors disclosed by epidemiological studies that may accelerate the pathogenetic process are: a cold environment, a high growth rate, infections and stressful life events. Risk factors that may initiate the autoimmune process include early exposure to cow's milk proteins, nitrosamines or early foetal events such as blood group incompatibility or foetal viral infections. In conclusion, population-based epidemiological studies have helped to confirm proposed aetiological models that have arisen from experimental research. These epidemiological studies have also introduced important new findings that may reveal the complex aetiology of the disease and advance understanding closer to the ultimate goal of primary prevention.",
"title": "The aetiology of type 1 diabetes: an epidemiological perspective."
},
{
"docid": "MED-2794",
"text": "Turmeric, a plant rhizome that is often dried, ground and used as a cooking spice, has also been used medicinally for several thousand years. Curcumin, the phytochemical that gives turmeric its golden color, is responsible for most of the therapeutic effects of turmeric. In recent years curcumin has been studied for its effects on chronic diseases such as diabetes, Alzheimer's, and cancer. Though many researchers are investigating turmeric/curcumin in cancer therapy, there is little epidemiologic information on the effects of turmeric consumption. With limited availability of pharmacologic interventions in many areas of the world, use of turmeric in the diet may help to alleviate some of the disease burden through prevention. Here we provide a brief overview of turmeric consumption in different parts of the world, cancer rates in those regions, possible biochemical mechanisms by which turmeric acts and practical recommendations based on the information available.",
"title": "Dietary turmeric potentially reduces the risk of cancer."
},
{
"docid": "MED-1714",
"text": "BACKGROUND: Western diets, obesity, and sedentary lifestyles are associated with increased cancer risk. The mechanisms responsible for this increased risk, however, are not clear. OBJECTIVE: We hypothesized that long-term low protein, low calorie intake and endurance exercise are associated with low concentrations of plasma growth factors and hormones that are linked to an increased risk of cancer. DESIGN: Plasma growth factors and hormones were evaluated in 21 sedentary subjects, who had been eating a low-protein, low-calorie diet for 4.4 +/- 2.8 y (x +/- SD age: 53.0 +/- 11 y); 21 endurance runners matched by body mass index (BMI; in kg/m2); and 21 age- and sex-matched sedentary subjects eating Western diets. RESULTS: BMI was lower in the low-protein, low-calorie diet (21.3 +/- 3.1) and runner (21.6 +/- 1.6) groups than in the Western diet (26.5 +/- 2.7; P < 0.005) group. Plasma concentrations of insulin, free sex hormones, leptin, and C-reactive protein were lower and sex hormone-binding globulin was higher in the low-protein, low-calorie diet and runner groups than in the sedentary Western diet group (all P < 0.05). Plasma insulin-like growth factor I (IGF-I) and the concentration ratio of IGF-I to IGF binding protein 3 were lower in the low-protein, low-calorie diet group (139 +/- 37 ng/mL and 0.033 +/- 0.01, respectively) than in the runner (177 +/- 37 ng/mL and 0.044 +/- 0.01, respectively) and sedentary Western (201 +/- 42 ng/mL and 0.046 +/- 0.01, respectively) diet groups (P < 0.005). CONCLUSIONS: Exercise training, decreased adiposity, and long-term consumption of a low-protein, low-calorie diet are associated with low plasma growth factors and hormones that are linked to an increased risk of cancer. Low protein intake may have additional protective effects because it is associated with a decrease in circulating IGF-I independent of body fat mass.",
"title": "Long-term low-protein, low-calorie diet and endurance exercise modulate metabolic factors associated with cancer risk."
},
{
"docid": "MED-2194",
"text": "Scope Anthocyanins, the natural pigments in plant foods, have been associated with cancer prevention. However, the content of anthocyanins in staple foods is typically low and the mechanisms by which they exert anti-cancer activity is not yet fully defined. Methods and results We selected an anthocyanin-enriched purple-fleshed sweet potato clone, P40, and investigated its potential anti-cancer effect in both in vitro cell culture and in vivo animal model. In addition to a high level of total phenolics and antioxidant capacity, P40 possesses a high content of anthocyanins at 7.5 mg/g dry matter. Treatment of human colonic SW480 cancer cells with P40 anthocyanin extracts at 0–40 μM of peonidin-3-glucoside equivalent resulted in a dose-dependent decrease in cell number due to cytostatic arrest of cell cycle at G1 phase but not cytotoxicity. Furthermore, dietary P40 at 10–30% significantly suppressed azoxymethane-induced formation of aberrant crypt foci in the colons of CF-1 mice in conjunction with, at least in part, a lesser proliferative PCNA and a greater apoptotic caspase-3 expression in the colon mucosal epithelial cells. Conclusion These observations, coupled with both in vitro and in vivo studies reported here, suggest anthocyanin-enriched sweet potato P40 may protect against colorectal cancer by inducing cell cycle arrest, anti-proliferative and apoptotic mechanisms.",
"title": "Role of Anthocyanin-enriched Purple-fleshed Sweet Potato P40 in Colorectal Cancer Prevention"
},
{
"docid": "MED-4457",
"text": "Sulforaphane (SFR), an isothiocyanate from cruciferous vegetables, possesses growth-inhibiting and apoptosis-inducing activities in cancer cell lines. Recently, SFR has been shown to promote the mitochondrial formation of reactive oxygen species (ROS) in human cancer cell lines. The present study was undertaken to see whether SFR-derived ROS might cause DNA damage in cultured human cells, namely T limphoblastoid Jurkat and human umbilical vein endothelial cells (HUVEC). 1-3 h treatments with 10-30 microM SFR elicited intracellular ROS formation (as assayed with dihydrorhodamine, DHR, oxidation) as well as DNA breakage (as assessed with fast halo assay, FHA). These effects lacked cell-type specificity, since could be observed in both Jurkat and HUVEC. Differential-pH FHA analysis of damaged DNA showed that SFR causes frank DNA single strand breaks (SSBs); no DNA double strand breaks (DSBs) were found within the considered treatment times (up to 3 h). SFR-derived ROS were formed at the mitochondrial respiratory chain (MRC) level: indeed rotenone or myxothiazol (MRC Complex I and III inhibitors, respectively) abrogated ROS formation. Furthermore ROS were not formed in Jurkat cells pharmacologically depleted of respiring mitochondria (MRC-/Jurkat). Formation of ROS was causally linked to the induction of SSBs: indeed all the experimental conditions capable of preventing ROS formation also prevented the damage of nuclear DNA from SFR-intoxicated cells. As to the toxicological relevance of SSBs, we found that their prevention slightly but significantly attenuated SFR cytotoxicity, suggesting that high-dose SFR toxicity is the result of a complex series of events among which GSH depletion seems to play a pivotal role. In conclusion, the present study identifies a novel mechanism contributing to SFR toxicity which - since DNA damage is a prominent mechanism underlying the cytotoxic activity of established antineoplastic agents - might help to exploit the therapeutic value of SFR in anticancer drug protocols. Copyright 2010 Elsevier B.V. All rights reserved.",
"title": "Sulforaphane induces DNA single strand breaks in cultured human cells."
},
{
"docid": "MED-4696",
"text": "Several epidemiologic studies have shown that chronic inflammation predisposes individuals to various types of cancer. Many cancers arise from sites of infection, chronic irritation, and inflammation. Conversely, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumors. Natural bioactive compounds in dietary plant products including fruits, vegetables, grains, legumes, tea, and wine are claimed to help prevent cancer, degenerative diseases, and chronic and acute inflammation. Modern methods in cell and molecular biology allow us to understand the interactions of different natural bioactive compounds with basic mechanisms of inflammatory response. The molecular pathways of this cancer-related inflammation are now unraveled. Natural bioactive compounds exert anti-inflammatory activity by modulating pro-inflammatory gene expressions have shown promising chemopreventive activity. This review summarizes current knowledge on natural bioactive compounds that act through the signaling pathways and modulate inflammatory gene expressions, thus providing evidence for these substances in cancer chemopreventive action.",
"title": "Modulation of inflammatory genes by natural dietary bioactive compounds."
},
{
"docid": "MED-1712",
"text": "Diet contributes to over one-third of cancer deaths in the Western world, yet the factors in the diet that influence cancer are not elucidated. A reduction in caloric intake dramatically slows cancer progression in rodents, and this may be a major contribution to dietary effects on cancer. Insulin-like growth factor I (IGF-I) is lowered during dietary restriction (DR) in both humans and rats. Because IGF-I modulates cell proliferation, apoptosis, and tumorigenesis, the mechanisms behind the protective effects of DR may depend on the reduction of this multifaceted growth factor. To test this hypothesis, IGF-I was restored during DR to ascertain if lowering of IGF-I was central to slowing bladder cancer progression during DR. Heterozygous p53-deficient mice received a bladder carcinogen, p-cresidine, to induce preneoplasia. After confirmation of bladder urothelial preneoplasia, the mice were divided into three groups: (a) ad libitum; (b) 20% DR; and (c) 20% DR plus IGF-I (IGF-I/DR). Serum IGF-I was lowered 24% by DR but was completely restored in the IGF-I/DR-treated mice using recombinant IGF-I administered via osmotic minipumps. Although tumor progression was decreased by DR, restoration of IGF-I serum levels in DR-treated mice increased the stage of the cancers. Furthermore, IGF-I modulated tumor progression independent of changes in body weight. Rates of apoptosis in the preneoplastic lesions were 10 times higher in DR-treated mice compared to those in IGF/DR- and ad libitum-treated mice. Administration of IGF-I to DR-treated mice also stimulated cell proliferation 6-fold in hyperplastic foci. In conclusion, DR lowered IGF-I levels, thereby favoring apoptosis over cell proliferation and ultimately slowing tumor progression. This is the first mechanistic study demonstrating that IGF-I supplementation abrogates the protective effect of DR on neoplastic progression.",
"title": "Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-defici..."
},
{
"docid": "MED-5203",
"text": "Fiber is not digested by endogenous enzymes but is fermented by microbes principally in the large intestine. With fermentable energy available, microbes synthesize protein by using ammonia released by their enzymes from urea and other nitrogenous substances in ingesta and intestinal secretions. Fibber fermentation also yields fatty acids that lower the concentration of free ammonia by lowering pH. Fiber increases bulk and water of intestinal contents, shortens transit time, and decreases the concentration of toxic substances in contact with the intestinal mucosa. These processes decrease duration and intensity of exposure of the intestinal mucosa to free ammonia, the form of nitrogen that is most toxic and most readily absorbed by cells. At concentrations found in the lower bowel on usual Western diets, ammonia destroys cells, alters nucleic acid synthesis, increases intestinal mucosal cell mass, increases virus infections, favors growth of cancerous cells over noncancerous cells in tissue culture, and increases virus infections. Ammonia in the bowel increases as protein intake increases. The attributes of ammonia and the epidemiological evidence comparing populations that maintain low intakes of unrefined carbohydrate with those that consume high intakes of protein, fat, and refined carbohydrates implicate ammonia in carcinogenesis and other disease processes.",
"title": "Diet and cell growth modulation by ammonia."
}
] |
220
|
Ca2+ cycling controls whole-body energy homeostasis in beige fat.
|
[
{
"docid": "19205437",
"text": "Uncoupling protein 1 (UCP1) plays a central role in nonshivering thermogenesis in brown fat; however, its role in beige fat remains unclear. Here we report a robust UCP1-independent thermogenic mechanism in beige fat that involves enhanced ATP-dependent Ca2+ cycling by sarco/endoplasmic reticulum Ca2+-ATPase 2b (SERCA2b) and ryanodine receptor 2 (RyR2). Inhibition of SERCA2b impairs UCP1-independent beige fat thermogenesis in humans and mice as well as in pigs, a species that lacks a functional UCP1 protein. Conversely, enhanced Ca2+ cycling by activation of α1- and/or β3-adrenergic receptors or the SERCA2b-RyR2 pathway stimulates UCP1-independent thermogenesis in beige adipocytes. In the absence of UCP1, beige fat dynamically expends glucose through enhanced glycolysis, tricarboxylic acid metabolism and pyruvate dehydrogenase activity for ATP-dependent thermogenesis through the SERCA2b pathway; beige fat thereby functions as a 'glucose sink' and improves glucose tolerance independently of body weight loss. Our study uncovers a noncanonical thermogenic mechanism through which beige fat controls whole-body energy homeostasis via Ca2+ cycling.",
"title": "UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis"
}
] |
[
{
"docid": "14865329",
"text": "Brown fat is a specialized fat depot that can increase energy expenditure and produce heat. After the recent discovery of the presence of active brown fat in human adults and novel transcription factors controlling brown adipocyte differentiation, the field of the study of brown fat has gained great interest and is rapidly growing. Brown fat expansion and/or activation results in increased energy expenditure and a negative energy balance in mice and limits weight gain. Brown fat is also able to utilize blood glucose and lipid and results in improved glucose metabolism and blood lipid independent of weight loss. Prolonged cold exposure and beta adrenergic agonists can induce browning of white adipose tissue. The inducible brown adipocyte, beige adipocyte evolving by thermogenic activation of white adipose tissue have different origin and molecular signature from classical brown adipocytes but share the characteristics of high mitochondria content, UCP1 expression and thermogenic capacity when activated. Increasing browning may also be an efficient way to increase whole brown fat activity. Recent human studies have shown possibilities that findings in mice can be reproduced in human, making brown fat a good candidate organ to treat obesity and its related disorders.",
"title": "Brown Fat and Browning for the Treatment of Obesity and Related Metabolic Disorders"
},
{
"docid": "25050364",
"text": "OBJECTIVE The proinflammatory cytokine interleukin-18 (IL-18) putatively modulates food intake and energy metabolism, but the effects of IL-18 in high-fat diet fed animals are unknown. Whether IL-18 alters basal metabolic rate or metabolic processes of living is unknown. Here, we tested the hypothesis that IL-18 modulates weight gain, energy intake, whole-body energy expenditure, and utilization of lipid as a fuel substrate in high-fat diet fed mice. METHODS Food intake, whole-body metabolism, and motor activity of IL-18 knockout mice were compared to those of wildtype littermates; anorectic effects of intracerebroventricular IL-18 administration were compared between IL-18 receptor knockout, IL-18/IL-18R knockout and wildtype mice. RESULTS Chow-reared IL-18 knockout mice were overweight at 6 months of age and then gained excess weight on both low-fat and high-fat diets, ate more high-fat diet, and showed reduced whole-body energy expenditure and increased respiratory exchange ratios. Reductions in energy expenditure of IL-18 knockout mice were seen across fasting vs. feeding conditions, low- vs. high-fat diets, high vs. low levels of physical activity and times of day, suggesting actions on basal metabolic rate. The circadian amplitude of energy expenditure, but not respiratory exchange ratio, food intake, or motor activity, also was blunted in IL-18 knockout mice. Central IL-18 administration reduced high-fat diet intake in wildtype mice, but not in mice lacking the IL-18 receptor. CONCLUSION The loss-of-function results support the hypothesis that endogenous IL-18 suppresses appetite and promote energy expenditure and lipid fuel substrate utilization not only during sickness, but also in healthy adults consuming high-fat diets.",
"title": "Interleukin-18 null mutation increases weight and food intake and reduces energy expenditure and lipid substrate utilization in high-fat diet fed mice"
},
{
"docid": "23369842",
"text": "Twenty-four hour whole body indirect calorimetry has been used to study the effects of feeding, during a sedentary test day, isoenergetic diets which varied in fat (3 or 40 per cent of total energy) and carbohydrate (82 or 45 per cent) content. Three groups of women were studied: lean, obese and 'post-obese' after slimming. Energy expenditure was greater in absolute terms in the obese women. Twenty-four hour energy expenditure was lower by only 3-7 per cent when fasting compared to that when fed to achieve energy balance. There were no large differences in energy expenditure between the two diets or between the groups but the thermogenic effect of the high carbohydrate diet was significantly greater than that of the high fat diet (5.8 vs 3.5 per cent of energy expenditure: P less than 0.01). The post-obese tended to have lower energy expenditure per kg FFM than controls when fasting and when high-fat fed, but this pattern was not shown by the obese. Sleeping energy expenditure was particularly low in the post-obese group when high-fat fed. Dirunal variations in RQ appear to show more marked rise in morning RQ from the nocturnal minimum in the obese and post-obese, which might be evidence for an energy-saving mechanism through greater availability of stored dietary carbohydrate.",
"title": "Metabolic effects of isoenergetic nutrient exchange over 24 hours in relation to obesity in women."
},
{
"docid": "15535511",
"text": "Dopaminergic midbrain neurons integrate signals on food palatability and food-associated reward into the complex control of energy homeostasis. To define the role of insulin receptor (IR) signaling in this circuitry, we inactivated IR signaling in tyrosine hydroxylase (Th)-expressing cells of mice (IR(ΔTh)). IR inactivation in Th-expressing cells of mice resulted in increased body weight, increased fat mass, and hyperphagia. While insulin acutely stimulated firing frequency in 50% of dopaminergic VTA/SN neurons, this response was abolished in IR(ΔTh) mice. Moreover, these mice exhibited an altered response to cocaine under food-restricted conditions. Taken together, these data provide in vivo evidence for a critical role of insulin signaling in catecholaminergic neurons to control food intake and energy homeostasis.",
"title": "Role for insulin signaling in catecholaminergic neurons in control of energy homeostasis."
},
{
"docid": "17973161",
"text": "Uncoupling protein 1 (UCP1) is highly expressed in brown adipose tissue, where it generates heat by uncoupling electron transport from ATP production. UCP1 is also found outside classical brown adipose tissue depots, in adipocytes that are termed 'brite' (brown-in-white) or 'beige'. In humans, the presence of brite or beige (brite/beige) adipocytes is correlated with a lean, metabolically healthy phenotype, but whether a causal relationship exists is not clear. Here we report that human brite/beige adipocyte progenitors proliferate in response to pro-angiogenic factors, in association with expanding capillary networks. Adipocytes formed from these progenitors transform in response to adenylate cyclase activation from being UCP1 negative to being UCP1 positive, which is a defining feature of the beige/brite phenotype, while displaying uncoupled respiration. When implanted into normal chow-fed, or into high-fat diet (HFD)-fed, glucose-intolerant NOD-scid IL2rg(null) (NSG) mice, brite/beige adipocytes activated in vitro enhance systemic glucose tolerance. These adipocytes express neuroendocrine and secreted factors, including the pro-protein convertase PCSK1, which is strongly associated with human obesity. Pro-angiogenic conditions therefore drive the proliferation of human beige/brite adipocyte progenitors, and activated beige/brite adipocytes can affect systemic glucose homeostasis, potentially through a neuroendocrine mechanism.",
"title": "Human ‘brite / beige’ adipocytes develop from capillary networks and their implantation improves metabolic homeostasis in mice"
},
{
"docid": "11742219",
"text": "Galanin (GAL) is known to stimulate feeding behavior. This peptide has different properties and functions from other feeding stimulants, e.g., neuropeptide Y and agouti-related protein. Hypothalamic GAL is relatively unresponsive to food deprivation and to changes in corticosterone, glucose utilization, dietary carbohydrate and leptin. This indicates that this peptide is not essential under conditions when food is scarce or low-energy, high-carbohydrate diets are being consumed. In contrast, recent evidence suggests that GAL in the paraventricular nucleus (PVN) functions in close relation to dietary fat and alcohol. In particular, it mediates functions that allow animals to adapt to conditions of positive energy balance involving excess consumption of these nutrients. This peptide in the PVN is stimulated by a high-fat diet and also by alcohol. It is stimulated by an increase in circulating lipids caused by a fat-rich meal or alcohol consumption, and it rises during the middle of the active feeding cycle, when fat consumption and triglycerides naturally rise. When centrally injected, GAL in the PVN increases the consumption of food and alcohol. Moreover, it produces a significantly stronger feeding response in rats maintained on a fat-rich diet, which also promotes alcohol intake. This evidence supports the existence of non-homeostatic, positive feedback circuits between GAL and both dietary fat and alcohol. These circuits are believed to contribute to the large meal size, over-consumption of alcohol, and obesity which are generally associated with fat-rich foods.",
"title": "Regulation and effects of hypothalamic galanin: relation to dietary fat, alcohol ingestion, circulating lipids and energy homeostasis."
},
{
"docid": "21547032",
"text": "Objective:In mice and in humans, treatment with the second-generation antipsychotic drug olanzapine (OLZ) produces excessive weight gain, adiposity and secondary metabolic complications, including loss of glucose and insulin homeostasis. In mice consuming a high-fat (HF) diet, a similar phenotype develops, which is inhibited by the analgesic acetaminophen (APAP) and by the antioxidant tetrahydroindenoindole (THII). Therefore, we examined the ability of APAP and THII to prevent metabolic changes in mice receiving OLZ.Design and Measurement:C57BL/6J mice received either a normal diet or a HF diet, and were administered daily dosages of OLZ (3 mg kg−1 body weight), alone or with APAP (30 mg kg−1 body weight) or THII (4.5 mg kg−1 body weight), for 10 weeks. Parameters of body composition and metabolism, including glucose and insulin homeostasis and oxidative stress, were examined. Results:OLZ treatment doubled the HF diet-induced increases in body weight and percent body fat. These increases were partially prevented by both APAP and THII, although food consumption was constant in all groups. The THII protection was associated with an increase in whole body and mitochondrial respiration. OLZ also exacerbated, and both APAP and THII prevented, HF diet-induced loss of glucose tolerance and insulin resistance. As increased body fat promotes insulin resistance by a pathway involving oxidative stress, we evaluated production of reactive oxygen and lipid peroxidation in white adipose tissue (WAT). HF diet caused an increase in lipid peroxidation, NADPH-dependent O2 uptake and H2O2 production, which were further exacerbated by OLZ. APAP, THII and the NADPH oxidase inhibitor, diphenyleneiodonium chloride, each abolished oxidative stress in WAT.Conclusions:We conclude that both APAP and THII intervene in the development of obesity and metabolic complications associated with OLZ treatment.",
"title": "Protection from olanzapine-induced metabolic toxicity in mice by acetaminophen and tetrahydroindenoindole"
},
{
"docid": "11201004",
"text": "Little is known about longitudinal associations between added sugar consumption (solid and liquid sources) and glucose-insulin homeostasis among youth. Caucasian children (8-10 y) with at least one obese biological parent were recruited in the QUébec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort (n = 630) and followed-up 2 y later (n = 564). Added sugars were assessed by 3 24-h dietary recalls at baseline. Two-year changes were examined in multivariate linear regression models, adjusting for baseline level, age, sex, Tanner stage, energy intake, fat mass (dual-energy X-ray absorptiometry), and physical activity (7 d accelerometer). Added sugar intake in either liquid or solid sources was not related to changes in adiposity measures (fat mass, body mass index, or waist circumference). However, a higher consumption (10 g/d) of added sugars from liquid sources was associated with 0.04 mmol/L higher fasting glucose, 2.3 pmol/L higher fasting insulin, 0.1 unit higher homeostasis model assessment of insulin resistance (HOMA-IR), and 0.4 unit lower Matsuda-insulin sensitivity index (Matsuda-ISI) in all participants (P < 0.01). No associations were observed with consumption of added sugars from solid sources. Overweight/obese children at baseline had greater increases in adiposity indicators, fasting insulin, and HOMA-IR and decreases in Matsuda-ISI during those 2 y than normal-weight children. Consumption of added sugars from liquid or solid sources was not associated with changes in adiposity, but liquid added sugars were a risk factor for the development of impaired glucose homeostasis and insulin resistance over 2 y among youth at risk of obesity.",
"title": "Consumption of added sugars from liquid but not solid sources predicts impaired glucose homeostasis and insulin resistance among youth at risk of obesity."
},
{
"docid": "11428884",
"text": "Adipose tissue is an important metabolic organ, the dysfunction of which is associated with the development of obesity, diabetes mellitus, and cardiovascular disease. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is considered the master regulator of adipocyte differentiation and function. Although its cell-autonomous role in adipogenesis has been clearly demonstrated in cell culture, previous fat-specific knockouts of the murine PPARγ gene did not demonstrate a dramatic phenotype in vivo. Here, using Adipoq-Cre mice to drive adipose-specific recombination, we report a unique fat-specific PPARγ knockout (PPARγ FKO) mouse model with almost no visible brown and white adipose tissue at age 3 mo. As a consequence, PPARγ FKO mice had hugely enlarged pancreatic islets, massive fatty livers, and dramatically elevated levels of blood glucose and serum insulin accompanied by extreme insulin resistance. PPARγ FKO mice also exhibited delayed hair coat formation associated with absence of dermal fat, disrupted mammary gland development with loss of mammary fat pads, and high bone mass with loss of bone marrow fat, indicating the critical roles of adipose PPARγ in these tissues. Together, our data reveal the necessity of fat PPARγ in adipose formation, whole-body metabolic homeostasis, and normal development of fat-containing tissues.",
"title": "Lipoatrophy and severe metabolic disturbance in mice with fat-specific deletion of PPARγ."
},
{
"docid": "1590744",
"text": "The AMP-activated protein kinase (AMPK) is a key regulator of cellular and whole-body energy homeostasis, which acts to restore energy homoeostasis whenever cellular energy charge is depleted. Over the last 2 decades, it has become apparent that AMPK regulates several other cellular functions and has specific roles in cardiovascular tissues, acting to regulate cardiac metabolism and contractile function, as well as promoting anticontractile, anti-inflammatory, and antiatherogenic actions in blood vessels. In this review, we discuss the role of AMPK in the cardiovascular system, including the molecular basis of mutations in AMPK that alter cardiac physiology and the proposed mechanisms by which AMPK regulates vascular function under physiological and pathophysiological conditions.",
"title": "AMP-Activated Protein Kinase: An Ubiquitous Signaling Pathway With Key Roles in the Cardiovascular System"
},
{
"docid": "11238784",
"text": "Liver X receptors (LXRs) and farnesoid X receptor (FXR) are nuclear receptors that function as intracellular sensors for sterols and bile acids, respectively. In response to their ligands, these receptors induce transcriptional responses that maintain a balanced, finely tuned regulation of cholesterol and bile acid metabolism. LXRs also permit the efficient storage of carbohydrate- and fat-derived energy, whereas FXR activation results in an overall decrease in triglyceride levels and modulation of glucose metabolism. The elegant, dual interplay between these two receptor systems suggests that they coevolved to constitute a highly sensitive and efficient system for the maintenance of total body fat and cholesterol homeostasis. Emerging evidence suggests that the tissue-specific action of these receptors is also crucial for the proper function of the cardiovascular, immune, reproductive, endocrine pancreas, renal, and central nervous systems. Together, LXRs and FXR represent potential therapeutic targets for the treatment and prevention of numerous metabolic and lipid-related diseases.",
"title": "LXRS and FXR: the yin and yang of cholesterol and fat metabolism."
},
{
"docid": "23017040",
"text": "Reduced dietary methionine intake (0.17% methionine, MR) and calorie restriction (CR) prolong lifespan in male Fischer 344 rats. Although the mechanisms are unclear, both regimens feature lower body weight and reductions in adiposity. Reduced fat deposition in CR is linked to preservation of insulin responsiveness in older animals. These studies examine the relationship between insulin responsiveness and visceral fat in MR and test whether, despite lower food intake observed in MR animals, decreased visceral fat accretion and preservation of insulin sensitivity is not secondary to CR. Accordingly, rats pair fed (pf) control diet (0.86% methinone, CF) to match the food intake of MR for 80 weeks exhibit insulin, glucose, and leptin levels similar to control-fed animals and comparable amounts of visceral fat. Conversely, MR rats show significantly reduced visceral fat compared to CF and PF with concomitant decreases in basal insulin, glucose, and leptin, and increased adiponectin and triiodothyronine. Daily energy expenditure in MR animals significantly exceeds that of both PF and CF. In a separate cohort, insulin responses of older MR animals as measured by oral glucose challenge are similar to young animals. Longitudinal assessments of MR and CF through 112 weeks of age reveal that MR prevents age-associated increases in serum lipids. By 16 weeks, MR animals show a 40% reduction in insulin-like growth factor-1 (IGF-1) that is sustained throughout life; CF IGF-1 levels decline much later, beginning at 112 weeks. Collectively, the results indicate that MR reduces visceral fat and preserves insulin activity in aging rats independent of energy restriction.",
"title": "Methionine restriction decreases visceral fat mass and preserves insulin action in aging male Fischer 344 rats independent of energy restriction."
},
{
"docid": "20363389",
"text": "In order to elucidate energy balance in the skeletal muscle, we cloned cDNA of a homologue of uncoupling protein (UCP) from rat skeletal muscle. We also cloned rat UCP-2 cDNA from rat brown adipose tissue (BAT). The UCP cloned from rat skeletal muscle showed 57% and 72% identity with rat UCP-1 and UCP-2. The mRNA was expressed abundantly in the skeletal muscle, moderately in the BAT, and slightly in the white adipose tissue (WAT) with a major band at 2.5 kb and a minor band at 2.8 kb, while the UCP-2 gene expression was widely detected in the whole body with substantial levels in the WAT and with slight levels in the skeletal muscle and BAT. The rat UCP cloned in the present study showed 86% identity with the recently cloned human UCP-3, which was also expressed abundantly in the skeletal muscle with a signal of 2.4 kb. Therefore, the rat UCP was considered to be rat UCP-3. In rats fed high-fat diet the UCP-3 gene expression was augmented 2-fold in the skeletal muscle while UCP-2 mRNA levels were increased significantly (1.6-fold) in the epididymal WAT. Augmented expression of UCPs may provide defense against high-fat induced obesity and impairment of glucose metabolism.",
"title": "Cloning of rat uncoupling protein-3 and uncoupling protein-2 cDNAs: their gene expression in rats fed high-fat diet."
},
{
"docid": "17231273",
"text": "Energy deficiency and dysfunction of the Na+, K+-ATPase are common consequences of many pathological insults. The nature and mechanism of cell injury induced by impaired Na+, K+-ATPase, however, are not well defined. We used cultured cortical neurons to examine the hypothesis that blocking the Na+, K+-ATPase induces apoptosis by depleting cellular K+ and, concurrently, induces necrotic injury in the same cells by increasing intracellular Ca2+ and Na+. The Na+, K+-ATPase inhibitor ouabain induced concentration-dependent neuronal death. Ouabain triggered transient neuronal cell swelling followed by cell shrinkage, accompanied by intracellular Ca2+ and Na+ increase, K+ decrease, cytochrome c release, caspase-3 activation, and DNA laddering. Electron microscopy revealed the coexistence of ultrastructural features of both apoptosis and necrosis in individual cells. The caspase inhibitor Z-Val-Ala-Asp(OMe)-fluoromethyl ketone (Z-VAD-FMK) blocked >50% of ouabain-induced neuronal death. Potassium channel blockers or high K+ medium, but not Ca2+ channel blockade, prevented cytochrome c release, caspase activation, and DNA damage. Blocking of K+, Ca2+, or Na+ channels or high K+ medium each attenuated the ouabain-induced cell death; combined inhibition of K+ channels and Ca2+ or Na+ channels resulted in additional protection. Moreover, coapplication of Z-VAD-FMK and nifedipine produced virtually complete neuroprotection. These results suggest that the neuronal death associated with Na+, K+-pump failure consists of concurrent apoptotic and necrotic components, mediated by intracellular depletion of K+ and accumulation of Ca2+ and Na+, respectively. The ouabain-induced hybrid death may represent a distinct form of cell death related to the brain injury of inadequate energy supply and disrupted ion homeostasis.",
"title": "Ionic mechanism of ouabain-induced concurrent apoptosis and necrosis in individual cultured cortical neurons"
},
{
"docid": "36558211",
"text": "OBJECTIVES To explore the different characteristics of high and low fat consumers, in particular their macronutrient intake and body mass index. DESIGN Reanalysis of data from the Dietary and Nutritional Survey of British Adults. Comparisons were made between groups defined as high and low fat consumers on the basis of 7-day weighed food records considered to be valid for energy intake. Individuals were classified in two ways according to the percentage energy from fat (FAT%) and the absolute amount of fat consumed (FATg). The criteria for classification of the high FAT% being > 45% (high fat) and < or = 35% (low fat). For the FATg group the threshold for the high fat group was > 138 g/day (men) and > 102 g/day (women), and for the low fat group < 85 g/day (men) and < 70 g/day (women). SETTING Dietary data was collected from private households in Great Britain between 1986 and 1987. SUBJECTS From the total population of 2197, individuals who were slimming, ill or had an EI: BMR of < 1.2 were excluded in order to use data which was most likely to represent habitual energy intakes. From the remaining 1240 subjects, 10.8% of this sample (6.1% of the total population) were classified as low fat consumers (76 men and 58 women) and 15.4% high fat (8.7% of the total population, 93 men and 98 women). MAIN OUTCOME MEASURES Macronutrient consumption and body mass index (BMI). RESULTS 30% of the subjects changed fat group classification when the criteria of defining high and low fat groups altered from FAT% to FATg. Nutrient intakes differed according to definition of the groups. The high fat FATg group ate significantly more of all nutrients than the low fat FATg group. However, this was not seen for the FAT% analysis, with the high fat group eating more fat and less carbohydrate. The average BMI tended to be higher in the high fat than the low fat groups, particularly in the FATg analysis. However, the high fat group contained a wide range of BMIs. Further exploration of BMI in the high fat groups, showed that age (an 11-year difference) was the only variable to distinguish individuals in the top and bottom quartiles of BMI. CONCLUSIONS High and low fat consumers differ according to a number of variables, and this is affected by how these groups are defined (FAT% or FATg). High fat consumers tend to have a higher BMI than low fat consumers, but not all high fat consumers are overweight or obese.",
"title": "High and low fat consumers, their macronutrient intake and body mass index: further analysis of the National Diet and Nutrition Survey of British Adults."
},
{
"docid": "12994780",
"text": "Rationale:Atypical antipsychotic drugs (AAD) induce significant weight gain in female C57BL/6J mice. The effect of dietary fat on weight gain and serum lipids in this model is unknown. Objectives: Test the hypothesis that the obesigenic effects of these drugs are greater in the presence of a high-fat diet. Methods:Female C57BL/6J mice were treated with atypical antipsychotics for 3 weeks and fed either a low-fat or high-fat diet (4.6 vs 15.6% fat by wt). Food intake (FI), body weight (BW), body composition, and serum lipids were measured during treatment with optimized doses of olanzapine, quetiapine, and risperidone. Energy intake (EI) and feed efficiency (FE) were calculated. Group differences in change were analyzed via repeated measures analysis of variance (ANOVA). Serum lipid concentrations, EI and FE were compared using two-way ANOVA.Results:AAD-treated mice gained significantly more weight than controls after 3 weeks (P<0.001). Treatment and diet had significant effects on FI and EI over time (P<0.001). AAD-treated mice had significantly higher FE than controls (P<0.05); however, there was no significant drug by diet interaction (P=0.65). Risperidone low-fat mice gained significantly more absolute fat mass than placebo low-fat mice (P<0.05). All treatment groups, except quetiapine low-fat and olanzapine high-fat, gained significantly more absolute lean mass than placebo controls (P<0.05). Cholesterol levels were significantly lower in quetiapine and risperidone than placebo (P<0.05). Risperidone low-fat mice had significantly higher triglyceride levels than placebo and risperidone high-fat mice (P<0.05).Conclusions:A high-fat diet does not increase AAD-induced BW gain in female mice during a 3-week treatment period.",
"title": "No effect of dietary fat on short-term weight gain in mice treated with atypical antipsychotic drugs"
},
{
"docid": "17150648",
"text": "Glial cells perform critical functions that alter the metabolism and activity of neurons, and there is increasing interest in their role in appetite and energy balance. Leptin, a key regulator of appetite and metabolism, has previously been reported to influence glial structural proteins and morphology. Here, we demonstrate that metabolic status and leptin also modify astrocyte-specific glutamate and glucose transporters, indicating that metabolic signals influence synaptic efficacy and glucose uptake and, ultimately, neuronal function. We found that basal and glucose-stimulated electrical activity of hypothalamic proopiomelanocortin (POMC) neurons in mice were altered in the offspring of mothers fed a high-fat diet. In adulthood, increased body weight and fasting also altered the expression of glucose and glutamate transporters. These results demonstrate that whole-organism metabolism alters hypothalamic glial cell activity and suggest that these cells play an important role in the pathology of obesity.",
"title": "Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes."
},
{
"docid": "1365188",
"text": "Several data suggest that fermentable dietary fiber could play a role in the control of obesity and associated metabolic disorders. The aim of this study was to investigate the putative role of short chain fructo-oligosaccharide (OFS) - a non-digestible oligosaccharide - in mice fed a standard diet and in mice fed two distinct high fat diets inducing metabolic disorders associated to obesity. We confirmed, in mice, several effects previously shown in rats fed a standard diet enriched with OFS, namely an increase in total and empty caecum weight, a significant decrease in epididymal fat mass, and an increase in colonic and portal plasma glucagon-like peptide-1 (GLP-1), a phenomenon positively correlated with a higher colonic proglucagon mRNA level. Curiously, 4-week treatment with OFS added at the same dose induced different effects when added in the two different high fat diets. OFS decreased energy intake, body weight gain, glycemia, and epididymal fat mass only when added together with the high fat-carbohydrate free diet, in which OFS promoted colonic proglucagon expression and insulin secretion. Our results support an association between the increase in proglucagon expression in the proximal colon and OFS effects on glycemia, fat mass development, and/or body weight gain. In conclusion, dietary oligosaccharides would constitute an interesting class of dietary fibers promoting, in certain conditions, endogenous GLP-1 production, with beneficial physiological consequences. This remains to be proven in human studies.",
"title": "Relation between colonic proglucagon expression and metabolic response to oligofructose in high fat diet-fed mice."
},
{
"docid": "33918970",
"text": "OBJECTIVE Oligofructose (OFS) is a prebiotic that reduces energy intake and fat mass via changes in gut satiety hormones and microbiota. The effects of OFS may vary depending on predisposition to obesity. The aim of this study was to examine the effect of OFS in diet-induced obese (DIO) and diet-resistant (DR) rats. METHODS Adult, male DIO, and DR rats were randomized to: high-fat/high-sucrose (HFS) diet or HFS diet + 10% OFS for 6 weeks. Body composition, food intake, gut microbiota, plasma gut hormones, and cannabinoid CB(1) receptor expression in the nodose ganglia were measured. RESULTS OFS reduced body weight, energy intake, and fat mass in both phenotypes (P < 0.05). Select gut microbiota differed in DIO versus DR rats (P < 0.05), the differences being eliminated by OFS. OFS did not modify plasma ghrelin or CB(1) expression in nodose ganglia, but plasma levels of GIP were reduced and PYY were elevated (P < 0.05) by OFS. CONCLUSIONS OFS was able to reduce body weight and adiposity in both prone and resistant obese phenotypes. OFS-induced changes in gut microbiota profiles in DIO and DR rats, along with changes in gut hormone levels, likely contribute to the sustained lower body weights.",
"title": "Interactive effects of oligofructose and obesity predisposition on gut hormones and microbiota in diet-induced obese rats."
},
{
"docid": "18084826",
"text": "Accurate measurement of fat mass has become increasingly important with the increasing incidence of obesity. We assessed fat and muscle mass of Koreans with the Korea National Health and Nutrition Examination Survey IV (KNHANES IV). We studied 10,456 subjects (aged 20 to 85 yr; 4,476 men, 5,980 women). Fat and muscle mass were measured by dual-energy x-ray absorptiometry. Reference values of body compositions were obtained using the LMS method. The fat mass index (FMI, body fat mass/height(2); kg/m(2)) of Korean men did not correlate with age (P = 0.452), but those of Korean women (P < 0.001) did. The ratio of percentage of fat in the trunk and legs was positively related with age in both the genders. The appendicular lean mass/height(2) (kg/m(2)) of Korean men was negatively related to age (P < 0.001). In women, this ratio increased with age (P < 0.001). When we defined obesity according to the FMI classification, the rates of obesity were 6.1% (FMI > 9 kg/m(2)) in men and 2.7% (FMI > 13 kg/m(2)) in women. It is concluded that the muscle mass decreases and obesity increases with aging in Korean men, whereas both fat mass and obesity increase with aging in Korean women.",
"title": "Characteristics of Body Fat, Body Fat Percentage and Other Body Composition for Koreans from KNHANES IV"
},
{
"docid": "29025270",
"text": "We examined the contributions of genetic factors and the family environment to human fatness in a sample of 540 adult Danish adoptees who were selected from a population of 3580 and divided into four weight classes: thin, median weight, overweight, and obese. There was a strong relation between the weight class of the adoptees and the body-mass index of their biologic parents - for the mothers, P less than 0.0001; for the fathers, P less than 0.02. There was no relation between the weight class of the adoptees and the body-mass index of their adoptive parents. Cumulative distributions of the body-mass index of parents showed similar results; there was a strong relation between the body-mass index of biologic parents and adoptee weight class and no relation between the index of adoptive parents and adoptee weight class. Furthermore, the relation between biologic parents and adoptees was not confined to the obesity weight class, but was present across the whole range of body fatness - from very thin to very fat. We conclude that genetic influences have an important role in determining human fatness in adults, whereas the family environment alone has no apparent effect.",
"title": "An adoption study of human obesity."
},
{
"docid": "28845338",
"text": "One of the primary limitations of many psychiatric medications is weight gain, the mechanism of which remains to be fully elucidated. We conducted a 2-week double-blind placebo-controlled study on weight gain with olanzapine, which is frequently but unpredictably associated with this side effect, to address the possible mechanisms of weight gain independent of changes in the psychiatric condition for which it is prescribed. Healthy male volunteers were randomly assigned to olanzapine (5 mg/day for 7 days, then 10 mg/day for 7 days) or a matching placebo. Of the 24 participants, 19 completed the study (olanzapine, n=13; placebo, n=6). Body weight, glucose, triglyceride, total cholesterol, lipid, leptin, insulin, and aldosterone levels, resting metabolic rate, body composition, physical activity, and 24-h dietary intake were assessed. A significant increase in weight as well as triglyceride, insulin, and leptin levels were found in the olanzapine group as a whole. In participants receiving olanzapine who actually gained weight (n=8), lean but not fat mass increased, as did insulin, fasting glucose, total cholesterol, low-density lipoprotein, and non-high-density lipoprotein levels, whereas aldosterone levels decreased. There were no significant metabolic or endocrine changes in participants receiving placebo or in those receiving olanzapine who did not gain weight. Early metabolic changes appear to be independent of accumulation of fat.",
"title": "Increased lean body mass as an early indicator of olanzapine-induced weight gain in healthy men."
},
{
"docid": "2575938",
"text": "The relationships between children's activity, aerobic fitness, and fatness are unclear. Indirect estimates of activity, e.g., heart rate (HR) and recall, may mask any associations. The purpose of this study was to assess these relationships by using the Tritrac-R3D, a pedometer, and heart rate. Thirty-four children, ages 8-10 yr, participated in the study. The Tritrac and pedometer were worn for up to 6 days. HR was measured for 1 day. Activity measured by Tritrac or pedometer correlated positively to fitness in the whole group (Tritrac, r = 0.66; pedometer, r = 0.59; P < 0.01) and in boys and girls separately (P < 0.05) and correlated negatively to fatness in the whole group (r = -0.42, P < 0.05). In contrast, HR did not correlate significantly to fitness, and HR of >139 beats/min correlated positively to fatness in girls (r = 0.64, P < 0.05). This suggests that HR is misleading as a measure of activity. This study supports a positive relationship between activity and fitness and suggests a negative relationship between fatness and activity.",
"title": "Relationship between activity levels, aerobic fitness, and body fat in 8- to 10-yr-old children."
},
{
"docid": "32955023",
"text": "The expansion of white adipose tissue (WAT) in obesity involves de novo differentiation of new adipocytes; however, the cellular origin of these cells remains unclear. Here, we utilize Zfp423(GFP) reporter mice to characterize adipose mural (Pdgfrβ(+)) cells with varying levels of the preadipocyte commitment factor Zfp423. We find that adipose tissue contains distinct mural populations, with levels of Zfp423 distinguishing adipogenic from inflammatory-like mural cells. Using our \"MuralChaser\" lineage tracking system, we uncover adipose perivascular cells as developmental precursors of adipocytes formed in obesity, with adipogenesis and precursor abundance regulated in a depot-dependent manner. Interestingly, Pdgfrβ(+) cells do not significantly contribute to the initial cold-induced recruitment of beige adipocytes in WAT; it is only after prolonged cold exposure that these cells differentiate into beige adipocytes. These results provide genetic evidence for a mural cell origin of white adipocytes in obesity and suggest that beige adipogenesis may originate from multiple sources.",
"title": "Pdgfrβ+ Mural Preadipocytes Contribute to Adipocyte Hyperplasia Induced by High-Fat-Diet Feeding and Prolonged Cold Exposure in Adult Mice."
},
{
"docid": "29691654",
"text": "Until recently, the mechanism of adaptive thermogenesis was ascribed to the expression of uncoupling protein 1 (UCP1) in brown and beige adipocytes. UCP1 is known to catalyze a proton leak of the inner mitochondrial membrane, resulting in uncoupled oxidative metabolism with no production of adenosine triphosphate and increased energy expenditure. Thus increasing brown and beige adipose tissue with augmented UCP1 expression is a viable target for obesity-related disorders. Recent work demonstrates an UCP1-independent pathway to uncouple mitochondrial respiration. A secreted enzyme, PM20D1, enriched in UCP1+ adipocytes, exhibits catalytic and hydrolytic activity to reversibly form N-acyl amino acids. N-acyl amino acids act as endogenous uncouplers of mitochondrial respiration at physiological concentrations. Administration of PM20D1 or its products, N-acyl amino acids, to diet-induced obese mice improves glucose tolerance by increasing energy expenditure. In short-term studies, treated animals exhibit no toxicity while experiencing 10% weight loss primarily of adipose tissue. Further study of this metabolic pathway may identify novel therapies for diabesity, the disease state associated with diabetes and obesity.",
"title": "Uncoupling Mitochondrial Respiration for Diabesity."
},
{
"docid": "20532591",
"text": "White adipose tissue displays high plasticity. We developed a system for the inducible, permanent labeling of mature adipocytes that we called the AdipoChaser mouse. We monitored adipogenesis during development, high-fat diet (HFD) feeding and cold exposure. During cold-induced 'browning' of subcutaneous fat, most 'beige' adipocytes stem from de novo–differentiated adipocytes. During HFD feeding, epididymal fat initiates adipogenesis after 4 weeks, whereas subcutaneous fat undergoes hypertrophy for a period of up to 12 weeks. Gonadal fat develops postnatally, whereas subcutaneous fat develops between embryonic days 14 and 18. Our results highlight the extensive differences in adipogenic potential in various fat depots.",
"title": "Tracking adipogenesis during white adipose tissue development, expansion and regeneration"
},
{
"docid": "13944805",
"text": "KEY POINTS Maternal obesity reduces adipogenic progenitor density in offspring adipose tissue. The ability of adipose tissue expansion in the offspring of obese mothers is limited and is associated with metabolic dysfunction of adipose tissue when challenged with a high-fat diet. Maternal obesity induces DNA demethylation in the promoter of zinc finger protein 423, which renders progenitor cells with a high adipogenic capacity. Maternal obesity demonstrates long-term effects on the adipogenic capacity of progenitor cells in offspring adipose tissue, demonstrating a developmental programming effect. ABSTRACT Maternal obesity (MO) programs offspring obesity and metabolic disorders, although the underlying mechanisms remain poorly defined. Progenitor cells are the source of new adipocytes. The present study aimed to test whether MO epigenetically predisposes adipocyte progenitors in the fat of offspring to adipogenic differentiation and subsequent depletion, which leads to a failure of adipose tissue plasticity under positive energy balance, contributing to adipose tissue metabolic dysfunction. C57BL/6 female mice were fed either a control diet (10% energy from fat) or a high-fat diet (45% energy from fat) for 8 weeks before mating. Male offspring of control (Con) and obese (OB) dams were weaned onto a regular (Reg) or obesogenic (Obe) diet until 3 months of age. At weaning, male OB offspring had a higher expression of Zinc finger protein 423 (zfp423), a key transcription factor in adipogenesis, as well as lower DNA methylation of its promoter in progenitors of epididymal fat compared to Con offspring, which was correlated with enhanced adipogenic differentiation. At 3 months of age, progenitor density was 30.9 ± 9.7% lower in OB/Obe compared to Con/Obe mice, accompanied by a limited expansion of the adipocyte number when challenged with a high-energy diet. This difference was associated with lower DNA methylation in the zfp423 promoter in the epididymal fat of OB/Obe offspring, which was correlated with greater macrophage chemotactic protein-1 and hypoxia-inducible factor 1α expression. In summary, MO epigenetically limits the expansion capacity of offspring adipose tissue, providing an explanation for the adipose metabolic dysfunction of male offspring in the setting of MO.",
"title": "Maternal obesity epigenetically alters visceral fat progenitor cell properties in male offspring mice."
},
{
"docid": "12805683",
"text": "Mammalian nuclear hormone receptors (NHRs), such as liver X receptor, farnesoid X receptor, and peroxisome proliferator-activated receptors (PPARs), precisely control energy metabolism. Consequently, these receptors are important targets for the treatment of metabolic diseases, including diabetes and obesity. A thorough understanding of NHR fat regulatory networks has been limited, however, by a lack of genetically tractable experimental systems. Here we show that deletion of the Caenorhabditis elegans NHR gene nhr-49 yielded worms with elevated fat content and shortened life span. Employing a quantitative RT-PCR screen, we found that nhr-49 influenced the expression of 13 genes involved in energy metabolism. Indeed, nhr-49 served as a key regulator of fat usage, modulating pathways that control the consumption of fat and maintain a normal balance of fatty acid saturation. We found that the two phenotypes of the nhr-49 knockout were linked to distinct pathways and were separable: The high-fat phenotype was due to reduced expression of enzymes in fatty acid β-oxidation, and the shortened adult life span resulted from impaired expression of a stearoyl-CoA desaturase. Despite its sequence relationship with the mammalian hepatocyte nuclear factor 4 receptor, the biological activities of nhr-49 were most similar to those of the mammalian PPARs, implying an evolutionarily conserved role for NHRs in modulating fat consumption and composition. Our findings in C. elegans provide novel insights into how NHR regulatory networks are coordinated to govern fat metabolism.",
"title": "Nuclear Hormone Receptor NHR-49 Controls Fat Consumption and Fatty Acid Composition in C. elegans"
},
{
"docid": "10883736",
"text": "CONTEXT The mechanisms that drive progression from fatty liver to steatohepatitis and cirrhosis are unknown. In animal models, obese mice with fatty livers are vulnerable to liver adenosine triphosphate (ATP) depletion and necrosis, suggesting that altered hepatic energy homeostasis may be involved. OBJECTIVE To determine if patients with fatty liver disease exhibit impaired recovery from hepatic ATP depletion. DESIGN Laboratory analysis of liver ATP stores monitored by nuclear magnetic resonance spectroscopy before and after transient hepatic ATP depletion was induced by fructose injection. The study was conducted between July 15 and August 30, 1998. SETTING University hospital. PATIENTS Eight consecutive adults with biopsy-proven nonalcoholic steatohepatitis and 7 healthy age- and sex-matched controls. MAIN OUTCOME MEASURE Level of ATP 1 hour after fructose infusion in patients vs controls. RESULTS In patients, serum aminotransferase levels were increased (P = .02 vs controls); albumin and bilirubin values were normal and clinical evidence of portal hypertension was absent in both groups. However, 2 patients had moderate fibrosis and 1 had cirrhosis on liver biopsy. Mean serum glucose, cholesterol, and triglyceride levels were similar between groups but patients weighed significantly more than controls (P = .02). Liver ATP levels were similar in the 2 groups before fructose infusion and decreased similarly in both after fructose infusion (P = .01 vs initial ATP levels). However, controls replenished their hepatic ATP stores during the 1-hour follow-up period (P<.02 vs minimum ATP) but patients did not. Hence, patients' hepatic ATP levels were lower than those of controls at the end of the study (P = .04). Body mass index (BMI) correlated inversely with ATP recovery, even in controls (R = -0.768; P = .07). Although BMI was greater in patients than controls (P = .02) and correlated strongly with fatty liver and serum aminotransferase elevations, neither of the latter 2 parameters nor the histologic severity of fibrosis strongly predicted hepatic ATP recovery. CONCLUSIONS These data suggest that recovery from hepatic ATP depletion becomes progressively less efficient as body mass increases in healthy controls and is severely impaired in patients with obesity-related nonalcoholic steatohepatitis.",
"title": "Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: a pilot study."
},
{
"docid": "26902591",
"text": "Cancer-associated cachexia (CAC) is a wasting syndrome characterized by systemic inflammation, body weight loss, atrophy of white adipose tissue (WAT) and skeletal muscle. Limited therapeutic options are available and the underlying mechanisms are poorly defined. Here we show that a phenotypic switch from WAT to brown fat, a phenomenon termed WAT browning, takes place in the initial stages of CAC, before skeletal muscle atrophy. WAT browning is associated with increased expression of uncoupling protein 1 (UCP1), which uncouples mitochondrial respiration toward thermogenesis instead of ATP synthesis, leading to increased lipid mobilization and energy expenditure in cachectic mice. Chronic inflammation and the cytokine interleukin-6 increase UCP1 expression in WAT, and treatments that reduce inflammation or β-adrenergic blockade reduce WAT browning and ameliorate the severity of cachexia. Importantly, UCP1 staining is observed in WAT from CAC patients. Thus, inhibition of WAT browning represents a promising approach to ameliorate cachexia in cancer patients.",
"title": "A switch from white to brown fat increases energy expenditure in cancer-associated cachexia."
}
] |
2830
|
Is there any instrument with real-estate-like returns?
|
[
{
"docid": "206368",
"text": "",
"title": ""
},
{
"docid": "113189",
"text": "Similarly to buying property on your own, REITs cannot get to good returns without leveraging. If you buy an investment property 100% cash only - chances are that 10% ROI is a very very optimistic scenario. If you use leveraging (i.e.: take out a mortgage) - you're susceptible to interest rate changes. REITs invest in properties all around all the time. They invest in mortgages themselves as well (In the US, that's the only security REITs can hold without being disqualified). You can't expect all that to be cash-only, there have to be loans and financing involved. When rates go up - financing costs go up. That brings net income down. Simple math. In the US, there's an additional benefit to investing in REIT vs directly holding real estate: taxes. REITs pay dividends, which have preferential (if qualified) taxation. You'll pay capital gains taxes on the dividends if you hold the fund long enough. If you own a rental property directly, your income after all the expenses is taxed at ordinary rates, which would usually be higher. Also, as you mentioned, you can use them as margin, and they're much much more liquid than holding real estate directly. Not to mention you don't need to deal with tenants or periods where you don't have any, or if local real-estate market tanks (while REITs are usually quite diversified in kinds of real estate they hold and areas). On the other hand, if you own real estate, you can leverage it at lower rates than margin (with HELOCs etc), and it provides some safety net in case of a stock market crash (which REITs are somewhat susceptible to). You can also live in your property, if needed, which is something that's hard to do with REITs....",
"title": ""
}
] |
[
{
"docid": "375965",
"text": "There is a subprime loaning bubble in the auto loan sector which is growing; while it's not in the $1 trillion range or as hidden as the real estate one was, it could cause issues down the road if it continues. The use of derivatives or specifically, CDS, is continuing for other suspect investments. It was used about 4 years ago to help hide Greece's sovereign default and like in 2008, it allowed the bad debt to be hidden and thrive to dangerous levels. The use isn't widespread and limited to several firms so far, but its return as an instrument of choice so soon after the financial crisis is a little worrying that it may be a cyclical crisis.",
"title": ""
},
{
"docid": "482077",
"text": "\"leverage amplifies gains and losses, when returns are positive leverage makes them more positive, but when returns are negative leverage makes them more negative. since most investments have a positive return in \"\"the long run\"\", leverage is generally considered a good idea for long term illiquid investments like real estate. that said, to quote keynes: in the long run we are all dead. in the case of real estate specifically, negative returns generally happen when house prices drop. assuming you have no intention of ever selling the properties, you can still end up with negative returns if rents fall, mortgage rates increase or tax rates rise (all of which tend to correlate with falling property values). also, if cash flow becomes negative, you may be forced to sell during a down market, thereby amplifying the loss. besides loss scenarios, leverage can turn a small gain into a loss because leverage has a price (interest) that is subtracted from any amplified gains (and added to any amplified losses). to give a specific example: if you realize a 0.1% gain on x$ when unleveraged, you could end up with a 17% loss if leveraged 90% at 2% interest. (gains-interest)/investment=(0.001*x-0.02*0.9*x)/(x/10)=-0.017*10=-0.17=17% loss one reason leveraged investments are popular (particularly with real estate), is that the investor can file bankruptcy to \"\"erase\"\" a large negative net worth. this means the down side of a leveraged investment is limited for the highly leveraged investor. this leads to a \"\"get rich or start over\"\" mentality common among the self-made millionaire (and failed entrepreneurs). unfortunately, this dynamic also leads to serious problems for the banking sector in the event of a large nation-wide devaluation of real estate prices.\"",
"title": ""
},
{
"docid": "190385",
"text": "\"No, it can really not. Look at Detroit, which has lost a million residents over the past few decades. There is plenty of real estate which will not go for anything like it was sold. Other markets are very risky, like Florida, where speculators drive too much of the price for it to be stable. You have to be sure to buy on the downturn. A lot of price drops in real estate are masked because sellers just don't sell, so you don't really know how low the price is if you absolutely had to sell. In general, in most of America, anyway, you can expect Real Estate to keep up with inflation, but not do much better than that. It is the rental income or the leverage (if you buy with a mortgage) that makes most of the returns. In urban markets that are getting an influx of people and industry, however, Real Estate can indeed outpace inflation, but the number of markets that do this are rare. Also, if you look at it strictly as an investment (as opposed to the question of \"\"Is it worth it to own my own home?\"\") there are a lot of additional costs that you have to recoup, from property taxes to bills, rental headaches etc. It's an investment like any other, and should be approached with the same due diligence.\"",
"title": ""
},
{
"docid": "112271",
"text": "I would go with the 2nd option (put down as little as possible) with a small caveat: avoid the mortgage insurance if you can and put down 20%. Holding your rental property(ies)'s mortgage has some benefits: You can write off the mortgage interest. In Canada you cannot write off the mortgage interest from your primary residence. You can write off stuff renovations and new appliances. You can use this to your advantage if you have both a primary residence and a rental property. Get my drift? P.S. I do not think it's a good time right now to buy a property and rent it out simply because the housing prices are over-priced. The rate of return of your investment is too low. P.S.2. I get the feeling from your question that you would like to purchase several properties in the long-term future. I would like to say that the key to good and low risk investing is diversification. Don't put all of your money into one basket. This includes real estate. Like any other investment, real estate goes down too. In the last 50 or so years real estate has only apprepriated around 2.5% per year. While, real estate is a good long term investment, don't make it 80% of your investment portfolio.",
"title": ""
},
{
"docid": "217478",
"text": "\"The loan is the loan, the down payment is not part of the loan. The principle amount owed on the loan at the beginning of the loan is the amount of the loan. If your loan amount is $390,000 then that's below the \"\"jumbo\"\" classification. Your down payment is irrelevant. Lenders may want or require 20% (or any other amount) down so the loan will meet certain \"\"loan to value\"\" ratio requirements. In the case of real estate the lenders in general want a 20% down side cushion before you're \"\"upside down\"\" (owe more than the home is worth). This is not unique to homes and is common in many secured lending instruments; like cars for example.\"",
"title": ""
},
{
"docid": "390751",
"text": "\"A REIT is a real estate investment trust. It is a company that derives most of its gross income from and holds most of its assets in real estate investments, which, in this case, include either real property, mortgages, or both. They provide a way for investors to get broad exposure in a real estate market without going to buy a bunch of properties themselves. It also provides diversification within the real estate segment since REITs will often (but not necessarily) have either way more properties than an individual could get or have very large properties (like a few resorts) that would be too expensive for any one investor. By law, they must pay at least 90% of their taxable income as dividends to investors, so they typically have a good dividend rate (possibly but not necessarily) at the expense of growth of the stock price. Some of those dividends may be tax advantaged and some will not. An MLP is a master limited partnership. These trade on the exchange like corporations, but they are not corporations. (Although often used in common language as synonyms, corporation and company are not the same thing. Corporation is one way to organize a company under the law.) They are partnerships, and when you buy a share you become a partner in the company. This is an alternative form of ownership to being a shareholding. In this case you are a limited partner, which means that you have limited liability as with stock. The shares may appreciate or not, just like a stock, and you can generally sell them back to the market for a capital gain or loss under the same rules as a stock. The main difference here from a practical point of view is taxes: Partnerships (of any type) do no pay tax - Instead their income and costs are passed to the individual partners, who must then include it on their personal returns (Form 1040, Schedule E). The partnership will send each shareholder a Schedule K-1 form at tax time. This means you may have \"\"phantom income\"\" that is taxable even though cash never flowed through your hands since you'll have to account for the income of the partnership. Many partnerships mitigate this by making cash distributions during the year so that the partners do actually see the cash, but this is not required. On the other hand, if it does happen, it's often characterized as a return of capital, which is not taxable in the year that you receive it. A return of capital reduces your cost basis in the partnership and will eventually result in a larger capital gain when you sell your shares. As with any investment, there are pros and cons to each investment type. Of the two, the MLP is probably less like a \"\"regular\"\" stock since getting the Schedule K-1 may require some extra work at tax time, especially if you've never seen one before. On the other hand, that may be worth it to you if you can find one that's appreciating in value and still returning capital at a good rate since this could be a \"\"best of everything\"\" situation where you defer tax and - when you eventually do pay, you pay at favorable capital gains rates - but still manage to get your cash back in hand before you sell. (In case not clear, my comments about tax are specific to the US. No idea how this is treated elsewhere.) By real world example, I guess you meant a few tickers in each category? You can find whole lists online. I just did a quick search (\"\"list of MLP\"\" and \"\"list of REIT\"\"), found a list, and have provided the top few off of the first list that I found. The lists were alphabetical by company name, so there's no explicit or implicit endorsement of these particular investments. Examples of REIT: Examples of MLP:\"",
"title": ""
},
{
"docid": "80797",
"text": "My equities portfolio breaks down like this: (I'm 26 years old, so it is quite aggressive) Additionally, I have a portfolio of direct real estate investments I have made over the past 4 years. I invested very aggressively into real estate due to the financial crisis. As a result of my aggressive investing & strong growth in real estate, my overall asset breakdown is quite out of balance. (~80% Real Estate, ~20% Equities) I will be bringing this into a more sensible balance over the next few years as I unwind some of my real estate investments & reinvest the proceeds into other asset classes. As for the alternative asset groups you mentioned, I looked quite seriously at Peer to Peer lending a few years back. (Lending Club) However, interest rates were quite low & I felt that Real Estate was a better asset class to be in at the time. Furthermore, I was borrowing heavily to fund real estate purchases at the time, and I felt it didn't make much sense to be lending cash & borrowing at the same time. I needed every dime I could get a hold of. :) I will give it another look once rates come back up. I've shied away from investing in things like actively managed mutual funds, hedge funds, etc ... not because I don't think good managers can get superior returns ... rather, in my humble opinion, if they DO get above average returns then they simply charge higher management fees to reflect their good performance. Hope this helps!",
"title": ""
},
{
"docid": "523310",
"text": "I rather like The Ascent of Money, by Niall Ferguson. This comes in several formats. There's a video version, a written version (ISBN-13: 978-1594201929), and an audio version. This book covers the history of financial instruments. It covers the rise of money, the history of bonds and stocks, insurance and hedge funds, real-estate, and the spread of finance across the world. It is a great introduction to finance, though its focus is very definitely on the history. It does not cover more advanced topics, and will not leave you with any sort of financial plan, but it's a great way to get a broad overview and historical understanding of money and markets. I strongly recommend both the video and the written or audio version.",
"title": ""
},
{
"docid": "108081",
"text": "I don't think the location of the funds is any of your concern. You're buying a CDI, which is: Australian financial instruments The US has no jurisdiction over you, being you an Australian, so unless you own a US-based asset (i.e.: a real-estate in the US, or a US brokerage account), US tax laws shouldn't matter to you.",
"title": ""
},
{
"docid": "509197",
"text": "\"There are five main drivers to real estate returns: Income (cash flow from rental payments); Depreciation (as an expense that can be used to reduce taxes); Equity (the gradual paydown of the mortgage the increases underlying equity in the property); Appreciation (any increase in the overall value of the property); Leverage (the impact of debt financing on the deal, increasing the effective \"\"cash-on-cash\"\" return). (Asset Rover has a detailed walk-through of the components, and a useful comparison to stocks) So interest rates are certainly a component (as they increase the expenses), but they are just one factor. Depending on a particular market's conditions, appreciation or rent increases could offset or (exceed) any increase in the interest expense. My own experience is mostly with non-listed REITs (including Reg A+ investments like the ones from Fundrise) and commercial syndicates, and for right now in both cases there's plenty of capital chasing yield to go around (and in fact competition among new funding sources like Reg D and Reg A+ platforms seems to be driving down borrowing rates as platforms compete both for borrowers and for investors). Personally I pay more attention to where each local market (and the broader national market) is along the ~18-year real estate cycle (spoiler: the last trough was 2008...). Dividend Capital puts out a quarterly report that's super useful.\"",
"title": ""
},
{
"docid": "578597",
"text": "You apparently assume that pouring money into a landlord's pocket is a bad thing. Not necessarily. Whether it makes sense to purchase your own home or to live in a rental property varies based on the market prices and rents of properties. In the long term, real estate prices closely follow inflation. However, in some areas it may be possible that real estate prices have increased by more than inflation in the past, say, 10 years. This may mean that some (stupid) people assume that real estate prices continue to appreciate at this rate in the future. The price of real estates when compared to rents may become unrealistically high so that the rental yield becomes low, and the only reasonable way of obtaining money from real estate investments is price appreciation continuing. No, it will not continue forever. Furthermore, an individual real estate is a very poorly diversified investment. And a very risky investment, too: a mold problem can destroy the entire value of your investment, if you invest in only one property. Real estates are commonly said to be less risky than stocks, but this applies only to large real estate portfolios when compared with large stock portfolios. It is easier to build a large stock portfolio with a small amount of money to invest when compared to building a large real estate portfolio. Thus, I would consider this: how much return are you going to get (by not needing to pay rent, but needing to pay some minor maintenance costs) when purchasing your own home? How much does the home cost? What is the annual return on the investment? Is it larger than smaller when compared to investing the same amount of money in the stock market? As I said, an individual house is a more risky investment than a well-diversified stock portfolio. Thus, if a well-diversified stock portfolio yields 8% annually, I would demand 10% return from an individual house before considering to move my money from stocks to a house.",
"title": ""
},
{
"docid": "419926",
"text": "\"Real Estate has historically been the most sound investment of all times. Not only does property consistant increase in value (which is what you want every investment to do), it does so at the highest rate with the lowest risk. Most return on investment (like a stock in the market) the potential rate of gain is proportionat to the potential loss. The more secure an investment, the lower the potential gain. But, with Real Estate, property typically doubles in value every 10 years. Our overall R.E. economy is on an upward turn, recovering from a time where values tanked. to jump in now, is probably better than waiting for any amount of time, be it 1 month, or 1 year. You concern about being \"\"tied in\"\" to this investment is a valid concern, however, since the market is in an upward turn, you should be more and more able to turn around and sell it later on. The best thing that you could potentially do would be to invest in a rental property where your cost of investment (your mortgage note) is paid by the renters. However, being a landlord is always a risky business (hence, the higher rate of return, which considering your investment is ultimately zero, the return rate is huge :-) The trick would be to take the reters payments to you and keep it in an account that you use to pay for any repairs, upgrades, or marketing in between when the unit is vacant. But, with your parents losing their house, this may not be possible - unless you take their home and then keep the living arrangments the same as they are now. One possibility to help you get your foot in the door of being a property owner (not necessarily \"\"investor\"\") and help your parents keep their house (if that is what they would like to do) is re-finance with them... if you can't afford the entire mortgage, but they are capable of filling the gap between what you can afford and what their property costs, then you become partnered with them, and when/if their circumstances change, they can always buy you out.\"",
"title": ""
},
{
"docid": "124230",
"text": "A general rule of thumb is to avoid having more than 5% of your investments in any single stock, to avoid excessive risk; it's usually even more risky if you're talking company stock because an adverse event could result in an inferior stock price and you getting laid off. Under other circumstances, the ideal amount of company stock is probably 0%. But there are tax benefits to waiting, as you've noted, and if you're reasonably confident that the stock isn't likely to jerk around too much, and you have a high risk tolerance (i.e. lots of extra savings besides this), and you're comfortable shouldering the risk of losing some money, it might make sense to hold onto the stock for a year - but never any longer. The real risk to holding a lot of company stock doesn't depend on how often you buy it and sell it per se, but having period purchases every month should make it easier for you to ladder the funds, and regularly sell your old shares as you purchase new shares. You might also consider a stop-loss order on the stock at or near the price you purchased it at. If the stock is at $100, then you buy at $85, and then the stock drops to $85, there are no more outstanding tax benefits and it makes no sense to have it as part of your portfolio instead of any other speculative instrument - you probably get better diversification benefits with any other speculative instrument, so your risk-adjusted returns would be higher.",
"title": ""
},
{
"docid": "217242",
"text": "You could look into an index fund or ETF that invests primarily in Real Estate Investment Trusts (REIT's). An REIT is any corporation, trust or association that acts as an investment agent specializing in real estate and real estate mortgages Many investment firms offer an index fund or ETF like this. For example, Vanguard and Fidelity have funds that invest primarily in real estate markets. You could also invest in a home construction ETF, like iShares' ITB, which invests in companies related to home construction. This ETF includes more companies than just REITs, so for example, Home Depot is included.",
"title": ""
},
{
"docid": "80519",
"text": "\"Frequently selling and buying properties is generally not advisable in Germany due to the high cost for property purchase tax (\"\"Grunderwerbssteuer\"\") and land registration fees (\"\"Grundbucheintrag\"\"). You can generally assume that ever time you trade homes, you pay about 10% extra. So it is likely a good idea to keep your property and rent it out while you don't need it so you can use the rent to pay for your new room. That's especially true if you expect the property to increase in value. Also, due to the low interest rate right now, real estate is practically the only good capital investment. A 85k asset which makes you 4.8k each year is a return of investment of 5.6%*. Any financial asset promising you that kind of dividend at the moment is likely equivalent to gambling. * yes, I ignored maintenance costs, but it's still a really good deal. If you want to rent out your flat as stress-free as possible, give it to a property management company (\"\"Hausverwalter\"\"). In exchange for a percentage of the monthly rent they will take care of all the small stuff (like hiring handymen to fix broken toilets). You might still have to pay for really expensive investments, though (like replacing a leaking roof). But when something like that happens, you should have no issue to finance it with a loan because you have a real estate as a security. However, keep in mind that the German tenancy law might make it difficult (but not impossible) to get rid of the tenant in case you want to move back into the apartment. Google \"\"Mietrecht Eigenbedarf\"\" for more details. Should you decide after your study that you don't want to move back, you can always sell the flat with the tenant. But rented properties usually get far lower prices on the real estate market than empty ones. Regarding covering your cost of living besides rent during your studies: If you are eligible for BAföG (state-sponsored student loan), you should take it, because it's an offer simply too good to refuse. It's literally free money. But unfortunately you are not, because you own too much real estate wealth you are not living in. But you should ask your bank for a loan backed by said property. That way you will likely pay far less interest than with a regular private student loan which isn't backed by anything except the hope for a relevant degree.\"",
"title": ""
},
{
"docid": "387141",
"text": "Well, Taking a short position directly in real estate is impossible because it's not a fungible asset, so the only way to do it is to trade in its derivatives - Investment Fund Stock, indexes and commodities correlated to the real estate market (for example, materials related to construction). It's hard to find those because real estate funds usually don't issue securities and rely on investment made directly with them. Another factor should be that those who actually do have issued securities aren't usually popular enough for dealers and Market Makers to invest in it, who make it possible to take a short position in exchange for some spread. So what you can do is, you can go through all the existing real estate funds and find out if any of them has a broker that let's you short it, in other words which one of them has securities in the financial market you can buy or sell. One other option is looking for real estate/property derivatives, like this particular example. Personally, I would try to computationally find other securities that may in some way correlate with the real estate market, even if they look a bit far fetched to be related like commodities and stock from companies in construction and real estate management, etc. and trade those because these have in most of the cases more liquidity. Hope this answers your question!",
"title": ""
},
{
"docid": "353415",
"text": "\"Another option you might consider is rolling over some of that 401K balance into a self-directed IRA or Solo 401K, specifically one with \"\"checkbook privileges\"\". That would permit you to invest directly in a property via your IRA/401K money without it being a loan, and preserving the tax benefits. (You may not be able to roll over from your current employer's 401K while still employed.) That said, regarding your argument that your loan is \"\"paying interest to yourself\"\", while that is technically true, that neglects the opportunity cost -- that money could potentially be earning a much higher (and tax-free) return if it remains in the 401K account than if you take it out and slowly repay it at a modest interest rate. Real Estate can be a great way to diversify, build wealth, and generate income, but a company match and tax-free growth via an employee sponsored retirement account can be a pretty sweet deal too (I actually recently wrote about comparing returns from having a tenant pay your mortgage on a rental property vs. saving in a retirement account on my blog -- in short, tax-free stock-market level returns are pretty compelling, even when someone else is paying your mortage). Before taking rather big steps like borrowing from a 401K or buying a rental property, you might also explore other ways to gain some experience with real estate investing, such as the new crop of REITs open to all investors under SEC Reg A+, some with minimums of $500 or less. In my own experience, there are two main camps of real estate investors: (1) those that love the diversification and income, but have zero interest in active management, and (2) those that really enjoy real estate as a lifestyle and avocation, happy to deal with tenant screening and contractors, etc. You'll want to be careful to be sure which camp you're in before signing on to active investment in a specific property.\"",
"title": ""
},
{
"docid": "332064",
"text": "It looks like you need a lot more education on the subject. I suggest you pick up a book on investing and portfolio management to get a first idea. Dividend yields are currently way below 5% on blue chips. Unlike coupons from fixed income instruments (which, in the same risk category, pay a lot less), dividend yields are not guaranteed and neither is the invested principal amount. In either case, your calculation is far away from reality. Sure, there are investments (such as the mentioned direct investments in companies or housings in emerging economies) that can potentially earn you two digit percentage returns. Just remember: risk always goes both ways. A higher earning potential means higher loss potential. Also, a direct investment is a lot less liquid than an investment on a publicly quoted high turnover market place. If you suddenly need money, you really don't want to be pressed to sell real estate in an emerging market (keyword: bid ask spread). My advice: the money that you can set aside for the long term (10 years plus), invest it in stock ETFs, globally. Everything else should be invested in bond funds or even deposits, depending on when you will need the access. As others have pointed out, consider getting professional advice.",
"title": ""
},
{
"docid": "429215",
"text": "I'm surprised to even hear this question with the current state of devaluation of real estate. One thing I'll add to the other answers is to make sure you are doing a true apples/apples comparison to other investments when considering real estate. You can't just take subtract the purchase price from the sales price to get your ROI. Real estate has very heavy carry costs that you need to factor into any ROI calculation including: One more point: A house that you live in shouldn't be considered an investment, but rather an expense. You have to be able to liquidate an investment and collect your return. Unless you plan to move back in with your parents, you are always going to need a place to live so you can never really cash out on that investment, except perhaps by downgrading your lifestyle or a reverse mortgage.",
"title": ""
},
{
"docid": "528206",
"text": "\"Rather than thinking of becoming a landlord as a passive \"\"investment\"\" (like a bank account or mutual fund), it may be useful to think of it as \"\"starting a small part-time business\"\". While certainly many people can and do start their own businesses, and there are many success stories, there are many cases where things don't work out quite as they hoped. I wouldn't call starting any new business \"\"low risk\"\", even one that isn't expected to be one's main full-time job, though some may be \"\"acceptable risk\"\" for your particular circumstances. But if you're going to start a part-time business, is there any particular reason you'd do so in real estate as opposed to some other activity? It sounds like you'd be completely new to real estate, so perhaps for your first business you're starting you'd want it to be something you're more familiar with. Or, if you do want to enter the real estate world (or any other new business), be sure to do a lot of research, come up with a business plan, and be prepared for the possibility of losing money as with any investment or new business.\"",
"title": ""
},
{
"docid": "6356",
"text": "Real Estate potentially has two components of profit, the increase in value, and the ongoing returns, similar to a stock appreciating and its dividends. It's possible to buy both badly, and in the case of stocks, there are studies that show the typical investor lags the market by many percent. Real estate is not a homogeneous asset class. A $200K house renting for $1,000 is a far different investment than a $100K 3 family renting for $2,000 total rents. Both exist depending on the part of the country you are in. If you simply divide the price to the rent you get either 16.7X or 4.2X. This is an oversimplification, and of course, interest rates will push these numbers in one direction or another. It's safe to say that at any given time, the ratio can help determine if home prices are too high, a bargain, or somewhere in between. As one article suggests, the median price tracks inflation pretty closely. And I'd add, that median home prices would track median income long term. To circle back, yes, real estate can be a good investment if you buy right, find good tenants, and are willing to put in the time. Note: Buying to rent and buying to live in are not always the same economic decision. The home buyer will very often buy a larger house than they should, and turn their own 'profit' into a loss. e.g. A buyer who would otherwise be advised to buy the $150K house instead of renting is talked into a bigger house by the real estate agent, the bank, the spouse. The extra cost of the $225K house is the 1/3 more cost of repair, utilities, interest, etc. It's identical to needing a 1000 sq ft apartment, but grabbing one that's 1500 sq ft for the view.",
"title": ""
},
{
"docid": "576375",
"text": "yes, i am incorporating monte carlo return scenarios for both equity and real estate. yeah there is a lot to consider in the case of the property being a condo where you have to account for property taxes as well as condo fees. the two projects have entirely different considerations and it's not like the money that is injected to one is similar to the other (very different) which is why i figured there should be differing discount rates. in any case, thanks for the discussion and suggestions.",
"title": ""
},
{
"docid": "485243",
"text": "Many people have provided very good answers to this question and all the answers provide sound advice and justification. Below are some of my thoughts on the questions that you have put forward. 1) The investment manager question: The returns on your capital for a half year has been quite low; having said that, some investments do take more than half year to show some growth. You could try talking to your investment manager and ask where your money has been deployed and why the returns are low. If there are no real explanation given forth (which would be more likely as you have mentioned your investment manager does not like to discuss your money with you) you should conside Xolorus & Pete's advice and forthwith take all your money from investment manager and park it in the bank till you figure out what to do next with it. 2) Finances are not my forte: At 22 finance is nobodies forte, it takes longer than that; however having said that, how do you know finance is actually not your forte? Being a computer science graduate you would be more than comfortable with the mathematics required for finance. You may not have looked seriously at finance till now (I assume by your statement). Once way to be certain about this would be self learning, some good books have been refered above and there are online information, courses and articles on the Internet, for example here. You could give some spare time and explore if finance interests you or not. 3) If finance interests you: Then consider the 30K as your seed fund and take a small portion of it say 2K and try out your hand at investing on your own in the instruments that you feel most comfortable and see how you fare, you are young enough to take the risk. Rest of the money you could put in other low risk instruments (that you have identified through self study) 4) If finance does not interest you: The probably you are better off with an investment manager, as observed above, it will take some time for you to identify him/her 5) On returns: As mentioned above different instruments produce returns differently, however, one question that is universally asked is how much return on an invetment shoule one expect (you were expecting more than $12 on your investment). It is a difficult question to answer as invetment returns and investment needs depend on a persons financial goals and risk taking profile. One way to have some measure is to take 15-20 years CAGR of the stock index return and reduce it by 2-3%, that is (in many cases, not all) a reasonable return expectation in medium-long term.",
"title": ""
},
{
"docid": "387717",
"text": "Real estate investment is a proven creator of wealth. Check into the history of the rich and you will find real estate investment. Starting your investment in multi-family is a great idea. It is a good way to gain experience in real estate while exponentially increasing cash flow. If you turn the properties over to a reputable property management company, your cash flow will be a little less but so will your headaches. (Expect to pay 8 - 10% of gross income.) You could start investing now by looking into discounted real estate such as foreclosures, tax sales, short sales etc while the market is still depressed. This way your return on investment should be higher. From there you could expand into land development (i.e. subdivision) or commercial investments. Commercial properties with triple net leases can be a great low-stress investment opportunity (but they take more cash upfront). Attending some local real estate investment classes would be a great idea for starters.",
"title": ""
},
{
"docid": "159652",
"text": "With out a doubt: commercial real estate. Those that have significant amounts of money, and want to make lots more usually end up investing a chunk of their portfolio in commercial real estate. Everyone finds a way to make money elsewhere, but there’s no comparison to the incentives and returns in real estate when you have tens or hundreds of millions of $ at your disposal. Have money, make money.",
"title": ""
},
{
"docid": "232651",
"text": "Well, this took some interesting facts and made some raving assumptions. Generally, I'd imagine it's more likely the Chinese capital controls and atrocious domestic savings opportunities have made any dollar denominated returns desirable and with us commercial real estate in cardiac arrest, places like toledo offer lots of great investment opportunities. I think a Chinrse city outside of Milan would be fantastic. Good knows the new money and population couldn't but help MI and fostering deeper cultural ties between one of the former great manufacturing regions and the worlds newest could benefit both.",
"title": ""
},
{
"docid": "187571",
"text": "I think you may be drawing the wrong conclusion about why you put what type of investment in a taxable vs. tax-advantaged account. It is not so much about risk, but type of return. If you're investing both tax-advantaged and taxable accounts, you can benefit by putting more tax-inefficient investments inside your tax-advantaged accounts. Some aggressive asset types, like real estate, can throw off a lot of taxable income. If your asset allocation calls for investing in real estate, holding it in a 401k or IRA can allow more of your money to remain invested, rather than having to use it to pay for taxes. And if you're holding in a Roth IRA, you get that tax free. But bonds, a decidedly non-aggressive asset, also throw off a lot of taxable income. You're able to hold them in a tax-advantaged account and not pay taxes on the income until you withdraw it from the account (or tax free in the case of a Roth account.) An aggressive stock fund that is primarily expected to provide returns via price appreciation would do well in a taxable account because there's likely little tax consequence to you until it is sold.",
"title": ""
},
{
"docid": "529435",
"text": "\"This forum is not intended to be a discussion group, but I would like to add a different perspective, especially for @MrChrister, on @littleadv's rhetorical question \"\"... estates are after-tax money, i.e.: income tax has been paid on them, yet the government taxes them again. Why?\"\" For the cash in an estate, yes, that is after-tax money, but consider other assets such as stocks and real estate. Suppose a rich man bought stock in a small computer start-up company at $10 a share about 35 years ago, and that stock is now worth $500 a share. The man dies and his will bequeaths the shares to his son. According to US tax law, the son's basis in the shares is $500 per share, that is, if the son sells the shares, his capital gains are computed as if he had purchased the shares for $500 each. The son pays no taxes on the inheritance he receives. The deceased father's last income tax return (filed by the executor of the father's will) does not list the $490/share gain as a capital gain since the father did not sell the stock (the gain is what is called an unrealized gain), and so there is no income tax due from the father on the $490/share. Now, if there is no estate tax whatsoever, the father's estate tax return pays no tax on that gain of $490 per share either. Would this be considered an equitable system? Should the government not tax the gain at all? It is worth noting that it would be possible for a government to eliminate estate taxes entirely, but instead have tax laws that say that unrealized gains on the deceased's property would be taxed (as capital gains) on the deceased's final tax return.\"",
"title": ""
},
{
"docid": "57960",
"text": "Apples and oranges. The stock market requires a tiny bit of your time. Perhaps a lot if you are interested in individual stocks, and pouring through company annual reports, but close to none if you have a mix of super low cost ETFs or index fund. The real estate investing you propose is, at some point, a serious time commitment. Unless you use a management company to handle incoming calls and to dispatch repair people. But that's a cost that will eat into your potential profits. If you plan to do this 'for real,' I suggest using the 401(k), but then having the option to take loans from it. The ability to write a check for $50K is pretty valuable when buying real estate. When you run the numbers, this will benefit you long term. Edit - on re-reading your question Rental Property: What is considered decent cash flow? (with example), I withdraw my answer above. You overestimated the return you will get, the actual return will likely be negative. It doesn't take too many years of your one per year strategy to wipe you out. Per your comment below, if bought right, rentals can be a great long term investment. Glad you didn't buy the loser.",
"title": ""
},
{
"docid": "437614",
"text": "Yes - it's called the rate of inflation. The rate of return over the rate of inflation is called the real rate of return. So if a currency experiences a 2% rate of inflation, and your investment makes a 3% rate of return, your real rate of return is only 1%. One problem is that inflation is always backwards-looking, while investment returns are always forward-looking. There are ways to calculate an expected rate of inflation from foreign exchange futures and other market instruments, though. That said, when comparing investments, typically all investments are in the same currency, so the effect of inflation is the same, and inflation makes no difference in a comparative analysis. When comparing investments in different currencies, then the rate of inflation may become important.",
"title": ""
}
] |
7432
|
Buy Php in Malaysia and sell to Philippines
|
[
{
"docid": "293483",
"text": "I noticed the buy/sell board table. Where did you notice this. Generally for a pair of currencies, there is Unit associated along with direction. The Unit is generally constant. These are only revised when there is large devaluation of a particular currency. Buying Php for MYR 8.52, Selling MYR 8.98. So in this case the Unit of PHP is 100, so Bank is Buying 100 PHP from you [you are selling PHP] and will give you MYR 8.52. If you now want to buy 100 PHP [so the Bank is selling you], you have to pay MYR 8.98. So you loose MYR 0.46 Why are they selling it way beyond the exchange rate? Why is this? As explained above, they are not. Its still within the range. The quote on internet are average price. This means before going back to Philippines, I can buy a lot of peso that I can buy and exchange it for higher price right? Generally an individual cannot make money by buying in one currency and selling in other. There are specialist who try and find arbitrage between multiple pair of currencies and make money out of it. Its a continuous process, if they start making profit, the market will react and put pressure on a pair and the prices would move to remove the arbitrage.",
"title": ""
},
{
"docid": "226321",
"text": "basically the selling (for banks) means you will exchange PHP to MYR buying simply MYR to PHP the bank will buy your MYR in exchange to PHP. and you will sell your MYR to PHP. I think it has something to do with processing fee..",
"title": ""
}
] |
[
{
"docid": "120490",
"text": "Interesting piece about Philippine, but there's still work to be done, especially from the state. As the [FT pointed out last week](http://blogs.ft.com/beyond-brics/2012/10/24/the-philippines-ready-for-business/#axzz2Aczv0yBy), one need 36 days to start a business and 16 different steps. That's 32 more days than in Indonesia and 13 more steps than in Malaysia. Considering the lack of resources, such a brake on entrepreneurship isn't really what Philippine needs.",
"title": ""
},
{
"docid": "266111",
"text": "I found this interesting list https://money.usnews.com/money/blogs/on-retirement/2011/12/05/the-most-tax-friendly-places-to-retire-abroad (mirror): Argentina Belize Colombia Costa Rica Croatia Ecuador France Ireland Italy Malaysia Mexico Panama Philippines Spain Thailand Uruguay One source confirming for Philippines: http://www.investopedia.com/ask/answers/052615/what-are-financial-benefits-retiring-philippines.asp : You are exempt from income taxes on annuities and pensions",
"title": ""
},
{
"docid": "557929",
"text": ">Pyramid schemes are illegal in many countries or regions including Albania, Australia,[20][21] Austria,[22] Belgium,[23] Brazil, Canada, China,[24] Colombia,[25] Denmark, the Dominican Republic,[26] Estonia,[27] Finland,[28] France, Germany, Hong Kong,[29] Hungary, Iceland, Iran,[30] the Republic of Ireland,[31] Italy,[32] Japan,[33] Malaysia, Maldives, Mexico, Nepal, the Netherlands,[34] New Zealand,[35] Norway,[36] Peru, Philippines,[37] Poland, Portugal, Romania,[38] Russian Federation, Serbia,[39] South Africa,[40] Spain, Sri Lanka,[41] Sweden,[42] Switzerland, Taiwan, Thailand,[43] Turkey,[44] Ukraine,[45] the United Kingdom,[46] and the United States.[7] https://en.wikipedia.org/wiki/Pyramid_scheme",
"title": ""
},
{
"docid": "579007",
"text": "I think the one single answer is that the answer depends on the two countries involved and their banks' practices. To find that answer, you need to ask other expats from your country living in France and ask them for their experience. Note that most expats do not know what fees they are paying. For example, in the Philippines, the lowest fee charged still involves waiting 30 days to get your money. Specifically, I opened a US dollar savings account with the minimum of US $500 required (other rules are involved for opening a bank account), deposited a personal check drawn on my US bank account (no fee charged), and waited 30 calendar days to withdraw USD bills. The Philippines bank did not have a branch in the US, but had financial arrangements with US banks. After getting USD dollars in my hand, I walked to a nearby exchange business store (which usually offered a better daily rate than a bank, but a rate between the banks' buy and sell rates) and exchange the dollars for pesos. Note that years ago, banks did not give USD bills, when dollars were scarce in the Philippines. However, this process does not work in Thailand, due to bank rules against private individuals opening a USD account, with exceptions. And there are still fees involved. March 2017",
"title": ""
},
{
"docid": "552138",
"text": "\"The country from which you purchase stock cannot charge you tax on either income or capital gains. Taxation is based on residency, so even when you purchase foreign stock its the tax laws of Malaysia (as your country of residence) that matter. At the time of writing, Malaysia does not levy any capital gains tax and there is no income tax charged on dividends so you won't have to declare or pay any tax on your stocks regardless of where you buy them from. The only exception to this is Dividend Withholding Tax, which is a special tax taken by the government of the country you bought the stock from before it is paid to your account. You do not need to declare this tax as it his already been taken by the time you receive your dividend. The US withholding tax rate on dividends is 30%, although this can be reduced to 15% if there as a tax treaty in place between the US and your country of residence. Malaysia does have a double taxation agreement with the US (see here: http://www.mida.gov.my/env3/index.php?page=double-taxation-agreement) but it is flagged as a \"\"limited\"\" agreement. You'd need to find the full text of the agreement to see whether a reduced rate of dividend withholding tax would be available in the Malaysia/US treaty. See my other answer for more details on withholding taxes and how to partially reclaim under a double tax treaty: What is the dividend tax rate for UK stock Note: Although the taxation rules of both countries are similar, I am a resident of Singapore not Malaysia so I can't speak from first hand experience, but current Malaysia tax rates are easy to find online. The rest of this information is common to any non-US/UK resident investor (as long as you're not a US person).\"",
"title": ""
},
{
"docid": "326559",
"text": "The link provided by DumbCoder (below) is only relevant to UK resident investors and does not apply if you live in Malaysia. I noticed that in a much older question you asked a similar question about taxes on US stocks, so I'll try and answer both situations here. The answer is almost the same for any country you decide to invest in. As a foreign investor, the country from which you purchase stock cannot charge you tax on either income or capital gains. Taxation is based on residency, so even when you purchase foreign stock its the tax laws of Malaysia (as your country of residence) that matter. At the time of writing, Malaysia does not levy any capital gains tax and there is no income tax charged on dividends so you won't have to declare or pay any tax on your stocks regardless of where you buy them from. The only exception to this is Dividend Withholding Tax, which is a special tax taken by the government of the country you bought the stock from before it is paid to your account. You do not need to declare this tax as it his already been taken by the time you receive your dividend. The rate of DWT that will be withheld is unique to each country. The UK does not have any withholding tax so you will always receive the full dividend on UK stocks. The withholding tax rate for the US is 30%. Other countries vary. For most countries that do charge a withholding tax, it is possible to have this reduced to 15% if there is a double taxation treaty in place between the two countries and all of the following are true: Note: Although the taxation rules of both countries are similar, I am a resident of Singapore not Malaysia so I can't speak from first hand experience, but current Malaysia tax rates are easy to find online. The rest of this information is common to any non-US/UK resident investor (as long as you're not a US person).",
"title": ""
},
{
"docid": "335287",
"text": "Yup, it's for Malaysia because as I said, it's for where I'm from. Can't say the same for the rest of the world, though I don't think it's just unique to Malaysia. edit: The boycott is not unique nor originate from Malaysia, so it is quite a widespread to ever reach Malaysia.",
"title": ""
},
{
"docid": "593621",
"text": "I am a web developer by day and financial systems programmer by night. You'll need to learn a compiled language and how to scale data storage if you want to code for finance. I would suggest you learn C# or Java if you really want a decent gig programming in the finance industry. Anybody using PHP and API's to trade isn't somebody you want to work for. It will cause way more headaches than it's worth and you miss opportunities due to speed and efficiency of a language like PHP. You will hit a wall with it at some point (some problem/bug/whatever that can't be solved), and it will really bring you down when you realize it has to be re-done in another language. That being said, PHP is great for the front end (showing people the data and letting them search etc), but the core of it that grabs stats and does the calculations should be in a compiled language. PHP can also be used to quickly test ideas to see if it's worth building a full system that will scale. Basically a rough draft of the program to see if it's going to work out. Why? Well in PHP you can get things done very quickly with very little code because a large amount of libraries and functions exist and it's a very easy language to understand. But it's not efficient, and that's why you create the real deal program using C, C#, or java, or whatever. Scalability of data storage will be important to. You'll need to store a ton of information and you'll need to be able to sort/change/remove/add it quickly. Many databases already exist to do this and I see you know MySQL already a good bit. You'll need to get very familiar with it because the database is going to be your biggest bottleneck in terms of speed. It doesn't matter how well your software works if the database is taking 5 seconds to return a query. Learn to tweak MySQL, learn about MSSQL, look into Firebird. Also learn about at least one NoSQL storage solution (these databases can store a massive amount of information, but they work differently than a sql database does). I would recommend learning MongoDB if you already know PHP. It is a good transition from SQL style databases to Key Storage databases. Hope this helps...",
"title": ""
},
{
"docid": "584242",
"text": "\"1. (a) \"\"Kim Jong Un Inspects KPA Strategic Force Command\"\" by Korean Central News Agency (KCNA), originally published at http://www.kcna.kp on 15 August 2017: https://kcnawatch.co/newstream/1502749950-753062439/kim-jong-un-inspects-kpa-strategic-force-command/ Original text: https://www.reddit.com/r/worldpolitics/comments/6tqkgn/north_korean_leader_kim_jong_un_has_decided_not/dlmrnnt (b) Mirror for the submitted article: https://archive.is/G32a2 2. (a) Where is Territory of Guam, United States of America (USA)? Where is Commonwealth of the Northern Mariana Islands (CNMI), USA? \\- http://chamorrobible.org/images/chamorrobibleproject/map-west-pacific-islands-1998.jpg \\- http://chamorrobible.org/images/chamorrobibleproject/map-federated-states-of-micronesia-1999.jpg \\- http://chamorrobible.org/images/chamorrobibleproject/map-guam-1991.jpg \\- http://chamorrobible.org/images/chamorrobibleproject/map-commonwealth-of-the-northern-mariana-islands-1989.jpg \\- http://chamorrobible.org/images/chamorrobibleproject/map-oceania-2002.jpg \\- [http://chamorrobible.org/images/photos/gpw-201304-NASA-Philippine-Sea-Pacific-Ocean-Guam-20111230-other.jpg](http://chamorrobible.org/images/photos/gpw-201304-NASA-Philippine-Sea-Pacific-Ocean-Guam-20111230-other.jpg \"\"1346 x 2020\"\") ([via](http://chamorrobible.org/gpw/gpw-201304.htm), [2013 x 3020](http://chamorrobible.org/images/photos/gpw-201304-NASA-Philippine-Sea-Pacific-Ocean-Guam-20111230-medium.jpg), [2680 x 4020](http://chamorrobible.org/images/photos/gpw-201304-NASA-Philippine-Sea-Pacific-Ocean-Guam-20111230-large.jpg), [4014 x 6021](http://chamorrobible.org/images/photos/gpw-201304-NASA-Philippine-Sea-Pacific-Ocean-Guam-20111230-huge.jpg)) Source: http://chamorrobible.org and http://chamorrobible.org/gpw/gpw.htm (b) Western Pacific Ocean sunset photographed from the International Space Station while orbiting above the Philippine Sea on 21 July 2003 at 10:17:20.420 GMT: [3032 x 1986 pixels](http://chamorrobible.org/images/photos/gpw-20050108-NASA-ISS007-E-10807-space-sunset-20030721-Pacific-Ocean-large.jpg) Source: http://chamorrobible.org/gpw/gpw-20050108.htm Via: http://chamorrobible.org/gpw/gpw-The-Great-Earthquake-and-Catastrophic-Tsunami-of-2004.htm 3. https://www.reddit.com/r/worldpolitics/comments/6nnhnl/one_of_just_17_remaining_colonies_worldwide_guam/dkasdpl 4. https://www.reddit.com/r/pics/comments/4zonlj/there_are_only_148_guam_kingfishers_known_in_the/d6xh2t9 5. https://www.reddit.com/r/environment/comments/6qqo3l/druglaced_mice_to_be_used_to_combat_brown_tree/dkz84p8 6. https://www.reddit.com/r/Anthropology/comments/6slxkq/3500_years_of_chamorro_history_its_like_an/dldpcqy 7. https://www.reddit.com/r/linguistics/comments/5b3iw1/our_language_isnt_dead_yet_by_michael_lujan/d9lfot8 8. \"\"Island Stealth: F-22A Raptors and a B-2 Spirit Over Guam, USA\"\" (Larger Version), April 2009: https://www.youtube.com/watch?v=kVP_8afut1s Source: http://chamorrobible.org/gpw/gpw-200905.htm\"",
"title": ""
},
{
"docid": "102076",
"text": "One of the many reasons why condominiums became popular in the Philippines as a modern family-home is because of its location, in which most of these types of [condo in Philippines](http://www.ayalalandpremier.com/One-serendra.php) are found outside Metro Manila, either in the outskirts or in some popular neighboring provinces surrounding the capital, such as in Tagaytay and Laguna. These types of condominiums are known as condominium complexes.",
"title": ""
},
{
"docid": "433807",
"text": "There's lots more entrepreneurship in the Philippines it's just under the radar. Big business is controlled by a handful of oligarchs. #1 problem in the Philippines would be corruption in government, IMO, followed by their bad weather/geological situation, and then terrorism. These are all huge roadblocks to overcoming poverty on their own. That difficulty to officially start a business does make things harder, and unfortunately the smarter folks who live there often find a way to put their skills to use abroad.",
"title": ""
},
{
"docid": "563350",
"text": "Masai Auto City is a good opportunity to buy the second hand used car at the affordable price. We have every car certified by our expert team. If you want to save the money to buy the car in new condition it is a perfect place for you. Now, it has been become a very popular place in Johor city. There is a lot of car dealer in Malaysia, but they haven't certified car. Locate the most Toyota companies that dependably give you the best opportunity to buy Masai used car Toyota at the moderate cost. You can sift through the chase in light of different parameters comprising Masai second hand car dealer.",
"title": ""
},
{
"docid": "366141",
"text": "Malaysia is a highly competitive country and well known for its prowess in various corporate sectors across the globe. As a result, many international investors have a keen interest to gain market penetration and invest in Malaysia to expand to their business empires.",
"title": ""
},
{
"docid": "566076",
"text": "For anyone looking to move to a better webhost, you will find many, many webhosting companies that are offering better deals, better service, and more up to date servers than GoDaddy. I can recommend a couple of companies for hosting. For your basic, economy hosting on solid hardware - http://www.serenity-networks.com/ is quite awesome. If you're hosting a site that demands serious performance and is PHP based, http://www.simplehelix.com/ SimpleHelix specializes in high performance PHP and e-commerce sites. Both will walk you through transferring a domain from GoDaddy. Both will migrate your site for free. Both are backed by 24/7 tech support. Happy trails.",
"title": ""
},
{
"docid": "81163",
"text": "Obviously it must have been an esthetics thing because they didn't sell, did they? And for any real change to occur is massive adoption of new modfes of transportation and massive capital outlays by Government. Anyone who thinks the private sector is capable of making this change on it's own is delusional. BTW - here are some new technologies that will be hitting the market in coming decade: http://www.popularmechanics.com/cars/news/fuel-economy/6-prototype-engines-to-get-your-brain-firing#fbIndex1 http://www.bbc.co.uk/news/technology-15735478 http://www.smartplanet.com/blog/science-scope/top-10-solar-power-advances-to-watch/1509 http://www.timesunion.com/business/article/Solar-power-advances-bringing-down-cost-1398100.php",
"title": ""
},
{
"docid": "348901",
"text": "\"Can confirm - when I owned my business I would outsource some of the \"\"lesser\"\" work to a guy in the Philippines - he was more than $15/hr. This was about 5 years ago, I don't remember exact rate, but I think was about $25/hr. And it was worth it. I had a guy in the US too, who was great and worth every penny, but I couldn't afford him for everything so I used the guy in Philippines for the smaller stuff. I would feel terrible and insulting asking my guy here to work for less. He was worth what he was asking.\"",
"title": ""
},
{
"docid": "306198",
"text": "Basically, Our organization arranges the marriage and all of the wedding ceremony features together with wedding videos, wedding cinematography, and wedding videography offerings in Malaysia. Our business enterprise gives the pleasant images, we consider ourselves storytellers, and that’s the identical method we have for Malaysia Wedding cinematic videography. We flow far from the concept that videography has been only a chronological series of wedding occasions",
"title": ""
},
{
"docid": "170372",
"text": "Now we will present some a site that offer casino games live mobile, so you can play blackjack and roulette live from your tablet or Smartphone, wherever you are. For all residents, we recommend the GD2 ONE for participating in malaysia cockfight, malaysia gambling website. There you will find everything from banking options to the most popular games, customer service and much more from the best casino sites.",
"title": ""
},
{
"docid": "236581",
"text": "\">If mounting debt is such an issue, why do all the markets act as though the US is perfectly solvent? They don't. China, Russia and most emerging markets are selling U.S. treasuries faster and faster. They have started doing so a couple years ago and are doing so at a higher pace now. They sold record numbers of U.S. treasuries in June. Many countries are forging trade partnerships with each other to get away from U.S. debt and even the U.N. and IMF are calling for an end to the dollar as the global reserve currency because it no longer deserves that status, largely due to increasing debt. By the way, the Fed is owning a larger and larger portion of U.S. debt these days. >Why is our interest rate so low, and why do investors around the world continue buying Treasury bonds? The federal reserve keeps rates low. Investors speculate about the future of the market all the time, but they are starting to dump them now http://www.bloomberg.com/news/2014-08-15/u-s-investment-outflow-reaches-record-as-china-sells-treasuries.html http://www.reuters.com/article/2014/08/15/usa-economy-capital-idUSL2N0QL0T520140815 http://www.ft.com/intl/cms/s/0/eaccbe18-aea6-11e3-aaa6-00144feab7de.html >The total net outflow of long-term U.S. securities and short-term funds such as bank transfers was $153.5 billion, after an inflow of $33.1 billion the previous month, the Treasury Department said in a report today. The June figure, and $40.8 billion in net selling of Treasury bonds and notes by private investors in June, **were the largest on record, the Treasury said.** >\"\"This is a disappointment and is a negative for the dollar. Clearly, the United States is having a hard time attracting investments to offset its current account deficit,\"\" said Michael Woolfolk, global market strategist at BNY Mellon in New York. >Central banks sold US Treasury debt at the start of the year, according to the latest official data released on Tuesday, as stress among emerging market countries intensified. Declines in Treasury holdings were seen for Thailand, Turkey and the Philippines, which sold $3.9bn, $3.3bn and $1.5bn respectively during January. Wow look at that. Did you just dismiss all evidence that proves you wrong? I think so!\"",
"title": ""
},
{
"docid": "272755",
"text": "I am also from Malaysia and I just purchase a property around Klang Valley area. Property market is just like share market. You will never know when is the highest peak point and when is the lowest peak point. Yes. Not only you, but everyone of us. What I would say that, just buy according to your need and your financial status. If you feel that you need a comfortable place to stay rather than renting a room, and buying that property will not burden your financial status too much, why not go for it? The best time to purchase property is perhaps last year when world economic is down turn. But thing is over and can never go back. Since all of us don't have a crystal ball to tell the future, why not just act according to your heart and common sense (Buy according to need) ;)",
"title": ""
},
{
"docid": "358018",
"text": "Now players from Malaysia can enjoy all online betting games through the best clubs that offer them privacy and safety in all, as well as the best variety of games, rewards and prizes offered by world-class casino clubs, all of which are in accordance with international law governing malaysia online betting games. Best offers in a way that makes them get the most benefit at all, especially after these games are the most acceptable among all the tools of entertainment, either on the personal computer or mobile phone.",
"title": ""
},
{
"docid": "219110",
"text": "I never said they're not going to change. I'm saying it will take far more than a year or two. The article say that a $10/barrel can happen in 2 years. I'm saying no. And it's not inefficiency that's causing expensive electricity. Philippines does not have the basic requirements to create cheap and renewable energy to supply what it needs. Nowhere to build a dam for hydro power. And too many strong typhoons/earthquakes for building wind. Solar power would not necessarily work either. The nation is one of the most biodiverse areas in the world. By blocking large chunks of the islands and depriving the land of sunlight, you are causing massive environmental destruction. Palm and agriculture has already devastated many parts of Philippines, what it needs is more vegetation. Tidal power isn't nearly as developed as the other forms of new energy. And it may also disrupt a very busy marine trade route.",
"title": ""
},
{
"docid": "118184",
"text": "So why are people still buying 15 year old Saturns or driving the same GM Denali for the last 13 years when the new cars are so much more efficient and cheaper to run? Poor people are fucking poor. Now you turn to Indonesia. How much do you think they are spending to maintain their vehicles? Next to nothing, that's what. They'll only fix it enough to get it running again. SAE certified mechanic? LOL, the guy between the whore house and the cigarette vendor can also do it. How much do you think electricity costs in the Philippines? It can cost $100 USD a month to run the AC at night to get a decent sleep...The average Filipino makes less than $10 a month.",
"title": ""
},
{
"docid": "363197",
"text": "malaysia sports betting We strive day and night to make everything work perfectly making sure that you can have fun without worrying about anything. The firm commitment to our users and a determined commitment to safe malaysia sports betting play have led us to implement all the measures and actions that are within our reach to achieve a fair, honest, complete, reliable and totally transparent gaming experience. We take our responsibilities very seriously and focus on what playing is always a fully satisfying experience. Therefore, we also actively work in the promotion of responsible play so that playing never ceases to be a leisure activity full of fun, we watch that strictly comply with the prohibition of access to minors and we turn to answer all your questions And needs.",
"title": ""
},
{
"docid": "347064",
"text": "\"Nope, you don't get what I mean. If you put a statement that is not only incorrect, but shows bias, you will get laughed at by anyone. Export means that you take something and then sell them to someone else. That's a positive, and actually exists (though still not quite the correct terminology, it is more apt). For example, the Philippines exports maids to the Middle East. That helps the Filipino economy, unlike what you are saying. But the other thing is that by saying \"\"export\"\", you are already assuming a net loss of jobs, which would not only goes against 90% of economists beliefs, and is the equivalent of starting an abortion debate with, \"\"why do you kill unborn babies\"\", and when anyone corrects you, you claim pedantry. You already showed your bias and pretty much invited a circle jerk by using those words. Which may be fine reddit, where the hive mind laps this up, but ask anyone who's gone beyond studying Macroeconomics, and you won't be taken seriously. The choice is yours, do you want a circle jerk, or do you want to engage in an actual conversation?\"",
"title": ""
},
{
"docid": "10247",
"text": "\"Going through the list of economies that currently use the dollar, all of them list cents as a fractional unit. In Hong Kong and Taiwan, the 1/100 fractional unit is still called a cent, but it's no longer in circulation in coin form and only finds use in financial markets or electronic payments. In countries like Malaysia, the word \"\"sen\"\" is used as the translation of the word \"\"cent\"\", even though the word for the actual currency, \"\"ringgit\"\", isn't a translation of the word \"\"dollar\"\". A similar situation occurs in Panama. The local currency is called the balboa, and it's priced on par (1:1) with the US dollar. US banknotes are also accepted as legal tender, and Panamanians sometimes use the terms balboa/dollar interchangeably. The 1/100 subdivision of the balboa is the centésimo, which is merely a translation of cent. Like Malaysia, the fractional unit is called \"\"cent\"\" (or a translation) but the main unit isn't merely a translation of the word \"\"dollar.\"\" On a historical note, the Spanish Dollar was subdivided into 8 reales in order to match the German thaler (the word that forms the basis for the English word \"\"dollar\"\").\"",
"title": ""
},
{
"docid": "368053",
"text": "FYI...during the housing boom here in the US many people spoke about ever increasing home prices. Many thought home prices could never go down. Until they did. If it seems like it is impossible for home prices to continue to go up then they probably will stop going up at some point, although the rising prices can continue for a lot longer than you think possible. I'm wondering if Malaysia is feeling the effects of the US FED which flooded the market with US dollars after the crisis. The Malaysian central bank holds US dollars as its foreign exchange reserves. In order to keep the ringgit from rising against the dollar the Malaysian central bank will print up ringgit to purchase dollars which suppresses the value of the ringgit. This has the effect of artificially lowering interest rates as ringgits become readily available leading to a boom - the boom being in real estate. Just a hunch. Is the dinar in Kelantan getting much attention in Malaysia? This is starting to make a little news here.",
"title": ""
},
{
"docid": "50759",
"text": "\"1. **[National Suicide Prevention Lifeline, http://www.suicidepreventionlifeline.org](http://www.suicidepreventionlifeline.org \"\"National Suicide Prevention Lifeline, 1-800-273-8255\"\")** **Call toll-free in the United States: 1-800-273-8255** **Chat: [http://www.suicidepreventionlifeline.org/GetHelp/LifelineChat.aspx](http://www.suicidepreventionlifeline.org/GetHelp/LifelineChat.aspx)** 2. \"\"[For long-unemployed, hiring bias rears its head](http://www.seattlepi.com/news/article/For-long-unemployed-hiring-bias-rears-its-head-3428844.php)\"\" by Stephen Singer, published on 23 March 2012: http://www.seattlepi.com/news/article/For-long-unemployed-hiring-bias-rears-its-head-3428844.php 3. \"\"[The Anxiety of Unemployment](http://opinionator.blogs.nytimes.com/2012/05/21/control/)\"\" by Dominick Brocato and DW Gibson, published on 21 May 2012: http://opinionator.blogs.nytimes.com/2012/05/21/control/ 4. \"\"[Long-term unemployment crisis rolls on](http://money.cnn.com/2012/06/11/news/economy/long-term-unemployment/index.htm)\"\" by Charles Riley, published on 11 June 2012: http://money.cnn.com/2012/06/11/news/economy/long-term-unemployment/index.htm 5. \"\"[Philadelphia Woman, 73, Says Age Has Kept Her Unemployed for Two Years](http://abcnews.go.com/Business/73-year-philadelphia-woman-testifies-age-discrimination-job/story?id=16352837&singlePage=true)\"\" by Susanna Kim, published on 16 May 2012: http://abcnews.go.com/Business/73-year-philadelphia-woman-testifies-age-discrimination-job/story?id=16352837&singlePage=true\"",
"title": ""
},
{
"docid": "239734",
"text": "Most of the points by MrChrister are valid. I can't say much for Philippines, however there is a reason for one to go with individual insurance from my experience in India.",
"title": ""
},
{
"docid": "511647",
"text": "\"This page from TripAdvisor may be of interest. Look at what fees are charged on your ATM cards and credit cards, and consider overpaying your credit card so you have a credit balance that you can draw on for cash \"\"advances\"\" from ATMs that will dispense in local currency. Depending on what fees your bank charges, you may get a better rate than the forex cash traders at the airport. Edit: Cards may not always have the best rate. I recently heard from a traveler who was able to use a locally but not globally dominant currency to buy cash of a major currency at a shopping mall (with competitive forex traders) at rates even better than the mid-market rates posted at xe.com and similar places; I don't think you'll have that experience going from Australia to Malaysia (but another traveler reading this might have a different pair). In my experience the card rates are slightly worse than those and the airport forex traders significantly worse.\"",
"title": ""
}
] |
3187
|
Mel Brooks has three films ranked in the American Film Institute's list.
|
[
{
"docid": "Mel_Brooks",
"text": "Melvin Brooks ( né Kaminsky , born June 28 , 1926 ) is an American filmmaker , comedian , actor and composer . He is known as a creator of broad film farces and comic parodies . Brooks began his career as a comic and a writer for the early TV variety show Your Show of Shows . He became well known as part of the comedy duo with Carl Reiner in the comedy skit The 2000 Year Old Man . He also created , with Buck Henry , the hit television comedy series Get Smart , which ran from 1965 to 1970 . In middle age , Brooks became one of the most successful film directors of the 1970s , with many of his films being among the top 10 moneymakers of the year they were released . His best-known films include The Producers , The Twelve Chairs , Blazing Saddles , Young Frankenstein , Silent Movie , High Anxiety , History of the World , Part I , Spaceballs and Robin Hood : Men in Tights . A musical adaptation of his first film , The Producers , ran on Broadway from 2001 to 2007 . In 2001 , having previously won an Emmy , a Grammy and an Oscar , he joined a small list of EGOT winners with his Tony award for The Producers . He received a Kennedy Center Honor in 2009 , the Hollywood Walk of Fame in 2010 , the 41st AFI Life Achievement Award in June 2013 , a British Film Institute Fellowship in March 2015 , a National Medal of Arts in September 2016 , and a BAFTA Fellowship in February 2017 . Three of his films ranked in the American Film Institute 's list of the top 100 comedy films of the past 100 years ( 1900 -- 2000 ) , all of which ranked in the top 15 of the list : Blazing Saddles at number 6 , The Producers at number 11 , and Young Frankenstein at number 13 . Brooks was married to Oscar-winning actress Anne Bancroft from 1964 until her death in 2005 .",
"title": ""
}
] |
[
{
"docid": "Blazing_Saddles",
"text": "Blazing Saddles is a 1974 American satirical Western comedy film directed by Mel Brooks . Starring Cleavon Little and Gene Wilder , the film was written by Brooks , Andrew Bergman , Richard Pryor , Norman Steinberg , and Al Uger , and was based on Bergman 's story and draft . The film received generally positive reviews from critics and audiences , was nominated for three Academy Awards , and is ranked No. 6 on the American Film Institute 's 100 Years ... 100 Laughs list . Brooks appears in two supporting roles , Governor William J. Le Petomane and a Yiddish-speaking Indian chief ; he also dubs lines for one of Lili von Shtupp 's backing troupe . The supporting cast includes Slim Pickens , Alex Karras , and David Huddleston , as well as Brooks regulars Dom DeLuise , Madeline Kahn , and Harvey Korman . Bandleader Count Basie has a cameo as himself . The film satirizes the racism obscured by myth-making Hollywood accounts of the American West , with the hero being a black sheriff in an all-white town . The film is full of deliberate anachronisms , from the Count Basie Orchestra playing `` April in Paris '' in the Wild West , to Slim Pickens referring to the Wide World of Sports , to the German army of World War II .",
"title": ""
},
{
"docid": "Young_Frankenstein",
"text": "Young Frankenstein is a 1974 American comedy horror film directed by Mel Brooks and starring Gene Wilder as the title character , a descendant of the infamous Dr. Victor Frankenstein . The supporting cast includes Teri Garr , Cloris Leachman , Marty Feldman , Peter Boyle , Madeline Kahn , Kenneth Mars , Richard Haydn and Gene Hackman . The screenplay was written by Wilder and Brooks . The film is an affectionate parody of the classic horror film genre , in particular the various film adaptations of Mary Shelley 's novel Frankenstein produced by Universal in the 1930s . Most of the lab equipment used as props was created by Kenneth Strickfaden for the 1931 film Frankenstein . To help evoke the atmosphere of the earlier films , Brooks shot the picture entirely in black and white , a rarity in the 1970s , and employed 1930s ' style opening credits and scene transitions such as iris outs , wipes , and fades to black . The film also features a period score by Brooks ' longtime composer John Morris . A critical favorite and box office smash , Young Frankenstein ranks No. 28 on Total Film magazine 's readers ' `` List of the 50 Greatest Comedy Films of All Time '' , No. 56 on Bravo TV 's list of the `` 100 Funniest Movies '' , and No. 13 on the American Film Institute 's list of the 100 funniest American movies . In 2003 , it was deemed `` culturally , historically or aesthetically significant '' by the United States National Film Preservation Board , and selected for preservation in the Library of Congress National Film Registry . On its 40th anniversary , Brooks considered it by far his finest ( though not his funniest ) film as a writer-director .",
"title": ""
},
{
"docid": "Michael_Hertzberg",
"text": "Michael Hertzberg is an American assistant director , writer , and film producer best known for his work with director Mel Brooks . Hertzberg was extremely influential on Brooks , having started working for Brooks as an assistant director on Brook 's first film The Producers , and going on to produce several of Brooks ' early films including box office hits , Blazing Saddles and Silent Movie . Blazing Saddles was awarded the # 6 slot on the American Film Institute 's list of Top 100 comedy films of all time . Hertzberg started working as an assistant director in commercials , television and feature films . He was the first assistant director to Frank Perry on the hit cult film , The Swimmer , starring Burt Lancaster . Hertzberg also wrote the story ( with Ronald Bass ) and produced Entrapment starring Sean Connery and Catherine Zeta-Jones . He produced Johnny Dangerously starring Michael Keaton and directed by Amy Heckerling ( director of Fast Times at Ridgemont High.Hertzberg has also been interviewed for several behind-the-scenes documentaries including Back in the Saddle ( featured on the 2003 DVD release of Blazing Saddles ) , The Making of The Producers ( featured on the MGM Special Edition DVD release of The Producers and The Story of the Swimmer ( featured on the 2014 Grindhouse Releasing/Box Office Spectaculars Blu-ray/DVD restoration ) .",
"title": ""
},
{
"docid": "Stinking_badges",
"text": "`` Badges ? We do n't need no stinkin ' badges ! '' is a widely quoted paraphrase of a line of dialogue from the 1948 film The Treasure of the Sierra Madre . That line was in turn derived from dialogue in the 1927 novel , The Treasure of the Sierra Madre , which was the basis for the film . In 2005 , the full quote from the film was chosen as # 36 on the American Film Institute list , AFI 's 100 Years ... 100 Movie Quotes . The shorter , better-known version of the quote was first heard in the 1967 episode of the TV series The Monkees , `` It 's a Nice Place to Visit '' . It was also included in the 1974 Mel Brooks film Blazing Saddles , and has since been included in many other films and television shows .",
"title": ""
},
{
"docid": "Carl_Reiner_and_Mel_Brooks_at_the_Cannes_Film_Festival",
"text": "Carl Reiner and Mel Brooks at the Cannes Film Festival is a live 1963 comedy album by the American comedians Carl Reiner and Mel Brooks , recorded at the Cannes Film Festival . It was the third album released by the pair , and their last recording for 12 years . It was nominated for the Grammy Award for Best Comedy Performance at the 6th Annual Grammy Awards in 1964 ; it lost to Allan Sherman 's song `` Hello Muddah , Hello Fadduh ( A Letter from Camp ) '' . Characters on the album include the Italian film director `` Federico Fetuchini '' ( inspired by Federico Fellini ) , the Nazi inspired `` Adolph Hartner '' , and the British Tippy Skittles K.C.V.B.",
"title": ""
},
{
"docid": "The_Producers_(1968_film)",
"text": "The Producers is a 1968 American satirical comedy film written and directed by Mel Brooks and starring Zero Mostel , Gene Wilder , Dick Shawn , and Kenneth Mars . The film was Brooks 's directorial debut , and he won an Academy Award for Best Original Screenplay . Although the release date was officially 1968 , the premier took place in Pittsburgh on November 22 , 1967 . Decades later , the film was selected for preservation in the National Film Registry and placed eleventh on the AFI 's 100 Years ... 100 Laughs list . It was later remade by Brooks as an acclaimed Broadway stage musical , which itself was adapted for a 2005 feature film starring Nathan Lane and Matthew Broderick .",
"title": ""
},
{
"docid": "Get_Smart",
"text": "Get Smart is an American comedy television series that satirizes the secret agent genre . It was created by Mel Brooks with Buck Henry and had its television premiere on September 18 , 1965 . The show stars Don Adams as Maxwell Smart , Agent 86 , Barbara Feldon as Agent 99 , and Edward Platt as Thaddeus , the Chief . Henry said that they created the show at the request of Daniel Melnick to capitalize on `` the two biggest things in the entertainment world today '' : James Bond and Inspector Clouseau . Brooks said : `` It 's an insane combination of James Bond and Mel Brooks comedy . '' The Museum of Broadcast Communications finds the show notable for `` broadening the parameters for the presentation of comedy on television . '' The show generated a number of popular catchphrases during its run , including `` Would you believe ... '' , `` Missed it by that much ! '' , `` Sorry about that , Chief '' , `` The old ( such-and-such ) trick '' , `` And loving it '' , and `` I asked you not to tell me that '' . The show was followed by the films The Nude Bomb ( a 1980 theatrical release ) and Get Smart , Again ! ( a 1989 made-for-TV sequel to the series ) , as well as a 1995 revival series , and a 2008 film remake . In 2010 , TV Guide ranked Get Smart 's opening title sequence at No. 2 on its list of TV 's Top 10 Credits Sequences as selected by readers . The show ended its 4 1/2 - year run on May 15 , 1970 , having a total of 5 seasons and 138 episodes .",
"title": ""
},
{
"docid": "Spaceballs",
"text": "Spaceballs is a 1987 American science fiction parody film co-written , produced and directed by Mel Brooks . Starring Brooks , Bill Pullman , John Candy , and Rick Moranis , the film also features Daphne Zuniga , Dick Van Patten , and the voice of Joan Rivers . In addition to Brooks in a supporting role , the film also features Brooks regulars Dom DeLuise and Rudy De Luca in cameo appearances . The film was released by Metro-Goldwyn-Mayer on June 24 , 1987 , and was met with a mixed reception . It has since become a cult classic on video and one of Brooks 's most popular films . Its setting and characters parody the original Star Wars trilogy , as well as other sci-fi franchises including Star Trek , Alien , and the Planet of the Apes films .",
"title": ""
},
{
"docid": "To_Be_or_Not_to_Be_(1983_film)",
"text": "To Be or Not to Be is a 1983 American war comedy film directed by Alan Johnson and produced by Mel Brooks . The screenplay was written by Ronny Graham and Thomas Meehan , based on the original story by Melchior Lengyel , Ernst Lubitsch and Edwin Justus Mayer . A remake of the 1942 film of the same name , the film starred Mel Brooks alongside his wife Anne Bancroft ; Tim Matheson , Charles Durning , Christopher Lloyd , and José Ferrer also had starring roles .",
"title": ""
},
{
"docid": "Blazing_Samurai",
"text": "Blazing Samurai is an upcoming American computer-animated action adventure comedy film inspired by Mel Brooks ' seminal 1974 Western comedy film Blazing Saddles , directed by Chris Bailey and written by Ed Stone and Nate Hopper . The film stars Michael Cera , Samuel L. Jackson , Ricky Gervais , George Takei , Gabriel Iglesias , Djimon Hounsou , Michelle Yeoh , and Mel Brooks . The film will be released by Open Road Films in the US and Canada , Huayi Brothers International in China , and Sony Pictures in Latin America .",
"title": ""
},
{
"docid": "Young_Frankenstein_(musical)",
"text": "Young Frankenstein , officially known as The New Mel Brooks Musical : Young Frankenstein , is a musical with a book by Mel Brooks and Thomas Meehan and music and lyrics by Brooks . It is based on the 1974 comedy film of the same name written by Brooks and Gene Wilder and directed by Brooks , who has described it as his best film . It is a parody of the horror film genre , especially the 1931 Universal Pictures adaptation of Mary Shelley 's Frankenstein and its 1939 sequel , Son of Frankenstein . After tryouts in Seattle , Washington and four weeks of previews , the musical opened on Broadway on November 8 , 2007 to mixed reviews . The Broadway production closed on January 4 , 2009 after 30 previews and 484 performances . A U.S. tour started on September 29 , 2009 in Providence , Rhode Island .",
"title": ""
},
{
"docid": "High_Anxiety",
"text": "High Anxiety is a 1977 American satirical comedy film produced and directed by Mel Brooks , who also plays the lead . This is Brooks ' first film as a producer and first speaking lead role ( his first lead role was in Silent Movie ) . Veteran Brooks ensemble members Harvey Korman , Cloris Leachman , and Madeline Kahn are also featured . The film is a parody of suspense films , most obviously the films directed by Alfred Hitchcock : Spellbound , Vertigo and The Birds . The film was dedicated to Hitchcock , who worked with Brooks on the screenplay and later sent Brooks a case containing six magnums of 1961 Château Haut-Brion wine to show his appreciation .",
"title": ""
},
{
"docid": "The_Twelve_Chairs_(1970_film)",
"text": "The Twelve Chairs is a 1970 American comedy film directed by Mel Brooks , starring Frank Langella , Ron Moody , and Dom DeLuise . The screenplay was written by Brooks . The film was one of at least 18 film adaptations of the Russian 1928 novel The Twelve Chairs by Ilf and Petrov .",
"title": ""
},
{
"docid": "Robert_Latham_Brown",
"text": "Robert Latham Brown ( born June 20 , 1947 ) is a film producer , line producer , production manager , author , and teacher . In his 30-year film career , he has worked with Mel Brooks , George Lucas , Paul Verhoeven , Steven Spielberg and many others . His expertise in budgeting and line producing inspired Mel Brooks to nickname Brown `` Mr. On-Budget '' .",
"title": ""
},
{
"docid": "List_of_Brooksfilms_productions",
"text": "This is a list of films produced by Brooksfilms , the studio founded by Oscar-winning filmmaker Mel Brooks . Brooksfilms",
"title": ""
},
{
"docid": "Robin_Hood:_Men_in_Tights",
"text": "Robin Hood : Men in Tights is a 1993 American musical adventure comedy film and a parody of the Robin Hood story . The film was produced and directed by Mel Brooks , co-written by Brooks , Evan Chandler , and J. David Shapiro based on a story by Chandler and Shapiro , and stars Cary Elwes , Richard Lewis , and Dave Chappelle in his film debut . It includes frequent comedic references to previous Robin Hood films ( particularly Prince of Thieves , upon which the plot is loosely structured , Disney 's Robin Hood , and the 1938 Errol Flynn adaptation , The Adventures of Robin Hood ) . The film also features Brooks in a minor role ; the first time he had appeared in one of his own films where he does not receive top billing or play the lead role since Young Frankenstein . In addition to Brooks , it features cameos from Brooks regulars Dom DeLuise , Dick Van Patten , and Rudy De Luca .",
"title": ""
},
{
"docid": "List_of_accolades_received_by_Forrest_Gump",
"text": "Forrest Gump is a 1994 epic romantic comedy-drama film based on the 1986 novel of the same name by Winston Groom . The film premiered in Los Angeles , California on June 23 , 1994 and was released into the United States and Canada on July 6 , 1994 , opening into 1,595 domestic theaters and earning $ 24,450,602 on its first weekend . Forrest Gump grossed $ 677 million and was at its time the fourth highest grossing film of all time ( behind only E.T. the Extra-Terrestrial , Star Wars IV : A New Hope , and Jurassic Park ) . Despite its praise , it has only a 72 % approval rating on Rotten Tomatoes . Forrest Gump won six Academy Awards for Best Picture , Best Actor in a Leading Role , Best Director , Best Visual Effects , Best Adapted Screenplay , and Best Film Editing . The film garnered for seven Golden Globe Award nominations , winning three of them , including Best Actor -- Motion Picture Drama , Best Director -- Motion Picture , and Best Motion Picture -- Drama . The film was also nominated for six Saturn Awards and won two for Best Fantasy Film and Best Supporting Actor ( Film ) . The film also won the Outstanding Achievement in Special Effects award at the 1995 BAFTA Film Awards . Forrest Gump received numerous other awards such as one win from the Screen Actors Guild Awards in its first year for Tom Hanks in a total of four nominations . The film received three nominations from the MTV Movie Awards , but left empty handed . The film swept the Peoples Choice Awards in its three nominations . The American Society of Cinematographers nominated the films cinematographer Don Burgess for Outstanding Achievement in Cinematography in Theatrical Release , but lost to Shawshank Redemption '' 's Roger Deakins . The film was selected for preservation by the Library of Congress in the United States National Film Registry in 2011 , being deemed `` culturally , historically , or aesthetically significant '' . The movie has made multiple American Film Institute lists including the quote `` Mama always said life was like a box of chocolates . You never know what you 're gon na get . '' ranking 40th on 100 Years ... 100 Movie Quotes . The film ranked 240 on Empire '' 's list of the 500 Greatest Movies Of All Time . The chain of restaurants , Bubba Gump Shrimp Company opened based on the film , and has opened many locations since its founding .",
"title": ""
},
{
"docid": "Fatso_(1980_film)",
"text": "Fatso is a 1980 American comedy film written and directed by Anne Bancroft , her only such credit , and starring Dom DeLuise , Ron Carey and Candice Azzara . It was the first film produced by Mel Brooks ' Brooksfilms company . The film examines the issue of obesity .",
"title": ""
},
{
"docid": "25th_Academy_Awards",
"text": "The 25th Academy Awards ceremony was held on March 19 , 1953 . It took place at the RKO Pantages Theatre in Hollywood , California , and the NBC International Theatre in New York City . It was the first Academy Awards ceremony to be televised , and the first ceremony to be held in Hollywood and New York City simultaneously . It was also the only year that the New York ceremonies were to be held in the NBC International Theatre on Columbus Circle , which was shortly thereafter demolished and replaced by the New York Coliseum convention center . A major upset occurred in the category of Best Picture . The heavily favored High Noon lost to Cecil B. DeMille 's The Greatest Show on Earth , eventually considered among the worst films to have won the Academy Award for Best Picture . The American film magazine Premiere placed the movie on its list of the 10 worst Oscar winners and the British film magazine Empire rated it # 3 on their list of the 10 worst Oscar winners . It has the lowest spot on Rotten Tomatoes ' list of the 81 films to win Best Picture . Of all the films nominated for the Oscar this year , only High Noon and Singin ' in the Rain would show up 46 years later on the American Film Institute list of the greatest American films of the 20th Century . For a film that only received two nominations , Singin ' in the Rain went on to be named as the greatest American musical film of all time and in the 2007 American Film Institute updated list as the fifth greatest American film of all time , while High Noon was ranked twenty-seventh on the same 2007 list , as well . The Bad and the Beautiful won five awards , the most wins ever for a film not nominated for Best Picture . It was also the second Academy Awards in which a film not nominated for Best Picture received the most awards of the evening , excluding years where there were ties for the most wins . The only other film to do this was The Thief of Bagdad at the 13th Academy Awards ; as of the 87th Academy Awards , it has not happened since . Until Spotlight won only Best Picture and Best Original Screenplay at the 88th Academy Awards , this was the last year in which the Best Picture winner won just two Oscars . It was also the second of three years to date in which two films not nominated for Best Picture received more nominations than the winner ( The Bad and the Beautiful and Hans Christian Andersen , both with six ) . This occurred again at the 79th Academy Awards . Shirley Booth also became the last person to win an Oscar in a Leading Role to be born in the 19th century . She also holds the distinction of being the first woman in her 50s to win the award , at the age of 54 ( the second woman in her 50s to win , Julianne Moore , was 54 when awarded at the 87th Academy Awards ) . John Ford 's fourth win for Best Director set a record for the most wins in this category that remains unmatched to this day . For the first time since the introduction of Supporting Actor and Actress awards in 1936 , Best Picture , Best Director , and all four acting Oscars went to six different films . This has happened only three times since , at the 29th Academy Awards for 1956 , the 78th for 2005 , and the 85th for 2012 .",
"title": ""
},
{
"docid": "Dracula:_Dead_and_Loving_It",
"text": "Dracula : Dead and Loving It is a 1995 satirical comedy horror film directed by Mel Brooks and starring Leslie Nielsen . It is a spoof of Bram Stoker 's novel Dracula , and of some of the films it inspired . As of the start of 2017 , this is the most recent film Brooks has directed . Brooks co-authored the screenplay with Steve Haberman and Rudy De Luca . He also appears as Dr. Van Helsing . The film 's other stars include Steven Weber , Amy Yasbeck , Peter MacNicol , Harvey Korman , and Anne Bancroft . The film follows the classic Dracula ( 1931 ) , starring Bela Lugosi , in its deviations from the novel . Its visual style and production values are particularly evocative of the Hammer Horror films . It spoofed , among other films , The Fearless Vampire Killers ( 1967 ) and Bram Stoker 's Dracula ( 1992 ) .",
"title": ""
},
{
"docid": "To_Kill_a_Mockingbird_(film)",
"text": "To Kill a Mockingbird is a 1962 American drama film directed by Robert Mulligan . The screenplay by Horton Foote is based on Harper Lee 's 1960 Pulitzer Prize-winning novel of the same name . It stars Gregory Peck as Atticus Finch and Mary Badham as Scout . The film , received overwhelmingly positive reviews from critics and was a box-office success , earning more than 10 times its budget . The film won three Academy Awards , including Best Actor for Peck , and was nominated for eight , including Best Picture . In 1995 , the film was listed in the National Film Registry . In 2003 , AFI named Atticus Finch the greatest movie hero of the 20th century . In 2007 the film ranked twenty-fifth on the American Film Institute 's 10th anniversary list of the greatest American movies of all time . To Kill a Mockingbird marked the film debuts of Robert Duvall , William Windom , and Alice Ghostley .",
"title": ""
},
{
"docid": "Peter_Wooley",
"text": "Peter Wesley Wooley ( born December 26 , 1934 ) is an American film producer , author , director , and production designer with 85 films and television Series to his credit , including the Mel Brooks ' films Blazing Saddles and High Anxiety . He was nominated for an Emmy Award for Production Design of the movie The Day After . Wooley was born in East Liverpool , Ohio and entered the Navy immediately upon graduating from High School . He studied architecture at Kent State . He married to Linda Lane , a singer who studied at the Pasadena Playhouse and performed at the Copacabana ( nightclub ) , and they have two children , Stephanie Wilson and musician Christopher Wooley . Wooley began a career in architecture . He went to work in the movie industry in 1966 as a draftsmen on the boards at Warner Brothers . He worked as a Set Designer at Warner Brothers and Universal Pictures . Wooley worked as an Assistant Art Director on several television series including Mod Squad . His first series as an Art Director was on the series My World and Welcome to It . Several television series followed and then a move into feature films . Wooley began a long-lasting working relationship with Mel Brooks and was the Production designer on Blazing Saddles and High Anxiety as well as the Brooks-produced film Fatso . He is the author of the book , What ! And Give Up Show Business ? and a novel called You Only Go ` Round Once .",
"title": ""
},
{
"docid": "Sidney_Glazier",
"text": "Sidney Glazier ( May 29 , 1916 -- December 14 , 2002 ) was an American film producer best known for his work on the Mel Brooks film The Producers .",
"title": ""
},
{
"docid": "History_of_the_World,_Part_I",
"text": "History of the World , Part I is a 1981 American anthology comedy film written , produced , and directed by Mel Brooks . Brooks also stars in the film , playing five roles : Moses , Comicus the stand-up philosopher , Tomás de Torquemada , King Louis XVI , and Jacques , le garçon de pisse . The large ensemble cast also features Sid Caesar , Shecky Greene , Gregory Hines ( in his film debut ) , Charlie Callas ; and Brooks regulars Ron Carey , Dom DeLuise , Madeline Kahn , Harvey Korman , Cloris Leachman , Andreas Voutsinas , and Spike Milligan . The film also has cameo appearances by Royce D. Applegate , Beatrice Arthur , Hugh Hefner , John Hurt , Phil Leeds , Barry Levinson , Jackie Mason , Paul Mazursky , Andrew Sachs and Henny Youngman , among others . Orson Welles narrates each story . Despite carrying the title Part 1 , there is no sequel ; the title is a play on The History of the World , Volume 1 by Sir Walter Raleigh , as detailed below .",
"title": ""
},
{
"docid": "List_of_awards_and_nominations_received_by_Alfred_Hitchcock",
"text": "The following is a list of awards and nominations received by English film director and producer Sir Alfred Hitchcock , chronicling his achievements in the film industry . The six-times Academy Awards-nominee and four times the Emmy Awards demonstrably won eight Golden Laurel Awards , two Golden Globes , the Irving G. Thalberg Memorial Award , the AFI Life Achievement Award , the Directors Guild of America Award , the Film Society of Lincoln Center 's Gala Tribute Award , the National Board of Review of Motion Pictures Award , the New York Film Critics Circle Award , and the Saturn Award . In England , Hitchcock was honored by the BAFTA Academy Fellowship Award and made a Knight Commander of the Order of the British Empire by the Queen Elizabeth II . Apart from his three Cannes Film Festival nominations , he also received two Silver Shell Awards at San Sebastián International Film Festival in Spain , the Jussi Award in Finland , the Kinema Junpo Award in Japan , the Mention Award at Locarno International Film Festival in Switzerland , and at Venice Film Festival in Italy a Golden Lion nomination . In addition , six of movies directed by Hitchcock were inducted into the National Film Registry and four of them are listed in the American Film Institute list of the 100 greatest American movies of all time ( along with Vertigo , which was ranked as the Best Mystery Movie Ever ) . Two other his pictures entered the list of the 100 Greatest British Films of the 20th Century , released by British Film Institute in UK .",
"title": ""
},
{
"docid": "Life_Stinks",
"text": "Life Stinks is a 1991 comedy-drama directed by and starring Mel Brooks . It is one of the few Mel Brooks comedies that is not a parody , nor at any time does the film break the fourth wall . It co-stars Lesley Ann Warren , Howard Morris and Jeffrey Tambor . The original music score was composed by John Morris . The film was both a critical and box office flop .",
"title": ""
},
{
"docid": "The_Critic_(film)",
"text": "The Critic is an American 1963 short animated film by director/producer Ernest Pintoff and creator/narrator Mel Brooks , that won an Academy Award for Short Subjects ( Cartoons ) in 1964 .",
"title": ""
},
{
"docid": "Brooke_Elliott",
"text": "Brooke Elliott ( born November 16 , 1974 ) is an American actress and singer . She has previously appeared in musical theatre , including the US tours of Beauty and the Beast and Wicked , and the Broadway productions of Taboo and The Pirate Queen . She is best known for her roles in the 2000 Mel Gibson film What Women Want , her big-screen debut , and as Jane Bingum on the Lifetime series Drop Dead Diva .",
"title": ""
},
{
"docid": "What's_Up,_Doc?_(1972_film)",
"text": "What 's Up , Doc ? is a 1972 American screwball comedy film released by Warner Bros. , directed by Peter Bogdanovich and starring Barbra Streisand , Ryan O'Neal , and Madeline Kahn in her first feature film role ( for which she was nominated for a Golden Globe ) . It was intended to pay homage to comedy films of the 1930s , especially Bringing Up Baby , as well as old Bugs Bunny cartoons ( another Warner Bros. character ) . The film was a success , and became the third-highest grossing film of 1972 . The film won the Writers Guild of America 1973 `` Best Comedy Written Directly for the Screen '' award for writers Buck Henry , David Newman and Robert Benton . It was ranked number 61 on the list of the 100 greatest American comedies published by the American Film Institute ( AFI ) , and ranked number 68 on the AFI 's list of 100 greatest love stories in American cinema . It was also ranked number 58 on the list of the WGA 's 101 Funniest Screenplays published by the Writers Guild of America .",
"title": ""
},
{
"docid": "Infestation_(film)",
"text": "Infestation is a 2009 Horror-Comedy feature film by American writer/director Kyle Rankin . It was produced by Mel Gibson 's Icon Entertainment and starring Chris Marquette , E. Quincy Sloan , Brooke Nevin , Kinsey Packard , Deborah Geffner and Ray Wise . It was filmed in Bulgaria .",
"title": ""
}
] |
4733
|
Why does Yahoo! Finance report different prices for the same index?
|
[
{
"docid": "309314",
"text": "\"Are you sure you're using the same date range? If you're using Max, then you're not, as ^FTMC goes back to 12/1/1985 while ^GDAXI only goes back to 11/1/1990. If I enter a custom date range of 11/1/1990 through 10/24/2015, I get: and: which, other than the dates it chose to use as labels on the x-axes, look identical. (I tried to add the URLs of the charts, but it looks like the Yahoo! URLs don't include the comparison symbol, which makes them useless for this answer. They're easy enough to construct though, just add the secondary symbol using the Comparison button and set the date range using the calendar button.) On your PS, I don't know, as you can see by my charts it even chose different labels when the date ranges were identical (although at least it didn't scale different dates differently), so maybe it's trying to be \"\"smart\"\" and choose dates based on the total amount of data available for the primary symbol, which is different in the two cases.\"",
"title": ""
}
] |
[
{
"docid": "532616",
"text": "At this time, Google Finance doesn't support historical return or dividend data, only share prices. The attributes for mutual funds such as return52 are only available as real-time data, not historical. Yahoo also does not appear to offer market return data including dividends. For example, the S&P 500 index does not account for dividends--the S&P ^SPXTR index does, but is unavailable through Yahoo Finance.",
"title": ""
},
{
"docid": "159471",
"text": "Why don't you look at the actual funds and etfs in question rather than seeking a general conclusion about all pairs of funds and etfs? For example, Vanguard's total stock market index fund (VTSAX) and ETF (VTI). Comparing the two on yahoo finance I find no difference over the last 5 years visually. For a different pair of funds you may find something very slightly different. In many cases the index fund and ETF will not have the same benchmark and fees so comparisons get a little more cloudy. I recall a while ago there was an article that was pointing out that at the time emerging market ETF's had higher fees than corresponding index funds. For this reason I think you should examine your question on a case-by-case basis. Index fund and ETF returns are all publicly available so you don't have to guess.",
"title": ""
},
{
"docid": "317666",
"text": "tl;dr: The CNN Money and Yahoo Finance charts are wildly inaccurate. The TD Ameritrade chart appears to be accurate and shows returns with reinvested dividends. Ignoring buggy data, CNN most likely shows reinvested dividends for quoted securities but not for the S&P 500 index. Yahoo most likely shows all returns without reinvested dividends. Thanks to a tip from Grade Eh Bacon, I was able to determine that TD Ameritrade reports returns with reinvested dividends (as it claims to do). Eyeballing the chart, it appears that S&P 500 grew by ~90% over the five year period the chart covers. Meanwhile, according to this S&P 500 return estimator, the five year return of S&P 500, with reinvested dividends, was 97.1% between July 2012 to July 2017 (vs. 78.4% raw returns). I have no idea what numbers CNN Money is working from, because it claims S&P 500 only grew about 35% over the last five years, which is less than half of the raw return. Ditto for Yahoo, which claims 45% growth. Even stranger still, the CNN chart for VFINX (an S&P 500 index fund) clearly shows the correct market growth (without reinvesting dividends from the S&P 500 index), so whatever problem exists is inconsistent: Yahoo also agrees with itself for VFINX, but comes in a bit low even if your assume no reinvestment of dividends (68% vs. 78% expected); I'm not sure if it's ever right. By way of comparison, TD's chart for VFINX seems to be consistent with its ABALX chart and with reality: As a final sanity check, I pulled historical ^GSPC prices from Yahoo Finance. It closed at $1406.58 on 27 Aug 2012 and $2477.55 on 28 Aug 2017, or 76.1% growth overall. That agrees with TD and the return calculator above, and disagrees with CNN Money (on ABALX). Worse, Yahoo's own charts (both ABALX and VFINX) disagree with Yahoo's own historical data.",
"title": ""
},
{
"docid": "410123",
"text": "\"To add on to the other answers, in asking why funds have different price points one might be asking why stocks aren't normalized so a unit price of $196 in one stock can be directly compared to the same price in another stock. While this might not make sense with AAPL vs. GOOG (it would be like comparing apples to oranges, pun intended, not to mention how would two different companies ever come to such an agreement) it does seem like it would make more sense when tracking an index. And in fact less agreement between different funds would be required as some \"\"natural\"\" price points exist such as dividing by 100 (like some S&P funds do). However, there are a couple of reasons why two different funds might price their shares of the same underlying index differently. Demand - If there are a lot of people wanting the issue, more shares might be issued at a lower price. Or, there might be a lot of demand centered on a certain price range. Pricing - shares that are priced higher will find fewer buyers, because it makes it harder to buy round lots (100 shares at $100/share is $10,000 while at $10/share it's only $1000). While not everyone buys stock in lots, it's important if you do anything with (standardized) options on the stock because they are always acting on lots. In addition, even if you don't buy round lots a higher price makes it harder to buy in for a specific amount because each unit share has a greater chance to be further away from your target amount. Conversely, shares that are priced too low will also find fewer buyers, because some holders have minimum price requirements due to low price (e.g. penny) stocks tending to be more speculative and volatile. So, different funds tracking the same index might pick different price points to satisfy demand that is not being filled by other funds selling at a different price point.\"",
"title": ""
},
{
"docid": "405474",
"text": "The difference is that Yahoo is showing the unadjusted price that the security traded for on that date, while google is adjusting for price splits. This means that Google is showing how much you would have had to pay to get what is now one share. Since 1979, JNJ has split 3-for-1 once, and 2-for-1 four times. 3x2x2x2x2 = 48. If you bought 1 share at that time, you would now have 48 shares today. Yahoo is showing a price of $66 for what was then 1 share. $66/48 = 1.375, which Google rounds to 1.38. You can see this if you get the prices from May 14-21, 1981. The stock split 3-for-1, and the price dropped from 108 to 36.38. Yahoo's adjusted close column has not been accurate since they re-wrote the Finance website. It now just represents the closing price. The other relevant field on Yahoo is the Adj. Close. This adjusts for splits, but also adjusts for dividends. Hence why this doesn't match either the Google or Yahoo numbers.",
"title": ""
},
{
"docid": "317803",
"text": "\"Maria, there are a few questions I think you must consider when considering this problem. Do fundamental or technical strategies provide meaningful information? Are the signals they produce actionable? In my experience, and many quantitative traders will probably say similar things, technical analysis is unlikely to provide anything meaningful. Of course you may find phenomena when looking back on data and a particular indicator, but this is often after the fact. One cannot action-ably trade these observations. On the other hand, it does seem that fundamentals can play a crucial role in the overall (typically long run) dynamics of stock movement. Here are two examples, Technical: suppose we follow stock X and buy every time the price crosses above the 30 day moving average. There is one obvious issue with this strategy - why does this signal have significance? If the method is designed arbitrarily then the answer is that it does not have significance. Moreover, much of the research supports that stocks move close to a geometric brownian motion with jumps. This supports the implication that the system is meaningless - if the probability of up or down is always close to 50/50 then why would an average based on the price be predictive? Fundamental: Suppose we buy stocks with the best P/E ratios (defined by some cutoff). This makes sense from a logical perspective and may have some long run merit. However, there is always a chance that an internal blowup or some macro event creates a large loss. A blended approach: for sake of balance perhaps we consider fundamentals as a good long-term indication of growth (what quants might call drift). We then restrict ourselves to equities in a particular index - say the S&P500. We compare the growth of these stocks vs. their P/E ratios and possibly do some regression. A natural strategy would be to sell those which have exceeded the expected return given the P/E ratio and buy those which have underperformed. Since all equities we are considering are in the same index, they are most likely somewhat correlated (especially when traded in baskets). If we sell 10 equities that are deemed \"\"too high\"\" and buy 10 which are \"\"too low\"\" we will be taking a neutral position and betting on convergence of the spread to the market average growth. We have this constructed a hedged position using a fundamental metric (and some helpful statistics). This method can be categorized as a type of index arbitrage and is done (roughly) in a similar fashion. If you dig through some data (yahoo finance is great) over the past 5 years on just the S&P500 I'm sure you'll find plenty of signals (and perhaps profitable if you calibrate with specific numbers). Sorry for the long and rambling style but I wanted to hit a few key points and show a clever methods of using fundamentals.\"",
"title": ""
},
{
"docid": "564338",
"text": "http://www.pacificrubiales.com/investor-relations/reports.html does have financial reports on their website for the example you list. There is the potential for some data to not be easily imported into a format that Yahoo! Finance uses would be my guess for why some data may be missing though an alternative explanation for some companies would be that they may not have been around for a long enough time period to report this information,e.g. if the company is a spin-off of an existing company.",
"title": ""
},
{
"docid": "148721",
"text": "\"Funds which track the same index may have different nominal prices. From an investors point of view, this is not important. What is important is that when the underlying index moves by a given percentage, the price of the tracking funds also move by an equal percentage. In other words, if the S&P500 rises by 5%, then the price of those funds tracking the S&P500 will also rise by 5%. Therefore, investing a given amount in any of the tracking funds will produce the same profit or loss, regardless of the nominal prices at which the individual funds are trading. To see this, use the \"\"compare\"\" function available on the popular online charting services. For example, in Google finance call up a chart of the S&P500 index, then use the compare textbox to enter the codes for the various ETFs tracking the S&P500. You will see that they all track the S&P500 equally so that your relative returns will be equal from each of the tracking funds. Any small difference in total returns will be attributable to management fees and expenses, which is why low fees are so important in passive investing.\"",
"title": ""
},
{
"docid": "100485",
"text": "On Monday, the 27th of June 2011, the XIV ETF underwent a 10:1 share split. The Yahoo Finance data correctly shows the historic price data adjusted for this split. The Google Finance data does not make the adjustment to the historical data, so it looks like the prices on Google Finance prior to 27 June 2011 are being quoted at 10 times what they should be. Coincidentally, the underlying VIX index saw a sudden surge on the Friday (24 June) and continued on the Monday (27 June), the date that the split took effect. This would have magnified the bearish moves seen in the historic price data on the XIV ETF. Here is a link to an article detailing the confusion this particular share split caused amongst investors. It appears that Google Finance was not the only one to bugger it up. Some brokers failed to adjust their data causing a lots of confusion amongst clients with XIV holdings at the time. This is a recurring problem on Google Finance, where the historic price data often (though not always) fails to account for share splits.",
"title": ""
},
{
"docid": "343042",
"text": "I work on a buy-side firm, so I know how these small data issues can drive us crazy. Hope my answer below can help you: Reason for price difference: 1. Vendor and data source Basically, data providers such as Google and Yahoo redistribute EOD data by aggregating data from their vendors. Although the raw data is taken from the same exchanges, different vendors tend to collect them through different trading platforms. For example, Yahoo, is getting stock data from Hemscott (which was acquired by Morningstar), which is not the most accurate source of EOD stocks. Google gets data from Deutsche Börse. To make the process more complicated, each vendor can choose to get EOD data from another EOD data provider or the exchange itself, or they can produce their own open, high, low, close and volume from the actual trade tick-data, and these data may come from any exchanges. 2. Price Adjustment For equities data, the re-distributor usually adjusts the raw data by applying certain customized procedures. This includes adjustment for corporate actions, such as dividends and splits. For futures data, rolling is required, and back-ward and for-warding rolling can be chosen. Different adjustment methods can lead to different price display. 3. Extended trading hours Along with the growth of electronic trading, many market tends to trade during extended hours, such as pre-open and post-close trading periods. Futures and FX markets even trade around the clock. This leads to another freedom in price reporting: whether to include the price movement during the extended trading hours. Conclusion To cross-verify the true price, we should always check the price from the Exchange where the asset is actually traded. Given the convenience of getting EOD data nowadays, this task should be easy to achieve. In fact, for professional traders and investors alike, they will never reply price on free providers such as Yahoo and Google, they will most likely choose Bloomberg, Reuters, etc. However, for personal use, Yahoo and Google should both be good choices, and the difference is small enough to ignore.",
"title": ""
},
{
"docid": "189341",
"text": "Another possibly more flexible option is Yahoo finance here is an example for the dow.. http://finance.yahoo.com/q/hp?s=%5EDJI&a=9&b=1&c=1928&d=3&e=10&f=2012&g=d&z=66&y=0 Some of the individual stocks you can dl directly to a spreadsheet (not sure why this isn't offer for indexs but copy and paste should work). http://finance.yahoo.com/q/hp?s=ACTC.OB+Historical+Prices",
"title": ""
},
{
"docid": "553377",
"text": "\"You could use any of various financial APIs (e.g., Yahoo finance) to get prices of some reference stock and bond index funds. That would be a reasonable approximation to market performance over a given time span. As for inflation data, just googling \"\"monthly inflation data\"\" gave me two pages with numbers that seem to agree and go back to 1914. If you want to double-check their numbers you could go to the source at the BLS. As for whether any existing analysis exists, I'm not sure exactly what you mean. I don't think you need to do much analysis to show that stock returns are different over different time periods.\"",
"title": ""
},
{
"docid": "365799",
"text": "The correct p/e for bp.l is 5.80. Bp.l is on the London stock exchange and prices are in local currency. The share price of 493 is reported in pence (not dollars). The EPS is reported in pounds. Using .85 pounds = 85 pence, you calculate the EPS as follows: 493.40/85 = 5.80 PE Yahoo totally screwed up. They converted the .85 pounds into US dollars ($1.34) but didn't convert the 493 pence. By using the 493 as dollars, they got 493.9/1.34 = 368 pe! Notice that Yahoo reports the American Depository Shares (symbol 'BP') with an EPS of $8.06. That correctly reflects that there are 6 shares of BP.l per ADS (1.34 * 6 = 8.04). But why is the share price listed at $46.69? Well... 493 GBp (pence) = 4.93 pounds 4.93 pounds = 7.73 USD 7.73 USD * 6 shares per ADS = 46.38 USD",
"title": ""
},
{
"docid": "91430",
"text": "\"What you need to do is go to yahoo finance and look at different stock's P/E ratios. You'll quickly see that the stocks can be sorted by this number. It would be an interesting exercise to get an idea of why P/E isn't a fixed number, how certain industries cluster around a certain number, but even this isn't precise. But, it will give you an idea as to why your question has no answer. \"\"Annual earnings are $1. What is the share price?\"\" \"\"Question has no answer\"\"\"",
"title": ""
},
{
"docid": "173967",
"text": "The S&P500 is an index, not an investment by itself. The index lists a large number of stocks, and the value of the index is the price of all the stocks added together. If you want to make an investment that tracks the S&P500, you could buy some shares of each stock in the index, in the same proportions as the index. This, however, is impractical for just about everyone. Index mutual funds provide an easy way to make this investment. SPY is an ETF (exchange-traded mutual fund) that does the same thing. An index CFD (contract for difference) is not the same as an index mutual fund. There are a number of differences between investing in a security fund and investing in a CFD, and CFDs are not available everywhere.",
"title": ""
},
{
"docid": "215540",
"text": "\"There are several reasons to pay for data instead of using Yahoo Finance, although these reasons don't necessarily apply to you if you're only planning to use the data for personal use. Yahoo will throttle you if you attempt to download too much data in a short time period. You can opt to use the Yahoo Query Language (YQL), which does provide another interface to their financial data apart from simply downloading the CSV files. Although the rate limit is higher for YQL, you may still run into it. An API that a paid data provider exposes will likely have higher thresholds. Although the reliability varies throughout the site, Yahoo Finance isn't considered the most reliable of sources. You can't beat free, of course, but at least for research purposes, the Center for Research in Security Prices (CRSP) at UChicago and Wharton is considered the gold standard. On the commercial side, data providers like eSignal, Bloomberg, Reuters also enjoy widespread popularity. Although both the output from YQL and Yahoo's current CSV output are fairly standard, they won't necessarily remain that way. A commercial API is basically a contract with the data provider that they won't change the format without significant prior notice, but it's reasonable to assume that if Yahoo wanted to, they could make minor changes to the format and break many commercial applications. A change in Yahoo's format would likely break many sites or applications too, but their terms of use do state that Yahoo \"\"may change, suspend, or discontinue any aspect of the Yahoo! Finance Modules at any time, including the availability of any Yahoo! Finance Modules. Yahoo! may also impose limits on certain features and services or restrict your access to parts or all of the Yahoo! Finance Modules or the Yahoo! Web site without notice or liability.\"\" If you're designing a commercial application, a paid provider will probably provide technical support for their API. According to Yahoo Finance's license terms, you can't use the data in a commercial application unless you specifically use their \"\"badges\"\" (whatever those are). See here. In this post, a Yahoo employee states: The Finance TOS is fairly specific. Redistribution of data is only allowed if you are using the badges the team has created. Otherwise, you can use YQL or whatever method to obtain data for personal use. The license itself states that you may not: sell, lease, or sublicense the Yahoo! Finance Modules or access thereto or derive income from the use or provision of the Yahoo! Finance Modules, whether for direct commercial or monetary gain or otherwise, without Yahoo!'s prior, express, written permission In short, for personal use, Yahoo Finance is more than adequate. For research or commercial purposes, a data provider is a better option. Furthermore, many commercial applications require more data than Yahoo provides, e.g. tick-by-tick data for equities, derivatives, futures, data on mergers, etc., which a paid data source will likely provide. Yahoo is also known for inaccuracies in its financial statements; I can't find any examples at the moment, but I had a professor who enjoyed pointing out flaws in the 10K's that he had come across. I've always assumed this is because the data were manually entered, although I would assume EDGAR has some method for automatic retrieval. If you want data that are guaranteed to be accurate, or at least have a support contract associated with them so you know who to bother if it isn't, you'll need to pay for it.\"",
"title": ""
},
{
"docid": "32282",
"text": "As others have pointed out, the value of Apple's stock and the NASDAQ are most likely highly correlated for a number of reasons, not least among them the fact that Apple is part of the NASDAQ. However, because numerous factors affect the entire market, or at least a significant subset of it, it makes sense to develop a strategy to remove all of these factors without resorting to use of an index. Using an index to remove the effect of these factors might be a good idea, but you run the risk of potentially introducing other factors that affect the index, but not Apple. I don't know what those would be, but it's a valid theoretical concern. In your question, you said you wanted to subtract them from each other, and only see an Apple curve moving around a horizontal line. The basic strategy I plan to use is similar but even simpler. Instead of graphing Apple's stock price, we can plot the difference between its stock price on business day t and business day t-1, which gives us this graph, which is essentially what you're looking for: While this is only the preliminaries, it should give you a basic idea of one procedure that's used extensively to do just what you're asking. I don't know of a website that will automatically give you such a metric, but you could download the price data and use Excel, Stata, etc. to analyze this. The reasoning behind this methodology builds heavily on time series econometrics, which for the sake of simplicity I won't go into in great detail, but I'll provide a brief explanation to satisfy the curious. In simple econometrics, most time series are approximated by a mathematical process comprised of several components: In the simplest case, the equations for a time series containing one or more of the above components are of the form that taking the first difference (the procedure I used above) will leave only the random component. However, if you want to pursue this rigorously, you would first perform a set of tests to determine if these components exist and if differencing is the best procedure to remove those that are present. Once you've reduced the series to its random component, you can use that component to examine how the process underlying the stock price has changed over the years. In my example, I highlighted Steve Jobs' death on the chart because it's one factor that may have led to the increased standard deviation/volatility of Apple's stock price. Although charts are somewhat subjective, it appears that the volatility was already increasing before his death, which could reflect other factors or the increasing expectation that he wouldn't be running the company in the near future, for whatever reason. My discussion of time series decomposition and the definitions of various components relies heavily on Walter Ender's text Applied Econometric Time Series. If you're interested, simple mathematical representations and a few relevant graphs are found on pages 1-3. Another related procedure would be to take the logarithm of the quotient of the current day's price and the previous day's price. In Apple's case, doing so yields this graph: This reduces the overall magnitude of the values and allows you to see potential outliers more clearly. This produces a similar effect to the difference taken above because the log of a quotient is the same as the difference of the logs The significant drop depicted during the year 2000 occurred between September 28th and September 29th, where the stock price dropped from 26.36 to 12.69. Apart from the general environment of the dot-com bubble bursting, I'm not sure why this occurred. Another excellent resource for time series econometrics is James Hamilton's book, Time Series Analysis. It's considered a classic in the field of econometrics, although similar to Enders' book, it's fairly advanced for most investors. I used Stata to generate the graphs above with data from Yahoo! Finance: There are a couple of nuances in this code related to how I defined the time series and the presence of weekends, but they don't affect the overall concept. For a robust analysis, I would make a few quick tweaks that would make the graphs less appealing without more work, but would allow for more accurate econometrics.",
"title": ""
},
{
"docid": "313421",
"text": "\"The Dow Jones Industrial Average (DJIA) is a Price-weighted index. That means that the index is calculated by adding up the prices of the constituent stocks and dividing by a constant, the \"\"Dow divisor\"\". (The value of the Dow divisor is adjusted from time to time to maintain continuity when there are splits or changes in the roster.) This has the curious effect of giving a member of the index influence proportional to its share price. That is, if a stock costing $100 per share goes up by 1%, that will change the index by 10 times as much as if a stock costing $10 per share goes up by the same 1%. Now look at the price of Google. It's currently trading at just a whisker under $700 per share. Most of the other stocks in the index trade somewhere between $30 and $150, so if Google were included in the index it would contribute between 5 and 20 times the weight of any other stock in the index. That means that relatively small blips in Google's price would completely dominate the index on any given day. Until June of 2014, Apple was in the same boat, with its stock trading at about $700 per share. At that time, Apple split its stock 7:1, and after that its stock price was a little under $100 per share. So, post-split Apple might be a candidate to be included in the Dow the next time they change up the components of the index. Since the Dow is fixed at 30 stocks, and since they try to keep a balance between different sectors, this probably wouldn't happen until they drop another technology company from the lineup for some reason. (Correction: Apple is in the DJIA and has been for a little over a year now. Mea culpa.) The Dow's price-weighting is unusual as stock indices go. Most indices are weighted by market capitalization. That means the influence of a single company is proportional to its total value. This causes large companies like Apple to have a lot of influence on those indices, but since market capitalization isn't as arbitrary as stock price, most people see that as ok. Also, notice that I said \"\"company\"\" and not \"\"stock\"\". When a company has multiple classes of share (as Google does), market-cap-weighted indices include all of the share classes, while the Dow has no provision for such situations, which is another, albeit less important, reason why Google isn't in the Dow. (Keep this in mind the next time someone offers you a bar bet on how many stocks are in the S&P 500. The answer is (currently) 505!) Finally, you might be wondering why the Dow uses such an odd weighting in its calculations. The answer is that the Dow averages go back to 1896, when Charles Dow used to calculate the averages by hand. If your only tools are a pencil and paper, then a price-weighted index with only 30 stocks in it is a lot easier to calculate than a market-cap-weighted index with hundreds of constituents. About the Dow Jones Averages. Dow constituents and prices Apple's stock price chart. The split in 2014 is marked. (Note that prices before the split are retroactively adjusted to show a continuous curve.)\"",
"title": ""
},
{
"docid": "591089",
"text": ".INX (the S&P 500 index itself) does not include reinvested dividens. You can figure total return by going to Yahoo finance, historical data. Choose the start year, and end year. You should find that data for SPY (going back to 1993) will show an adjusted close, and takes dividends into account. This isn't perfect as SPY has a .09% expense ratio, but it's better than just the S&P index. One of the more popular Dow ETF is DIA, this will let you similarly track the Dow while accounting for dividends.",
"title": ""
},
{
"docid": "477162",
"text": "The GuruFocus Link is just reporting the high and low price of the quarter. Price Range (Average) – The estimated trade prices. The average price is calculated from the time weighted average during the period. If no price range is shown, the trade prices are estimated trade prices, which are more accurate estimates. AAPL: $420.05 - $549.03 ($467.26) The numbers for the high and low match what I found for AAPL on Yahoo Finance. Keep in mind their definition uses estimate 3 times.",
"title": ""
},
{
"docid": "239137",
"text": "If you use Google Finance, you will get incorrect results because Google Finance does not show the dividend history. Since your requirement is that dividends are re-invested, you should use Yahoo Finance instead, downloading the historical 'adjusted' price.",
"title": ""
},
{
"docid": "107462",
"text": "So, why or why should I not invest in the cheaper index fund? They are both same, one is not cheaper than other. You get something that is worth $1000. To give a simple illustration; There is an item for $100, Vanguard creates 10 Units out of this so price per unit is $10. Schwab creates 25 units out of this, so the per unit price is $4. Now if you are looking at investing $20; with Vanguard you would get 2 units, with Schwab you would get 5 units. This does not mean one is cheaper than other. Both are at the same value of $20. The Factors you need to consider are; Related question What differentiates index funds and ETFs?",
"title": ""
},
{
"docid": "24979",
"text": "There is most likely an error in the WSJ's data. Yahoo! Finance reports the P/E on the Russell 2000 to be 15 as of 8/31/11 and S&P 500 P/E to be 13 (about the same as WSJ). Good catch, though! E-mail WSJ, perhaps they will be grateful.",
"title": ""
},
{
"docid": "532178",
"text": "\"It's almost like why don't you wake up in the morning feeling exactly like you slept the earlier night? yeah, once in a while that'll happen, but it's not designed to be that way. Stuff happens. The close of the stock is what happened at 4 PM (for US stocks). The \"\"open\"\" is simply the first price ever, or an open price auction like NimChimpsky said. Most things that trade have an open/close cycle, even what seemingly trades all the time (some markets trade 23 hours). Forex trades in different exchanges which have overlapping timing but each market will have an open, high, low and close for each day - for what is the same underlying currency. Also, it's not exactly true that close<>open. Take the GS chart, Oct 1 2010 and Oct 4 2010 (there was a weekend in between). The Oct 1 close was the same as the Oct 4 open. Note that Oct 4 was a down day so it's in red - the open is the upper end of the body (not including the wick), and Oct 1 was an up day so its close was the upper end too. (Candles are drawn so that the open ends of the wicks are the High and Low of the period respectively, and the lower end of the body is the open if it was an up-day, meaning the stock closed higher than it opened, and the body in coloured green below. If the stock went down that day from the open, the body's in red and the lower end is the close. Vice-versa for the other end) The way to get to this: Go to yahoo finance, choose a stock, go to historical prices, click download data (you should have about 10 years of data), paste into excel, insert a formula to check if prev day's close = current day's open, and I'm sure you'll see at least one instance per stock.\"",
"title": ""
},
{
"docid": "181909",
"text": "\"The Yahoo Finance API is no longer available, so Finance::Quote needs to point at something else. Recent versions of Finance::Quote can use AlphaVantage as a replacement for the Yahoo Finance API, but individual users need to acquire and input an AlphaVantage API key. Pretty decent documentation for how to this is available at the GnuCash wiki. Once you've followed the directions on the wiki and set the API key, you still need to tell each individual security to use AlphaVantage rather than Yahoo Finance: As a warning, I've been having intermittent trouble with AlphaVantage. From the GnuCash wiki: Be patient. Alphavantage does not have the resources that Yahoo! did and it is common for quote requests to time out, which GnuCash will present as \"\"unknown error\"\". I've certainly been experiencing those errors, though not always.\"",
"title": ""
},
{
"docid": "546379",
"text": "Google Finance and Yahoo Finance have been transitioning their API (data interface) over the last 3 months. They are currently unreliable. If you're just interested in historical price data, I would recommend either Quandl or Tiingo (I am not affiliated with either, but I use them as data sources). Both have the same historical data (open, close, high, low, dividends, etc.) on a daily closing for thousands of Ticker symbols. Each service requires you to register and get a unique token. For basic historical data, there is no charge. I've been using both for many months and the data quality has been excellent and API (at least for python) is very easy! If you have an inclination for python software development, you can read about the drama with Google and Yahoo finance at the pandas-datareader group at https://github.com/pydata/pandas-datareader.",
"title": ""
},
{
"docid": "357685",
"text": "The big websites, Yahoo and the like, only give the 10 biggest positions of any fund. Download the annual report of the fund, go to page 18, you will find the positions on the 31st of December. However the actual positions could be different. The same applies to all funds. You need the annual report.",
"title": ""
},
{
"docid": "66753",
"text": "\"Asking why the p/e was so high is best answered \"\"because reported earnings were so low\"\". Recall that the S&P500 bottomed in early March 2009 when the panic of the financial crisis reached exhaustion. As noted on the page you have linked, the reported p/e ratios are computed using reported earnings from the trailing twelve months. During those twelve months the banks were writing down all of the bad debt associated with the mortgage backed securities that has lost so much value. This meant that the banks were reporting negative earnings. Since the financial sector is a large part of the S&P500, this alone had an enormous effect on the index p/e. However, the problem was compounded by a general collapse in earnings across the economy as consumers reacted to the resulting uncertainty. The same site reports earnings for the previous years at $17.11 for the S&P500, compared to $76.17 for the year prior to 2008. That is a collapse of about 78% in earnings. Although the S&P500 has suffered badly during this time, stock market investors being forward looking were starting to price in improved earnings by May 2009. Indeed, the S&P500 was up about 33% in just two months, from its low in March2009 to mid May2009. Thus, by May of 2009 prices were not suffering to the same extent as reported trailing earnings. This would account for the anomalous p/e value reporting in May2009.\"",
"title": ""
},
{
"docid": "535343",
"text": "Yahoo Finance's Historical Prices section allows you to look up daily historical quotes for any given stock symbol, you don't have to hit a library for this information. Your can choose a desired time frame for your query, and the dataset will include High/Low/Close/Volume numbers. You can then download a CSV version of this report and perform additional analysis in a spreadsheet of your choice. Below is Twitter report from IPO through yesterday: http://finance.yahoo.com/q/hp?s=TWTR&a=10&b=7&c=2013&d=08&e=23&f=2014&g=d",
"title": ""
},
{
"docid": "465536",
"text": "\"P/E is Price divided by Earnings Per Share (EPS). P/E TTM is Price divided by the actual EPS earned over the previous 12 months - hence \"\"Trailing Twelve Month\"\". In Forward P/E is the \"\"E\"\" is the average of analyst expectations for the next year in EPS. Now, as to what's being displayed. Yahoo shows EPS to be 1.34. 493.90/1.34 = P/E of 368.58 Google shows EPS to be 0.85. 493.40/0.85 = P/E of 580.47 (Prices as displayed, respectively) So, by the info that they are themselves displaying, it's Google, not Yahoo, that's displaying the wrong P/E. Note that the P/E it is showing is 5.80 -- a decimal misplacement from 580 Note that CNBC shows the Earnings as 0.85 as well, and correctly show the P/E as 580 http://data.cnbc.com/quotes/BP.L A quick use of a currency calculator reveals a possible reason why EPS is listed differently at yahoo. 0.85 pounds is 1.3318 dollars, currently. So, I think the Yahoo EPS listing is in dollars. A look at the last 4 quarters on CNBC makes that seem reasonable: http://data.cnbc.com/quotes/BP.L/tab/5 those add up to $1.40.\"",
"title": ""
}
] |
53073
|
Nice & Slow was released by Usher.
|
[
{
"docid": "Nice_&_Slow",
"text": "`` Nice & Slow '' is a 1998 single from Usher 's second album My Way . It became his first number-one single on the Billboard Hot 100 chart in early 1998 . The song was written by Usher , Brian and Brandon Casey of the R&B group Jagged Edge , Manuel Seal Jr. and Jermaine Dupri .",
"title": ""
}
] |
[
{
"docid": "My_Way_(Usher_song)",
"text": "`` My Way '' is a 1998 single from Usher 's 1997 album of the same name . It features an uncredited rap and background vocals from Jermaine Dupri . Despite moderate airplay , the single sold well and reached # 2 on the U.S. Billboard Hot 100 . Its rise to # 1 , however , was halted due to the success of the mega-hit `` The Boy Is Mine '' by Brandy and Monica , during its 13-week run atop the summit . Due to the disappointment of the `` Nice and Slow '' single in the U.K. , `` My Way '' was not released as a single there . The song features in the Refrain part of the lyrics and the music of the song by Lil ' Troy `` Wan na Be a Baller '' from his debut album `` Sittin ' Fat Down South '' published officially one month before Usher 's song .",
"title": ""
},
{
"docid": "My_Way_(Usher_album)",
"text": "My Way is the second studio album by American singer Usher . It was released on September 16 , 1997 by LaFace Records , in North America . The album features guest appearances from Monica , Jermaine Dupri , and Lil ' Kim . The album was supported by three singles ; including these platinum-selling singles with `` Nice & Slow '' , `` My Way '' , and `` You Make Me Wan na ... '' . With most of the album production by Babyface and Dupri , the album debuted at number 15 on Billboard 200 selling 66,000 units and at number 4 on Billboard R&B / Hip-Hop Albums chart . The album eventually topped the Billboard R&B / Hip-Hop Albums chart for 3 weeks , while it had peaked at number 4 on the Billboard 200 and became a commercial success . It earned the record a six-platinum certifications in the United States . My Way earned Usher Grammy-nominations and became his breakthrough album . My Way has sold over 6 million in the United States alone , and over 7 million worldwide .",
"title": ""
},
{
"docid": "Nice_'N'_Slow",
"text": "`` Nice 'N' Slow '' is a 1988 single recorded by Freddie Jackson and written by Barry J. Eastmond and Jolyon Skinner . As the lead single from his third album , Do n't Let Love Slip Away , it was Jackson 's seventh number one on the Hot Black Singles chart , staying at the top spot for three weeks . `` Nice 'N' Slow '' was the last of Jackson 's releases to chart on the Hot 100 , peaking at number sixty-one .",
"title": ""
},
{
"docid": "Dive_(Usher_song)",
"text": "`` Dive '' is a song recorded by American recording artist Usher for his seventh studio album Looking 4 Myself ( 2012 ) . It was written and produced by Rico Love , Jim Jonsin , Danny Morris and Frank Romano . `` Dive '' is a slow-paced R&B ballad with elements of pop music , with Usher making use of his falsetto range . Its lyrics use the metaphor of diving , which was interpreted by critics to discuss a commitment to a relationship . The song was announced by Usher via Twitter as the fifth single from Looking 4 Myself on August 21 , 2012 . It was released to urban radio on August 28 , 2012 . `` Dive '' was received well by critics , who praised its production and Usher 's vocals , particularly his falsetto . An accompanying music video directed by Chris Applebaum , portrays Victoria 's Secret Angel model Chanel Iman as Usher 's love interest , showing them being intimate and making love in several scenes . Upon the release of Looking 4 Myself , the song debuted at number 50 on the South Korea Gaon International Chart , with sales of 6,546 digital copies . `` Dive '' peaked at number 34 on the US Hot R&B / Hip-Hop Songs , remaining on the chart for twelve weeks before dropping out .",
"title": ""
},
{
"docid": "Usher_discography",
"text": "American recording artist and entertainer Usher has released eight studio albums , nine compilation albums , eight extended plays , and fifty-three singles ( including eleven as a featured artist ) . His music has been released on the LaFace , Arista , Jive , and RCA record labels . 23 million of his albums were shipped in the United States , and sold over 43 million albums worldwide , leading to a combined 75 million records and making him one of the best selling music artists . He also has 9 Hot 100 number-one singles ( all as a lead ) and 18 Hot 100 top-ten singles . In 1994 , Usher released his self-titled debut album in North America , producing three singles that had moderate chart success , and the album sold more than 500,000 copies . His follow-up 1997 album My Way sold 8 million copies , becoming his breakthrough album . It was certified six-times platinum in the US , and spawned three successful singles , including his first US Billboard Hot 100 number-one hit `` Nice & Slow '' . Usher 's success continued in 2001 with his third studio album 8701 . It debuted at number four on the Billboard 200 . The album produced two number-one singles -- `` U Remind Me '' and `` U Got It Bad '' . It has sold more than 4.7 million copies and has been certified four-times platinum in the US . Its worldwide sales stand at over 8 million . Usher 's success increased in 2004 , with the release of his fourth studio album Confessions . It was his first US number-one album , and had the highest first-week sales for an R&B artist , with 1.1 million copies sold . It spawned four Hot 100 number-one hits ; `` Yeah ! '' , `` Burn '' , `` Confessions Part II '' , and `` My Boo '' . `` Yeah ! '' and `` Burn '' stayed atop the Hot 100 for a combined 20 weeks and were the best-selling singles of 2004 , ranking first and second , respectively . Confessions received a diamond certification from the Recording Industry Association of America ( RIAA ) , and has sold over 20 million copies worldwide . The album ranked second on the 2000 -- 2009 Billboard 200 Decade-end chart . In 2008 , Usher issued Here I Stand . Its lead single `` Love in This Club '' topped the Hot 100 , marking Usher 's eighth number-one on the chart . Follow-up single `` Love in This Club Part II '' became a top 20 hit , while the album 's fourth and fifth singles , `` Trading Places '' and `` Moving Mountains '' , charted below the top 40 . Here I Stand was deemed as a commercial failure relative to Confessions , which had sold nineteen million copies worldwide compared to Here I Stand 's two million during the same period . It was certified platinum by the RIAA and has sold 1.3 million copies in the United States . Its worldwide sales stand over 5 million copies . In 2010 , Usher released Raymond v. Raymond , and it became his third consecutive number-one album . The album produced five singles : `` Papers '' , `` Hey Daddy '' , `` Lil Freak '' and `` There Goes My Baby '' all reaching the Hot 100 's top 40 , while `` Papers '' and `` There Goes My Baby '' topped the Hot R&B / Hip-Hop Songs chart . The album 's two other singles , `` OMG '' and `` More '' , achieved worldwide success , with `` OMG '' topping the Hot 100 to give him his ninth number-one single . Raymond v. Raymond was certified platinum by the RIAA , and sold 1.3 million copies in the US . It sold over 2 million copies worldwide . In the same year , a follow-up set entitled Versus was released , and became Usher 's sixth top ten album . The EP 's lead single `` DJ Got Us Fallin ' in Love '' reached the top ten in many countries . Usher 's seventh studio album Looking 4 Myself was released in June 2012 and became his fourth number-one album in the US . Its first single `` Climax '' peaked in the top twenty on the Hot 100 , and topped the Hot R&B / Hip-Hop Songs chart for eleven weeks . The album 's second single `` Scream '' reached the top ten in various countries , including the US , Canada and the UK . In 2014 , Usher released `` Good Kisser '' , `` She Came to Give It to You '' and `` I Do n't Mind '' as successes in the UK , with the latter reaching the top 15 of the Hot 100 and topping the Hot R&B / Hip-Hop Songs to give him his 13th number-one on that chart .",
"title": ""
},
{
"docid": "Climax_(Usher_song)",
"text": "`` Climax '' is a song by American R&B singer Usher . It was released on February 22 , 2012 , by RCA Records as the lead single from 2012 studio album Looking 4 Myself . The song was written by Usher , Ariel Rechtshaid , Redd Stylez , and Diplo , who also produced the song . Usher and Diplo worked on the song for two months as part of their collaboration for the former 's album . The song is a quiet storm slow jam with electronic influences , and lyrics about the turning point of a relationship . According to Usher , the song is primarily about the complications of a relationship , despite the lyrics ' sexual overtones . As a single , `` Climax '' debuted at number 81 on the Billboard Hot 100 , with 31,000 digital units sold in its first week . It peaked at number 17 and charted for 20 weeks , and also reached number one on the Billboard Hot R&B / Hip-Hop Songs , becoming Usher 's 12th number-one single on the chart . `` Climax '' was well received by music critics , who commended its musical direction , Usher 's singing , and Diplo 's production . Rolling Stone and Entertainment Weekly named it one of the best singles of 2012 . In 2013 , `` Climax '' won Usher a Grammy Award for Best R&B Performance .",
"title": ""
},
{
"docid": "Nice_and_Smooth_(album)",
"text": "Nice & Smooth is the debut album of the hip-hop duo Nice & Smooth . The album is notable for its sense of humor and comedy rhymes . Although the album contains explicit lyrics on it , it is also at its best with Greg Nice 's crazy rhyming with humor and Smooth B 's slow lover rhymes . The release singles of the album are `` Early to Rise '' and `` Funky for You . '' This was the duo 's only release on Fresh/Sleeping Bag Records before it signed with Def Jam Recordings sub-label RAL Records . It was included in The Source 's 100 Best Rap Albums . It was one of three titles acquired by Priority Records when Sleeping Bag went out of business in 1992 .",
"title": ""
},
{
"docid": "Trading_Places_(song)",
"text": "`` Trading Places '' is a song by American recording artist Usher . Released on October 17 , 2008 as the fifth and final single from his fifth studio album Here I Stand , Usher wrote the song with The-Dream and Carlos `` Los Da Mystro '' McKinney . Produced by McKinney , it is a slow-tempo R&B number with hip hop influences , and focuses on an idea of role reversal in a relationship . The song received mixed reviews from critics ; its production drew differing opinions . It appeared on the US Billboard Hot 100 and Hot R&B / Hip-Hop Songs , peaking at numbers forty-five and four , respectively . A music video was filmed for the song , which demonstrated intimate sexual scenes , and promoted Usher 's lingerie line . Usher performed `` Trading Places '' on both his One Night Stand : Ladies Only Tour ( 2008 ) and OMG Tour ( 2010 -- 11 ) .",
"title": ""
},
{
"docid": "Love_in_This_Club",
"text": "`` Love in This Club '' is a song by American R&B singer Usher . Featuring rapper Young Jeezy , it was released on February 22 , 2008 as the lead single from Usher 's fifth studio album , Here I Stand . The song was written by Usher , Polow da Don , Young Jeezy , Darnell Dalton , Ryon Lovett , Lamar Taylor and Keith Thomas , and produced by da Don with a Las Vegas-inspired synth-driven beat . Its lyrics refer to seducing someone in a nightclub . The song was originally leaked by da Don prior to its release . `` Love in This Club '' received mixed reviews from critics , who praised the song 's production , but criticized it for its slow tempo and lack of originality . The song topped the Billboard Hot 100 as well as the New Zealand Singles Chart , while appearing on multiple other record charts . The accompanying music video , which received a nomination at the 2008 MTV Video Music Awards , features cameo appearances from several musicians . In the video , R&B singer Keri Hilson plays Usher 's love interest in a club . Usher performed the song at the 2008 BET Awards , as well as on several television programs . A remix of the song , titled `` Love in This Club Part II '' , features Beyoncé and Lil Wayne .",
"title": ""
},
{
"docid": "Usher_(musician)",
"text": "Usher Raymond IV ( born October 14 , 1978 ) is an American singer , songwriter , dancer , and actor . Born in Dallas , Texas but raised and lived in Chattanooga , Tennessee until moving to Atlanta , Georgia . At the age of 12 , his mother put him in local singing competitions , before catching the attention of a music A&R from LaFace Records . In 1994 , he released his self-titled debut album , Usher . He rose to fame in the late 1990s with the release of his sophomore album My Way ( 1997 ) , which spawned his first U.S. Billboard Hot 100 number-one single , `` Nice & Slow '' , amongst top-two singles `` You Make Me Wan na ... '' and `` My Way '' . 8701 ( 2001 ) produced the number-one singles `` U Remind Me '' and `` U Got It Bad '' , and top-three single `` U Do n't Have to Call '' . It sold 8 million copies worldwide and won his first two Grammy Awards as Best Male R&B Vocal Performance in 2002 and 2003 . Confessions ( 2004 ) established him as one of the best-selling musical artists of the 2000s decade , selling 20 million copies worldwide . Bolstered by its four consecutive Billboard Hot 100 number one singles ; `` Yeah ! '' , `` Burn '' , `` Confessions Part II '' , and `` My Boo '' , it has been certified Diamond by the RIAA . Here I Stand ( 2008 ) and Raymond v. Raymond ( 2010 ) , debuted atop of the Billboard 200 , and produced the Billboard Hot 100 number-one singles `` Love in This Club '' and `` OMG '' . The EP , Versus , also produced the Hot 100 top-five single `` DJ Got Us Fallin ' in Love '' . Looking 4 Myself ( 2012 ) , also debuted atop the Billboard 200 chart and produced the Hot 100 top-ten single `` Scream '' . Raymond v. Raymond and Looking 4 Myself received Grammy Awards for R&B singles `` There Goes My Baby '' and `` Climax '' . Hard II Love ( 2016 ) peaked at number five on the Billboard 200 albums chart . Usher has sold 23.8 million albums and 38.2 million digital songs in the United States . To date , his worldwide sales stand at 43 million albums and 75 million records overall , making him one of the best-selling music artists of all time . Usher has won numerous awards and accolades including 18 Billboard Music Awards and 8 Grammy Awards . At the end of 2009 , Billboard named him the second most successful artist of the 2000s decade , the number-one Hot 100 artist of the 2000s decade , and ranked Confessions as the top solo album of the 2000s decade . Billboard also placed him at number 6 on their list of `` Top 50 R&B / Hip-Hop Artists of the Past 25 Years '' . Usher has attained 9 US Hot 100 number-one singles . Considered an icon and sex symbol , he was inducted into the Georgia Music Hall of Fame and Hollywood Walk of Fame . In 2008 , he started his own record label Raymond-Braun Media Group ( RBMG ) ; a joint venture with talent manager Scooter Braun that includes Canadian singer Justin Bieber .",
"title": ""
},
{
"docid": "U_Got_It_Bad",
"text": "`` U Got It Bad '' is a song by American recording artist Usher , released through Arista as the second single from his third studio album , 8701 ( 2001 ) . It was written by Usher , Jermaine Dupri and Bryan-Michael Cox , and produced by the former and co-produced by the latter . It was released as a CD Single in the US on September 4 , 2001 . `` U Got It Bad '' is an R&B ballad that , according to MTV , incorporates `` digi-coustic '' guitars , a `` slow-burning bass line '' and `` sex funk '' drums . The lyrics notably contain some quick direct allusions to other soul music ballads , mainly Maxwell 's `` Fortunate '' , and Prince 's `` Adore '' . `` U Got It Bad '' topped the US Billboard Hot 100 chart for one week before being replaced for four weeks by Nickelback 's `` How You Remind Me '' . `` U Got It Bad '' then returned to number one , going on to stay atop for five consecutive weeks . With the song and previous single `` U Remind Me '' , Usher was the only solo male act of 2001 to have a number 1 hit on the Hot 100 . The song 's music video features TLC 's Chilli as Usher 's love interest . Due the success of the song , it was featured on the 2001 compilation album Now That 's What I Call Music ! 8",
"title": ""
},
{
"docid": "Abbott_Payson_Usher",
"text": "Abbott Payson Usher ( 1883 -- June 18 , 1965 ) was an American economic historian . The Society of the History of Technology has awarded the Abbott Payson Usher Prize , named in his honor , annually since 1961 . In the late 1920s Usher , the American historian Lewis Mumford and the Swiss art historian Sigfried Giedion began to systematically investigate the social consequences of technology . In A History of Mechanical Inventions he argued that technological innovation was a slow , collective process with many contributors , not relying on the genius of great inventors .",
"title": ""
},
{
"docid": "John_Usher_(cricketer)",
"text": "John Usher ( 26 February 1859 -- 10 August 1905 ) was an Irish first-class cricketer , who played one match for Yorkshire County Cricket Club in 1888 . Born in Templemore , County Tipperary , Ireland , Usher was a slow left arm orthodox spinner , who took two wickets for 31 runs , and scored seven runs at an average of 3.50 , in his match against the MCC . The MCC won the game by 103 runs . Usher died in August 1905 in Haslingden , Lancashire , England .",
"title": ""
},
{
"docid": "U_Remind_Me",
"text": "`` U Remind Me '' is a song by American entertainer Usher . It was written by Anita McCloud and Edmund Clement and produced by the latter along with Jimmy Jam and Terry Lewis for Usher 's third studio album 8701 ( 2001 ) . A fast-paced mid-tempo R&B track , the song is about a man who meets a woman who seems like a nice catch , but he decides not to enter a relationship with her because she looks too much like an ex-girlfriend with whom he had a bad breakup . The song served as the lead American single from 8701 following the release of previous single `` Pop Ya Collar '' which was only included in some editions of the album . A commercial success , `` U Remind Me '' topped the US Billboard Hot 100 on July 7 , 2001 and also reached the top five in Australia , Belgium , France , the Netherlands , New Zealand , and the United Kingdom . Critically acclaimed , the song won Usher his first Grammy Award for Best Male R&B Vocal Performance in 2002 . Its accompanying music video features Chilli of TLC as one the female leads .",
"title": ""
},
{
"docid": "Nice_(programming_language)",
"text": "Nice is an object-oriented programming language released under the GNU General Public License . It features a powerful type system which can help eliminate many common bugs , such as null pointer dereferences and invalid casts , by detecting potential runtime errors at compile-time ; the goal of the designers was to provide safety features comparable to those found in languages such as ML and Haskell , but using a more conventional syntax . Nice aims to be feature-rich , and as such , in addition to the common features of modern object-oriented programming languages , it implements contracts in the style of Eiffel , class extensibility through multimethods , and many concepts drawn from functional programming such as anonymous functions , tuples , pattern matching ( `` value dispatch '' ) , and parametric polymorphism . Source programs are compiled to Java bytecode , and can therefore interact with libraries written in Java and other programming languages targeting the Java Virtual Machine . Work on the Nice language appears to have slowed since early 2006 .",
"title": ""
},
{
"docid": "Moving_Mountains_(song)",
"text": "`` Moving Mountains '' is a song recorded by American R&B singer Usher . It was released on May 23 , 2008 , as the third single from his fifth studio album , Here I Stand . It was written by Usher with Christopher `` Tricky '' Stewart , Kuk Harrell and The-Dream , and was produced by Stewart and The-Dream . `` Moving Mountains '' is a slow tempo ballad , with lyrics describing a love struggle . The song received mostly positive attention from critics , with comparisons made to 2004 's `` Burn '' . The song appeared on the Billboard Hot 100 and Hot R&B / Hip-Hop Songs , as well as the single charts of several European countries . It peaked highest in New Zealand , where it reached number six on the singles chart and was certified gold . The music video for `` Moving Mountains '' was filmed in front of a green screen as a sequel to the video of `` Love in This Club '' .",
"title": ""
},
{
"docid": "Usher_videography",
"text": "American entertainer Usher has released six video albums and appeared in forty-one music videos , eleven films , nine television programs , and four commercials . Usher released his debut single , `` Call Me a Mack '' in 1993 from the soundtrack Poetic Justice . Directed by Bille Woodruff , Usher appeared in the video for `` You Make Me Wan na ... '' , the lead single from his break-through album My Way ( 1997 ) . The video shows Usher flanked by four dancers , to which the scene is then replaced by five clones of Usher performing dance routines around chairs . The latter song was sung by the singer on the sitcom Moesha , where he made his television debut . Usher appeared in four episodes for the show , portraying his character , Jeremy Davis . Live ( 1999 ) was released to keep Usher 's fans satisfied during his four-year break between My Way and 8701 ( 2001 ) . The video album version was certified gold by the Recording Industry Association of America ( RIAA ) , denoting shipments of 50,000 units . During his musical break , he made his film debut in the 1998 science fiction horror film The Faculty , which received mixed reviews , but was a box office success . Following this , he starred in three films : She 's All That ( 1999 ) , Light It Up ( 1999 ) and Texas Rangers ( 2000 ) . In 2001 , Usher released his third studio album 8701 -- four music videos for singles from the album were shot . Dave Meyers directed the video for `` U Remind Me '' , in which Chilli of TLC makes a cameo appearance . Usher made several television appearances in 2002 , including Sabrina , the Teenage Witch portraying his role as The Love Doctor . The same year , he released concert video album , Usher Live Evolution 8701 , which was certified platinum by the RIAA and gold by the British Phonographic Industry ( BPI ) . In 2004 , Usher released Confessions , his fourth studio album which featured the lead single `` Yeah ! '' . Directed by Little X with co-direction by Usher , the video features blue lasers , drawing inspiration from Michael Jackson 's 1979 `` Rock with You '' video . The video for `` Yeah ! '' received four MTV Video Music Award nominations , winning the awards for Best Male Video and Best Dance Video . The same year , Usher made a guest appearance in the music for Beyoncé Knowles ' `` Naughty Girl '' . In 2005 , Usher starred in the crime-comedy film In the Mix , portraying the role of Darrell ; the film received negative reviews .",
"title": ""
},
{
"docid": "Here_I_Stand_(Usher_song)",
"text": "`` Here I Stand '' is a song by American recording artist Usher . It was sent to urban adult contemporary radio on August 18 , 2008 by LaFace Records and RCA Records as the fifth single from Usher 's fifth studio album , Here I Stand ( Usher album ) . Penned by the singer with Polow da Don , Adam Blackstone , Gerrell Gaddis , and Dre & Vidal , and produced by Dre & Vidal , `` Here I Stand '' is a slow soul ballad and contains similarities to Stevie Wonder 's music . The record received critical acclaim , and was nominated for the Best Male R&B Vocal Performance award at the 51st Grammy Awards . `` Here I Stand '' maintained a position on the United States Hot R&B / Hip-Hop Songs for several weeks in 2008 and 2009 , reaching the top twenty . It also appeared on the US Radio Songs and Bubbling Under Hot 100 Singles charts , peaking at numbers seventy-two and six , respectively .",
"title": ""
},
{
"docid": "Go_Missin'",
"text": "`` Go Missin ' '' is a song recorded by American singer-songwriter Usher . It was produced by Diplo and was released on Valentine 's Day 2013 through SoundCloud as a free download . The year before , Usher released `` Climax '' on Valentine 's Day , the lead single from his seventh studio album , Looking 4 Myself ( 2012 ) . Prior to its release , the singer tweeted that he had a `` special delivery from the cloud '' for his fans , who responded positively to the release of `` Climax '' on Valentine 's Day the preceding year . `` Go Missin ' '' contains similar characteristics to `` Climax '' ; it is a quiet storm mid-tempo R&B track , and incorporates heavy bass and synthesizers . Usher utilizes his falsetto range throughout , with Billboard writing that the song 's lyrics follow Usher attempting to `` convince a stranded woman at a club to come home with him '' . The song received positive reviews from music critics , who praised Diplo 's production and Usher 's vocals .",
"title": ""
},
{
"docid": "List_of_songs_recorded_by_Usher",
"text": "This is a list of songs recorded by Usher . Usher is an American singer and songwriter . He has released 7 studio albums , 9 compilation albums and 52 singles . He has also appeared on 22 albums released by other artists . His songs have been released on other compilation albums , including Disneymania , a compilation of Disney songs covered by popular artists . Usher has recorded songs with other popular artists including Mariah Carey , Justin Bieber , Pitbull , Afrojack and Wiz Khalifa among others . As of 2016 , he has recorded more than 150 songs .",
"title": ""
},
{
"docid": "Here_I_Stand_(Usher_album)",
"text": "Here I Stand is the fifth studio album by American singer Usher , released on May 13 , 2008 by LaFace Records . Inspired by love for his new wife -- Tameka Foster -- and son , Usher recorded many ballads for the album . Prior to the album 's recording , Usher split with his mother , Jonnetta Patton , as manager and hired Benny Medina . Usher 's estranged father died months before the release of Here I Stand ; this also influenced themes of the album . It was originally to be titled `` Measure of a Man '' , but Usher named it Here I Stand to mark `` a new chapter in -LSB- his -RSB- life '' . Usher promoted Here I Stand by performing on several television shows including Total Request Live , 106 & Park and Good Morning America . Among other concert appearances , he embarked on a One Night Stand : Ladies Only Tour , performing fifteen shows in November 2008 . Six singles were released from Here I Stand : `` Love in This Club '' , `` Love in This Club Part II '' , `` Moving Mountains '' , `` What 's Your Name '' , `` Here I Stand '' and `` Trading Places '' . `` Love in This Club '' , which features rapper Young Jeezy , topped the Billboard Hot 100 and New Zealand Singles Chart . Here I Stand received generally positive reviews from music critics , who viewed it as a sign of growth and maturity from Usher , although others were unimpressed by the change in style from his 2004 album Confessions . It debuted atop the Billboard 200 , and sold 433,000 copies in the US in its first week of release , and has since sold 1.3 million copies in that country . The album also reached number one on the Canadian Albums Chart , UK Albums Chart and Australian Albums Chart , and has sold five million units worldwide . Although it had sold two million copies by August 2008 , Here I Stand was seen as a commercial failure relative to Confessions , which had sold nineteen million copies . Tyler Lewis of PopMatters put the album 's limited success down to Usher 's and Foster 's marriage ; he believed that Usher 's fans disliked Foster .",
"title": ""
},
{
"docid": "Crash_(Usher_song)",
"text": "`` Crash '' is a song by American singer Usher , recorded for his upcoming eighth studio album , Hard II Love . It was released by RCA on June 10 , 2016 , available for digital download and online streaming . The audio for the song was also released on his Vevo and YouTube accounts the same day . `` Crash '' is the follow-up single to `` No Limit '' , released the day before . Both singles are to appear on Usher 's eighth studio album , Hard II Love . The song was written by Usher , Corey Latif , Lee Stashenko , Carlos St. John , while production was handled by St. John and f a l l e n.",
"title": ""
},
{
"docid": "Don't_Let_Love_Slip_Away",
"text": "Do n't Let Love Slip Away is the third studio album by American R&B / Soul singer Freddie Jackson . Released on July 29 , 1988 by Capitol Records , the album reached number one on the U.S. R&B albums chart and peaked at number 48 on the Billboard 200 . It was certified gold by the RIAA in April 1989 . The singles , `` Nice 'N' Slow '' and `` Hey Lover '' , reached number one on the R&B singles chart .",
"title": ""
},
{
"docid": "Usher_Live_Evolution_8701",
"text": "Usher Live Evolution 8701 is a live album by Usher . It was released on November 12 , 2002 , by LaFace Records and includes all of Usher 's top hits up to that time in his career .",
"title": ""
},
{
"docid": "There_Goes_My_Baby_(Usher_song)",
"text": "`` There Goes My Baby '' is a song by American recording artist Usher . It was written by James Scheffer , Frank Romano , Danny Morris and Rico Love , with the latter producing the song with Jim Jonsin . The song was first released as the second promo single for his sixth studio album , Raymond v. Raymond ( 2010 ) on February 9 , 2010 , and later released to rhythmic and urban airplay as the album 's fourth U.S. single from the album on June 15 , 2010 . It was later included the album 's follow-up set , Versus . `` There Goes My Baby '' is a down-tempo R&B piece , which makes use of Usher 's falsetto range . Critics received the song positively , complimenting Usher 's falsetto . While reaching a peak of twenty-five on the Billboard Hot 100 , it topped the Hot R&B / Hip-Hop Songs chart . The charting gave Usher his eleventh number-one on the chart , tying Ray Charles and R. Kelly for the fifth-most number-one 's since the chart 's inception . The song 's accompanying music video features Usher pursuing his love interest in risque scenes . Critics generally favored the video , calling it classic Usher , while some noted its theme was played-out . Usher performed the song a number of times , including at the 2010 BET Awards . The song earned Usher a Grammy Award for Best Male R&B Vocal Performance , at the 53rd Grammy Awards in 2011 .",
"title": ""
},
{
"docid": "Confessions_Part_II",
"text": "`` Confessions Part II '' is a song by R&B singer Usher , produced by Jermaine Dupri and Bryan-Michael Cox for Usher 's fourth album Confessions . Written by Usher , Dupri and Cox , the song is a confession of a man to his woman about his impregnated mistress , a continuation of `` Confessions Part I '' which relates to a man 's infidelity . Its personal content evoked rumors and early responses from the public even before its release , believing that Usher was asserting the truth ; however , Dupri divulged that the story behind the album is his and Usher explained that he only took inspiration from his friends ' similar experiences . `` Confessions Part II '' received mixed reviews from critics . The song was released as the third single from the album , following the success of `` Burn '' . The single reached number one on Billboard Hot 100 for two weeks , becoming the album 's third consecutive number-one single . Internationally , the single had lesser success than the album 's previous releases .",
"title": ""
},
{
"docid": "Lady_Eleanor",
"text": "`` Lady Eleanor '' is a song written by Alan Hull , featured on the first Lindisfarne album , Nicely Out of Tune . Initially released as a single in 1971 , it failed to chart . In 1972 , following the success of the band 's single `` Meet me on the Corner '' ( which reached No. 5 in the UK ) , and the highly successful second album Fog on the Tyne , it was re-released and became their second consecutive hit single , reaching Number 3 in the UK charts . Its B-Side was `` Nothing But the Marvellous is Beautiful '' . The song features the folk rock band Lindisfarne 's characteristic combination of mandolin playing ( by Ray Jackson ) and close harmony singing . Its lyrics are inspired by Edgar Allan Poe 's 1839 short story `` The Fall of the House of Usher '' . The verse is in the key of B minor , while the chorus is in the relative key of D major . Simon Cowe 's lead guitar work betrays the influence of Peter Green , while the song 's instrumental coda - like Green 's hit composition `` Man of the World '' - ends on a D major sixth chord .",
"title": ""
},
{
"docid": "Hey_Daddy_(Daddy's_Home)",
"text": "`` Hey Daddy ( Daddy 's Home ) '' is a song by American R&B singer , Usher . The song is the first single in the United States from Usher 's sixth studio album Raymond v. Raymond , following the buzz single `` Papers '' . The song was written by longtime Usher collaborator Rico Love , Usher , Plies and The Runners and it was also produced by the Love and The Runners . The remix version of the song , featuring Plies , was released to radio stations on December 8 , 2009 , and subsequently available for digital download on December 15 , 2009 . A second remix was released , featuring Jadakiss , on February 5 , 2010 with a different beat that samples the 1997 hit by Lord Tariq and Peter Gunz , `` Deja Vu ( Uptown Baby ) '' ( which in turn samples Steely Dan 's `` Black Cow '' ) . The song received positive reviews with critics praising Usher 's return to the style of music in 2004 's Confessions , as also with `` Papers '' . The song has peaked at number twenty-four on the Billboard Hot 100 , and at number two on the Hot R&B / Hip-Hop Songs , giving Usher his third consecutive U.S. R&B top five hit .",
"title": ""
},
{
"docid": "8701",
"text": "8701 is the third studio album by American singer Usher ; it was first released on August 7 , 2001 , by Arista Records . Recording was handled by several producers including The Neptunes , Jermaine Dupri , Babyface , Kevin `` She ` kspere '' Briggs , Mike City , Bryan Michael Cox , Jimmy Jam & Terry Lewis . Although intended for an October 31 , 2000 , release under the title All About U , the album was delayed numerous times , following the leak of several tracks onto the online music store Napster . Usher subsequently recorded new tracks and released the album under the new title , 8701 , which is derived from Usher singing for the first time in his local church in 1987 and the album 's release date of 2001 . 8701 takes inspiration from multiple artists , including Donny Hathaway , Stevie Wonder , Marvin Gaye , and Michael Jackson . It follows the theme of Usher 's relationship experience , along with the emotions of love and heartache . Usher promoted the album by embarking on the supporting tour , Evolution 8701 Tour in 2002 , to which it he performed in forty-four shows across North America . He also made appearances in television shows , including Live ! with Kelly and Total Request Live . 8701 produced two Billboard Hot 100 number one singles -- `` U Remind Me '' and `` U Got It Bad '' stayed on top for four and five weeks , respectively . The album debuted at number four on the US Billboard 200 chart , with 210,000 copies sold in its first week . It has sold over 4.7 million copies in the United States , receiving a 4 × platinum certification from the Recording Industry Association of America ( RIAA ) ; worldwide sales stand at over eight million . 8701 received generally positive reviews from critics , who praised Usher 's vocals and development as an artist , but were ambivalent towards some of the album 's material . The album earned Usher numerous awards , including two Grammy Awards , three Billboard Music Awards and a BET Award .",
"title": ""
},
{
"docid": "My_Boo_(Usher_and_Alicia_Keys_song)",
"text": "`` My Boo '' is a duet between American R&B singers Usher and Alicia Keys , written by Usher , Keys , Jermaine Dupri , Adonis Shropshire , and Manuel Seal , Jr. . The song was released as the album 's fourth single in 2004 . Set over a hip hop-style track , it was produced by Dupri and No I.D. . It was included on the re-release of Usher 's fourth studio album , Confessions ( 2004 ) . The song received positive reviews from critics , and has garnered awards . The single stayed on top of the Billboard Hot 100 for six weeks , making it the third most-successful single from the album after `` Yeah ! '' and `` Burn '' , respectively . It was also ranked as the 36th biggest song of the 2000 -- 2009 decade in the US .",
"title": ""
}
] |
PLAIN-694
|
biomarkers
|
[
{
"docid": "MED-4738",
"text": "BACKGROUND: Isothiocyanates (ITCs), hydrolysis products from glucosinolates, are a family of biologically active compounds originating from cruciferous vegetables. Many ITCs are assumed to have cancer preventive effects and to further evaluate these potential health effects, reliable biomarkers of ITC exposure are needed. AIM OF THE STUDY: In this study we investigated the ability of urinary ITC excretion to reflect a low or high daily intake of cruciferous vegetables. METHODS: The design was a controlled human crossover study (n = 6). Subjects consumed a self-restricted glucosinolate-free diet 48 h before the study-day where a basic diet supplemented with 80 or 350 g of mixed cruciferous vegetables was consumed. All urine was collected in intervals during the 48 h period after ingestion of the cruciferous vegetables. Total ITC in the cruciferous mixture and total ITC and their metabolites in urine was quantified as the cyclocondensation product of 1,2-bezenedithiol by high performance liquid chromatography. RESULTS: The total urinary excretion of ITCs correlated significantly with the two doses of ITC from diets with high or low cruciferous content (r (s )= 0.90, P < 0.01). The fraction of urinary ITC excreted was 69.02 +/- 11.57% and 74.53 +/- 8.39% of the amounts ingested for 80 and 350 g cruciferous vegetables, respectively. CONCLUSION: The results in this study indicate that the urinary excretion of ITCs, measured by use of the cyclocondesation reaction, is a useful and precise tool that may be used as a biomarker of ITC exposure in population based studies.",
"title": "Urinary excretion of total isothiocyanates from cruciferous vegetables shows high dose-response relationship and may be a useful biomarker for isot..."
},
{
"docid": "MED-4733",
"text": "OBJECTIVES: Mercury and most of its compounds are extremely toxic and should be handled with care. It can be inhaled and absorbed through the skin and mucous membranes. The most toxic forms of mercury are its organic compounds such as dimethylmercury and methylmercury. Fish have a natural tendency to accumulate mercury. Methylmercury is produced by microbial methylation of inorganic mercury in water sediment then it infiltrates the food chain and it consequently accumulates in fish. Fish are the main source of methylmercury in human food. Mercury is transferred into a hair; and this can be than used to monitor the long-term exposure to mercury. The content of mercury in hair depends on the frequency of fish consumption. The aim of our study was to compare mercury content in the hair of children that had various amounts of fish consumption (increased or reduced). DESIGN: Total mercury content in hair was determined by direct method of cold vapors using an AMA 245 analyzer. A total of 174 hair samples from the children (9-17 years old) were analyzed. In this study, the following localities were compared: Neratovice (n=42), Jeseníky (n=44), Prague (n=59) in Czech Republic and Olsztyn in Poland (n=29). Every sample was accompanied with questionnaire about age, gender, regions, amalgam fillings and fish consumption. RESULTS: We did not find a correlation between the content of mercury in hair with age, gender or amalgam fillings. We did find a correlation between fish consumption and the amount of mercury found in the hair samples. CONCLUSION: The amount of mercury in hair increases with more frequent consumption of freshwater and marine fish.",
"title": "Mercury in human hair as an indicator of the fish consumption."
},
{
"docid": "MED-4739",
"text": "Contemporary reproductive aged women and their offspring are facing an unprecedented onslaught of toxicant exposures from myriad sources in their day-to-day life. Public health recommendations regarding optimal diet and nutrition in pregnancy must incorporate several considerations including safety of available foodstuffs, cultural practices and lifestyle issues. Gestational consumption of contaminated seafood remains a potential source of toxicant exposure, including mercury, for the developing child. Health care professionals responsible for the care of women and their developing children need to become apprised of: a) risks associated with toxicant bioaccumulation in pregnancy; b) ongoing information emerging in the important field of reproductive toxicology; and c) strategies within the clinical setting to facilitate nutritional sufficiency and precautionary avoidance of adverse exposure among young women.",
"title": "Nowhere to hide: Chemical toxicants and the unborn child."
},
{
"docid": "MED-4735",
"text": "BACKGROUND/OBJECTIVES: To assess biomarkers and frequency questions as measures of fish consumption. SUBJECTS/METHODS: Participants in the Fishermen substudy numbered 125 men and 139 women (aged 22-74), and in the Health 2000 substudy, 577 men and 712 women (aged 45-74) participated. The aim of the Fishermen study was to examine the overall health effect of fish consumption in a high-consumption population, whereas the aim of the Health 2000 substudy was to obtain in-depth information on cardiovascular diseases and diabetes. Fish consumption was measured by the same validated food frequency questionnaire (FFQ) in both the studies, with a further two separate frequency questions used in the Fishermen substudy. Dioxins, polychlorinated biphenyls (PCBs) and methyl mercury (MeHg) (in the Fishermen substudy alone), and omega-3 polyunsaturated fatty acids (omega-3 PUFAs) (in both studies) were analyzed from fasting serum/blood samples. RESULTS: The Spearman's correlation coefficients between FFQ fish consumption and dioxins, PCBs, MeHg and omega-3 PUFAs were respectively 0.46, 0.48, 0.43 and 0.38 among the Fishermen substudy men, and 0.28, 0.36, 0.45 and 0.31 among women. Similar correlation coefficients were observed between FFQ fish consumption and serum omega-3 PUFAs in the Health 2000 substudy, and also between FFQ fish consumption and the frequency questions on fish consumption in the Fishermen substudy. According to multiple regression modeling and LMG metrics, the most important fish consumption biomarkers were dioxins and PCBs among the men and MeHg among the women. CONCLUSIONS: Environmental contaminants seemed to be slightly better fish consumption biomarkers than omega-3 PUFAs in the Baltic Sea area. The separate frequency questions measured fish consumption equally well when compared with the FFQ.",
"title": "Dioxins, polychlorinated biphenyls, methyl mercury and omega-3 polyunsaturated fatty acids as biomarkers of fish consumption."
},
{
"docid": "MED-4736",
"text": "OBJECTIVE: Few biomarkers for dietary intake of various food groups have been established. The aim of the present study was to explore whether selenium (Se), iodine, mercury (Hg) or arsenic may serve as a biomarker for total fish and seafood intake in addition to the traditionally used n-3 fatty acids EPA and DHA. DESIGN: Intake of fish and seafood estimated by an FFQ was compared with intake assessed by a 4 d weighed food diary and with biomarkers in blood and urine. SETTING: Validation study in the Norwegian Mother and Child Cohort Study (MoBa). SUBJECTS: One hundred and nineteen women. RESULTS: Total fish/seafood intake (median 39 g/d) calculated with the MoBa FFQ was comparable to intake calculated by the food diary (median 30 g/d, rS = 0.37, P < 0.001). Erythrocyte DHA and blood Hg, Se and arsenic concentrations were positively correlated with intake of fish and seafood, but the association for DHA was weakened by the widespread use of supplements. The main finding was the consistent positive association between the intake of fish/seafood and blood arsenic concentration. In multivariate analyses, blood arsenic was associated with blood Hg and fish and seafood intake. In these models, arsenic turned out to be the best indicator of intake of fish and seafood, both totally and in subgroups of fish/seafood intake. CONCLUSIONS: While DHA reflected the intake of fatty fish and n-3 PUFA supplements, blood arsenic concentration also reflected the intake of lean fish and seafood. Blood arsenic appears to be a useful biomarker for total fish and seafood intake.",
"title": "Exploration of biomarkers for total fish intake in pregnant Norwegian women."
},
{
"docid": "MED-4894",
"text": "SUMMARY: This cross-sectional study showed that, although vegans had lower dietary calcium and protein intakes than omnivores, veganism did not have adverse effect on bone mineral density and did not alter body composition. INTRODUCTION: Whether a lifelong vegetarian diet has any negative effect on bone health is a contentious issue. We undertook this study to examine the association between lifelong vegetarian diet and bone mineral density and body composition in a group of postmenopausal women. METHODS: One hundred and five Mahayana Buddhist nuns and 105 omnivorous women (average age = 62, range = 50-85) were randomly sampled from monasteries in Ho Chi Minh City and invited to participate in the study. By religious rule, the nuns do not eat meat or seafood (i.e., vegans). Bone mineral density (BMD) at the lumbar spine (LS), femoral neck (FN), and whole body (WB) was measured by DXA (Hologic QDR 4500). Lean mass, fat mass, and percent fat mass were also obtained from the DXA whole body scan. Dietary calcium and protein intakes were estimated from a validated food frequency questionnaire. RESULTS: There was no significant difference between vegans and omnivores in LSBMD (0.74 +/- 0.14 vs. 0.77 +/- 0.14 g/cm(2); mean +/- SD; P = 0.18), FNBMD (0.62 +/- 0.11 vs. 0.63 +/- 0.11 g/cm(2); P = 0.35), WBBMD (0.88 +/- 0.11 vs. 0.90 +/- 0.12 g/cm(2); P = 0.31), lean mass (32 +/- 5 vs. 33 +/- 4 kg; P = 0.47), and fat mass (19 +/- 5 vs. 19 +/- 5 kg; P = 0.77) either before or after adjusting for age. The prevalence of osteoporosis (T scores < or = -2.5) at the femoral neck in vegans and omnivores was 17.1% and 14.3% (P = 0.57), respectively. The median intake of dietary calcium was lower in vegans compared to omnivores (330 +/- 205 vs. 682 +/- 417 mg/day, P < 0.001); however, there was no significant correlation between dietary calcium and BMD. Further analysis suggested that whole body BMD, but not lumbar spine or femoral neck BMD, was positively correlated with the ratio of animal protein to vegetable protein. CONCLUSION: These results suggest that, although vegans have much lower intakes of dietary calcium and protein than omnivores, veganism does not have adverse effect on bone mineral density and does not alter body composition.",
"title": "Veganism, bone mineral density, and body composition: a study in Buddhist nuns."
}
] |
[
{
"docid": "MED-5193",
"text": "BACKGROUND: The relation between dairy product intake and the risk of ischemic heart disease (IHD) remains controversial. OBJECTIVE: We aimed to explore biomarkers of dairy fat intake in plasma and erythrocytes and to assess the hypothesis that higher concentrations of these biomarkers are associated with a greater risk of IHD in US women. DESIGN: Among 32,826 participants in the Nurses' Health Study who provided blood samples in 1989-1990, 166 incident cases of IHD were ascertained between baseline and 1996. These cases were matched with 327 controls for age, smoking, fasting status, and date of blood drawing. RESULTS: Among controls, correlation coefficients between average dairy fat intake in 1986-1990 and 15:0 and trans 16:1n-7 content were 0.36 and 0.30 for plasma and 0.30 and 0.32 for erythrocytes, respectively. In multivariate analyses, with control for age, smoking, and other risk factors of IHD, women with higher plasma concentrations of 15:0 had a significantly higher risk of IHD. The multivariate-adjusted relative risks (95% CI) from the lowest to highest tertile of 15:0 concentrations in plasma were 1.0 (reference), 2.18 (1.20, 3.98), and 2.36 (1.16, 4.78) (P for trend = 0.03). Associations for other biomarkers were not significant. CONCLUSIONS: Plasma and erythrocyte contents of 15:0 and trans 16:1n-7 can be used as biomarkers of dairy fat intake. These data suggest that a high intake of dairy fat is associated with a greater risk of IHD.",
"title": "Plasma and erythrocyte biomarkers of dairy fat intake and risk of ischemic heart disease."
},
{
"docid": "MED-1511",
"text": "Aims Prolonged sedentary time is ubiquitous in developed economies and is associated with an adverse cardio-metabolic risk profile and premature mortality. This study examined the associations of objectively assessed sedentary time and breaks (interruptions) in sedentary time with continuous cardio-metabolic and inflammatory risk biomarkers, and whether these associations varied by sex, age, and/or race/ethnicity. Methods and results Cross-sectional analyses with 4757 participants (≥20 years) from the 2003/04 and 2005/06 US National Health and Nutrition Examination Survey (NHANES). An Actigraph accelerometer was used to derive sedentary time [<100 counts per minute (cpm)] and breaks in sedentary time. Independent of potential confounders, including moderate-to-vigorous exercise, detrimental linear associations (P for trends <0.05) of sedentary time with waist circumference, HDL-cholesterol, C-reactive protein, triglycerides, insulin, HOMA-%B, and HOMA-%S were observed. Independent of potential confounders and sedentary time, breaks were beneficially associated with waist circumference and C-reactive protein (P for trends <0.05). There was limited evidence of meaningful differences in associations with biomarkers by age, sex, or race/ethnicity. Notable exceptions were sex-differences in the associations of sedentary time and breaks with HDL-cholesterol, and race/ethnicity differences in the association of sedentary time with waist circumference with associations detrimental in non-Hispanic whites, null in Mexican Americans, and beneficial in non-Hispanic blacks. Conclusion These are the first population-representative findings on the deleterious associations of prolonged sedentary time with cardio-metabolic and inflammatory biomarkers. The findings suggest that clinical communications and preventive health messages on reducing and breaking up sedentary time may be beneficial for cardiovascular disease risk.",
"title": "Sedentary time and cardio-metabolic biomarkers in US adults: NHANES 2003–06"
},
{
"docid": "MED-5358",
"text": "Alkylresorcinols (ARs) are shown to be good biomarkers of consumption of rye and whole-grain wheat products in man. The aim of this pilot study was to investigate AR metabolites as potential biomarkers of breast cancer (BC) risk in Finnish women since intake of cereal fiber and its components has been proposed to reduce this risk through an effect on the enterohepatic circulation of estrogens. This was a cross-sectional and observational pilot study. A total of 20 omnivores, 20 vegetarians, and 16 BC women (6-12 mo after operation) were investigated on 2 occasions 6 mo apart. Dietary intake (5-days record), plasma/urinary AR metabolites [3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA)] and plasma/urinary enterolactone were measured. The groups were compared using nonparametric tests. We observed that plasma DHBA (P = 0.007; P = 0.03), plasma DHPPA (P = 0.02; P = 0.01), urinary DHBA (P = 0.001; P = 0.003), urinary DHPPA (P = 0.001; P = 0.001), and cereal fiber intake (P = 0.007; P = 0.003) were significantly lower in the BC group compared to the vegetarian and omnivore groups, respectively. Based on measurements of AR metabolites in urine and in plasma, whole-grain rye and wheat cereal fiber intake is low in BC subjects. Thus, urinary and plasma AR metabolites may be used as potential biomarkers of BC risk in women. This novel approach will likely also facilitate studies of associations between rye and whole-grain wheat cereal fiber intake and other diseases. Our findings should, however, be confirmed with larger subject populations.",
"title": "Plasma and urinary alkylresorcinol metabolites as potential biomarkers of breast cancer risk in Finnish women: a pilot study."
},
{
"docid": "MED-4206",
"text": "Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.",
"title": "Vegetarian diets and public health: biomarker and redox connections."
},
{
"docid": "MED-4687",
"text": "Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.",
"title": "Vegetarian diets and public health: biomarker and redox connections."
},
{
"docid": "MED-2411",
"text": "The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from seafood (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant (alpha-linolenic acid, ALA) sources and risk of type 2 diabetes mellitus (DM) remains unclear. We systematically searched multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of DM. Data were independently extracted in duplicate by 2 investigators, including multivariate-adjusted relative risk (RR) estimates and corresponding 95% CIs. Generalized least-squares trend estimation was used to assess dose-response relationships, with pooled summary estimates calculated by both fixed-effect and random-effect models. From 288 identified abstracts, 16 studies met inclusion criteria, including 18 separate cohorts comprising 540,184 individuals and 25,670 cases of incident DM. Consumption of fish and/or seafood was not significantly associated with DM (n=13 studies; RR per 100g/d=1.12, 95% CI=0.94, 1.34); nor were consumption of EPA+DHA (n=16 cohorts; RR per 250mg/d=1.04, 95% CI=0.97, 1.10) or circulating levels of EPA+DHA biomarkers (n=5 cohorts; RR per 3% of total fatty acids=0.94, 95% CI=0.75, 1.17). Both dietary ALA (n=7 studies; RR per 0.5g/d=0.93, 95% CI=0.83, 1.04) and circulating ALA biomarker levels (n=6 studies; RR per 0.1% of total fatty acid=0.90, 95% CI=0.80, 1.00, P=0.06) were associated with non-significant trend towards lower risk of DM. Substantial heterogeneity (I2~80%) was observed among studies of fish/seafood or EPA+DHA and DM; moderate heterogeneity (<55%) was seen for dietary and biomarker ALA and DM. In unadjusted meta-regressions, study location (Asia vs. North America/Europe), mean BMI, and duration of follow-up each modified the association between fish/seafood and EPA+DHA consumption and DM risk (P-Interaction ≤ 0.02 each). We had limited statistical power to determine the independent effect of these sources of heterogeneity due to their high collinearity. The overall pooled findings do not support either major harms or benefits of fish/seafood or EPA+DHA on development of DM, and suggest that ALA may be associated with modestly lower risk. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation.",
"title": "Omega-3 Fatty Acids and incident Type 2 Diabetes: A Systematic Review and Meta-Analysis"
},
{
"docid": "MED-1682",
"text": "Background The health positive effects of diets high in fruits and vegetables are generally not replicated in supplementation trials with isolated antioxidants and vitamins, and as a consequence the emphasis of chronic disease prevention has shifted to whole foods and whole food products. Methods We carried out a human intervention trial with the golden kiwifruit, Actinidia chinensis, measuring markers of antioxidant status, DNA stability, plasma lipids, and platelet aggregation. Our hypothesis was that supplementation of a normal diet with kiwifruits would have an effect on biomarkers of oxidative status. Healthy volunteers supplemented a normal diet with either one or two golden kiwifruits per day in a cross-over study lasting 2 × 4 weeks. Plasma levels of vitamin C, and carotenoids, and the ferric reducing activity of plasma (FRAP) were measured. Malondialdehyde was assessed as a biomarker of lipid oxidation. Effects on DNA damage in circulating lymphocytes were estimated using the comet assay with enzyme modification to measure specific lesions; another modification allowed estimation of DNA repair. Results Plasma vitamin C increased after supplementation as did resistance towards H2O2-induced DNA damage. Purine oxidation in lymphocyte DNA decreased significantly after one kiwifruit per day, pyrimidine oxidation decreased after two fruits per day. Neither DNA base excision nor nucleotide excision repair was influenced by kiwifruit consumption. Malondialdehyde was not affected, but plasma triglycerides decreased. Whole blood platelet aggregation was decreased by kiwifruit supplementation. Conclusion Golden kiwifruit consumption strengthens resistance towards endogenous oxidative damage.",
"title": "Supplementation of a western diet with golden kiwifruits (Actinidia chinensis var.'Hort 16A':) effects on biomarkers of oxidation damage and antioxidant protection"
},
{
"docid": "MED-2523",
"text": "Background The ‘Blood-Type’ diet advises individuals to eat according to their ABO blood group to improve their health and decrease risk of chronic diseases such as cardiovascular disease. However, the association between blood type-based dietary patterns and health outcomes has not been examined. The objective of this study was to determine the association between ‘blood-type’ diets and biomarkers of cardiometabolic health and whether an individual's ABO genotype modifies any associations. Methods Subjects (n = 1,455) were participants of the Toronto Nutrigenomics and Health study. Dietary intake was assessed using a one-month, 196-item food frequency questionnaire and a diet score was calculated to determine relative adherence to each of the four ‘Blood-Type’ diets. ABO blood group was determined by genotyping rs8176719 and rs8176746 in the ABO gene. ANCOVA, with age, sex, ethnicity, and energy intake as covariates, was used to compare cardiometabolic biomarkers across tertiles of each ‘Blood-Type’ diet score. Results Adherence to the Type-A diet was associated with lower BMI, waist circumference, blood pressure, serum cholesterol, triglycerides, insulin, HOMA-IR and HOMA-Beta (P<0.05). Adherence to the Type-AB diet was also associated with lower levels of these biomarkers (P<0.05), except for BMI and waist circumference. Adherence to the Type-O diet was associated with lower triglycerides (P<0.0001). Matching the ‘Blood-Type’ diets with the corresponding blood group did not change the effect size of any of these associations. No significant association was found for the Type-B diet. Conclusions Adherence to certain ‘Blood-Type’ diets is associated with favorable effects on some cardiometabolic risk factors, but these associations were independent of an individual's ABO genotype, so the findings do not support the ‘Blood-Type’ diet hypothesis.",
"title": "ABO Genotype, ‘Blood-Type’ Diet and Cardiometabolic Risk Factors"
},
{
"docid": "MED-2276",
"text": "A limited number of studies have demonstrated that some modulators of inflammation can be altered by the consumption of sweet cherries. We have taken a proteomics approach to determine the effects of dietary cherries on targeted gene expression. The purpose was then to determine changes caused by cherry consumption in the plasma concentrations of multiple biomarkers for several chronic inflammatory diseases in healthy humans with modestly elevated C-reactive protein (CRP; range, 1-14 mg/L; mean, 3.5 mg/L; normal, <1.0 mg/L). Eighteen men and women (45-61 y) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. Fasting blood samples were taken before the start of consuming the cherries (study d 7), 28 d after the initiation of cherry supplementation (d 35), and 28 d after the discontinuation (d 63). Of the 89 biomarkers assessed, cherry consumption for 28 d altered concentrations of 9, did not change those of 67, and the other 13 were below the detection limits. Cherry consumption decreased (P < 0.05) plasma concentrations of extracellular newly identified ligand for the receptor for advanced glycation end products (29.0%), CRP (20.1%), ferritin (20.3%), plasminogen activator inhibitor-1 (19.9%), endothelin-1 (13.7%), epidermal growth factor (13.2%), and IL-18 (8.1%) and increased that of IL-1 receptor antagonist (27.9%) compared with corresponding values on study d 7. The ferritin concentration continued to decrease between d 35 and 63 and it was significantly lower on d 63 than on d 7. Because the participants in this study were healthy, no clinical pathology end points were measured. However, results from the present study demonstrate that cherry consumption selectively reduced several biomarkers associated with inflammatory diseases.",
"title": "Sweet bing cherries lower circulating concentrations of markers for chronic inflammatory diseases in healthy humans."
},
{
"docid": "MED-2830",
"text": "OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.",
"title": "Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks."
},
{
"docid": "MED-1389",
"text": "BACKGROUND & AIMS: Metabolic syndrome (MetS), in which a non-classic feature is an increase in systemic oxidative biomarkers, presents a high risk of diabetes and cardiovascular disease (CVD). Adherence to the Mediterranean Diet (MedDiet) is associated with a reduced risk of MetS. However, the effect of the MedDiet on biomarkers for oxidative damage has not been assessed in MetS individuals. We have investigated the effect of the MedDiet on systemic oxidative biomarkers in MetS individuals. METHODS: Randomized, controlled, parallel clinical trial in which 110 female with MetS, aged 55-80, were recruited into a large trial (PREDIMED Study) to test the efficacy of the traditional MedDiet on the primary prevention of CVD. Participants were assigned to a low-fat diet or two traditional MedDiets (MedDiet + virgin olive oil or MedDiet + nuts). Both MedDiet group participants received nutritional education and either free extra virgin olive oil for all the family (1 L/week), or free nuts (30 g/day). Diets were ad libitum. Changes in urine levels of F2-Isoprostane (F2-IP) and the DNA damage base 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) were evaluated at 1-year trial. RESULTS: After 1-year urinary F2-IP decreased in all groups, the decrease in MedDiet groups reaching a borderline significance versus that of the Control group. Urinary 8-oxo-dG was also reduced in all groups, with a higher decrease in both MedDiet groups versus the Control one (P < 0.001). CONCLUSIONS: MedDiet reduces oxidative damage to lipids and DNA in MetS individuals. Data from this study provide evidence to recommend the traditional MedDiet as a useful tool in the MetS management. Registered under Clinical Trials.gov Identifier no. NCT00123456. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.",
"title": "The Mediterranean diet improves the systemic lipid and DNA oxidative damage in metabolic syndrome individuals. A randomized, controlled, trial."
},
{
"docid": "MED-4097",
"text": "The identification of modifiable lifestyle factors that could reduce the risk of breast cancer is a research priority. Despite the enormous chemo preventive potential of green tea and compelling evidence from animal studies, its role in breast cancer development in humans is still unclear. Part of the uncertainty is related to the relatively small number of epidemiological studies on green tea and breast cancer and that the overall results from case-control studies and prospective cohort studies are discordant. In addition, the mechanisms by which green tea intake may influence risk of breast cancer in humans remains not well studied. We review the human studies that have evaluated the relationship between green tea intake and four biomarkers (sex steroid hormones, mammographic density, insulin-like growth factor, adiponectin) that are believed to be important in breast cancer development. Results from these biomarker studies are also inconclusive. Limitations of human studies and areas of further investigations are discussed.",
"title": "Green Tea and Breast Cancer"
},
{
"docid": "MED-3866",
"text": "Background Obesity leads to an increase in inflammation and insulin resistance. This study determined antioxidant activity of flaxseed and its role in inflammation and insulin resistance in obese glucose intolerant people. Methods Using a randomized crossover design, nine obese glucose intolerant people consumed 40 g ground flaxseed or 40 g wheat bran daily for 12 weeks with a 4-week washout period. Plasma inflammation biomarkers (CRP, TNF-α, and IL-6), glucose, insulin, and thiobaribituric acid reactive substance (TBARS) were measured before and after of each supplementation. Results Flaxseed supplementation decreased TBARS (p = 0.0215) and HOMA-IR (p = 0.0382). Flaxseed or wheat bran supplementation did not change plasma inflammatory biomarkers. A positive relationship was found between TBARS and HOMA-IR (r = 0.62, p = 0.0003). Conclusions The results of the study weakly support that decreased insulin resistance might have been secondary to antioxidant activity of flaxseed. However, the mechanism(s) of decreased insulin resistance by flaxseed should be further determined using flaxseed lignan.",
"title": "Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design"
},
{
"docid": "MED-4553",
"text": "Alzheimer's disease (AD) is the most common dementing disorder of late life. Although there might be various different triggering events in the early stages of the disease, they seem to converge on a few characteristic final pathways in the late stages, characterized by inflammation and neurodegeneration. In this review, we put forward the hypothesis that advanced glycation end products (AGEs) and their precursors, including methylglyoxal, are both biomarkers and causative agents (\"gerontotoxins\") characteristic for this disorder. Accumulation of AGEs is a normal feature of aging, but is accelerated in AD, where AGEs can be detected in amyloid plaques and neurofibrillary tangles. AGE modification may explain many of the neuropathological and biochemical features of AD such as extensive protein cross-linking, inflammation, oxidative stress and neuronal cell death. We suggest that methylglyoxal is one of the major carbonyl species responsible for the formation of AGEs. We propose that one promising pharmacological approach to prevent the formation of AGEs would be to lower the methylglyoxal concentration. This can be achieved, for example, by decreasing the concentration of methylglyoxal precursors such as d-glyceraldehyde-3-phosphate by allowing a higher flux through the pentose phosphate pathway or by increasing methylglyoxal detoxification through the glyoxalase system. Alternatively, methylglyoxal could be scavenged by various types of carbonyl scavengers. Copyright © 2010 Elsevier Inc. All rights reserved.",
"title": "Advanced glycation end products as biomarkers and gerontotoxins - A basis to explore methylglyoxal-lowering agents for Alzheimer's disease?"
},
{
"docid": "MED-3921",
"text": "BACKGROUND: To evaluate health benefits attributed to Hibiscus sabdariffa L. a randomized, open-label, two-way crossover study was undertaken to compare the impact of an aqueous H. sabdariffa L. extract (HSE) on the systemic antioxidant potential (AOP; assayed by ferric reducing antioxidant power (FRAP)) with a reference treatment (water) in eight healthy volunteers. The biokinetic variables were the areas under the curve (AUC) of plasma FRAP, ascorbic acid and urate that are above the pre-dose concentration, and the amounts excreted into urine within 24 h (Ae(0-24) ) of antioxidants as assayed by FRAP, ascorbic acid, uric acid, malondialdehyde (biomarker for oxidative stress), and hippuric acid (metabolite and potential biomarker for total polyphenol intake). RESULTS: HSE caused significantly higher plasma AUC of FRAP, an increase in Ae(0-24) of FRAP, ascorbic acid and hippuric acid, whereas malondialdehyde excretion was reduced. Furthermore, the main hibiscus anthocyanins as well as one glucuronide conjugate could be quantified in the volunteers' urine (0.02% of the administered dose). CONCLUSION: The aqueous HSE investigated in this study enhanced the systemic AOP and reduced the oxidative stress in humans. Furthermore, the increased urinary hippuric acid excretion after HSE consumption indicates a high biotransformation of the ingested HSE polyphenols, most likely caused by the colonic microbiota. Copyright © 2012 Society of Chemical Industry.",
"title": "Consumption of Hibiscus sabdariffa L. aqueous extract and its impact on systemic antioxidant potential in healthy subjects."
},
{
"docid": "MED-4978",
"text": "Human risk assessment of exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through the diet may be improved by conducting biomonitoring studies comparing metabolism in humans and rodents. Eleven volunteers ingested a meal of cooked chicken containing 4 -OH-PhIP and PhIP in amounts of 0.6 and 0.8microg/kg, respectively and urine was collected for the next 16h. The large number of PhIP metabolites was by treatment of the urine samples with hydrazine hydrate and hydrolytic enzymes reduced to three substances, 4'-OH-PhIP, PhIP and 5-OH-PhIP of which the first is a biomarker for detoxification and the last a biomarker for activation. The eleven volunteers eliminated large amounts of 4'-OH-PhIP in the urine. The majority of which could be accounted for by the presence of 4'-OH-PhIP in the fried chicken, showing that PhIP only to a small extent (11%) was metabolised to 4'-OH-PhIP. A larger fraction of the PhIP exposure, 38%, was recovered as PhIP and the largest fraction (51%) was recovered as 5-OH-PhIP suggesting that PhIP in humans to a large extent is metabolised to reactive substances. In rats, less than 1% of the dose of PhIP was eliminated as 5-OH-PhIP, suggesting that human cancer risk from exposure to PhIP is considerable higher than risk estimations based on extrapolation from rodent bioassays.",
"title": "Biomonitoring of urinary metabolites of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) following human consumption of cooked chicken."
},
{
"docid": "MED-1711",
"text": "Summary Objectives The insulin-like growth factor (IGF) signaling pathway has been implicated in the pathogenesis of numerous tumor types, including non-small cell lung cancer (NSCLC). Figitumumab is a fully human IgG2 monoclonal antibody against IGF-1 receptor (IGF-1R). Methods This phase I, open-label, dose-escalation study (ClinicalTrials.gov: NCT00603538) assessed the safety and tolerability of figitumumab (6, 10 and 20 mg/kg) in combination with carboplatin (area under the curve: 6 mg·min/mL) and paclitaxel (200 mg/m2) in Japanese patients (N = 19) with chemotherapy-naïve, advanced NSCLC. Treatments were administered intravenously on day 1 of a 21-day cycle for four to six cycles. Pharmacokinetics, biomarkers, and antitumor activity were also evaluated. Results Figitumumab in combination with carboplatin and paclitaxel was well tolerated at doses up to 20 mg/kg; no dose-limiting toxicities were observed at this dose level. When given in combination, figitumumab plasma exposure increased in an approximately dose-proportional manner. The approximate 2-fold accumulation following repeated administration supported the 21-day regimen as appropriate for figitumumab administration. Serum total IGF-1 and IGF binding protein-3 concentrations increased following figitumumab dosing, but a clear dose-dependent relationship was not demonstrated. Seven of 18 evaluable patients experienced a partial response. Conclusions Figitumumab 20 mg/kg in combination with carboplatin and paclitaxel was well tolerated in chemotherapy-naïve Japanese patients with NSCLC. Further analysis of biomarker data is necessary for the development of figitumumab therapy.",
"title": "Figitumumab combined with carboplatin and paclitaxel in treatment-naïve Japanese patients with advanced non-small cell lung cancer"
},
{
"docid": "MED-2226",
"text": "BACKGROUND: Studies of cocoa suggest an array of cardiovascular benefits; however, the effects of daily intake of sugar-free and sugar-sweetened cocoa beverages on endothelial function (EF) have yet to be established. METHODS: 44 adults (BMI 25-35 kg/m2) participated in a randomized, controlled, crossover trial. Participants were randomly assigned to a treatment sequence: sugar-free cocoa beverage, sugar-sweetened cocoa beverage, and sugar-sweetened cocoa-free placebo. Treatments were administered daily for 6 weeks, with a 4-week washout period. RESULTS: Cocoa ingestion improved EF measured as flow-mediated dilation (FMD) compared to placebo (sugar-free cocoa: change, 2.4% [95% CI, 1.5 to 3.2] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 3.2% [95% CI, 1.8 to 4.6]; p<0.001 and sugar-sweetened cocoa: change, 1.5% [95% CI, 0.6 to 2.4] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 2.3% [95% CI, 0.9 to 3.7]; p=0.002). The magnitude of improvement in FMD after consumption of sugar-free versus sugar-sweetened cocoa was greater, but not significantly. Other biomarkers of cardiac risk did not change appreciably from baseline. BMI remained stable throughout the study. CONCLUSIONS: Daily cocoa ingestion improves EF independently of other biomarkers of cardiac risk, and does not cause weight gain. Sugar-free preparations may further augment endothelial function. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.",
"title": "Effects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults."
},
{
"docid": "MED-3833",
"text": "Preclinical and correlative studies suggest reduced breast cancer with higher lignan intake or blood levels. We conducted a pilot study of modulation of risk biomarkers for breast cancer in premenopausal women after administration of the plant lignan secoisolariciresinol given as the diglycoside (SDG). Eligibility criteria included regular menstrual cycles, no oral contraceptives, a greater than 3-fold increase in 5 year risk, and baseline Ki-67 ≥2% in areas of hyperplasia in breast tissue sampled by random periareolar fine needle aspiration (RPFNA) during the follicular phase of the menstrual cycle. SDG 50 mg daily was given for 12 months, followed by repeat RPFNA. The primary endpoint was change in Ki-67. Secondary endpoints included change in cytomorphology, mammographic breast density, serum bioavailable estradiol, and testosterone IGF-I and IGFBP-3, and plasma lignan levels. Forty-five of 49 eligible women completed the study with excellent compliance (median = 96%) and few serious side effects (4% grade 3). Median plasma enterolactone increased ~ 9-fold, and total lignans 16 fold. Thirty-six (80%) of the 45 evaluable subjects demonstrated a decrease in Ki-67, from a median of 4% (range 2–16.8 %) to 2% (range 0–15.2%) (p<0.001 by Wilcoxon signed rank test). A decrease from baseline in the proportion of women with atypical cytology (p=0.035) was also observed. Based on favorable risk biomarker modulation and lack of adverse events, we are initiating a randomized trial of SDG vs. placebo in premenopausal women.",
"title": "Reduction in Ki-67 in Benign Breast Tissue of High Risk Women with the Lignan Secoisolariciresinol Diglycoside (SDG)"
},
{
"docid": "MED-3841",
"text": "Preclinical and correlative studies suggest reduced breast cancer with higher lignan intake or blood levels. We conducted a pilot study of modulation of risk biomarkers for breast cancer in premenopausal women after administration of the plant lignan secoisolariciresinol given as the diglycoside (SDG). Eligibility criteria included regular menstrual cycles, no oral contraceptives, a greater than 3-fold increase in 5 year risk, and baseline Ki-67 ≥2% in areas of hyperplasia in breast tissue sampled by random periareolar fine needle aspiration (RPFNA) during the follicular phase of the menstrual cycle. SDG 50 mg daily was given for 12 months, followed by repeat RPFNA. The primary endpoint was change in Ki-67. Secondary endpoints included change in cytomorphology, mammographic breast density, serum bioavailable estradiol, and testosterone IGF-I and IGFBP-3, and plasma lignan levels. Forty-five of 49 eligible women completed the study with excellent compliance (median = 96%) and few serious side effects (4% grade 3). Median plasma enterolactone increased ~ 9-fold, and total lignans 16 fold. Thirty-six (80%) of the 45 evaluable subjects demonstrated a decrease in Ki-67, from a median of 4% (range 2–16.8 %) to 2% (range 0–15.2%) (p<0.001 by Wilcoxon signed rank test). A decrease from baseline in the proportion of women with atypical cytology (p=0.035) was also observed. Based on favorable risk biomarker modulation and lack of adverse events, we are initiating a randomized trial of SDG vs. placebo in premenopausal women.",
"title": "Reduction in Ki-67 in Benign Breast Tissue of High Risk Women with the Lignan Secoisolariciresinol Diglycoside (SDG)"
},
{
"docid": "MED-4973",
"text": "Urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) are a class of PAH metabolites used as biomarkers for assessing human exposure to PAHs. The Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey (NHANES) uses OH-PAHs to establish reference range concentrations for the US population, and to set benchmarks for future epidemiologic and biomonitoring studies. For the years 2001 and 2002, 22 OH-PAH metabolites were measured in urine specimens from 2748 NHANES participants. Percentages of samples with detectable levels ranged from nearly 100% for metabolites of naphthalene, fluorene, phenanthrene, and pyrene, to less than 5% for metabolites from parent compounds with higher molecular weight such as chrysene, benzo[c]phenanthrene, and benz[a]anthracene. The geometric mean for 1-hydroxypyrene (1-PYR)--the most commonly used biomarker for PAH exposure--was 49.6 ng/L urine, or 46.4 ng/g creatinine. Children (ages 6-11) generally had higher levels than did adolescents (ages 12-19) or adults (ages 20 and older). Model-adjusted, least-square geometric means for 1-PYR were 87, 53 and 43 ng/L for children, adolescents (ages 12-19) and adults (ages 20 years and older), respectively. Log-transformed concentrations for major detectable OH-PAHs were significantly correlated with each other. The correlation coefficients between 1-PYR and other metabolites ranging from 0.17 to 0.63 support the use of 1-PYR as a useful surrogate representing PAH exposure.",
"title": "Concentration and profile of 22 urinary polycyclic aromatic hydrocarbon metabolites in the US population."
},
{
"docid": "MED-5087",
"text": "Acrylamide, a probable human carcinogen, is formed in several foods during high-temperature processing. So far, epidemiological studies have not shown any association between human cancer risk and dietary exposure to acrylamide. The purpose of this study was to conduct a nested case control study within a prospective cohort study on the association between breast cancer and exposure to acrylamide using biomarkers. N-terminal hemoglobin adduct levels of acrylamide and its genotoxic metabolite, glycidamide in red blood cells were analyzed (by LC/MS/MS) as biomarkers of exposure on 374 breast cancer cases and 374 controls from a cohort of postmenopausal women. The adduct levels of acrylamide and glycidamide were similar in cases and controls, with smokers having much higher levels (approximately 3 times) than nonsmokers. No association was seen between acrylamide-hemoglobin levels and breast cancer risk neither unadjusted nor adjusted for the potential confounders HRT duration, parity, BMI, alcohol intake and education. After adjustment for smoking behavior, however, a positive association was seen between acrylamide-hemoglobin levels and estrogen receptor positive breast cancer with an estimated incidence rate ratio (95% CI) of 2.7 (1.1-6.6) per 10-fold increase in acrylamide-hemoglobin level. A weak association between glycidamide hemoglobin levels and incidence of estrogen receptor positive breast cancer was also found, this association, however, entirely disappeared when acrylamide and glycidamide hemoglobin levels were mutually adjusted. (c) 2008 Wiley-Liss, Inc.",
"title": "Acrylamide exposure and incidence of breast cancer among postmenopausal women in the Danish Diet, Cancer and Health Study."
},
{
"docid": "MED-1063",
"text": "BACKGROUND: The results of some epidemiologic studies conducted by using questionnaires suggest that dietary fat composition influences diabetes risk. Confirmation of this finding with use of a biomarker is warranted. OBJECTIVE: We prospectively investigated the relation of plasma cholesterol ester (CE) and phospholipid (PL) fatty acid composition with the incidence of diabetes mellitus. DESIGN: In 2909 adults aged 45-64 y, plasma fatty acid composition was quantified by using gas-liquid chromatography and was expressed as a percentage of total fatty acids. Incident diabetes (n = 252) was identified during 9 y of follow-up. RESULTS: After adjustment for age, sex, baseline body mass index, waist-to-hip ratio, alcohol intake, cigarette smoking, physical activity, education, and parental history of diabetes, diabetes incidence was significantly and positively associated with the proportions of total saturated fatty acids in plasma CE and PL. The rate ratios of incident diabetes across quintiles of saturated fatty acids were 1.00, 1.36, 1.16, 1.60, and 2.08 (P = 0.0013) in CE and 1.00, 1.75, 1.87, 2.40, and 3.37 (P < 0.0001) in PL. In CE, the incidence of diabetes was also positively associated with the proportions of palmitic (16:0), palmitoleic (16:1n-7), and dihomo-gamma-linolenic (20:3n-6) acids and inversely associated with the proportion of linoleic acid (18:2n-6). In PL, incident diabetes was positively associated with the proportions of 16:0 and stearic acid (18:0). CONCLUSIONS: The proportional saturated fatty acid composition of plasma is positively associated with the development of diabetes. Our findings with the use of this biomarker suggest indirectly that the dietary fat profile, particularly that of saturated fat, may contribute to the etiology of diabetes.",
"title": "Plasma fatty acid composition and incidence of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study."
},
{
"docid": "MED-2076",
"text": "BACKGROUND: Berries are a particularly rich source of polyphenols. They also contain other bioactive substances, such as vitamin C. Previous studies indicated that the consumption of polyphenol-rich foods (eg, cocoa, tea, and red wine) may induce beneficial changes in pathways related to cardiovascular health. Whether the consumption of berries has similar effects is unknown. OBJECTIVE: We aimed to investigate the effects of berry consumption on hemostatic function, serum lipids, and blood pressure (BP). DESIGN: Middle-aged unmedicated subjects (n = 72) with cardiovascular risk factors consumed moderate amounts of berry or control products for 8 wk in a single-blind, randomized, placebo-controlled intervention trial. RESULTS: Berry consumption inhibited platelet function as measured with a platelet function analyzer (using collagen and ADP as platelet activator) [changes: 11% and -1.4% in the berry and control groups, respectively; P = 0.018, analysis of covariance (ANCOVA)]. Plasma biomarkers of platelet activation, coagulation, and fibrinolysis did not change during the intervention. Serum HDL-cholesterol concentrations increased significantly more (P = 0.006, ANCOVA) in the berry than in the control group (5.2% and 0.6%, respectively), but total cholesterol and triacylglycerol remained unchanged. Systolic BP decreased significantly (P = 0.050, ANCOVA); the decrease mostly occurred in subjects with high baseline BP (7.3 mm Hg in highest tertile; P = 0.024, ANCOVA). Polyphenol and vitamin C concentrations in plasma increased, whereas other nutritional biomarkers (ie, folate, tocopherols, sodium, and potassium) were unaffected. CONCLUSION: The consumption of moderate amounts of berries resulted in favorable changes in platelet function, HDL cholesterol, and BP. The results indicate that regular consumption of berries may play a role in the prevention of cardiovascular disease.",
"title": "Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol."
},
{
"docid": "MED-2386",
"text": "OBJECTIVE Emerging in vitro and animal evidence suggests that methylmercury could increase type 2 diabetes, but little evidence exists in humans. We aimed to prospectively determine associations of mercury exposure, as assessed by biomarker measurement, with incident diabetes. RESEARCH DESIGN AND METHODS We used neutron activation analysis to measure toenail mercury, an objective biomarker of methylmercury exposure, in 9,267 adults free of diabetes at baseline in two separate U.S. prospective cohorts. Incident diabetes was identified from biennial questionnaires and confirmed by validated supplementary questionnaire using symptoms, diagnostic tests, and medical therapy. Associations of mercury exposure with incident diabetes were assessed using Cox proportional hazards. RESULTS During mean ± SD follow-up of 19.7 ± 7.0 years, 1,010 new cases of diabetes were diagnosed. The 95th percentile of toenail mercury was 1.32 μg/g in men and 0.76 μg/g in women, corresponding to exposures ∼3.5-fold and 2-fold higher than the U.S. Environmental Protection Agency reference dose. In multivariable analyses, toenail mercury concentrations were not associated with higher incidence of diabetes in women, men, or both cohorts combined. Comparing the highest to lowest quintile of exposure, the hazard ratio (95% CI) for incident diabetes was 0.86 (0.66–1.11) in women, 0.69 (0.42–1.15) in men, and 0.77 (0.61–0.98) in the combined cohorts. Findings were similar when more extreme categories (deciles) of mercury were compared, and in analyses stratified by fish or omega-3 consumption, BMI, and age. CONCLUSIONS These findings from two separate large prospective cohorts do not support adverse effects of methylmercury on development of diabetes in men or women at usual levels of exposure seen in these populations.",
"title": "Methylmercury Exposure and Incident Diabetes in U.S. Men and Women in Two Prospective Cohorts"
},
{
"docid": "MED-4059",
"text": "2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine formed in meat and fish during cooking and can be used as a model compound for this class of chemicals possibly involved in human carcinogenesis. Knowing the exposure to heterocyclic amines is important for establishing their role in human diseases. Serum albumin (SA) and globin (Gb) adducts were first tested as biomarkers of exposure to PhIP in male Fischer 344 rats given oral doses of 0.1, 0.5, 1 and 10 mg/kg. Blood samples were collected 24 hr after treatment and PhIP released from SA and Gb after acidic hydrolysis was analyzed by gas chromatography-mass spectrometry or liquid chromatography-tandem mass spectrometry. PhIP-SA and Gb adducts increased linearly with the dose. Studies on 35 volunteers with different dietary habits exhibited that diet was a major determinant in the formation of both adducts. PhIP-SA adducts were significantly higher in meat consumers than in vegetarians (6.7 +/- 1.6 and 0.7 +/- 0.3 fmol/mg SA; respectively, mean +/- SE; p = 0.04, Mann-Whitney U test). The Gb adduct pattern was quantitatively lower but paralleled SA (3 +/- 0.8 in meat consumers and 0.3 +/- 0.1 in vegetarians). PhIP-SA adducts were no different in smokers and in non-smokers. The results show for the first time that PhIP-blood protein adducts are present in humans not given the synthetic compound. Both biomarkers appear to be suitable for assessing dietary exposure and internal PhIP dose and may be promising tools for studying the role of heterocyclic amines in the etiology of colon cancer and other diseases. Copyright 2000 Wiley-Liss, Inc.",
"title": "Effect of diet on serum albumin and hemoglobin adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans."
},
{
"docid": "MED-4458",
"text": "Background Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine with keto-enol tautomerase activity, rises rapidly in response to inflammation, and is elevated in many chronic diseases. Isothiocyanates, such as sulforaphane from broccoli, are very potent inactivators of MIF tautomerase activity. A simple rapid method for determining this activity in tissues and body fluids may therefore be valuable for assessing severity of inflammation and efficacy of intervention. Methods Existing spectrophotometric assays of MIF, based on conversion of methyl L-dopachrome to methyl 5,6-dihydroxyindole-2-carboxylate and associated loss of absorption at 475 nm, lack sensitivity. Assay sensitivity and efficiency were markedly improved by reducing the nonenzymatic rate, by lowering pH to 6.2, replacing phosphate (which catalyzes the reaction) with Bis-Tris buffer, and converting to a microtiter plate format. Results A structure-potency study of MIF tautomerase inactivation by isothiocyanates showed that sulforaphane, benzyl, n-hexyl, and phenethyl isothiocyanates were especially potent. MIF tautomerase could be readily quantified in human urine concentrated by ultrafiltration. This activity comprised: (i) a heat-labile, sulforaphane-inactivated macromolecular fraction (presumably MIF) that was concentrated during ultrafiltration; (ii) a flow-through fraction, with constant activity during filtration, that was heat-stable, and insensitive to sulforaphane. Administration of the sulforaphane precursor glucoraphanin to human volunteers almost completely abolished urinary tautomerase activity, which was recovered over many hours. Conclusions A simple, rapid, quantitative MIF tautomerase assay has been developed as a potential biomarker for assessing inflammatory severity and effectiveness of intervention. Impact An improved assay for measuring MIF tautomerase activity and its applications are described.",
"title": "Inactivation of Tautomerase Activity of Macrophage Migration Inhibitory Factor by Sulforaphane: A Potential Biomarker for Anti-inflammatory Intervention"
},
{
"docid": "MED-3444",
"text": "Research on the relationship between iodine exposure and thyroid cancer risk is limited, and the findings are inconclusive. In most studies, fish/shellfish consumption has been used as a proxy measure of iodine exposure. The present study extends this research by quantifying dietary iodine exposure as well as incorporating a biomarker of long-term (1 year) exposure, i.e., from toenail clippings. This study is conducted in a multiethnic population with a wide variation in thyroid cancer incidence rates and substantial diversity in exposure. Women, ages 20-74, residing in the San Francisco Bay Area and diagnosed with thyroid cancer between 1995 and 1998 (1992-1998 for Asian women) were compared with women selected from the general population via random digit dialing. Interviews were conducted in six languages with 608 cases and 558 controls. The established risk factors for thyroid cancer were found to increase risk in this population: radiation to the head/neck [odds ratio (OR), 2.3; 95% confidence interval (CI), 0.97-5.5]; history of goiter/nodules (OR, 3.7; 95% CI, 2.5-5.6); and a family history of proliferative thyroid disease (OR, 2.5; 95% CI, 1.6-3.8). Contrary to our hypothesis, increased dietary iodine, most likely related to the use of multivitamin pills, was associated with a reduced risk of papillary thyroid cancer. This risk reduction was observed in \"low-risk\" women (i.e., women without any of the three established risk factors noted above; OR, 0.53; 95% CI, 0.33-0.85) but not in \"high-risk\" women, among whom a slight elevation in risk was seen (OR, 1.4; 95% CI, 0.56-3.4). However, no association with risk was observed in either group when the biomarker of exposure was evaluated. In addition, no ethnic differences in risk were observed. The authors conclude that iodine exposure appears to have, at most, a weak effect on the risk of papillary thyroid cancer.",
"title": "Iodine and thyroid cancer risk among women in a multiethnic population: the Bay Area Thyroid Cancer Study."
},
{
"docid": "MED-5012",
"text": "This study investigated the effect of coconut flakes on serum cholesterol levels of humans with moderately raised serum cholesterol in 21 subjects. The serum total cholesterol of subjects differed and ranged from 259 to 283 mg/dL. The study was conducted in a double-blind randomized crossover design on a 14-week period, consisting of four 2-week experimental periods, with each experimental period separated by a 2-week washout period. The test foods were as follows: corn flakes as the control food, oat bran flakes as the reference food, and corn flakes with 15% and 25% dietary fiber from coconut flakes (made from coconut flour production). Results showed a significant percent reduction in serum total and low-density lipoprotein (LDL) cholesterol (in mg/dL) for all test foods, except for corn flakes, as follows: oat bran flakes, 8.4 +/- 1.4 and 8.8 +/- 6.0, respectively; 15% coconut flakes, 6.9 +/- 1.1 and 11.0 +/- 4.0, respectively; and 25% coconut flakes, 10.8 +/- 1.3 and 9.2 +/- 5.4, respectively. Serum triglycerides were significantly reduced for all test foods: corn flakes, 14.5 +/- 6.3%; oat bran flakes, 22.7 +/- 2.9%; 15% coconut flakes, 19.3 +/- 5.7%; and 25% coconut flakes, 21.8 +/- 6.0%. Only 60% of the subjects were considered for serum triglycerides reduction (serum triglycerides >170 mg/dL). In conclusion, both 15% and 25% coconut flakes reduced serum total and LDL cholesterol and serum triglycerides of humans with moderately raised serum cholesterol levels. Coconut flour is a good source of both soluble and insoluble dietary fiber, and both types of fiber may have significant role in the reduction of the above lipid biomarker. To our knowledge, this is the first study conducted to show a relationship between dietary fiber from a coconut by-product and a lipid biomarker. Results from this study serves as a good basis in the development of coconut flakes/flour as a functional food, justifying the increased production of coconut and coconut by-products.",
"title": "The cholesterol-lowering effect of coconut flakes in humans with moderately raised serum cholesterol."
},
{
"docid": "MED-1338",
"text": "Objective To examine whether high milk consumption is associated with mortality and fractures in women and men. Design Cohort studies. Setting Three counties in central Sweden. Participants Two large Swedish cohorts, one with 61 433 women (39-74 years at baseline 1987-90) and one with 45 339 men (45-79 years at baseline 1997), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997. Main outcome measure Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture. Results During a mean follow-up of 20.1 years, 15 541 women died and 17 252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow-up of 11.2 years, 10 112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF2α (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker). Conclusions High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.",
"title": "Milk intake and risk of mortality and fractures in women and men: cohort studies"
}
] |
200598
|
The Prestige stars an actor.
|
[
{
"docid": "David_Bowie",
"text": "David Robert Jones ( 8 January 1947 -- 10 January 2016 ) , known professionally as David Bowie ( -LSB- ˈboʊi -RSB- ) , was an English singer , songwriter and actor . He was a figure in popular music for over five decades , becoming acclaimed by critics and other musicians for his innovative work . His career was marked by reinvention and visual presentation , his music and stagecraft significantly influencing popular music . During his lifetime , his record sales , estimated at 140 million worldwide , made him one of the world 's best-selling music artists . In the UK , he was awarded nine platinum album certifications , eleven gold and eight silver , releasing eleven number-one albums . In the US , he received five platinum and seven gold certifications . He was inducted into the Rock and Roll Hall of Fame in 1996 . Born in Brixton , South London , Bowie developed an interest in music as a child , eventually studying art , music and design before embarking on a professional career as a musician in 1963 . `` Space Oddity '' became his first top-five entry on the UK Singles Chart after its release in July 1969 . After a period of experimentation , he re-emerged in 1972 during the glam rock era with his flamboyant and androgynous alter ego Ziggy Stardust . The character was spearheaded by the success of his single `` Starman '' and album The Rise and Fall of Ziggy Stardust and the Spiders from Mars , which won him widespread popularity . In 1975 , Bowie 's style shifted radically towards a sound he characterised as `` plastic soul '' , initially alienating many of his UK devotees but garnering him his first major US crossover success with the number-one single `` Fame '' and the album Young Americans . In 1976 , Bowie starred in the cult film The Man Who Fell to Earth and released Station to Station . The following year , he further confounded musical expectations with the electronic-inflected album Low ( 1977 ) , the first of three collaborations with Brian Eno that would come to be known as the `` Berlin Trilogy '' . `` Heroes '' ( 1977 ) and Lodger ( 1979 ) followed ; each album reached the UK top five and received lasting critical praise . After uneven commercial success in the late 1970s , Bowie had UK number ones with the 1980 single `` Ashes to Ashes '' , its parent album Scary Monsters and Super Creeps , and `` Under Pressure '' , a 1981 collaboration with Queen . He then reached his commercial peak in 1983 with Let 's Dance , with its title track topping both UK and US charts . Throughout the 1990s and 2000s , Bowie continued to experiment with musical styles , including industrial and jungle . He also continued acting ; his roles included Major Celliers in Merry Christmas , Mr. Lawrence ( 1983 ) , the Goblin King Jareth in Labyrinth ( 1986 ) , Pontius Pilate in The Last Temptation of Christ ( 1988 ) , and Nikola Tesla in The Prestige ( 2006 ) , among other film and television appearances and cameos . He stopped concert touring after 2004 , and his last live performance was at a charity event in 2006 . In 2013 , Bowie returned from a decade-long recording hiatus with the release of The Next Day . He remained musically active until he died of liver cancer two days after the release of his final album , Blackstar ( 2016 ) .",
"title": ""
},
{
"docid": "Christian_Bale",
"text": "Christian Charles Philip Bale ( born 30 January 1974 ) is an English actor . He has starred both in blockbuster films and smaller projects from independent producers and art houses . Bale first caught the public eye at the age of 13 , when he was cast in the starring role of Steven Spielberg 's Empire of the Sun ( 1987 ) . Based on the original story by J. G. Ballard , Bale played an English boy who is separated from his parents and subsequently finds himself lost in a Japanese internment camp during World War II . In 2000 , he garnered critical acclaim for his portrayal of serial killer Patrick Bateman in American Psycho . He is known for going to great lengths to portray characters in films , notably for the psychological thriller The Machinist ( 2004 ) , where he lost 63 pounds ( 28.5 kg ) to play the role of Trevor Reznik . Bale went on to receive greater commercial recognition for his starring role as Batman in Christopher Nolan 's Batman Begins ( 2005 ) , The Dark Knight ( 2008 ) and The Dark Knight Rises ( 2012 ) . His portrayal of Dicky Eklund in the David O. Russell-directed biographical film The Fighter ( 2010 ) , earned him critical acclaim and a number of awards , including the Academy Award for Best Supporting Actor . He has since gained further acclaim as well as subsequent Academy Award , Screen Actors Guild Award and Golden Globe nominations for his roles in Russell 's American Hustle ( 2013 ) and Adam McKay 's The Big Short ( 2015 ) .",
"title": ""
},
{
"docid": "Hugh_Jackman",
"text": "Hugh Michael Jackman ( born 12 October 1968 ) is an Australian actor , singer , and producer . Jackman has won international recognition for his roles in a variety of film genres . He is known for his long-running role as Wolverine in the X-Men film series , as well as for his lead roles in films such as the romantic-comedy fantasy Kate & Leopold ( 2001 ) , the action-horror film Van Helsing ( 2004 ) , the magic-themed drama The Prestige ( 2006 ) , the epic fantasy drama The Fountain ( 2006 ) , the epic historical romantic drama Australia ( 2008 ) , the film version of Les Misérables ( 2012 ) , and the thriller Prisoners ( 2013 ) . His work in Les Misérables earned him his first Academy Award nomination for Best Actor and his first Golden Globe Award for Best Actor -- Motion Picture Musical or Comedy in 2013 . In Broadway theatre , Jackman won a Tony Award for his role in The Boy from Oz . A four-time host of the Tony Awards themselves , he won an Emmy Award for one of these appearances . Jackman also hosted the 81st Academy Awards on 22 February 2009 .",
"title": ""
},
{
"docid": "The_Prestige_(film)",
"text": "The Prestige is a 2006 British-American mystery thriller film directed by Christopher Nolan , from a screenplay adapted by Nolan and his brother Jonathan from Christopher Priest 's 1995 World Fantasy Award-winning novel of the same name . Its story follows Robert Angier and Alfred Borden , rival stage magicians in London at the end of the 19th century . Obsessed with creating the best stage illusion , they engage in competitive one-upmanship with tragic results . The film stars Hugh Jackman as Robert Angier , Christian Bale as Alfred Borden , and David Bowie as Nikola Tesla . It also stars Michael Caine , Scarlett Johansson , Piper Perabo , Andy Serkis , and Rebecca Hall . The film reunites Nolan with actors Bale and Caine from Batman Begins and returning cinematographer Wally Pfister , production designer Nathan Crowley , film score composer David Julyan , and editor Lee Smith . The film was released on October 20 , 2006 , receiving positive reviews and strong box office results , and received Academy Award nominations for Best Cinematography and Best Art Direction . Along with The Illusionist and Scoop , The Prestige was one of three films released in 2006 to explore the world of stage magicians .",
"title": ""
},
{
"docid": "Michael_Caine",
"text": "Sir Michael Caine , ( -LSB- keɪn -RSB- born Maurice Joseph Micklewhite Jr. ; 14 March 1933 ) is an English actor and author . Renowned for his distinctive working class cockney accent , Caine has appeared in over 115 films and is regarded as a British film icon . He made his breakthrough in the 1960s with starring roles in a number of acclaimed British films , including Zulu ( 1964 ) , The Ipcress File ( 1965 ) , Alfie ( 1966 ) , for which he was nominated for an Academy Award , The Italian Job ( 1969 ) , and Battle of Britain ( 1969 ) . His most notable roles in the 1970s included Get Carter ( 1971 ) , The Last Valley , Sleuth ( 1972 ) , for which he earned his second Academy Award nomination , The Man Who Would Be King ( 1975 ) , and A Bridge Too Far ( 1977 ) . He achieved some of his greatest critical success in the 1980s , with Educating Rita ( 1983 ) earning him the BAFTA and Golden Globe Award for Best Actor . In 1986 , he received an Academy Award for Best Supporting Actor for his performance in Woody Allen 's Hannah and Her Sisters . Caine played Ebenezer Scrooge in The Muppet Christmas Carol ( 1992 ) . Having by that time practically retired from acting on the big screen , he enjoyed a career resurgence in the late 1990s , receiving his second Golden Globe Award for his performance in Little Voice in 1998 and receiving his second Academy Award for Best Supporting Actor for The Cider House Rules the following year . Caine played Nigel Powers in the 2002 parody Austin Powers in Goldmember , and Alfred Pennyworth in Christopher Nolan 's The Dark Knight Trilogy . He appeared in several other of Nolan 's films including The Prestige ( 2006 ) , Inception ( 2010 ) , and Interstellar ( 2014 ) . He also appeared as a supporting character in Alfonso Cuarón 's Children of Men and Pixar 's 2011 film Cars 2 . As of February 2017 , films in which he has starred have grossed over $ 3.5 billion domestically and over $ 7.8 billion worldwide . Caine is ranked as the twelfth highest grossing box office star . Caine is one of only two actors nominated for an Academy Award for acting in every decade from the 1960s to 2000s ( the other one being Jack Nicholson ; Laurence Olivier was also nominated for an acting Academy Award in five different decades , beginning in 1939 and ending in 1978 ) . In 2000 , Caine was knighted by Queen Elizabeth II in recognition of his contribution to cinema .",
"title": ""
},
{
"docid": "Andy_Serkis",
"text": "Andrew Clement Serkis ( born 20 April 1964 ) is an English film actor and director . He is best known for his performance capture roles comprising motion capture acting , animation and voice work for such computer-generated characters as Gollum in The Lord of the Rings film trilogy ( 2001 -- 2003 ) and The Hobbit : An Unexpected Journey ( 2012 ) , King Kong in the eponymous 2005 film , Caesar in the Planet of the Apes reboot series ( 2011 -- present ) , Captain Haddock / Sir Francis Haddock in Steven Spielberg 's The Adventures of Tintin ( 2011 ) and Supreme Leader Snoke in Star Wars : The Force Awakens ( 2015 ) . Upcoming performance capture roles include Caesar in War for the Planet of the Apes ( 2017 ) , Supreme Leader Snoke in Star Wars : The Last Jedi ( 2017 ) , and Baloo in Jungle Book ( 2018 ) . Serkis ' film work in motion capture has been critically acclaimed . He has received an Empire Award , and two Saturn Awards for his motion-capture acting . He earned a Golden Globe nomination for his portrayal of serial killer Ian Brady in the British television film Longford ( 2006 ) and was nominated for a BAFTA for his portrayal of new wave and punk rock musician Ian Dury in the biopic Sex & Drugs & Rock & Roll ( 2010 ) . In 2015 , he began playing Ulysses Klaue in the Marvel Cinematic Universe beginning with Avengers : Age of Ultron . Serkis has his own motion capture workshop , The Imaginarium Studios in London , which he will use for his directorial debut , Jungle Book .",
"title": ""
}
] |
[
{
"docid": "James_Otis_(actor)",
"text": "James Otis ( born June 10 , 1943 in Stamford , Connecticut ) is an American film and television actor . Otis began his film career in the 1970s , where he first appeared in the film Dragonfly in 1976 , then made until 1998 , he made his first appearance in television including Profiler , he starred in one episode . In 1999 , Otis appeared in 3 episodes of Star Trek : Deep Space Nine . In 2006 , Otis appeared in the true story film The Black Dahlia , which starred Josh Hartnett and Scarlett Johansson . He also appeared in The Prestige , which starred Hugh Jackman and Christian Bale . Otis has performed in numerous audio plays for Peabody-winner Yuri Rasovsky . Otis appeared in the film Nite Tales : The Movie , which was released in December 2007 .",
"title": ""
},
{
"docid": "Prestige_picture",
"text": "A prestige picture is a film produced to bolster the film studio 's perceived artistic integrity , rather than to turn a large profit ; the studio may even expect the film to lose money . Prestige pictures are largely the province of major Hollywood film studios -- such as MGM and Warner Bros. -- that produce numerous films every year . In the 1930s , such studios might release one prestige picture per year . The films ' screenwriters drew material from historical events , well-known literary classics , or popular novels or plays . In many cases , Hollywood film studios have enlisted British actors and directors for the production of prestige films . One producer of prestige pictures within the United Kingdom 's own film industry was Alexander Korda ( 1893 -- 1956 ) .",
"title": ""
},
{
"docid": "Prestige_Hong_Kong",
"text": "Prestige Hong Kong is Hong Kong 's first luxury lifestyle and society magazine . Launched in September 2005 , Prestige Hong Kong is a monthly magazine with a mix of fashion , celebrities , culture , travel , high society and interviews with movie stars .",
"title": ""
},
{
"docid": "Coolin'",
"text": "Coolin ' is an album by the Prestige All Stars nominally led by vibraphonist Teddy Charles recorded in 1957 and released on the Prestige label .",
"title": ""
},
{
"docid": "Earthy_(Kenny_Burrell_album)",
"text": "Earthy is an album by the Prestige All Stars nominally led by guitarist Kenny Burrell recorded in 1957 and released on the Prestige label .",
"title": ""
},
{
"docid": "Olio_(Thad_Jones_album)",
"text": "Olio is an album by the Prestige All Stars nominally led by trumpeter Thad Jones recorded in 1957 and released on the Prestige label .",
"title": ""
},
{
"docid": "All_Night_Long_(Kenny_Burrell_album)",
"text": "All Night Long is an album by the Prestige All Stars nominally led by guitarist Kenny Burrell recorded in 1956 and released on the Prestige label .",
"title": ""
},
{
"docid": "Bruce_Lester",
"text": "Bruce Lester ( 6 June 1912 -- 13 June 2008 ) was a South African-born English film actor with over 60 screen appearances to his credit between 1934 and his retirement from acting in 1958 . Lester 's career divided into two distinct periods . Between 1934 and 1938 , billed as Bruce Lister , he appeared in upwards of 20 British films , mostly of the cheaply shot and quickly forgotten quota quickie variety . He then moved to the U.S. , where he changed his surname to Lester , and found himself for a time appearing in some of the biggest prestige productions of their day , alongside stars such as Bette Davis , Joan Crawford , Tyrone Power and Errol Flynn . Lester himself never achieved star-billing , but was said to have remarked that this at least meant that if a film was a flop , no blame ever fell on his shoulders .",
"title": ""
},
{
"docid": "Tenor_Conclave",
"text": "Tenor Conclave is an album by Hank Mobley , Al Cohn , John Coltrane and Zoot Sims . The album was originally recorded in 1956 and issued in 1957 on Prestige Records as PRLP 7074 , and was credited to the Prestige All Stars . However , as Coltrane 's fame grew during the 1960s after he had stopped recording for the label , Prestige would re-release it in 1962 as a new album , with a different cover prominently displaying Coltrane 's name . This reissue of the album was given the catalogue number PRLP 7249 .",
"title": ""
},
{
"docid": "Dakar_(album)",
"text": "Dakar is an album credited to jazz musician John Coltrane , released in 1963 on Prestige Records , catalogue 7280 . Dakar is a reissue of one side of a 16 rpm LP called Baritones and French Horns released in 1957 , and originally credited to the `` Prestige All Stars '' . As Coltrane 's fame grew during the 1960s after he had stopped recording for Prestige , the record company assembled and reissued varied Coltrane recordings with his name prominently displayed , though in many cases , as on Dakar , he had originally been a sideman .",
"title": ""
},
{
"docid": "After_Hours_(Thad_Jones_album)",
"text": "After Hours is an album by the Prestige All Stars nominally led by trumpeter Thad Jones recorded in 1957 and released on the Prestige label . The album was also re-released as Steamin ' by Frank Wess and Kenny Burrell in 1963 .",
"title": ""
},
{
"docid": "Baritones_and_French_Horns",
"text": "Baritones and French Horns is a 16 rpm album released in 1957 on Prestige Records . The album is one of a series of releases attributed to the Prestige All Stars . Each side of the album was a distinct date with distinct personnel . From a jazz.com review , Kenny Berger wrote , `` Among the many innovative technological failures of the mid - and late - 1950s , the 16-rpm phonograph record stands as the industry 's answer to the Edsel . One of Prestige 's contributions to this auditory dustbin was an LP on steroids titled Baritones and French Horns under the supervision of vibist , composer , arranger , A&R man Teddy Charles . The baritone side of this album was reissued twice on LP and twice more on CD under John Coltrane 's name -LSB- as Dakar -RSB- , though Pepper Adams was the actual leader on these sessions . '' The `` french horns '' side of the album was reissued as Prestige ST 8305 , Curtis Fuller and Hampton Hawes with French Horns .",
"title": ""
},
{
"docid": "Prestige_(film)",
"text": "Prestige is a 1932 American Pre-Code drama film directed by Tay Garnett and written by Tay Garnett , Rollo Lloyd and Francis Edward Faragoh . The film stars Ann Harding , Adolphe Menjou , Melvyn Douglas and Guy Bates Post . The film was released on January 22 , 1932 , by RKO Pictures .",
"title": ""
},
{
"docid": "Star_Bag",
"text": "Star Bag is an album by saxophonist Willis Jackson which was recorded in 1968 and released on the Prestige label .",
"title": ""
},
{
"docid": "Wheelin'_&_Dealin'",
"text": "Wheelin ' & Dealin ' is an album credited to The Prestige All Stars , a group including John Coltrane , Frank Wess and other jazz musicians who were under contract with the Prestige label . It was originally released in 1958 as PRLP 7131 , then reissued on New Jazz Records in 1964 as NJLP 8327 . The compact disc reissue adds two alternate takes that did not appear on the initial vinyl releases .",
"title": ""
},
{
"docid": "All_Star_Sessions",
"text": "All Star Sessions is an album by saxophonist Gene Ammons recorded between 1950 and 1955 and released on the Prestige label .",
"title": ""
},
{
"docid": "The_Total_Picture_Seminar",
"text": "The Total Picture Seminar , a California LLC , was formed by actor Martin Landau , director Mark Rydell , and screenwriter/playwright Lyle Kessler . The purpose is to educate actors , writers , and directors in the aspects of filmmaking . Martin Landau , Mark Rydell , and Lyle Kessler have worked together for many decades at The Actors Studio . They each bring industry experience , prestige , personal success , and a lifetime of teaching experience to this endeavor . The Seminar producer is Jeffry A. DeCola .",
"title": ""
},
{
"docid": "Lease_of_Life",
"text": "Lease of Life is a 1954 British film drama made by Ealing Studios and directed by Charles Frend . The film was designed as a star-vehicle for Robert Donat , representing his return to the screen after an absence of over three years during which he had been battling the chronic asthma which plagued his life and career . It was a prestige production which was generally respectfully , if not over-enthusiastically , received and gained Donat a nomination as ` Best British Actor ' at the 1955 British Academy Film Awards . In common with a number of other Ealing films of the era , Lease of Life focuses on a specific English milieu -- in this case a Yorkshire village and its nearby cathedral city -- and examines the nuances , quirks and foibles of its day-to-day life . The film is unique in the Ealing canon in having religion as its dominant theme .",
"title": ""
},
{
"docid": "Miles_Davis_All_Stars,_Volume_2",
"text": "Miles Davis All Stars , Volume 2 ( PRLP 200 ) is a 10-inch LP album by Miles Davis , released in 1955 by Prestige Records . The two side-long tracks on this LP , and two others , were recorded at Rudy Van Gelder 's Studio , Hackensack , New Jersey , on December 24 , 1954 . This was the second of two 10 '' LPs sourced from the same session , which featured major be-bop contemporaries Milt Jackson and Thelonious Monk , along with the same rhythm section that had been used on Davis ' other recent albums . Jackson , Heath , and Clarke were at the time of recording three-quarters of the Modern Jazz Quartet . After the 10 '' LP format was discontinued , both tracks were reissued on the 12 '' LP Miles Davis and the Modern Jazz Giants ( PRLP 7150 ) , along with `` Swing Spring '' from Volume 1 ( PRLP 196 ) , a previously unreleased alternate take of `` The Man I Love '' , from the same session , and an unrelated track from a later session with his First Great Quintet . This would be the last Miles Davis LP issued by Prestige in the short-lived 10 '' format . His next album , Musings of Miles ( PRLP 7007 ) , would be his first 12 '' LP , followed by Dig ( PRLP 7012 ) , which would be the first to repackage the older 10 '' material . Alternating albums of new and repackaged material would follow , until all the early Prestige material was now available in the new format .",
"title": ""
},
{
"docid": "Jiří_Bartoška",
"text": "Jiří Bartoška ( born March 24 , 1947 in Děčín ) is a Czech actor and the president of the Karlovy Vary International Film Festival . Bartoška is a popular Czech actor , and played a number of roles in Czech films . In 2000 , he won the Best Supporting Actor Award at the Czech Lion awards for his performance in All My Loved Ones , being nominated for the same award also the previous year for his performance in Sekal Has to Die . In 1994 , he became the president of the Karlovy Vary Film Festival . Together with Eva Zaoralová he managed to return popularity and prestige to the almost dead festival .",
"title": ""
},
{
"docid": "Order_of_the_Star_of_Italy",
"text": "Contains information from the corresponding article in the Italian Wikipedia The Order of the Star of Italy was formed in 2011 . The order was reformed from the Order of the Star of Italian Solidarity by the 11th President of Italy , Giorgio Napolitano . The emphasis of the reformed award was shifted from post-war reconstruction to the preservation and promotion of national prestige abroad , promoting friendly relations and co-operation with other countries and ties with Italy .",
"title": ""
},
{
"docid": "All_Day_Long",
"text": "All Day Long is a jazz album by guitarist Kenny Burrell , although it is nominally credited to the `` Prestige All Stars '' . It was released in 1957 under Prestige label as PRLP 7081 . It 's characterized by fast pieces and also was one of the first albums in which Burrell was presented as a leader . All the pieces were composed by the members of the band . The cover shows Verrazano-Narrows Bridge in the daytime and by night . Ira Gitler in the original liner notes points out that `` A.T '' is dedicated to Art Taylor ( hence the initials ) ; `` Say Listen '' `` derives its name from the attention calling phrase that -LSB- Byrd -RSB- often verbally employs .",
"title": ""
},
{
"docid": "Prestige_Group",
"text": "Prestige Group is a property development company in South India . It was founded by Razack Sattar in 1986 and is based in Bangalore , Karnataka , India . Prestige Group has several national and international awards in 11 various categories . Prestige has developed several residential colonies and commercial spaces in Bangalore , Chennai , Kochi , Hyderabad , Mangalore and Mysore including Prestige Shantiniketan , UB City , Prestige Golfshire , Prestige Acropolis , The Forum , The Forum Value , The Forum Vijaya",
"title": ""
},
{
"docid": "King_Baggot_(cinematographer)",
"text": "Stephen King Baggot , A.S.C. ( born August 15 , 1943 ) is an American cinematographer . Baggot is a member of the American Society of Cinematographers , a mark of prestige and distinction . He is the grandson of actor/director of the early 20th century , King Baggot .",
"title": ""
},
{
"docid": "Todd_Kerns",
"text": "Todd `` Dammit '' Kerns ( born December 5 , 1967 , Estevan , Saskatchewan , Canada ) is a Canadian musician who has worked with several successful Canadian bands , most notably gold certified Age of Electric . Kerns is currently the bass guitarist and back up vocalist for Slash . Kerns formed the group Static in Stereo with brother John Kerns ( also of Age of Electric ) , younger brother Ryan Kerns , and drummer Scott MacCargar . They released a self-titled album in 2002 . The band was nominated for a Canadian Radio Music Award for `` Best New Group '' in 2002 . Kerns is also known for his sold out acoustic solo shows featuring music from `` Borrowing Trouble '' , `` Go Time '' , `` TKO '' , etc. . Kerns also starred in the 1997 independent Canadian film Horsey . Along with Prestige Guitars Todd has released the signature Todd ` DAMMIT ' Kerns Anti-Star VI Guitar in both black and white , and also Signature Todd ` DAMMIT ' Kerns Anti-Star Bass . Todd Kerns also has his own clothing line Dammitwear that is currently in production with the Canadian Clothing line Agent Royale , and can be found in stores such as `` Steve 's Music '' and in the Prestige Guitar showrooms . He is currently touring with The Age of Electric across Canada on their reunion tour . <citation needed>",
"title": ""
},
{
"docid": "Prestige",
"text": "Prestige refers to a good reputation or high esteem ; in earlier usage , prestige meant `` showiness '' . ( 19th c. ) Prestige may also refer to : Prestige ( sociolinguistics ) , esteem in which languages or dialects are held",
"title": ""
},
{
"docid": "Occupational_prestige",
"text": "Occupational prestige ( also known as job prestige ) is a way for sociologists to describe the relative social class positions people have . It refers to the consensual nature of rating a job based on the belief of its worthiness . The term prestige itself refers to the admiration and respect that a particular occupation holds in a society . Occupational prestige is prestige independent of the particular individual who occupies a job . Sociologists have identified prestige rankings for more than 700 occupations based on results from a series of national surveys . They created a scale with 0 being the lowest possible score to 100 being the highest , and then ranked the occupations based on the results of the survey .",
"title": ""
},
{
"docid": "List_of_prestige_classes",
"text": "This is a list of prestige classes in the 3rd edition of the Dungeons and Dragons role-playing game . Prestige classes were introduced in third edition as a further means of individualizing a character . This list includes content for both the original 3rd edition and the 3.5 revision . Nearly every official supplement source book and most issues of Dragon magazine introduced new prestige classes . This list does not include prestige classes from third-party material offered under the d20 System or the Open Game License . It also does not include prestige classes in video games based on Dungeons & Dragons , such as the Neverwinter Nights series . Some prestige classes , such as the Bladesinger , Ur-Priest , and the Purple Dragon Knight , are printed in multiple sources . Sometimes there are slight revisions between these reprints , while others are exact duplications . As a result , there are fewer total prestige classes than the sum of those appearing in each source .",
"title": ""
},
{
"docid": "Prestige_Public_School",
"text": "Prestige Public School ( also known as Prestige International School ) , Indore is a public school located in Indore , India , at Prestige Vihar , Vijay Nagar . The school is affiliated with the Central Board of Secondary Education ( CBSE ) , and CBSE-i ( CBSE-International ) , it is one of the only 50 schools affiliated with CBSEi across India . It recently came up with its new ventures in Dewas ( Prestige Public School , Dewas ) and Gwalior ( Prestige Public School , Gwalior ) .",
"title": ""
},
{
"docid": "Walkin'",
"text": "Walkin '' '' ( PRLP 7076 ) is a Miles Davis compilation album released in 1957 by Prestige Records . The album compiles material previously released on two 10 inch LPs in 1954 , along with one previously unreleased tune . Here credited to the `` Miles Davis All-Stars '' , the songs were recorded on 3 April and 29 April 1954 by two slightly different groups led by Davis . Both sessions were recorded at Rudy Van Gelder 's home studio . The earlier session was a quintet with David Schildkraut on alto saxophone , and produced the three tracks on side two . Schildkraut is the only musician not credited on the cover , and is otherwise almost unknown . Two of these tracks were originally released on the 10 '' LP Miles Davis Quintet , Prestige PRLP 185 . The earlier release also included `` I 'll Remember April '' , recorded at the same time , now found on the Prestige album Blue Haze ( PRLP 7054 ) . Another tune from this session , `` Love Me or Leave Me , '' was previously unreleased and substituted here for `` I 'll Remember April . '' The second session , which makes up all of side one , was a sextet with J. J. Johnson on trombone and Lucky Thompson on tenor saxophone . The rhythm section was the same as the earlier session . These two tracks were originally issued on the 10 `` LP Miles Davis All-Star Sextet PRLP 182 . The album 's title track , a staple of Davis 's live set for many years , was key to the emerging hard bop approach developed in the mid-1950s , Davis providing it with an anthem . Written by Davis , the composition royalties for `` Walkin ' '' were credited to his friend Richard Carpenter . The song was also covered by Bobby McFerrin on his 1987 album Spontaneous Inventions '' .",
"title": ""
}
] |
107927
|
Katie Holmes' birth year is 1978.
|
[
{
"docid": "Katie_Holmes",
"text": "Kate Noelle Holmes ( born December 18 , 1978 ) is an American actress who first achieved fame for her role as Joey Potter on The WB television teen drama Dawson 's Creek from 1998 to 2003 . She appeared in 1998 's Disturbing Behavior , a thriller , which won her an MTV Movie Award for Best Breakthrough Performance . In 2000 Holmes featured in Wonder Boys which got positive attention from many leading critics . Holmes had a starring role in 2003 's Pieces of April , a gritty comedy about a dysfunctional family on Thanksgiving . In the 2005 film Batman Begins , the highest-grossing film of her career to date , she played Rachel Dawes , Gotham City 's assistant district attorney and Bruce Wayne 's childhood sweetheart . She also appeared in art house films such as The Ice Storm , horror films such as Do n't Be Afraid of the Dark and thrillers including Abandon . She has also played on Broadway in a production of Arthur Miller 's All My Sons and had numerous guest roles on television programs such as How I Met Your Mother . In 2011 , she starred as Jacqueline Kennedy in the The Kennedys miniseries , a role she later reprised in the 2017 miniseries The Kennedys : After Camelot . Her marriage to actor Tom Cruise from 2006 to 2012 led to a great deal of media attention , with the pair being called a supercouple and given the nickname `` TomKat '' .",
"title": ""
}
] |
[
{
"docid": "Katie_Holmes_(historian)",
"text": "Katie Holmes is a professor of history at La Trobe University , Melbourne , Australia .",
"title": ""
},
{
"docid": "Kate_Holmes",
"text": "Kate Holmes may refer to : Katie Holmes -- American actress Kate Holmes -- British keyboarder and head of the band Client known as Client A Kate Holmes -- one of pen names of the American writer Anne Holmberg",
"title": ""
},
{
"docid": "All_We_Had",
"text": "All We Had is a 2016 American drama film directed by Katie Holmes and written by Josh Boone . It is based on the 2014 novel All We Had by Annie Weatherwax . The film stars Katie Holmes , Stefania LaVie Owen , Luke Wilson , Richard Kind , Mark Consuelos , Judy Greer and Eve Lindley . The film was released on December 9 , 2016 , by Gravitas Ventures .",
"title": ""
},
{
"docid": "Katie_King_(spirit)",
"text": "Katie King was the name given by Spiritualists in the 1870s to what they believed to be a materialized spirit . The question of whether the spirit was real or a fraud was a notable public controversy of the mid-1870s . The spirit was said to have appeared first between 1871 and 1874 in séances conducted by Florence Cook in London , and later in 1874-1875 in New York in séances held by the mediums Jennie Holmes and her husband Nelson Holmes . Katie King was believed by Spiritualists to be the daughter of John King , a spirit control of the 1850s through the 1870s that appeared in many séances involving materialized spirits . ( A spirit control is a powerful and communicative spirit that organizes the appearance of other spirits at a séance . John King claimed to be the spirit of Henry Morgan , the buccaneer ( Doyle 1926 : volume 1 , 241 , 277 ) . )",
"title": ""
},
{
"docid": "Larry_Holmes",
"text": "Larry Holmes ( born November 3 , 1949 ) is an American former professional boxer who competed from 1973 to 2002 . He grew up in Easton , Pennsylvania , which gave birth to his boxing nickname of the `` Easton Assassin '' . Holmes , whose left jab is rated among the best in boxing history , held the WBC heavyweight title from 1978 to 1983 , The Ring magazine and lineal heavyweight titles from 1980 to 1985 , and the inaugural IBF heavyweight title from 1983 to 1985 . He made 20 successful title defenses , placing him third all time , behind only Joe Louis at 25 and Wladimir Klitschko at 22 . Holmes is one of only five boxers -- along with Joe Frazier , Ken Norton , Leon Spinks and Trevor Berbick -- to defeat Muhammad Ali ; he is the only one to have stopped Ali . Holmes won his first 48 professional bouts , including victories over Norton , Ali , Earnie Shavers , Mike Weaver , Gerry Cooney , Tim Witherspoon , Carl Williams and Marvis Frazier , and falling one short of matching Rocky Marciano 's career record of 49 -- 0 when he lost to Michael Spinks in 1985 . Holmes retired after losing a rematch to Spinks the following year , but made repeated comebacks . He was unsuccessful in three further attempts ( against Mike Tyson , Evander Holyfield and Oliver McCall ) to regain the heavyweight title , the last in 1995 . Holmes fought for the final time in 2002 , against Eric `` Butterbean '' Esch , and ended his career with a record of 69 wins and 6 losses . He is frequently ranked as one of the greatest heavyweights of all time and has been inducted into both the International Boxing Hall of Fame and World Boxing Hall of Fame .",
"title": ""
},
{
"docid": "Robert_E._Holmes",
"text": "Robert Edward Holmes ( November 14 , 1922 -- July 28 , 2004 ) was an associate justice of the Ohio Supreme Court from 1978 until 1992 . A conservative jurist , he had previously represented his native Franklin County in the Ohio House of Representatives from 1961 until 1968 and on Ohio Tenth District Court of Appeals from 1968 until 1978 when he moved to the Supreme Court and was replaced on the Appeals Court bench by Thomas J. Moyer . In 1978 , Governor Rhodes appointed Holmes to the seat on the Supreme Court vacated when Frank Celebrezze was elected as Chief Justice . He won election to six-year terms in 1980 and 1986 , but was prevented from running again in 1992 , because the new term would not begin until after his 70th birthday , the mandatory age limit to begin a term on the court . He was a graduate of Ohio University where he was a member of Phi Kappa Tau fraternity and the Ohio State University 's Moritz College of Law . Holmes married Marjory Jean Holmes on August 23 , 1952 , and they had two sons . She died in 1977 . Holmes later married Patricia S. Mishey , who died in 1999 . Holmes died at home in Powell , Ohio in 2004 .",
"title": ""
},
{
"docid": "Katie_Scalamandre",
"text": "Katie Scalamandre became World Backgammon champion in 2000 on defeating Thomas Holm of Denmark . Her husband Gino is a noted backgammon player as well . She was ranked 62nd on a list of `` 100 of the Best Backgammon Players . ''",
"title": ""
},
{
"docid": "Sheila_Cameron_(artist)",
"text": "Sheila Cameron is an American artist , blogger , graphic designer and producer based in California . She is mostly known for initiating the `` Free Katie '' campaign , in which she designed and sold merchandise in response to the news of Katie Holmes 's engagement to Tom Cruise .",
"title": ""
},
{
"docid": "Katie_Spencer",
"text": "Katie Spencer is a set director . She has been nominated for an Academy Award four times : for her set directing in Pride and Prejudice and Atonement ; and for her set decoration in Sherlock Holmes and Anna Karenina . She has worked many films and TV series with Sarah Greenwood .",
"title": ""
},
{
"docid": "Josh_Holmes",
"text": "Josh or Joshua Holmes may refer to : Josh Holmes ( rugby union ) ( born 1987 ) , Australian rugby union player Josh Holmes ( singer-songwriter ) ( born 1978 ) , Josh Holmes ( video game designer ) ( born 1973 ) , Canadian game producer and video game designer Joshua Holmes ( model ) ( born 1978 ) , American model and ultramarathoner",
"title": ""
},
{
"docid": "Katie_Wagner",
"text": "Katharine `` Katie '' Wagner ( born May 11 , 1964 ) is an American television personality and Hollywood reporter . She was named after actress and family friend Katharine Hepburn . Wagner was born in Los Angeles , California . Her parents are actress Marion Marshall and actor Robert Wagner . They divorced in 1971 when she was seven years old . On her mother 's side she has two older half-brothers , Josh Donen and Peter Donen . On her father 's side , she has a younger half-sister , Courtney Wagner . She has a former stepsister Natasha Gregson Wagner from her father 's marriage to Natalie Wood . Her stepmother is Jill St. John . Katie graduated from Beverly Hills High School in 1982 and attended Santa Barbara City College for a semester . After dropping out of college , she dabbled in modeling , which allowed her to live in Tokyo and London . Katie received a break in 1987 , when she and her father were featured on the TV show Born Famous . The show 's host asked her what she hoped to do for a living . Her answer : `` I would like to do what you do . '' Katie 's first media job was for the Don Mischer special M & W on ABC , for which she interviewed Dan Aykroyd and his wife , Donna Dixon . This resulted in a two-and-a-half-year run at the Movietime Cable Network ( Now E! Network ) . Katie went on to work at HBO , Cinemax , V , and MTV . At MTV , she guest-hosted from both coasts . She also co-hosted Awake on the Wildside , filled in for Chris Connelly on The Big Picture , and introduced videos at night . For two years , Katie Wagner co-hosted an international entertainment show called Hollywood Report with Richard Jobson on ITV in Great Britain . The show was seen in 11 countries . Katie then co-hosted 22 episodes of Live From the House of Blues on TBS . She joined Robin Leach for the final two seasons of Lifestyles of the Rich and Famous as co host and contributing reporter . Then , Katie was asked to narrate and co-produce Intimate Portrait : Natalie Wood , about her late stepmother . With the cooperation of her family , Katie shared private details of Ms. Wood 's life for the first time . In 1999 , she began working for the TV Guide Channel . Her hosting duties included Music News , TV Talk , Family Do 's and Do n'ts , and What 's On . In 2004 , after 5 1/2 years , she left the TV Guide Channel to do her own show . Later that year , she played a news reporter in the Charmed episode , `` Styx Feet Under '' and was a guest star on the talk show , Good Day Live . In 2005 , Katie was host of the WB show , The Starlet . On September 21 , 2006 , she gave birth to her first child , Riley John Wagner-Lewis . She married her boyfriend , Leif Lewis , in July 2007 . Katie currently hosts an online radio show with psychic medium `` Voxx '' at The JOINT Studios called `` Inner View with Katie & Voxx '' .",
"title": ""
},
{
"docid": "Katie_(disambiguation)",
"text": "Katie is a feminine given name . It may also refer to : Katie , Oklahoma , United States , a town , a United States Navy patrol vessel in commission from 1917 to 1918 Katie ( talk show ) , a syndicated American talk show ( 2012 -- 2014 ) hosted by Katie Couric Katie ( TV series ) , a reality TV show about Katie Price Katie : Portrait of a Centerfold , a 1978 American TV movie starring Kim Basinger",
"title": ""
},
{
"docid": "James_Atkins_(defensive_tackle)",
"text": "James Hodges Atkins IV ( born June 23 , 1978 in Brooklyn , New York ) is a former professional American football player who played defensive tackle for two seasons for the Tennessee Titans and the San Francisco 49ers . Category :1978 births Category : Living people Category : Sportspeople from Brooklyn Category : Players of American football from New York Category : American football defensive tackles Category : Undrafted National Football League players Category : Holmes Bulldogs football players Category : Virginia Union Panthers football players Category : Tennessee Titans players Category : San Francisco 49ers players",
"title": ""
},
{
"docid": "Howdy_Holmes",
"text": "Howdy S. Holmes ( born December 14 , 1947 , Ann Arbor , Michigan ) , is a former driver in the CART Championship Car series . He began racing in the early 1970s and was based in Stockbridge , Michigan , about 15 mi northeast of Chelsea , Michigan where his family owned a milling company . He raced in the CART series for 7 seasons ( 1979-1980 , 1982-1985 , and 1988 ) , with 72 career starts , including the Indianapolis 500 each of those years except 1980 . He finished in the top ten 26 times , with his best finish in 2nd position in 1984 at Phoenix . He was the Indianapolis 500 Rookie of the year in 1979 , with a 7th-place finish . In 1978 , he was the Formula Atlantic champion . Holmes is currently the President of Chelsea Milling Company , his family 's firm that was founded in 1901 . Holmes ' grandmother Mabel became famous for inventing the Jiffy line of baking mixes in 1930 , and the family brand served as a sponsor for Holmes ' cars .",
"title": ""
},
{
"docid": "Adams_Fall",
"text": "Adams Fall is writer Sean Desmond 's first novel . It recounts the events which occur to a college student in his senior year at Harvard University . In the midst of completing his thesis and applying for a study abroad program , the narrator copes with his stresses by resorting to alcohol and drugs . Adams House , a real House at Harvard , features prominently in the novel ; the author is himself a Harvard graduate . The novel was the ( loose ) basis for the 2002 film Abandon starring Katie Holmes .",
"title": ""
},
{
"docid": "Kid_Acne",
"text": "Kid Acne is an artist , illustrator and hip-hop musician . He was born in Lilongwe , Malawi in 1978 . He grew up in Lutterworth , Leicestershire and currently lives and works in Sheffield , South Yorkshire , England . He spent his formative years painting graffiti , creating fanzines and making limited run records on his own Invisible Spies imprint . Nowadays , his artwork can been seen throughout the world -- both inside and outside of galleries . His signature style has adorned products for leading brands such as Prada , Kenzo , Elle , Kid Robot , Brompton and Warp Records . In 2014 Kid Acne collaborated with Dr Katie Edwards , an academic at The University of Sheffield , on ` The Word Made Fresh ' project for the university 's The Festival of the Mind . As part of the project , Kid Acne painted a mural version of his work ` The Birth of Hip Hop ' on the side of the Old Junior School in Sharrowvale , Sheffield . He also created a new rap , ` The Universe Rap ' , for the project .",
"title": ""
},
{
"docid": "Michelle_Stith",
"text": "Michelle Stith , née Henderson , also known as Chel Stith , is as of August 6 , 2005 President of the Church of Scientology of Los Angeles . Stith has been quoted in the press answering questions about Scientology and its practices . According to Scientology publications , Stith has attained the Operating Thetan level of `` OT III Expanded '' . In 2005 , she stated that she had been a member of Scientology for thirty-four years . Stith commented on the 2004 production of A Very Merry Unauthorized Children 's Scientology Pageant , stating that Scientology did not want to protest the theatre production , and was quoted as saying `` This is not litigation material . '' In July 2005 , Stith defended Scientology in media sources , after the Tom Cruise incident with Matt Lauer on The Today Show where Brooke Shields ' use of medication for postpartum depression was discussed . Stith called criticism by the media `` hogwash '' , and stated `` This is a very practical religion . '' In August 2005 , Stith was quoted as asserting that Scientology has 40,000 members in the Los Angeles area alone . In 2005 , Stith has asserted that Scientology has grown more internationally in the past five years , than in all previous years combined , and that its current membership numbered 10 million . Stith stated that her sister was a member of the Sea Org , and has five children , when asked about rumors of coerced abortions within Scientology . She went on to note that she herself is a mother of four , works as an artist , and also works forty-hours per week for Scientology . In 2006 , Stith 's pregnancy and delivery was reported on in the Chicago Daily Herald , in a report analyzing the silent birth practices of Scientology , and how this would apply to Katie Holmes . The birth of Stith 's fifth child , a boy , was described , in which Stith refused painkillers , and there was silence in the delivery room . All of the medical personnel were also quiet , and when the baby was born , the physician whispered to Stith `` It 's a boy . '' When asked about L. Ron Hubbard 's own use of medications , and the presence of certain medications in the coroner 's toxicology report after Hubbard 's death , Stith stated : `` He might have been taking some medicine for asthma , but he certainly was not under any medicine for psychiatric reasons . ''",
"title": ""
},
{
"docid": "Gavrielle_Holmes",
"text": "Gavrielle Holmes also known as Gavrielle Gemma was a third-party candidate ( Workers World Party ) for President of the United States in the U.S. presidential election , 1984 , receiving votes in Ohio ( 2,565 ) and Rhode Island . For other states , the presidential candidate that year was Larry Holmes . She had also been the running mate for Deirdre Griswold in the 1980 U.S. presidential election . She is currently a Workers World Party organizer in New York City . Category : Year of birth missing ( living people ) Category : Living people Category : Female United States presidential candidates Category : United States presidential candidates , 1984 Category :20 th-century American politicians Category : United States vice-presidential candidates , 1980 Category : Workers World Party presidential nominees Category : Female United States vice-presidential candidates Category : Workers World Party vice-presidential nominees Category :20 th-century women politicians",
"title": ""
},
{
"docid": "Arne_E._Holm",
"text": "Arne Ellerhusen Holm ( 11 June 1911 -- 31 January 2009 ) was a Norwegian painter , graphic artist and architect . He was born in Bergen as a son of banker Arne Holm ( 1880 -- 1975 ) og Anne Sophie Wibye Ellerhusen ( 1880 -- 1920 ) . He was a grandson of Ingebrigt Holm . He grew up in Bergen until the age of seven , then in Kristiania for a few years and finally Trondhjem . He enrolled in architect studies at his hometown 's Norwegian Institute of Technology . He took one year off at the Norwegian National Academy of Fine Arts , studying under Axel Revold and Jean Heiberg from 1934 to 1935 , but returned to finish his architect 's degree in 1937 . He followed with one additional year at the National Academy of Fine Arts , now under Georg Jacobsen . In 1938 he married Else Hagen . He was a teacher at the Norwegian National Academy of Craft and Art Industry from 1938 , but in 1947 he was appointed as a professor at the Norwegian Institute of Technology . He remained here until his retirement in 1978 . He made his exhibition debut as a painter in 1942 , and the painting Juninatt ( 1945 ) was bought by the National Gallery of Norway in 1946 . He is also known for designing several stamps in the 1960s , for his altarpiece at Herøya Church as well as decorating corporate headquarters . He served as vice chairman , later chairman of Trondhjems Kunstforening between 1955 and 1971 . He was decorated as a Knight , First Class of the Order of St. Olav in 1978 and was awarded the Gunnerus Medal in 1989 . Himself a numismatist , he donated his coin collection to the Royal Norwegian Society of Sciences and Letters museum . He died in January 2009 in Oslo , where he lived after retiring .",
"title": ""
},
{
"docid": "Rachel_Dawes",
"text": "Rachel Dawes is a fictional character who first appeared in Christopher Nolan 's 2005 feature film Batman Begins . She was portrayed in that film by Katie Holmes , with Emma Lockhart as a younger version of the character in early scenes . Holmes also voiced the character in the video game adaptation . Maggie Gyllenhaal replaced Holmes in the 2008 sequel The Dark Knight after Holmes chose not to reprise the role . Gyllenhaal also appeared as Dawes on the viral marketing website I Believe in Harvey Dent , giving Harvey Dent her endorsement in the District Attorney election . In the Dark Knight Trilogy , Rachel is Bruce Wayne 's childhood sweetheart and one of the few people who truly knows him . The conflict between Bruce 's love for her and his secret life as Batman is one of the main themes of the first two films in the trilogy , while her death in The Dark Knight in part motivates his actions in the third and final film , The Dark Knight Rises .",
"title": ""
},
{
"docid": "Joseph_Holmes",
"text": "Joseph or Joe Holmes may refer to : Joseph Holmes ( New Jersey ) ( 1736 -- 1809 ) , American politician Joseph Erskine Holmes ( born 1940 ) , Northern Irish politician Joseph John Holmes ( 1866 -- 1942 ) , Australian politician Joseph Warren Holmes ( 1824 -- 1912 ) , American sea captain Joseph William Holmes ( 1842 -- 19 ?? ) , Canadian politician Joe Holmes ( born 1963 ) , American heavy metal guitarist Joe Holmes ( rugby league ) , rugby league footballer Joe Holmes ( singer ) ( 1906 -- 1978 ) , Irish fiddler , lilter and singer",
"title": ""
},
{
"docid": "Holme_Wood",
"text": "Holme Wood is a housing estate in Bradford , West Yorkshire , England . It borders Tyersal . It is the birthplace of actresses Sophie McShera and Jennifer Metcalfe . The estate is managed by Incommunities and Bradford Council . It is also one of the largest former council estate in Europe . The estate is situated off Wakefield Road in the south-east of the city . Pockets of Holme Wood are in the top 5 % and 1 % of the Governments Index of Deprivation ( 2015 ) . Voluntary sector groups , churches and schools work tirelessly to address the issues of poverty and deprivation on this 1950 's housing estate . The estate is predominately white British ; however , there has been in an increase in ethnic minority groups over recent years . Place of birth - residents of Tong Ward - United Kingdom 82.8 % Republic of Ireland 0.4 % Other EU Countries 3.1 % Outside the EU 13.6 % The estate is in Tong Ward and is often spelt as Holmewood ; however , residents refer to it as Holme Wood . The estate is rambling ; however , there are many pleasant green areas dotted around the estate and close by is the village of Tong , which is in the green belt .",
"title": ""
},
{
"docid": "Coup_d'Etat_(2017_film)",
"text": "Coup d'Etat is an upcoming American satirical comedy film by Lisa Addario and Joe Syracuse . The film stars Michael Caine , Odeya Rush and Katie Holmes .",
"title": ""
},
{
"docid": "Ketevan_(album)",
"text": "Ketevan '' is the sixth studio album by Georgian-British singer Katie Melua , released in the United Kingdom on 16 September 2013 through Dramatico . At birth Melua was given the name Ketevan , but later she adopted the name Katie .",
"title": ""
},
{
"docid": "Katie_Gold",
"text": "Katie Gold ( born March 7 , 1978 ) is an American pornographic actress .",
"title": ""
},
{
"docid": "Katie_Stewart",
"text": "Katharine Elizabeth Allen Stewart ( 23 July 1934 -- 13 January 2013 ) , known as Katie Stewart , was an English cookery writer whose columns in The Times made her a household name in the 1960s and 1970s . After training at the Westminster Hotel School , she worked as nanny for a rich family in Paris , where she gained a diploma from the Cordon Bleu school , and then spent two years working in the test kitchens of the Nestlé company in White Plains , New York . There she learned how to record recipes accurately and how to prepare food to be photographed . On return to England in 1959 she joined the magazine company Fleetway Publications as a junior cookery writer , and in 1966 became cookery editor on the Woman 's Journal , a post she held for 32 years . In 1966 she also began to contribute to The Times , where until 1978 she had a column every Saturday and a whole page of recipes once a month . In 1972 she published The Times Cookery Book , a classic of which her obituary in The Telegraph said : `` Unlike some recipe books from the early 1970s , Katie Stewart 's book remains timelessly useful . Alongside the glossily pristine productions of Gordon Ramsay , Sophie Dahl , Ottolenghi et al , The Times Cookery Book is almost always recognizable from its broken spine and pages dog-eared and stained with the oil and gravy of many years ' service . Clean replacements are hard to find . '' She published a number of other books , including The Pooh Cook Book ( 1971 ) and The Sociable Cook ( 2001 ) , and in the early 1970s made three series of Cooking with Katie programmes for Grampian Television .",
"title": ""
},
{
"docid": "Terry_Holmes",
"text": "Terence David `` Terry '' Holmes ( born 10 March 1957 , Cardiff ) is a Welsh former rugby union and professional rugby league footballer who won 25 caps for as a scrum-half and later played rugby league for Bradford Northern . Holmes joined the Cardiff Youth side at the age of sixteen and went on to play for the senior side for ten seasons . Given the task of filling the Wales scrum-half position after the retirement of Gareth Edwards , aged 21 Holmes won his first cap for Wales in 1978 against . He went on to play in the Triple Crown winning side of 1979 . He won 25 caps , playing his last match against in 1985 , and scored 9 tries for Wales . Holmes also played for the British and Irish Lions on their 1980 tour to South Africa and 1983 tour to New Zealand , but was forced to return home early through injury from both tours . In late 1985 , Holmes became one of the biggest names of the time to turn professional , when he joined Bradford Northern for # 80,000 . However injuries meant that he only played 40 games for the club before his retirement two years later . After retirement , Holmes coached Cardiff and then Caerphilly rugby union teams , resigning as Caerphilly coach owing to business commitments in 2002 .",
"title": ""
},
{
"docid": "You_Made_It_Weird_with_Pete_Holmes",
"text": "You Made It Weird is a semi-weekly comedy interview podcast hosted by comedian Pete Holmes on the Nerdist network since October 25 , 2011 . The show originated under the premise that Holmes would ask his guest , usually a fellow comedian , about three `` weird '' things he knew about them , but the show has since evolved into a much more loose conversation about such complex topics as comedy , religion , and sexuality . While initially focusing on interviews with comedians , an increasing number of guests from other fields have appeared on the show , including musicians , pastors , scientists , and authors . Many guests comment on Holmes ' unique laugh , which tends to be very loud and borderline obnoxious . Katie Levine is the producer of the podcast . The show is usually recorded in-studio at the Nerdist studio at Meltdown Comics in Los Angeles , California . Since March 21 , 2012 , Holmes has recorded multiple live episodes of the podcast , in Austin at South by Southwest , New York , Bloomington , Chicago , Montreal , Quebec , San Francisco , Los Angeles at the LA Riot Festival , and Toronto at Just For Laughs . These have featured several guests rather than the usual one , and focus more on comedy rather than the in-depth discussion of a regular episode .",
"title": ""
},
{
"docid": "Stephen_Holmes",
"text": "Stephen , Steven or Steve Holmes may refer to : Stephen Holmes ( academic ) , American political scientist Stephen Holmes ( CIA ) , American intelligence officer Steve Holmes ( actor ) ( born 1961 ) , Romanian-born German pornographic actor Steve Holmes ( footballer ) ( born 1971 ) , retired English footballer Steven Holmes ( born 1965 ) , Canadian curator Stephen Holmes ( politician ) , member of the New Hampshire House of Representatives 2012-2014 Stephen Holmes ( businessman ) , CEO of Wyndham Worldwide hotels Stephen Holmes ( High Commissioner ) , British High Commissioner to Australia 1952-56 Stephen Holmes ( actor ) , guest actor in Gehenna ( Millennium ) TV episode Stephen Holmes ( died 1978 ) , first victim of UK serial killer Dennis Nilsen Stephen Holmes , candidate in 2007 Ontario provincial election",
"title": ""
},
{
"docid": "Katy_Kurtzman",
"text": "Katy Kurtzman ( born September 16 , 1965 , Washington , D.C. ) is an American actress . She began her career as a child actress . In 1977 , Michael Landon cast Katy as stuttering Anna who was abused by Nellie on Little House on the Prairie . Katy also starred in the `` Little House on the Prairie '' fourth season episode `` I Remember , I Remember '' with Matthew Laborteaux , playing young Caroline and young Charles , respectively . This episode aired on January 23 , 1978 and is Production # 4016 . She is probably best remembered for her roles as Heidi in The New Adventures of Heidi ( 1978 ) and as Lindsay Blaisdel in the television drama Dynasty ( 1981 ) . She starred in the NBC pilot Allison Sydney Harrison with Ted Danson , playing an amateur detective . She played Nettie in episode 21 ( The Scavengers ) of How the West Was Won . In 2001 , she wrote and directed the 14-minute short titled The Pool Boy . Her most recent acting role came in 2004 when she guest-starred on an episode of Grey 's Anatomy .",
"title": ""
}
] |
PLAIN-1984
|
rash
|
[
{
"docid": "MED-5128",
"text": "BACKGROUND: Elevated total homocysteine (tHcy) concentrations have been associated with cognitive impairment, but it is unclear whether low vitamin B-12 or folate status is responsible for cognitive decline. OBJECTIVE: We examined the associations of cognitive decline with vitamin B-12 and folate status in a longitudinal cohort study performed from 1993 to 2003 in Oxford, United Kingdom. DESIGN: Cognitive function was assessed with the Mini-Mental State Examination on >/=3 occasions during 10 y and related to serum concentrations of vitamin B-12, holotranscobalamin (holoTC), tHcy, methylmalonic acid (MMA), and folate with the use of linear mixed models in 1648 participants who provided blood in 1995. RESULTS: Cognitive function declined abruptly at younger ages in some participants but remained intact in others until very old age. In multivariate regression analyses after adjustment for established risk factors, concentrations of holoTC (a marker of reduced vitamin B-12 status), tHcy, and MMA predicted cognitive decline, but folate did not. A doubling in holoTC concentrations (from 50 to 100 pmol/L) was associated with a 30% slower rate of cognitive decline (-0.137 to -0.083), whereas a doubling in tHcy (from 10 to 20 micromol/L) or MMA (from 0.25 to 0.50 micromol/L) was associated with >50% more rapid cognitive decline (-0.090 to -0.169) and (-0.104 to -0.169), respectively. After adjustment for all vitamin markers simultaneously, the associations of cognitive decline with holoTC and MMA remained significant. CONCLUSIONS: Low vitamin B-12 status was associated with more rapid cognitive decline. Randomized trials are required to determine the relevance of vitamin B-12 supplementation for prevention of dementia.",
"title": "Low vitamin B-12 status and risk of cognitive decline in older adults."
},
{
"docid": "MED-2016",
"text": "BACKGROUND: Coeliac disease is a common, autoimmune disorder, for which the only treatment is lifelong adherence to a gluten-free diet. This study evaluates the economic burden of adhering to a gluten-free diet. METHODS: A market basket of products identified by name brand, weight or package size for both regular wheat-based products and gluten-free counterparts was developed. The differences in price between purchase venues, both type of store (general grocery store, an upscale grocery store and a health food store and four internet-based grocery sites) and region was also analysed. RESULTS: Availability of gluten-free products varied between the different venues, regular grocery stores carried 36%, while upscale markets carried 41%, and health food stores 94%, compared with 100% availability on the internet. Overall, every gluten-free product was more expensive than their wheat-based counterpart (P <or= 0.05). Bread and pasta was twice as expensive as their wheat-based counterparts. Cost was affected more by shopping venue than geographic location. CONCLUSIONS: This study demonstrated that gluten-free foods have poor availability and are more expensive than their gluten-containing counterparts. The impact of these findings on dietary compliance and the quality of life needs to be addressed.",
"title": "Economic burden of a gluten-free diet."
},
{
"docid": "MED-5131",
"text": "The usual dietary sources of vitamin B(12) are animal foods, meat, milk, egg, fish, and shellfish. As the intrinsic factor-mediated intestinal absorption system is estimated to be saturated at about 1.5-2.0 microg per meal under physiologic conditions, vitamin B(12) bioavailability significantly decreases with increasing intake of vitamin B(12) per meal. The bioavailability of vitamin B(12) in healthy humans from fish meat, sheep meat, and chicken meat averaged 42%, 56%-89%, and 61%-66%, respectively. Vitamin B(12) in eggs seems to be poorly absorbed (< 9%) relative to other animal food products. In the Dietary Reference Intakes in the United States and Japan, it is assumed that 50% of dietary vitamin B(12) is absorbed by healthy adults with normal gastro-intestinal function. Some plant foods, dried green and purple lavers (nori) contain substantial amounts of vitamin B(12), although other edible algae contained none or only traces of vitamin B(12). Most of the edible blue-green algae (cyanobacteria) used for human supplements predominantly contain pseudovitamin B(12), which is inactive in humans. The edible cyanobacteria are not suitable for use as vitamin B(12) sources, especially in vegans. Fortified breakfast cereals are a particularly valuable source of vitamin B(12) for vegans and elderly people. Production of some vitamin B(12)-enriched vegetables is also being devised.",
"title": "Vitamin B12 sources and bioavailability."
},
{
"docid": "MED-2037",
"text": "Celiac disease is an immune-mediated inflammatory disorder of the small intestine caused by sensitivity to dietary gluten and related proteins in genetically predisposed individuals. Over the past several years, the concept of non-celiac gluten sensitivity (NCGS) has gained significant interest from the scientific community and mass media and the number of individuals embracing a gluten-free diet is rapidly growing. This condition is characterized by gastrointestinal or extraintestinal symptoms that respond to gluten withdrawal without evidence for underlying celiac disease or wheat allergy. Symptoms display significant overlap with the irritable bowel syndrome. Many important factors regarding this relatively novel condition remain to be elucidated; no discriminative markers to support a diagnosis of gluten sensitivity have been identified yet and its pathogenesis remains obscure. Here we review the current knowledge on NCGS, and outline potential pathogenic pathways of different gluten related disorders in order to gain clues about the pathophysiology of this novel condition.",
"title": "Non-celiac gluten sensitivity. Is it in the gluten or the grain?"
},
{
"docid": "MED-1317",
"text": "A high intake of whole grain foods is associated with reduced risk of colon cancer, but the mechanism underlying this protection has yet to be elucidated. Chronic inflammation and associated cyclooxygenase-2 (COX-2) expression in the colon epithelium are causally related to epithelial carcinogenesis, proliferation, and tumor growth. We examined the effect of avenanthramides (Avns), unique polyphenols from oats with anti-inflammatory properties, on COX-2 expression in macrophages, colon cancer cell lines, and on proliferation of human colon cancer cell lines. We found that Avns-enriched extract of oats (AvExO) had no effect on COX-2 expression, but it did inhibit COX enzyme activity and prostaglandin E(2) (PGE(2)) production in lipopolysaccharide-stimulated mouse peritoneal macrophages. Avns (AvExO, Avn-C, and the methylated form of Avn-C (CH3-Avn-C)) significantly inhibited cell proliferation of both COX-2-positive HT29, Caco-2, and LS174T, and COX-2-negative HCT116 human colon cancer cell lines, CH3-Avn-C being the most potent. However, Avns had no effect on COX-2 expression and PGE(2) production in Caco-2 and HT29 colon cancer cells. These results indicate that the inhibitory effect of Avns on colon cancer cell proliferation may be independent of COX-2 expression and PGE(2) production. Thus, Avns might reduce colon cancer risk through inhibition of macrophage PGE(2) production and non-COX-related antiproliferative effects in colon cancer cells. Interestingly, Avns had no effect on cell viability of confluence-induced differentiated Caco-2 cells, which display the characteristics of normal colonic epithelial cells. Our results suggest that the consumption of oats and oat bran may reduce the risk of colon cancer not only because of their high fiber content but also due to Avns, which attenuate proliferation of colonic cancer cells.",
"title": "Avenanthramides inhibit proliferation of human colon cancer cell lines in vitro."
},
{
"docid": "MED-2027",
"text": "Background: Nonceliac gluten sensitivity (NCGS), occurring in patients without celiac disease yet whose gastrointestinal symptoms improve on a gluten-free diet (GFD), is largely a self-reported diagnosis and would appear to be very common. The aims of this study were to characterize patients who believe they have NCGS. Materials and Methods: Advertising was directed toward adults who believed they had NCGS and were willing to participate in a clinical trial. Respondents were asked to complete a questionnaire about symptoms, diet, and celiac investigation. Results: Of 248 respondents, 147 completed the survey. Mean age was 43.5 years, and 130 were women. Seventy-two percent did not meet the description of NCGS due to inadequate exclusion of celiac disease (62%), uncontrolled symptoms despite gluten restriction (24%), and not following a GFD (27%), alone or in combination. The GFD was self-initiated in 44% of respondents; in other respondents it was prescribed by alternative health professionals (21%), dietitians (19%), and general practitioners (16%). No celiac investigations had been performed in 15% of respondents. Of 75 respondents who had duodenal biopsies, 29% had no or inadequate gluten intake at the time of endoscopy. Inadequate celiac investigation was common if the GFD was initiated by self (69%), alternative health professionals (70%), general practitioners (46%), or dietitians (43%). In 40 respondents who fulfilled the criteria for NCGS, their knowledge of and adherence to the GFD were excellent, and 65% identified other food intolerances. Conclusions: Just over 1 in 4 respondents self-reporting as NCGS fulfill criteria for its diagnosis. Initiation of a GFD without adequate exclusion of celiac disease is common. In 1 of 4 respondents, symptoms are poorly controlled despite gluten avoidance. © 2014 American Society for Parenteral and Enteral Nutrition.",
"title": "Characterization of Adults With a Self-Diagnosis of Nonceliac Gluten Sensitivity."
},
{
"docid": "MED-1312",
"text": "The aim of this study was to evaluate the antiinflammatory effect of oatmeal extract oligomer on skin fragments stimulated by a neuromediator, vasoactive intestinal peptide (VIP). Skin fragments (from plastic surgery) were maintained in survival conditions for 6 h. To induce inflammation, VIP was placed in contact with dermis by culture medium. Histological analysis was then performed on hematoxylin- and eosin-stained slides. Edema was evaluated with semiquantitative scores. Vasodilation was studied by quantifying the percentage of dilated vessels according to scores and by measuring their surface by morphometrical image analysis. TNF-alpha dosage was made on culture supernatants. Vasodilation was significantly increased after application of VIP. After treatment with oatmeal extract oligomer, the mean surface of dilated vessels and edema were significantly decreased compared with VIP-treated skin. Moreover, treatment with this extract decreased TNF-alpha.",
"title": "Inhibitory effect of oatmeal extract oligomer on vasoactive intestinal peptide-induced inflammation in surviving human skin."
},
{
"docid": "MED-5132",
"text": "Vitamin B12 deficiency anemia may have psychiatric manifestations preceding the hematological symptoms. Although a variety of symptoms are described, there are only sparse data on the role of vitamin B12 in depression. We report a case of vitamin B12 deficiency presenting with recurrent episodes of depression.",
"title": "Role of vitamin B12 in depressive disorder--a case report."
},
{
"docid": "MED-2013",
"text": "As the gluten-free diet (GFD) gains in popularity with the general public, health practitioners are beginning to question its real health benefits. For those patients with celiac disease (CD), the GFD is considered medical nutrition therapy, as well as the only proven treatment that results in improvements in symptomatology and small bowel histology. Those with wheat allergy also benefit from the GFD, although these patients often do not need to restrict rye, barley, and oats from their diet. Gluten sensitivity is a controversial subject, where patients who have neither CD nor wheat allergy have varying degrees of symptomatic improvement on the GFD. Conditions in this category include dermatitis herpetiformis (DH), irritable bowel syndrome (IBS), and neurologic diseases such as gluten-sensitive ataxia and autism. It is important for patients and healthcare practitioners to understand the differences between these conditions, even though they may all respond to a GFD. Patients with CD can experience comorbid nutrition deficiencies and are at higher risk for the development of cancers and other autoimmune conditions. Those with wheat allergy and gluten sensitivity are thought not to be at higher risk for these complications. Defining the symptoms and biochemical markers for gluten-sensitive conditions is an important area for future investigations, and high-quality, large-scale randomized trials are needed to prove the true benefits of the GFD in this evolving field.",
"title": "Celiac disease, wheat allergy, and gluten sensitivity: when gluten free is not a fad."
},
{
"docid": "MED-1313",
"text": "Current treatment modalities for epidermal growth factor (EGFR)-positive cancers have recently included the use of antibodies and small-molecule tyrosine-kinase inhibitors (TKI). A significant limiting step in the use of these agents is dermatological toxicity, frequently in the form of an acneiform eruption. Present management modalities for this toxicity are largely ineffective. Colloidal oatmeal lotion demonstrates multiple anti-inflammatory properties with known effects on arachidonic acid, cytosolic phospholipase A2 and tumour necrosis factor-alpha pathways, along with an excellent side-effect profile. Treatment with colloidal oatmeal was applied to 11 patients with a rash induced by cetuximab, erlotinib, panitumumab and sorafenib. Of the 10 assessable patients, 6 had complete response and 4 partial response, giving a response rate of 100% with no associated toxicities. Treatment with colloidal oatmeal lotion is efficient in controlling the rash associated with EGFR and multiple TKI, and allows continuation of the antineoplastic treatment.",
"title": "Effect of treatment with a colloidal oatmeal lotion on the acneform eruption induced by epidermal growth factor receptor and multiple tyrosine-kina..."
},
{
"docid": "MED-1316",
"text": "Oatmeal has been used for centuries as a soothing agent to relieve itch and irritation associated with various xerotic dermatoses. In 1945, a ready to use colloidal oatmeal, produced by finely grinding the oat and boiling it to extract the colloidal material, became available. Today, colloidal oatmeal is available in various dosage forms from powders for the bath to shampoos, shaving gels, and moisturizing creams. Currently, the use of colloidal oatmeal as a skin protectant is regulated by the U.S. Food and Drug Administration (FDA) according to the Over-The-Counter Final Monograph for Skin Protectant Drug Products issued in June 2003. Its preparation is also standardized by the United States Pharmacopeia. The many clinical properties of colloidal oatmeal derive from its chemical polymorphism. The high concentration in starches and beta-glucan is responsible for the protective and water-holding functions of oat. The presence of different types of phenols confers antioxidant and anti-inflammatory activity. Some of the oat phenols are also strong ultraviolet absorbers. The cleansing activity of oat is mostly due to saponins. Its many functional properties make colloidal oatmeal a cleanser, moisturizer, buffer, as well as a soothing and protective anti-inflammatory agent.",
"title": "Colloidal oatmeal: history, chemistry and clinical properties."
},
{
"docid": "MED-5129",
"text": "BACKGROUND: Vitamin B(12) deficiency can occur in individuals with dietary patterns that exclude animal foods and patients who are unable to absorb vitamin B(12 )in food. MATERIAL AND METHOD: Our clinic serves a high-income population living in Southern Israel. We hypothesize that a tendency to decrease of level of vitamin B(12) in our population is caused by a premeditated decrease in consumption of animal products. We analyzed 512 medical histories of patients undergoing blood tests for vitamin B(12) level for various reasons. RESULT: The level of vitamin B(12) in 192 patients (37.5%) was less than 250 pg/ml. CONCLUSION: As a result of media information disseminating the relationship between meat, cholesterol and cardiovascular diseases, consumption of meat, particularly beef, has decreased. Changes in life style among segments of the population with high socioeconomic level, on one hand, and the existence of poverty, on the other, are two main factors in the decreasing consumption of animal products. This causes a decrease in the level of vitamin B(12) in the general population, and as a consequence, this will increase pathology due to vitamin B(12) deficiency. In lieu of these possible developments and in order to prevent serious health problems, vitamin B(12) fortification should be seriously considered and discussed. (c) 2007 S. Karger AG, Basel.",
"title": "Modern society and prospects of low vitamin B12 intake."
},
{
"docid": "MED-5130",
"text": "Although cobalamin deficiency is widely known and usually presents with hematologic and neuropsychiatric manifestations, the psychiatric symptoms are not usually the predominant manifestation. We describe a young single male vegetarian who developed a cobalamin-induced psychotic episode without preceding neurologic manifestations and without any hematologic symptoms. He recovered after a short course of antipsychotics and oral cobalamin supplementation and remained asymptomatic and functionally independent at 1 year of follow-up.",
"title": "Schizophrenia-like psychotic episode precipitated by cobalamin deficiency."
},
{
"docid": "MED-1314",
"text": "The use of epidermal growth factor receptor (EGFR) inhibitors for the treatment of solid tumours is increasing. However, the tolerability profile for EGFR-inhibitors, such as the monoclonal antibody cetuximab and the tyrosine kinase inhibitor erlotinib, is characterised by a unique group of skin reactions dominated by an acneiform eruption, xerosis, eczema and changes in the hair and nails. The possibility that this skin toxicity correlates with anti-tumour activity offers the potential to titrate dosing on a case-by-case basis. These skin effects may constitute a significant obstacle to treatment compliance. Accordingly, there is a need for consistent, multi-disciplinary management strategies that will allow patients to receive the recommended dosages of such targeted therapies. The eruption responds well to some acne therapies and xerosis can be controlled by standard emollients. Here we present an overview of the treatment options for skin reactions that are available today, and evaluate some of the ways in which the treatment of such EGFR-inhibitor-related skin reactions may be improved in the future. Evidence-based studies are needed to determine the best way to manage these effects.",
"title": "The management of skin reactions in cancer patients receiving epidermal growth factor receptor targeted therapies."
},
{
"docid": "MED-2033",
"text": "BACKGROUND: A significant percentage of the general population report problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy (WA), because they test negative both for CD-specific serology and histopathology and for immunoglobulin E (IgE)-mediated assays. Most patients report both gastrointestinal and nongastrointestinal symptoms, and all report improvement of symptoms on a gluten-free diet. This clinical condition has been named non-celiac gluten sensitivity (NCGS). AIM: We attempt to define the current pathogenic, clinical, and diagnostic criteria of this \"new\" disease, to provide a practical view that might be useful to evaluate, diagnose, and manage NCGS patients. METHODS: We reviewed the international literature through PubMed and Medline, using the search terms \"wheat (hyper)sensitivity,\" \"wheat allergy,\" \"wheat intolerance,\" \"gluten (hyper)sensitivity,\" and \"gluten intolerance,\" and we discuss current knowledge about NCGS. RESULTS: It has been demonstrated that patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. NCGS diagnosis can be reached only by excluding CD and WA. Recent evidence shows that a personal history of food allergy in infancy, coexistent atopy, positive for immunoglobulin G (IgG) antigliadin antibodies and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. CONCLUSIONS: Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroups. Key teaching points: • Most patients report both gastrointestinal and nongastrointestinal symptoms, and all agree that there is an improvement of symptoms on a gluten-free diet. • NCGS diagnosis can be reached only by excluding celiac disease and wheat allergy. • Patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. • A personal history of food allergy in infancy, coexistent atopy, positive IgG antigliadin antibodies (AGA) and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. • Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroup.",
"title": "Non-celiac gluten sensitivity: literature review."
},
{
"docid": "MED-5135",
"text": "Vitamin B(12) deficiency in infants often produces haematological and neurological deficits, including macrocytic anaemia, neurodevelopmental delay or regression, irritability, weakness, hypotonia, ataxia, apathy, tremor, and seizures. The diagnosis of vitamin B(12) deficiency can be difficult when the typical macrocytic anaemia is absent. We report the case of a 10-month-old female diagnosed with West syndrome associated with vitamin B(12) deficiency but without macrocytic anaemia caused by nutritional inadequacy in the mother. The patient's motor skills and cognitive development were normal until she was 9 months old, when she began to exhibit a series of sudden flexions of the head, trunk, arms, and legs. She was exclusively breast-fed and had received no vitamin supplementation. Results of electroencephalography (EEG) indicated modified hypsarrhythmia and the patient was diagnosed as having West syndrome. Synthetic adrenocorticotropic hormone was administered and although her spasms had resolved, the patient remained apathic and could not sit without assistance. EEG results indicated generalized slow activity. After she was diagnosed as having vitamin B(12) deficiency, parenteral treatment with vitamin B(12) was initiated. Her symptoms resolved and EEG was completely normal. When she was 20 months old she exhibited an age-appropriate developmental and neurological profile. To our knowledge, this is the first report of West syndrome as a presenting symptom of vitamin B(12) deficiency.",
"title": "West syndrome in an infant with vitamin B12 deficiency in the absence of macrocytic anaemia."
},
{
"docid": "MED-1311",
"text": "Although Erbitux (cetuximab) has proven therapeutic benefit in the clinical setting, the molecular determinants predicting responsiveness to this agent are still not very well understood. Here, we assessed the relationship between basal total and activated (pY1068) epidermal growth factor receptor (EGFR) levels in a tumor and the responsiveness to cetuximab monotherapy or combination-based treatment using human xenograft models. Cetuximab treatment alone (0.25-1 mg/mouse/injection, q3d, i.p.) effectively delayed the growth of GEO and L2987 tumors by a minimum of 10 days corresponding to log cell kill values of >or=1.0. Borderline activity was seen in the A549 and WiDr xenografts. However, cetuximab failed to show any significant antitumor activity in the HT29, HCT116, LOVO, Colo205, LX-1, HCC70, and N87 models. All of the studied tumors had detectable yet variable levels of EGFR. For combination regimens, cetuximab (1 mg/mouse/injection, q3dx5, i.p.) and cisplatin (4.5 mg/kg/injection, q3dx5, i.v.) proved to be significantly more efficacious than individual monotherapies in the cisplatin-refractory yet cetuximab-responsive GEO tumor model (P < 0.001). However, no therapeutic enhancement was observed in the cisplatin and cetuximab weakly responsive A549 xenograft. Similarly, combinations of CPT-11 (48 mg/kg/injection, q3dx5, i.v.) with cetuximab (1 mg/mouse/injection, q3dx5, i.p.) failed to show any improvements over individual monotherapies in the cetuximab resistant/weakly responsive HT29, A549, and WiDr models. We conclude that preclinical activity associated with cetuximab monotherapy does not correlate directly with relative basal levels of total or activated (pY1068) EGFR in a tumor. Moreover, robust single-agent activity by cetuximab may be the best predictor for this agent to potentiate chemotherapy-mediated antitumor activities.",
"title": "Cetuximab preclinical antitumor activity (monotherapy and combination based) is not predicted by relative total or activated epidermal growth facto..."
},
{
"docid": "MED-1315",
"text": "PURPOSE: The EGFR-independent activation of the RAS/RAF/MEK/MAPK pathway is one of the resistance mechanisms to cetuximab. EXPERIMENTAL DESIGN: We have evaluated, in vitro and in vivo, the effects of BAY 86-9766, a selective MEK1/2 inhibitor, in a panel of human colorectal cancer cell lines with primary or acquired resistance to cetuximab. RESULTS: Among the colorectal cancer cell lines, five with a KRAS mutation (LOVO, HCT116, HCT15, SW620, and SW480) and one with a BRAF mutation (HT29) were resistant to the antiproliferative effects of cetuximab, whereas two cells (GEO and SW48) were highly sensitive. Treatment with BAY 86-9766 determined dose-dependent growth inhibition in all cancer cells, including two human colorectal cancer cells with acquired resistance to cetuximab (GEO-CR and SW48-CR), with the exception of HCT15 cells. Combined treatment with cetuximab and BAY 86-9766 induced a synergistic antiproliferative and apoptotic effects with blockade in the MAPK and AKT pathway in cells with either primary or acquired resistance to cetuximab. The synergistic antiproliferative effects were confirmed using other two selective MEK1/2 inhibitors, selumetinib and pimasertib, in combination with cetuximab. Moreover, inhibition of MEK expression by siRNA restored cetuximab sensitivity in resistant cells. In nude mice bearing established human HCT15, HCT116, SW48-CR, and GEO-CR xenografts, the combined treatment with cetuximab and BAY 86-9766 caused significant tumor growth inhibition and increased mice survival. CONCLUSION: These results suggest that activation of MEK is involved in both primary and acquired resistance to cetuximab and the inhibition of EGFR and MEK could be a strategy for overcoming anti-EGFR resistance in patients with colorectal cancer. ©2014 American Association for Cancer Research.",
"title": "Primary and acquired resistance of colorectal cancer cells to anti-EGFR antibodies converge on MEK/ERK pathway activation and can be overcome by co..."
},
{
"docid": "MED-2014",
"text": "BACKGROUND: Gastrointestinal symptoms that respond to the removal of wheat and/or gluten are becoming more common. Patients who avoid wheat and/or gluten (PWAWG) are a heterogeneous group and predominantly self-diagnosed prior to presenting for clinical evaluation. SPECIFIC AIM: We characterized PWAWGs seen at a tertiary care referral center and compared them to patients with celiac disease (CD) and subjects in the National Health and Nutrition examination survey (NHANES). METHODS: This was a cross-sectional study evaluating patients seen by four gastroenterologists at a CD referral center. Baseline characteristics, laboratory values, and medical comorbidities were compared to CD patients who presented at the same center and subjects enrolled in NHANES. RESULTS: Eighty-four PWAWGs were identified and compared to 585 CD patients and 2,686 NHANES patients. Thirty-two alternative diagnoses were made in 25 (30%) PWAWGs, including small intestinal bacterial overgrowth and fructose/lactose intolerance. When compared to patients with CD, PWAWGs had similar body mass index (BMI, 23.1 vs. 23.5, p = 0.54) and mean hemoglobin value (13.4 vs. 13.3, p = 0.6). When compared to male and female patients in NHANES, BMI, folate, and mean hemoglobin values were lower in PWAWGs. Both male and female PWAWGs had a lower prevalence of hypertension. CONCLUSION: While there are similarities between CD and PWAWGs that could possibly be due to shared HLA haplotypes or an effect of the gluten-free diet, alternative diagnoses are common in these patients. PWAWGs have a similar cardiovascular profile as CD patients in terms of lower BMI and lower prevalence of hypertension.",
"title": "Characteristics of patients who avoid wheat and/or gluten in the absence of Celiac disease."
},
{
"docid": "MED-5134",
"text": "This position paper on complementary feeding summarizes evidence for health effects of complementary foods. It focuses on healthy infants in Europe. After reviewing current knowledge and practices, we have formulated these conclusions: Exclusive or full breast-feeding for about 6 months is a desirable goal. Complementary feeding (ie, solid foods and liquids other than breast milk or infant formula and follow-on formula) should not be introduced before 17 weeks and not later than 26 weeks. There is no convincing scientific evidence that avoidance or delayed introduction of potentially allergenic foods, such as fish and eggs, reduces allergies, either in infants considered at increased risk for the development of allergy or in those not considered to be at increased risk. During the complementary feeding period, >90% of the iron requirements of a breast-fed infant must be met by complementary foods, which should provide sufficient bioavailable iron. Cow's milk is a poor source of iron and should not be used as the main drink before 12 months, although small volumes may be added to complementary foods. It is prudent to avoid both early (<4 months) and late (>or=7 months) introduction of gluten, and to introduce gluten gradually while the infant is still breast-fed, inasmuch as this may reduce the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy. Infants and young children receiving a vegetarian diet should receive a sufficient amount ( approximately 500 mL) of breast milk or formula and dairy products. Infants and young children should not be fed a vegan diet.",
"title": "Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition."
},
{
"docid": "MED-5133",
"text": "We report the case of a 7 month-old girl that presented with acute anemia, generalized muscular hypotonia and failure to thrive. Laboratory evaluation revealed cobalamin deficiency, due to a vegan diet of the mother. The clinical triad of an acquired floppy baby syndrome with megaloblastic anemia and failure to thrive is pathognomic for infantile cobalamin deficiency. Neurological abnormalities are often irreversible and may be associated with delayed myelinization in the MRI. A normal cobalamin level in maternal serum and absence of anemia do not exclude subclinical deficiency. If cobalamin deficiency is suspected, e.g. in pregnant women on vegan diet, urinary methylmalonic acid excretion and plasma homocysteine levels should be determined and cobalamin substitution should be started at an early stage to avoid potentially irreversible damage of the fetus.",
"title": "[Floppy baby with macrocytic anemia and vegan mother]."
}
] |
[
{
"docid": "MED-2361",
"text": "The most common clinical manifestation of Lyme disease is the characteristic rash, erythema migrans (EM). In the 1980s EM-like eruptions were reported in Missouri and other southeastern states. The EM-like eruptions, which were of unknown etiology, often followed the bite of the Lone Star tick (Amblyomma americanum) and the rash is called STARI (southern tick-associated rash illness). Although the Lone Star tick is found in the Lyme disease-endemic areas of New England and Mid-Atlantic regions of the United States, STARI has been reported only once from the Northeast and Mid-Atlantic regions. We report a child from Connecticut who visited Long Island, New York, and developed a rash that was thought to be EM. Because the patient failed to respond to antibiotics used to treat Lyme disease, an investigation ensued, and the diagnosis of STARI was established.",
"title": "Southern Tick-Associated Rash Illness (STARI) in the North: STARI following a tick bite in Long Island, New York."
},
{
"docid": "MED-2759",
"text": "A commercial weight loss program with a client base composed of >95% women experienced sporadic complaints of nausea and vomiting after changing its multivitamin supplier. This retrospective and observational study was designed to determine if related adverse event reports were significant, and to investigate potential mechanism for their occurrence in this group of subjects, many of whom were concurrently receiving oral contraceptives or hormone replacement therapy. Incidence of nausea, vomiting, rash, and total complaints in the 3 months following the change of the multivitamin formulation was compared with the same complaints in the 3 months before the change. In the 3 months following the multivitamin change, there were 166 complaints of nausea and vomiting, 9 complaints of rash and 194 total complaints from a group of 88,468 patients. In the 3 months before the change in the multivitamin, there had been 2 complaints of nausea and vomiting, no complaints of rash, and 11 total complaints from 88,252 patients. The difference detected by a chi-squared test was significant for all events studied; nausea and vomiting (P < 0.0001), rash (P < 0.02), and total complaints (P < 0.0001). The altered multivitamins contained added citrus bioflavanoids not included in the original formula. Citrus bioflavanoids decrease the clearance of exogenous estrogens by inhibiting cytochrome P450 enzyme systems. Elevated estrogen levels could account for the increased incidence of nausea and vomiting. This experience demonstrates that adding dietary herbal supplements to multivitamins may be associated with adverse interactions with prescription drugs.",
"title": "Vomiting from multivitamins: a potential drug interaction."
},
{
"docid": "MED-2360",
"text": "Lyme-like illness (also known as southern tick-associated rash illness [STARI] or Masters disease) is vectored by the Lone Star tick (Amblyomma americanum). Lyme-like illness lesions, which are similar to the erythema migrans rash of Lyme disease, tend to have lymphocytic dermal infiltrates. With the exception of Borrelia lonestari, the possible causative agent or agents of Lyme-like illness have not been cultured. More research is needed to fully understand this newly recognized zoonosis. Clinicians are encouraged to increase their knowledge and awareness of this Lyme disease mimic.",
"title": "STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness."
},
{
"docid": "MED-2052",
"text": "The addition of direct-acting antivirals (DAAs) to hepatitis C virus (HCV) treatment regimens has made treatment more effective and patient management more complex. Shepherding patients through a full course of HCV therapy requires motivation and involvement on the part of the patient and the physician. Indeed, physician inexperience and lack of confidence in guiding patients through the challenges of treatment appears to be a primary reason for early discontinuation of therapy. Among the many complications of HCV treatment that must be managed efficiently and effectively are depression and other psychiatric disorders; hematologic abnormalities including DAA- and ribavirin-associated anemia and peginterferon alfa-associated neutropenia and thrombocytopenia; rash and drug eruptions, including telaprevir-associated rash; and weight loss. Practical considerations in management of these common complications are offered. This article summarizes a presentation by Kenneth E. Sherman, MD, PhD, at the IAS-USA live continuing medical education course held in New York in June 2012.",
"title": "Managing adverse effects and complications in completing treatment for hepatitis C virus infection."
},
{
"docid": "MED-2815",
"text": "Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin, a component of turmeric: from farm to pharmacy."
},
{
"docid": "MED-824",
"text": "OBJECTIVE: To compare the clinical results and reproductive outcome in obese women with polycystic ovary syndrome (PCOS) following dietary intervention or treatment with metformin. METHODS: Forty-six patients with PCOS were studied prospectively in Prince Rashed Hospital, Irbid, Jordan, between January 2003 and April 2005. The women were randomly divided into 2 groups: Group 1 (n=24) was prescribed with 1200-1400 kcal/day diet (25% proteins, 25% fat, and 50% carbohydrates plus 25-30 gm of fiber per week). Group 2 (n=22) was assigned to take 850 mg of metformin twice in a continuous manner. Both treatments continued for 6 months. Clinical and biochemical data, before and after both treatments along with the reproductive outcome were compared between the 2 groups. RESULTS: There were no significant differences between the 2 groups in terms of age, body mass index (BMI) and duration of infertility. Both groups had a significant improvement after treatment in the menstrual cyclicity (66.7% and 68.2% versus 12.5% and 18.2%) and significant reduction in BMI (mean of 27.4 and 27.8 versus 32.2 and 31.9), luteinizing hormone levels (7.9+/-1.7 and 6.9+/-1.8 versus 11.8+/-2.2 and 11.5+/-1.8), and androgen (testosterone, androstenedione, dehydroepiandrosterone sulfate) concentration. The clinical, biochemical, and reproductive outcome including menstrual cycle pattern, ovulation, and pregnancy rates were similar in both groups after treatment. CONCLUSION: Amelioration of hyperinsulinemia and hyperandrogenemia with dietary intervention or metformin treatment improves significantly the clinical features and reproductive function in overweight PCOS women.",
"title": "Dietary intervention versus metformin to improve the reproductive outcome in women with polycystic ovary syndrome. A prospective comparative study."
},
{
"docid": "MED-1820",
"text": "Background This study aims to comprehensively summarize the currently available evidences on the efficacy and safety of gemcitabine plus erlotinib for treating advanced pancreatic cancer. Methodology/Principal Findings PubMed, EMBASE, The Cochrane Library and abstracts of recent major conferences were systematically searched to identify relevant publications. Studies that were conducted in advanced pancreatic cancer patients treated with gemcitabine plus erlotinib (with or without comparison with gemcitabine alone) and reporting objective response rate, disease control rate, progression-free survival, time-to-progression, overall survival, 1-year survival rate and/or adverse events were included. Data on objective response rate, disease control rate, 1-year survival rate and adverse events rate, respectively, were combined mainly by using Meta-Analyst software with a random-effects model. Data on progression-free survival, time-to-progression and overall survival were summarized descriptively. Sixteen studies containing 1,308 advanced pancreatic cancer patients treated with gemcitabine plus erlotinib were included. The reported median progression-free survival (or time-to-progression), median overall survival, 1-year survival rates, objective response rates and disease control rates were 2–9.6 months, 5–12.5 months, 20%–51%, 0%–28.6% and 25.0%–83.3%, respectively. The weighted 1-year survival rate, objective response rate and disease control rate based on studies reporting robust results were 27.9%, 9.1% and 57.0%, respectively. According to the studies with relevant data, the incidences of total and severe adverse events were 96.3% and 62.9%, respectively. The most frequently reported adverse events were leucopenia, rash, diarrhea, vomitting, neutropenia, thrombocytopenia, anaemia, stomatitis, drug-induced liver injury, fatigue and fever. Compared with gemcitabine alone, the progression-free survival and overall survival with gemcitabine plus erlotinib were significantly longer, but there were also more deaths and interstitial lung disease-like syndrome related to this treatment. Conclusions/Significance Gemcitabine plus erlotinib represent a new option for the treatment of advanced pancreatic cancer, with mild but clinically meaningful additive efficacy compared with gemcitabine alone. Its safety profile is generally acceptable, although careful management is needed for some specific adverse events.",
"title": "Gemcitabine Plus Erlotinib for Advanced Pancreatic Cancer: A Systematic Review with Meta-Analysis"
},
{
"docid": "MED-2030",
"text": "Background Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. We carried out a prospective survey on NCGS in Italian centers for the diagnosis of gluten-related disorders, with the aim of defining the clinical picture of this new syndrome and to establish roughly its prevalence compared with celiac disease. Methods From November 2012 to October 2013, 38 Italian centers (27 adult gastroenterology, 5 internal medicine, 4 pediatrics, and 2 allergy) participated in this prospective survey. A questionnaire was used in order to allow uniform and accurate collection of clinical, biochemical, and instrumental data. Results In total, 486 patients with suspected NCGS were identified in this 1-year period. The female/male ratio was 5.4 to 1, and the mean age was 38 years (range 3–81). The clinical picture was characterized by combined gastrointestinal (abdominal pain, bloating, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and systemic manifestations (tiredness, headache, fibromyalgia-like joint/muscle pain, leg or arm numbness, 'foggy mind,' dermatitis or skin rash, depression, anxiety, and anemia). In the large majority of patients, the time lapse between gluten ingestion and the appearance of symptoms varied from a few hours to 1 day. The most frequent associated disorders were irritable bowel syndrome (47%), food intolerance (35%) and IgE-mediated allergy (22%). An associated autoimmune disease was detected in 14% of cases. Regarding family history, 18% of our patients had a relative with celiac disease, but no correlation was found between NCGS and positivity for HLA-DQ2/-DQ8. IgG anti-gliadin antibodies were detected in 25% of the patients tested. Only a proportion of patients underwent duodenal biopsy; for those that did, the biopsies showed normal intestinal mucosa (69%) or mild increase in intraepithelial lymphocytes (31%). The ratio between suspected NCGS and new CD diagnoses, assessed in 28 of the participating centers, was 1.15 to 1. Conclusions This prospective survey shows that NCGS has a strong correlation with female gender and adult age. Based on our results, the prevalence of NCGS seems to be only slightly higher than that of celiac disease. Please see related article http://www.biomedcentral.com/1741-7015/12/86.",
"title": "An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity"
},
{
"docid": "MED-4197",
"text": "Human diet may contain many mutagenic or carcinogenic aromatic compounds as well as some beneficial physiologically active dietary components, especially plant food phytochemicals, which act as mutagenesis or carcinogenesis inhibitors. This study compared the binding properties of natural compounds in the human diet (caffeine, theophylline, theobromine, and resveratrol) with a water-soluble derivative of chlorophyll to bind to acridine orange, a known mutagen. An analysis was conducted to determine which substances were effective binding agents and may thus be useful in prevention of chemical-induced mutagenesis and carcinogenesis. Data indicated that in order to bind 50% of the mutagen in a complex, less than twice the concentration of chlorophyllin was needed, the resveratrol concentration was 20-fold higher, while a 1000-fold or even 10,000-fold excess of xanthines were required to bind acridine orange.",
"title": "Natural compounds in the human diet and their ability to bind mutagens prevents DNA-mutagen intercalation."
},
{
"docid": "MED-4133",
"text": "BACKGROUND: Yersinia enterocolitica (YE) infection has long been implicated in the pathogenesis of Graves' disease (GD). The association between YE and GD could, however, also be due to common genetic or environmental factors affecting the development of both YE infection and GD. This potential confounding can be minimized by investigation of twin pairs discordant for GD. AIM: To examine whether YE infection is associated with GD. DESIGN: We first conducted a classical case-control study of individuals with (61) and without (122) GD, and then a case-control study of twin pairs (36) discordant for GD. METHODS: Immunoglobulin (Ig)A and IgG antibodies to virulence-associated Yersinia outer membrane proteins (YOPs) were measured. MAIN OUTCOME MEASURES: The prevalence of YOP IgA and IgG antibodies. RESULTS: Subjects with GD had a higher prevalence of YOP IgA (49%vs. 34%, P = 0.054) and YPO IgG (51%vs. 35%, P = 0.043) than the external controls. The frequency of chronic YE infection, reflected by the presence of both IgA and IgG YOP antibodies, was also higher among cases than controls (49%vs. 33%, P = 0.042). Similar results were found in twin pairs discordant for GD. In the case-control analysis, individuals with GD had an increased odds ratio (OR) of YE infection: IgA 1.84 (95% CI 0.99-3.45) and IgG 1.90 (95% CI 1.02-3.55). In the co-twin analysis, the twin with GD also had an increased OR of YE infection: IgA 5.5 (95% CI 1.21-24.81) and IgG 5.0 (95% CI 1.10-22.81). CONCLUSION: The finding of an association between GD and YE in the case-control study and within twin pairs discordant for GD supports the notion that YE infection plays an aetiological role in the occurrence of GD, or vice versa. Future studies should examine the temporal relationship of this association in more depth.",
"title": "Too early to dismiss Yersinia enterocolitica infection in the aetiology of Graves' disease: evidence from a twin case-control study."
},
{
"docid": "MED-1247",
"text": "Background: This study is aimed at determining the efficacy of Mentha spicata (M. spicata) and Mentha × piperita (M. × piperita) in preventing chemotherapy-induced nausea and vomiting (CINV). Methods: This was a randomised, double-blind clinical trial study. Prior to the study, patients were randomly assigned into four groups to receive M. spicata or M. × piperita. Statistical analysis included the χ2 test, relative risk, and Student’s t-test. Fifty courses were analysed for each group that met our eligibility criteria. The treatment and placebo groups applied essential oils of M. spicata, M. × piperita, or a placebo, while the control group continued with their previous antiemetic regimen. Patients or guardians recorded the number of emetic events, the intensity of nausea over 20 h of chemotherapy, as well as any possible adverse effects that occurred during this time. Results: There was a significant reduction in the intensity and number of emetic events in the first 24 h with M. spicata and M. × piperita in both treatment groups (p < 0.05) when compared with the control and no adverse effects were reported. The cost of treatment was also reduced when essential oils were used. Conclusion: M. spicata or M. × piperita essential oils are safe and effective for antiemetic treatment in patients, as well as being cost effective.",
"title": "Antiemetic activity of volatile oil from Mentha spicata and Mentha × piperita in chemotherapy-induced nausea and vomiting"
},
{
"docid": "MED-1098",
"text": "The first U.S. nationwide food sampling with measurement of dioxins, dibenzofurans, and coplanar, mono-ortho and di-ortho polychlorinated biphenyls (PCBs) is reported in this study. Twelve separate analyses were conducted on 110 food samples divided into pooled lots by category. The samples were purchased in 1995 in supermarkets in Atlanta, GA, Binghamton, NY, Chicago, IL, Louisville, KY, and San Diego, CA. Human milk also was collected to estimate nursing infants' consumption. The food category with highest World Health Organization (WHO) dioxin toxic equivalent (TEQ) concentration was farm-grown freshwater fish fillet with 1.7 pg/g, or parts per trillion (ppt), wet, or whole, weight. The category with the lowest TEQ level was a simulated vegandiet, with 0.09 ppt. TEQ concentrations in ocean fish, beef, chicken, pork, sandwich meat, eggs, cheese, and ice cream, as well as human milk, were in the range O.33 to 0.51 ppt, wet weight. In whole dairy milk TEQ was 0.16 ppt, and in butter 1.1 ppt. Mean daily intake of TEQ for U.S. breast-fed infants during the first year of life was estimated at 42 pg/kg body weight. For children aged 1-11 yr the estimated daily TEQ intake was 6.2 pg/kg body weight. For males and females aged 12-19 yr, the estimated TEQ intake was 3.5 and 2.7 pg/kg body weight, respectively. For adult men and women aged 20-79 yr, estimated mean daily TEQ intakes were 2.4 and 2.2 pg/kg body weight, respectively. Estimated mean daily intake of TEQ declined with age to a low of 1.9 pg/kg body weight at age 80 yr and older. For all ages except 80 yr and over, estimates were higher for males than females. For adults, dioxins, dibenzofurans, and PCBs contributed 42%, 30%, and 28% of dietary TEQ intake, respectively. DDE was also analyzed in the pooled food samples.",
"title": "Intake of dioxins and related compounds from food in the U.S. population."
},
{
"docid": "MED-2432",
"text": "It is likely that plant food consumption throughout much of human evolution shaped the dietary requirements of contemporary humans. Diets would have been high in dietary fiber, vegetable protein, plant sterols and associated phytochemicals, and low in saturated and trans-fatty acids and other substrates for cholesterol biosynthesis. To meet the body's needs for cholesterol, we believe genetic differences and polymorphisms were conserved by evolution, which tended to raise serum cholesterol levels. As a result modern man, with a radically different diet and lifestyle, especially in middle age, is now recommended to take medications to lower cholesterol and reduce the risk of cardiovascular disease. Experimental introduction of high intakes of viscous fibers, vegetable proteins and plant sterols in the form of a possible Myocene diet of leafy vegetables, fruit and nuts, lowered serum LDL-cholesterol in healthy volunteers by over 30%, equivalent to first generation statins, the standard cholesterol-lowering medications. Furthermore, supplementation of a modern therapeutic diet in hyperlipidemic subjects with the same components taken as oat, barley and psyllium for viscous fibers, soy and almonds for vegetable proteins and plant sterol-enriched margarine produced similar reductions in LDL-cholesterol as the Myocene-like diet and reduced the majority of subjects' blood lipids concentrations into the normal range. We conclude that reintroduction of plant food components, which would have been present in large quantities in the plant based diets eaten throughout most of human evolution into modern diets can correct the lipid abnormalities associated with contemporary eating patterns and reduce the need for pharmacological interventions.",
"title": "The Garden of Eden--plant based diets, the genetic drive to conserve cholesterol and its implications for heart disease in the 21st century."
},
{
"docid": "MED-2448",
"text": "A double-blind comparative study was conducted on cedar pollinosis patients in order to evaluate the treatment efficacy of apple polyphenol (Ap). Ap was administered (500 mg) once daily for 12 weeks, starting about 2 weeks prior to cedar pollen dispersion. Pollinosis symptoms during the study were evaluated according to the classification in the guidelines for allergic rhinitis diagnosis and treatment. The results show that the sneezing score was significantly lower for the Ap group than with the placebo group during the early period of pollen dispersion and during the main dispersion period. In addition, no adverse reactions were induced by Ap during the study. These results suggest that Ap may alleviate the symptoms of cedar pollinosis.",
"title": "Clinical efficacy of apple polyphenol for treating cedar pollinosis."
},
{
"docid": "MED-2608",
"text": "The effects of curcumin, the yellow pigment of the spice, turmeric (Curcuma longa) on the mutagenicity of several environmental mutagens were investigated in the Salmonella/microsome test with or without Aroclor 1254-induced rat-liver homogenate (S-9 mix). With Salmonella typhimurium strain TA98 in the presence of S-9 mix, curcumin inhibited the mutagenicity of bidi and cigarette smoke condensates, tobacco and masheri extracts, benzo[a]pyrne and dimethyl benzo[a]anthracene in a dose-dependent manner. Curcumin did not influence the mutagenicity without S-9 mix of sodium azide, monoacetylhydrazine and streptozocin in strain TA100 nor of 4-nitrophenylenediamine in strain TA98. Our observations indicate that curcumin may alter the metabolic activation and detoxification of mutagens.",
"title": "In vitro antimutagenicity of curcumin against environmental mutagens."
},
{
"docid": "MED-886",
"text": "BACKGROUND: Both hempseed oil (HO) and flaxseed oil (FO) contain high amounts of essential fatty acids (FAs); i.e. linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (ALA, 18:3n-3), but almost in opposite ratios. An excessive intake of one essential FA over the other may interfere with the metabolism of the other while the metabolisms of LA and ALA compete for the same enzymes. It is not known whether there is a difference between n-3 and n-6 FA of plant origin in the effects on serum lipid profile. AIM OF THE STUDY: To compare the effects of HO and FO on the profile of serum lipids and fasting concentrations of serum total and lipoprotein lipids, plasma glucose and insulin, and haemostatic factors in healthy humans. METHODS: Fourteen healthy volunteers participated in the study. A randomised, double-blind crossover design was used. The volunteers consumed HO and FO (30 ml/day) for 4 weeks each. The periods were separated by a 4-week washout period. RESULTS: The HO period resulted in higher proportions of both LA and gamma-linolenic acid in serum cholesteryl esters (CE) and triglycerides (TG) as compared with the FO period (P < 0.001), whereas the FO period resulted in a higher proportion of ALA in both serum CE and TG as compared with the HO period (P < 0.001). The proportion of arachidonic acid in CE was lower after the FO period than after the HO period (P < 0.05). The HO period resulted in a lower total-to-HDL cholesterol ratio compared with the FO period (P = 0.065). No significant differences were found between the periods in measured values of fasting serum total or lipoprotein lipids, plasma glucose, insulin or hemostatic factors. CONCLUSIONS: The effects of HO and FO on the profile of serum lipids differed significantly, with only minor effects on concentrations of fasting serum total or lipoprotein lipids, and no significant changes in concentrations of plasma glucose or insulin or in haemostatic factors.",
"title": "Effects of hempseed and flaxseed oils on the profile of serum lipids, serum total and lipoprotein lipid concentrations and haemostatic factors."
},
{
"docid": "MED-4799",
"text": "To determine the presence of Clostridium difficile, we sampled cooked and uncooked meat products sold in Tucson, Arizona. Forty-two percent contained toxigenic C. difficile strains (either ribotype 078/toxinotype V [73%] or 027/toxinotype III [NAP1 or NAP1-related; 27%]). These findings indicate that food products may play a role in interspecies C. difficile transmission.",
"title": "Clostridium difficile in Retail Meat Products, USA, 2007"
},
{
"docid": "MED-2315",
"text": "Background The word selectivity describes a drug's ability to affect a particular cell population in preference to others. As part of the current state of art in the search for new therapeutic agents, the property of selectivity is a mode of action thought to have a high degree of desirability. Consequently there is a growing activity in this area of research. Selectivity is generally a worthy property in a drug because a drug having high selectivity may have a dramatic effect when there is a single agent that can be targeted against the appropriate molecular-driver involved in the pathogenesis of a disease. An example is chronic myeloid leukemia (CML). CML has a specific chromosomal abnormality, the Philadelphia chromosome, that results in a single gene that produces an abnormal protein Discussion There is a burgeoning understanding of the cellular mechanisms that control the etiology and pathogeneses of diseases. This understanding both enables and motivates the development of drugs that induce a specific action in a selected cell population; i.e., a targeted treatment. Consequently, drugs that can target distinct molecular targets involved in pathologic/pathogenetic processes, or signal-transduction pathways, are being developed. However, in most cases, diseases involve multiple abnormalities. A disease may be associated with more than one dysfunctional protein and these may be out-of-balance with each other. Likewise a drug might strongly target a protein that shares a similar active domain with other proteins. A drug may also target pleiotropic cytokines, or other proteins that have multi-physiological functions. In this way multiple normal cellular pathways can be simultaneously influenced. Long term experience with drugs supposedly designed for only a single target, but which unavoidably involve other functional effects, is uncovering the fact that molecular targeting is not medically flawless. Summary We contend that an ideal drug may be one whose efficacy is based not on the inhibition of a single target, but rather on the rebalancing of the several proteins or events, that contribute to the etiology, pathogeneses, and progression of diseases, i.e., in effect a promiscuous drug. Ideally, if this could be done at minimum drug concentration, side effects could be minimized. Corollaries to this argument are that the growing fervor for researching truly selective drugs may be imprudent when considering the totality of responses; and that the expensive screening techniques used to discover these, may be both medically and financially inefficient.",
"title": "Promiscuous drugs compared to selective drugs (promiscuity can be a virtue)"
},
{
"docid": "MED-4701",
"text": "BACKGROUND: Vinegar reduces postprandial glycemia (PPG) in healthy adults. This study investigated the vinegar dosage (10 vs. 20 g), timing (during mealtime vs. 5 h before meal) and application (acetic acid as vinegar vs. neutralized salt) for reducing PPG. METHODS: Four randomized crossover trials were conducted in adults (n = 9-10/trial) with type 2 diabetes (1 trial) or without diabetes (3 trials). All trials followed the same protocol: a standardized meal the evening prior to testing, an overnight fast ( 1 10 h) and 2-hour glucose testing following consumption of a bagel and juice test meal (3 trials) or dextrose solution (1 trial). For each trial, PPG was compared between treatments using area-under-the-curve calculations 120 min after the meal. RESULTS: Two teaspoons of vinegar ( 10 g) effectively reduced PPG, and this effect was most pronounced when vinegar was ingested during mealtime as compared to 5 h before the meal. Vinegar did not alter PPG when ingested with monosaccharides, suggesting that the antiglycemic action of vinegar is related to the digestion of carbohydrates. Finally, sodium acetate did not alter PPG, indicating that acetate salts lack antiglycemic properties. CONCLUSIONS: The antiglycemic properties of vinegar are evident when small amounts of vinegar are ingested with meals composed of complex carbohydrates. In these situations, vinegar attenuated PPG by 20% compared to placebo. 2009 S. Karger AG, Basel.",
"title": "Examination of the antiglycemic properties of vinegar in healthy adults."
},
{
"docid": "MED-3355",
"text": "OBJECTIVE: To evaluate the effects of a high-fat and low-fat diet on taste sensitivity to oleic acid (C18:1) in lean and overweight/obese (OW/OB) subjects. DESIGN: Randomized cross-over dietary intervention involving the consumption of a high-fat (>45% fat) and low-fat (<20% fat) diet, both consumed over a 4-week period. SUBJECTS: A total of 19 lean, mean age 33±13 years, mean body mass index (BMI) 23.2±2.2 kg m(-2) and 12 OW/OB, mean age 39.5±3 years, mean BMI 28±2.6 kg m(-2), subjects participated in the study, which measured taste thresholds for C18:1, fat perception and hedonic ratings for regular (RF) and lowered-fat (LF) foods before, and following consumption of a high- and low-fat diet. RESULTS: Consumption of the low-fat diet increased taste sensitivity to C18:1 among lean and OW/OB subjects (P<0.05) and increased the subjects ability to perceive small differences in the fat content of custard (P=0.05). Consumption of the high-fat diet significantly decreased taste sensitivity to C18:1 among lean subjects (P<0.05), with no change in sensitivity among OW/OB persons (P=0.609). The hedonic ratings for several RF and LF foods differed following the diets. CONCLUSION: Alterations in the fat content of the diet modulated taste sensitivity to C18:1 among lean subjects, which was increased following a 4-week period of fat restriction and attenuated following the high-fat diet. The failure of the high-fat diet to alter fatty acid taste thresholds among OW/OB subjects suggests that these individuals were 'adapted' to high-fat exposure, perhaps because of differences in habitual fat consumption. Taken together, these data suggest that excessive dietary fat attenuates nutrient sensing epithelia response in the oral cavity, which could be associated with changes in diet and weight status.",
"title": "Recent fat intake modulates fat taste sensitivity in lean and overweight subjects."
},
{
"docid": "MED-4667",
"text": "Cows with isolation of Staphylococcus aureus approximately 1 week after calving and milk yield, somatic cell count (SCC), clinical mastitis (CM), and culling risk through the remaining lactation were assessed in 178 Norwegian dairy herds. Mixed models with repeated measures were used to compare milk yield and SCC, and survival analyses were used to estimate the hazard ratio for CM and culling. On average, cows with an isolate of Staph. aureus had a significantly higher SCC than culture-negative cows. If no post-milking teat disinfection (PMTD) was used, the mean values of SCC were 42,000, 61,000, 68,000 and 77,000 cells/ml for cows with no Staph. aureus isolate, with Staph. aureus isolated in 1 quarter, in 2 quarters and more than 2 quarters respectively. If iodine PMTD was used, SCC means were 36,000; 63,000; 70,000 and 122,000, respectively. Primiparous cows testing positive for Staph. aureus had the same milk yield curve as culture-negative cows, except for those with Staph. aureus isolated in more than 2 quarters. They produced 229 kg less during a 305-d lactation. Multiparous cows with isolation of Staph. aureus in at least 1 quarter produced 94-161 kg less milk in 2nd and >3rd parity, respectively, and those with isolation in more than 2 quarters produced 303-390 kg less than multiparous culture-negative animals during a 305-d lactation. Compared with culture-negative cows, the hazard ratio for CM and culling in cows with isolation of Staph. aureus in at least 1 quarter was 2.0 (1.6-2.4) and 1.7 (1.5-1.9), respectively. There was a decrease in the SCC and in the CM risk in culture-negative cows where iodine PMTD had been used, indicating that iodine PMTD has a preventive effect on already healthy cows. For cows testing positive for Staph. aureus in more than 2 quarters at calving, iodine PMTD had a negative effect on the CM risk and on the SCC through the remaining lactation.",
"title": "Association between isolation of Staphylococcus aureus one week after calving and milk yield, somatic cell count, clinical mastitis, and culling th..."
},
{
"docid": "MED-5004",
"text": "BACKGROUND: Cross-sectional studies have shown that vegetarians and vegans are leaner than omnivores. Longitudinal data on weight gain in these groups are sparse. OBJECTIVE: We investigated changes in weight and body mass index (BMI) over a 5-year period in meat-eating, fish-eating, vegetarian, and vegan men and women in the UK. DESIGN: Self-reported anthropometric, dietary and lifestyle data were collected at baseline in 1994-1999 and at follow-up in 2000-2003; the median duration of follow-up was 5.3 years. SUBJECTS: A total of 21,966 men and women participating in Oxford arm of the European Prospective Investigation into Cancer and Nutrition aged 20-69 years at baseline. RESULTS: The mean annual weight gain was 389 (SD 884) g in men and 398 (SD 892) g in women. The differences between meat-eaters, fish-eaters, vegetarians and vegans in age-adjusted mean BMI at follow-up were similar to those seen at baseline. Multivariable-adjusted mean weight gain was somewhat smaller in vegans (284 g in men and 303 g in women, P<0.05 for both sexes) and fish-eaters (338 g, women only, P<0.001) compared with meat-eaters. Men and women who changed their diet in one or several steps in the direction meat-eater --> fish-eater --> vegetarian --> vegan showed the smallest mean annual weight gain of 242 (95% CI 133-351) and 301 (95% CI 238-365) g, respectively. CONCLUSION: During 5 years follow-up, the mean annual weight gain in a health-conscious cohort in the UK was approximately 400 g. Small differences in weight gain were observed between meat-eaters, fish-eaters, vegetarians and vegans. Lowest weight gain was seen among those who, during follow-up, had changed to a diet containing fewer animal food.",
"title": "Weight gain over 5 years in 21,966 meat-eating, fish-eating, vegetarian, and vegan men and women in EPIC-Oxford."
},
{
"docid": "MED-5192",
"text": "High dietary intakes of calcium and dairy products have been hypothesized to enhance prostate cancer risk, but available prospective data regarding these associations are inconsistent. We examined dietary intakes of calcium and dairy products in relation to risk of prostate cancer in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study, a cohort of 29,133 male smokers aged 50-69 years at study entry. Dietary intake was assessed at baseline using a validated 276-item food use questionnaire. Cox proportional hazards regression was used to adjust for known or suspected risk factors for prostate cancer. During 17 years of follow-up, we ascertained 1,267 incident cases of prostate cancer. High versus low intake of dietary calcium was associated with a marked increase in prostate cancer risk. The multivariate relative risk (RR) of prostate cancer for > or =2,000 mg/day compared to <1,000 mg/day of calcium intake was 1.63 (95% confidence interval (CI), 1.27-2.10; p trend < 0.0001). Total dairy intake was also positively associated with risk of prostate cancer. The multivariate RR of prostate cancer comparing extreme quintiles of intake was 1.26 (95% CI, 1.04-1.51; p trend = 0.03). However, no association with total dairy intake remained after we adjusted for calcium (p trend = 0.17). Findings were similar by stage and grade of prostate cancer. The results from this large prospective study suggest that intake of calcium or some related component contained in dairy foods is associated with increased prostate cancer risk.",
"title": "A prospective study of dietary calcium, dairy products and prostate cancer risk (Finland)."
},
{
"docid": "MED-3163",
"text": "Exercise promotes longevity and ameliorates type 2 diabetes mellitus and insulin resistance. However, exercise also increases mitochondrial formation of presumably harmful reactive oxygen species (ROS). Antioxidants are widely used as supplements but whether they affect the health-promoting effects of exercise is unknown. We evaluated the effects of a combination of vitamin C (1000 mg/day) and vitamin E (400 IU/day) on insulin sensitivity as measured by glucose infusion rates (GIR) during a hyperinsulinemic, euglycemic clamp in previously untrained (n = 19) and pretrained (n = 20) healthy young men. Before and after a 4 week intervention of physical exercise, GIR was determined, and muscle biopsies for gene expression analyses as well as plasma samples were obtained to compare changes over baseline and potential influences of vitamins on exercise effects. Exercise increased parameters of insulin sensitivity (GIR and plasma adiponectin) only in the absence of antioxidants in both previously untrained (P < 0.001) and pretrained (P < 0.001) individuals. This was paralleled by increased expression of ROS-sensitive transcriptional regulators of insulin sensitivity and ROS defense capacity, peroxisome-proliferator-activated receptor gamma (PPARγ), and PPARγ coactivators PGC1α and PGC1β only in the absence of antioxidants (P < 0.001 for all). Molecular mediators of endogenous ROS defense (superoxide dismutases 1 and 2; glutathione peroxidase) were also induced by exercise, and this effect too was blocked by antioxidant supplementation. Consistent with the concept of mitohormesis, exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans.",
"title": "Antioxidants prevent health-promoting effects of physical exercise in humans"
},
{
"docid": "MED-2252",
"text": "Studies suggested the intake of Cd from diet can be approximately equivalent to that from smoking. Moreover, a mutual metabolic influence between Cd and nutrients has been reported. The purpose of this study was to evaluate the relationship between blood cadmium concentration (BCdC) and food consumption, nutrients intake (Ca, Fe, Zn, vitamin C, and vitamin D), tobacco smoking, and some other variables (age, body mass index, and residence) in 243 adults living in the Italian island of Sardinia (Sassari Province). Specifically, we hypothesized that offal consumption contributes to Cd intakes and blood levels. The BCdC was quantified by graphite furnace atomic absorption spectrometry, and information on personal data was collected through questionnaires. Smoke significantly contributed to the BCdC (P < .001). Nonsmoker subjects who eat offal showed significantly higher BCdC (P = .04). Moreover, slightly higher BCdCs were also observed in nonsmoker subjects who eat rice, fish, and bread. The BCdC positively correlated with age of subjects (r = 0.144; P = .025) and offal daily intake in nonsmokers (r = 0.393; P < .001). The intake of Ca was negatively correlated (r = -0.281; P = .001) with the BCdC in females. The multiple linear regression analysis showed smoking > consumption of offal > body mass index ≈ age as the most important risk factors for the BCdC in the selected population. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Diet and nutrients are contributing factors that influence blood cadmium levels."
},
{
"docid": "MED-3506",
"text": "BACKGROUND: A reduced rectal perceptual threshold has been reported in patients with irritable bowel syndrome (IBS), but this phenomenon may be induced by a comorbid psychological state. We evaluated the rectal pain threshold at baseline and after conditioning (repetitive rectal painful distention: RRD) in patients with IBS or functional abdominal pain syndrome (FAPS), which is an abdominal pain disorder, and in healthy controls, and determined whether rectal hypersensitivity is a reliable marker for IBS. METHODS: The rectal sensory threshold was assessed by a barostat. First, a ramp distention of 40 ml/min was induced, and the threshold of pain and the maximum tolerable pressure (mmHg) were measured. Next, RRD (phasic distentions of 60-s duration separated by 30-s intervals) was given with a tracking method until the subjects had complained of pain six times. Finally, ramp distention was induced again, and the same parameters were measured. The normal value was defined by calculating the 95% confidence intervals of controls. RESULTS: Five or six of the seven IBS patients showed a reduced rectal pain threshold or maximum tolerable pressure, respectively, at baseline. In all patients with IBS, both thresholds were reduced after RRD load, but they were reduced in none of the patients with FAPS. RRD significantly reduced both thresholds in the IBS group (P < 0.05), but it had no effect in the control or FAPS groups. CONCLUSIONS: Rectal hypersensitivity induced by RRD may be a reliable marker for IBS. Conditioning-induced visceral hypersensitivity may play a pathophysiologic role in IBS.",
"title": "Repetitive rectal painful distention induces rectal hypersensitivity in patients with irritable bowel syndrome."
},
{
"docid": "MED-3295",
"text": "Background Few studies have investigated mortality in seafood workers worldwide, and no such study has been conducted in the United States. The objective of this study was to investigate mortality in American seafood workers. Methods The study population was derived from 4 states and consisted of 4116 subjects who worked mainly in seafood processing plants. They were followed up from 1966 to 2003. Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated, using the US general population for comparison. Results About 45% of the cohort was born after 1949. A total of 788 deaths were recorded; 53% of the decedents were female, and 88% were white. The SMRs for stomach cancer and disorders of the thyroid gland in the cohort as a whole were 2.1 (95% confidence interval [CI], 1.1–3.8) and 6.1 (95% CI 1.3–18.0), respectively. The SMRs for breast cancer, and occlusion/stenosis of the pre-cerebral/cerebral arteries in the cohort as a whole were 0.5 (95% CI, 0.3–0.9) and 0.5 (95% CI, 0.2–0.8), respectively. The SMR for ischemic heart disease in white females was 0.8 (95% CI, 0.6–0.9). Conclusions This cohort had excess deaths from stomach cancer and disorders of the thyroid gland, and deficit of deaths from breast cancer, stroke and ischemic heart disease. The significance of these findings is unknown, especially as less than 20% of the cohort were deceased. Nevertheless, the cohort is unique and important, and further follow-up may shed more light on mortality patterns in this occupational group.",
"title": "Cancer and Noncancer Mortality Among American Seafood Workers"
},
{
"docid": "MED-4824",
"text": "In Japan, the number of patients with both chronic pancreatitis (CP) and pancreatic cancer (PC) is increasing. A nationwide survey on CP revealed that the total number of patients treated for CP in Japan in 2002 was estimated as 45,200 (95% confidence interval, 35,600-54,700), and 20,137 patients died of PC in 2002. Alcoholic pancreatitis was the most common type of pancreatitis (67.5 %). Cigarette smoking was an independent and significant risk factor for CP. The risks of pancreatic and nonpancreatic cancers increased in the course of CP. While alcohol consumption may increase the risk of PC via CP, smoking was important as a risk factor for both CP and PC. The increasing incidence of PC was closely related to the increasing intake of animal fat. Lifestyle in patients with CP appeared to be the same as that in patients with PC. Environmental factors such as lifestyle in combination with genetic factors may increase the risk for both CP and PC. Therefore, changing and improving lifestyle habits such as drinking, smoking and nutrition may reduce the risks for both CP and PC.",
"title": "4. Chronic pancreatitis and pancreatic cancer, lifestyle-related diseases."
},
{
"docid": "MED-4181",
"text": "Exposure of pregnant women to organochlorine (OC) pesticides largely derives from contaminated food, but environmental, occupational, and domestic factors have also been implicated. We investigated the presence of nine OC residues in the umbilical cord blood of newborns in Southern Spain and analyzed the relationship of this exposure with maternal and pregnancy variables, including maternal adherence to the Mediterranean Diet (MD). OCs were detected in 95% of umbilical cord blood samples from the 318 mothers, who had a mean degree of adherence to the MD of 56.77 (SD: 16.35) (range, 0-100). The MD prioritizes consumption of vegetable and fruit over meat and dairy products, and OCs are generally lipophilic molecules that accumulate in foods of animal origin. Consumption of meat, fish, and dairy products was associated with dichlorodiphenyldichloroethylene (DDE) in umbilical cord serum, and dairy product intake with lindane. Vegetable consumption was also associated with lindane and fruit intake with endosulfan I. We found no significant association between MD adherence and the presence of OC residues in serum. However, closer adherence to the MD may offer greater protection against OC exposure because of its reduced content in meat and dairy products. Copyright (c) 2010 Elsevier Ltd. All rights reserved.",
"title": "Organochlorine pesticides in umbilical cord blood serum of women from Southern Spain and adherence to the Mediterranean diet."
},
{
"docid": "MED-1551",
"text": "In a controlled trial, 21 strict vegetarians were studied prospectively for eight weeks: a two-week control period of the usual vegetarian diet was followed by four weeks, during which 250 g of beef was added isocalorically to the daily vegetarian diet and then by two weeks of the control diet. Plasma high-density lipoprotein-cholesterol did not change during the study, whereas plasma total cholesterol rose significantly by 19% at the end of the meat-eating period. Systolic blood pressure (BP) increased significantly during the meat eating by 3% over control values, whereas diastolic BP showed no major changes. Plasma renin activity, prostaglandin A and E levels, and urinary kallikrein, norepinephrine, and epinephrine excretions were within normal limits and did not change notably throughout the trial. The study suggests an adverse effect of consumption of beef on plasma lipid and BP levels.",
"title": "Effect of ingestion of meat on plasma cholesterol of vegetarians."
}
] |
191388
|
It Happened One Night cast Clark Gable.
|
[
{
"docid": "Clark_Gable",
"text": "William Clark Gable ( February 1 , 1901 -- November 16 , 1960 ) was an American film actor , often referred to as `` The King of Hollywood '' or just simply as `` The King '' . Gable began his career as a stage actor and appeared as an extra in silent films between 1924 and 1926 , and progressed to supporting roles with a few films for Metro-Goldwyn-Mayer in 1931 . The next year , he landed his first leading Hollywood role and over the next three decades he became a leading man in more than 60 motion pictures . Gable won an Academy Award for Best Actor for It Happened One Night ( 1934 ) , and was nominated for leading roles in Mutiny on the Bounty ( 1935 ) and for his arguably best-known role as Rhett Butler in the epic Civil War drama Gone with the Wind ( 1939 ) . Gable also found success commercially and critically with films such as Red Dust ( 1932 ) , Manhattan Melodrama ( 1934 ) , San Francisco ( 1936 ) , Saratoga ( 1937 ) Boom Town ( 1940 ) , The Hucksters ( 1947 ) , Homecoming ( 1948 ) , and The Misfits ( 1961 ) , which was his final screen appearance . Gable appeared opposite some of the most popular actresses of the time . Joan Crawford was his favorite actress to work with , and she was partnered with Gable in eight films . Myrna Loy worked with him seven times , and he was paired with Jean Harlow in six productions . He also starred with Lana Turner in four features , and with Norma Shearer and Ava Gardner in three each . Gable 's final film , The Misfits ( 1961 ) , united him with Marilyn Monroe ( also in her last screen appearance ) . Gable is considered one of the most consistent box-office performers in history , appearing on Quigley Publishing 's annual Top Ten Money Making Stars Poll 16 times . He was named the seventh-greatest male star of classic American cinema by the American Film Institute .",
"title": ""
}
] |
[
{
"docid": "It_Happened_One_Night",
"text": "It Happened One Night is a 1934 American pre-Code romantic comedy film with elements of screwball comedy directed and co-produced by Frank Capra , in collaboration with Harry Cohn , in which a pampered socialite ( Claudette Colbert ) tries to get out from under her father 's thumb and falls in love with a roguish reporter ( Clark Gable ) . The plot is based on the August 1933 short story `` Night Bus '' by Samuel Hopkins Adams , which provided the shooting title . One of the last romantic comedies created before the MPAA began enforcing the 1930 production code in 1934 , the film was released on February 22 , 1934 . It Happened One Night was the first movie to win all five major Academy Awards ( Best Picture , Director , Actor , Actress , and Screenplay ) , a feat that would not be matched until One Flew Over the Cuckoo 's Nest ( 1975 ) and later by The Silence of the Lambs ( 1991 ) . In 1993 , It Happened One Night was selected for preservation in the United States National Film Registry by the Library of Congress , being deemed `` culturally , historically , or aesthetically significant '' . In 2013 , the film underwent an extensive restoration .",
"title": ""
},
{
"docid": "Cross-Country_Romance",
"text": "Cross-Country Romance is a 1940 American romantic comedy film starring Gene Raymond and Wendy Barrie . With the huge success of It Happened One Night , the 1934 American romantic comedy film directed by Frank Capra and starring Claudette Colbert and Clark Gable , every studio in Hollywood attempted to cash in with a similar storyline . In addition to this film , there was also Love on the Run ( 1936 ) from MGM , The Bride Came C.O.D. ( 1941 ) by Warner Bros. ; even Columbia Pictures , which had made It Happened One Night , produced the musical remake Eve Knew Her Apples ( 1945 ) .",
"title": ""
},
{
"docid": "Peter_Warne",
"text": "Peter Warne may refer to : Peter Warne , a character played by Clark Gable in the 1934 film It Happened One Night Peter Warne , a character played by Jack Lemmon in the 1956 remake You Ca n't Run Away from It Peter Warne , alternate name of British songwriter Michael Julien",
"title": ""
},
{
"docid": "William_Wright_(actor)",
"text": "William Wright ( January 5 , 1911 -- January 19 , 1949 ) was an American leading man in films who was most popular in the 1940s when he was typically compared to Clark Gable , whose career was temporarily derailed by World War II . Wright even played Gable 's part in a 1945 musical comedy remake of It Happened One Night entitled Eve Knew Her Apples . He also played Philo Vance in Philo Vance Returns ( 1947 ) and the title role in King of the Gamblers ( 1948 ) . Wright 's other films include Eadie Was a Lady ( 1945 ) , Rose of the Yukon ( 1949 ) , Daughter of the Jungle ( 1949 ) , and Impact ( 1949 ) . Wright died from cancer in 1949 at the age of 38 .",
"title": ""
},
{
"docid": "Charles_C._Wilson_(actor)",
"text": "Charles Cahill Wilson ( July 29 , 1894 -- January 7 , 1948 ) was an American character actor of the early sound film . The white-haired , burly actor was often typecast as an earnest police officer , newspaper editor or principal . He appeared in over 250 films between 1928 and 1948 , mostly playing small supporting roles with a few sentences . Charles Wilson began his acting career at the theatre , including roles in six Broadway plays between 1918 and 1931 . In 1928 , he directed the Hollywood comedy Lucky Boy ( 1928 ) , where he also made his film debut . According to the Internet Movie Database , Lucky Boy was Wilson 's only film as a director . His most notable role was probably Clark Gable 's `` wonderfully aggravated '' newspaper boss in Frank Capra 's comedy It Happened One Night , which won five Academy Awards in 1935 . He was also cast in small roles in other Capra movies such as Mr. Deeds Goes to Town ( 1936 ) and It 's a Wonderful Life ( 1946 ) . Shortly before his death , Wilson appeared as the boss of the Three Stooges in the two-reel comedy Crime on Their Hands ( 1948 ) . He died at the age of 53 of esophageal varices .",
"title": ""
},
{
"docid": "You_Can't_Run_Away_from_It",
"text": "You Ca n't Run Away from It is a 1956 Technicolor and CinemaScope musical comedy starring June Allyson and Jack Lemmon . Directed and produced by Dick Powell , the film is a remake of the 1934 Academy Award-winning film It Happened One Night . The supporting cast features Charles Bickford , Jim Backus , Stubby Kaye , Jack Albertson and Howard McNear . It Happened One Night had also been remade as a musical comedy in 1945 as Eve Knew Her Apples .",
"title": ""
},
{
"docid": "The_Finger_Points",
"text": "The Finger Points is a 1931 American Pre-Code drama film directed by John Francis Dillon and written by John Monk Saunders , W.R. Burnett and Robert Lord . The film stars Richard Barthelmess , Fay Wray , Regis Toomey , Robert Elliott , Clark Gable , Oscar Apfel and Robert Gleckler . The film was released by Warner Bros. on April 11 , 1931 . Clark Gable was chosen to be Louis J. Blanco , the chief enforcer of the mob . Contracted with MGM , Gable filmed scenes for The Finger Points , Night Nurse , and The Easiest Way simultaneously .",
"title": ""
},
{
"docid": "The_Misfits_(film)",
"text": "The Misfits is a 1961 American drama film written by Arthur Miller , directed by John Huston , and starring Clark Gable , Marilyn Monroe and Montgomery Clift . The supporting cast features Thelma Ritter , Eli Wallach and Kevin McCarthy . It marked the last completed film of Gable and Monroe . For Gable , the film was posthumously released , while Monroe died the following year . The plot centers on a recently divorced woman ( Monroe ) and her time spent with a cowboy ( Gable ) and his rodeo-riding friend ( Clift ) in the Western Nevada desert in the 1960s . The film was a commercial failure at the time of its release , but received positive critical comments for its script and performances , and is highly regarded today .",
"title": ""
},
{
"docid": "Night_Nurse_(1931_film)",
"text": "Night Nurse is a 1931 American pre-Code crime drama and mystery film produced and distributed by Warner Bros. and directed by William A. Wellman . The film stars Barbara Stanwyck , Ben Lyon , Joan Blondell , Clark Gable and Vera Lewis . It was based on the 1930 novel of the same name , written by Grace Perkins , later Mrs. Fulton Oursler ( under the pen name Dora Macy ) . The film was considered risqué at the time of its release , particularly the scene where Stanwyck is seen in her lingerie . Gable portrays a vicious chauffeur gradually starving two little girls to death .",
"title": ""
},
{
"docid": "Frankly,_my_dear,_I_don't_give_a_damn",
"text": "`` Frankly , my dear , I do n't give a damn '' is a line from the 1939 film Gone with the Wind starring Clark Gable and Vivien Leigh . The line is spoken by Rhett Butler ( Gable ) , as his last words to Scarlett O'Hara ( Leigh ) , in response to her tearful question : `` Where shall I go ? What shall I do ? '' Scarlett , however , clings to the hope that she can win him back . This line is partially spoken by Rhett Butler in Margaret Mitchell 's novel Gone with the Wind , published in 1936 , from which the movie is derived . The line demonstrates that Rhett has finally given up on Scarlett and their tumultuous relationship . After more than a decade of fruitlessly seeking her love , he no longer cares what happens to her . This quotation was voted the number one movie line of all time by the American Film Institute in 2005 .",
"title": ""
},
{
"docid": "Clark_James_Gable",
"text": "Clark James Gable ( born September 20 , 1988 in Malibu , California ) is an American actor , model , and television presenter . He is the former television host of the reality show Cheaters . Gable is the grandson of the actor Clark Gable , son of John Clark Gable and Tracy Yarro , and younger brother of actress Kayley Gable . His stepfather is Chicago bassist , Jason Scheff . Gable was arrested in 2011 for shining a laser pointer at a police helicopter in Los Angeles . He pleaded guilty and was sentenced to ten days in jail and three years ' probation .",
"title": ""
},
{
"docid": "The_Hucksters",
"text": "The Hucksters is a 1947 Metro-Goldwyn-Mayer film directed by Jack Conway and starring Clark Gable that marked the debut of Deborah Kerr in an American film . The supporting cast includes Sydney Greenstreet , Adolphe Menjou , Keenan Wynn , Edward Arnold and Ava Gardner . The movie is based on the novel The Hucksters by Frederic Wakeman , Sr. , a skewering of the post-World War II radio advertising industry with a racy backdrop for its day involving Gable and his alternating pursuit of Kerr and Gardner .",
"title": ""
},
{
"docid": "Strange_Cargo_(1940_film)",
"text": "Strange Cargo is a 1940 American romantic drama film by Metro-Goldwyn-Mayer , directed by Frank Borzage and starring Joan Crawford and Clark Gable in a story about a group of fugitive prisoners from a French penal colony . The screenplay by Lawrence Hazard was based upon the 1936 novel , Not Too Narrow , Not Too Deep , by Richard Sale . The film was produced by Joseph L. Mankiewicz and was the eighth and last film pairing of Crawford and Gable . The supporting cast includes Peter Lorre .",
"title": ""
},
{
"docid": "Hotel_Monte_Vista",
"text": "The Hotel Monte Vista is a famous and historic hotel located one block north of U.S. Route 66 in Flagstaff , Arizona . The hotel was built in 1927 and is a centerpiece of the historic downtown district . The hotel contains 73 rooms and suites on three floors . Many famous people have spent the night at the Hotel Monte Vista , including : John Wayne , Spencer Tracy , Humphrey Bogart , Clark Gable , Anthony Hopkins , Esther Williams , and Barbara Stanwyck . There have been many alleged ghost sightings at the Hotel Monte Vista . One of the sightings involves a `` Phantom Bell Boy '' that knocks on guests ' doors in the middle of the night and will talk to the guest . The hotel is located at 100 N. San Francisco Street . It was also a filming location for the 1942 American romantic drama Casablanca . The Monte Vista Lounge , or `` Monte V '' as it is known , is a popular bar and entertainment venue .",
"title": ""
},
{
"docid": "Hoppy_Serves_a_Writ",
"text": "Hoppy Serves a Writ is a 1943 Western film directed by George Archainbaud and starring William Boyd as Hopalong Cassidy . The supporting cast features Andy Clyde , Victor Jory and George Reeves . The film remains noteworthy today as one of the earliest performances ( his 3rd ) of unshaven newcomer Robert Mitchum , who made an impression upon the studio by generating a surprising fan mail response exactly as Clark Gable had after playing an extremely similar unshaven role in The Painted Desert , a Western starring William Boyd produced a dozen years earlier .",
"title": ""
},
{
"docid": "You_Made_Me_Love_You_(I_Didn't_Want_to_Do_It)",
"text": "`` You Made Me Love You ( I Did n't Want to Do It ) '' is a popular song . The music was written by James V. Monaco , the lyrics by Joseph McCarthy . The song was published in 1913 . It was introduced in the Broadway revue The Honeymoon Express and used in the 1973 revival of the musical Irene . One of the earliest recordings of the song was by Al Jolson . Jolson recorded the song on June 4 , 1913 . It was released on Columbia A-1374 . He performed it on the soundtrack of the 1946 film The Jolson Story and recorded it on March 20 , 1946 . The record was released on Decca 23613 . Roger Edens wrote additional lyrics to the song for Judy Garland . The new lyrics cast Garland in the role of a teenage fan of Clark Gable . Garland sang the song to Gable at a birthday party thrown for him by Metro-Goldwyn-Mayer . MGM executives were so charmed by her rendition that she and the song were added to the film Broadway Melody of 1938 . Garland recorded the `` Gable '' version on September 24 , 1937 . It was released on Decca 1463 . MGM released the song as a b-side in 1939 , opposite Garland 's recording of `` Over the Rainbow '' for The Wizard of Oz .",
"title": ""
},
{
"docid": "Honky_Tonk_(1941_film)",
"text": "Honky Tonk is a 1941 black-and-white western film directed by Jack Conway , produced by Pandro S. Berman , and starring Clark Gable and Lana Turner . The supporting cast features Claire Trevor , Frank Morgan , Marjorie Main , Albert Dekker and Chill Wills .",
"title": ""
},
{
"docid": "Randy_Clark_(boxer)",
"text": "Randy Clark was a professional American Heavyweight boxer from Miami , Florida . Before turning to Boxing Clark was a High School Football star at Coral Gables High School in Coral Gables , Florida . Additionally , before beginning his boxing career Clark served four years with the United States Marine Corps . Clark turned professional boxer without ever having an amateur fight . He turned professional on October 21 , 1969 and scored a first round Knockout over Moses Green . Clark quickly became a fan favorite and gained a lot of support from blue collar workers in the South Florida area . Clark worked as a plasterer in the Miami area . After compiling a record of eleven wins and no losses Clark appeared in his first main event . On June 20 , 1972 Clark scored a ten round decision over Fred Williams at the Miami Marine Stadium on Key Biscayne . Clark was continuously plagued by injured hands throughout his career . Clark 's unofficial professional record was thirteen wins and one loss .",
"title": ""
},
{
"docid": "Saturday_Night_Live_(season_18)",
"text": "The eighteenth season of Saturday Night Live , an American sketch comedy series , originally aired in the United States on NBC between September 26 , 1992 , and May 15 , 1993 . Many changes happened before the start of the season . Long term cast member Victoria Jackson left the show after six seasons . Newer cast members Beth Cahill and Siobhan Fallon were both fired to make room in the cast . Unlike the past two seasons Lorne Michaels did not hire any new cast members . Rob Schneider was upgraded to repertory status . Ellen Cleghorne , Tim Meadows , Adam Sandler , and David Spade remained in the middle category . Melanie Hutsell was promoted to the middle category . Robert Smigel remained as a featured cast member . Long-term cast member Dana Carvey decided to leave the show mid season . This would also be the final season for Chris Rock and Robert Smigel . After three years with the show , Rock decided to quit the show at the end of the season . Rock had become frustrated with never quite finding a voice on the show and wanted to instead focus on his stand-up career . Writer and featured player Smigel left to become the head writer for Late Night with Conan O'Brien , but would later return to the show in 1996 to write and produce the `` TV Funhouse '' cartoons . This was also the last season to feature three separate categories for cast members . Starting next season , the show returned to the original `` repertory '' and `` featured '' cast lists . This season was also home to one of SNL '' 's most infamous moments : Sinéad O'Connor tore a photograph of Pope John Paul II at the end of her second performance on the episode hosted by Tim Robbins . Due to the success of the film Wayne 's World , Michaels decided it was a good idea to jump onto the popularity of the film and make more movies based on SNL characters . However , none would prove to be as successful as Wayne 's World '' , critically or commercially .",
"title": ""
},
{
"docid": "Gable_(surname)",
"text": "Gable is a surname . Notable people with the surname include : Ashley Gable , American screenwriter and producer Bob Gable , American businessman and political candidate Brian Gable , Canadian cartoonist C. J. Gable , American football player Chad Gable ( born 1986 ) , ring name of American professional wrestler Charles Betts Christopher Gable , English dancer and actor Clark Gable ( 1901 -- 1960 ) , American actor Clark James Gable , American actor Dan Gable ( born 1948 ) , American freestyle wrestler and wrestling coach Ellen Gable , American author Eric Gable , American singer Gerry Gable , British activist Guitar Gable , American musician Howard Gable , Australian record producer Jennifer Gable , American actress and writer Jeremy Gable , American playwright John Allen Gable , American historian June Gable , American actress Mark Gable , member of the Choirboys",
"title": ""
},
{
"docid": "Betrayed_(1954_film)",
"text": "Betrayed is a 1954 war drama film directed by Gottfried Reinhardt from a screenplay by Ronald Millar and George Froeschel , and starring Clark Gable , Lana Turner , and Victor Mature . The music score was by Walter Goehr and Bronislau Kaper , and the cinematography by Freddie Young . The picture , Gable 's last for Metro-Goldwyn-Mayer , was filmed on location in the Netherlands and England and was based on the story of turncoat Dutch resistance leader Christiaan Lindemans , also known as `` King Kong '' . The supporting cast features Louis Calhern , O. E. Hasse , Wilfrid Hyde-White , Ian Carmichael , Niall MacGinnis , and Theodore Bikel . Betrayed was the fourth and final movie in which Gable played opposite Turner , and their third pairing set during World War II . Diana Coupland provided Turner 's singing voice in the song , `` Johnny Come Home '' . Betrayed was spoofed in the film Top Secret ! ( 1984 ) .",
"title": ""
},
{
"docid": "It_Started_in_Naples",
"text": "It Started in Naples is an American romantic comedy film made by Paramount Pictures and released in August 1960 . It was directed by Melville Shavelson and produced by Jack Rose from a screenplay by Suso Cecchi d'Amico based on the story by Michael Pertwee and Jack Davies . The Technicolor cinematography was by Robert Surtees . The film stars Clark Gable , Sophia Loren , Vittorio De Sica and an Italian cast .",
"title": ""
},
{
"docid": "Key_to_the_City_(film)",
"text": "Key to the City is a 1950 American romantic comedy film starring Clark Gable and Loretta Young as mayors who meet at San Francisco , and despite their contrasting personalities and views , they fall in love . It marked the final film role of Frank Morgan , who died before the film was released , and the last credited film appearance of his Wizard of Oz cast mate Clara Blandick .",
"title": ""
},
{
"docid": "Bridgeville_Public_Library",
"text": "Bridgeville Public Library was housed in a historic library building located in Bridgeville , Sussex County , Delaware . It was built in 1866 , and is a 1 1/2 - story , three bay , frame structure in the Gothic Revival style . It has a steeply pitched gable roof . There is a one-story gable roofed wing and one-story rear addition . To the front there is a two-story , gable-roofed bell tower and a gable-roofed Colonial Revival open portico . It was originally built to provide a place of worship for the First Presbyterian Church of Bridgeville . In 1917 , the Tuesday Night Club bought the building . In 1919 , the club 's Literary Guild organized a circulating library and in 1964 , the Tuesday Night Club signed the building over to the Town of Bridgeville for use as a library . The new 13,500 square foot library was opened in 2009 . It was added to the National Register of Historic Places in 1990 .",
"title": ""
},
{
"docid": "Boom_Town_(film)",
"text": "Boom Town is a 1940 American adventure film starring Clark Gable , Spencer Tracy , Claudette Colbert , and Hedy Lamarr , and directed by Jack Conway . The supporting cast features Frank Morgan , Lionel Atwill , and Chill Wills . A story written by James Edward Grant in Cosmopolitan magazine entitled `` A Lady Comes to Burkburnett '' provided the inspiration for the film . The film was produced and released by Metro-Goldwyn-Mayer .",
"title": ""
},
{
"docid": "Truman_Spain",
"text": "Truman `` Big Dog '' Spain ( January 10 , 1913 -- February 12 , 1968 ) was an American football player who was selected as an All-American at the tackles position for the 1935 National Champion Southern Methodist University Mustangs . At the end of the 1935 season , Spain was selected as a first-team All-American by Grantland Rice for Collier 's Weekly and by a board of coaches for Pathé News . He was also selected as a second-team All-American by the Associated Press and in a consensus All-American team . The 1935 SMU team had 12 -- 0 record , scoring 288 points while only giving up 39 . The team was invited to play in the 1936 Rose Bowl , and Spain became the center of attention in the newspapers ' coverage of the game . Much of the coverage focused on Spain 's good looks and indications that Spain would be signed by Hollywood as a movie star . One syndicated feature article compared Spain to Clark Gable under the headline : `` IF MOVIE COLONY GRABS OFF ONE OF MUSTANGS , IT LIKELY WILL BE CLARK GABLE SPAIN . '' The article noted that Spain was `` all man '' and reported on the reaction of co-eds to his `` rumba king '' good looks : `` If it 's a new movie idol California desires out of the Rose Bowl classic New Year 's between the Southern Methodist Mustangs and the Redmen of Stanford , the No. 1 nominee of the galloping Ponies Is Truman Spain giant all-American tackle . This Spain fellow , young ladies , is definitely of the Latin type except that instead of being sleek he is as hard as ship 's steel and as torrid as a foundry furnace . He is tall , very bronzed and handsome enough . His smile dashes from white and very even teeth and according to campus co-eds , he is a ` honey . ' He has straight black hair , which like Clark Gables , klnda ' likes to fall down over his forehead . ... No mere man could use the correct expression , but a co-ed said : ` His large , black eyes burn into you and make you feel that something is going to happen . ' '' An article in a Texas newspaper reported on the attention being focused on Spain : `` Spain , towering well over six feet and going past the two hundred pound mark , was the center of attention . He played high school football in the Oil Belt , and many of his old friends met the train to wish him well . He came in for a lot of kidding about trying to crash the movies . '' In late January 1936 , the publicity drew an offer for Spain to enter the boxing game , which he turned down . Spain said he was due a movie tryout , and `` a bunged-up face would n't be any help in Hollywood , unless Truman wanted a gangster role . '' After retiring from football , Spain worked as an oil drilling contractor in Ardmore , Oklahoma . He died in 1968 of an apparent heart attack at age 55 .",
"title": ""
},
{
"docid": "Otis_Clark",
"text": "Otis Clark ( February 13 , 1903 -- May 21 , 2012 ) was one of the last survivors of the May 31 , 1921 , Tulsa race riot , considered to be the worst ethnic riot in American history . He later worked as a Hollywood butler for movie stars Clark Gable , Charlie Chaplin , and Joan Crawford . Clark 's wife lived at the Crawford residence working as the cook for Joan Crawford .",
"title": ""
},
{
"docid": "Josephine_City_School",
"text": "Josephine City School is a historic school building for African-American children located at Berryville , Clarke County , Virginia . It was built about 1882 , and is a rectangular , one-story , frame building with a gable roof and a four-bay side gable entrance facade . The school measures approximately 40 feet long and 30 feet wide . It is part of a school complex for African American children that included the Josephine City School ; the 1930 brick Clarke County Training School ; and a 1941 frame building that was constructed as additional agriculture classrooms . It was used as an elementary school until 1930 , when it was moved a short distance from its original location , and used as the Clarke County Training School 's home economics and agriculture classrooms . It was used for classrooms until 1971 , when it was turned into storage space , after which it was converted into low/moderate-income elderly housing . It was listed on the National Register of Historic Places in 1995 . Part of the building now houses the Josephine School Community Museum and Clarke County African-American Cultural Center . Opened in 2003 , the museum displays the history of Clarke County 's African-American community .",
"title": ""
},
{
"docid": "Night_Heat",
"text": "Night Heat was a Canadian police drama series , which aired on both CTV in Canada and CBS in the United States . Original episodes were broadcast from 1985 to 1989 in the United States , and until 1990 in Canada . Night Heat was the first Canadian-produced drama series to air on an American network . CBS aired the series as part of CBS Late Night , a late night block of drama programming . Despite its late hour , Night Heat received good ratings for CBS , sometimes even beating NBC 's Johnny Carson Show . After it was canceled , reruns continued to air on CBS for another two years , and on Canadian TV well into the early 2000s . Night Heat reruns were available on Showcase , TVtropolis and DejaView . The show starred Allan Royal as journalist Tom Kirkwood , who chronicled the nightly police beat of detectives Kevin O'Brien ( Scott Hylands ) and Frank Giambone ( Jeff Wincott ) . For Hylands , a 21-year veteran actor , frequently seen playing villains in U.S. TV shows during the 1970s and early 1980s , this was the first time he had been given a leading role , or the role of a `` good guy . '' The Kevin O'Brien character was described as `` a somewhat cynical , hardened hero . '' The cast also included Susan Hogan , Wendy Crewson , Sean McCann , Louise Vallance , Stephen Mendel , Eugene Clark , and Clark Johnson . Concurrent with her work on Night Heat , Vallance was starring in the children 's series Zoobilee Zoo .",
"title": ""
},
{
"docid": "Night_Flight_(1933_film)",
"text": "Night Flight ( also known as Dark to Dawn ) is a 1933 American pre-Code aviation drama film produced by David O. Selznick and distributed by Metro-Goldwyn-Mayer and directed by Clarence Brown . The film stars John Barrymore , Lionel Barrymore , Clark Gable , Helen Hayes , Robert Montgomery , and Myrna Loy . It is based on the 1931 novel of the same name which won the Prix Femina the same year , by French writer and pioneering aviator Antoine de Saint-Exupéry . Based on Saint-Exupéry 's personal experiences while flying on South American mail routes , Night Flight recreates a 24-hour period of the operations of a fictional airline based on Aéropostale , Trans-Andean European Air Mail . In 1942 , Night Flight was withdrawn from circulation as a result of a dispute between MGM and Saint Exupéry . Its public re-release had to wait until 2011 , when legal obstacles were overcome .",
"title": ""
}
] |
2441
|
Is building a corporation a good option?
|
[
{
"docid": "487870",
"text": "Creating a corporation is not necessarily less taxes. In fact, you'll face the problem of double taxation, and since you must pay yourself a reasonable salary, if your corporation doesn't earn much to give you as dividend after the salary, and/or your tax bracket is low, you'll in fact may end up paying more taxes. Also there's a lot of bureaucracy involved in managing a corporation. Liability on the other hand is important, and what's more important - is asset separation and limiting the liability to the corporation assets, keeping your personal assets safe. To achieve that, you don't have to create a corporation, but you can create a Limited Liability Company (LLC). LLC are disregarded entities for tax purposes (i.e.: you won't have to pay taxes twice, only once as a sole proprietor/partner), but provide the liability limitation and asset separation. LLC's are much less formal, and require much less paperwork reducing the risk of corporate veil piercing because of non-compliance. I myself decided to manage my investments through LLC's for that very reason (asset separation).",
"title": ""
},
{
"docid": "346374",
"text": "Compared with a Sole Proprietorship, the main disadvantages of an S-Corporation or an LLC are that it adds a lot of management overhead (time, and possibly money if you don't do it all yourself), and there are fees you must pay to incorporate, as well as additional yearly maintenance fees which vary by state. You should be able to weigh the tax savings and liability protection against the extra costs and hassle, and see which way the scales tip. As a rule of thumb, the bigger your business gets or the more income you make, the more attractive incorporating becomes. Note there are some additional taxes that certain jurisdictions impose on business income. For example, IL and CA charge 1.5% tax, NY is less, but NYC is 8.85%! In NYC specifically, you could actually end up paying slightly more tax as an S-Corp than you would as a Sole Proprietorship. In most places though, the nominal local taxes will still be less than the FICA taxes you could potentially save.",
"title": ""
}
] |
[
{
"docid": "530902",
"text": "\"I don't want to hate on those other comments but as a college student having a 4.0 and going to a \"\"target\"\" school are not realistic goals for everyone. The best advice I would give you is to be passionate about the field. It sounds dumb on its face but being involved in student investment clubs/funds or competing in investment competitions are great ways to get exposure and meet people in the field while building your resume. Internships are incredibly important because that's where you prove to yourself and others that you are a capable person. You also have a lot of options ahead of you. You can do research, client facing roles (CFP), and even corporate finance. I wasn't a finance major but I spent 3 years in college working in our student managed investment fund and it absolutely paid off (now doing corporate finance). You have to want to learn and grow. It's not realistic for a college student with limited resources to get your CFA level 1 or series exams, especially if it doesn't suit your field. Be open to different types of jobs and build relationships with your professors who are well connected. It does help to have stellar grades and it helps to be at a top school but our state school has put kids on the Street. You just have to be hungry and realistic about your talents and passion. Good luck to you.\"",
"title": ""
},
{
"docid": "426677",
"text": "\"Yeah, well, and corporations used to only be chartered by states for the express purpose of fulfilling some public function, on the order of building a bridge, etc. Now, anybody at all gets the limited liability advantages of a corporation without any of the corresponding duty to serve the public good. Now I'm sure the overall \"\"fix\"\" that will be floated will be the government basically dismantling capitalism and principles enjoyed by all private businesses, instead of just going back and fixing what was erroneously handed to corporations in the first place.\"",
"title": ""
},
{
"docid": "144660",
"text": "It is a good opportunity for those people who want to spend the vacation and make rememberable events, You should find the good rated great escapist team inside escape rooms. We have the fabulous event which is unforgetable services. It is good pleasure things for us that we get the chance to serve you. Escape rooms diversions as in Corporate team building escape rooms fort Lauderdale plan to test your critical thinking and analyst aptitudes. If you want to come here with your family, you can bring your family without hesitation. We provide the full security and corporate with our customers. There is no more place so beautiful and attractive.",
"title": ""
},
{
"docid": "324531",
"text": "Best for team building escape rooms WPB for your office colleagues and best friends for making an unforgettable memory with them by a top event planner in the West Palm Beach, Florida by the corporateteambuildingescaperooms for the corporate events. There are various things to do over here with your team and team building escape rooms WPB, You can choose best escape room, apart from this it is game where your team can build up trust and bond between with each other and let know them they can do good work better with each other your colleagues.",
"title": ""
},
{
"docid": "274974",
"text": "It is a good events here to get the full entertainment with our team building who gives you a target such as solving puzzles inside the escape rooms . There are more activity here for your special fun. The Escape Rooms Palm Beach is so amazing place in USA, Florida. It is so excellent place for the couple and many individuals comes here to get real entertainment that would help the teammates. We corporate events west palm beach with a team building.",
"title": ""
},
{
"docid": "527090",
"text": "\"When one says that \"\"corporations are people\"\", in a legal sense, they are saying that they have the ability to enter into binding legal agreements in a manner similar to people. This allows corporations to do things like own a building or a car, or enter into a contract. This is so that an individual does not have to do so. This keeps individuals from being liable for the activities of the corporation (it also keeps the individual from running off the the corporation's car or selling the corporation's building). If they are using it in any sense other than the legal sense, it's either hyperbole, ignorance, or pandering. Now, if you set yourself up as LettersFromTheSky, Inc, then you would very well be able to get all the same tax deductions and benefits as a corporation. But you would also be liable for everything that a corporation is liable for (namely, a higher standard of reporting and different accounting methods).\"",
"title": ""
},
{
"docid": "483991",
"text": "The finance sector is comprised of such enterprises as banks, investment funds, insurance companies and real estate. It is traditionally contrasted with what has been called the 'real economy' because funds created and utilized in this sector produce neither goods, services or fixed capital. The unproductive nature of transactions can easily be seen in such things as real estate. When a company undertakes to build a house or whatever its input goes directly to the labor and goods necessary for such a project. At its worst the financial sector mobilizes funds not just for production but for simple acquisition. Should a company raise the funds to buy an already existing building or the mortgage on same quite obviously nothing is produced. Same building on day one as when it was owned by another. That, of course, is an extreme example as are corporate takeovers via private equity. In that case the efforts of the financial sector are not just non-productive but are often in fact ''anti-productive'' as they destroy or prevent the use of real factors of production. This 'anti-productive' action was demonstrated on a massive global scale during the last financial crisis. The basically parasitic nature of the financial sector isn't always so blatant. There are some that argue that its 'services' can be valuable to the real economy. Perhaps, but that has to be determined on a case by case examination **and** while keeping the idea ''is there a better way to do this** in one's mind.",
"title": ""
},
{
"docid": "154841",
"text": "The short answer, probably not much. Unless you have a controlling interest in the company. If at least 50%+1 of the shareholder votes are in favor of the dilution then it can be done. There are some SEC rules that should protect against corporate looting and theft like what the Severin side is trying to make it appear as happened. However it would appear that Severin did something stupid. He signed away all of his voting right to someone who would use them to make his rights basically worthless. Had he kept his head in the game he could probably have saved himself. But he didn't. If your average startup started issuing lots of stock and devaluing existing shares significantly then I would expect it would be harder to find investors willing to watch as their investment dwindled. But if you are issuing a limited amount stock to get leverage to grow bigger then it is worth it. In the .com bubble there were quite a few companies that just issued stock to buy other companies. Eventually most of these companies got delisted because they diluted them selves to much when they were overvalued. Any company not just a startup can dilute its shares. Many if not most major companies issue stock to raise capital. This capital is then generally used to build the business further and increase the value of all shares. Most of the time this dilution is very minor (<.1%) and has little if any impact on the stock. There are rules that have to be followed as listed companies are regulated by the SEC. There are less regulations with private corporations. It looks like the dilution was combined with the buyout of the Florida company which probably contributed to the legality of the dilution. With options they are generally issued at a set price. This may be higher or lower than the reported sell price of the stock when the option is issued. The idea is over time the stock will increase in value so that those people who hold on to their options can buy the stock for the price listed on the option. I worked at an ISP start up in the 90's that made it pretty well. I left before the options were issued but I had friends still there that were issued an option at $16 a share the value of the stock at the time of the issue of the option was about 12. Well the company diluted the shares and used them to acquire more ISP's unfortunately this was about the time that DSL And cable internet took off so the dial up market tanked. The value eventually fell to .10 they did a reverse split and when they did the called in all options. The options did not have a positive cash value at any time. Had RMI ever made it big then the options could have been worth millions. There are some people from MS and Yahoo that were in early that made millions off of their options. This became a popular way for startups to attract great talent paying peanuts. They invested their time in the business hoping to strike gold. A lot of IT people got burned so this is less popular among top talent as the primary compensation anymore.",
"title": ""
},
{
"docid": "174016",
"text": "They will just break the company up into subsidiaries. A smaller company will run the mail room, another will run the computer repair, yet another will run the sales team and so on an so forth. There will be one small executive company that runs all those companies and siphons all the revenue from all of the subsidiaries. Using your scheme they can make you a 30% owner of a subsidiary that services another subsidiary and makes no money at all and in fact is a money loser and stock options will mean nothing. Major motion pictures do something similar: each movie is its own entity/company, lets call it BigExpensiveMovie397 Co., that is only around for a single movie. BigExpensiveMovie397 then hires other companies to do the work: catering, set building, production and everything else that makes a movie. And here is the fun part: if BigExpensiveMove397 is a hit, then it will pay a lot of licensing fees to yet other corporations that allowed it the use of its characters, story and anything else they can think of. Those licensing fees tend to *always* be more that whatever profit BigExpensiveMove397 makes. And that is how movies like LOTR is a money loser...no matter how much money it makes. Which is why the convinced Congress to ban using actual money with HSX... There is no way to beat such accounting. The only choice is not to take jobs like that. But since we are competing with the World and a good annual salary is $6K a year....we have a long way to go down to hit equilibrium.",
"title": ""
},
{
"docid": "399885",
"text": "\"Just as a matter of research, apparently there is a way to find high option volumes such as a site here: https://www.barchart.com/options/volume-leaders/stocks However, that information is going to be heavily skewed by \"\"underlying security that moved a lot more than expected and probably got a lot of positions filled incidentally today\"\", but I think it is a good place to start building up a list of securities with a lot of option interest. There is also a tab there for ETFs. This will not tell you exactly that a particular stock always has high option volume, but most of the ones that show up there repeatedly and across multiple strike prices will meet your criteria.\"",
"title": ""
},
{
"docid": "502242",
"text": "Get the perfect team to inspect the home before buying, it is a big investment to buy the house in a better place. In that case, we will help you. Now, no need to go anywhere in Australia. The Assured Building Inspections have wonderful experience of the inspection the building, now we are expert in this work. Always, we provide the affordable service for our clients. It is a mandatory procedure for each homeowner, we are a good protection organization inside the Australia. There is lots of inspection service company in Australia, however, they may be not proper certified in this work. It is one among most inspector and trustable corporation. We are specializing the most problems in property inspections and reports. Our impartial opinions, provide our clients with the self assurance and peace of thoughts they need to do properly knowledgeable.",
"title": ""
},
{
"docid": "9161",
"text": "What do you think happens when cash gets paid out to investors? People don't just collect the cash and stuff it in their mattress. They reinvest it, sometimes in other giant corporations, sometimes in start-ups, sometimes in government bonds. Some of it goes to fund R&D elsewhere, some of it goes to fund building bridges and roads, some of it goes toward buying houses. Ultimately, how much goes to each piece of the pie depends on the attractiveness of each opportunity. If there are a lot of good R&D projects that would generate good returns, people will invest in them.",
"title": ""
},
{
"docid": "395759",
"text": "This is the section that I was referring to: >We are unable to build bridges, we're unable to build airports, our inner city school kids are not graduating. >I was just in France, I was recently in Argentina, I was in Israel, I was in Ireland. We met with the prime minister of India and China. It's amazing to me that every single one of those countries understands that practical policies to promote business and growth is good for the average citizens of those countries, for jobs and wages, and that somehow this great American free enterprise system, we no longer get it. >Corporate taxation is critical to that, by the way. We've been driving capital earnings overseas, which is why there's $2 trillion overseas benefiting all these other countries and stuff like that. So if we don't get our act together — we can still grow.",
"title": ""
},
{
"docid": "131117",
"text": "Disclaimer: I don't work in the finance industry, and simply took a few classes in corporate finance and management during my undergrad. It depends on what type of investing you're talking about. If you're talking about building a portfolio of securities, then CAPM is the basis for most valuation models. Generally, CAPM will have you discount based on your best available risk-free rate (usually t-bills or some other fixed income source with a reliable backer). Even after your valuation, the basic theory of risk management for an investment portfolio is still to maintain a diverse basket of poorly correlated products. If you're talking about corporate finance where a firm is considering an investment such as a new project, then a determining a WACC and using it as a discount rate for your cash flow is a basic strategy. This is a basic strategy, but there are better ones depending on the specifics of the investment. This is where evaluating exposures is important. To hedge counterparty risk, you might discount by the estimated probability of non-payment or buy trade insurance. To hedge currency risk, you might buy forwards, options, or look into a money market hedge. To hedge political risks like repatriation or changes in tax laws or regulation you might buy political risk insurance. To hedge exposure to a particular commodity price, you can trade futures.",
"title": ""
},
{
"docid": "149820",
"text": "\"Corporate restructuring makes everything a flux, so you might as well revisit some core fundamental questions. Here's how to do this professionally: Start floating your CV now. Line up interviews in competing companies. Attend to them. Score a job offer, and have it put into writing, with exact salary, which should be at least 10%++ of your current one. Take a clear empty page, and write on top: \"\"Business value provided\"\". Put down your major contributions, and achievements. Wherever possible, put the company's expected dollar value near to it. For bonus points, sum it up on the bottom, and minus your current salary. Difference is \"\"Profit provided directly to the company's bottom line\"\". Float this to your manager's desk. At this position, you have only one fundamental question to your boss: \"\"match or pass?\"\" :) A corporate spin-off is a good time to do this: 1, to ensure, that your position will not be made redundant; 2, if it is, you have a backup plan. If the parent company's \"\"getting rid of you\"\", however, there are even more fundamental questions you might want to ask yourself: is this really a profitable division, or merely a loss leader? Does this company have a future, and the adequate growing options for you, personally? To answer these questions, you must have an opportunity cost estimation; and for that, you must have second (and preferably, third) options -hence, the strategy above. To conclude, the best time to do your job research is every other month; and the best time to ask for a raise is always now :) Good luck!\"",
"title": ""
},
{
"docid": "66267",
"text": "\"When I look at debt I try to think of myself as a corporation. In life, you have a series of projects that you can undertake which may yield a positive net present value (for simplicity, let's define positive net present value as a project that yields more benefit than its cost). Let's say that one of the projects that you have is to build a factory to make clothing. The factory will cost 1 million dollars and will generate revenue of 1.5 million dollars over the next year, afterwhich it wears out. Although you have the knowledge to build this wonderful factory, you don't have a million bucks laying around, so instead, you go borrow it from the bank. The bank charges you 10% interest on the loan, which means that at the end of the year, the project has yielded a return of 400k. This is an extremely simplified example of what you call \"\"good\"\" debt. It is good if you are taking the debt and purchasing something with a positive value. In reality, this should be how people should approach all purchases, even if they are with cash. Everything that you buy is an investment in yourself - even entertainment and luxury items all could be seen as an investment in your happiness and relaxation. If more people approached their finances in this way, people would have much more money to spend, William\"",
"title": ""
},
{
"docid": "238474",
"text": "If it helps you to think about it, long is equivalent to betting for the upside and short is equivalent to betting for the downside. If you are long on options, then you expect the value of such options to increase. If you are long an option, then you own the option. If you are short an option, then generally you sold the option. Someone who is short a call (sometimes called the writer or occasionally the issuer) has sold a call option to someone who is now long a call. Buying a call option that will increase in value is itself a form of investment, just as it's investment to buy stock or other instruments hoping they will appreciate in value. An option's value will rise or fall with the underlying, so being long an option is a way to be long in the underlying. Someone can be long in a stock by buying the stock, or long in a call by buying call options in the stock. The long call generally requires less initial investment than buying the underlying, and lets the option-holder avoid the asset downside during the option term. The risk is that the asset may not appreciate to the point that the call option will pay off. In the conceptual sense, a share of stock is a particular right to the profits and assets of a corporation, both in form of dividends and in liquidation. An option is a particular right to the the share of stock. It's just a further way to formalize and subdivide the various property rights that exist in a corporation. If you can buy a piece of paper with particular rights to corporate profits and assets, then you can buy another piece of paper with particular rights to the former piece of paper.",
"title": ""
},
{
"docid": "111466",
"text": "When you start living in US, it doesn't actually matter what was your Credit history in another country. Your Credit History in US is tied to your SSN (Social Security Number), which will be awarded once you are in the country legally and apply for it. Getting an SSN also doesn't guarantee you nothing and you have to build your credit history slowly. Opening a Checking or Savings account will not help you in building a credit history. You need to have some type of Credit Account (credit card, car loan, mortgage etc.) linked to your SSN to start building your credit history. When you are new to US, you probably won't find any bank that will give you a Credit Card as you have no Credit history. One alternative is to apply for a secured credit card. A secured credit card is one you get by putting money or paying money to a bank and open a Credit Card against that money, thereby the bank can be secure that they won't lose any money. Once you have that, you can use that to build up your credit history slowly and once you have a good credit history and score, apply for regular Credit Card or apply for a car loan, mortgage etc. When I came to US 8 years ago, my Credit History was nothing, even though I had pretty good balance and credit history back in my country. I applied for secured credit card by paying $500 to a bank ( which got acquired by CapitalOne ), got it approved and used it for everything, for three years. I applied for other cards in the mean time but got rejected every time. Finally got approved for a regular credit card after three years and in one year added a mortgage and car loan, which helped me to get a decent score now. And Yes, a good Credit Score is important and essential for renting an apartment, leasing a car, getting a Credit Card etc. but normally your employer can always arrange for an apartment given your situation or you need to share apartment with someone else. You can rent a car without and credit score, but need a valid US / International Drivers license and a Credit Card :-) Best option will be to open a secured credit card and start building your credit. When your wife and family arrives, they also will be assigned individual SSN and can start building their credit history themselves. Please keep in mind that Credit Score and Credit History is always individual here...",
"title": ""
},
{
"docid": "293389",
"text": "\"This is the sad state of US stock markets and Regulation T. Yes, while options have cleared & settled for t+1 (trade +1 day) for years and now actually clear \"\"instantly\"\" on some exchanges, stocks still clear & settle in t+3. There really is no excuse for it. If you are in a margin account, regulations permit the trading of unsettled funds without affecting margin requirements, so your funds in effect are available immediately after trading but aren't considered margin loans. Some strict brokers will even restrict the amount of uncleared margin funds you can trade with (Scottrade used to be hyper safe and was the only online discount broker that did this years ago); others will allow you to withdraw a large percentage of your funds immediately (I think E*Trade lets you withdraw up to 90% of unsettled funds immediately). If you are in a cash account, you are authorized to buy with unsettled funds, but you can't sell purchases made on unsettled funds until such funds clear, or you'll be barred for 90 days from trading as your letter threatened; besides, most brokers don't allow this. You certainly aren't allowed to withdraw unsettled funds (by your broker) in such an account as it would technically constitute a loan for which you aren't even liable since you've agreed to no loan contract, a margin agreement. I can't be sure if that actually violates Reg T, but when I am, I'll edit. While it is true that all marketable options are cleared through one central entity, the Options Clearing Corporation, with stocks, clearing & settling still occurs between brokers, netting their transactions between each other electronically. All financial products could clear & settle immediately imo, and I'd rather not start a firestorm by giving my opinion why not. Don't even get me started on the bond market... As to the actual process, it's called \"\"clearing & settling\"\". The general process (which can generally be applied to all financial instruments from cash deposits to derivatives trading) is: The reason why all of the old financial companies were grouped on Wall St. is because they'd have runners physically carting all of the certificates from building to building. Then, they discovered netting so slowed down the process to balance the accounts and only cart the net amounts of certificates they owed each other. This is how we get the term \"\"bankers hours\"\" where financial firms would close to the public early to account for the days trading. While this is all really done instantly behind your back at your broker, they've conveniently kept the short hours.\"",
"title": ""
},
{
"docid": "180148",
"text": "\"There are a couple of different things that could be referenced by \"\"cheap money\"\": The money supply itself - This is the Federal Reserve printing more money which could devalue the existing US dollars and thus make the dollars even cheaper since there would be more of them. Interest rates - Currently in the US interest rates are rather low which means that borrowers could possibly get good rates on that money thus making it relatively cheap. Compare current interest rates to the early 1980s and there is a major difference. In terms of implications on the stock market, there are a couple that come to my mind: Investment options - With low interest rates, cash and bonds aren't necessarily yielding that much and thus some people may be more likely to invest elsewhere with stocks being an option. Thus, there may be some people that would rather invest in stocks than hold their investments in lower-yielding options. Corporate spending - If rates stay low, then for companies with good financial track records, they could borrow money to expand operations rather than sell more stock and thus there may be companies that borrow to grow so that they take advantage of these interest rates.\"",
"title": ""
},
{
"docid": "71614",
"text": "\">As a legal matter, shareholders who purchase shares of stock in a corporation own nothing more than that—shares of stock. Similarly, bondholders own only bonds, and executives with employment contracts own their contracts. None of these types of ownership give shareholders, bondholders or executives the right to control the firm. The right to control the firm’s assets and actions rests in the hands of its board of directors, and only when they act as a body and follow proper board procedures. All this says is \"\"decisions are made by the board.\"\" This is not news, and it doesn't mean that shareholders do not own the company. Shareholders elect the board, by the way. >An important consequence of this governance structure is that shareholders not only have no legal right to control the firm, they also have no legal right to help themselves to the corporation’s assets. Well, that's wrong. >In fact, the only time shareholders receive any funds directly from the corporation’s coffers is when they receive a dividend or the corporation repurchases their shares. Or, you know, in the case of bankruptcy. >This only happens when the directors vote to declare a dividend or a corporate repurchase. The same directors who were appointed by shareholders. >At law, a principal has a right to control her agent. But shareholders can’t exercise direct control over corporate directors. I suppose this is true in the sense that shareholders cannot practice slavery. But shareholders can, again, vote on issues relating to the governance of the company. >It is thus wildly misleading to describe shareholders as the sole residual claimants in companies that aren’t actually in bankruptcy. This is only true if you're retarded and don't know what \"\"residual\"\" means. >This idea is supported by modern options theory. In effect, bondholders own the right to access cash flow but have sold a call to shareholders, while shareholders own the right to access the cash flow but have sold a put to bondholders. Neither shareholders nor bondholders can claim an exclusive right to “own” the company’s cash flow, much less the company. This is a made up explanation that doesn't mean anything. The real options model of corporate assets is that corporate debt is a risk-free bond with a short put option and equity is a call option. There is no \"\"deal,\"\" in actuality or in spirit, between debt and equity owners. You can dismiss the article as \"\"shit.\"\"\"",
"title": ""
},
{
"docid": "11721",
"text": "Whenever you want to spend the weekend with your family, then you can come here to make the special evening in West Palm Beach Escape Rooms. It is a full secure place for the girl, we have good corporate team building escape rooms WPB. We are working together and using your time wisely will you find the clues. We serve you better service all of those escape room, our services are less than expected. The escape rooms are amazing design for those people who want to spend the time with fun and get participate in our activities.",
"title": ""
},
{
"docid": "265965",
"text": "Great. But the policies aren’t targeted at him. The government isn’t conspiring to build monopolies. But corporations are definitely conspiring to take advantage of government policies. How about we force corporations to give back to the country relative to what they get from it? Or is the idea of responsible corporations just too much to handle?",
"title": ""
},
{
"docid": "96563",
"text": "\"Today sure, but that market is similar to day trading in it's volatility. It's great for individuals to make some money in the short term but it's not a good product to build a company around. Especially since the corporate giants already own the entire marketplace. And you need to take seriously that they have a 50/50 success/fail rate. Facebook is succeeding, Twitter is failing. That's not an indication of stability. Anyway you need to understand the technology and the consumer marketplace to really know what you're talking about and I suspect you don't. No offense intended. I've been using the internet since before computers were \"\"cool\"\" and I do know what I'm talking about.\"",
"title": ""
},
{
"docid": "411375",
"text": "\"Because the returns are not good. One of the big drivers in Australia is \"\"negative gearing\"\": if your investment loses money you can offset losses against your tax on other income. Institutional investors and corporations are in the business of making money: not losing it. Housing market investors are betting that these year to year revenue losses will ultimately be made up in a big capital gain: for which individuals get a huge tax break that is also not available to corporations. Capital gains are not guaranteed. Australia has benefited from 25+ years of economic, employment and wages growth: a result of good government planning, strong corporate governance and a fair slice of luck. If this were to end housing prices would plateau at best and crash at worst. A person who has negative cash flow investments has to sell them urgently if they lose their job. A glut of mortgagee sales and property prices could easily come off 20-30%. Rental yields on residential property in Sydney are about 4% with a capital gain of currently 10% but this has been flat or negative within the last 5 years and no doubt will be again within the next 5. Rental yields for residential property are constrained by mortgage rates: if it significantly cheaper to buy then to rent, why would anyone rent? In contrast, industrial and commercial property gets a yield of about 7% and gets exactly the same capital gain. This is because land is land and if the price of industrial land doesn't grow at the same rate as the residential land next door eventually one will be converted into the other. Retail rentals are even higher. In addition commercial tenants are responsible for more outgoings and have fewer legal rights than residential tenants. Further, individual residential properties are horribly illiquid and have large transaction costs. While it is possible to bundle them up into property trusts so that units can be sold on the stock exchange it is far more common to do this with office and retail buildings. This is what companies like Westfield and AMP Capital do. Notwithstanding, heavily geared property trusts can get into deep water because of the illiquid nature of property as the failure of Centro illustrates. That said, there are plenty of companies that develop residential houses and units for sale to owner occupiers or investors because that's where the money is.\"",
"title": ""
},
{
"docid": "110674",
"text": "Reversing your math, I am assuming you have $312K to work with. In that case, I would simply shop around your local banks and/or credit unions and have them compete for your money and you might be quite surprised how much they are willing to pay. A couple of months ago, you would be able to get about 4.25% from Israel Bonds in Canada on 5 years term (the Jubilee product, with minimum investment of $25K). It's a bit lower now, but you should still be able to get very good rates if you shop around tier-2 banks or credit unions (who are more hungry for capital than the well-funded tier-1 banks). Or you could look at preferred shares of a large corporation. They are different from common shares in the sense they are priced according to the payout rate (i.e. people buy it for the dividend). A quick screen from your favorite stock exchange ought to find you a few options. Another option is commercial bonds. You should be able to get that kind of return from investment grade (BBB- and higher) bonds on large corporations these days. I just did a quick glance at MarketWatch's Bond section (http://cxa.marketwatch.com/finra/BondCenter/Default.aspx) and found AAA grade bonds that will yield > 5%. You will need to investigate their underlying fundamentals, coupon rate and etc before investing (second thought, grab a introduction to bonds book from Chapters first). Hope these helps.",
"title": ""
},
{
"docid": "30959",
"text": "\"Disclosure: I don't have an iPhone, so I don't use RobinHood. That being said, I have a less \"\"they're-out-to-get-ya\"\" view of what they're doing. As a small business owner (2 businesses), employees cost the most. If you can create a solid business with few (or no) employees and let robots run it, you will drastically reduce your costs. Joe Polish said it similarly with sales letters, something along the lines of they never complain about a headache, need to take a year off to discover themself, or just need a personal day. Robots are the same; they do not have human limits. Most simple trading can be done and maintained by well written code and AI, there's very little need for humans to do anything other than build it. Think about the efficiency of bitcoin versus all the central banks combined; how many people are employed by central banks? Robinhood states that they are using technology in these ways to minimize costs and they're using a system that doesn't need physical branches (this doesn't mean they will never have them, just that they don't need them). Robinhood does not indicate that they allow everything to happen for free; only stock trading. I worked for a large trading firm once and observed that stock trading wasn't the bulk of where they made their money anyway; trading options, futures, index funds, etc are where the big money was and Robinhood says nothing about those being free. Like the CQM mentioned too, they'll be charging for margin as well. In a way, the individual stock trader is dead; many people - including this forum - prefer index funds, so more than likely, Robinhood will strike up a deal with an index fund company or create their own (this is just easy, passive income with an expense ratio). In this category, the markets are their playground, but they do need to attract enough people to their platform, thus free stock trading is a good way to do it. As for selling your information for advertising, that is always a possibility, but they have quite a few other options that would be good for most investors (index funds, affiliating with financial fund companies, etc) where they can start before ever needing to dip their toe in selling information. This isn't to say they won't do it, but that there are few other options they have. The major concern I have for Robinhood is ongoing security. Just building it and letting it run kind of assumes that there won't be major compromises in the future and as AI evolves, superior AI might be able to crush older AI.\"",
"title": ""
},
{
"docid": "457805",
"text": "Delaware llc incorporation When someone want to do some business, but the person want to have some extremely flexible business so that he can able to start up with low cost and with affordable franchise text they Delaware llc incorporation is a very good choice for doing so. It mainly help to customize the corporation and can also help to choose that option which user want to have.",
"title": ""
},
{
"docid": "257168",
"text": "\"A tax return is a document you sign and file with the government to self-report your tax obligations. A tax refund is the payment you receive from the government if your payments into the tax system exceeded your obligations. As others have mentioned, if an extra $2K in income generated $5K in taxes, chances are your return was prepared incorrectly. The selection of an appropriate entity type for your business depends a lot on what you expect to see over the next several years in terms of income and expenses, and the extent to which you want or need to pay for fringe benefits or make pretax retirement contributions from your business income. There are four basic flavors of entity which are available to you: Sole proprietorship. This is the simplest option in terms of tax reporting and paperwork required for ongoing operations. Your net (gross minus expenses) income is added to your wage income and you'll pay tax on the total. If your wage income is less than approximately $100K, you'll also owe self-employment tax of approximately 15% in addition to income tax on your business income. If your business runs at a loss, you can deduct the loss from your other income in calculating your taxable income, though you won't be able to run at a loss indefinitely. You are liable for all of the debts and obligations of the business to the extent of all of your personal assets. Partnership. You will need at least two participants (humans or entities) to form a partnership. Individual items of income and expense are identified on a partnership tax return, and each partner's proportionate share is then reported on the individual partners' tax returns. General partners (who actively participate in the business) also must pay self-employment tax on their earnings below approximately $100K. Each general partner is responsible for all of the debts and obligations of the business to the extent of their personal assets. A general partnership can be created informally or with an oral agreement although that's not a good idea. Corporation. Business entities can be taxed as \"\"S\"\" or \"\"C\"\" corporations. Either way, the corporation is created by filing articles of incorporation with a state government (doesn't have to be the state where you live) and corporations are typically required to file yearly entity statements with the state where they were formed as well as all states where they do business. Shareholders are only liable for the debts and obligations of the corporation to the extent of their investment in the corporation. An \"\"S\"\" corporation files an information-only return similar to a partnership which reports items of income and expense, but those items are actually taken into account on the individual tax returns of the shareholders. If an \"\"S\"\" corporation runs at a loss, the losses are deductible against the shareholders' other income. A \"\"C\"\" corporation files a tax return more similar to an individual's. A C corporation calculates and pays its own tax at the corporate level. Payments from the C corporation to individuals are typically taxable as wages (from a tax point of view, it's the same as having a second job) or as dividends, depending on how and why the payments are made. (If they're in exchange for effort and work, they're probably wages - if they're payments of business profits to the business owners, they're probably dividends.) If a C corporation runs at a loss, the loss is not deductible against the shareholders' other income. Fringe benefits such as health insurance for business owners are not deductible as business expenses on the business returns for S corps, partnerships, or sole proprietorships. C corporations can deduct expenses for providing fringe benefits. LLCs don't have a predefined tax treatment - the members or managers of the LLC choose, when the LLC is formed, if they would like to be taxed as a partnership, an S corporation, or as a C corporation. If an LLC is owned by a single person, it can be considered a \"\"disregarded entity\"\" and treated for tax purposes as a sole proprietorship. This option is not available if the LLC has multiple owners. The asset protection provided by the use of an entity depends quite a bit on the source of the claim. If a creditor/plaintiff has a claim based on a contract signed on behalf of the entity, then they likely will not be able to \"\"pierce the veil\"\" and collect the entity's debts from the individual owners. On the other hand, if a creditor/plaintiff has a claim based on negligence or another tort-like action (such as sexual harassment), then it's very likely that the individual(s) involved will also be sued as individuals, which takes away a lot of the effectiveness of the purported asset protection. The entity-based asset protection is also often unavailable even for contract claims because sophisticated creditors (like banks and landlords) will often insist the the business owners sign a personal guarantee putting their own assets at risk in the event that the business fails to honor its obligations. There's no particular type of entity which will allow you to entirely avoid tax. Most tax planning revolves around characterizing income and expense items in the most favorable ways possible, or around controlling the timing of the appearance of those items on the tax return.\"",
"title": ""
},
{
"docid": "444511",
"text": "Most banks offer a college card that has low limits so you can start building credit. Another good option is to get a rewards credit card and do your everyday spending on it, then immediately turn around and pay it. I have seen people that just overpay their credit card just to use it like a debit card, all while earning credit and getting rewarded for it. I work for a bank so I see this alot.",
"title": ""
}
] |
24173
|
The Silence of the Lambs is a religion.
|
[
{
"docid": "The_Silence_of_the_Lambs_(film)",
"text": "The Silence of the Lambs is a 1991 American horror-thriller film directed by Jonathan Demme and starring Jodie Foster , Anthony Hopkins , and Scott Glenn . Adapted by Ted Tally from the 1988 novel of the same name by Thomas Harris , his second to feature the character of Dr. Hannibal Lecter ; a brilliant psychiatrist and cannibalistic serial killer , the film was the second adaptation of a Harris novel featuring Lecter , preceded by the Michael Mann-directed Manhunter in 1986 . In the film , Clarice Starling , a young U.S. FBI trainee , seeks the advice of the imprisoned Dr. Lecter to apprehend another serial killer , known only as `` Buffalo Bill '' . The Silence of the Lambs was released on February 14 , 1991 , and grossed $ 272.7 million worldwide against its $ 19 million budget . It was only the third film , the other two being It Happened One Night and One Flew Over the Cuckoo 's Nest , to win Academy Awards in all the top five categories : Best Picture , Best Actor , Best Actress , Best Director , and Adapted Screenplay . It is also the first ( and so far only ) Best Picture winner widely considered to be a horror film , and only the third such film to be nominated in the category , after The Exorcist in 1973 and Jaws in 1975 . The film is considered `` culturally , historically or aesthetically '' significant by the U.S. Library of Congress and was selected to be preserved in the National Film Registry in 2011 . A sequel titled Hannibal was released in 2001 with Hopkins reprising his role , followed by two prequels : Red Dragon ( 2002 ) and Hannibal Rising ( 2007 ) .",
"title": ""
}
] |
[
{
"docid": "The_Silence_of_the_Lambs",
"text": "The Silence of the Lambs or Silence of the Lamb may refer to : The Silence of the Lambs ( novel ) , a 1988 novel by Thomas Harris The Silence of the Lambs ( film ) , a 1991 film directed by Jonathan Demme based on the novel and starring Jodie Foster and Anthony Hopkins `` Silence of the Lamb '' ( Veronica Mars ) , a 2005 television episode of Veronica Mars Waldsinfonie : The Silence of the Lamb , a 1993 Autopsia CD",
"title": ""
},
{
"docid": "Red_Dragon_(film)",
"text": "Red Dragon is a 2002 American psychological horror film based on the novel of the same name by Thomas Harris , featuring psychiatrist and serial killer Dr. Hannibal Lecter . It is a prequel to The Silence of the Lambs ( 1991 ) and Hannibal ( 2001 ) . The novel was originally adapted into the film Manhunter ( 1986 ) . The film was directed by Brett Ratner and written for the screen by Ted Tally , who also wrote the screenplay for The Silence of the Lambs . It stars Anthony Hopkins as Lecter , a role he played twice before in The Silence of the Lambs and Hannibal , and Edward Norton as FBI agent Will Graham . The film also stars Ralph Fiennes , Harvey Keitel , Emily Watson , Mary-Louise Parker , and Philip Seymour Hoffman .",
"title": ""
},
{
"docid": "The_Silence_of_the_Lambs_(novel)",
"text": "The Silence of the Lambs is a novel by Thomas Harris . First published in 1988 , it is the sequel to Harris ' 1981 novel Red Dragon . Both novels feature the cannibalistic serial killer Dr. Hannibal Lecter , this time pitted against FBI Special Agent Clarice Starling . Its film adaptation directed by Jonathan Demme was released in 1991 to box office success and critical acclaim .",
"title": ""
},
{
"docid": "Silence!_The_Musical",
"text": "Silence ! The Musical is an award-winning 2005 musical created by Jon and Al Kaplan as a parody of the 1991 Academy Award-winning film The Silence of the Lambs .",
"title": ""
},
{
"docid": "Clarice_Starling",
"text": "Clarice M. Starling is a fictional character who appears in the novels The Silence of the Lambs and Hannibal by Thomas Harris . In the film adaptation of The Silence of the Lambs , she was played by Jodie Foster , while in the film adaptation of Hannibal , she was played by Julianne Moore . Clarice Starling , as portrayed by Foster , was ranked the sixth greatest protagonist in film history on AFI 's 100 Years ... 100 Heroes and Villains , making her the highest-ranking heroine .",
"title": ""
},
{
"docid": "Chicago_Film_Critics_Association_Awards_1991",
"text": "4th CFCA Awards Best Film : Silence of the Lambs The 4th Chicago Film Critics Association Awards were announced on March 5 , 1992 during a ceremony at The Pump Room . They honored the finest achievements in 1991 filmmaking . The nominees were revealed in January 1992 . Thelma & Louise and Barton Fink tied for the most nominations with six each . The Silence of the Lambs earned the most awards ( 5 ) , including Best Film .",
"title": ""
},
{
"docid": "Silence_of_the_Lamb_(Veronica_Mars)",
"text": "`` Silence of the Lamb '' is the eleventh episode of the first season of the American mystery television series Veronica Mars . Written by Jed Seidel and Dayna Lynne North and directed by John Kretchmer , the episode premiered on UPN on January 4 , 2005 , as the series ' first episode in the new year . The series depicts the adventures of Veronica Mars ( Kristen Bell ) as she deals with life as a high school student while moonlighting as a private detective . In this episode , Veronica helps Cindy `` Mac '' Mackenzie ( Tina Majorino ) find and reconnect with her birth parents and siblings . Meanwhile , Keith ( Enrico Colantoni ) is temporarily reassigned to the sheriff 's department in order to help with a case involving a serial killer .",
"title": ""
},
{
"docid": "Hannibal_(film)",
"text": "Hannibal is a 2001 American crime thriller film directed by Ridley Scott , adapted from the novel of the same name by Thomas Harris . It is the sequel to the 1991 Academy Award -- winning film The Silence of the Lambs in which Anthony Hopkins returns to his role as the iconic serial killer , Hannibal Lecter . Julianne Moore co-stars , in the role first held by Jodie Foster , as FBI Special Agent Clarice Starling . The film had a difficult and occasionally troubling pre-production history . When the novel was published in 1999 , The Silence of the Lambs director Jonathan Demme , screenwriter Ted Tally , and actress Jodie Foster all declined to be involved in its adaptation . Ridley Scott became attached as director after the success of Gladiator ( 2000 ) , and eventually signed onto the project after reading the script pitched by Dino DeLaurentiis , who produced Manhunter ( 1986 ) , based on the 1981 Harris novel Red Dragon . After the departure of Foster and screenwriter Tally , Julianne Moore took on Foster 's role while David Mamet and Steven Zaillian wrote the screenplay . Set ten years after The Silence of the Lambs , Hannibal follows Starling 's attempts to apprehend Lecter before his surviving victim , Mason Verger ( Gary Oldman ) , captures him . It is set in Italy and the United States . The novel Hannibal drew attention for its violence . Hannibal broke box office records in the United States , Australia , Canada and the United Kingdom in February 2001 , but was met with a mixed critical reception .",
"title": ""
},
{
"docid": "Sacrificial_lamb",
"text": "A sacrificial lamb is a metaphorical reference to a person or animal sacrificed for the common good . The term is derived from the traditions of Abrahamic religion where a lamb is a highly valued possession .",
"title": ""
},
{
"docid": "State_of_Negation",
"text": "State of Negation was a 5-member metal group from Haarlem , Netherlands and winner of 2011 's Dutch National Metal Battle and the IJmond Popmusic Prize . The band has played over 300 shows , 1 European tour , 5 festivals ( Beeckestijn Pop , Occultfest , Strudelfest , Bashfest and Metalcon ) and have released a successful music video on YouTube titled Corruption . Being the young band they are , State of Negation has left a great impression with both audience and professionals : `` Young , talented and an incredible sense of performance ! '' With the coming of their debut EP , Project Payback , released in early 2013 , they made quite a step forward by doing support for Suicide Silence in Patronaat , Haarlem , leaving a great impression and convincing many people of their talent . The band 's main musical influences are Lamb of God , Trivium and Machine Head , which listeners will definitely hear back in both music and lyrics , which are based on political issues , personal experiences , religion and a hint of rebellion .",
"title": ""
},
{
"docid": "Agnus",
"text": "Agnus ( Latin for lamb ) can be used to refer to : Religion Agnus Dei ( Latin : `` Lamb of God '' ) referring to Jesus Christ as divine sacrificial lamb an early prayer of the breviary Places and jurisdictioni Agnus ( Egypt ) , an Ancient city and former bishopric in Aegyptus Primus , now a Latin Catholic titular see Biology Agnus scythicus , Latin for Vegetable Lamb of Tartary , a mythologic lamb-plant Agnus ( beetle ) , a stag beetle genus Vitex agnus-castus , a Mediterranean plant Technology MOS Technology Agnus , an integrated circuit in the OCS chipset of the Commodore Amiga computer",
"title": ""
},
{
"docid": "Frederick_Chilton",
"text": "Dr. Frederick Chilton is a fictional character appearing in Thomas Harris ' novels Red Dragon and The Silence of the Lambs .",
"title": ""
},
{
"docid": "List_of_American_films_of_1991",
"text": "A list of American films released in 1991 . The Silence of the Lambs won the Academy Award for Best Picture .",
"title": ""
},
{
"docid": "Ron_Bozman",
"text": "Ron Bozman is an American film producer who won an Academy Award for Best Picture in 1991 for the film The Silence of the Lambs .",
"title": ""
},
{
"docid": "Darla_(dog)",
"text": "Darla ( 1975-1992 ) was a Bichon Frise and animal actress most known for her role as Precious in the 1991 thriller , The Silence of the Lambs .",
"title": ""
},
{
"docid": "SOTL",
"text": "SOTL can refer to : The Silence of the Lambs Stars of the Lid Scholarship of Teaching and Learning Ship of the Line Spec Ops : The Line School of the Legends",
"title": ""
},
{
"docid": "End_of_Silence_(Red_album)",
"text": "End of Silence is the debut album by the Christian alternative metal band Red , released on June 6 , 2006 . According to Billboard , the album made it up to position 194 on its top 200 album chart . This is the only Red album to feature drummer Hayden Lamb . Guitarist Jasen Rauch explained that `` Breathe Into Me '' is about '' ` falling , ' finally reaching the end of our rope , where we realize at last ... we need God . '' The album was nominated for a Grammy for Best Rock or Rap Gospel Album at the 49th Grammy Awards .",
"title": ""
},
{
"docid": "Boston_Society_of_Film_Critics_Awards_1991",
"text": "12th BSFC Awards December 26 , 1991 Best Film : The Silence of the Lambs The 12th Boston Society of Film Critics Awards honored the best filmmaking of 1991 .",
"title": ""
},
{
"docid": "Kenneth_Utt",
"text": "Kenneth Utt ( July 13 , 1921 -- January 19 , 1994 ) , was an American film producer and unit production manager , notable for producing The Silence of the Lambs , for which he won an Oscar for Best Picture .",
"title": ""
},
{
"docid": "Ted_Levine",
"text": "Frank Theodore `` Ted '' Levine ( born May 29 , 1957 ) is an American actor . He is known for his roles as Buffalo Bill in The Silence of the Lambs and as Captain Leland Stottlemeyer in the television series Monk .",
"title": ""
},
{
"docid": "The_Silence_of_the_Hams",
"text": "The Silence of the Hams ( Italian : Il Silenzio dei Prosciutti ) is a 1994 Italian-American satirical comedy film written , directed by , and starring Italian comedian Ezio Greggio . It is a parody of many popular thriller and horror films , notably The Silence of the Lambs and Psycho . Alongside Greggio , the film features an ensemble cast featuring Dom DeLuise , Billy Zane , Joanna Pacuła , Charlene Tilton , and Martin Balsam . The comedy , like many of its contemporaries ( including The Naked Gun ) , is largely driven by word-play , sight gags , running jokes , and multiple references to popular culture of the time , like Michael Jackson 's Thriller , and tongue-in-cheek references to the then-current state of American politics ( such as a fight scene between Presidents George H. W. Bush and Bill Clinton ) . As a curiosity , there is a Mel Brooks cameo in this film , who made a number of well regarded parodies ( Blazing Saddles , Young Frankenstein , Spaceballs ) .",
"title": ""
},
{
"docid": "Jon_and_Al_Kaplan",
"text": "Jonathan Z. `` Jon '' Kaplan ( born April 6 , 1976 ) and Alexander `` Al '' Kaplan ( born July 23 , 1978 ) are brothers who are American composers , lyricists and comedy writers . They are best known for creating the musical Silence ! The Musical , a parody of the film The Silence of the Lambs , which began life on the internet in 2002 before becoming a successful stage musical starting in 2005 . They have also created musical parodies of other films and television shows , including various Arnold Schwarzenegger films such as Conan the Barbarian , Predator and Commando . Jon and Al scored and co-wrote the film Zombeavers ( 2014 ) .",
"title": ""
},
{
"docid": "Belvedere,_Ohio",
"text": "Belvedere is a populated place near Bloomingdale in Jefferson County , Ohio , United States . Belvedere , Ohio is also the name of a fictional town depicted in the novel The Silence of the Lambs by Thomas Harris , as well as the 1991 motion picture based on the novel .",
"title": ""
},
{
"docid": "Sangharsh_(1999_film)",
"text": "Sangharsh ( सँघर्ष , translation : Struggle ) is a 1999 Hindi psychological crime thriller film directed by Tanuja Chandra . It stars Akshay Kumar , Preity Zinta , and Ashutosh Rana in the lead role . It is inspired by the hollywood movie The Silence of the lambs .",
"title": ""
},
{
"docid": "The_Seventh_Seal",
"text": "The Seventh Seal ( Det sjunde inseglet ) is a 1957 Swedish drama-fantasy film written and directed by Ingmar Bergman . Set in Sweden during the Black Death , it tells of the journey of a medieval knight ( Max von Sydow ) and a game of chess he plays with the personification of Death ( Bengt Ekerot ) , who has come to take his life . Bergman developed the film from his own play Wood Painting . The title refers to a passage from the Book of Revelation , used both at the very start of the film , and again towards the end , beginning with the words `` And when the Lamb had opened the seventh seal , there was silence in heaven about the space of half an hour '' . Here the motif of silence refers to the `` silence of God , '' which is a major theme of the film . The Seventh Seal is considered a classic of world cinema , as well as one of the greatest movies of all time . It established Bergman as a world-renowned director , containing scenes which have become iconic through homages , critical analysis , and parodies .",
"title": ""
},
{
"docid": "Charles_Napier_(actor)",
"text": "Charles Lewis Napier ( April 12 , 1936 -- October 5 , 2011 ) was an American character actor in film and television , known for his prolific career playing memorable supporting and leading roles in genre cinema , often in the role of a cop , soldier , or authority figure . After leaving his Kentucky hometown to serve in the army , he graduated college and worked as a sports coach and art teacher before settling on acting as a career . Napier established himself in character roles and worked steadily for the next 35 years . He made numerous collaborations with director Jonathan Demme , including roles in the critically acclaimed drama Philadelphia , comedy Married to the Mob , historical horror-drama Beloved , the political-thriller remake The Manchurian Candidate -RSB- -RSB- , and the Best Picture-winning psychological horror film adaptation -LSB- -LSB- The Silence of the Lambs ( film ) | The Silence of the Lambs . Other notable roles include the short-tempered country singer Tucker McElroy in The Blues Brothers , gruff army Commander Gilmour in Austin Powers : International Man of Mystery , and bureaucratic CIA officer Marshall Murdock in Rambo : First Blood Part II . He also had numerous voiceover roles in television , most notably the character of Duke Phillips on the prime time animated sitcom The Critic .",
"title": ""
},
{
"docid": "Hannibal_Lecter",
"text": "Dr. Hannibal Lecter is a character in a series of suspense novels by Thomas Harris . Lecter was introduced in the 1981 thriller novel Red Dragon as a forensic psychiatrist and cannibalistic serial killer . The novel and its sequel , The Silence of the Lambs , feature Lecter as one of the primary antagonists after the two serial killers in both novels . In the third novel , Hannibal , Lecter becomes a protagonist . His role as the antihero occurs in the fourth novel , Hannibal Rising , which explores his childhood and development into a serial killer . The first film adapted from the Harris novels was Manhunter ( based on Red Dragon ) which features Brian Cox as Lecter , spelled `` Lecktor '' . In 1991 , Anthony Hopkins won an Academy Award for his portrayal of the character in The Silence of the Lambs . He would reprise the role in Hannibal in 2001 and in a second adaptation of Red Dragon made in 2002 under the original title . The NBC television series Hannibal debuted in 2013 , and focuses on the development of the relationship between Lecter and Will Graham , an FBI profiler . In the series , Lecter is portrayed by Danish actor Mads Mikkelsen , who won a Saturn Award for his performance . In 2003 , Hannibal Lecter ( as portrayed by Hopkins ) was chosen by the American Film Institute as the # 1 movie villain . In June 2010 , Entertainment Weekly named him one of the 100 Greatest Characters of the Last 20 Years .",
"title": ""
},
{
"docid": "National_Board_of_Review_Awards_1991",
"text": "63rd National Board of Review Awards Best Picture : The Silence of the Lambs The 63rd National Board of Review Awards , honoring the best in filmmaking in 1991 , were announced on 16 December 1991 and given on 24 February 1992 .",
"title": ""
},
{
"docid": "Producers_Guild_of_America_Awards_1991",
"text": "3rd Producers Guild of America Awards March 4 , 1992 Best Producer - Motion Picture : The Silence of the Lambs The 3rd PGA Golden Laurel Awards , announced on 4 March 1992 , honored the best film and television producers of 1991 .",
"title": ""
},
{
"docid": "Q_Lazzarus",
"text": "Q Lazzarus ( full name Quiana Diana , last name unknown ) is an American singer , best known as a one-hit wonder for her 1988 song `` Goodbye Horses , '' written by Wiliam Garvey , which was featured in Married to the Mob and The Silence of the Lambs ( the Buffalo Bill song ) .",
"title": ""
}
] |
119985
|
Bangladesh can be found on the Indian subcontinent.
|
[
{
"docid": "Bengal",
"text": "Bengal ( -LSB- bɛŋˈɡɔːl -RSB- বাংলা / বঙ্গ ) is a geopolitical , cultural and historical region in Asia , which is located in the eastern part of the Indian subcontinent at the apex of the Bay of Bengal . Geographically , it is made up by the Ganges-Brahmaputra delta system , the largest such formation in the world ; along with mountains in its north ( bordering the Himalayan states ) and east ( bordering Northeast India and Burma ) . Politically , Bengal is divided between the sovereign republic of Bangladesh , which covers two-thirds of the region , and West Bengal , which is a part of the Republic of India , in the western part of the region . In 2011 , the population of Bengal was estimated to be 250 million , making it one of the most densely populated regions in the world . An estimated 160 million people live in Bangladesh , while 91.3 million people live in West Bengal . The predominant ethno-linguistic group are the Bengali people , who speak the Indo-Aryan Bengali language . Bengali Muslims are the majority in Bangladesh . Bengali Hindus are the majority in West Bengal . Outside Bengal proper , the Indian territories of Tripura , Assam and the Andaman and Nicobar Islands , as well as Myanmar 's Rakhine State , are also home to significant communities with Bengali heritage . Dense woodlands , including hilly rainforests , cover Bengal 's northern and eastern areas ; while an elevated forested plateau covers its central area . In the littoral southwest are the Sunderbans , the world 's largest mangrove forest and home of the Bengal tiger . In the coastal southeast lies Cox 's Bazaar , the longest beach in the world at . The region has a monsoon climate , which the Bengali calendar divides into six seasons . Bengal has played a major role in the history of Asia . In antiquity , its kingdoms were known as seafaring nations . At times an independent regional empire , the historical region was a leading power of the Indian subcontinent and the Islamic East . It had extensive trade networks . Bengali culture has been particularly influential in the fields of literature , music , art , architecture , sports , currency , commerce , politics and cuisine .",
"title": ""
},
{
"docid": "Bangladesh",
"text": "Bangladesh ( -LSB- bæŋɡləˈdɛʃ -RSB- -LSB- ˌbɑːŋɡləˈdɛʃ -RSB- -LSB- : bn : বাংলাদেশ , বাংলাদেশ -RSB- , -LSB- ˈbaŋlad̪eʃ -RSB- , lit . `` The country of Bengal '' ) , officially the People 's Republic of Bangladesh , is a country in South Asia . It shares land borders with India and Myanmar ( Burma ) . Nepal , Bhutan and China are located near Bangladesh but do not share a border with it . The country 's maritime territory in the Bay of Bengal is roughly equal to the size of its land area . Bangladesh is the world 's eighth most populous country . Dhaka is its capital and largest city , followed by Chittagong , which has the country 's largest port . Bangladesh forms the largest and eastern part of the Bengal region . Bangladeshis include people of different ethnic groups and religions . Bengalis , who speak the official Bengali language , make up 98 % of the population . The politically dominant Bengali Muslims make the nation the world 's third largest Muslim-majority country . Most of Bangladesh is covered by the Bengal delta , the largest delta on Earth . The country has 700 rivers and 8,046 km ( 5,000 miles ) of inland waterways . Highlands with evergreen forests are found in the northeastern and southeastern regions of the country . Bangladesh has many islands and a coral reef . It is home to the Sundarbans , the largest mangrove forest in the world . The country 's biodiversity includes a vast array of plant and wildlife , including critically endangered Bengal tigers , the national animal . The Greeks and Romans identified the region as Gangaridai , a powerful kingdom of the historical subcontinent , in the 3rd century BCE . Archaeological research has unearthed several ancient cities in Bangladesh , which had international trade links for millennia . The Bengal Sultanate and Mughal Bengal transformed the region into a cosmopolitan Islamic imperial power between the 14th and 18th centuries . The region was home to many principalities that had inland naval prowess . It was also a notable center of the worldwide muslin and silk trade . As part of British India , the region was influenced by the Bengali renaissance and played an important role in anti-colonial movements . The Partition of British India made East Bengal a part of the Dominion of Pakistan ; and was renamed as East Pakistan . The region witnessed the Bengali Language Movement in 1952 and the Bangladesh Liberation War in 1971 . After independence , a parliamentary republic was established . A presidential government was in place between 1975 and 1990 , followed by a return to parliamentary democracy . The country has also been affected by poverty , natural disasters , hunger , dominant party systems and military coups . Bangladesh is a middle power and a major developing nation . Within South Asia , the country ranks first in gender equality , second in foreign exchange earnings and third in life expectancy and peacefulness . Listed as one of the Next Eleven , its economy ranks 46th in terms of nominal gross domestic product ( GDP ) and 29th in terms of purchasing power parity ( PPP ) . It is one of the largest textile exporters in the world . Its major trading partners are the European Union , the United States , China , India , Japan , Malaysia and Singapore . With its strategically vital location between Southern , Eastern and Southeast Asia , Bangladesh is an important promoter of regional connectivity and cooperation . It is a founding member of SAARC , BIMSTEC , the Bangladesh-China-India-Myanmar Forum for Regional Cooperation and the Bangladesh Bhutan India Nepal Initiative . It is also a member of the Commonwealth of Nations , the Developing 8 Countries , the OIC , the Non Aligned Movement , the Group of 77 and the World Trade Organization . Bangladesh is one of the largest contributors to United Nations peacekeeping forces .",
"title": ""
},
{
"docid": "Gangaridai",
"text": "Gangaridai ( Γανγαρίδαι Latin Gangaridae ) was an ancient region corresponding to the Ganges delta region of the Indian subcontinent , which was mentioned in the records of numerous Greco-Roman writers . The term means `` nation of the Ganges '' in Greek and Latin . It is one of the earliest references to the Bengal region in the Indian subcontinent ( now divided between Bangladesh and the Indian state of West Bengal ) . According to ancient Indian records , the Vanga Kingdom and Samatata Kingdom occupied the region during the same period . The capital of the Gangaridai is thought to be situated at Kotalipara in present-day Gopalganj District , Bangladesh.But , many archaeologists have considered Chandraketugarh ( situated in West Bengal , India ) as the ancient port city of Gange , the capital of Gangaridai . The region was described as a kingdom with one of the largest cavalries of chariots and war elephants . It was described by the Greek traveller Megasthenes in his work Indica . Greek and Roman historians suggested that Alexander the Great withdrew from the Indian subcontinent , anticipating a counterattack from an alliance of Gangaridai and the Nanda Empire . Later writers noted merchant shipping links between Gangaridai 's cities and Roman Egypt .",
"title": ""
},
{
"docid": "Ganges_Delta",
"text": "The Ganges-Brahmaputra Delta ( also known as the Brahmaputra Delta , the Sunderbans Delta , or the Bengal Delta ) in Bangladesh and in West Bengal ( India ) is a river delta in the Bengal region of the Indian subcontinent , consisting of Bangladesh and the Indian state of West Bengal . It is the world 's largest delta , and empties into the Bay of Bengal . It is also one of the most fertile regions in the world , thus earning the nickname The Green Delta . The delta stretches from the Hooghly River on the west to the Meghna River on the east . It is approximately 354 km across at the Bay of Bengal . Kolkata ( formerly Calcutta ) and Haldia in India and Mongla and Chittagong in Bangladesh are the principal seaports of the delta . A number of large rivers flow through the Brahmaputra Delta , including the Padma ( main distributary of the Ganges ) and the Jamuna ( main distributary of the Brahmaputra ) , which merge and then join the Meghna before entering the sea .",
"title": ""
}
] |
[
{
"docid": "Indian_subcontinent",
"text": "The Indian subcontinent or the subcontinent , also called the Indian continent , is a southern region of Asia , mostly situated on the Indian Plate and projecting southwards into the Indian Ocean from the Himalayas . Geologically , the Indian subcontinent is related to the land mass that rifted from Gondwana and merged with the Eurasian plate nearly 55 million years ago . Geographically , it is the peninsular region in south-central Asia delineated by the Himalayas in the north , the Hindu Kush in the west , and the Arakanese in the east . Politically , the Indian subcontinent usually includes Bangladesh , Bhutan , India , Maldives , Nepal , Pakistan and Sri Lanka . Sometimes , the term South Asia is used interchangeably with Indian subcontinent . There is no consensus about which countries should be included in each .",
"title": ""
},
{
"docid": "Indian_cuckoo",
"text": "The Indian cuckoo ( Cuculus micropterus ) is a member of the cuckoo order of birds , the Cuculiformes , that is found in the Indian subcontinent and Southeast Asia . It ranges from India , Bangladesh , Bhutan , Nepal and Sri Lanka east to Indonesia and north to China and Russia . It is a solitary and shy bird , found in forests and open woodland at up to 3,600 m.",
"title": ""
},
{
"docid": "Al-Qaeda_in_the_Indian_Subcontinent",
"text": "Al-Qaeda in the Indian Subcontinent ( -LSB- جماعة قاعدة الجهاد في شبه القارة الهندية , Jamā ` at Qā ` idat al-Jihād fī Shibh al-Qārrah al-Hindīyah , lit = Organisation of the Base of Jihad in the Indian Subcontinent -RSB- ) usually abbreviated as AQIS , is an Islamist militant organization which aims to fight the governments of Pakistan , India , Myanmar and Bangladesh in order to establish an Islamic state . The militant group has also stated its intentions to attack American targets in the Indian Subcontinent .",
"title": ""
},
{
"docid": "Bengal_fox",
"text": "The Bengal fox ( Vulpes bengalensis ) , also known as the Indian fox , is a fox endemic to the Indian subcontinent and is found from the Himalayan foothills and Terai of Nepal through southern India and from southern and eastern Pakistan to eastern India and southeastern Bangladesh .",
"title": ""
},
{
"docid": "Music_in_ancient_India",
"text": "Music in ancient India , encompassing the modern-day Indian subcontinent of India , Pakistan , and Bangladesh , can be reproduced from written works dating to the Indian classical period , such as the Nātya Shastra , and through surviving examples of liturgical music such as the hymns of the Samaveda . Musical instruments dating to the prehistoric period have been recovered from archaeological excavations .",
"title": ""
},
{
"docid": "Lagenandra",
"text": "Lagenandra is a genus of flowering plants in the Araceae family . It is endemic to the Indian Subcontinent ( Bangladesh , Sri Lanka , and India ) . The genus is similar to Cryptocoryne , but can be distinguished from it by its involute vernation . Cryptocoryne on the other hand exhibit convolute vernation .",
"title": ""
},
{
"docid": "Indian_Memory_Project",
"text": "The Indian Memory Project is an online archive that aims to trace the history of the Indian subcontinent using images and narratives offered by families and individuals in several countries . It was founded in India in February 2010 by Anusha Yadav , photographer and designer for The Memory Company . The ongoing project attempts to convey in a unified way the history of the subcontinent , its experiences , humanity , choices and its circumstances that have made the region and its people who they are . It is also intended to promote greater tolerance , understanding , and capacity for learning among the citizens of India , its neighbouring countries and the world . Yadav runs the project from Mumbai . There is no restriction on nationality and origin of the contributors , but only contributions related to the Indian subcontinent are accepted . The project employs photographs , contextualised narratives and letters found in personal archives , highlighting themes such as social transformation , new professions , partition , education , war , marriage , religion and culture , and the impact they had on families living during these times . With personal images serving as evidence , each post on the archive reveals information about people , families and ancestors , cultures , lifestyles , traditions , choices , circumstances and thereby consequences . Indian Memory Project has received images from families and people based in Canada , USA , Ireland , Bangladesh , Pakistan , India , United Kingdom . Currently the oldest photograph is from 1860 . The website also provides a list of books curated by the Memory Company on subcontinental histories .",
"title": ""
},
{
"docid": "Indian_cobra",
"text": "The Indian cobra ( Naja naja ) also known as the spectacled cobra , Asian cobra or binocellate cobra is a species of the genus Naja found in the Indian subcontinent ( India , Pakistan , Bangladesh , Sri Lanka , Nepal ) and a member of the `` big four '' species that inflict the most snakebites on humans in India . This snake is revered in Indian mythology and culture , and is often seen with snake charmers . It is now protected in India under the Indian Wildlife Protection Act ( 1972 ) .",
"title": ""
},
{
"docid": "Pakora",
"text": "Pakora ( -LSB- pəˈkoːɽaː -RSB- ) , also called pakoda , pakodi , or ponako , is a fried snack ( fritter ) . It is found across the Indian subcontinent , especially in India , Bangladesh , Nepal and Pakistan .",
"title": ""
},
{
"docid": "Talwar",
"text": "The talwar ( -LSB- t̪əlʋaːr -RSB- ) , also spelled talwaar and tulwar , is a type of curved sword or sabre from the Indian Subcontinent , and is found in the modern countries of India , Pakistan , Bangladesh and Nepal .",
"title": ""
},
{
"docid": "Sen_(surname)",
"text": "Sen ( pronounced Shen ) is a Bengali Hindu surname derived from the Sanskrit word for `` Army '' , Sena . It is found in the east of the Indian Subcontinent ; namely Bangladesh & West Bengal , India mainly among Baidya and Kayastha communities . Instances of the surname are also found in the Nepalese community .",
"title": ""
},
{
"docid": "Sylhet_Government_Pilot_High_School",
"text": "The Sylhet Govt . Pilot High School is one of the oldest schools of Bangladesh as well as the Indian Subcontinent . Founded in 1836 , it is situated in the Kalighat area of Sylhet , on the bank of the Surma River .",
"title": ""
},
{
"docid": "Striated_prinia",
"text": "The striated prinia ( Prinia crinigera ) is a species of bird in the Cisticolidae family . It is found in the Indian Subcontinent , with a smaller disjunct populations in parts of Southeast Asia . It ranges across Bangladesh , Bhutan , India , Myanmar , Nepal and Taiwan .",
"title": ""
},
{
"docid": "Pottery_in_the_Indian_subcontinent",
"text": "Pottery in the Indian subcontinent has an ancient history and is one of the most tangible and iconic elements of regional art . Evidence of pottery has been found in the early settlements of Mehrgarh from the Indus Valley Civilization . Today , it is a cultural art that is still practiced extensively in India , Bangladesh , Nepal , Sri Lanka and Pakistan . Until recent times all Indian pottery has been earthenware , including terracotta . Hindu traditions historically discouraged the use of pottery for eating off , which probably explains the noticeable lack of traditions of fine or luxury pottery in South Asia , in contrast to East Asia and other parts of Eurasia . Today , pottery thrives as an art form in India , and it is slowly gaining awareness as a functional items as well . Various platforms , including potters ' markets and online pottery boutiques have contributed to this trend .",
"title": ""
},
{
"docid": "Rain_quail",
"text": "The rain quail or black-breasted quail ( Coturnix coromandelica ) is a species of quail found in the Indian subcontinent , its range including Pakistan , India , Nepal , Sri Lanka , Bangladesh , Myanmar , Thailand , Cambodia and Viet Nam .",
"title": ""
},
{
"docid": "Blue_pitta",
"text": "The blue pitta ( Hydrornis cyaneus ) is a species of bird in the family Pittidae found in the Indian Subcontinent and Southeast Asia . The species is closely related to the Indian Pitta and Mangrove Pitta , and ranges across Bangladesh , Bhutan , Cambodia , India , Laos , Myanmar , Thailand , and Vietnam . Its natural habitats are subtropical or tropical moist lowland forests and subtropical or tropical moist montane forests .",
"title": ""
},
{
"docid": "Lineated_barbet",
"text": "The lineated barbet ( Psilopogon lineatus ) is a large barbet found in the northern parts of the Indian subcontinent , along the southern foothills of the Himalayas and also in parts of Bangladesh and West Bengal . Like other barbets it is a frugivore . In nests inside holes bored into tree trunks .",
"title": ""
},
{
"docid": "Small_niltava",
"text": "The small niltava ( Niltava macgrigoriae ) is a species of bird in the family Muscicapidae , native to the Indian subcontinent and Southeast Asia . It is found in Bangladesh , Bhutan , India , Laos , Myanmar , Nepal , Thailand , Tibet and Vietnam . Its natural habitat is subtropical or tropical moist montane forests .",
"title": ""
},
{
"docid": "Hygrophila_difformis",
"text": "Hygrophila difformis , commonly known as water wisteria ( though it is not closely related to true wisteria ) , is an aquatic plant in the acanthus family . It is found in marshy habitats on the Indian subcontinent in Bangladesh , Bhutan , India and Nepal . It grows to a height of 20 to 50 cm with a width of 15 to 25 cm .",
"title": ""
},
{
"docid": "Ahmede_Hussain",
"text": "Ahmede Hussain ( born 16 July 1978 ) is a Bangladeshi writer . His ancestors hail from the former Portuguese enclave of Patherghata , Chittagong in Bangladesh . He works as the Literary Editor of The Daily Star ( Bangladesh ) . He edited The New Anthem : The Subcontinent in its Own Words , an anthology of fiction from the Indian subcontinent . The book has been greeted with acclaim : `` The richness is all , both in terms of the writers brought together and in the quality of the tales that come to you one after the other . '' As of February 2015 , he is working on his first novel . He is also a senior journalist . He was in charge of The Daily Star ( Bangladesh ) 's weekly supplement The Star ( Bangladesh ) for a long time . He is also a popular English literature and language teacher at Vertical Horizon , an educational service providing institution based in Dhaka . Hussain lives and works in Dhaka .",
"title": ""
},
{
"docid": "White-collared_blackbird",
"text": "The white-collared blackbird ( Turdus albocinctus ) is a species of bird in the family Turdidae . It is found in the Indian subcontinent , ranging across Bangladesh , Bhutan , India , Myanmar , Nepal and Pakistan . Its natural habitats are subtropical or tropical moist montane forests and subtropical or tropical high-altitude shrubland .",
"title": ""
},
{
"docid": "Asiatic_Society_(disambiguation)",
"text": "Asiatic Society is a society founded by British in the Indian subcontinent in early 18th century with a view to encourage science , literature and the arts in relation to Asia . It could refer to any of the following : The Asiatic Society located in Kolkata , India . Asiatic Society , Mumbai located in Mumbai , India . Asiatic Society of Japan located in Yokohama , Japan . Royal Asiatic Society of Great Britain and Ireland located in London , England . Asiatic Society of Bangladesh located in Dhaka , Bangladesh . Royal Asiatic Society Hong Kong Branch located in Hong Kong",
"title": ""
},
{
"docid": "Rufous-gorgeted_flycatcher",
"text": "The rufous-gorgeted flycatcher ( Ficedula strophiata ) is a species of bird in the family Muscicapidae . It is found in the Indian Subcontinent and Southeast Asia , ranging across Bangladesh , Bhutan , Hong Kong , India , Laos , Myanmar , Nepal , Thailand , and Vietnam . Its natural habitat is subtropical or tropical moist montane forests .",
"title": ""
},
{
"docid": "Black-backed_forktail",
"text": "The black-backed forktail ( Enicurus immaculatus ) is a species of bird in the family Muscicapidae , found in the Indian subcontinent and in some adjoining regions of Southeast Asia . It ranges across Bangladesh , Bhutan , India , Myanmar , Nepal and Thailand . Its natural habitats are temperate forests and subtropical or tropical moist lowland forests .",
"title": ""
},
{
"docid": "Indian_languages",
"text": "Indian languages may refer to : Languages of India , or of the Indian subcontinent , including : Languages of Bangladesh Languages of Nepal Languages of Pakistan Languages of Sri Lanka Indigenous languages of the Americas",
"title": ""
},
{
"docid": "Lesser_racket-tailed_drongo",
"text": "The lesser racket-tailed drongo ( Dicrurus remifer ) is a species of bird in the family Dicruridae . It is found in the Indian Subcontinent and Southeast Asia , ranging across Bangladesh , Bhutan , Cambodia , India , Indonesia , Laos , Malaysia , Myanmar , Nepal , Thailand , and Vietnam . Its natural habitat is subtropical or tropical moist montane forests .",
"title": ""
},
{
"docid": "Ashy_bulbul",
"text": "The ashy bulbul ( Hemixos flavala ) is a species of songbird in the family Pycnonotidae . It is found in the Indian subcontinent and Southeast Asia , ranging across Bangladesh , Bhutan , Cambodia , India , Indonesia , Laos , Malaysia , Burma , Nepal , Singapore , Thailand , and Vietnam . Its natural habitats are subtropical or tropical moist lowland forests and subtropical or tropical moist montane forests .",
"title": ""
},
{
"docid": "Grey-winged_blackbird",
"text": "The grey-winged blackbird ( Turdus boulboul ) is a species of bird in the family Turdidae . It is found in the northern parts of the Indian subcontinent , stretching all the way to the nearer parts of Southeast Asia , including in Bangladesh , Bhutan , India , Laos , Myanmar , Nepal , Thailand , Tibet and Vietnam . Its natural habitat is subtropical or tropical moist montane forests .",
"title": ""
},
{
"docid": "Little_pied_flycatcher",
"text": "The little pied flycatcher ( Ficedula westermanni ) is a species of bird in the family Muscicapidae . It is found in the Indian Subcontinent and Southeast Asia , ranging across Bangladesh , Bhutan , Cambodia , India , Indonesia , Laos , Malaysia , Myanmar , Nepal , the Philippines , Thailand , and Vietnam . Its natural habitats are subtropical or tropical moist lowland forests and subtropical or tropical moist montane forests .",
"title": ""
},
{
"docid": "Dipterocarpus_tuberculatus",
"text": "Dipterocarpus tuberculatus ( Khmer khlông , Indian English gurjuntree ) is a species of tree in the family Dipterocarpaceae found in Bangladesh , Myanmar , Thailand , Cambodia , Laos and Vietnam . The tree is found in clear forests of plains , at altitudes up to 800-1000m . It grows to height of 5 -- 25 m. The lipids and wood are used in the Indian subcontinent . Uses in Cambodia include : using the leaves for packaging and sometimes for covering huts ; the wood , resistant to bad weather , is used to make beams , boards and for the manufacture of boats ; and the roots are used in traditional medicine to cure fractures . At least recently , the tree is an important firewood source in some areas of the Cambodian province of Kompong Chhnang .",
"title": ""
}
] |
PLAIN-1870
|
pistachio principle
|
[
{
"docid": "MED-4292",
"text": "There is currently no single dietary or lifestyle intervention that is effective in long-term weight loss. Traditional weight loss diets tend to be low in total fat and therefore often restrict nut consumption. However, nuts are an important source of many vitamins, minerals, monounsaturated and polyunsaturated fatty acids. This paper reviewed all the available evidence from the literature in relation to nut consumption and body weight. The findings show that the role of nut consumption in body weight management is varied. Nuts, when included as part of an energy-controlled diet, were found in some instances to assist with weight loss. However, when nuts were added to an existing diet without controlling for energy intake, body weight increased, although to a lesser extent than theoretically predicted. There is limited evidence on the effect nut consumption has on type 2 diabetes, although available evidence indicates that nuts as part of a healthy diet do not cause weight gain and can have a positive influence on the fatty acid profile of a person with diabetes. This review shows there is a lack of evidence to support the restriction of nut consumption in weight management, indicating that further research is needed to assess the role of nuts in weight management.",
"title": "A review of the evidence: nuts and body weight."
},
{
"docid": "MED-4286",
"text": "Nuts are rich sources of multiple nutrients and phytochemicals associated with health benefits, including reduced cardiovascular disease risk. This has prompted recommendations to increase their consumption. However, they are also high in fat and are energy dense. The associations between these properties, positive energy balance and body weight raise questions about such recommendations. Numerous epidemiological and clinical studies show that nuts are not associated with weight gain. Mechanistic studies indicate this is largely attributable to the high satiety and low metabolizable energy (poor bioaccessibility leading to inefficient energy absorption) properties of nuts. Compensatory dietary responses account for 55-75% of the energy provided by nuts. Limited data suggest that routine nut consumption is associated with elevated resting energy expenditure and the thermogenic effect of feeding, resulting in dissipation of another portion of the energy they provide. Additionally, trials contrasting weight loss through regimens that include or exclude nuts indicate improved compliance and greater weight loss when nuts are permitted. Nuts may be included in the diet, in moderation, to enhance palatability, nutrient quality, and chronic disease risk reduction without compromising weight loss or maintenance.",
"title": "Nuts and healthy body weight maintenance mechanisms."
},
{
"docid": "MED-4284",
"text": "Peanuts and peanut butter are commonly consumed as a snack, meal component and ingredient in various commercial products. Their consumption is associated with reduced CVD risk and they pose little threat to positive energy balance. However, questions have arisen as to whether product form (e.g. whole nut v. butter) and processing properties (e.g. roasting and adding flavours) may compromise their positive health effects. The present study investigated the effects of peanut form and processing on two CVD risk factors: fasting plasma lipids and body weight. One hundred and eighteen adults (forty-seven males and seventy-one females; age 29.2 (sd 8.4) years; BMI 30.0 (sd 4.5) kg/m2) from Brazil, Ghana and the United States were randomised to consume 56 g of raw unsalted (n 23), roasted unsalted (n 24), roasted salted (n 23) or honey roasted (n 24) peanuts, or peanut butter (n 24) daily for 4 weeks. Peanut form and processing did not differentially affect body weight or fasting plasma lipid responses in the total sample. However, HDL-cholesterol increased significantly at the group level, and total cholesterol, LDL-cholesterol and TAG concentrations decreased significantly in individuals classified as having elevated fasting plasma lipids compared with those with normal fasting plasma lipids. These observations suggest that the processing attributes assessed in this trial do not compromise the lipid-lowering effects of peanuts, and do not negatively impact body weight. Further studies are warranted to determine the effects of form and processing on other health risk factors.",
"title": "Effects of peanut processing on body weight and fasting plasma lipids."
}
] |
[
{
"docid": "MED-3399",
"text": "We investigated the effects of Antep pistachio on International Index of Erectile Function (IIEF) scores, penile color Doppler ultrasound (PCDU) parameters and serum lipid levels in patients with ED. A total of 17 married male patients with ED for at least 12 months were included in this prospective study. Patients were put on a 100 g pistachio nuts diet for 3 weeks. IIEF and PCDU were evaluated before and after the pistachio diet. In addition, plasma total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride were measured before and after dietary modifications from all subjects. Mean IIEF-15 score was 36 ± 7.5 before the diet and 54.2 ± 4.9 after the diet (P=0.001). Similarly, an increase in all five domains of IIEF was observed after the diet (P<0.05). Mean peak systolic velocity values before and after the pistachio diet were 35.5 ± 15.2 and 43.3 ± 12.4 cm s(-1), respectively (P=0.018). After the pistachio diet, TC and LDL levels decreased significantly, whereas HDL level increased (P=0.008, 0.007 and 0.001, respectively). We demonstrated that a pistachio diet improved IIEF scores and PCDU parameters without any associated side effects in patients with ED. Furthermore, the lipid parameters showed statistically significant improvements after this diet.",
"title": "Pistachio diet improves erectile function parameters and serum lipid profiles in patients with erectile dysfunction."
},
{
"docid": "MED-2592",
"text": "Background Studies have shown that pistachios can improve blood lipid profiles in subjects with moderate hypercholesterolemia which could reduce the risk of cardiovascular disease. However, there is also a widely perceived view that eating nuts can lead to body weight gain due to their high fat content. Purpose To investigate the impact of different dosages of pistachios on body weight, blood pressure, blood lipids, blood glucose and insulin in subjects with metabolic syndrome. Methods Ninety subjects with metabolic syndrome (consistent with 2005 International Diabetes Federation metabolic syndrome standard without diabetes) were enrolled in three endocrinology outpatient clinics in Beijing. All subjects received dietary counseling according to the guidelines of the American Heart Association Step I diet. After a 4 week run-in, subjects were randomized to consume either the recommended daily serving of 42 g pistachios (RSG), a higher daily serving of 70 g pistachio (HSG) or no pistachios (DCG) for 12 weeks. Results Subjects in all three groups were matched at baseline for BMI: DCG 28.03 ± 4.3; RSG 28.12 ± 3.22; and HSG 28.01 ± 4.51 kg/m2. There were no significant changes in body weight or BMI in any groups during the study nor any change from baseline at any time point in any group. During the entire study, there were no significant differences in waist-to-hip ratio among the groups or any change from baseline in any group (DCG -0.00 ± 0.03, RSG -0.01 ± 0.02 and HSG 0.01 ± 0.04). There were no significant differences detected among groups in triglycerides, fasting glucose and 2 hour postprandial glucose following a 75 gram glucose challenge. Exploratory analyses demonstrated that glucose values 2 h after a 75 gm glucose challenge were significantly lower at week 12 compared with baseline values in the HSG group (-1.13 ± 2.58 mmol/L, p = 0.02), and a similar trend was noted in the RSG group (-0.77 ± 2.07 mmol/L, p = 0.06), while no significant change was seen in the DCG group (-0.15 ± 2.27 mmol/L, p = 0.530). At the end of study, serum triglyceride levels were significantly lower compared with baseline in the RSG group (-0.38 ± 0.79 mmol/L, p = 0.018), but no significant changes were observed in the HSG or DCG groups. Conclusion Despite concerns that pistachio nut consumption may promote weight gain, the daily ingestion of either 42 g or 70 g of pistachios for 12 weeks did not lead to weight gain or an increase in waist-to-hip ratio in Chinese subjects with metabolic syndrome. In addition, pistachio consumption may improve the risk factor associated with the metabolic syndrome.",
"title": "Effects of pistachios on body weight in Chinese subjects with metabolic syndrome"
},
{
"docid": "MED-4710",
"text": "OBJECTIVE: Recent studies have suggested that nuts have favorable effects beyond lipid lowering. We aimed to investigate effect of the Antep pistachio (Pistacia vera L.) on blood glucose, lipid parameters, endothelial function, inflammation, and oxidation in healthy young men living in a controlled environment. METHODS: A Mediterranean diet was administered to normolipidemic 32 healthy young men (mean age 22 y, range 21-24) for 4 wk. After 4 wk, participants continued to receive the Mediterranean diet but pistachio was added for 4 wk by replacing the monounsaturated fat content constituting approximately 20% of daily caloric intake. Fasting blood samples and brachial endothelial function measurements were performed at baseline and after each diet. RESULTS: Compared with the Mediterranean diet, the pistachio diet decreased glucose (P<0.001, -8.8+/-8.5%), low-density lipoprotein (P<0.001, -23.2+/-11.9%), total cholesterol (P<0.001, -21.2+/-9.9%), and triacylglycerol (P=0.008, -13.8+/-33.8%) significantly and high-density lipoprotein (P=0.069, -3.1+/-11.7%) non-significantly. Total cholesterol/high-density lipoprotein and low-density lipoprotein/high-density lipoprotein ratios decreased significantly (P<0.001 for both). The pistachio diet significantly improved endothelium-dependent vasodilation (P=0.002, 30% relative increase), decreased serum interleukin-6, total oxidant status, lipid hydroperoxide, and malondialdehyde and increased superoxide dismutase (P<0.001 for all), whereas there was no significant change in C-reactive protein and tumor necrosis factor-alpha levels. CONCLUSION: In this trial, we demonstrated that a pistachio diet improved blood glucose level, endothelial function, and some indices of inflammation and oxidative status in healthy young men. These findings are in accordance with the idea that nuts, in particular pistachio nuts, have favorable effects beyond lipid lowering that deserve to be evaluated with prospective follow-up studies. Copyright 2010. Published by Elsevier Inc.",
"title": "Effect of pistachio diet on lipid parameters, endothelial function, inflammation, and oxidative status: a prospective study."
},
{
"docid": "MED-1726",
"text": "Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone.",
"title": "Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles"
},
{
"docid": "MED-4295",
"text": "Phytosterols were quantified in nuts and seeds commonly consumed in the United States. Total lipid extracts were subjected to acid hydrolysis and then alkaline saponfication, and free sterols were analyzed as trimethylsilyl derivatives by capillary GC-FID and GC-MS. Delta5-Avenasterol was quantified after alkaline saponification plus direct analysis of the glucoside. Sesame seed and wheat germ had the highest total phytosterol content (400-413 mg/100 g) and Brazil nuts the lowest (95 mg/100 g). Of the products typically consumed as snack foods, pistachio and sunflower kernel were richest in phytosterols (270-289 mg/100 g). beta-Sitosterol, Delta5-avenasterol, and campesterol were predominant. Campestanol ranged from 1.0 to 12.7 mg/100 g. Only 13 mg/100 g beta-sitosterol was found in pumpkin seed kernel, although total sterol content was high (265 mg/100 g). Phytosterol concentrations were greater than reported in existing food composition databases, probably due to the inclusion of steryl glycosides, which represent a significant portion of total sterols in nuts and seeds.",
"title": "Phytosterol composition of nuts and seeds commonly consumed in the United States."
},
{
"docid": "MED-5137",
"text": "Black pepper (Piper nigrum) is one of the most widely used among spices. It is valued for its distinct biting quality attributed to the alkaloid, piperine. Black pepper is used not only in human dietaries but also for a variety of other purposes such as medicinal, as a preservative, and in perfumery. Many physiological effects of black pepper, its extracts, or its major active principle, piperine, have been reported in recent decades. Dietary piperine, by favorably stimulating the digestive enzymes of pancreas, enhances the digestive capacity and significantly reduces the gastrointestinal food transit time. Piperine has been demonstrated in in vitro studies to protect against oxidative damage by inhibiting or quenching free radicals and reactive oxygen species. Black pepper or piperine treatment has also been evidenced to lower lipid peroxidation in vivo and beneficially influence cellular thiol status, antioxidant molecules and antioxidant enzymes in a number of experimental situations of oxidative stress. The most far-reaching attribute of piperine has been its inhibitory influence on enzymatic drug biotransforming reactions in the liver. It strongly inhibits hepatic and intestinal aryl hydrocarbon hydroxylase and UDP-glucuronyl transferase. Piperine has been documented to enhance the bioavailability of a number of therapeutic drugs as well as phytochemicals by this very property. Piperine's bioavailability enhancing property is also partly attributed to increased absorption as a result of its effect on the ultrastructure of intestinal brush border. Although initially there were a few controversial reports regarding its safety as a food additive, such evidence has been questionable, and later studies have established the safety of black pepper or its active principle, piperine, in several animal studies. Piperine, while it is non-genotoxic, has in fact been found to possess anti-mutagenic and anti-tumor influences.",
"title": "Black pepper and its pungent principle-piperine: a review of diverse physiological effects."
},
{
"docid": "MED-2521",
"text": "A streptomycete was isolated from an Easter Island soil sample and found to inhibit Candida albicans, Microsporum gypseum and Trichophyton granulosum. The antibiotic-producing microorganism was characterized and identified as Streptomyces hygroscopicus. The antifungal principle was extracted with organic solvent from the mycelium, isolated in crystalline form and named rapamycin. Rapamycin is mainly active against Candida albicans; minimum inhibitory concentration against ten strains ranged from 0.02 to 0.2 mug/ml. Its apparent activity against Microsporum gypseum and Trichophyton granulosum is lower because of its instability in culture media on prolonged incubation required by these fungi. No activity was observed against gram-positive and gram-negative bacteria. Acute toxicity in mice is low.",
"title": "Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle."
},
{
"docid": "MED-2384",
"text": "BACKGROUND: Tree nuts, particularly almonds, walnuts, and pistachios, have been shown to possess cardioprotective effects. However, there is little information on the effects of hazelnut consumption on cardiovascular risk markers. METHODS: The antiatherogenic effect of hazelnut before and after consumption in hypercholesterolemic subjects was investigated. Twenty-one hypercholesterolemic volunteers (18 men and 3 women) were recruited in a double control sandwich model intervention study with a single group and three isoenergetic diet periods. These were control diet I (4 weeks), hazelnut-enriched diet (4 weeks; hazelnut contributing 18%-20% of the total daily energy intake), and control diet period II (4 weeks). The cardiovascular risk biomarkers such as endothelial function, using flow-mediated dilation (FMD) technique, low-density lipoprotein (LDL) oxidation products and inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 (sVCAM-1) as well as lipids and lipoprotein levels were monitored. RESULTS: Consumption of a hazelnut-enriched diet significantly improved FMD (56.6%), total cholesterol (-7.8%), triacylglycerol (-7.3%), LDL-cholesterol (-6.17%), and high-density lipoprotein cholesterol (6.07%) compared with the control diet I. Oxidized-LDL, hs-CRP, and sVCAM-1 levels were significantly lower in the group ingesting a hazelnut-enriched diet compared with the control diets I and II. Modest correlations between sVCAM-1 and FMD and between sVCAM-1 and hs-CRP were observed (r = -0.49, P < .025; r = 0.66, P < .001, respectively). CONCLUSION: Hazelnut-enriched diets may exert antiatherogenic effect by improving endothelial function, preventing LDL oxidation, and inflammatory markers, in addition to their lipid and lipoprotein-lowering effects. These beneficial effects appeared to be reversible after 4 weeks on a hazelnut-free diet. Therefore, hazelnut may be incorporated into daily diet without change in total caloric intake for sustained health benefit. Copyright © 2013 National Lipid Association. All rights reserved.",
"title": "Hazelnut-enriched diet improves cardiovascular risk biomarkers beyond a lipid-lowering effect in hypercholesterolemic subjects."
},
{
"docid": "MED-3274",
"text": "Objective To determine whether dogs can be trained to identify people with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. Design Experimental, “proof of principle” study in which six dogs were trained to discriminate between urine from patients with bladder cancer and urine from diseased and healthy controls and then evaluated in tests requiring the selection of one bladder cancer urine sample from six controls. Participants 36 male and female patients (age range 48-90 years) presenting with new or recurrent transitional cell carcinoma of the bladder (27 samples used for training; 9 used for formal testing); 108 male and female controls (diseased and healthy, age range 18-85 years—54 samples used in training; 54 used for testing). Main outcome measure Mean proportion of successes per dog achieved during evaluation, compared with an expected value of 1 in 7 (14%). Results Taken as a group, the dogs correctly selected urine from patients with bladder cancer on 22 out of 54 occasions. This gave a mean success rate of 41% (95% confidence intervals 23% to 58% under assumptions of normality, 26% to 52% using bootstrap methods), compared with 14% expected by chance alone. Multivariate analysis suggested that the dogs' capacity to recognise a characteristic bladder cancer odour was independent of other chemical aspects of the urine detectable by urinalysis. Conclusions Dogs can be trained to distinguish patients with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. This suggests that tumour related volatile compounds are present in urine, imparting a characteristic odour signature distinct from those associated with secondary effects of the tumour, such as bleeding, inflammation, and infection.",
"title": "Olfactory detection of human bladder cancer by dogs: proof of principle study"
},
{
"docid": "MED-2997",
"text": "If disease patterns emerge which show that certain diseases can be related, this is a valuable pointer to a common cause. This article traces the principle of interpreting disease relationships, illustrated by several common conditions of western civilization, for which the common cause is postulated as being removal of fiber from the diet.",
"title": "The Etiological Significance of Related Diseases"
},
{
"docid": "MED-4600",
"text": "Enough solid evidence now exists to offer women several fundamental strategies for healthy eating. They include emphasizing healthful unsaturated fats, whole grains, good protein “packages,” and fruits and vegetables; limiting consumption of trans and saturated fats, highly refined grains, and sugary beverages; and taking a multivitamin with folic acid and extra vitamin D as a nutritional safety net. A diet based on these principles is healthy through virtually all life stages, from young adulthood through planning for pregnancy, pregnancy, and on into old age.",
"title": "Essentials of Healthy Eating: A Guide"
},
{
"docid": "MED-2335",
"text": "Xenohormesis is a biological principle that explains how environmentally stressed plants produce bioactive compounds that can confer stress resistance and survival benefits to animals that consume them. Animals can piggyback off products of plants' sophisticated stress response which has evolved as a result of their stationary lifestyle. Factors eliciting the plant stress response can judiciously be employed to maximize yield of health-promoting plant compounds. The xenohormetic plant compounds can, when ingested, improve longevity and fitness by activating the animal's cellular stress response and can be applied in drug discovery, drug production, and nutritional enhancement of diet.",
"title": "Xenohormesis: health benefits from an eon of plant stress response evolution"
},
{
"docid": "MED-2606",
"text": "Curcumin, the active principle of turmeric, is known to act as an anti-oxidant, anti-mutagen and anti-carcinogen in experimental animals. In the present study, anti-mutagenic effects of turmeric were assessed in 16 chronic smokers. It was observed that turmeric, given in doses of 1.5 g/day for 30 days, significantly reduced the urinary excretion of mutagens in smokers. In contrast, in six non-smokers, who served as control, there was no change in the urinary excretion of mutagens after 30 days. Turmeric had no significant effect on serum aspartate aminotransferase and alanine aminotransferase, blood glucose, creatinine and lipid profile. These results indicate that dietary turmeric is an effective anti-mutagen and it may be useful in chemoprevention.",
"title": "Effect of turmeric on urinary mutagens in smokers."
},
{
"docid": "MED-3728",
"text": "On the basis of copious preclinical data supporting the preventive efficacy of small fruits such as berries and grapes, Chen and colleagues conducted a randomized (noncomparative) phase II trial evaluating two doses of strawberry powder (60 g/d or 30 g/d for six months) to prevent esophageal cancer in China (reported in this issue of the journal, beginning on page 41); 60 g/d reduced the histologic grade of dysplastic lesions and reduced localized biomarkers, whereas 30 g/d was not effective. Fundamental questions remain such as the best formulation of strawberry powder, the active components associated with powder, and the actual mechanism of action, and standardized preparations will be required to permit the widespread use of strawberry powder with a predicable outcome. Clearly, however, this work is a good example of proof-of-principle and highlights the important role of diet, nutrition, and natural products in cancer prevention. ©2012 AACR.",
"title": "Strawberry fields forever?"
},
{
"docid": "MED-744",
"text": "This paper presents a new interpretation of a unique Bronze Age (c. 3000-1100 BCE) Aegean wall painting in the building of Xeste 3 at Akrotiri,Thera. Crocus carturightianus and its active principle, saffron, are the primary subjects at Xeste 3. Several lines of evidence suggest that the meaning of these frescoes concerns saffron and healing: (1) the unusual degree of visual attention given to the crocus, including the variety of methods for display of the stigmas; (2) the painted depiction of the line of saffron production from plucking blooms to the collection of stigmas; and (3) the sheer number (ninety) of medical indications for which saffron has been used from the Bronze Age to the present. The Xeste 3 frescoes appear to portray a divinity of healing associated with her phytotherapy, saffron. Cultural and commercial interconnections between the Therans, the Aegean world, and their neighboring civilizations in the early 2nd millennium BCE indicate a close network of thematic exchange, but there is no evidence that Akrotiri borrowed any of these medicinal (or iconographic) representations. The complex production line, the monumental illustration of a goddess of medicine with her saffron attribute, and this earliest botanically accurate image of an herbal medication are all Theran innovations.",
"title": "Therapy with saffron and the goddess at Thera."
},
{
"docid": "MED-1578",
"text": "Crohn's disease is a complex inherited disorder of unknown pathogenesis with environmental, genetic and microbial factors involved in the development of the disease. A remarkable feature of this disease in childhood is the effective response to exclusive enteral nutrition (EEN) therapy and the need for complete exclusion of normal diet required for success (principle of exclusivity). EEN or dietary interventions might act through removal of dietary components, which affect microbial composition, decrease a proinflammatory response and promote restitution of the epithelial barrier, likewise allowing termination of this vicious disease-forming cycle before a critical threshold is reached. Multiple traditional and nontraditional dietary components may affect the microbiome, mucous layer, intestinal permeability, or adherence and translocation of pathobionts. We review the epidemiological data, as well as data from animal models and cell lines, and propose a model for pathogenesis we have termed the 'bacterial penetration cycle', whereby dietary components such as animal fat, high sugar intake and gliadin, and consumption of emulsifiers, maltodextrin as well as low-fiber diets may be able to cause a localized acquired bacterial clearance defect, leading to bacterial adhesion and penetration, and subsequently inflammation in the gut. © 2014 S. Karger AG, Basel.",
"title": "Dietary clues to the pathogenesis of Crohn's disease."
},
{
"docid": "MED-3607",
"text": "The development of radioprotective agents has been the subject of intense research in view of their potential for use within a radiation environment, such as space exploration, radiotherapy and even nuclear war. However, no ideal, safe synthetic radioprotectors are available to date, so the search for alternative sources, including plants, has been on going for several decades. In Ayurveda, the traditional Indian system of medicine, several plants have been used to treat free radical-mediated ailments and, therefore, it is logical to expect that such plants may also render some protection against radiation damage. A systematic screening approach can provide leads to identifying potential new candidate drugs from plant sources, for mitigation of radiation injury. This article reviews some of the most promising plants, and their bioactive principles, that are widely used in traditional systems of medicine, and which have rendered significant radioprotection in both in vitro and in vivo model systems. Plants and their constituents with pharmacological activities that may be relevant to amelioration of radiation-mediated damage, including antiemetic, antiinflammatory, antioxidant, cell proliferative, wound healing and haemopoietic stimulatories are also discussed. Copyright (c) 2005 John Wiley & Sons, Ltd.",
"title": "Radioprotection by plant products: present status and future prospects."
},
{
"docid": "MED-3887",
"text": "Summary: Antimicrobials are valuable therapeutics whose efficacy is seriously compromised by the emergence and spread of antimicrobial resistance. The provision of antibiotics to food animals encompasses a wide variety of nontherapeutic purposes that include growth promotion. The concern over resistance emergence and spread to people by nontherapeutic use of antimicrobials has led to conflicted practices and opinions. Considerable evidence supported the removal of nontherapeutic antimicrobials (NTAs) in Europe, based on the “precautionary principle.” Still, concrete scientific evidence of the favorable versus unfavorable consequences of NTAs is not clear to all stakeholders. Substantial data show elevated antibiotic resistance in bacteria associated with animals fed NTAs and their food products. This resistance spreads to other animals and humans—directly by contact and indirectly via the food chain, water, air, and manured and sludge-fertilized soils. Modern genetic techniques are making advances in deciphering the ecological impact of NTAs, but modeling efforts are thwarted by deficits in key knowledge of microbial and antibiotic loads at each stage of the transmission chain. Still, the substantial and expanding volume of evidence reporting animal-to-human spread of resistant bacteria, including that arising from use of NTAs, supports eliminating NTA use in order to reduce the growing environmental load of resistance genes.",
"title": "Food Animals and Antimicrobials: Impacts on Human Health"
},
{
"docid": "MED-1439",
"text": "BACKGROUND AND PURPOSE: The purpose of this study is to investigate the longitudinal age-related changes in human brain volume using stereological methods. METHODS: Sixty-six older participants (34 men, 32 women, age [mean +/- SD] 78.9 +/- 3.3 years, range 74-87 years) with normal baseline and follow-up examinations underwent 2 MRIs (magnetic resonance imaging) of the brain on average 4.4 years apart. The volumes of the cerebrum (defined as cortex, basal ganglia, thalamus, and white matter), lateral ventricles, and cerebellum were estimated on the 2 MRIs using an unbiased stereological method (Cavalieri principle). RESULTS: The annual decrease (mean +/- SD) of the cerebral volume was 2.1% +/- 1.6% (P < .001). The average volume of the lateral ventricles on the second MRI was increased by 5.6% +/- 3.6% per year (P < .001). The average volume of the cerebellum on the second MRI was decreased by 1.2% +/- 2.2% per year (P < .001). Even though the average cerebral volume was significantly different between men and women on initial MRI and second MRI, the percentage change of the age-related cerebral volume decrease in male and female brains between initial MRI and second MRI were identical. CONCLUSIONS: The findings showed that there was age-related atrophy of cerebrum and cerebellum and age-related disproportional enlargement of lateral ventricles in normal older men and women.",
"title": "Brain volume changes on longitudinal magnetic resonance imaging in normal older people."
},
{
"docid": "MED-1878",
"text": "Excerpt Second in a series of publications from the Institute of Medicine's Quality of Health Care in America project Today's health care providers have more research findings and more technology available to them than ever before. Yet recent reports have raised serious doubts about the quality of health care in America. Crossing the Quality Chasm makes an urgent call for fundamental change to close the quality gap. This book recommends a sweeping redesign of the American health care system and provides overarching principles for specific direction for policymakers, health care leaders, clinicians, regulators, purchasers, and others. In this comprehensive volume the committee offers: A set of performance expectations for the 21st century health care system. A set of 10 new rules to guide patient-clinician relationships. A suggested organizing framework to better align the incentives inherent in payment and accountability with improvements in quality. Key steps to promote evidence-based practice and strengthen clinical information systems. Analyzing health care organizations as complex systems, Crossing the Quality Chasm also documents the causes of the quality gap, identifies current practices that impede quality care, and explores how systems approaches can be used to implement change. Copyright 2001 by the National Academy of Sciences. All rights reserved.",
"title": "Crossing the Quality Chasm: A New Health System for the 21st Century"
},
{
"docid": "MED-3292",
"text": "The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.",
"title": "The Restriction of Zoonotic PERV Transmission by Human APOBEC3G"
},
{
"docid": "MED-3309",
"text": "The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.",
"title": "The Restriction of Zoonotic PERV Transmission by Human APOBEC3G"
},
{
"docid": "MED-4602",
"text": "The strategy of \"manufacturing uncertainty\" has been used with great success by polluters and manufacturers of dangerous products to oppose public health and environmental regulation. This strategy entails questioning the validity of scientific evidence on which the regulation is based. While this approach is most identified with the tobacco industry, it has been used by producers of asbestos, benzene, beryllium, chromium, diesel exhaust, lead, plastics, and other hazardous products to avoid environmental and occupational health regulation. It is also central to the debate on global warming. The approach is now so common that it is unusual for the science not to be challenged by an industry facing regulation. Manufacturing uncertainty has become a business in itself; numerous technical consulting firms provide a service often called \"product defense\" or \"litigation support.\" As these names imply, the usual objective of these activities is not to generate knowledge to protect public health but to protect a corporation whose products are alleged to have toxic properties. Evidence in the scientific literature of the funding effect--the close correlation between the results of a study desired by a study's funder and the reported results of that study--suggests that the financial interest of a study's sponsors should be taken into account when considering the study's findings. Similarly, the interpretation of data by scientists with financial conflicts should be seen in this light. Manufacturing uncertainty is antithetical to the public health principle that decisions be made using the best evidence currently available.",
"title": "Manufactured uncertainty: protecting public health in the age of contested science and product defense."
},
{
"docid": "MED-5115",
"text": "The potential health benefits of soy-derived phytoestrogens include their reported utility as anticarcinogens, cardioprotectants and as hormone replacement alternatives in menopause. Although there is increasing popularity of dietary phytoestrogen supplementation and of vegetarian and vegan diets among adolescents and adults, concerns about potential detrimental or other genotoxic effects persist. While a variety of genotoxic effects of phytoestrogens have been reported in vitro, the concentrations at which such effects occurred were often much higher than the physiologically relevant doses achievable by dietary or pharmacologic intake of soy foods or supplements. This review focuses on in vitro studies of the most abundant soy phytoestrogen, genistein, critically examining dose as a crucial determinant of cellular effects. In consideration of levels of dietary genistein uptake and bioavailability we have defined in vitro concentrations of genistein >5 microM as non-physiological, and thus \"high\" doses, in contrast to much of the previous literature. In doing so, many of the often-cited genotoxic effects of genistein, including apoptosis, cell growth inhibition, topoisomerase inhibition and others become less obvious. Recent cellular, epigenetic and microarray studies are beginning to decipher genistein effects that occur at dietarily relevant low concentrations. In toxicology, the well accepted principle of \"the dose defines the poison\" applies to many toxicants and can be invoked, as herein, to distinguish genotoxic versus potentially beneficial in vitro effects of natural dietary products such as genistein.",
"title": "Genistein genotoxicity: critical considerations of in vitro exposure dose."
},
{
"docid": "MED-1951",
"text": "Late preterm (LP) birth (34 0/7 - 36 6/7 weeks' gestation) accounts for nearly three-fourths of all preterm births, making this population a sizeable public health concern. The immature fetal development associated with LP delivery increases the risk of mortality and short-term medical complications. Which combination of maternal, fetal, or neonatal risk factors may be most critical has only recently begun to be addressed, and whether LP birth's disruptive impact on brain development will exert adverse effects on neuropsychological functioning in childhood and adolescence has been understudied. Early data have shown a graded response, with LP children often functioning better than very preterm children but worse than term children, and with subtle intellectual and neuropsychological deficits in LP children compared with healthy children born at term gestational age. Further characterization of the neuropsychological profile is required and would be best accomplished through prospective longitudinal studies. Moreover, since moderate and LP births result in disparate medical and psychological outcomes, the common methodology of combining these participants into a single research cohort to assess risk and outcome should be reconsidered. The rapidly growing LP outcomes literature reinforces a critical principle: fetal development occurs along a dynamic maturational continuum from conception to birth, with each successive gestational day likely to improve overall outcome.",
"title": "Late preterm birth: a review of medical and neuropsychological childhood outcomes."
},
{
"docid": "MED-2810",
"text": "Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be \"Curecumin\".",
"title": "Curcumin as \"Curecumin\": from kitchen to clinic."
},
{
"docid": "MED-2811",
"text": "Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and Crohn's disease (CD) is a major ailment affecting the small and large bowel. In clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and immunomodulators. Unfortunately, the long term usages of these agents are associated with undue side effects and compromise the therapeutic advantage. Accordingly, there is a need for novel agents that are effective, acceptable and non toxic to humans. Preclinical studies in experimental animals have shown that curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or ameliorating UC and inflammation. Over the last few decades there has been increasing interest in the possible role of curcumin in IBD and several studies with various experimental models of IBD have shown it to be effective in mediating the inhibitory effects by scavenging free radicals, increasing antioxidants, influencing multiple signaling pathways, especially the kinases (MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS; inhibiting the transcription factor NF-κB. Clinical studies have also shown that co-administration of curcumin with conventional drugs was effective, to be well-tolerated and treated as a safe medication for maintaining remission, to prevent relapse and improve clinical activity index. Large randomized controlled clinical investigations are required to fully understand the potential of oral curcumin for treating IBD.",
"title": "Curcumin, an active component of turmeric in the prevention and treatment of ulcerative colitis: preclinical and clinical observations."
},
{
"docid": "MED-2824",
"text": "Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called \"curry powder\") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an \"old-age\" disease such as cancer requires an \"age-old\" treatment.",
"title": "Curcumin and cancer: an \"old-age\" disease with an \"age-old\" solution."
},
{
"docid": "MED-4394",
"text": "Acne vulgaris, the most common skin disease of western civilization, has evolved to an epidemic affecting more than 85% of adolescents. Acne can be regarded as an indicator disease of exaggerated insulinotropic western nutrition. Especially milk and whey protein-based products contribute to elevations of postprandial insulin and basal insulin-like growth factor-I (IGF-I) plasma levels. It is the evolutional principle of mammalian milk to promote growth and support anabolic conditions for the neonate during the nursing period. Whey proteins are most potent inducers of glucose-dependent insulinotropic polypeptide secreted by enteroendocrine K cells which in concert with hydrolyzed whey protein-derived essential amino acids stimulate insulin secretion of pancreatic β-cells. Increased insulin/IGF-I signaling activates the phosphoinositide-3 kinase/Akt pathway, thereby reducing the nuclear content of the transcription factor FoxO1, the key nutrigenomic regulator of acne target genes. Nuclear FoxO1 deficiency has been linked to all major factors of acne pathogenesis, i.e. androgen receptor transactivation, comedogenesis, increased sebaceous lipogenesis, and follicular inflammation. The elimination of the whey protein-based insulinotropic mechanisms of milk will be the most important future challenge for nutrition research. Both, restriction of milk consumption or generation of less insulinotropic milk will have an enormous impact on the prevention of epidemic western diseases like obesity, diabetes mellitus, cancer, neurodegenerative diseases and acne. Copyright © 2011 S. Karger AG, Basel.",
"title": "Evidence for acne-promoting effects of milk and other insulinotropic dairy products."
},
{
"docid": "MED-5059",
"text": "This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives. A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives: branching glycosyltransferase from Rhodothermus obamensis expressed in Bacillus subtilis, cassia gum, cyclamic acid and its salts (dietary exposure assessment), cyclotetraglucose and cyclotetraglucose syrup, ferrous ammonium phosphate, glycerol ester of gum rosin, glycerol ester of tall oil rosin, lycopene from all sources, lycopene extract from tomato, mineral oil (low and medium viscosity) class II and class III, octenyl succinic acid modified gum arabic, sodium hydrogen sulfate and sucrose oligoesters type I and type II. Specifications for the following food additives were revised: diacetyltartaric acid and fatty acid esters of glycerol, ethyl lauroyl arginate, glycerol ester of wood rosin, nisin preparation, nitrous oxide, pectins, starch sodium octenyl succinate, tannic acid, titanium dioxide and triethyl citrate. Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives considered.",
"title": "Evaluation of certain food additives. Seventy-first report of the Joint FAO/WHO Expert Committee on Food Additives."
}
] |
941
|
Why do sole proprietors in India generally use a current account?
|
[
{
"docid": "456636",
"text": "Current account offers a lot of benefits for sole proprietors. Think of it like bank account for a company. The bank provides a host of facilities for the company. A sole proprietor does not have enough value as that of a company for a bank but needs similar services. Thus Indian banks offer a toned down version of the account offered to a company. Current account offer very good overdraft ( withdrawing money even if balance is zero). This feature is very useful as business cycles and payment schedules can be different for each supplier/customer the sole proprietor does business with. Imagine the sole proprietor account has balance of zero on day 0. customer X made payment by cheque on day 1. Cheques will get credited only on Day 3 (Assume Day 2 is a national holiday or weekend). Sole proprietor gave a cheque to his supplier on day 0. The supplier deposited the cheque on Day 0 and the sole proprietor's bank will debit the the proprietor's account on day 1. As customer's cheque will get credited only day 3, the overdraft facility will let the proprietor borrow from the bank Interestingly, current accounts were offered long before Indian banks started offering customized accounts to corporate customers. The payment schedule mentioned in my example is based on a clearing system > 10 years ago. Systems have become much simpler now but banks have always managed to offer something significantly extra on lines similar to my example above to proprietor over a savings bank account",
"title": ""
},
{
"docid": "295203",
"text": "No. Current account is not a requirement. You can use savings account. You would need to pay taxes on interest. Savings account have limitation on number of withdrawal in a quarter, hence most sole proprietorship have current account.",
"title": ""
}
] |
[
{
"docid": "109203",
"text": "You could, but the bank won't let you... If you're a sole proprietor - then you could probably open a personal account and just use it, and never tell them that is actually a business. However, depending on your volume of operations, they may switch you on their own to business account by the pattern of your transactions. For corporations, you cannot use a personal account since the corporation is a separate legal entity that owns the funds. Also, you're generally required to separate corporate and personal funds to keep the limited liability protection (which is why you have the corporation to begin with). Generally, business accounts have much higher volumes and much more transactions than personal accounts, and it costs more for the banks to run them. In the US, some banks offer free, or very low-cost, business accounts for small businesses that don't need too many transactions. I'm sure if you shop around, you'll find those in Canada as well.",
"title": ""
},
{
"docid": "377152",
"text": "\"According to IRS Publication 1635, Understanding your EIN (PDF), under \"\"What is an EIN?\"\" on page 2: Caution: An EIN is for use in connection with your business activities only. Do not use your EIN in place of your social security number (SSN). As you say your EIN is for your business as a sole proprietor, I would also refer to Publication 334, Tax Guide for Small Business, under \"\"Identification Numbers\"\": Social security number (SSN). Generally, use your SSN as your taxpayer identification number. You must put this number on each of your individual income tax forms, such as Form 1040 and its schedules. Employer identification number (EIN). You must also have an EIN to use as a taxpayer identification number if you do either of the following. Pay wages to one or more employees. File pension or excise tax returns. If you must have an EIN, include it along with your SSN on your Schedule C or C-EZ as instructed. While I can't point to anything specifically about bank accounts, in general the guidance I see is that your SSN is used for your personal stuff, and you have an EIN for use in your business where needed. You may be able to open a bank account listing the EIN as the taxpayer identification number on the account. I don't believe there's a legal distinction between what makes something a \"\"business\"\" account or not, though a bank may have different account offerings for different purposes, and only offer some of them to entities rather than individuals. If you want to have a separate account for your business transactions, you may want them to open it in the name of your business and they may allow you to use your EIN on it. Whether you can do this for one of their \"\"personal\"\" account offerings would be up to the bank. I don't see any particular advantages to using your EIN on a bank account for an individual, though, and I could see it causing a bit of confusion with the bank if you're trying to do so in a way that isn't one of their \"\"normal\"\" account types for a business. As a sole proprietor, there really isn't any distinction between you and your business. Any interest income is taxable to you in the same way. But I don't think there's anything stopping you legally other than perhaps your particular bank's policy on such things. I would suggest contacting your bank (or trying several banks) to get more information on what account offerings they have available and what would best fit you and your business's needs.\"",
"title": ""
},
{
"docid": "179066",
"text": "\"Your own site/business. I’m in freelancing and internet business for 15 years, 20 years IT experience. Currently i use freelance websites for cheap Asian employees, very seldom for EU/USA employees, and if only if local competition is heavily out-pricing qualified staff. Till I went \"\"limited\"\" i.e., founded a limited corporation I was jobbing as freelancer and sole proprietor, both with limited success due to the strong Asian competition i myself currently hire. The point where freelancing got \"\"not sustainable\"\" as primary income was 2006 for me, don’t want to get into detail but every freelancer who was active back then knows what I mean, it was like whole India got internet. If you have absolutely no references, do it for the references a limited time and see the fee you pay as service for you to get references, then start your own web identity, either as freelancer or as corporation. Make sure you take your very satisfied customers with you. Every \"\"very satisfied\"\" customer in your contact list means 10 new customers which mean 2 new customers which mean 0.2 new customers and so on. Honestly, this info is solely based on experience of this niche fro ma European citizen perspective, if you’re based anywhere else the situation might be totally different.\"",
"title": ""
},
{
"docid": "506108",
"text": "\"LLC is, as far as I know, just a US thing, so I'm assuming that you are in the USA. Update for clarification: other countries do have similar concepts, but I'm not aware of any country that uses the term LLC, nor any other country that uses the single-member LLC that is disregarded for income tax purposes that I'm referring to here (and that I assume the recruiter also was talking about). Further, LLCs vary by state. I only have experience with California, so some things may not apply the same way elsewhere. Also, if you are located in one state but the client is elsewhere, things can get more complex. First, let's get one thing out of the way: do you want to be a contractor, or an employee? Both have advantage, and especially in the higher-income areas, contractor can be more beneficial for you. Make sure that if you are a contractor, your rate must be considerably higher than as employee, to make up for the benefits you give up, as well as the FICA taxes and your expense of maintaining an LLC (in California, it costs at least $800/year, plus legal advice, accounting, and various other fees etc.). On the other hand, oftentimes, the benefits as an employee aren't actually worth all that much when you are in high income brackets. Do pay attention to health insurance - that may be a valuable benefit, or it may have such high deductibles that you would be better off getting your own or paying the penalty for going uninsured. Instead of a 401(k), you can set up an IRA (update or various other options), and you can also replace all the other benefits. If you decide that being an employee is the way to go, stop here. If you decide that being a contractor is a better deal for you, then it is indeed a good idea to set up an LLC. You actually have three fundamental options: work as an individual (the legal term is \"\"sole proprietorship\"\"), form a single-member LLC disregarded for income tax purposes, or various other forms of incorporation. Of these, I would argue that the single-member LLC combines the best of both worlds: taxation is almost the same as for sole proprietorship, the paperwork is minimal (a lot less than any other form of incorporation), but it provides many of the main benefits of incorporating. There are several advantages. First, as others have already pointed out, the IRS and Department of Labor scrutinize contractor relationships carefully, because of companies that abused this status on a massive scale (Uber and now-defunct Homejoy, for instance, but also FedEx and other old-economy companies). One of the 20 criteria they use is whether you are incorporated or not. Basically, it adds to your legal credibility as a contractor. Another benefit is legal protection. If your client (or somebody else) sues \"\"you\"\", they can usually only sue the legal entity they are doing business with. Which is the LLC. Your personal assets are safe from judgments. That's why Donald Trump is still a billionaire despite his famous four bankruptcies (which I believe were corporate, not personal, bankrupcies). Update for clarification Some people argue that you are still liable for your personal actions. You should consult with a lawyer about the details, but most business liabilities don't arise from such acts. Another commenter suggested an E&O policy - a very good idea, but not a substitute for an LLC. An LLC does require some minimal paperwork - you need to set up a separate bank account, and you will need a professional accounting system (not an Excel spreadsheet). But if you are a single member LLC, the paperwork is really not a huge deal - you don't need to file a separate federal tax return. Your income will be treated as if it was personal income (the technical term is that the LLC is disregarded for IRS tax purposes). California still does require a separate tax return, but that's only two pages or so, and unless you make a large amount, the tax is always $800. That small amount of paperwork is probably why your recruiter recommended the LLC, rather than other forms of incorporation. So if you want to be a contractor, then it sounds like your recruiter gave you good advice. If you want to be an employee, don't do it. A couple more points, not directly related to the question, but hopefully generally helpful: If you are a contractor (whether as sole proprietor or through an LLC), in most cities you need a business license. Not only that, but you may even need a separate business license in every city you do business (for instance, in the city where your client is located, even if you don't live there). Business licenses can range from \"\"not needed\"\" to a few dollars to a few hundred dollars. In some cities, the business license fee may also depend on your income. And finally, one interesting drawback of a disregarded LLC vs. sole proprietorship as a contractor has to do with the W-9 form and your Social Security Number. Generally, when you work for somebody and receive more than $600/year, they need to ask you for your Social Security Number, using form W-9. That is always a bit of a concern because of identity theft. The IRS also recognizes a second number, the EIN (Employer Identification Number). This is basically like an SSN for corporations. You can also apply for one if you are a sole proprietor. This is a HUGE benefit because you can use the EIN in place of your SSN on the W-9. Instant identity theft protection. HOWEVER, if you have a disregarded LLC, the IRS says that you MUST use your SSN; you cannot use your EIN! Update: The source for that information is the W-9 instructions; it specifically only excludes LLCs.\"",
"title": ""
},
{
"docid": "100764",
"text": "\"You don't specify which country you are in, so my answers are more from a best practice view than a legal view.. I don't intend on using it for personal use, but I mean it's just as possible. This is a dangerous proposition.. You shouldn't co-mingle business expenses with personal expenses. If there is a chance this will happen, then stop, make it so that it won't happen. The big danger is in being able to have traceability between what you are doing for the business, and what you are doing for yourself. If you are using this as a \"\"staging\"\" account for investments, etc., are those investments for yourself? Or for the business? Is tax treatment on capital gains and/or dividends the same for personal and business in your jurisdiction? If you buy a widget, is the widget an expense against business income? Or is it an out of pocket expense for personal consumption? The former reduces your taxable income, the latter does not. I don't see the benefit of a real business account because those have features specific to maybe corporations, LLC, and etc. -- nothing beneficial to a sole proprietor who has no reports/employees. The real benefit is that there is a clear delineation between business income/expenses and personal income/expenses. This account can also accept money and hold it from business transactions/sales, and possibly transfer some to the personal account if there's no need for reinvesting said amount/percentage. What you are looking for is a commonly called a current account, because it is used for current expenses. If you are moving money out of the account to your personal account, that speaks to paying yourself, which has other implications as well. The safest/cleanest way to do this is to: While this may sound like overkill, it is the only way to guarantee that income/expenses are allocated to the correct entity (i.e. you, or your business). From a Canadian standpoint:\"",
"title": ""
},
{
"docid": "418647",
"text": "Do you need to incorporate? This depends on whether the company prefers you to be incorporated. If you are going through a recruiting company, some of them are willing to deal with non-incorporated people (Sole Proprietor) and withhold taxes from your cheques for you. If you do want to incorporate, you can do it yourself, go through a paralegal, or you can even do it online. I did mine in Ontario for about $300 (no name search - i just have a numbered corporation like 123456 Ontario Inc.) through www.oncorp.com - there are other sites that do it as well. Things to consider - if you're contracting through a corporation you most likely need to: Talk to an accountant about these for clarification - most of them will give you an initial consultation for free. Generally speaking, accountant fees for corporate filing taxes averages about $1000-2000 a year.",
"title": ""
},
{
"docid": "513051",
"text": "\"Interesting as I am in the exact same situations as yourself. I, in fact, just incorporated. You will be able \"\"save\"\" more in taxes in the end. The reason I put \"\"save\"\" in quotes, is that you don't necessarily save on taxes, but you can defer taxes. The driving factor behind this is that you specify your own fiscal calendar/year. Incorporating allows you to defer income for up to 6 months. Meaning that if you make your fiscal year starting in August or September, for example, you can claim that income on the following year (August + 6 months = February). It allows you to keep the current year taxes down. Also, any income left over at year end, is taxed at 15% (the Corporation rate) rather than the 30-40% personal rate you get with a sole-proprietorship. In a nutshell, with sole-proprietorship, all income is taxable (after write-offs)... in a corporation, you can take some of that income and keep it in the corporation (gives your company a \"\"value\"\"), and is only taxed at 15% - big saving there. I primarily work with US businesses. I am, however, a dual-citizen, US and Canadian, which allowed me as a sole-proprietor, to easily work with US companies. However, as a sole-proprietor or a Corporation, you simply need to get an EIN from the IRS and any US company will report earnings to that number, with no deductions. At year end, it is your responsibility to file the necessary tax forms and pay the necessary taxes to both countries. Therefore you can solicit new US business if you choose, but this is not restricted to corporations. The real benefit in incorporating is what I mentioned above. My suggestion to you is to speak with you CA, who can outline all benefits. Revenue Canada's website had some good information on this topic as well. Please let me know if you need anything else explained.\"",
"title": ""
},
{
"docid": "1873",
"text": "\"I expect the company wanted to pay you for a product (on a purchase order) rather than as a contract laborer. Whatever. Would they be willing to re-issue the check to you as a sole proprietor of a business named ABC Consulting (or anything like that)? You can register your sole proprietor business with the state using a \"\"Doing Business As\"\" (DBA, or fictitious name), and then open the bank account for your business using the check provided by the customer as the first deposit. (There is likely a smaller registration fee for the DBA.) If they won't re-issue the check and you have to go the LLC route... Scrounge up $125 doing odd jobs or borrowing from a friend or parents. Seriously, anyone can earn that amount of money in a week or two. Besides the filing fee for the LLC, your bank may require you to provide an Operating Agreement (which is not required by the State). The Operating Agreement can be simple, or more complex if you have a partner (even if it's a spouse). If you do have a partner, it is essential to have such an agreement because it would specify the responsibilities and benefits allocated to each partner, particularly in the event of equity distributions (taking money out of the business, or liquidating and ending the LLC). There are websites that will provide you a boilerplate form for Operating Agreements. But if your business is anything more than just single member LLC, you should pay an attorney to draw one up for you so the wording is right. It's a safeguard against potential future lawsuits. And, while we're at it, don't forget to obtain a EIN (equivalent to a SSN) from the IRS for your LLC. There's no cost, but you'll have to have it to file taxes as a business for every year the LLC exists and has income. Good luck!\"",
"title": ""
},
{
"docid": "523564",
"text": "\"While she can certainly get an LLC or EIN, it isn't necessarily required or needed. She can file as a sole-proprietor on her (or your joint) taxes by filling out a schedule-C addition to the 1040. Any income or losses will pass through to your existing income situation (from W-2's and such). The general requirement for filing as a business in this regard has nothing to do with any minimum income, revenue, or size. It is simply the intent to treat it as a business, and unlike a hobby, the overall intent to earn a profit eventually. If you're currently reporting the 1099-MISC income, but not deducting the expenses, this would be a means for you to offset the income with the expenses you mentioned (and possibly other legitimate ones). There is no \"\"2% AGI\"\" restriction for schedule-C.\"",
"title": ""
},
{
"docid": "202570",
"text": "I think you are asking quite a few questions here; If you have Rs 10000, its better you get it converted in India before you leave. Most Banks and Exchange houses like Western Union would take Rupees and Give you USD. What do they do with USD, there are other who give them USD and need Rupees. They make a spread in this process. If you are getting a salary in USD in US, whenever you want to transfer money to India, the Banks or Remittance services like Western Union would take USD from your US Account and Transfter equivalent Money into your Bank Account in India in Rupees. They will tell the exchange rate applicable. Depending on why visa type & the duration you are going, your company should be able to tell you your tax liabilities in the US. Read similar questions here to get a general idea.",
"title": ""
},
{
"docid": "590310",
"text": "Alright, team! I found answers to part 1) and part 2) that I've quote below, but still need help with 3). The facts in the article below seem to point to the ability for the LLC to contribute profit sharing of up to 25% of the wages it paid SE tax on. What part of the SE tax is that? I assume the spirit of the law is to only allow the 25% on the taxable portion of the income, but given that I would have crossed the SS portion of SE tax, I am not 100%. (From http://www.sensefinancial.com/services/solo401k/solo-401k-contribution/) Sole Proprietorship Employee Deferral The owner of a sole proprietorship who is under the age of 50 may make employee deferral contributions of as much as $17,500 to a Solo 401(k) plan for 2013 (Those 50 and older can tack on a $5,500 annual catch-up contribution, bringing their annual deferral contribution to as much as $23,000). Solo 401k contribution deadline rules dictate that plan participant must formally elect to make an employee deferral contribution by Dec. 31. However, the actual contribution can be made up until the tax-filing deadline. Pretax and/or after-tax (Roth) funds can be used to make employee deferral contributions. Profit Sharing Contribution A sole proprietorship may make annual profit-sharing contributions to a Solo 401(k) plan on behalf of the business owner and spouse. Internal Revenue Code Section 401(a)(3) states that employer contributions are limited to 25 percent of the business entity’s income subject to self-employment tax. Schedule C sole-proprietors must base their maximum contribution on earned income, an additional calculation that lowers their maximum contribution to 20 percent of earned income. IRS Publication 560 contains a step-by-step worksheet for this calculation. In general, compensation can be defined as your net earnings from self-employment activity. This definition takes into account the following eligible tax deductions: (1) the deduction for half of self-employment tax and (2) the deduction for contributions on your behalf to the Solo 401(k) plan. A business entity’s Solo 401(k) contributions for profit sharing component must be made by its tax-filing deadline. Single Member LLC Employee Deferral The owner of a single member LLC who is under the age of 50 may make employee deferral contributions of as much as $17,500 to a Solo 401(k) plan for 2013 (Those 50 and older can tack on a $5,500 annual catch-up contribution, bringing their annual deferral contribution to as much as $23,000). Solo 401k contribution deadline rules dictate that plan participant must formally elect to make an employee deferral contribution by Dec. 31. However, the actual contribution can be made up until the tax-filing deadline. Pretax and/or after-tax (Roth) funds can be used to make employee deferral contributions. Profit Sharing Contribution A single member LLC business may make annual profit-sharing contributions to a Solo 401(k) plan on behalf of the business owner and spouse. Internal Revenue Code Section 401(a)(3) states that employer contributions are limited to 25 percent of the business entity’s income subject to self-employment tax. Schedule C sole-proprietors must base their maximum contribution on earned income, an additional calculation that lowers their maximum contribution to 20 percent of earned income. IRS Publication 560 contains a step-by-step worksheet for this calculation. In general, compensation can be defined as your net earnings from self-employment activity. This definition takes into account the following eligible tax deductions: (i) the deduction for half of self-employment tax and (ii) the deduction for contributions on your behalf to the Solo 401(k). A single member LLC’s Solo 401(k) contributions for profit sharing component must be made by its tax-filing deadline.",
"title": ""
},
{
"docid": "448981",
"text": "am I allowed to transfer into NRE account from paypal? Credits into NRE accounts are restricted. It has to be established that the funds being credited are income outside of India. In case of paypal, paypal uses local clearing to credit funds into Bank Accounts. So essentially one cannot credit NRE account by domestic clearing network like NEFT. It is best that you withdraw the funds into Bank Account outside India and use SWIFT or remittance service to credit your NRE account. I do not want to transfer to an NRO account since the money credited into it will become taxable. This is not the right assumption. Credits into NRO are not taxable by default; if you establish that the funds are from outside India, there is no tax on the income money transferred from abroad into the NRO account. However, the interest that will be paid by the bank on the balance of the NRO account is taxable income in India and is subject to TDS. In contrast, interest paid on the balance in an NRE account is not taxable in India and is not subject to TDS as long as you maintain NRI status. However it does make sense to keep accounts segregated, i.e. income generated in India, credit the NRO account and income generated outside India credit to NRE.",
"title": ""
},
{
"docid": "418884",
"text": "Book keeping as a sole proprietor will seem like a headache. Basically you have to have two accounts for everything and track specifics for any company assets that are mixed use (such as mileages). No real downsides aside from that. We just bought a start up kit and then modified it an then did a lot of research on proper registrations. I found out later you can have a legal expert do it for like 250-300. If we had known that it would have been worth it. The state and fed registration is a boring headache. Your time is better spent earning.",
"title": ""
},
{
"docid": "483942",
"text": "This depends on the state law. In case of the State of New York - these are the criteria for sourcing the NY income: As a sole proprietor or partnership, your New York source income includes: Business activities As a nonresident sole proprietor or partnership, you carry on a business, trade, profession, or occupation within New York State if you (or your business): As you can see, the qualification depends on the way you do business, and the amount of business transactions you have in New York. If it is not clear to you - talk to a CPA/EA licensed to practice in the State of New York to give you an advice.",
"title": ""
},
{
"docid": "58611",
"text": "Can I still use the old EIN from partnership times for the new sole proprietorship? Or should I apply for a new EIN? You cannot use the same EIN. Unless you have employees, you should use your SSN for the sole proprietorship. If you have employees - you should get a new EIN (if you don't have one already for yourself as a sole proprietor - you can only have one). Can I actually start to use my SSN in this situation for the sole proprietorship? In this particular case, not only you can - you should.",
"title": ""
},
{
"docid": "365456",
"text": "There are quite a few questions as to how you are recording your income and expenses. If you are running the bakery as a Sole Proprietor, with all the income and expense in a business account; then things are easy. You just have to pay tax on the profit [as per the standard tax bracket]. If you running it as individual, you are still only liable to pay tax on profit and not turnover, however you need to keep a proper book of accounts showing income and expense. Get a Accountant to do this for you there are some thing your can claim as expense, some you can't.",
"title": ""
},
{
"docid": "390368",
"text": "As a sole proprietor, the tax liability of your business is calculated based on combining your business income with your personal income together. It is good advice to keep all personal and business financial matters separate. This makes it easier to prove to the IRS that all your business expenses are actually business related. In this case however, the two items [tax payment for personal income vs tax payment for business income] are inseparable. What you can do, however, for your own personal records, is calculate how much of your tax payment relates to your business. I wouldn't get complicated about this; I would simply take the net income of your business as a % of your taxable income, and multiply that against your tax payment. ie: if your business net income is $10,000, and your total taxable income is $50,000, and you paid $6,000 in taxes, I would record that 20% of the $6k was related to business income. If you have a separate bank account for your sole proprietorship, you could make a transfer to your personal account of $1,200, and then make the $6k payment from your personal account. Remember that tax payments for either your sole proprietorship and your personal income will be treated the same: federal tax payments are not tax deductible, and state tax payments are tax deductible, whether they were paid for your sole proprietorship or the rest of your personal income. So even though this method is simplistic [for example, it doesn't factor in that different investment income types earned personally will have a lower rate than your sole proprietorship income], any difference wouldn't have an impact on any future tax liability. This would only be for your own personal record keeping.",
"title": ""
},
{
"docid": "367754",
"text": "I feel the need to separate my freelance accounts from my personal accounts. Yes, you should. Should I start another savings account or a current account? Do you need the money for daily spending? Do you need to re-invest in your business? Use a current account. If you don't need the money for business expenses, put it away in your savings account or even consider term deposits. Don't rule out a hybrid approach either (some in savings account, some in current account). What criteria should I keep in mind while choosing a bank? (I thought of SBI since it has a lot of branches and ATMs). If you are involved in online banking and that is sufficient for most of your needs, bank and ATM locations shouldn't matter all that much. If you are saving a good chunk of money, you want to at least have that keep up with inflation. Research bank term deposit interest rates. The tend to be higher than just having your money sit in a savings account. Again, it depends on how and when you expect to need the money. What do I keep in mind while paying myself? Paying yourself could have tax implications. This depends on how are set up to freelance. Are you a business entity or are you an individual? You should look in to the following in India: The other thing to consider is rewarding yourself for the good work done. Pay yourself a reasonable amount. If you decide to expand and hire people going forward, you will have a better sense of business expenses involved when paying salaries. Tips on managing money in the business account. This is a very generic question. I can only provide a generic response. Know how much you are earning and how much your are putting back in to the business. Be reasonable in how much you pay yourself and do the proper research and paperwork from a taxation point of view.",
"title": ""
},
{
"docid": "234510",
"text": "\"TL;DR: Get a tax adviser (EA/CPA licensed in your State) for tax issues, and a lawyer for the Operating Agreement, labor law and contract related issues. Some things are not suitable for DIY unless you know exactly what you're doing. We both do freelance work currently just through our personal names. What kind of taxes are we looking into paying into the business (besides setup of everything) compared to being a self proprietor? (I'm seeing that the general answer is no, as long as income is <200k, but not certain). Unless you decide to have your LLC taxed as a corporation, there's no change in taxes. LLC, by default, is a pass-through entity and all income will flow to your respective tax returns. From tax perspective, the LLC will be treated as a partnership. It will file form 1065 to report its income, and allocate the income to the members/partners on schedules K-1 which will be given to you. You'll use the numbers on the K-1 to transfer income allocated to you to your tax returns and pay taxes on that. Being out of state, will she incur more taxes from the money being now filtered through the business? Your employee couldn't care less about your tax problems. She will continue receiving the same salary whether you are a sole proprietor or a LLC, or Corporatoin. What kind of forms are we looking into needing/providing when switching to a LLC from freelance work? Normally we just get 1099's, what would that be now? Your contract counterparts couldn't care less about your tax problems. Unless you are a corporation, people who pay you more than $600 a year must file a 1099. Since you'll be a partnership, you'll need to provide the partnership EIN instead of your own SSN, but that's the only difference. Are LLC's required to pay taxes 4 times per year? We would definitely get an accountant for things, but being as this is side work, there will be times where we choose to not take on clients, which could cause multiple months of no income. Obviously we would save for when we need to pay taxes, but is there a magic number that says \"\"you must now pay four times per year\"\". Unless you choose to tax your LLC as a corporation, LLC will pay no taxes. You will need to make sure you have enough withholding to cover for the additional income, or pay the quarterly estimates. The magic number is $1000. If your withholding+estimates is $1000 less than what your tax liability is, you'll be penalized, unless the total withholding+estimates is more than 100% of your prior year tax liability (or 110%, depending on the amounts). The LLC would be 50% 50%, but that work would not always be that. We will be taking on smaller project through the company, so there will be times where one of us could potentially be making more money. Are we setting ourselves up for disaster if one is payed more than the other while still having equal ownership? Partnerships can be very flexible, and equity split doesn't have to be the same as income, loss or assets split. But, you'll need to have a lawyer draft your operational agreement which will define all these splits and who gets how much in what case. Make sure to cover as much as possible in that agreement in order to avoid problems later.\"",
"title": ""
},
{
"docid": "570639",
"text": "\"Transferring the money or keeping it in US does has no effect on taxes. Your residency status has. Assuming you are Resident Alien in US for tax purpose and have paid the taxes to IRS and you are \"\"Non-Resident\"\" Indian for tax purposes in India as you are more than 182 outside India. How would it effect my Tax in US and India If you are \"\"Non-Resident\"\" in India for tax purposes, there is no tax liability of this in India. I have transferred an amount of approx 15-20k$ to Indian Account (not NRE) By RBI regulation, if you are \"\"Non-Resident\"\" then you should get your savings account converted to \"\"NRO\"\". You may not may not choose to open an NRE account. To keep the paper work clear it helps that you open an NRE account in India. Any investment needed ? Where do i need to declare if any ? These are not relevant. Note any income generated in India, i.e. interest in Savings account / FDs / Rent etc; taxes need to be paid in India and declared in US and taxes paid in US as well. There is some relief under DTAA. There are quite a few question on this site that will help you clarify what needs to be done.\"",
"title": ""
},
{
"docid": "344290",
"text": "foreign income, transfer it to my savings account in India Yes you can transfer to India. The right account would be NRO/NRE. As an NRI one should not hold a regular savings account. forum that foreign income is not taxable unless used to buy stocks, fds etc If you are an NRI, income earned outside of India is not taxable in India. However any income you generate in India is taxable, i.e. interest income, gains from shares etc. Do we need to pay taxes for the money transferred No tax if you are an NRI even if you transfer funds to India. Taxation does not depend on whether or not you transfer the money, it depends on your status used to pay home EMIs or principle amount? You can use the money for what ever you like.",
"title": ""
},
{
"docid": "314339",
"text": "\"So it seems like a lot of people here aren't exactly sure about why this works and its financial implications. So what you are referring to is in Finance something called Funds Transfer Pricing or FTP (often referred to as just Transfer Pricing). Like anything else, FTP has its place. Most companies; however, don't use it properly. FTP, theoretically, has one primary purpose (although it's developed a second): to properly allocate opportunity costs across divisions. Let's say Company A produces widgets. They sell these widgets for $200 at a TOTAL COST of $150 and book profits of $50. Now to produce the widget Division 1 makes a computer chip at a cost of $50 that it then \"\"sells\"\" to Division 2 for $60. Division 1 then books a profit of $10. Division 2 then makes some plastic stuff and assembles the device. This is labor intensive so Division 2's costs are $100. Company A sells the completed device for $150. Division 2 subsequently books profits of $40, and appears much more profitable than Division 1, on the surface. The problem arises when Division 1 could sell the chip to the open market for $125. Now it costs them $50 to produce, and they could make a theoretical profit of $75. This is MORE than the company makes AS A WHOLE on the entire device. By having Division 2 pay effectively \"\"fair market price\"\" for that chip, you realize that Division 2 is really operating at a loss (the *opportunity cost* of not selling the chip to market is greater than producing the completed device). Company A would be better off getting rid of Division 2 and solely focusing on Division 1. In a good FTP system, Division 2 would pay the fair market price of $125. If done properly, management would hopefully realize it should divest Division 2. That's the ***fundamental premise*** behind FTP. In actuality things get much more complicated because of economics, the company itself, branding, IT, operations, management, PPE, labor laws, etc. Thats why most companies screw it up. All that other stuff falls under whats called cost allocation accounting. It gets VERY complex and entire masters courses are dedicated to it (different methods, etc.) The other thing you can do with FTP is get crazy tax breaks due to various tax laws. The simplified explanation is that divisions pay taxes on profits to the government ***that division*** is located in (this works on the state level, too btw.). GE does a lot of this and it's a big part of why they pay almost no-taxes. Again, it gets more complicated when you involve audits as there's some grey area legally. For simplicity, assume tax rates are 40% in the US and 10% in India. So let's say GE makes an airplane engine in the US but \"\"finishes\"\" manufacturing in India. These specific engines costs $5,000,000 for the US division to make, up to a certain point. The US division can then sell the engine at a break even to India. So India \"\"pays\"\" $5,000,000 for the engine. The US division then books no profit. India finishes the manufacturing with additional costs of $1,000,000. The India division then sells the engine to the open market for $9,000,000 . Therefore, the India division books a profit of $3,000,000 and pays taxes of $300,000. Now GE as a whole makes a profit of $3,000,000 less taxes of $300,000 = net profit of $2,700,00. Further, let's say the fair market value of the engine, as is, when the US sells to India is $7,000,000. That would mean US ***should*** book profits of $2,000,000 and India ***should*** book profits of $1,000,000. Total taxes by GE are now $800,000 (US) + $100,000 (India) = $900,000. However, what's important is that NET PROFIT is now $2,100,000. ***GE just saved $600,000 in taxes by doing this***. The beauty of this is, divisions are supposed to charge fair market value for products FTP'd internationally; however, it's REALLY hard for the IRS to say what the value of an unfinished product really is (heck, you could be offering bulk discounts, etc.)... The fact is, often, US divisions have skilled labor that is difficult to replicate elsewhere. They just show US divisions operating at losses to make the company as a whole better. The problem, again, arises when top management don't fully appreciate or understand the reasoning behind this stuff. They end up making cuts to US labor because it's \"\"unprofitable\"\" without thinking about the entire story. I know this is very long winded but hope it helps! ***tldr; companies FTP to recognizes profitability and opportunity costs of divisions as well as use it for overseas tax breaks.*** Side note: Politically speaking, people who know how this works are pissed off about it in the U.S. (don't worry though, most politicians on both sides don't have a clue). We have high corporate tax rates relative to other countries and IRS loopholes allow this kind of thing (lobbying $$). It's also why, economically, you can't just raise ***corporate*** tax rates to increase domestic tax reciepts as more companies will just implement this process (it's complicated to do properly). Also, please don't say 50 years ago tax rates were higher and raising taxes increased receipts. The fact is most companies couldn't even FATHOM doing this 50 years ago, no less even 20. edit: some clarification in wording\"",
"title": ""
},
{
"docid": "133235",
"text": "\"Do I understand correctly, that we still can file as \"\"Married filing jointly\"\", just add Schedule C and Schedule SE for her? Yes. Business registration information letter she got once registered mentions that her due date for filing tax return is January 31, 2016. Does this prevent us from filing jointly (as far as I understand, I can't file my income before that date)? IRS sends no such letters. IRS also doesn't require any registration. Be careful, you might be a victim to a phishing attack here. In any case, sole proprietor files a regular individual tax return with the regular April 15th deadline. Do I understand correctly that we do not qualify as \"\"Family partnership\"\" (I do not participate in her business in any way other than giving her money for initial tools/materials purchase)? Yes. Do I understand correctly that she did not have to do regular estimated tax payments as business was not expected to generate income this year? You're asking or saying? How would we know what she expected? In any case, you can use your withholding (adjust the W4) to compensate.\"",
"title": ""
},
{
"docid": "166977",
"text": "If you sell through an intermediate who sets up the shop for you, odds are they collect and pay the sales tax for you. My experience is with publishing books through Amazon, where they definitely handle this for you. If you can find a retailer that will handle the tax implications, that might be a good reason to use them. It looks like Etsy uses a different model where you yourself are responsible for the sales tax, which requires you to register with your state (looks like this is the information for New York) and pay the taxes yourself on a regular basis; see this link for a simple guide. If you're doing this, you'll need to keep track of how much tax you owe from your sales each month, quarter, or year (depending on the state laws). You can usually be a sole proprietor, which is the easiest business structure to set up; if you want to limit your legal liability, or work with a partner, you may want to look into other forms of business structure, but for most craftspeople a sole proprietorship is fine to start out with. If you do a sole proprietorship, you can probably file the income on a 1040 Schedule C when you do your personal taxes each year.",
"title": ""
},
{
"docid": "440370",
"text": "The essential difference b/n ADR and a common share is that ADR do not have Voting rights. Common share has. There are some ADR that would in certain conditions get converted to common stock, but by and large most ADR's would remain ADR's without any voting rights. If you are an individual investor, this difference should not matter as rarely one would hold such a large number of shares to vote on General meeting on various issues. The other difference is that since many countries have regulations on who can buy common shares, for example in India an Non Resident cannot directly buy any share, hence he would buy ADR. Thus ADR would be priced more in the respective market if there is demand. For example Infosys Technologies, an India Company has ADR on NYSE. This is more expensive around 1.5 times the price of the common share available in India (at current exchange rate). Thus if you are able to invest with equal ease in HK (have broker / trading account etc), consider the taxation of the gains in HK as well the tax treatment in US for overseas gains then its recommended that you go for Common Stock in HK. Else it would make sense to buy in US.",
"title": ""
},
{
"docid": "271568",
"text": "\"From your explanation the Sole Trader option is more appropriate and certainly easier to manage. There are many differences but the pertinent and most important ones are as follows. The main difference in your case would be tax and administration. As a sole trader you would need to do a tax return once a year and if you earned less than £11.5k you wouldn't have to pay any UK tax, assuming you have no other income and are a \"\"standard\"\" tax payer. The current tax allowance is £11.5k although this can change. Submitting your own tax return is relatively straighforward although you may want to consult an accountant. It is generally easier to run as sole trader versus a Limited Company, ie less paperwork and beaureaucracy. If you go down the Limited Company route, the company would be liable to pay Corporation Tax on any profits and this process is more complicated and you would probably need an accountant to do that for you, which is likely to cost a few hundred pounds every year. You can do it yourself but the process is not as simple as doing your own income tax return. Also as a sole trader you can do what you like with any income, you can spend it and treat it as your own wages. You can't do that if you set up a Limited Company as the income is \"\"owned\"\" by the company and so you would need to in effect pay yourself a wage from the company. In other words it's more complex than if you are a sole trader. The main advantage to a Limited Company is that it is easier to sell the business if you want to at a later date. There is nothing stopping you setting up a Limited Company later on, after beign a sole trader if you want to. They can also be more tax-efficient but this would not be relevant to your case if you are earning relatively small sums, if your income increases then you may want to reconsider. You can see more information here: https://www.duport.co.uk/company-formation/sole-trader-vs-limited-company.php (I have been both a sole trader and also set up my own Limited Company)\"",
"title": ""
},
{
"docid": "530119",
"text": "I'm no tax expert by any means. I do know that a disreagarded entity is considered a sole proprietor for federal tax purposes. My understanding is that this means your personal tax year and your business tax year must be one and the same. Nevertheless, it is technically possible to have a non-calendar fiscal year as an individual. This is so rare that I'm unable to find a an IRS reference to this. The best reference I could find was this article written by two CPAs. If you really want to persue this, you basically need to talk with an accountant, since this is complicated, and required keeping propper accounting records for your personal life, in addition to your business. A ledger creqated after-the-fact by an accountant has been ruled insufficent. You really need to live by the fiscal year you choose.",
"title": ""
},
{
"docid": "486744",
"text": "This is a scam. Do you know why Bank of America is doing a refund? Did you own any accounts? Why is India involved in this? If Bank of America in US wants to transfer money to you in US, India is not involved at all. Stop all communications with the scammer and don't transfer any money.",
"title": ""
},
{
"docid": "508754",
"text": "\"I have checked with Bank of America, and they say the ONLY way to cash (or deposit, or otherwise get access to the funds represented by a check made out to my business) is to open a business account. They tell me this is a Federal regulation, and every bank will say the same thing. To do this, I need a state-issued \"\"dba\"\" certificate (from the county clerk's office) as well as an Employer ID Number (EIN) issued by the IRS. AND their CHEAPEST business banking account costs $15 / month. I think I can go to the bank that the check is drawn upon, and they will cash it, assuming I have documentation showing that I am the sole proprietor. But I'm not sure.... What a racket!!\"",
"title": ""
},
{
"docid": "355897",
"text": "\"First, point: The CRA wants you to start a business with a \"\"Reasonable expectation of profit\"\". They typically expect to see a profit within 5 years, so you may be inviting unwanted questions from future auditors by using a breakeven strategy. Second point: If the goal is to pay as little tax as possible, you may want to consider having the corporation pay you as little as possible. Corporate income taxes are much lower than personal income taxes, according to these two CRA links: How it works is that your company pays you little as an outright salary and offers you perks like a leased company car, expense account for lunch and entertainment, a mobile phone, computer, etc. The company owns all of this stuff and lets you use it as part of the job. The company pays for all this stuff with corporate pre-tax dollars as opposed to you paying for it with personal after-tax dollars. There are specifics on meals & entertainment which modify this slightly (you can claim 50%) but you get the idea. The actual rate difference will depend on your province of residence and your corporate income level. There is also a requirement for \"\"Reasonable Expenses\"\", such that the expenses have to be in line with what you are doing. If you need to travel to a conference each year, that would be a reasonable expense. Adding your family and making it a vacation for everyone would not. You can claim such expenses as a sole proprietor or a corporation. The sole-proprietorship option puts any after-expense profits into your pocket as taxable income, where the corporate structure allows the corporation to hold funds and limit the amount paid out to you. I've seen this strategy successfully done first-hand, but have not done it myself. I am not a lawyer or accountant, consult these professionals about this tax strategy before taking any action.\"",
"title": ""
}
] |
1068
|
ScPif1p has reduced binding ability to G-rich ssDNA compared to non-G-rich ssDNA.
|
[
{
"docid": "4429668",
"text": "The Saccharomyces cerevisiae Pif1 helicase is the prototypical member of the Pif1 DNA helicase family, which is conserved from bacteria to humans. Here we show that exceptionally potent G-quadruplex unwinding is conserved among Pif1 helicases. Moreover, Pif1 helicases from organisms separated by more than 3 billion years of evolution suppressed DNA damage at G-quadruplex motifs in yeast. The G-quadruplex-induced damage generated in the absence of Pif1 helicases led to new genetic and epigenetic changes. Furthermore, when expressed in yeast, human PIF1 suppressed both G-quadruplex-associated DNA damage and telomere lengthening.",
"title": "Pif1 family helicases suppress genome instability at G-quadruplex motifs"
}
] |
[
{
"docid": "16217855",
"text": "The product of the gene mutated in Bloom's syndrome, BLM, is a 3′–5′ DNA helicase belonging to the highly conserved RecQ family. In addition to a conventional DNA strand separation activity, BLM catalyzes both the disruption of non-B-form DNA, such as G-quadruplexes, and the branch migration of Holliday junctions. Here, we have characterized a new activity for BLM: the promotion of single-stranded DNA (ssDNA) annealing. This activity does not require Mg2+, is inhibited by ssDNA binding proteins and ATP, and is dependent on DNA length. Through analysis of various truncation mutants of BLM, we show that the C-terminal domain is essential for strand annealing and identify a 60 amino acid stretch of this domain as being important for both ssDNA binding and strand annealing. We present a model in which the ssDNA annealing activity of BLM facilitates its role in the processing of DNA intermediates that arise during repair of damaged replication forks.",
"title": "The Bloom's syndrome helicase promotes the annealing of complementary single-stranded DNA"
},
{
"docid": "15659108",
"text": "Rad52 promotes the annealing of complementary strands of DNA bound by replication protein A (RPA) during discrete repair pathways. Here, we used a fluorescence resonance energy transfer (FRET) between two fluorescent dyes incorporated into DNA substrates to probe the mechanism by which human Rad52 (hRad52) interacts with and mediates annealing of ssDNA-hRPA complexes. Human Rad52 bound ssDNA or ssDNA-hRPA complex in two, concentration-dependent modes. At low hRad52 concentrations, ssDNA was wrapped around the circumference of the protein ring, while at higher protein concentrations, ssDNA was stretched between multiple hRad52 rings. Annealing by hRad52 occurred most efficiently when each complementary DNA strand or each ssDNA-hRPA complex was bound by hRad52 in a wrapped configuration, suggesting homology search and annealing occur via two hRad52-ssDNA complexes. In contrast to the wild type protein, hRad52(RQK/AAA) and hRad52(1-212) mutants with impaired ability to bind hRPA protein competed with hRPA for binding to ssDNA and failed to counteract hRPA-mediated duplex destabilization highlighting the importance of hRad52-hRPA interactions in promoting efficient DNA annealing.",
"title": "Human Rad52 binds and wraps single-stranded DNA and mediates annealing via two hRad52–ssDNA complexes"
},
{
"docid": "799586",
"text": "Bacteria encode a single-stranded DNA (ssDNA) binding protein (SSB) crucial for genome maintenance. In Bacillus subtilis and Streptococcus pneumoniae, an alternative SSB, SsbB, is expressed uniquely during competence for genetic transformation, but its precise role has been disappointingly obscure. Here, we report our investigations involving comparison of a null mutant (ssbB(-)) and a C-ter truncation (ssbBΔ7) of SsbB of S. pneumoniae, the latter constructed because SSBs' acidic tail has emerged as a key site for interactions with partner proteins. We provide evidence that SsbB directly protects internalized ssDNA. We show that SsbB is highly abundant, potentially allowing the binding of ~1.15 Mb ssDNA (half a genome equivalent); that it participates in the processing of ssDNA into recombinants; and that, at high DNA concentration, it is of crucial importance for chromosomal transformation whilst antagonizing plasmid transformation. While the latter observation explains a long-standing observation that plasmid transformation is very inefficient in S. pneumoniae (compared to chromosomal transformation), the former supports our previous suggestion that SsbB creates a reservoir of ssDNA, allowing successive recombination cycles. SsbBΔ7 fulfils the reservoir function, suggesting that SsbB C-ter is not necessary for processing protein(s) to access stored ssDNA. We propose that the evolutionary raison d'être of SsbB and its abundance is maintenance of this reservoir, which contributes to the genetic plasticity of S. pneumoniae by increasing the likelihood of multiple transformation events in the same cell.",
"title": "Role of the Single-Stranded DNA–Binding Protein SsbB in Pneumococcal Transformation: Maintenance of a Reservoir for Genetic Plasticity"
},
{
"docid": "6386930",
"text": "Four-stranded nucleic acid structures called G-quadruplexes have been associated with important cellular processes, which should require G-quadruplex-protein interaction. However, the structural basis for specific G-quadruplex recognition by proteins has not been understood. The DEAH (Asp-Glu-Ala-His) box RNA helicase associated with AU-rich element (RHAU) (also named DHX36 or G4R1) specifically binds to and resolves parallel-stranded G-quadruplexes. Here we identified an 18-amino acid G-quadruplex-binding domain of RHAU and determined the structure of this peptide bound to a parallel DNA G-quadruplex. Our structure explains how RHAU specifically recognizes parallel G-quadruplexes. The peptide covers a terminal guanine base tetrad (G-tetrad), and clamps the G-quadruplex using three-anchor-point electrostatic interactions between three positively charged amino acids and negatively charged phosphate groups. This binding mode is strikingly similar to that of most ligands selected for specific G-quadruplex targeting. Binding to an exposed G-tetrad represents a simple and efficient way to specifically target G-quadruplex structures.",
"title": "Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide-quadruplex complex."
},
{
"docid": "15305881",
"text": "Deinococcus spp. are renowned for their amazing ability to recover rapidly from severe genomic fragmentation as a result of exposure to extreme levels of ionizing radiation or desiccation. Despite having been originally characterized over 50 years ago, the mechanism underlying this remarkable repair process is still poorly understood. Here, we report the 2.8 A structure of DdrB, a single-stranded DNA (ssDNA) binding protein unique to Deinococcus spp. that is crucial for recovery following DNA damage. DdrB forms a pentameric ring capable of binding single-stranded but not double-stranded DNA. Unexpectedly, the crystal structure reveals that DdrB comprises a novel fold that is structurally and topologically distinct from all other single-stranded binding (SSB) proteins characterized to date. The need for a unique ssDNA binding function in response to severe damage, suggests a distinct role for DdrB which may encompass not only standard SSB protein function in protection of ssDNA, but also more specialized roles in protein recruitment or DNA architecture maintenance. Possible mechanisms of DdrB action in damage recovery are discussed.",
"title": "The structure of DdrB from Deinococcus: a new fold for single-stranded DNA binding proteins"
},
{
"docid": "2758012",
"text": "Based on its in vitro unwinding activity on G-quadruplex (G4) DNA, the Bloom syndrome-associated helicase BLM is proposed to participate in telomere replication by aiding fork progression through G-rich telomeric DNA. Single molecule analysis of replicated DNA (SMARD) was used to determine the contribution of BLM helicase to telomere replication. In BLM-deficient cells, replication forks initiating from origins within the telomere, which copy the G-rich strand by leading strand synthesis, moved slower through the telomere compared with the adjacent subtelomere. Fork progression through the telomere was further slowed in the presence of a G4 stabilizer. Using a G4-specific antibody, we found that deficiency of BLM, or another G4-unwinding helicase, the Werner syndrome-associated helicase WRN, resulted in increased G4 structures in cells. Importantly, deficiency of either helicase led to greater increases in G4 DNA detected in the telomere compared with G4 seen genome-wide. Collectively, our findings are consistent with BLM helicase facilitating telomere replication by resolving G4 structures formed during copying of the G-rich strand by leading strand synthesis.",
"title": "BLM helicase facilitates telomere replication during leading strand synthesis of telomeres"
},
{
"docid": "29098525",
"text": "PriB is a primosomal protein required for re-initiation of replication in bacteria. We characterized and compared the DNA-binding properties of PriB from Salmonella enterica serovar Typhimurium LT2 (StPriB) and Escherichia coli (EcPriB). Only one residue of EcPriB, V6, was different in StPriB (replaced by A6). Previous structural information revealed that this residue is located on the putative dimer-dimer interface of PriB and is not involved in single-stranded DNA (ssDNA) binding. The cooperative binding mechanism of StPriB to DNA is, however, very different from that of EcPriB. Unlike EcPriB, which forms a single complex with ssDNAs of various lengths, StPriB forms two or more distinct complexes. Based on these results, as well as information on structure, binding modes for forming a stable complex of PriB with ssDNA of 25 nucleotides (nt), (EcPriB)25, and (StPriB)25 are proposed.",
"title": "A single residue determines the cooperative binding property of a primosomal DNA replication protein, PriB, to single-stranded DNA."
},
{
"docid": "10486817",
"text": "BACKGROUND Cellular nucleic acid binding protein (CNBP) has been implicated in vertebrate craniofacial development and in myotonic dystrophy type 2 (DM2) and sporadic inclusion body myositis (sIBM) human diseases by controlling cell proliferation and survival to mediate neural crest expansion. CNBP has been found to bind single-stranded nucleic acid and promote rearrangements of nucleic acid secondary structure in an ATP-independent manner, acting as a nucleic acid chaperone. METHODS A variety of methods were used, including cell viability assays, wound-scratch assays, chemotaxis assays, invasion assays, circular dichroic (CD) spectroscopy, NMR spectroscopy, chromatin immunoprecipitation, expression and purification of recombinant human CNBP, electrophoretic mobility shift assay (EMSA), surface plasmon resonance (SPR), fluorescence resonance energy transfer (FRET) analyses, luciferase reporter assay, Western blotting, and isothermal titration calorimetry (ITC). RESULTS Up-regulation of CNBP induced human fibrosarcoma cell death and suppressed fibrosarcoma cell motility and invasiveness. It was found that CNBP transcriptionally down-regulated the expression of heterogeneous ribonucleoprotein K (hnRNP K) through its conversion of a G-rich sequence into G-quadruplex in the promoter of hnRNP K. G-quadruplex stabilizing ligand tetra-(N-methyl-4-pyridyl) porphyrin (TMPyP4) could interact with and stabilize the G-quadruplex, resulting in downregulation of hnRNP K transcription. CONCLUSIONS CNBP overexpression caused increase of cell death and suppression of cell metastasis through its induction of G-quadruplex formation in the promoter of hnRNP K resulting in hnRNP K down-regulation. GENERAL SIGNIFICANCE The present result provided a new solution for controlling hnRNP K expression, which should shed light on new anticancer drug design and development.",
"title": "Cellular nucleic acid binding protein suppresses tumor cell metastasis and induces tumor cell death by downregulating heterogeneous ribonucleoprotein K in fibrosarcoma cells."
},
{
"docid": "16472469",
"text": "G-quadruplex (G4)-forming genomic sequences, including telomeres, represent natural replication fork barriers. Stalled replication forks can be stabilized and restarted by homologous recombination (HR), which also repairs DNA double-strand breaks (DSBs) arising at collapsed forks. We have previously shown that HR facilitates telomere replication. Here, we demonstrate that the replication efficiency of guanine-rich (G-rich) telomeric repeats is decreased significantly in cells lacking HR. Treatment with the G4-stabilizing compound pyridostatin (PDS) increases telomere fragility in BRCA2-deficient cells, suggesting that G4 formation drives telomere instability. Remarkably, PDS reduces proliferation of HR-defective cells by inducing DSB accumulation, checkpoint activation, and deregulated G2/M progression and by enhancing the replication defect intrinsic to HR deficiency. PDS toxicity extends to HR-defective cells that have acquired olaparib resistance through loss of 53BP1 or REV7. Altogether, these results highlight the therapeutic potential of G4-stabilizing drugs to selectively eliminate HR-compromised cells and tumors, including those resistant to PARP inhibition.",
"title": "Targeting BRCA1 and BRCA2 Deficiencies with G-Quadruplex-Interacting Compounds"
},
{
"docid": "17897801",
"text": "BACKGROUND Abciximab plus aspirin improves the TIMI 3 flow rate of the infarct-related artery in patients treated with either percutaneous coronary intervention or thrombolysis. The present study investigated whether the reperfusion efficacy of abciximab relates to modifications of clot architecture in patients admitted for acute myocardial infarction (AMI). METHODS AND RESULTS A total of 23 AMI patients in the Abciximab before Direct angioplasty and stenting in Myocardial Infarction Regarding Acute and Long term follow-up (ADMIRAL) trial received, in a double-blind fashion, either abciximab (n=13) or placebo (n=10) before primary stenting. Viscoelastic (G' in dyne/cm(2)) and morphological (mean platelet aggregate surface area [SAG] in micrometer(2)) indexes of ex vivo platelet-rich clots (PRC) were assessed in a double-blind fashion before and after the bolus administration of abciximab or placebo. G' and SAG reflect the mechanical and morphological impact of activated platelets on the PRC fibrin network, respectively. Abciximab administration reduced G' by 63% (P=0.0001) and SAG by 65% (P=0.0007), and no effect was seen in the placebo group. These abciximab-related changes increased fibrin exposure as a consequence of the platelet-aggregate surface reduction and may have improved endogenous fibrinolysis. These effects were identified in all patients, independent of previous heparin administration. CONCLUSIONS Abciximab dramatically reduces platelet aggregate size and increases the fibrin accessibility of ex vivo PRC in AMI patients. These modifications could participate in the better coronary artery patency observed with abciximab.",
"title": "Effects of Abciximab on the architecture of platelet-rich clots in patients with acute myocardial infarction undergoing primary coronary intervention."
},
{
"docid": "1914588",
"text": "Single-stranded DNA-binding protein (SSB) plays an important role in DNA metabolism, such as in DNA replication, repair, and recombination, and is essential for cell survival. We characterized the single-stranded DNA (ssDNA)-binding properties of Pseudomonas aeruginosa PAO1 SSB (PaSSB) by using fluorescence quenching measurements and electrophoretic mobility shift analysis (EMSA). Analysis of purified PaSSB by gel filtration chromatography revealed a stable tetramer in solution. In fluorescence titrations, PaSSB bound 22-32 nucleotides (nt) per tetramer depending on salt concentration. Using EMSA, we characterized the stoichiometry of PaSSB complexed with a series of ssDNA homopolymers, and the size of the binding site was determined to be 29 ± 1 nt. Furthermore, EMSA results indicated that the dissociation constants of PaSSB for the first tetramer were less than those for the second tetramer. On the basis of these biophysical analyses, the ssDNA binding mode of PaSSB is expected to be noncooperative.",
"title": "Characterization of a single-stranded DNA-binding protein from Pseudomonas aeruginosa PAO1."
},
{
"docid": "12207340",
"text": "The repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) is initiated by nucleolytic degradation of the 5'-terminated strands in a process termed end resection. End resection generates 3'-single-stranded DNA tails, substrates for Rad51 to catalyze homologous pairing and DNA strand exchange, and for activation of the DNA damage checkpoint. The commonly accepted view is that end resection occurs by a two-step mechanism. In the first step, Sae2/CtIP activates the Mre11-Rad50-Xrs2/Nbs1 (MRX/N) complex to endonucleolytically cleave the 5'-terminated DNA strands close to break ends, and in the second step Exo1 and/or Dna2 nucleases extend the resected tracts to produce long 3'-ssDNA-tailed intermediates. Initiation of resection commits a cell to repair a DSB by HR because long ssDNA overhangs are poor substrates for non-homologous end joining (NHEJ). Thus, the initiation of end resection has emerged as a critical control point for repair pathway choice. Here, I review recent studies on the mechanism of end resection and how this process is regulated to ensure the most appropriate repair outcome.",
"title": "Mechanism and regulation of DNA end resection in eukaryotes."
},
{
"docid": "8698857",
"text": "TNF expression of macrophages is under stringent translational control that depends on the p38 MAPK/MK2 pathway and the AU-rich element (ARE) in the TNF mRNA. Here, we elucidate the molecular mechanism of phosphorylation-regulated translation of TNF. We demonstrate that translation of the TNF-precursor at the ER requires expression of the ARE-binding and -stabilizing factor human antigen R (HuR) together with either activity of the p38 MAPK/MK2 pathway or the absence of the ARE-binding and -destabilizing factor tristetraprolin (TTP). We show that phosphorylation of TTP by MK2 decreases its affinity to the ARE, inhibits its ability to replace HuR, and permits HuR-mediated initiation of translation of TNF mRNA. Since translation of TTP's own mRNA is also regulated by this mechanism, an intrinsic feedback control of the inflammatory response is ensured. The phosphorylation-regulated TTP/HuR exchange at target mRNAs provides a reversible switch between unstable/non-translatable and stable/efficiently translated mRNAs.",
"title": "The p38/MK2-Driven Exchange between Tristetraprolin and HuR Regulates AU–Rich Element–Dependent Translation"
},
{
"docid": "20083834",
"text": "Background/Objective:To investigate the effect of soy protein containing isoflavones on homocysteine (Hcy), C-reactive protein (CRP), soluble E-selectin (sE-selectin), soluble vascular adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1).Subject/Methods:In a randomized crossover design, 34 postmenopausal women consumed soy protein isolate (26±5 g protein containing 44±8 mg isoflavones per day) or milk protein isolate (26±5 g protein per day) for 6 weeks each. Fasting blood samples were collected at the end of each diet period and end points analyzed by enzyme-linked immunosorbent assay. Results:Concentrations of Hcy, CRP, sE-selectin, sVCAM-1 and sICAM-1 were not different between soy and milk diet treatments. Results did not differ by equol production status or by baseline lipid concentration. Adjustment for intake of folate and methionine did not alter the Hcy results. Conclusions:These data suggest that decreasing vascular inflammation and Hcy concentration are not likely mechanisms by which soy consumption reduces coronary heart disease risk.",
"title": "Consumption of isoflavone-rich soy protein does not alter homocysteine or markers of inflammation in postmenopausal women"
},
{
"docid": "13931771",
"text": "Various specialized domains have been described in the cytosol and the nucleus; however, little is known about compartmentalization within the mitochondrial matrix. GRSF1 (G-rich sequence factor 1) is an RNA binding protein that was previously reported to localize in the cytosol. We found that an isoform of GRSF1 accumulates in discrete foci in the mitochondrial matrix. These foci are composed of nascent mitochondrial RNA and also contain RNase P, an enzyme that participates in mitochondrial RNA processing. GRSF1 was found to interact with RNase P and to be required for processing of both classical and tRNA-less RNA precursors. In its absence, cleavage of primary RNA transcripts is abnormal, leading to decreased expression of mitochondrially encoded proteins and mitochondrial dysfunction. Our findings suggest that the foci containing GRSF1 and RNase P correspond to sites where primary RNA transcripts converge to be processed. We have termed these large ribonucleoprotein structures \"mitochondrial RNA granules. \"",
"title": "GRSF1 Regulates RNA Processing in Mitochondrial RNA Granules"
},
{
"docid": "20943272",
"text": "ADAM13 is a member of the disintegrin and metalloprotease protein family that is expressed on cranial neural crest cells surface and is essential for their migration. ADAM13 is an active protease that can cleave fibronectin in vitro and remodel a fibronectin substrate in vivo. Using a recombinant secreted protein containing both disintegrin and cysteine-rich domains of ADAM13, we show that this \"adhesive\" region of the protein binds directly to fibronectin. Fibronectin fusion proteins corresponding to the various functional domains were used to define the second heparin-binding domain as the ADAM13 binding site. Mutation of the syndecan-binding site (PPRR --> PPTM) within this domain abolishes binding of the recombinant disintegrin and cysteine-rich domains of ADAM13. We further show that the adhesive disintegrin and cysteine-rich domain of ADAM13 can promote cell adhesion via beta(1) integrins. This adhesion requires integrin activation and can be prevented by antibodies to the cysteine-rich domain of ADAM13 and beta(1) integrin. Finally, wild type, but not the E/A mutant of ADAM13 metalloprotease domain, can be shed from the cell surface, releasing the metalloprotease domain associated with the disintegrin and cysteine-rich domains. This suggests that ADAM13 shedding may involve its own metalloprotease activity and that the released protease may interact with both integrins and extracellular matrix proteins.",
"title": "ADAM13 disintegrin and cysteine-rich domains bind to the second heparin-binding domain of fibronectin."
},
{
"docid": "4422868",
"text": "Intestinal cancer is initiated by Wnt-pathway-activating mutations in genes such as adenomatous polyposis coli (APC). As in most cancers, the cell of origin has remained elusive. In a previously established Lgr5 (leucine-rich-repeat containing G-protein-coupled receptor 5) knockin mouse model, a tamoxifen-inducible Cre recombinase is expressed in long-lived intestinal stem cells. Here we show that deletion of Apc in these stem cells leads to their transformation within days. Transformed stem cells remain located at crypt bottoms, while fuelling a growing microadenoma. These microadenomas show unimpeded growth and develop into macroscopic adenomas within 3-5weeks. The distribution of Lgr5+ cells within stem-cell-derived adenomas indicates that a stem cell/progenitor cell hierarchy is maintained in early neoplastic lesions. When Apc is deleted in short-lived transit-amplifying cells using a different cre mouse, the growth of the induced microadenomas rapidly stalls. Even after 30weeks, large adenomas are very rare in these mice. We conclude that stem-cell-specific loss of Apc results in progressively growing neoplasia.",
"title": "Crypt stem cells as the cells-of-origin of intestinal cancer"
},
{
"docid": "4442799",
"text": "BACKGROUND Soy protein or its components may protect against the atherosclerotic cardiovascular disease (CVD) risk factors total homocysteine (tHcy), C-reactive protein (CRP), and excess body iron, which generally increase with menopause. OBJECTIVE The primary objective of this study was to determine the independent effect of the soy protein components isoflavones and phytate on CVD risk factors in postmenopausal women. The secondary objective was to identify factors [blood lipids, oxidative stress indexes, serum ferritin, plasma folate, plasma vitamin B-12, and body mass index (BMI)] contributing to tHcy and CRP concentrations. DESIGN In a double-blind, 6-wk study, 55 postmenopausal women aged 47-72 y were randomly assigned to 1 of 4 soy protein (40 g/d) isolate treatments: native phytate and native isoflavone (n = 14), native phytate and low isoflavone (n = 13), low phytate and native isoflavone (n = 14), or low phytate and low isoflavone (n = 14). We measured iron indexes, tHcy, CRP, and BMI. RESULTS Soy protein with native phytate significantly reduced tHcy (P = 0.017), transferrin saturation (P = 0.027), and ferritin (P = 0.029), whereas soy protein with native isoflavones had no effect on any variables. At baseline, BMI was highly correlated with tHcy (r = 0.39, P = 0.003) and CRP (r = 0.55, P < 0.0001), whereas HDL cholesterol was correlated with CRP (r = -0.30, P = 0.02). Multiple regression analysis showed that LDL cholesterol and BMI contributed significantly (R2= 19.9%, P = 0.003) to the overall variance in tHcy. CONCLUSION Consuming phytate-rich foods and maintaining a healthy weight may reduce atherosclerotic CVD risk factors in postmenopausal women.",
"title": "Effects of soy isoflavones and phytate on homocysteine, C-reactive protein, and iron status in postmenopausal women."
},
{
"docid": "10874408",
"text": "DNA double-strand breaks (DSBs), which are formed by the Spo11 protein, initiate meiotic recombination. Previous DSB-mapping studies have used rad50S or sae2Δ mutants, which are defective in break processing, to accumulate Spo11-linked DSBs, and report large (≥ 50 kb) “DSB-hot” regions that are separated by “DSB-cold” domains of similar size. Substantial recombination occurs in some DSB-cold regions, suggesting that DSB patterns are not normal in rad50S or sae2Δ mutants. We therefore developed a novel method to map genome-wide, single-strand DNA (ssDNA)–associated DSBs that accumulate in processing-capable, repair-defective dmc1Δ and dmc1Δ rad51Δ mutants. DSBs were observed at known hot spots, but also in most previously identified “DSB-cold” regions, including near centromeres and telomeres. Although approximately 40% of the genome is DSB-cold in rad50S mutants, analysis of meiotic ssDNA from dmc1Δ shows that most of these regions have substantial DSB activity. Southern blot assays of DSBs in selected regions in dmc1Δ, rad50S, and wild-type cells confirm these findings. Thus, DSBs are distributed much more uniformly than was previously believed. Comparisons of DSB signals in dmc1, dmc1 rad51, and dmc1 spo11 mutant strains identify Dmc1 as a critical strand-exchange activity genome-wide, and confirm previous conclusions that Spo11-induced lesions initiate all meiotic recombination.",
"title": "Mapping Meiotic Single-Strand DNA Reveals a New Landscape of DNA Double-Strand Breaks in Saccharomyces cerevisiae"
},
{
"docid": "1583134",
"text": "Autoimmune polyglandular syndrome type I (APS 1, also called APECED) is an autosomal-recessive disorder that maps to human chromosome 21q22.3 between markers D21S49 and D21S171 by linkage studies. We have isolated a novel gene from this region, AIRE (autoimmune regulator), which encodes a protein containing motifs suggestive of a transcription factor including two zinc-finger (PHD-finger) motifs, a proline-rich region and three LXXLL motifs. Two mutations, a C→T substitution that changes the Arg 257 (CGA) to a stop codon (TGA) and an A→G substitution that changes the Lys 83 (AAG) to a Glu codon (GAG), were found in this novel gene in Swiss and Finnish APECED patients. The Arg257stop (R257X) is the predominant mutation in Finnish APECED patients, accounting for 10/12 alleles studied. These results indicate that this gene is responsible for the pathogenesis of APECED. The identification of the gene defective in APECED should facilitate the genetic diagnosis and potential treatment of the disease and further enhance our general understanding of the mechanisms underlying autoimmune diseases.",
"title": "Positional cloning of the APECED gene"
},
{
"docid": "11742219",
"text": "Galanin (GAL) is known to stimulate feeding behavior. This peptide has different properties and functions from other feeding stimulants, e.g., neuropeptide Y and agouti-related protein. Hypothalamic GAL is relatively unresponsive to food deprivation and to changes in corticosterone, glucose utilization, dietary carbohydrate and leptin. This indicates that this peptide is not essential under conditions when food is scarce or low-energy, high-carbohydrate diets are being consumed. In contrast, recent evidence suggests that GAL in the paraventricular nucleus (PVN) functions in close relation to dietary fat and alcohol. In particular, it mediates functions that allow animals to adapt to conditions of positive energy balance involving excess consumption of these nutrients. This peptide in the PVN is stimulated by a high-fat diet and also by alcohol. It is stimulated by an increase in circulating lipids caused by a fat-rich meal or alcohol consumption, and it rises during the middle of the active feeding cycle, when fat consumption and triglycerides naturally rise. When centrally injected, GAL in the PVN increases the consumption of food and alcohol. Moreover, it produces a significantly stronger feeding response in rats maintained on a fat-rich diet, which also promotes alcohol intake. This evidence supports the existence of non-homeostatic, positive feedback circuits between GAL and both dietary fat and alcohol. These circuits are believed to contribute to the large meal size, over-consumption of alcohol, and obesity which are generally associated with fat-rich foods.",
"title": "Regulation and effects of hypothalamic galanin: relation to dietary fat, alcohol ingestion, circulating lipids and energy homeostasis."
},
{
"docid": "188911",
"text": "Antigen-presenting, major histocompatibility complex (MHC) class II-rich dendritic cells are known to arise from bone marrow. However, marrow lacks mature dendritic cells, and substantial numbers of proliferating less-mature cells have yet to be identified. The methodology for inducing dendritic cell growth that was recently described for mouse blood now has been modified to MHC class II-negative precursors in marrow. A key step is to remove the majority of nonadherent, newly formed granulocytes by gentle washes during the first 2-4 d of culture. This leaves behind proliferating clusters that are loosely attached to a more firmly adherent \"stroma. \" At days 4-6 the clusters can be dislodged, isolated by 1-g sedimentation, and upon reculture, large numbers of dendritic cells are released. The latter are readily identified on the basis of their distinct cell shape, ultrastructure, and repertoire of antigens, as detected with a panel of monoclonal antibodies. The dendritic cells express high levels of MHC class II products and act as powerful accessory cells for initiating the mixed leukocyte reaction. Neither the clusters nor mature dendritic cells are generated if macrophage colony-stimulating factor rather than granulocyte/macrophage colony-stimulating factor (GM-CSF) is applied. Therefore, GM-CSF generates all three lineages of myeloid cells (granulocytes, macrophages, and dendritic cells). Since > 5 x 10(6) dendritic cells develop in 1 wk from precursors within the large hind limb bones of a single animal, marrow progenitors can act as a major source of dendritic cells. This feature should prove useful for future molecular and clinical studies of this otherwise trace cell type.",
"title": "Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor"
},
{
"docid": "15655418",
"text": "Long-term memory and synaptic plasticity are thought to require the synthesis of new proteins at activated synapses. The CPEB family of RNA binding proteins, including Drosophila Orb2, has been implicated in this process. The precise mechanism by which these molecules regulate memory formation is however poorly understood. We used gene targeting and site-specific transgenesis to specifically modify the endogenous orb2 gene in order to investigate its role in long-term memory formation. We show that the Orb2A and Orb2B isoforms, while both essential, have distinct functions in memory formation. These two isoforms have common glutamine-rich and RNA-binding domains, yet Orb2A uniquely requires the former and Orb2B the latter. We further show that Orb2A induces Orb2 complexes in a manner dependent upon both its glutamine-rich region and neuronal activity. We propose that Orb2B acts as a conventional CPEB to regulate transport and/or translation of specific mRNAs, whereas Orb2A acts in an unconventional manner to form stable Orb2 complexes that are essential for memory to persist.",
"title": "Drosophila CPEB Orb2A Mediates Memory Independent of Its RNA-Binding Domain"
},
{
"docid": "2014909",
"text": "Myeloid-derived suppressor cells (MDSCs) play critical roles in primary and metastatic cancer progression. MDSC regulation is widely variable even among patients harbouring the same type of malignancy, and the mechanisms governing such heterogeneity are largely unknown. Here, integrating human tumour genomics and syngeneic mammary tumour models, we demonstrate that mTOR signalling in cancer cells dictates a mammary tumour's ability to stimulate MDSC accumulation through regulating G-CSF. Inhibiting this pathway or its activators (for example, FGFR) impairs tumour progression, which is partially rescued by restoring MDSCs or G-CSF. Tumour-initiating cells (TICs) exhibit elevated G-CSF. MDSCs reciprocally increase TIC frequency through activating Notch in tumour cells, forming a feedforward loop. Analyses of primary breast cancers and patient-derived xenografts corroborate these mechanisms in patients. These findings establish a non-canonical oncogenic role of mTOR signalling in recruiting pro-tumorigenic MDSCs and show how defined cancer subsets may evolve to promote and depend on a distinct immune microenvironment.",
"title": "Oncogenic mTOR signaling recruits myeloid-derived suppressor cells to promote tumor initiation"
},
{
"docid": "12922760",
"text": "BACKGROUND G-quadruplexes (G4s) are stable non-canonical DNA secondary structures consisting of stacked arrays of four guanines, each held together by Hoogsteen hydrogen bonds. Sequences with the ability to form these structures in vitro, G4 motifs, are found throughout bacterial and eukaryotic genomes. The budding yeast Pif1 DNA helicase, as well as several bacterial Pif1 family helicases, unwind G4 structures robustly in vitro and suppress G4-induced DNA damage in S. cerevisiae in vivo. RESULTS We determined the genomic distribution and evolutionary conservation of G4 motifs in four fission yeast species and investigated the relationship between G4 motifs and Pfh1, the sole S. pombe Pif1 family helicase. Using chromatin immunoprecipitation combined with deep sequencing, we found that many G4 motifs in the S. pombe genome were associated with Pfh1. Cells depleted of Pfh1 had increased fork pausing and DNA damage near G4 motifs, as indicated by high DNA polymerase occupancy and phosphorylated histone H2A, respectively. In general, G4 motifs were underrepresented in genes. However, Pfh1-associated G4 motifs were located on the transcribed strand of highly transcribed genes significantly more often than expected, suggesting that Pfh1 has a function in replication or transcription at these sites. CONCLUSIONS In the absence of functional Pfh1, unresolved G4 structures cause fork pausing and DNA damage of the sort associated with human tumors.",
"title": "The essential Schizosaccharomyces pombe Pfh1 DNA helicase promotes fork movement past G-quadruplex motifs to prevent DNA damage"
},
{
"docid": "432261",
"text": "The generation of gene-edited animals using the CRISPRs/Cas9 system is based on microinjection into zygotes which is inefficient, time consuming and demands high technical skills. We report the optimization of an electroporation method for intact rat zygotes using sgRNAs and Cas9 protein in combination or not with ssODNs (~100 nt). This resulted in high frequency of knockouts, between 15 and 50% of analyzed animals. Importantly, using ssODNs as donor template resulted in precise knock-in mutations in 25-100% of analyzed animals, comparable to microinjection. Electroporation of long ssDNA or dsDNA donors successfully used in microinjection in the past did not allow generation of genome-edited animals despite dsDNA visualization within zygotes. Thus, simultaneous electroporation of a large number of intact rat zygotes is a rapid, simple, and efficient method for the generation of a variety of genome-edited rats.",
"title": "Generation of gene-edited rats by delivery of CRISPR/Cas9 protein and donor DNA into intact zygotes using electroporation"
},
{
"docid": "42314147",
"text": "Sp1-like proteins are characterized by three conserved C-terminal zinc finger motifs that bind GC-rich sequences found in promoters of numerous genes essential for mammalian cell homeostasis. These proteins behave as transcriptional activators or repressors. Although significant information has been reported on the molecular mechanisms by which Sp1-like activators function, relatively little is known about mechanisms for repressor proteins. Here we report the functional characterization of BTEB3, a ubiquitously expressed Sp1-like transcriptional repressor. GAL4 assays show that the N terminus of BTEB3 contains regions that can act as direct repressor domains. Immunoprecipitation assays reveal that BTEB3 interacts with the co-repressor mSin3A and the histone deacetylase protein HDAC-1. Gel shift assays demonstrate that BTEB3 specifically binds the BTE site, a well characterized GC-rich DNA element, with an affinity similar to that of Sp1. Reporter and gel shift assays in Chinese hamster ovary cells show that BTEB3 can also mediate repression by competing with Sp1 for BTE binding. Thus, the characterization of this protein expands the repertoire of BTEB-like members of the Sp1 family involved in transcriptional repression. Furthermore, our results suggest a mechanism of repression for BTEB3 involving direct repression by the N terminus via interaction with mSin3A and HDAC-1 and competition with Sp1 via the DNA-binding domain.",
"title": "The Sp1-like protein BTEB3 inhibits transcription via the basic transcription element box by interacting with mSin3A and HDAC-1 co-repressors and competing with Sp1."
},
{
"docid": "2904102",
"text": "RecQ family helicases function as safeguards of the genome. Unlike Escherichia coli, the Gram-positive Bacillus subtilis bacterium possesses two RecQ-like homologues, RecQ[Bs] and RecS, which are required for the repair of DNA double-strand breaks. RecQ[Bs] also binds to the forked DNA to ensure a smooth progression of the cell cycle. Here we present the first biochemical analysis of recombinant RecQ[Bs]. RecQ[Bs] binds weakly to single-stranded DNA (ssDNA) and blunt-ended double-stranded DNA (dsDNA) but strongly to forked dsDNA. The protein exhibits a DNA-stimulated ATPase activity and ATP- and Mg(2+)-dependent DNA helicase activity with a 3' → 5' polarity. Molecular modeling shows that RecQ[Bs] shares high sequence and structure similarity with E. coli RecQ. Surprisingly, RecQ[Bs] resembles the truncated Saccharomyces cerevisiae Sgs1 and human RecQ helicases more than RecQ[Ec] with regard to its enzymatic activities. Specifically, RecQ[Bs] unwinds forked dsDNA and DNA duplexes with a 3'-overhang but is inactive on blunt-ended dsDNA and 5'-overhung duplexes. Interestingly, RecQ[Bs] unwinds blunt-ended DNA with structural features, including nicks, gaps, 5'-flaps, Kappa joints, synthetic replication forks, and Holliday junctions. We discuss these findings in the context of RecQ[Bs]'s possible functions in preserving genomic stability.",
"title": "Characterization of biochemical properties of Bacillus subtilis RecQ helicase."
},
{
"docid": "2679511",
"text": "Werner's syndrome (WS) and Bloom's syndrome (BS) are cancer predisposition disorders caused by loss of function of the RecQ helicases WRN or BLM, respectively. BS and WS are characterized by replication defects, hyperrecombination events and chromosomal aberrations, which are hallmarks of cancer. Inefficient replication of the G-rich telomeric strand contributes to chromosome aberrations in WS cells, demonstrating a link between WRN, telomeres and genomic stability. Herein, we provide evidence that BLM also contributes to chromosome-end maintenance. Telomere defects (TDs) are observed in BLM-deficient cells at an elevated frequency, which is similar to cells lacking a functional WRN helicase. Loss of both helicases exacerbates TDs and chromosome aberrations, indicating that BLM and WRN function independently in telomere maintenance. BLM localization, particularly its recruitment to telomeres, changes in response to replication dysfunction, such as in WRN-deficient cells or after aphidicolin treatment. Exposure to replication challenge causes an increase in decatenated deoxyribonucleic acid (DNA) structures and late-replicating intermediates (LRIs), which are visible as BLM-covered ultra-fine bridges (UFBs) in anaphase. A subset of UFBs originates from telomeric DNA and their frequency correlates with telomere replication defects. We propose that the BLM complex contributes to telomere maintenance through its activity in resolving LRIs.",
"title": "The BLM helicase contributes to telomere maintenance through processing of late-replicating intermediate structures"
},
{
"docid": "11360768",
"text": "OBJECTIVE To evaluate the effects of dietary and lifestyle interventions in pregnancy on maternal and fetal weight and to quantify the effects of these interventions on obstetric outcomes. DESIGN Systematic review and meta-analysis. DATA SOURCES Major databases from inception to January 2012 without language restrictions. STUDY SELECTION Randomised controlled trials that evaluated any dietary or lifestyle interventions with potential to influence maternal weight during pregnancy and outcomes of pregnancy. DATA SYNTHESIS Results summarised as relative risks for dichotomous data and mean differences for continuous data. RESULTS We identified 44 relevant randomised controlled trials (7278 women) evaluating three categories of interventions: diet, physical activity, and a mixed approach. Overall, there was 1.42 kg reduction (95% confidence interval 0.95 to 1.89 kg) in gestational weight gain with any intervention compared with control. With all interventions combined, there were no significant differences in birth weight (mean difference -50 g, -100 to 0 g) and the incidence of large for gestational age (relative risk 0.85, 0.66 to 1.09) or small for gestational age (1.00, 0.78 to 1.28) babies between the groups, though by itself physical activity was associated with reduced birth weight (mean difference -60 g, -120 to -10 g). Interventions were associated with a reduced the risk of pre-eclampsia (0.74, 0.60 to 0.92) and shoulder dystocia (0.39, 0.22 to 0.70), with no significant effect on other critically important outcomes. Dietary intervention resulted in the largest reduction in maternal gestational weight gain (3.84 kg, 2.45 to 5.22 kg), with improved pregnancy outcomes compared with other interventions. The overall evidence rating was low to very low for important outcomes such as pre-eclampsia, gestational diabetes, gestational hypertension, and preterm delivery. CONCLUSIONS Dietary and lifestyle interventions in pregnancy can reduce maternal gestational weight gain and improve outcomes for both mother and baby. Among the interventions, those based on diet are the most effective and are associated with reductions in maternal gestational weight gain and improved obstetric outcomes.",
"title": "Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence"
}
] |
947
|
What are useful indexes for rapid evaluation of country investment risk?
|
[
{
"docid": "194682",
"text": "Rather than using the Human Development Index or Ease of Doing Business, if you primary purpose is for investments, you need to consider the Country rating provided by various agencies like These would tell as to how good the country is for investment in general. Just to highlight a difference, China may not fare very high in Human Development Index, however right now from investment point of view its a pretty good market. once you have decided the countries, you can either invest in funds specalizing in these countries or if legally permitted invest directly into the leading stock index in such countries. If your intention is to start a business in these countries, then you need to look at some other indexes. http://www.standardandpoors.com/ratings/articles/en/us/?assetID=1245219962821 http://www.fitchratings.com/jsp/sector/Sector.faces?selectedTab=Overview&Ne=4293330737%2b11&N=0 http://v3.moodys.com/Pages/default.aspx",
"title": ""
}
] |
[
{
"docid": "425586",
"text": "There is no typical return for an IRA. Understand that an IRA is not an investment type, it is just an account that gets special tax treatment by the Federal Government. The money in the IRA could be invested in almost anything including Gold, Stocks, Bonds, Cash, CDs, etc. So the question as phrased isn't exactly meaningful. It is kind of like asking what is the typical price of things if I use $10 bills. As for a 10.6% annualized return on your portfolio. That's not a bad return. At that rate you will double your investment (with compounding) every 7.2 years. Again, however, some context is needed. You can really only evaluate investment returns with your risk profile in mind. If you are invested in super safe investments like CDs, that is an absolutely incredible return. You compare it to several indexes, which is a good way to do it if you are investing in the types of investments tracked by those indexes.",
"title": ""
},
{
"docid": "469599",
"text": "The Investopedia article you linked to is a good start. Its key takeaway is that you should always consider risk-adjusted return when evaluating your portfolio. In general, investors seeking a higher level of return must face a higher likelihood of taking a loss (risk). Different types of stocks (large vs small; international vs US; different industry sectors) have different levels of historical risk and return. Not to mention stocks vs bonds or other financial instruments... So, it's key to make an apples-to-apples comparison against an appropriate benchmark. A benchmark will tell you how your portfolio is doing versus a comparable portfolio. An index, such as the S&P 500, is often used, because it tells you how your portfolio is doing compared against simply passively investing in a diversified basket of securities. First, I would start with analyzing your portfolio to understand its asset allocation. You can use a tool like the Morningstar X-Ray to do this. You may be happy with the asset allocation, or this tool may inform you to adjust your portfolio to meet your long-term goals. The next step will be to choose a benchmark. Given that you are investing primarily in non-US securities, you may want to pick a globally diversified index such as the Dow Jones Global Index. Depending on the region and stock characteristics you are investing in, you may want to pick a more specialized index, such as the ones listed here in this WSJ list. With your benchmark set, you can then see how your portfolio's returns compare to the index over time. IRR and ROI are helpful metrics in general, especially for corporate finance, but the comparison-based approach gives you a better picture of your portfolio's performance. You can still calculate your personal IRR, and make sure to include factors such as tax treatment and investment expenses that may not be fully reflected by just looking at benchmarks. Also, you can calculate the metrics listed in the Investopedia article, such as the Sharpe ratio, to give you another view on the risk-adjusted return.",
"title": ""
},
{
"docid": "98461",
"text": "There are some ETF's on the Indian market that invest in broad indexes in other countries Here's an article discussing this Be aware that such investments carry an additional risk you do not have when investing in your local market, which is 'currency risk' If for example you invest in a ETF that represents the US S&P500 index, and the US dollar weakens relative to the indian rupee, you could see the value if your investment in the US market go down, even if the index itself is 'up' (but not as much as the change in currency values). A lot of investment advisors recommend that you have at least 75% of your investments in things which are denominated in your local currency (well technically, the same currency as your liabilities), and no more than 25% invested internationally. In large part the reason for this advice is to reduce your exposure to currency risk.",
"title": ""
},
{
"docid": "135879",
"text": "If you are younger, and you not under undue pressure to buy a home at any particular time, investing in the market is a reasonable way to prepare. Your risk tolerance should be high. Understand that this means you may buy in 3-4 years instead of 1-2 if the market takes a down turn. It took ~3-4 years for the S&P 500 to recover from the 2008 crash. I doubt anything that severe is in the making, but there is always an element of risk involved in investing. If you and your family will be busting at the seams of your current rental in a year, then maybe the bond fund advice others have provided is a better option. If you are willing to be flexible, a more aggressive strategy might be appropriate. Likely, you want something along the lines of the Vanguard S&P 500 mutual fund - something that is diversified (a large number of stocks), in relatively safe companies (in this case the 500 companies that Standard and Poor's think are most likely to repay corporate bonds), and 'indexed' vice 'actively managed' (indexed funds have lower fees because they are using 'rules' to pick the stocks rather than paying a person to evaluate them.) It's going to depend on you and your situation - and regardless of what you choose consistency will be key: put your investment on automatic so it happens every month without your input.",
"title": ""
},
{
"docid": "59468",
"text": "First thing to know about investing is that you make money by taking risks. That means the possibility of losing money as well as making it. There are low risk investments that pretty much always pay out but they don't earn much. Making $200 a month on $10,000 is about 26% per year. That's vastly more than you are going to earn on low risk assets. If you want that kind of return, you can invest in a diversified portfolio of equities through an equity index fund. Some years you may make 26% or more. Other years you may make nothing or lose that much or more. On average you may earn maybe 7%-10% hopefully. Overall, investing is a game of making money over long horizons. It's very useful for putting away your $10k now and having hopefully more than that when it comes time to buy a house or retire or something some years into the future. You have to accept that you might also end up with less than $10K in the end, but you are more likely to make money than to use it. What you describe doesn't seem like a possible situation. In developed markets, you can't reliably expect anything close to the return you desire from assets that are unlikely to lose you money. It might be time to re-evaluate your financial goals. Do you want spending money now, or do you want to invest for use down the road?",
"title": ""
},
{
"docid": "231863",
"text": "\"The \"\"ideal world\"\" index fund of any asset class is a perfect percentage holding of all underlying assets with immediate rebalancing that aligns to every change in the index weighting while trading in a fully liquid market with zero transaction costs. One finance text book that describes this is Introduction to Finance: Markets, Investments, and Financial Management, see chapter 11. Practically, the transaction costs and liquidity make this unworkable. There are several deviations between what the \"\"ideal world algorithm\"\" (\"\"the algorithm\"\") says you should do and what is actually done. Each of these items addresses a real-world solution to various costs of managing a passive index fund. (And they are good solutions.) However, any deviation from the ideal index fund will have a risk. An investor evaluating their choices is left to pick the lowest fees with the least deviation from the ideal index fund. (It is customary to ignore whether the results are in excess or deficit to the ideal). So your formula is: This is also described in the above book.\"",
"title": ""
},
{
"docid": "146632",
"text": "\"Yes. There are several downsides to this strategy: You aren't taking into account commissions. If you pay $5 each time you buy or sell a stock, you may greatly reduce or even eliminate any possible gains you would make from trading such small amounts. This next point sounds obvious, but remember that you pay a commission on every trade regardless of profit, so every trade you make that you make at a loss also costs you commissions. Even if you make trades that are profitable more often than not, if you make quite a few trades with small amounts like this, your commissions may eat away all of your profits. Commissions represent a fixed cost, so their effect on your gains decreases proportionally with the amount of money you place at risk in each trade. Since you're in the US, you're required to follow the SEC rules on pattern day trading. From that link, \"\"FINRA rules define a “pattern day trader” as any customer who executes four or more “day trades” within five business days, provided that the number of day trades represents more than six percent of the customer’s total trades in the margin account for that same five business day period.\"\" If you trip this rule, you'll be required to maintain $25,000 in a margin brokerage account. If you can't maintain the balance, your account will be locked. Don't forget about capital gains taxes. Since you're holding these securities for less than a year, your gains will be taxed at your ordinary income tax rates. You can deduct your capital losses too (assuming you don't repurchase the same security within 30 days, because in that case, the wash sale rule prevents you from deducting the loss), but it's important to think about gains and losses in real terms, not nominal terms. The story is different if you make these trades in a tax-sheltered account like an IRA, but the other problems still apply. You're implicitly assuming that the stock's prices are skewed in the positive direction. Remember that you have limit orders placed at the upper and lower bounds of the range, so if the stock price decreases before it increases, your limit order at the lower bound will be triggered and you'll trade at a loss. If you're hoping to make a profit through buying low and selling high, you want a stock that hits its upper bound before hitting the lower bound the majority of the time. Unless you have data analysis (not just your intuition or a pattern you've talked yourself into from looking at a chart) to back this up, you're essentially gambling that more often than not, the stock price will increase before it decreases. It's dangerous to use any strategy that you haven't backtested extensively. Find several months or years of historical data, either intra-day or daily data, depending on the time frame you're using to trade, and simulate your strategy exactly. This helps you determine the potential profitability of your strategy, and it also forces you to decide on a plan for precisely when you want to invest. Do you invest as soon as the stock trades in a range (which algorithms can determine far better than intuition)? It also helps you figure out how to manage your risk and how much loss you're willing to accept. For risk management, using limit orders is a start, but see my point above about positively skewed prices. Limit orders aren't enough. In general, if an active investment strategy seems like a \"\"no-brainer\"\" or too good to be true, it's probably not viable. In general, as a retail investor, it's foolish to assume that no one else has thought of your simple active strategy to make easy money. I can promise you that someone has thought of it. Trading firms have quantitative researchers that are paid to think of and implement trading strategies all the time. If it's viable at any scale, they'll probably already have utilized it and arbitraged away the potential for small traders to make significant gains. Trust me, you're not the first person who thought of using limit orders to make \"\"easy money\"\" off volatile stocks. The fact that you're asking here and doing research before implementing this strategy, however, means that you're on the right track. It's always wise to research a strategy extensively before deploying it in the wild. To answer the question in your title, since it could be interpreted a little differently than the body of the question: No, there's nothing wrong with investing in volatile stocks, indexes, etc. I certainly do, and I'm sure many others on this site do as well. It's not the investing that gets you into trouble and costs you a lot of money; it's the rapid buying and selling and attempting to time the market that proves costly, which is what you're doing when you implicitly bet that the distribution of the stock's prices is positively skewed. To address the commission fee problem, assuming a fee of $8 per trade ... and a minimum of $100 profit per sale Commissions aren't your only problem, and counting on $100 profit per sale is a significant assumption. Look at point #4 above. Through your use of limit orders, you're making the implicit assumption that, more often than not, the price will trigger your upper limit order before your lower limit order. Here's a simple example; let's assume you have limit orders placed at +2 and -2 of your purchase price, and that triggering the limit order at +2 earns you $100 profit, while triggering the limit order at -2 incurs a loss of $100. Assume your commission is $5 on each trade. If your upper limit order is triggered, you earn a profit of 100 - 10 = 90, then set up the same set of limit orders again. If your lower limit order is triggered this time, you incur a loss of 100 + 10 = 110, so your net gain is 90 - 110 = -20. This is a perfect example of why, when taking into account transaction costs, even strategies that at first glance seem profitable mathematically can actually fail. If you set up the same situation again and incur a loss again (100 + 10 = 110), you're now down -20 - 110 = -130. To make a profit, you need to make two profitable trades, without incurring further losses. This is why point #4 is so important. Whenever you trade, it's critical to completely understand the risk you're taking and the bet you're actually making, not just the bet you think you're making. Also, according to my \"\"algorithm\"\" a sale only takes place once the stock rises by 1 or 2 points; otherwise the stock is held until it does. Does this mean you've removed the lower limit order? If yes, then you expose yourself to downside risk. What if the stock has traded within a range, then suddenly starts declining because of bad earnings reports or systemic risks (to name a few)? If you haven't removed the lower limit order, then point #4 still stands. However, I never specified that the trades have to be done within the same day. Let the investor open up 5 brokerage accounts at 5 different firms (for safeguarding against being labeled a \"\"Pattern Day Trader\"\"). Each account may only hold 1 security at any time, for the span of 1 business week. How do you control how long the security is held? You're using limit orders, which will be triggered when the stock price hits a certain level, regardless of when that happens. Maybe that will happen within a week, or maybe it will happen within the same day. Once again, the bet you're actually making is different from the bet you think you're making. Can you provide some algorithms or methods that do work for generating some extra cash on the side, aside from purchasing S&P 500 type index funds and waiting? When I purchase index funds, it's not to generate extra liquid cash on the side. I don't invest nearly enough to be able to purchase an index fund and earn substantial dividends. I don't want to get into any specific strategies because I'm not in the business of making investment recommendations, and I don't want to start. Furthermore, I don't think explicit investment recommendations are welcome here (unless it's describing why something is a bad idea), and I agree with that policy. I will make a couple of points, however. Understand your goals. Are you investing for retirement or a shorter horizon, e.g. some side income? You seem to know this already, but I include it for future readers. If a strategy seems too good to be true, it probably is. Educate yourself before designing a strategy. Research fundamental analysis, different types of orders (e.g., so you fully understand that you don't have control over when limit orders are executed), different sectors of the market if that's where your interests lie, etc. Personally, I find some sectors fascinating, so researching them thoroughly allows me to make informed investment decisions as well as learn about something that interests me. Understand your limits. How much money are you willing to risk and possibly lose? Do you have a risk management strategy in place to prevent unexpected losses? What are the costs of the risk management itself? Backtest, backtest, backtest. Ideally your backtesting and simulating should be identical to actual market conditions and incorporate all transaction costs and a wide range of historical data. Get other opinions. Evaluate those opinions with the same critical eye as I and others have evaluated your proposed strategy.\"",
"title": ""
},
{
"docid": "188497",
"text": "The idea of an index is that it is representative of the market (or a specific market segment) as a whole, so it will move as the market does. Thus, past performance is not really relevant, unless you want to bank on relative differences between different countries' economies. But that's not the point. By far the most important aspect when choosing index funds is the ongoing cost, usually expressed as Total Expense Ratio (TER), which tells you how much of your investment will be eaten up by trading fees and to pay the funds' operating costs (and profits). This is where index funds beat traditional actively managed funds - it should be below 0.5% The next question is how buying and selling the funds works and what costs it incurs. Do you have to open a dedicated account or can you use a brokerage account at your bank? Is there an account management fee? Do you have to buy the funds at a markup (can you get a discount on it)? Are there flat trading fees? Is there a minimum investment? What lot sizes are possible? Can you set up a monthly payment plan? Can you automatically reinvest dividends/coupons? Then of course you have to decide which index, i.e. which market you want to buy into. My answer in the other question apparently didn't make it clear, but I was talking only about stock indices. You should generally stick to broad, established indices like the MSCI World, S&P 500, Euro Stoxx, or in Australia the All Ordinaries. Among those, it makes some sense to just choose your home country's main index, because that eliminates currency risk and is also often cheaper. Alternatively, you might want to use the opportunity to diversify internationally so that if your country's economy tanks, you won't lose your job and see your investment take a dive. Finally, you should of course choose a well-established, reputable issuer. But this isn't really a business for startups (neither shady nor disruptively consumer-friendly) anyway.",
"title": ""
},
{
"docid": "477646",
"text": "\"Diversification is spreading your investments around so that one point of risk doesn't sink your whole portfolio. The effect of having a diversified portfolio is that you've always got something that's going up (though, the corollary is that you've also always got something going down... winning overall comes by picking investments worth investing in (not to state the obvious or anything :-) )) It's worth looking at the different types of risk you can mitigate with diversification: Company risk This is the risk that the company you bought actually sucks. For instance, you thought gold was going to go up, and so you bought a gold miner. Say there are only two -- ABC and XYZ. You buy XYZ. Then the CEO reveals their gold mine is played out, and the stock goes splat. You're wiped out. But gold does go up, and ABC does gangbusters, especially now they've got no competition. If you'd bought both XYZ and ABC, you would have diversified your company risk, and you would have been much better off. Say you invested $10K, $5K in each. XYZ goes to zero, and you lose that $5K. ABC goes up 120%, and is now worth $11K. So despite XYZ bankrupting, you're up 10% on your overall position. Sector risk You can categorize stocks by what \"\"sector\"\" they're in. We've already talked about one: gold miners. But there are many more, like utilities, bio-tech, transportation, banks, etc. Stocks in a sector will tend to move together, so you can be right about the company, but if the sector is out of favor, it's going to have a hard time going up. Lets extend the above example. What if you were wrong about gold going up? Then XYZ would still be bankrupt, and ABC would be making less money so they went down as well; say, 20%. At that point, you've only got $4K left. But say that besides gold, you also thought that banks were cheap. So, you split your investment between the gold miners and a couple of banks -- lets call them LMN and OP -- for $2500 each in XYZ, ABC, LMN, and OP. Say you were wrong about gold, but right about banks; LMN goes up 15%, and OP goes up 40%. At that point, your portfolio looks like this: XYZ start $2500 -100% end $0 ABC start $2500 +120% end $5500 LMN start $2500 +15% end $2875 OP start $2500 +40% end $3500 For a portfolio total of: $11,875, or a total gain of 18.75%. See how that works? Region/Country/Currency risk So, now what if everything's been going up in the USA, and everything seems so overpriced? Well, odds are, some area of the world is not over-bought. Like Brazil or England. So, you can buy some Brazilian or English companies, and diversify away from the USA. That way, if the market tanks here, those foreign companies aren't caught in it, and could still go up. This is the same idea as the sector risk, except it's location based, instead of business type based. There is an additional twist to this -- currencies. The Brits use the pound, and the Brazilians use the real. Most small investors don't think about this much, but the value of currencies, including our dollar, fluctuates. If the dollar has been strong, and the pound weak (as it has been, lately), then what happens if that changes? Say you own a British bank, and the dollar weakens and the pound strengthens. Even if that bank doesn't move at all, you would still make a gain. Example: You buy British bank BBB for 40 pounds a share, when each pound costs $1.20. Say after a while, BBB is still 40 pounds/share, but the dollar weakened and the pound strengthened, such that each pound is now worth $1.50. You could sell BBB, and because of the currency exchange once you've got it converted back to dollars you'd have a 25% gain. Market cap risk Sometimes big companies do well, sometimes it's small companies. The small caps are riskier but higher returning. When you think about it, small and mid cap stocks have much more \"\"room to run\"\" than large caps do. It's much easier to double a company worth $1 billion than it is to double a company worth $100 billion. Investment types Stocks aren't the only thing you can invest in. There's also bonds, convertible bonds, CDs, preferred stocks, options and futures. It can get pretty complicated, especially the last two. But each of these investment behaves differently; and again the idea is to have something going up all the time. The classical mix is stocks and bonds. The idea here is that when times are good, the stocks go up; when times are bad, the bonds go up (because they're safer, so more people want them), but mostly they're there to providing steady income and help keep your portfolio from cratering along with the stocks. Currently, this may not work out so well; stocks and bonds have been moving in sync for several years, and with interest rates so low they don't provide much income. So what does this mean to you? I'm going make some assumptions here based on your post. You said single index, self-managed, and don't lower overall risk (and return). I'm going to assume you're a small investor, young, you invest in ETFs, and the single index is the S&P 500 index ETF -- SPY. S&P 500 is, roughly, the 500 biggest companies in the USA. Further, it's weighted -- how much of each stock is in the index -- such that the bigger the company is, the bigger a percentage of the index it is. If slickcharts is right, the top 5 companies combined are already 11% of the index! (Apple, Microsoft, Exxon, Amazon, and Johnson & Johnson). The smallest, News Corp, is a measly 0.008% of the index. In other words, if all you're invested in is SPY, you're invested in a handfull of giant american companies, and a little bit of other stuff besides. To diversify: Company risk and sector risk aren't really relevant to you, since you want broad market ETFs; they've already got that covered. The first thing I would do is add some smaller companies -- get some ETFs for mid cap, and small cap value (not small cap growth; it sucks for structural reasons). Examples are IWR for mid-cap and VBR for small-cap value. After you've done that, and are comfortable with what you have, it may be time to branch out internationally. You can get ETFs for regions (such as the EU - check out IEV), or countries (like Japan - see EWJ). But you'd probably want to start with one that's \"\"all major countries that aren't the USA\"\" - check out EFA. In any case, don't go too crazy with it. As index investing goes, the S&P 500 is not a bad way to go. Feed in anything else a little bit at a time, and take the time to really understand what it is you're investing in. So for example, using the ETFs I mentioned, add in 10% each IWR and VBR. Then after you're comfortable, maybe add 10% EFA, and raise IWR to 20%. What the ultimate percentages are, of course, is something you have to decide for yourself. Or, you could just chuck it all and buy a single Target Date Retirement fund from, say, Vanguard or T. Rowe Price and just not worry about it.\"",
"title": ""
},
{
"docid": "231195",
"text": "I am not interested in watching stock exchange rates all day long. I just want to place it somewhere and let it grow Your intuition is spot on! To buy & hold is the sensible thing to do. There is no need to constantly monitor the stock market. To invest successfully you only need some basic pointers. People make it look like it's more complicated than it actually is for individual investors. You might find useful some wisdom pearls I wish I had learned even earlier. Stocks & Bonds are the best passive investment available. Stocks offer the best return, while bonds are reduce risk. The stock/bond allocation depends of your risk tolerance. Since you're as young as it gets, I would forget about bonds until later and go with a full stock portfolio. Banks are glorified money mausoleums; the interest you can get from them is rarely noticeable. Index investing is the best alternative. How so? Because 'you can't beat the market'. Nobody can; but people like to try and fail. So instead of trying, some fund managers simply track a market index (always successfully) while others try to beat it (consistently failing). Actively managed mutual funds have higher costs for the extra work involved. Avoid them like the plague. Look for a diversified index fund with low TER (Total Expense Ratio). These are the most important factors. Diversification will increase safety, while low costs guarantee that you get the most out of your money. Vanguard has truly good index funds, as well as Blackrock (iShares). Since you can't simply buy equity by yourself, you need a broker to buy and sell. Luckily, there are many good online brokers in Europe. What we're looking for in a broker is safety (run background checks, ask other wise individual investors that have taken time out of their schedules to read the small print) and that charges us with low fees. You probably can do this through the bank, but... well, it defeats its own purpose. US citizens have their 401(k) accounts. Very neat stuff. Check your country's law to see if you can make use of something similar to reduce the tax cost of investing. Your government will want a slice of those juicy dividends. An alternative is to buy an index fund on which dividends are not distributed, but are automatically reinvested instead. Some links for further reference: Investment 101, and why index investment rocks: However the author is based in the US, so you might find the next link useful. Investment for Europeans: Very useful to check specific information regarding European investing. Portfolio Ideas: You'll realise you don't actually need many equities, since the diversification is built-in the index funds. I hope this helps! There's not much more, but it's all condensed in a handful of blogs.",
"title": ""
},
{
"docid": "200477",
"text": "Firstly, sorry about the accident. I am afraid you will need to do your own legwork, because you cannot trust other people with your money. It's a good thing you do not need to rush. Take your time to learn things. One thing is certain, you cannot let your money sit in a bank - inflation will digest them. You need to learn about investing yourself, or you run a risk of someone taking advantage of you. And there are people who specialise in exploiting people who have money and no idea what to do with them. There is no other way, if you have money, you need to know how to deal with it, or you are likely to lose it all. Since you need to have monthly income and also income that makes more money to make further investments, you need to look at two most common investments that are safe enough and also give good returns on investment: Property and index funds. You might also have a look at National bonds as this is considered safest investment possible (country has to go bust for you to lose money), but you are too young for that. Young = you can take more risk so Property and shares (indexes). You want to have your property investments in a country that is stable and has a good ROI (like Netherlands or Lithuania). Listen to some audio lectures: https://www.audible.co.uk/pd/Health-Personal-Development/Investing-in-Real-Estate-6th-Edition-Audiobook/B008SEH1R0 https://www.audible.co.uk/pd/Business/The-Secrets-of-Buy-to-Let-Success-Audiobook/B00UVVM222 https://www.audible.co.uk/pd/Non-fiction/Economics-3rd-Edition-Audiobook/B00D8J7VUC https://www.audible.co.uk/pd/Advanced-Investments-Part-1-Audiobook/B00HU81B80 After you sorted your investment strategy, you might want to move to a country that is Expat friendly and has lower living costs than US and you should be able to live like a king... best of luck.",
"title": ""
},
{
"docid": "568624",
"text": "Index funds are well-known to give the best long-term investment. Are they? Maybe not all the time! If you had invested in an index fund tracking the S&P500 at the start of 2000 you would still be behind in terms of capital appreciation when taking inflation into considerations. Your only returns in 13.5 years would have been any dividends you may have received. See the monthly chart of the S&P500 below. Diversification can be good for your overall returns, but diversification simply for diversification sake is as you said, a way of reducing your overall returns in order of smoothing out your equity curve. After looking up indexes for various countries the only one that had made decent returns over a 13.5 year period was the Indian BSE 30 index, almost 400% over 13.5 years, although it also has gone nowhere since the end of 2007 (5.5 years). See monthly chart below. So investing internationally (especially in developing countries when developed nations are stagnating) can improve your returns, but I would learn about the various international markets first before plunging straight in. Regarding investing in an Index fund vs direct investment in a select group of shares, I did a search on the US markets with the following criteria on the 3rd January 2000: If the resulting top 10 from the search were bought on 3rd January 2000 and held up until the close of the market on the 19th June 2013, the results would be as per the table below: The result, almost 250% return in 13.5 years compared to almost no return if you had invested into the whole S&P 500 Index. Note, this table lists only the top ten from the search without screening through the charts, and no risk management was applied (if risk management was applied the 4 losses of 40%+ would have been limited to a maximum of 20%, but possibly much smaller losses or even for gains, as they might have gone into positive territory before coming back down - as I have not looked at any of the charts I cannot confirm this). This is one simple example how selecting good shares can result in much better returns than investing into a whole Index, as you are not pulled down by the bad stocks.",
"title": ""
},
{
"docid": "306232",
"text": "\"General advice is to keep 6 months worth of income liquid -- in your case, you might want to leave 1 year liquid since, even though your income is stable now, it is not static (i.e., you're not drawing salary from an employer). The rest of it? If you don't plan on using it for any big purchases in the next 5 or so years, invest it. If you don't, you will probably lose money in the long term due to inflation (how's that for a risk? :). There are plenty of options for the risk averse, many of which handily beat inflation, though without knowing your country of residence, it's hard to say. In all likelihood, though, you'll want to invest in index funds -- such as ETFs -- that basically track industries, rather than individual companies. This is basically free portfolio diversity -- they lose money only when an entire sector loses value. Though even with funds of this type, you still want to ensure you purchase multiple different funds that track different industries. Don't just toss all of your funds into an IT index, for example. Before buying, just look at the history of the fund and make sure it has had a general upward trajectory since 2008 (I've bought a few ETFs that remained static...not what we're looking for in an investment!). If the brokerage account you choose doesn't offer commission free trades on any of the funds you want (personally, I use Schwab and their ETF portfolio), try to \"\"buy in bulk.\"\" That way you're not spending so much on trades. There are other considerations (many indexed funds have high management costs, but if you go with ETFs, they don't, and there's the question of dividends, etc), but that is getting into the weeds as far as investing knowledge is concerned. Beyond that, just keep in mind it'll take 1-2 weeks for you to see that money if you need it, and there's obviously no guarantee it'll be there if you do need it for an emergency.\"",
"title": ""
},
{
"docid": "60032",
"text": "\"This turned out be a lot longer than I expected. So, here's the overview. Despite the presence of asset allocation calculators and what not, this is a subjective matter. Only you know how much risk you are willing to take. You seem to be aware of one rule of thumb, namely that with a longer investing horizon you can stand to take on more risk. However, how much risk you should take is subject to your own risk aversion. Honestly, the best way to answer your questions is to educate yourself about the individual topics. There are just too many variables to provide neat, concise answers to such a broad question. There are no easy ways around this. You should not blindly rely on the opinions of others, but rather use your own judgment to asses their advice. Some of the links I provide in the main text: S&P 500: Total and Inflation-Adjusted Historical Returns 10-year index fund returns The Motley Fool Risk aversion Disclaimer: These are the opinions of an enthusiastic amateur. Why should I invest 20% in domestic large cap and 10% in developing markets instead of 10% in domestic large cap and 20% in developing markets? Should I invest in REITs? Why or why not? Simply put, developing markets are very risky. Even if you have a long investment horizon, you should pace yourself and not take on too much risk. How much is \"\"too much\"\" is ultimately subjective. Specific to why 10% in developing vs 20% in large cap, it is probably because 10% seems like a reasonable amount of your total portfolio to gamble. Another way to look at this is to consider that 10% as gone, because it is invested in very risky markets. So, if you're willing to take a 20% haircut, then by all means do that. However, realize that you may be throwing 1/5 of your money out the window. Meanwhile, REITs can be quite risky as investing in the real estate market itself can be quite risky. One reason is that the assets are very much fixed in place and thus can not be liquidated in the same way as other assets. Thus, you are subject to the vicissitudes of a relatively small market. Another issue is the large capital outlays required for most commercial building projects, thus typically requiring quite a bit of credit and risk. Another way to put it: Donald Trump made his name in real estate, but it was (and still is) a very bumpy ride. Yet another way to put it: you have to build it before they will come and there is no guarantee that they will like what you built. What mutual funds or index funds should I investigate to implement these strategies? I would generally avoid actively managed mutual funds, due to the expenses. They can seriously eat into the returns. There is a reason that the most mutual funds compare themselves to the Lipper average instead of something like the S&P 500. All of those costs involved in managing a mutual fund (teams of people and trading costs) tend to weigh down on them quite heavily. As the Motley Fool expounded on years ago, if you can not do better than the S&P 500, you should save yourself the headaches and simply invest in an S&P 500 index fund. That said, depending on your skill (and luck) picking stocks (or even funds), you may very well have been able to beat the S&P 500 over the past 10 years. Of course, you may have also done a whole lot worse. This article discusses the performance of the S&P 500 over the past 60 years. As you can see, the past 10 years have been a very bumpy ride yielding in a negative return. Again, keep in mind that you could have done much worse with other investments. That site, Simple Stock Investing may be a good place to start educating yourself. I am not familiar with the site, so do not take this as an endorsement. A quick once-over of the material on the site leads me to believe that it may provide a good bit of information in readily digestible forms. The Motley Fool was a favorite site of mine in the past for the individual investor. However, they seem to have turned to the dark side, charging for much of their advice. That said, it may still be a good place to get started. You may also decide that it is worth paying for their advice. This blog post, though dated, compares some Vanguard index funds and is a light introduction into the contrarian view of investing. Simply put, this view holds that one should not be a lemming following the crowd, rather one should do the opposite of what everyone else is doing. One strong argument in favor of this view is the fact that as more people pile onto an investing strategy or into a particular market, the yields thin out and the risk of a correction (i.e. a downturn) increases. In the worst case, this leads to a bubble, which corrects itself suddenly (or \"\"pops\"\" thus the term \"\"bubble\"\") leading to quite a bit of pain for the unprepared participants. An unprepared participant is one who is not hedged properly. Basically, this means they were not invested in other markets/strategies that would increase in yield as a result of the event that caused the bubble to pop. Note that the recent housing bubble and resulting credit crunch beat quite heavily on the both the stock and bond markets. So, the easy hedge for stocks being bonds did not necessarily work out so well. This makes sense, as the housing bubble burst due to concerns over easy credit. Unfortunately, I don't have any good resources on hand that may provide starting points or discuss the various investing strategies. I must admit that I am turning my interests back to investing after a hiatus. As I stated, I used to really like the Motley Fool, but now I am somewhat suspicious of them. The main reason is the fact that as they were exploring alternatives to advertising driven revenue for their site, they promised to always have free resources available for those unwilling to pay for their advice. A cursory review of their site does show a decent amount of general investing information, so take these words with a grain of salt. (Another reason I am suspicious of them is the fact that they \"\"spammed\"\" me with lots of enticements to pay for their advice which seemed just like the type of advice they spoke against.) Anyway, time to put the soapbox away. As I do that though, I should explain the reason for this soapboxing. Simply put, investing is a risky endeavor, any way you slice it. You can never eliminate risk, you can only hope to reduce it to an acceptable level. What is acceptable is subject to your situation and to the magnitude of your risk aversion. Ultimately, it is rather subjective and you should not blindly follow someone else's opinion (professional or otherwise). Point being, use your judgment to evaluate anything you read about investing. If it sounds too good to be true, it probably is. If someone purports to have some strategy for guaranteed (steady) returns, be very suspicious of it. (Read up on the Bernard Madoff scandal.) If someone is putting on a heavy sales pitch, be weary. Be especially suspicious of anyone asking you to pay for their advice before giving you any solid understanding of their strategy. Sure, many people want to get paid for their advice in some way (in fact, I am getting \"\"paid\"\" with reputation on this site). However, if they take the sketchy approach of a slimy salesmen, they are likely making more money from selling their strategy, than they are from the advice itself. Most likely, if they were getting outsized returns from their strategy they would keep quiet about it and continue using it themselves. As stated before, the more people pile onto a strategy, the smaller the returns. The typical model for selling is to make money from the sale. When the item being sold is an intangible good, your risk as a buyer increases. You may wonder why I have written at length without much discussion of asset allocation. One reason is that I am still a relative neophyte and have a mostly high level understanding of the various strategies. While I feel confident enough in my understanding for my own purposes, I do not necessarily feel confident creating an asset allocation strategy for someone else. The more important reason is that this is a subjective matter with a lot of variables to consider. If you want a quick and simple answer, I am afraid you will be disappointed. The best approach is to educate yourself and make these decisions for yourself. Hence, my attempt to educate you as best as I can at this point in time. Personally, I suggest you do what I did. Start reading the Wall Street Journal every day. (An acceptable substitute may be the business section of the New York Times.) At first you will be overwhelmed with information, but in the long run it will pay off. Another good piece of advice is to be patient and not rush into investing. If you are in a hurry to determine how you should invest in a 401(k) or other such investment vehicle due to a desire to take advantage of an employer's matching funds, then I would place my money in an S&P 500 index fund. I would also explore placing some of that money into broad index funds from other regions of the globe. The reason for broad index funds is to provide some protection from the normal fluctuations and to reduce the risk of a sudden downturn causing you a lot pain while you determine the best approach for yourself. In this scenario, think more about capital preservation and hedging against inflation then about \"\"beating\"\" the market.\"",
"title": ""
},
{
"docid": "259145",
"text": "\"Is evaluating stocks just a loss of time if the stock is traded very much? Not at all! Making sound investment decisions based on fundamental analysis of companies will help you to do decide whether a given company is right for you and your risk appetite. Investing is not a zero-sum game, and you can achieve a positive long-term (or short-term, depending on what you're after) outcome for yourself without compromising your ability to sleep at night if you take the time to become acquainted with the companies that you are investing in. How can you ensure that your evaluation is more precise than the market ones which consists of the evaluation of thousands of people and professionals? For the average individual, the answer is often simply \"\"you probably cannot\"\". But you don't have to set the bar that high - what you can do is ensure that your evaluation gives you a better understanding of your investment and allows you to better align it with your investment objectives. You don't have to beat the professionals, you just have to lose less money than you would by paying them to make the decision for you.\"",
"title": ""
},
{
"docid": "144261",
"text": "\"Index funds are well-known to give the best long-term investment. Not exactly. Indexes give the best long term performance when compared to actively managing investments directly in the underlying stocks. That is, if you compare an S&P500 index to trying to pick stocks that are part of it, you're more likely to succeed with blindly following the index than trying to actively beat it. That said, no-one promises that investing in S&P500 is better than investing in DJIA, for example. These are two different indexes tracking different stocks and areas. So when advisers say \"\"diversify\"\" they don't mean it that you should diversify between different stocks that build up the S&P500 index. They mean that you should diversify your investments in different areas. Some in S&P500, some in DJIA, some in international indexes, some in bond indexes, etc. Still, investing in various indexes will likely yield better results than actively managing the investments trying to beat those indexes, but you should not invest in only one, and that is the meaning of diversification. In the comments you asked \"\"why diversify at all?\"\", and that is entirely a different question from your original \"\"what diversification is?\"\". You diversify to reduce the risk of loss from one side, and widen the net for gains from another. The thing is that any single investment can eventually fail, regardless of how it performed before. You can see that the S&P500 index lost 50% of its value twice within ten years, whereas before it was doubling itself every several years. Many people who were only invested in that index (or what's underlying to it) lost a lot of money. But consider you've diversified, and in the last 20 years you've invested in a blend of indexes that include the S&P500, but also other investments like S&P BSE SENSEX mentioned by Victor below. You would reduce your risk of loss on the American market by increasing your gains on the Indian market. Add to the mix soaring Chinese Real Estate market during the time of the collapse of the US real-estate, gains on the dollar losing its value by investing in other currencies (Canadian dollar, for example), etc. There are many risks, and by diversifying you mitigate them, and also have a chance to create other potential gains. Now, another question is why invest in indexes. That has been answered before on this site. It is my opinion that some methods of investing are just gambling by trying to catch the wave and they will almost always fail, and rarely will individual stock picking beat the market. Of course, after the fact its easy to be smart and pick the winning stocks. But the problem is to be able to predict those charts ahead of time.\"",
"title": ""
},
{
"docid": "293679",
"text": "Googling vanguard target asset allocation led me to this page on the Bogleheads wiki which has detailed breakdowns of the Target Retirement funds; that page in turn has a link to this Vanguard PDF which goes into a good level of detail on the construction of these funds' portfolios. I excerpt: (To the question of why so much weight in equities:) In our view, two important considerations justify an expectation of an equity risk premium. The first is the historical record: In the past, and in many countries, stock market investors have been rewarded with such a premium. ... Historically, bond returns have lagged equity returns by about 5–6 percentage points, annualized—amounting to an enormous return differential in most circumstances over longer time periods. Consequently, retirement savers investing only in “safe” assets must dramatically increase their savings rates to compensate for the lower expected returns those investments offer. ... The second strategic principle underlying our glidepath construction—that younger investors are better able to withstand risk—recognizes that an individual’s total net worth consists of both their current financial holdings and their future work earnings. For younger individuals, the majority of their ultimate retirement wealth is in the form of what they will earn in the future, or their “human capital.” Therefore, a large commitment to stocks in a younger person’s portfolio may be appropriate to balance and diversify risk exposure to work-related earnings (To the question of how the exact allocations were decided:) As part of the process of evaluating and identifying an appropriate glide path given this theoretical framework, we ran various financial simulations using the Vanguard Capital Markets Model. We examined different risk-reward scenarios and the potential implications of different glide paths and TDF approaches. The PDF is highly readable, I would say, and includes references to quant articles, for those that like that sort of thing.",
"title": ""
},
{
"docid": "501395",
"text": "\"Those who say a person should invest in riskier assets when young are those who equate higher returns with higher risk. I would argue that any investment you do not understand is risky and allows you to lose money at a more rapid rate than someone who understands the investment. The way to reduce risk is to learn about what you want to invest in before you invest in it. Learning afterward can be a very expensive proposition, possibly costing you your retirement. Warren Buffet told the story on Bloomberg Radio in late 2013 of how he read everything in his local library on investing as a teenager and when his family moved to Washington he realized he had the entire Library of Congress at his disposal. One of Mr. Buffett's famous quotes when asked why he doesn't invest in the tech sector was: \"\"I don't invest in what I do not understand.\"\". There are several major asset classes: Paper (stocks, bonds, mutual funds, currency), Commodities (silver, gold, oil), Businesses (creation, purchase or partnership as opposed to common stock ownership) and Real Estate (rental properties, flips, land development). Pick one that interests you and learn everything about it that you can before investing. This will allow you to minimize and mitigate risks while increasing the rewards.\"",
"title": ""
},
{
"docid": "349417",
"text": "Your definition of 'outside your country' might need some redefinition, as there are three different things going on here . . . Your financial adviser appears to be highlighting the currency risk associated with point three. However, consider these risk scenarios . . . A) Your country enters a period of severe financial difficulty, and money markets shut down. Your brokerage becomes insolvent, and your investments are lost. In this scenario the fact of whether your investments were in an overseas index such as the S&P, or were purchased from an account denominated in a different currency, would be irrelevant. The only thing that would have mitigated this scenario is an account with an overseas broker. B) Your country's stock market enters a sustained and deep bear market, decimating the value of shares in its companies. In this scenario the fact of whether your investments were made in from a brokerage overseas, or were purchased from an account denominated in a different currency, would be irrelevant. The only thing that would have mitigate this scenario is investment in shares and indices outside your home country. Your adviser has a good point; as long as you intend to enjoy your retirement in your home country then it might be advisable to remove currency risk by holding an account in Rupees. However, you might like to consider reducing the other forms of risk by holding non-Indian securities to create a globally diversified portfolio, and also placing some of your capital in an account with a broker outside your home country (this may be very difficult to do in practice).",
"title": ""
},
{
"docid": "476517",
"text": "Your idea is a good one, but, as usual, the devil is in the details, and implementation might not be as easy as you think. The comments on the question have pointed out your Steps 2 and 4 are not necessarily the best way of doing things, and that perhaps keeping the principal amount invested in the same fund instead of taking it all out and re-investing it in a similar, but different, fund might be better. The other points for you to consider are as follows. How do you identify which of the thousands of conventional mutual funds and ETFs is the average-risk / high-gain mutual fund into which you will place your initial investment? Broadly speaking, most actively managed mutual fund with average risk are likely to give you less-than-average gains over long periods of time. The unfortunate truth, to which many pay only Lipper service, is that X% of actively managed mutual funds in a specific category failed to beat the average gain of all funds in that category, or the corresponding index, e.g. S&P 500 Index for large-stock mutual funds, over the past N years, where X is generally between 70 and 100, and N is 5, 10, 15 etc. Indeed, one of the arguments in favor of investing in a very low-cost index fund is that you are effectively guaranteed the average gain (or loss :-(, don't forget the possibility of loss). This, of course, is also the argument used against investing in index funds. Why invest in boring index funds and settle for average gains (at essentially no risk of not getting the average performance: average performance is close to guaranteed) when you can get much more out of your investments by investing in a fund that is among the (100-X)% funds that had better than average returns? The difficulty is that which funds are X-rated and which non-X-rated (i.e. rated G = good or PG = pretty good), is known only in hindsight whereas what you need is foresight. As everyone will tell you, past performance does not guarantee future results. As someone (John Bogle?) said, when you invest in a mutual fund, you are in the position of a rower in rowboat: you can see where you have been but not where you are going. In summary, implementation of your strategy needs a good crystal ball to look into the future. There is no such things as a guaranteed bond fund. They also have risks though not necessarily the same as in a stock mutual fund. You need to have a Plan B in mind in case your chosen mutual fund takes a longer time than expected to return the 10% gain that you want to use to trigger profit-taking and investment of the gain into a low-risk bond fund, and also maybe a Plan C in case the vagaries of the market cause your chosen mutual fund to have negative return for some time. What is the exit strategy?",
"title": ""
},
{
"docid": "113786",
"text": "\"There are two umbrellas in investing: active management and passive management. Passive management is based on the idea \"\"you can't beat the market.\"\" Passive investors believe in the efficient markets hypothesis: \"\"the market interprets all information about an asset, so price is equal to underlying value\"\". Another idea in this field is that there's a minimum risk associated with any given return. You can't increase your expected return without assuming more risk. To see it graphically: As expected return goes up, so does risk. If we stat with a portfolio of 100 bonds, then remove 30 bonds and add 30 stocks, we'll have a portfolio that's 70% bonds/30% stocks. Turns out that this makes expected return increase and lower risk because of diversification. Markowitz showed that you could reduce the overall portfolio risk by adding a riskier, but uncorrelated, asset! Basically, if your entire portfolio is US stocks, then you'll lose money whenever US stocks fall. But, if you have half US stocks, quarter US bonds, and quarter European stocks, then even if the US market tanks, half your portfolio will be unaffected (theoretically). Adding different types of uncorrelated assets can reduce risk and increase returns. Let's tie this all together. We should get a variety of stocks to reduce our risk, and we can't beat the market by security selection. Ideally, we ought to buy nearly every stock in the market so that So what's our solution? Why, the exchange traded fund (ETF) of course! An ETF is basically a bunch of stocks that trade as a single ticker symbol. For example, consider the SPDR S&P 500 (SPY). You can purchase a unit of \"\"SPY\"\" and it will move up/down proportional to the S&P 500. This gives us diversification among stocks, to prevent any significant downside while limiting our upside. How do we diversify across asset classes? Luckily, we can purchase ETF's for almost anything: Gold ETF's (commodities), US bond ETF's (domestic bonds), International stock ETFs, Intl. bonds ETFs, etc. So, we can buy ETF's to give us exposure to various asset classes, thus diversifying among asset classes and within each asset class. Determining what % of our portfolio to put in any given asset class is known as asset allocation and some people say up to 90% of portfolio returns can be determined by asset allocation. That pretty much sums up passive management. The idea is to buy ETFs across asset classes and just leave them. You can readjust your portfolio holdings periodically, but otherwise there is no rapid trading. Now the other umbrella is active management. The unifying idea is that you can generate superior returns by stock selection. Active investors reject the idea of efficient markets. A classic and time proven strategy is value investing. After the collapse of 07/08, bank stocks greatly fell, but all the other stocks fell with them. Some stocks worth $100 were selling for $50. Value investors quickly snapped up these stocks because they had a margin of safety. Even if the stock didn't go back to 100, it could go up to $80 or $90 eventually, and investors profit. The main ideas in value investing are: have a big margin of safety, look at a company's fundamentals (earnings, book value, etc), and see if it promises adequate return. Coke has tremendous earnings and it's a great company, but it's so large that you're never going to make 20% profits on it annually, because it just can't grow that fast. Another field of active investing is technical analysis. As opposed to the \"\"fundamental analysis\"\" of value investing, technical analysis involves looking at charts for patterns, and looking at stock history to determine future paths. Things like resistance points and trend lines also play a role. Technical analysts believe that stocks are just ticker symbols and that you can use guidelines to predict where they're headed. Another type of active investing is day trading. This basically involves buying and selling stocks every hour or every minute or just at a rapid pace. Day traders don't hold onto investments for very long, and are always trying to predict the market in the short term and take advantage of it. Many individual investors are also day traders. The other question is, how do you choose a strategy? The short answer is: pick whatever works for you. The long answer is: Day trading and technical analysis is a lot of luck. If there are consistent systems for trading , then people are keeping them secret, because there is no book that you can read and become a consistent trader. High frequency trading (HFT) is an area where people basically mint money, but it s more technology and less actual investing, and would not be categorized as day trading. Benjamin Graham once said: In the short run, the market is a voting machine but in the long run it is a weighing machine. Value investing will work because there's evidence for it throughout history, but you need a certain temperament for it and most people don't have that. Furthermore, it takes a lot of time to adequately study stocks, and people with day jobs can't devote that kind of time. So there you have it. This is my opinion and by no means definitive, but I hope you have a starting point to continue your study. I included the theory in the beginning because there are too many monkeys on CNBC and the news who just don't understand fundamental economics and finance, and there's no sense in applying a theory until you can understand why it works and when it doesn't.\"",
"title": ""
},
{
"docid": "205685",
"text": "In general, to someone in a similar circumstance I might suggest that the lowest-risk option is to immediately convert your excess currency into the currency you will be spending. Note that 'risk' here refers only to the variance in possible outcomes. By converting to EUR now (assuming you are moving to an EU country using the EUR), you eliminate the chance that the GBP will weaken. But you also eliminate the chance that the GBP will strengthen. Thus, you have reduced the variance in possible outcomes so that you have a 'known' amount of EUR. To put money in a different currency than what you will be using is a form of investing, and it is one that can be considered high risk. Invest in a UK company while you plan on staying in the UK, and you take on the risk of stock ownership only. But invest in a German company while you plan on staying in the UK, you take on the risk of stock ownership + the risk of currency volatility. If you are prepared for this type of risk and understand it, you may want to take on this type of risk - but you really must understand what you're getting into before you do this. For most people, I think it's fair to say that fx investing is more accurately called gambling [See more comments on the risk of fx trading here: https://money.stackexchange.com/a/76482/44232]. However, this risk reduction only truly applies if you are certain that you will be moving to an EUR country. If you invest in EUR but then move to the US, you have not 'solved' your currency volatility problem, you have simply replaced your GBP risk with EUR risk. If you had your plane ticket in hand and nothing could stop you, then you know what your currency needs will be in 2 years. But if you have any doubt, then exchanging currency now may not be reducing your risk at all. What if you exchange for EUR today, and in a year you decide (for all the various reasons that circumstances in life may change) that you will stay in the UK after all. And during that time, what if the GBP strengthened again? You will have taken on risk unnecessarily. So, if you lack full confidence in your move, you may want to avoid fully trading your GBP today. Perhaps you could put away some amount every month into EUR (if you plan on moving to an EUR country), and leave some/most in GBP. This would not fully eliminate your currency risk if you move, but it would also not fully expose yourself to risk if you end up not moving. Just remember that doing this is not a guarantee that the EUR will strengthen and the GBP will weaken.",
"title": ""
},
{
"docid": "285560",
"text": "\"If I invest in index funds or other long term stocks that pay dividend which I reinvest, they don't need to be worth more per share for me to make a profit, right? That is, if I sell part of the stocks, it's GOOD if they're worth more than I bought them at, but the real money comes from the QUANTITY of stocks that you get by reinvesting your dividends, right? I would say it is more the other way around. It is nice to get dividends and reinvest them, but overall the main gain comes from the stocks going up in value. The idea with index funds, however, is that you don't rely on any particular stock going up in value; instead you just rely on the aggregate of all the funds in the index going up. By buying lots of stocks bundled in an index fund, you avoid being too reliant on any one company's performance. Can I invest \"\"small amounts\"\" (part of paycheck) into index funds on a monthly basis, like €500, without taking major \"\"transaction fees\"\"? (Likely to be index fund specific... general answers or specific answers using popular stocks welcomed). Yes, you can. At least in the US, whether you can do this automatically from your paycheck depends on whether you employer has that set up. I don't know that work in the Netherlands. However, at the least, you can almost certainly set up an auto-invest program that takes $X out of your bank account every month and buys shares of some index fund(s). Is this plan market-crash proof? My parents keep saying that \"\"Look at 2008 and think about what such a thing would do to your plan\"\", and I just see that it will be a setback, but ultimately irrelevant, unless it happens when I need the money. And even then I'm wondering whether I'll really need ALL of my money in one go. Doesn't the index fund go back up eventually? Does a crash even matter if you plan on holding stocks for 10 or more years? Crashes always matter, because as you say, there's always the possibility that the crash will occur at a time you need the money. In general, it is historically true that the market recovers after crashes, so yes, if you have the financial and psychological fortitude to not pull your money out during the crash, and to ride it out, your net worth will probably go back up after a rough interlude. No one can predict the future, so it's possible for some unprecedented crisis to cause an unprecedented crash. However, the interconnectedness of stock markets and financial systems around the world is now so great that, were such a no-return crash to occur, it would probably be accompanied by the total collapse of the whole economic system. In other words, if the stock market dies suddenly once and for all, the entire way of life of \"\"developed countries\"\" will probably die with it. As long as you live in such a society, you can't really avoid \"\"gambling\"\" that it will continue to exist, so gambling on there not being a cataclysmic market crash isn't much more of a gamble. Does what I'm planning have similarities with some financial concept or product (to allow me to research better by looking at the risks of that concept/product)? Maybe like a mortgage investment plan without the bank eating your money in between? I'm not sure what you mean by \"\"what you're planning\"\". The main financial products relevant to what you're describing are index funds (which you already mentioned) and index ETFs (which are basically similar with regard to the questions you're asking here). As far as concepts, the philosophy of buying low-fee index funds, holding them for a long time, and not selling during crashes, is essentially that espoused by Jack Bogle (not quite the inventor of the index fund, but more or less its spiritual father) and the community of \"\"Bogleheads\"\" that has formed around his ideas. There is a Bogleheads wiki with lots of information about the details of this approach to investing. If this strategy appeals to you, you may find it useful to read through some of the pages on that site.\"",
"title": ""
},
{
"docid": "98920",
"text": "What you're getting at is the same as investing with leverage. Usually this comes in the form in a margin account, which an investor uses to borrow money at a low interest rate, invest the money, and (hopefully!) beat the interest rate. is this approach unwise? That completely depends on how your investments perform and how high your loan's interest rate is. The higher your loan's interest rate, the more risky your investments will have to be in order to beat the interest rate. If you can get a return which beats the interest rates of your loan then congratulations! You have come out ahead and made a profit. If you can keep it up you should make the minimum payment on your loan to maximize the amount of capital you can invest. If not, then it would be better to just use your extra cash to pay down the loan. [are] there really are investments (aside from stocks and such) that I can try to use to my advantage? With interest rates as low as they are right now (at least in the US) you'll probably be hard-pressed to find a savings account or CD that will return a higher interest rate than your loan's. If you're nervous about the risk associated with investing in stocks and bonds (as is healthy!), then know that they come in a wide spectrum of risk. It's up to you to evaluate how much risk you're willing to take on to achieve a higher return.",
"title": ""
},
{
"docid": "483123",
"text": "\"The question is: how do you quantify investment risk? As Michael S says, one approach is to treat investment returns as a random variable. Bill Goetzmann (Yale finance professor) told me that if you accept that markets are efficient or that the price of an asset reflects it's underlying value, then changes in price represent changes in value, so standard deviation naturally becomes the appropriate measure for riskiness of an asset. Essentially, the more volatile an asset, the riskier it is. There is another school of thought that comes from Ben Graham and Warren Buffett, which says that volatility is not inherently risky. Rather, risk should be defined as the permanent loss of capital, so the riskiness of an asset is the probability of a permanent loss of capital invested. This is easy to do in casino games, based on basic probability such as roulette or slots. But what has been done with the various kinds of investment risks? My point is saying that certain bonds are \"\"low risk\"\" isn't good enough; I'd like some numbers--or at least a range of numbers--and therefore one could calculate expected payoff (in the statistics sense). Or can it not be done--and if not, why not? Investing is more art than science. In theory, a Triple-A bond rating means the asset is riskless or nearly riskless, but we saw that this was obviously wrong since several of the AAA mortgage backed securities (MBS) went under prior to the recent US recession. More recently, the current threat of default suggests that bond ratings are not entirely accurate, since US Treasuries are considered riskless assets. Investors often use bond ratings to evaluate investments - a bond is considered investment grade if it's BBB- or higher. To adequately price bonds and evaluate risk, there are too many factors to simply refer to a chart because things like the issuer, credit quality, liquidity risk, systematic risk, and unsystematic risk all play a factor. Another factor you have to consider is the overall portfolio. Markowitz showed that adding a riskier asset can actually lower the overall risk of a portfolio because of diversification. This is all under the assumption that risk = variance, which I think is bunk. I'm aware that Wall Street is nothing like roulette, but then again there must be some math and heavy economics behind calculating risk for individual investors. This is, after all, what \"\"quants\"\" are paid to do, in part. Is it all voodoo? I suspect some of it is, but not all of it. Quants are often involved in high frequency trading as well, but that's another note. There are complicated risk management products, such as the Aladdin system by BlackRock, which incorporate modern portfolio theory (Markowitz, Fama, Sharpe, Samuelson, etc) and financial formulas to manage risk. Crouhy's Risk Management covers some of the concepts applied. I also tend to think that when people point to the last x number of years of stock market performance, that is of less value than they expect. Even going back to 1900 provides \"\"only\"\" 110 years of data, and in my view, complex systems need more data than those 40,500 data points. 10,000 years' worth of data, ok, but not 110. Any books or articles that address these issues, or your own informed views, would be helfpul. I fully agree with you here. A lot of work is done in the Santa Fe Institute to study \"\"complex adaptive systems,\"\" and we don't have any big, clear theory as of yet. Conventional risk management is based on the ideas of modern portfolio theory, but a lot of that is seen to be wrong. Behavioral finance is introducing new ideas on how investors behave and why the old models are wrong, which is why I cannot suggest you study risk management and risk models because I and many skilled investors consider them to be largely wrong. There are many good books on investing, the best of which is Benjamin Graham's The Intelligent Investor. Although not a book on risk solely, it provides a different viewpoint on how to invest and covers how to protect investments via a \"\"Margin of Safety.\"\" Lastly, I'd recommend Against the Gods by Peter Bernstein, which covers the history of risk and risk analysis. It's not solely a finance book but rather a fascinating historical view of risk, and it helps but many things in context. Hope it helps!\"",
"title": ""
},
{
"docid": "592661",
"text": "Google 'information ratio'. It is better suited to what you want than the Sharpe or Sortino ratios because it only evaluates the *excess* return you get from your investment, ie. return from your investment minus the return from a benchmark investment. The benchmark here could be an index like the S&P500.",
"title": ""
},
{
"docid": "549270",
"text": "For most people, you don't want individual bonds. Unless you are investing very significant amounts of money, you are best off with bond funds (or ETFs). Here in Canada, I chose TDB909, a mutual fund which seeks to roughly track the DEX Universe Bond index. See the Canadian Couch Potato's recommended funds. Now, you live in the U.S. so would most likely want to look at a similar bond fund tracking U.S. bonds. You won't care much about Canadian bonds. In fact, you probably don't want to consider foreign bonds at all, due to currency risk. Most recommendations say you want to stick to your home country for your bond investments. Some people suggest investing in junk bonds, as these are likely to pay a higher rate of return, though with an increased risk of default. You could also do fancy stuff with bond maturities, too. But in general, if you are just looking at an 80/20 split, if you are just looking for fairly simple investments, you really shouldn't. Go for a bond fund that just mirrors a big, low-risk bond index in your home country. I mean, that's the implication when someone recommends a 60/40 split or an 80/20 split. Should you go with a bond mutual fund or with a bond ETF? That's a separate question, and the answer will likely be the same as for stock mutual funds vs stock ETFs, so I'll mostly ignore the question and just say stick with mutual funds unless you are investing at least $50,000 in bonds.",
"title": ""
},
{
"docid": "317533",
"text": "\"You are your own worst enemy when it comes to investing. You might think that you can handle a lot of risk but when the market plummets you don't know exactly how you'll react. Many people panic and sell at the worst possible time, and that kills their returns. Will that be you? It's impossible to tell until it happens. Don't just invest in stocks. Put some of your money in bonds. For example TIPS, which are inflation adjusted treasury bonds (very safe, and the return is tied to the rate of inflation). That way, when the stock market falls, you'll have a back-stop and you'll be less likely to sell at the wrong time. A 50/50 stock/bond mix is probably reasonable. Some recommend your age in bonds, which for you means 20% or so. Personally I think 50/50 is better even at your young age. Invest in broad market indexes, such as the S&P 500. Steer clear of individual stocks except for maybe 5-10% of your total. Individual stocks carry the risk of going out of business, such as Enron. Follow Warren Buffet's two rules of investing: a) Don't lose money b) See rule a). Ignore the \"\"investment porn\"\" that is all around you in the form of TV shows and ads. Don't chase hot companies, sectors or countries. Try to estimate what you'll need for retirement (if that's what your investing for) and don't take more risk than you need to. Try to maintain a very simple portfolio that you'll be able to sleep well with. For example, check into the coffeehouse investor Pay a visit to the Bogleheads Forum - you can ask for advice there and the advice will be excellent. Avoid investments with high fees. Get advice from a good fee-only investment advisor if needed. Don't forget to enjoy some of your money now as well. You might not make it to retirement. Read, read, read about investing and retirement. There are many excellent books out there, many of which you can pick up used (cheap) through amazon.com.\"",
"title": ""
},
{
"docid": "352557",
"text": "Use a currency ETF. there are many. Specific to your question there is WisdomTree Dreyfus Brazilian Real Fund (BZF) I don't happen to find a currency ETF for Thailand, so the closest you could come to a Thai currency fund would be something that's an Index fund ETF that is based on an index in the Thai Market such as: MSCI Thailand Investable Market Index Fund Because that fund is investing in an index of stocks that trade on the Thai market, you are in effect investing in something denominated in Baht. This is spelled out in the prospectus where it discusses 'currency risk'. The problem is that you are however not investing in just the currency, but rather a broad index of stocks denominated in that currency. Still to the extent the market holds fairly steady, you get much the same effect of investing in just the currency. to the extent the market is moving, you get the net effect of what the thai market does, plus how the bhat trades relative to the dollar.",
"title": ""
},
{
"docid": "8012",
"text": "It is worth noting first that interest and short-term dividends/capital gains are all taxed at the same rate. So all the investments below I mention (even savings accounts) will be taxed at the same rate. Also, even short-term capital losses can often be harvested to reduce your tax rate in many countries. While it is worth paying attention to the taxes when investing in the short term the more important factor is how much risk that you can take or want to take with the money. Most equity portfolios like the S&P index give a much higher risk that there will be much less in the account when you need to buy. You generally have a higher expected return with equity but as you mention that return is very random over such a short period. Over such a short variable period many people will invest in short term bond-index funds or just keep the fund in a high-yielding savings account. With the savings account your money is guaranteed. Short term bond funds will have generally higher yields but a small chance you may lose money in the short term. Some people can trade short-term bond indices for free with their broker but if you can't be sure to include the trading costs when thinking about which investment to use as with how low yields are currently the fees may eat up any advantage you gain.",
"title": ""
}
] |
PLAIN-1045
|
Dr. Benjamin Feingold
|
[
{
"docid": "MED-5062",
"text": "BACKGROUND: We undertook a randomised, double-blinded, placebo-controlled, crossover trial to test whether intake of artificial food colour and additives (AFCA) affected childhood behaviour. METHODS: 153 3-year-old and 144 8/9-year-old children were included in the study. The challenge drink contained sodium benzoate and one of two AFCA mixes (A or B) or a placebo mix. The main outcome measure was a global hyperactivity aggregate (GHA), based on aggregated z-scores of observed behaviours and ratings by teachers and parents, plus, for 8/9-year-old children, a computerised test of attention. This clinical trial is registered with Current Controlled Trials (registration number ISRCTN74481308). Analysis was per protocol. FINDINGS: 16 3-year-old children and 14 8/9-year-old children did not complete the study, for reasons unrelated to childhood behaviour. Mix A had a significantly adverse effect compared with placebo in GHA for all 3-year-old children (effect size 0.20 [95% CI 0.01-0.39], p=0.044) but not mix B versus placebo. This result persisted when analysis was restricted to 3-year-old children who consumed more than 85% of juice and had no missing data (0.32 [0.05-0.60], p=0.02). 8/9-year-old children showed a significantly adverse effect when given mix A (0.12 [0.02-0.23], p=0.023) or mix B (0.17 [0.07-0.28], p=0.001) when analysis was restricted to those children consuming at least 85% of drinks with no missing data. INTERPRETATION: Artificial colours or a sodium benzoate preservative (or both) in the diet result in increased hyperactivity in 3-year-old and 8/9-year-old children in the general population.",
"title": "Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled..."
},
{
"docid": "MED-5063",
"text": "Evidence supports a trial period of eliminating colourings and preservatives from the diet",
"title": "Food additives and hyperactivity"
}
] |
[
{
"docid": "MED-3380",
"text": "Attention deficit hyperactivity disorder (ADHD) is one of the most common behavioral disorders in children. Symptoms of ADHD include hyperactivity, low frustration tolerance, impulsivity, and inattention. While the biological pathways leading to ADHD are not clearly delineated, a number of genetic and environmental risk factors for the disorder are recognized. In the early 1970s, research conducted by Dr. Benjamin Feingold found that when hyperactive children were given a diet free of artificial food additives and dyes, symptoms of hyperactivity were reduced. While some clinical studies supported these findings, more rigorous empirical studies conducted over the next 20 years were less positive. As a result, research on the role of food additives in contributing to ADHD waned. In recent years, however, interest in this area has revived. In response to more recent research and public petitions, in December 2009 the British government requested that food manufacturers remove most artificial food dyes from their products. While these strictures could have positive effects on behavior, the removal of food dyes is not a panacea for ADHD, which is a multifaceted disorder with both biological and environmental underpinnings. © 2011 International Life Sciences Institute.",
"title": "Artificial food dyes and attention deficit hyperactivity disorder."
},
{
"docid": "MED-1712",
"text": "Diet contributes to over one-third of cancer deaths in the Western world, yet the factors in the diet that influence cancer are not elucidated. A reduction in caloric intake dramatically slows cancer progression in rodents, and this may be a major contribution to dietary effects on cancer. Insulin-like growth factor I (IGF-I) is lowered during dietary restriction (DR) in both humans and rats. Because IGF-I modulates cell proliferation, apoptosis, and tumorigenesis, the mechanisms behind the protective effects of DR may depend on the reduction of this multifaceted growth factor. To test this hypothesis, IGF-I was restored during DR to ascertain if lowering of IGF-I was central to slowing bladder cancer progression during DR. Heterozygous p53-deficient mice received a bladder carcinogen, p-cresidine, to induce preneoplasia. After confirmation of bladder urothelial preneoplasia, the mice were divided into three groups: (a) ad libitum; (b) 20% DR; and (c) 20% DR plus IGF-I (IGF-I/DR). Serum IGF-I was lowered 24% by DR but was completely restored in the IGF-I/DR-treated mice using recombinant IGF-I administered via osmotic minipumps. Although tumor progression was decreased by DR, restoration of IGF-I serum levels in DR-treated mice increased the stage of the cancers. Furthermore, IGF-I modulated tumor progression independent of changes in body weight. Rates of apoptosis in the preneoplastic lesions were 10 times higher in DR-treated mice compared to those in IGF/DR- and ad libitum-treated mice. Administration of IGF-I to DR-treated mice also stimulated cell proliferation 6-fold in hyperplastic foci. In conclusion, DR lowered IGF-I levels, thereby favoring apoptosis over cell proliferation and ultimately slowing tumor progression. This is the first mechanistic study demonstrating that IGF-I supplementation abrogates the protective effect of DR on neoplastic progression.",
"title": "Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-defici..."
},
{
"docid": "MED-2510",
"text": "Dietary restriction (DR) extends the lifespan of a wide range of species, although the universality of this effect has never been quantitatively examined. Here, we report the first comprehensive comparative meta-analysis of DR across studies and species. Overall, DR significantly increased lifespan, but this effect is modulated by several factors. In general, DR has less effect in extending lifespan in males and also in non-model organisms. Surprisingly, the proportion of protein intake was more important for life extension via DR than the degree of caloric restriction. Furthermore, we show that reduction in both age-dependent and age-independent mortality rates drives life extension by DR among the well-studied laboratory model species (yeast, nematode worms, fruit flies and rodents). Our results suggest that convergent adaptation to laboratory conditions better explains the observed DR-longevity relationship than evolutionary conservation although alternative explanations are possible. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.",
"title": "Comparative and meta-analytic insights into life extension via dietary restriction."
},
{
"docid": "MED-1021",
"text": "CONTEXT: Diabetic retinopathy (DR) is the leading cause of blindness in the working-aged population in the United States. There are many new interventions for DR, but evidence to support their use is uncertain. OBJECTIVE: To review the best evidence for primary and secondary intervention in the management of DR, including diabetic macular edema. EVIDENCE ACQUISITION: Systematic review of all English-language articles, retrieved using a keyword search of MEDLINE (1966 through May 2007), EMBASE, Cochrane Collaboration, the Association for Research in Vision and Ophthalmology database, and the National Institutes of Health Clinical Trials Database, and followed by manual searches of reference lists of selected major review articles. All English-language randomized controlled trials (RCTs) with more than 12 months of follow-up and meta-analyses were included. Delphi consensus criteria were used to identify well-conducted studies. EVIDENCE SYNTHESIS: Forty-four studies (including 3 meta-analyses) met the inclusion criteria. Tight glycemic and blood pressure control reduces the incidence and progression of DR. Pan-retinal laser photocoagulation reduces the risk of moderate and severe visual loss by 50% in patients with severe nonproliferative and proliferative retinopathy. Focal laser photocoagulation reduces the risk of moderate visual loss by 50% to 70% in eyes with macular edema. Early vitrectomy improves visual recovery in patients with proliferative retinopathy and severe vitreous hemorrhage. Intravitreal injections of steroids may be considered in eyes with persistent loss of vision when conventional treatment has failed. There is insufficient evidence for the efficacy or safety of lipid-lowering therapy, medical interventions, or antivascular endothelial growth factors on the incidence or progression of DR. CONCLUSIONS: Tight glycemic and blood pressure control remains the cornerstone in the primary prevention of DR. Pan-retinal and focal retinal laser photocoagulation reduces the risk of visual loss in patients with severe DR and macular edema, respectively. There is currently insufficient evidence to recommend routine use of other treatments.",
"title": "Management of diabetic retinopathy: a systematic review."
},
{
"docid": "MED-2498",
"text": "Dietary restriction (DR) and reduced growth factor signaling both elevate resistance to oxidative stress, reduce macromolecular damage, and increase lifespan in model organisms. In rodents, both DR and decreased growth factor signaling reduce the incidence of tumors and slow down cognitive decline and aging. DR reduces cancer and cardiovascular disease and mortality in monkeys, and reduces metabolic traits associated with diabetes, cardiovascular disease and cancer in humans. Neoplasias and diabetes are also rare in humans with loss of function mutations in the growth hormone receptor. DR and reduced growth factor signaling may thus slow aging by similar, evolutionarily conserved, mechanisms. We review these conserved anti-aging pathways in model organisms, discuss their link to disease prevention in mammals, and consider the negative side effects that might hinder interventions intended to extend healthy lifespan in humans.",
"title": "Dietary Restriction, Growth Factors and Aging: from yeast to humans"
},
{
"docid": "MED-3283",
"text": "Available information indicates that long-lived mammals have low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, many studies have consistently shown that dietary restriction (DR) in rodents also decreases mitochondrial ROS (mtROS) production and oxidative damage to mitochondrial DNA and proteins. It has been observed that protein restriction also decreases mtROS generation and oxidative stress in rat liver, whereas neither carbohydrate nor lipid restriction change these parameters. This is interesting because protein restriction also increases maximum longevity in rodents (although to a lower extent than DR) and is a much more practicable intervention for humans than DR, whereas neither carbohydrate nor lipid restriction seem to change rodent longevity. Moreover, it has been found that isocaloric methionine restriction also decreases mtROS generation and oxidative stress in rodent tissues, and this manipulation also increases maximum longevity in rats and mice. In addition, excessive dietary methionine also increases mtROS generation in rat liver. These studies suggest that the reduced intake of dietary methionine can be responsible for the decrease in mitochondrial ROS generation and the ensuing oxidative damage that occurs during DR, as well as for part of the increase in maximum longevity induced by this dietary manipulation. In addition, the mean intake of proteins (and thus methionine) of Western human populations is much higher than needed. Therefore, decreasing such levels to the recommended ones has a great potential to lower tissue oxidative stress and to increase healthy life span in humans while avoiding the possible undesirable effects of DR diets.",
"title": "Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible i..."
},
{
"docid": "MED-2324",
"text": "The level of food restriction that results in life extension and retarded aging in rodents also enhances their ability to cope with intense stressors. Moreover, this level of dietary restriction (DR) leads to a modest increase in the daily peak concentration of plasma free corticosterone, which strongly points to DR as a low-intensity stressor. These findings suggest that hormesis plays a role in the life-extending and anti-aging actions of DR. The evidence for and against this possibility is considered, and it is concluded that hormesis does have an important role.",
"title": "The role of hormesis in life extension by dietary restriction."
},
{
"docid": "MED-2509",
"text": "DR (dietary restriction), or reduced food intake without malnutrition, is associated with extended longevity, improved metabolic fitness and increased stress resistance in a wide range of organisms. DR is often referred to as calorie restriction, implying that reduced energy intake is responsible for its widespread and evolutionarily conserved benefits. However, recent data indicate dietary amino acid restriction as a key mediator of DR benefits. In fruitflies, an imbalance in essential amino acid intake is thought to underlie longevity benefits of DR. In mammals, reduced dietary protein or essential amino acid intake can extend longevity, improve metabolic fitness and increase stress resistance. In the present paper we review two evolutionarily conserved signal transduction pathways responsible for sensing amino acid levels. The eIF2α (eukaryotic initiation factor 2α) kinase GCN2 (general amino acid control non-derepressible 2) senses the absence of one or more amino acids by virtue of direct binding to uncharged cognate tRNAs. The presence of certain amino acids, such as leucine, permits activation of the master growth regulating kinase TOR (target of rapamycin). These two signal transduction pathways react to amino acid deprivation by inhibiting general protein translation while at the same time increasing translation of specific mRNAs involved in restoring homoeostasis. Together, these pathways may contribute to the regulation of longevity, metabolic fitness and stress resistance.",
"title": "Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR"
},
{
"docid": "MED-2502",
"text": "Dietary restriction (DR) without malnutrition is widely regarded to be a universal mechanism for prolonging lifespan. It is generally believed that the benefits of DR arise from eating fewer calories (termed caloric restriction, CR). Here we argue that, rather than calories, the key determinant of the relationship between diet and longevity is the balance of protein to non-protein energy ingested. This ratio affects not only lifespan, but also total energy intake, metabolism, immunity and the likelihood of developing obesity and associated metabolic disorders. Among various possible mechanisms linking macronutrient balance to lifespan, the nexus between the TOR and AMPK signaling pathways is emerging as a central coordinator.",
"title": "Macronutrient balance and lifespan"
},
{
"docid": "MED-2603",
"text": "FAS-associated protein with death domain (FADD) is the key adaptor protein transmitting apoptotic signals mediated by the main death receptors (DRs). Besides being an essential instrument in cell death, FADD is also implicated in proliferation, cell cycle progression, tumor development, inflammation, innate immunity, and autophagy. Recently, many of these new functions of FADD were shown to be independent of DRs. Moreover, FADD function is dictated by protein localization and phosphorylation state. Thus, FADD is a crucial and unique controller of many essential cellular processes. The full understanding of the networks dictating the ultimate function of FADD may provide a new paradigm for other multifaceted proteins. Copyright 2010 Elsevier Ltd. All rights reserved.",
"title": "FADD: a regulator of life and death."
},
{
"docid": "MED-3381",
"text": "Background: The proposition that synthetic food colors can induce adverse behavioral effects in children was first enunciated in 1975 by Feingold [Why Your Child Is Hyperactive. New York:Random House (1975)], who asserted that elevated sensitivity to food additives underlies the signs of hyperactivity observed in some children. Although the evidence suggested that some unknown proportion of children did respond to synthetic food colors, the U.S. Food and Drug Administration (FDA) interpreted the evidence as inconclusive. A study published in 2007 [McCann et al. Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial. Lancet 370:1560–1567 (2007)] drew renewed attention to the hypothesis because of the study’s size and scope. It led the FDA to review the evidence, hold a public hearing, and seek the advice of its Food Advisory Committee. In preparation for the hearing, the FDA reviewed the available evidence and concluded that it did not warrant further agency action. Objectives: In this commentary I examine the basis of the FDA’s position, the elements of the review that led to its decision and that of the Food Advisory Committee, and the reasons that this is an environmental health issue. Discussion: The FDA review confined itself, in essence, to the clinical diagnosis of hyperactivity, as did the charge to the committee, rather than asking the broader environmental question of behavioral effects in the general population; it failed to recognize the significance of vulnerable subpopulations; and it misinterpreted the meaning of effect size as a criterion of risk. The FDA’s response would have benefited from adopting the viewpoints and perspectives common to environmental health research. At the same time, the food color debate offers a lesson to environmental health researchers; namely, too narrow a focus on a single outcome or criterion can be misleading.",
"title": "Synthetic Food Colors and Neurobehavioral Hazards: The View from Environmental Health Research"
},
{
"docid": "MED-1116",
"text": "Molecular mimicry is one of the pathological mechanisms proposed to explain the association between microorganisms and autoimmune diseases. This review deals with the association between bacteria and rheumatic diseases with a special emphasis on rheumatoid arthritis where upper urinary tract infection by Proteus mirabilis is the possible cause of this severe, arthritic condition. Prospective trials involving anti-Proteus therapy should be carried out.",
"title": "Molecular mimicry between HLA-DR alleles associated with rheumatoid arthritis and Proteus mirabilis as the Aetiological basis for autoimmunity."
},
{
"docid": "MED-2763",
"text": "Despite compelling statistics that show we could eliminate 80%of all heart disease and strokes, 90% of all diabetes, and 60% of all cancers with basic lifestyle changes, we have failed to motivate the public to make these changes and failed to motivate policy makers to make healthy choices the easiest choice. Dr. Katz suggests we have failed because we have focused too much on statistics and too little on passion. He implores all of us to tap into people's passion by connecting each of these statistics with a human story.",
"title": "Facing the facelessness of public health: what's the public got to do with it?"
},
{
"docid": "MED-1709",
"text": "In the preceding point narrative, Drs. Bray and Popkin provide their opinion and review data that suggest to them that we need to reconsider the consumption of dietary sugar based on the growing concern of obesity and type 2 diabetes. In the counterpoint narrative below, we argue that there is no clear or convincing evidence that any dietary or added sugar has a unique or detrimental impact relative to any other source of calories on the development of obesity or diabetes. Sugar is purely a highly palatable source of energy; because it has no other property that appears to contribute to our nutritional well-being, it is not an essential food for most of us. For those who wish to reduce energy consumption, ingesting less sugar is a good place to start. However, doing so does not automatically portend any clinical benefit.",
"title": "Dietary sugar and body weight: have we reached a crisis in the epidemic of obesity and diabetes?: we have, but the pox on sugar is overwrought and ..."
},
{
"docid": "MED-2820",
"text": "Scope The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Methods and results Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Conclusion Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways.",
"title": "Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis"
},
{
"docid": "MED-1707",
"text": "Sugar-sweetened drinks have been associated with several health problems. In the point narrative as presented below, we provide our opinion and review of the data to date that we need to reconsider consumption of dietary sugar based on the growing concern of obesity and type 2 diabetes. In the counterpoint narrative following our contribution, Drs. Kahn and Sievenpiper provide a defense and suggest that dietary sugar is not the culprit. Data from the National Health and Nutrition Examination Survey and U.S. Department of Agriculture dietary surveys along with commercial Homescan data on household purchases were used to understand changes in sugar and fructose consumption. Meta-analyses and randomized clinical trials were used to evaluate outcomes of beverage and fructose intake. About 75% of all foods and beverages contain added sugar in a large array of forms. Consumption of soft drinks has increased fivefold since 1950. Meta-analyses suggest that consumption of sugar-sweetened beverages (SSBs) is related to the risk of diabetes, the metabolic syndrome, and cardiovascular disease. Drinking two 16-ounce SSBs per day for 6 months induced features of the metabolic syndrome and fatty liver. Randomized controlled trials in children and adults lasting 6 months to 2 years have shown that lowering the intake of soft drinks reduced weight gain. Recent studies suggest a gene-SSB potential relationship. Consumption of calorie-sweetened beverages has continued to increase and plays a role in the epidemic of obesity, the metabolic syndrome, and fatty liver disease. Reducing intake of soft drinks is associated with less weight gain.",
"title": "Dietary sugar and body weight: have we reached a crisis in the epidemic of obesity and diabetes?: health be damned! Pour on the sugar."
},
{
"docid": "MED-2812",
"text": "Curcumin derived from the tropical plant Curcuma longa has a long history of use as a dietary agent, food preservative, and in traditional Asian medicine. It has been used for centuries to treat biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. The preventive and therapeutic properties of curcumin are associated with its antioxidant, anti-inflammatory, and anticancer properties. Extensive research over several decades has attempted to identify the molecular mechanisms of curcumin action. Curcumin modulates numerous molecular targets by altering their gene expression, signaling pathways, or through direct interaction. Curcumin regulates the expression of inflammatory cytokines (e.g., TNF, IL-1), growth factors (e.g., VEGF, EGF, FGF), growth factor receptors (e.g., EGFR, HER-2, AR), enzymes (e.g., COX-2, LOX, MMP9, MAPK, mTOR, Akt), adhesion molecules (e.g., ELAM-1, ICAM-1, VCAM-1), apoptosis related proteins (e.g., Bcl-2, caspases, DR, Fas), and cell cycle proteins (e.g., cyclin D1). Curcumin modulates the activity of several transcription factors (e.g., NF-κB, AP-1, STAT) and their signaling pathways. Based on its ability to affect multiple targets, curcumin has the potential for the prevention and treatment of various diseases including cancers, arthritis, allergies, atherosclerosis, aging, neurodegenerative disease, hepatic disorders, obesity, diabetes, psoriasis, and autoimmune diseases. This review summarizes the molecular mechanisms of modulation of gene expression by curcumin. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Molecular mechanisms of curcumin action: gene expression."
},
{
"docid": "MED-1711",
"text": "Summary Objectives The insulin-like growth factor (IGF) signaling pathway has been implicated in the pathogenesis of numerous tumor types, including non-small cell lung cancer (NSCLC). Figitumumab is a fully human IgG2 monoclonal antibody against IGF-1 receptor (IGF-1R). Methods This phase I, open-label, dose-escalation study (ClinicalTrials.gov: NCT00603538) assessed the safety and tolerability of figitumumab (6, 10 and 20 mg/kg) in combination with carboplatin (area under the curve: 6 mg·min/mL) and paclitaxel (200 mg/m2) in Japanese patients (N = 19) with chemotherapy-naïve, advanced NSCLC. Treatments were administered intravenously on day 1 of a 21-day cycle for four to six cycles. Pharmacokinetics, biomarkers, and antitumor activity were also evaluated. Results Figitumumab in combination with carboplatin and paclitaxel was well tolerated at doses up to 20 mg/kg; no dose-limiting toxicities were observed at this dose level. When given in combination, figitumumab plasma exposure increased in an approximately dose-proportional manner. The approximate 2-fold accumulation following repeated administration supported the 21-day regimen as appropriate for figitumumab administration. Serum total IGF-1 and IGF binding protein-3 concentrations increased following figitumumab dosing, but a clear dose-dependent relationship was not demonstrated. Seven of 18 evaluable patients experienced a partial response. Conclusions Figitumumab 20 mg/kg in combination with carboplatin and paclitaxel was well tolerated in chemotherapy-naïve Japanese patients with NSCLC. Further analysis of biomarker data is necessary for the development of figitumumab therapy.",
"title": "Figitumumab combined with carboplatin and paclitaxel in treatment-naïve Japanese patients with advanced non-small cell lung cancer"
},
{
"docid": "MED-4909",
"text": "Oral aluminum (Al) bioavailability from drinking water has been previously estimated, but there is little information on Al bioavailability from foods. It was suggested that oral Al bioavailability from drinking water is much greater than from foods. The objective was to further test this hypothesis. Oral Al bioavailability was determined in the rat from basic [26Al]-sodium aluminum phosphate (basic SALP) in a process cheese. Consumption of ~ 1 gm cheese containing 1.5 or 3% basic SALP resulted in oral Al bioavailability (F) of ~ 0.1 and 0.3%, respectively, and time to maximum serum 26Al concentration (Tmax) of 8 to 9 h. These Al bioavailability results were intermediate to previously reported results from drinking water (F ~ 0.3%) and acidic-SALP incorporated into a biscuit (F ~ 0.1%), using the same methods. Considering the similar oral bioavailability of Al from food vs. water, and their contribution to the typical human’s daily Al intake (~ 95 and 1.5%, respectively), these results suggest food contributes much more Al to systemic circulation, and potential Al body burden, than does drinking water. These results do not support the hypothesis that drinking water provides a disproportionate contribution to total Al absorbed from the gastrointestinal tract.",
"title": "Aluminum bioavailability from basic sodium aluminum phosphate, an approved food additive emulsifying agent, incorporated in cheese"
},
{
"docid": "MED-1181",
"text": "Demand for organic foods is partially driven by consumers' perceptions that they are more nutritious. However, scientific opinion is divided on whether there are significant nutritional differences between organic and non-organic foods, and two recent reviews have concluded that there are no differences. In the present study, we carried out meta-analyses based on 343 peer-reviewed publications that indicate statistically significant and meaningful differences in composition between organic and non-organic crops/crop-based foods. Most importantly, the concentrations of a range of antioxidants such as polyphenolics were found to be substantially higher in organic crops/crop-based foods, with those of phenolic acids, flavanones, stilbenes, flavones, flavonols and anthocyanins being an estimated 19 (95 % CI 5, 33) %, 69 (95 % CI 13, 125) %, 28 (95 % CI 12, 44) %, 26 (95 % CI 3, 48) %, 50 (95 % CI 28, 72) % and 51 (95 % CI 17, 86) % higher, respectively. Many of these compounds have previously been linked to a reduced risk of chronic diseases, including CVD and neurodegenerative diseases and certain cancers, in dietary intervention and epidemiological studies. Additionally, the frequency of occurrence of pesticide residues was found to be four times higher in conventional crops, which also contained significantly higher concentrations of the toxic metal Cd. Significant differences were also detected for some other (e.g. minerals and vitamins) compounds. There is evidence that higher antioxidant concentrations and lower Cd concentrations are linked to specific agronomic practices (e.g. non-use of mineral N and P fertilisers, respectively) prescribed in organic farming systems. In conclusion, organic crops, on average, have higher concentrations of antioxidants, lower concentrations of Cd and a lower incidence of pesticide residues than the non-organic comparators across regions and production seasons.",
"title": "Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses"
},
{
"docid": "MED-3844",
"text": "Low lignan status has been reported to be related to an elevated risk of breast cancer. Since lignan status is reduced by antibacterial medications, it is plausible to hypothesize that repeated use of antibiotics may also be a risk factor for breast cancer. History of treatment for urinary tract infection was studied for its prediction of breast cancer among 9461 Finnish women 19–89 years of age and initially cancer-free. During a follow-up in 1973–1991, a total of 157 breast cancer cases were diagnosed. Women reporting previous or present medication for urinary tract infection at baseline showed an elevated breast cancer risk in comparison with other women. The age-adjusted relative risk was 1.34 (95% confidence interval (CI) = 0.98–1.83). The association was concentrated to women under 50 years of age. The relative risk for these women was 1.74 (95% CI 1.13–2.68), whereas it was 0.97 (95% CI 0.59–1.58) for older women. The relative risk in the younger age-group was 1.47 (95% CI 0.73–2.97) during the first 10 years of follow-up, and 1.93 (95% CI 1.11–3.37) for follow-up times longer than 10 years. These data suggest that premenopausal women using long-term medication for urinary tract infections show a possible elevated risk of future breast cancer. The results are, however, still inconclusive and the hypothesis needs to be tested by other studies. © 2000 Cancer ResearchCampaign",
"title": "Does antibacterial treatment for urinary tract infection contribute to the risk of breast cancer?"
},
{
"docid": "MED-3656",
"text": "The etiology of bacterial vaginosis is unknown, and there are no long-term therapies for preventing this frequently recurring condition. Vaginal douching has been reported to be associated with bacterial vaginosis in observational studies. However, this association may be due to confounding by indication—that is, confounding by women douching in response to vaginal symptoms associated with bacterial vaginosis. The authors used marginal structural modeling to estimate the causal effect of douching on bacterial vaginosis risk while controlling for this confounding effect. In 1999–2002, nonpregnant women (n = 3,620) were recruited into a prospective study when they visited one of 12 public health clinics in Birmingham, Alabama, for routine care. Participants were assessed quarterly for 1 year. Bacterial vaginosis was based on a Nugent's Gram stain score of 7 or higher. Thirty-two percent of participants douched in every study interval, and 43.0% never douched. Of the 12,349 study visits, 40.2% were classified as involving bacterial vaginosis. The relative risk for regular douching as compared with no douching was 1.21 (95% confidence interval: 1.08, 1.38). These findings indicate that douching confers increased risk of disruption of vaginal flora. In the absence of a large randomized trial, these findings provide the best evidence to date for a risk of bacterial vaginosis associated with douching.",
"title": "A Longitudinal Study of Vaginal Douching and Bacterial Vaginosis—A Marginal Structural Modeling Analysis"
},
{
"docid": "MED-4609",
"text": "Two pandemics of heart attack deaths have plagued the world's population during the past 130 years. The first pandemic, induced by beriberi, was caused by the industrial revolution altering the nutritional composition of rice. By 1892 a simple working knowledge, then at hand, could have terminated the beriberi plague; however, orthodox medicine being then enchanted with the false concept that all disease was caused by germs, permitted millions of Asians to die needlessly of beriberi by refusing to tell them to eat rice bran or to drink rice bran tea. A second pandemic of heart attack deaths, called myocardial infarction (MI), struck the developed nations of the Western World in full force after 1930. As a hypothesis, it is suggested that this MI pandemic, still raging today, was caused by a change in food processing that occurred after 1920, when the new oil seed industry introduced into our food three greatly harmful lipid substances. The unnatural trans-trans isomer of linoleic acid, which had never been in human food prior to 1920 and which entered our food in margarines and refined oils, blocked the conversion of natural cis-cis linoleic acid to prostaglandin E1, which tends to prevent MI, both by acting as a vasodilator and by minimizing platelet aggregation. Harmful lactones were also introduced into our food, increasing the risk of MI by decreasing the fibrinolytic activity of our blood. The oil seed industry also introduced into our diet free radical lipid peroxides that make the myocardium more vulnerable to infarction. It is suggested that except for the one in 500 of us who is afflicted by familial hypercholesterolemia, the cholesterol concept of MI is as false today as was the concept in 1900 that germs caused beriberi. It is further suggested that a working knowledge is at hand today that can make death from MI just as rare as death is now from a beriberi-induced heart attack.",
"title": "The beriberi analogy to myocardial infarction."
},
{
"docid": "MED-851",
"text": "Barrett's oesophagus normally affects the distal oesophagus when metaplastic columnar lined epithelium replaces stratified squamous epithelium which predisposes to cancer development. This develops as a consequence of chronic gastroesophageal reflux (GORD). Those with Barrett's have a 40 fold increased risk of oesophageal adenocarcinoma [1]. There are is still a lack of understanding of the natural history of the cell of origin. This does hamper research into this area. We accept that there is a limitation in testing of the pathogenesis of Barrett's oesophagus due to a lack of a universally accepted animal model. The major questions surrounding Barrett's oesophagus include validity of surveillance strategies, the optimal treatment and more importantly an agent that can prevent progression to cancer without unacceptable side effects. The main chemopreventative agents that show promise are aspirin and proton pump inhibitors (PPIs). There are other agents such as green tea, berries and antioxidants and diet that have been suggested; we discuss the evidence available for these strategies. We hope for continued improvement in the clinical trial infrastructure to facilitate testing of new pharmacological and endoscopic interventions for Barrett's oesophagus. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Chemoprevention in Barrett's oesophagus."
},
{
"docid": "MED-1500",
"text": "BACKGROUND: Regular consumption of fruit and vegetables has been considered to be associated with a reduced risk of dementia and age-associated cognitive decline, although the association is currently unsupported by a systematic review of the literature. METHODS: We searched Medline, Embase, Biosis, ALOIS, the Cochrane library, different publisher databases as well as bibliographies of retrieved articles. All cohort studies with a follow-up of 6 months or longer were included if they reported an association of Alzheimer's disease or cognitive decline in regard to the frequency of fruit and vegetables consumption. FINDINGS: Nine studies with a total of 44,004 participants met the inclusion criteria. Six studies analyzed fruit and vegetables separately and five of them found that higher consumption of vegetables, but not fruit is associated with a decreased risk of dementia or cognitive decline. The same association was found by three further studies for fruit and vegetable consumption analytically combined. CONCLUSION: Increased intake of vegetables is associated with a lower risk of dementia and slower rates of cognitive decline in older age. Yet, evidence that this association is also valid for high fruit consumption is lacking.",
"title": "Fruit, vegetables and prevention of cognitive decline or dementia: a systematic review of cohort studies."
},
{
"docid": "MED-3549",
"text": "Studies have shown that fisetin, a small phytochemical molecule, has antitumor activity; however, its antiangiogenic activity has not yet been examined. Accordingly, herein, we investigated the antiangiogenic efficacy and associated mechanisms of fisetin in human umbilical vein endothelial cells (HUVECs). Fisetin (10-50 μM) strongly inhibited the regular serum plus growth supplement- and vascular endothelial growth factor (VEGF)-induced growth (up to 92%, P < 0.001) and survival (up to 16%, P < 0.001) of HUVEC in a dose- and time-dependent manner. Fisetin also caused cell cycle arrest at G(1) (strong) and G(2)/M (moderate) phases together with a decrease in cyclin D1 and an increase in p53 levels. Fisetin-caused cell death was accompanied by decreased expression of survivin and an increase in cleaved levels of caspases-3 and -7 and poly-(ADP-ribose) polymerase along with an increased ratio of Bax to Bcl-2. Furthermore, fisetin inhibited capillary-like tube formation on Matrigel (up to 85%, P < 0.001) as well as migration (up to 66%, P < 0.001), which were associated with decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF in HUVEC. It also decreased the expression of eNOS, VEGF, inducible nitric oxide synthase, matrix metalloproteinase-2 and -9 in A549 and DU145 human cancer cells. In vivo matrigel plug assay in mice showed significant decrease in size (up to 43%, P < 0.001), vascularization and hemoglobin content (up to 94%, P < 0.001) in the plugs from fisetin-treated, compared with control mice. Overall, these results suggest that fisetin inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects, and therefore, fisetin warrants further investigation for its angiopreventive potential toward cancer control.",
"title": "Fisetin inhibits various attributes of angiogenesis in vitro and in vivo--implications for angioprevention."
},
{
"docid": "MED-5209",
"text": "A 5-year-old boy with autism developed dry eye and xerophthalmia. Serum vitamin A was undetectable. Dietary history revealed a markedly altered intake consisting of only fried potatoes and rice balls for 2 years. Fried potatoes contain no vitamin A. Autism is a multifaceted developmental disorder infrequently accompanied by abnormal eating practices. To the authors' knowledge, most children with autism who develop dietary vitamin A deficiency have consumed an excess of fried potatoes. Attention to possible vitamin A deficiency is essential when fried potatoes are consumed exclusively.",
"title": "Fried-potato diet causes vitamin A deficiency in an autistic child."
},
{
"docid": "MED-5045",
"text": "Helicobacter pylori (H. pylori) is one of the most widespread human pathogens, and plays major roles in chronic gastritis and gastric cancer. CD74 of gastric epithelial cells has recently been identified as an adhesion molecule to urease in H. pylori. In this study, we found that CD74 is highly expressed in a constitutive manner in NCI-N87 human gastric carcinoma cells at both the protein and mRNA levels as compared with Hs738St./Int fetal gastric cells. Subsequently, a novel cell-based ELISA able to rapidly screen the suppressive agents of CD74 expression was established. NCI-N87 cells were treated separately with 25 different food phytochemicals (4–100 µM) for 48 h and subjected to our novel assay. From those results, a citrus coumarin, bergamottin, was indicated to be the most promising compound with an LC50/IC50 value greater than 7.1, followed by luteolin (>5.4), nobiletin (>5.3), and quercetin (>5.1). Our findings suggest that these CD74 suppressants are unique candidates for preventing H. pylori adhesion and subsequent infection with reasonable action mechanisms.",
"title": "Suppressive Effects of Selected Food Phytochemicals on CD74 Expression in NCI-N87 Gastric Carcinoma Cells"
},
{
"docid": "MED-5161",
"text": "Dietary flavonols and flavones are subgroups of flavonoids that have been suggested to decrease the risk of coronary heart disease (CHD). The authors prospectively evaluated intakes of flavonols and flavones in relation to risk of nonfatal myocardial infarction and fatal CHD in the Nurses' Health Study. They assessed dietary information from the study's 1990, 1994, and 1998 food frequency questionnaires and computed cumulative average intakes of flavonols and flavones. Cox proportional hazards regression with time-varying variables was used for analysis. During 12 years of follow-up (1990-2002), the authors documented 938 nonfatal myocardial infarctions and 324 CHD deaths among 66,360 women. They observed no association between flavonol or flavone intake and risk of nonfatal myocardial infarction or fatal CHD. However, a weak risk reduction for CHD death was found among women with a higher intake of kaempferol, an individual flavonol found primarily in broccoli and tea. Women in the highest quintile of kaempferol intake relative to those in the lowest had a multivariate relative risk of 0.66 (95% confidence interval: 0.48, 0.93; p for trend = 0.04). The lower risk associated with kaempferol intake was probably attributable to broccoli consumption. These prospective data do not support an inverse association between flavonol or flavone intake and CHD risk.",
"title": "Dietary intakes of flavonols and flavones and coronary heart disease in US women."
},
{
"docid": "MED-3978",
"text": "SUMMARY The aim of this study was to investigate the relationship between dog and cat ownership and gastroenteritis in young children. A diary study of 965 children aged 4–6 years living in rural or semi-rural South Australia was undertaken. Data were collected on pet ownership, drinking water and other risk factors for gastroenteritis. Overall 89% of households had pets and dog ownership was more common than cat ownership. The multivariable models for gastroenteritis and pet ownership indicated that living in a household with a dog or cat was associated with a reduced risk of gastroenteritis (adj. OR 0·71, 95% CI 0·55–0·92; OR 0·70, % CI 0·51–0·97 respectively). This paper adds to the evidence that pets are not a major source of gastroenteritis in the home and lends support to the health benefits of pet ownership. However, this must be weighed against the potential negative consequences, such as dog bites, particularly for this age group.",
"title": "Does dog or cat ownership lead to increased gastroenteritis in young children in South Australia?"
}
] |
PLAIN-330
|
Soymilk: shake it up!
|
[
{
"docid": "MED-3087",
"text": "Sixty random samples of bulk farm milk, market milk, locally manufactured processed cheese, and milk powder were collected to be analyzed for aluminum (Al) concentration using graphite furnace atomic absorption spectrometry (GFAAS). The results were compared with provisional acceptable permissible limits (PAPLs). The maximum estimated dietary intake (MEDI) of Al for the examined samples was calculated. In addition, an experimental study was conducted to determine the possible leaching of Al from cookware in milk during boiling. The obtained results showed that Al concentration in examined bulk farm milk samples was found to be negligible. In contrast, market milk revealed higher concentration, 65.0% of the examined samples were above the PAPLs. The results revealed significant difference of Al concentration among them. The Al levels in processed cheese wrapped in Al foil were significantly higher than those found in samples packed in glass containers with a significant difference of Al concentration between them. Also, 20% of the examined milk powder samples exceeded the PAPLs (0.01 to 0.4 mg/kg). The MEDI for Al in bulk farm milk, control market milk, market milk boiled in Al cookware, market milk boiled in stainless-steel cookware, processed cheese wrapped in Al foil, processed cheese packed in glass containers, and milk powder were calculated as 3.0%, 61.0%, 63.0%, 61.0%, 428.0%, 220.0%, and 166.0% from \"PTDI,\" respectively. The results of the experimental study showed no marked significant differences of Al concentration between market milk (control group) and those boiled in Al cookware, as well as to those boiled in stainless-steel cookware. PRACTICAL APPLICATION: The results of the present study indicate that Al level in milk kept in Al containers and dairy products packed in Al foil is beyond the permissible limits, suggesting health hazard. Therefore, all milk cans should be constructed of stainless steel, prevent the entrance of tap water into milk, and the processed cheese should be packed in glass containers and not wrapped in Al foil. Leaching of Al increased to a significant percent more during storage than during boiling, so milk should be kept in stainless steel or glass containers in the refrigerator.",
"title": "Prevalence and public health significance of aluminum residues in milk and some dairy products."
},
{
"docid": "MED-754",
"text": "CONTEXT: Combining foods with recognized cholesterol-lowering properties (dietary portfolio) has proven highly effective in lowering serum cholesterol under metabolically controlled conditions. OBJECTIVE: To assess the effect of a dietary portfolio administered at 2 levels of intensity on percentage change in low-density lipoprotein cholesterol (LDL-C) among participants following self-selected diets. DESIGN, SETTING, AND PARTICIPANTS: A parallel-design study of 351 participants with hyperlipidemia from 4 participating academic centers across Canada (Quebec City, Toronto, Winnipeg, and Vancouver) randomized between June 25, 2007, and February 19, 2009, to 1 of 3 treatments lasting 6 months. INTERVENTION: Participants received dietary advice for 6 months on either a low-saturated fat therapeutic diet (control) or a dietary portfolio, for which counseling was delivered at different frequencies, that emphasized dietary incorporation of plant sterols, soy protein, viscous fibers, and nuts. Routine dietary portfolio involved 2 clinic visits over 6 months and intensive dietary portfolio involved 7 clinic visits over 6 months. MAIN OUTCOME MEASURES: Percentage change in serum LDL-C. RESULTS: In the modified intention-to-treat analysis of 345 participants, the overall attrition rate was not significantly different between treatments (18% for intensive dietary portfolio, 23% for routine dietary portfolio, and 26% for control; Fisher exact test, P = .33). The LDL-C reductions from an overall mean of 171 mg/dL (95% confidence interval [CI], 168-174 mg/dL) were -13.8% (95% CI, -17.2% to -10.3%; P < .001) or -26 mg/dL (95% CI, -31 to -21 mg/dL; P < .001) for the intensive dietary portfolio; -13.1% (95% CI, -16.7% to -9.5%; P < .001) or -24 mg/dL (95% CI, -30 to -19 mg/dL; P < .001) for the routine dietary portfolio; and -3.0% (95% CI, -6.1% to 0.1%; P = .06) or -8 mg/dL (95% CI, -13 to -3 mg/dL; P = .002) for the control diet. Percentage LDL-C reductions for each dietary portfolio were significantly more than the control diet (P < .001, respectively). The 2 dietary portfolio interventions did not differ significantly (P = .66). Among participants randomized to one of the dietary portfolio interventions, percentage reduction in LDL-C on the dietary portfolio was associated with dietary adherence (r = -0.34, n = 157, P < .001). CONCLUSION: Use of a dietary portfolio compared with the low-saturated fat dietary advice resulted in greater LDL-C lowering during 6 months of follow-up. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00438425.",
"title": "Effect of a dietary portfolio of cholesterol-lowering foods given at 2 levels of intensity of dietary advice on serum lipids in hyperlipidemia: a r..."
}
] |
[
{
"docid": "MED-4682",
"text": "Calcium loss after menopause increases the risk of osteoporosis in aging women. Soymilk is often consumed to reduce menopausal symptoms, although in its native form, it contains significantly less calcium than cow's milk. Moreover, when calcium is added as a fortificant, it may not be absorbed efficiently. This study compares calcium absorption from soymilk fortified with a proprietary phosphate of calcium versus absorption from cow's milk. Preliminary studies compared methods for labelling the calcium fortificant either before or after its addition to soymilk. It was established that fortificant labelled after it was added to soymilk had a tracer distribution pattern very similar to that shown by fortificant labelled before adding to soymilk, provided a heat treatment (90?C for 30 min) was applied. This method was therefore used for further bioavailability studies. Calcium absorption from fortified soy milk compared to cow's milk was examined using a randomised single-blind acute cross-over design study in 12 osteopenic post-menopausal women aged (mean +/- SD) 56.7+/-5.3 years, with a body mass index of 26.5+/-5.6 kg/m2. Participants consumed 20 mL of test milk labelled after addition of fortificant with 185 kBq of 45Ca in 44 mg of calcium carrier, allowing the determination of the hourly fractional calcium absorption rate (alpha) using a single isotope radiocalcium test. The mean hourly fractional calcium absorption from fortified soymilk was found to be comparable to that of cows' milk: alpha = 0.65+/-0.19 and alpha =0.66+/-0.22, p>0.05, respectively.",
"title": "Calcium absorption in Australian osteopenic post-menopausal women: an acute comparative study of fortified soymilk to cows' milk."
},
{
"docid": "MED-4873",
"text": "The use of over-the-counter supplements is commonplace in today's health conscious society. We present an unusual case of intrahepatic cholestasis caused by vitamin A intoxication. The patient consumed one Herbalife shake with two multivitamin tablets of the same brand for 12 years. When calculated this equated to more than the recommended daily allowance for vitamin A consumption. Deranged liver function tests were consistent with a cholestatic process. Liver biopsy was obtained and revealed features pathognomonic of vitamin A toxicity, without the usual fibrosis. When the supplements were ceased, his jaundice and alkaline phosphatase completely normalized. This case highlights the importance of health care providers documenting non-prescribed dietary supplements and considering them in the etiology of cholestatic liver disease. Copyright 2009 Elsevier Inc. All rights reserved.",
"title": "Hypervitaminosis A inducing intra-hepatic cholestasis--a rare case report."
},
{
"docid": "MED-1253",
"text": "OBJECTIVES: To investigate the effect of replacing lean meat with a soy product, tofu, on serum lipoprotein concentrations. STUDY AND DESIGN: Randomized cross-over dietary intervention study. SUBJECTS: Forty-two free-living healthy males aged 35-62 y completed the dietary intervention. Three additional subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing lean meat (150 g/d) was compared with one with 290 g/d tofu in an isocaloric and isoprotein substitution. Both diet periods were 1 month, and fat intake was carefully controlled. RESULTS: Seven-day diet records showed the two diets were similar in energy, macronutrients and fibre. Total cholesterol (mean difference 0.23 mmol/l, 95% CI 0.02, 0.43; P=0.03) and triglycerides (mean difference 0.15 mmol/l, 95% CI 0.02, 0.31; P=0.017) were significantly lower on the tofu diet than the lean meat diet. However, HDL-C was also significantly lower on the tofu diet (mean difference 0.08 mmol/l, 95% CI 0.02, 0.14; P=0.01) although the LDL-C:HDL-C ratio was similar. CONCLUSION: The effect on HDL-C and the small LDL-C reduction differ from some other studies, where fat was often less controlled, and the comparison was of soy as textured protein or soymilk against casein. This suggests a differential effect of the various proteins compared to the soy may influence the findings. In practice, the replacement of meat with tofu would usually be associated with a decrease in saturated fat and an increase in polyunsaturated fat and this should enhance any small benefits due to the soy protein. SPONSOR: Deakin University with some contribution from a Commonwealth Department of Veterans Affairs research grant. European Journal of Clinical Nutrition (2000) 54, 14-19",
"title": "Effects of soy as tofu vs meat on lipoprotein concentrations."
},
{
"docid": "MED-4804",
"text": "BACKGROUND: Alcohol-based hand rubs (ABHRs) are an effective means of decreasing the transmission of bacterial pathogens. Alcohol is not effective against Clostridium difficile spores. We examined the retention of C. difficile spores on the hands of volunteers after ABHR use and the subsequent transfer of these spores through physical contact. METHODS: Nontoxigenic C. difficile spores were spread on the bare palms of 10 volunteers. Use of 3 ABHRs and chlorhexidine soap-and-water washing were compared with plain water rubbing alone for removal of C. difficile spores. Palmar cultures were performed before and after hand decontamination by means of a plate stamping method. Transferability of C. difficile after application of ABHR was tested by having each volunteer shake hands with an uninoculated volunteer. RESULTS: Plain water rubbing reduced palmar culture counts by a mean (+/- standard deviation [SD]) of 1.57 +/- 0.11 log10 colony-forming units (CFU) per cm2, and this value was set as the zero point for the other products. Compared with water washing, chlorhexidine soap washing reduced spore counts by a mean (+/- SD) of 0.89 +/- 0.34 log10 CFU per cm2; among the ABHRs, Isagel accounted for a reduction of 0.11 +/- 0.20 log10 CFU per cm2 (P = .005), Endure for a reduction of 0.37 +/- 0.42 log10 CFU per cm2 (P = .010), and Purell for a reduction of 0.14 +/- 0.33 log10 CFU per cm2 (P = .005). There were no statistically significant differences between the reductions achieved by the ABHRs; only Endure had a reduction statistically different from that for water control rubbing (P = .040). After ABHR use, handshaking transferred a mean of 30% of the residual C. difficile spores to the hands of recipients. CONCLUSIONS: Hand washing with soap and water is significantly more effective at removing C. difficile spores from the hands of volunteers than are ABHRs. Residual spores are readily transferred by a handshake after use of ABHR.",
"title": "Effectiveness of alcohol-based hand rubs for removal of Clostridium difficile spores from hands."
},
{
"docid": "MED-4989",
"text": "BACKGROUND: A high nutrient density (HND) vegetable-based diet offers a dietary model extremely low in saturated fat as well as refined carbohydrates and emphasizes a liberal intake of fresh fruits, vegetables, beans, and nuts. We conducted a retrospective chart review of patients who came to a family practice office seeking nutritional counseling for weight loss. All of these patients were prescribed an HND diet in an extended counseling session with a family physician. METHODS: A convenience sample (N = 56) of all patients seeking dietary counseling for weight loss from a family practice physician in a 3-year period was included in the chart review. No personal identifying data were recorded. The initial counseling sessions averaged 1 hour in length. Patients were provided with a sample HND daily meal plan and recipes and with verbal and written information about the rationale for the diet. Data recorded from patients' charts at 6-month intervals for up to 2 years of follow-up (when available) included weight, blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and cholesterol:HDL ratio. Non-parametric statistical testing using the Friedman rank order (exact) test for k-related samples was conducted. A follow-up survey on adherence and medication use was completed by 38 patients. RESULTS: Of the 33 patients who returned for follow-up after 1 year, the mean weight loss was 31 lbs (P = .000). Of the 19 patients who returned after 2 years, the mean weight loss was 53 lbs (P = .000), mean cholesterol fell by 13 points, LDL by 15 points, triglycerides by 17 points, and cardiac risk ratio dropped from 4.5 to 3.8. Changes in systolic and diastolic blood pressure were highly significant at all follow-up time intervals (P < or = .001). There was a significant correlation between adherence and degree of weight loss (P = .011). CONCLUSIONS: Weight loss was sustained in patients who returned for follow-up and was more substantial in those who reported good adherence to the recommendations. However, many patients were lost to follow-up. Favorable changes in lipid profile and blood pressure were noted. An HND diet has the potential to provide sustainable, significant, long-term weight loss and may provide substantial lowering of cardiac risk in patients who are motivated and provided with extended one-on-one counseling and follow-up visits. Development of tools to aid in patient retention is an area for possible further study. Clinical trials with long-term follow-up are needed to further test the therapeutic potential and to examine adherence and follow-up issues related to this dietary approach. An HND diet as demonstrated with this group may be the most health-favorable and effective way to lose weight for appropriately motivated patients.",
"title": "Effect of a high nutrient density diet on long-term weight loss: a retrospective chart review."
},
{
"docid": "MED-3549",
"text": "Studies have shown that fisetin, a small phytochemical molecule, has antitumor activity; however, its antiangiogenic activity has not yet been examined. Accordingly, herein, we investigated the antiangiogenic efficacy and associated mechanisms of fisetin in human umbilical vein endothelial cells (HUVECs). Fisetin (10-50 μM) strongly inhibited the regular serum plus growth supplement- and vascular endothelial growth factor (VEGF)-induced growth (up to 92%, P < 0.001) and survival (up to 16%, P < 0.001) of HUVEC in a dose- and time-dependent manner. Fisetin also caused cell cycle arrest at G(1) (strong) and G(2)/M (moderate) phases together with a decrease in cyclin D1 and an increase in p53 levels. Fisetin-caused cell death was accompanied by decreased expression of survivin and an increase in cleaved levels of caspases-3 and -7 and poly-(ADP-ribose) polymerase along with an increased ratio of Bax to Bcl-2. Furthermore, fisetin inhibited capillary-like tube formation on Matrigel (up to 85%, P < 0.001) as well as migration (up to 66%, P < 0.001), which were associated with decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF in HUVEC. It also decreased the expression of eNOS, VEGF, inducible nitric oxide synthase, matrix metalloproteinase-2 and -9 in A549 and DU145 human cancer cells. In vivo matrigel plug assay in mice showed significant decrease in size (up to 43%, P < 0.001), vascularization and hemoglobin content (up to 94%, P < 0.001) in the plugs from fisetin-treated, compared with control mice. Overall, these results suggest that fisetin inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects, and therefore, fisetin warrants further investigation for its angiopreventive potential toward cancer control.",
"title": "Fisetin inhibits various attributes of angiogenesis in vitro and in vivo--implications for angioprevention."
},
{
"docid": "MED-3306",
"text": "OBJECTIVES: Occupation as a farmer has been associated with increased risks of haematological cancers in adults. This study aimed to examine whether farm exposures in childhood contribute to these risks, by using parental occupation in farming as a proxy for growing up on a farm. METHODS: New Zealand death records (1998-2003) of persons aged 35-85 were extracted (n=114 289). For 82.3% usual occupation and the occupation of at least one of the parents could be coded (n=94 054). Unconditional logistic regression analyses included 3119 haematological cancer deaths (cases) and 90 935 deaths from other causes (controls). ORs for farming and growing up on a farm were adjusted for each other, year of birth, age at death, socio-economic status, Māori ethnicity, immigration status and sex. RESULTS: Growing up on a livestock farm was positively associated with haematological cancer (OR 1.22, 95% CI 1.05 to 1.41), particularly for poultry farms (OR 2.99, 95% CI 1.44 to 6.21), while growing up on a crop farm was not (OR 0.81, 95% CI 0.64 to 1.03). Crop farming in adulthood was associated with an increased haematological cancer risk (OR 1.49, 95% CI 1.13 to 1.96), while livestock farming was not (OR 0.80, 95% CI 0.63 to 1.00), except for beef cattle farming (OR 2.99, 95% CI 1.28 to 7.00). These results did not change appreciably when different control groups with different causes of death were used. CONCLUSIONS: These results could suggest a role for early life biological exposures in the development of haematological cancers.",
"title": "Farming, growing up on a farm, and haematological cancer mortality."
},
{
"docid": "MED-4829",
"text": "BACKGROUND: Statin therapy can cause myopathy, however it is unclear whether this exacerbates age-related muscle function declines. AIM: To describe differences between statin users and non-users in muscle mass, muscle function and falls risk in a group of community-dwelling older adults. DESIGN: A prospective, population-based cohort study with a mean follow-up of 2.6 years. METHODS: Total 774 older adults [48% female; mean (standard deviation) age = 62 (7) years] were examined at baseline and follow-up. Differences in percentage appendicular lean mass (%ALM), leg strength, leg muscle quality (LMQ; specific force) and falls risk were compared for statin users and non-users. RESULTS: There were 147 (19%) statin users at baseline and 179 (23%) at follow-up. Longitudinal analyses revealed statin use at baseline predicted increased falls risk scores over 2.6 years (0.14, 95% CI 0.01 to 0.27) and a trend towards increased %ALM (0.45%, 95% CI -0.01 to 0.92). Statin users at both time points demonstrated decreased leg strength (-5.02 kg, 95% CI -9.65 to -0.40) and LMQ (-0.30 kg/kg, 95% CI -0.59 to -0.01), and trended towards increased falls risk (0.13, 95% CI -0.01 to 0.26) compared to controls. Finally, statin users at both baseline and follow-up demonstrated decreased leg strength (-16.17 kg, 95% CI -30.19 to -2.15) and LMQ (-1.13 kg/kg, 95% CI -2.02 to -0.24) compared to those who had ceased statin use at follow-up. CONCLUSION: Statin use may exacerbate muscle performance declines and falls risk associated with aging without a concomitant decrease in muscle mass, and this effect may be reversible with cessation.",
"title": "Statin therapy, muscle function and falls risk in community-dwelling older adults."
},
{
"docid": "MED-5004",
"text": "BACKGROUND: Cross-sectional studies have shown that vegetarians and vegans are leaner than omnivores. Longitudinal data on weight gain in these groups are sparse. OBJECTIVE: We investigated changes in weight and body mass index (BMI) over a 5-year period in meat-eating, fish-eating, vegetarian, and vegan men and women in the UK. DESIGN: Self-reported anthropometric, dietary and lifestyle data were collected at baseline in 1994-1999 and at follow-up in 2000-2003; the median duration of follow-up was 5.3 years. SUBJECTS: A total of 21,966 men and women participating in Oxford arm of the European Prospective Investigation into Cancer and Nutrition aged 20-69 years at baseline. RESULTS: The mean annual weight gain was 389 (SD 884) g in men and 398 (SD 892) g in women. The differences between meat-eaters, fish-eaters, vegetarians and vegans in age-adjusted mean BMI at follow-up were similar to those seen at baseline. Multivariable-adjusted mean weight gain was somewhat smaller in vegans (284 g in men and 303 g in women, P<0.05 for both sexes) and fish-eaters (338 g, women only, P<0.001) compared with meat-eaters. Men and women who changed their diet in one or several steps in the direction meat-eater --> fish-eater --> vegetarian --> vegan showed the smallest mean annual weight gain of 242 (95% CI 133-351) and 301 (95% CI 238-365) g, respectively. CONCLUSION: During 5 years follow-up, the mean annual weight gain in a health-conscious cohort in the UK was approximately 400 g. Small differences in weight gain were observed between meat-eaters, fish-eaters, vegetarians and vegans. Lowest weight gain was seen among those who, during follow-up, had changed to a diet containing fewer animal food.",
"title": "Weight gain over 5 years in 21,966 meat-eating, fish-eating, vegetarian, and vegan men and women in EPIC-Oxford."
},
{
"docid": "MED-3452",
"text": "Vitamins have traditionally been considered as food components that are required in the normal diet to prevent deficiencies. However, a newer concept of the function of vitamins in nutrition has taken them beyond simply prevention of deficiency symptoms. This concept considers that many vitamins, when taken in relatively large doses, have important functions beyond preventing deficiencies. Linus Pauling was instrumental in putting forward this concept, particularly for vitamin C. Thus, relatively high intakes of vitamins, and in particular vitamins C and E which are antioxidants, are considered to be healthy for the human population. This may be true in some special situations such as, for instance, the prevention of Alzheimer's disease progression. However, recent epidemiological evidence has not supported the claim that antioxidant vitamins increase well-being and prolong life span. In fact, vitamin supplementation may be even detrimental and reduce life span. A new concept that we would like to put forward is that nutrients up-regulate the endogenous antioxidant defences. This is particularly true in the case of phytoestrogens for example, which bind to oestrogen receptors and eventually up-regulate the expression of antioxidant genes. In this review we discuss the pros and cons of antioxidant vitamin supplementation and also the possibility that the ingestion of some nutrients may be very effective in increasing antioxidant defences by up-regulating the activity of antioxidant enzymes which are normally present in the cell.",
"title": "Fostering antioxidant defences: up-regulation of antioxidant genes or antioxidant supplementation?"
},
{
"docid": "MED-3979",
"text": "Respiratory infections are the most frequent health problem in childhood. There is little precise information on how many respiratory illness episodes can be expected in a normal child. This study was designed to create reference values for the frequency of respiratory infections as recordable by history. Respiratory illnesses were recorded in a prospective birth cohort of 1314 German children born in 1990 and tracked until age 12 yr (760 children). Parents recorded the child's illnesses in a diary and answered structured questions yearly up to age 12. Age of study subjects was categorized into infancy (0-2 yr), pre-school age (3-5 yr), and school age (6-12 yr). The mean cumulative number of respiratory infection episodes up to age 12 yr was 21.9 (s.d. 9.0) episodes. In infancy, the mean annual number was 3.4 (3.7) episodes; at pre-school age, 2.3 (2.6) episodes; and at school, age 1.1 (1.2) episodes. The mean cumulative time of episodes up to age 7 yr was 20.1 (15.2) wk. Forty-five percent of the infants in the upper episode incidence tertile continued to be in the upper tertile at school age. Based on a twofold standard deviation of the mean number, up to 11 respiratory infection episodes per year in infancy, 8 episodes per year at pre-school age, and 4 episodes per year at school age could be regarded as normal. Episodes within these reference values per se should not cause unwarranted concern or intervention because of suspected immunodeficiency.",
"title": "History of respiratory infections in the first 12 yr among children from a birth cohort."
},
{
"docid": "MED-1388",
"text": "OBJECTIVE: The aim of this study was to assess the association between nut consumption and all-cause mortality after 5-y follow-up in a Spanish cohort. METHODS: The SUN (Seguimiento Universidad de Navarra, University of Navarra Follow-up) project is a prospective cohort study, formed by Spanish university graduates. Information is gathered by mailed questionnaires collected biennially. In all, 17 184 participants were followed for up to 5 y. Baseline nut consumption was collected by self-reported data, using a validated 136-item semi-quantitative food frequency questionnaire. Information on mortality was collected by permanent contact with the SUN participants and their families, postal authorities, and the National Death Index. The association between baseline nut consumption and all-cause mortality was assessed using Cox proportional hazards models to adjust for potential confounding. Baseline nut consumption was categorized in two ways. In a first analysis energy-adjusted quintiles of nut consumption (measured in g/d) were used. To adjust for total energy intake the residuals method was used. In a second analysis, participants were categorized into four groups according to pre-established categories of nut consumption (servings/d or servings/wk). Both analyses were adjusted for potential confounding factors. RESULTS: Participants who consumed nuts ≥2/wk had a 56% lower risk for all-cause mortality than those who never or almost never consumed nuts (adjusted hazard ratio, 0.44; 95% confidence intervals, 0.23-0.86). CONCLUSION: Nut consumption was significantly associated with a reduced risk for all-cause mortality after the first 5 y of follow-up in the SUN project. Copyright © 2014 Elsevier Inc. All rights reserved.",
"title": "Nut consumption and 5-y all-cause mortality in a Mediterranean cohort: the SUN project."
},
{
"docid": "MED-4919",
"text": "OBJECTIVE: Mass screening for celiac disease is controversial. The objective of this study was to determine whether detection of childhood celiac disease by mass screening improves long-term health status and health-related quality of life. METHODS: We conducted a prospective 10-year follow-up study of 32 children who were aged 2 to 4 years, had celiac disease identified by mass screening, and had a gluten-free diet (19) or a normal gluten-containing diet (13). The follow-up included assessments of general health status, celiac disease-associated symptoms, celiac disease-associated serum antibodies, and health-related quality of life. RESULTS: Ten years after mass screening, 81% of the children were adhering to a gluten-free diet. The health status improved in 66% of the treated children: in 41% by early treatment and in 25% by prevention of the gluten-dependent symptoms that they developed after diagnosis. For 19% of the children, treatment after screening would not have improved their health status, because they had no symptoms at screening and have remained symptom-free while consuming gluten. The health-related quality of life of the children with symptoms improved significantly after 1 year of gluten-free diet. Ten years after screening, the health-related quality of life of the children with celiac disease was similar to that of the reference population. CONCLUSION: Identification by mass screening led 10 years later to health improvement in 66% of children without deterioration of generic health-related quality of life. There is a good compliance after mass screening. In a research setting, delaying treatment for children without symptoms seems to be an option after a positive screening test. Long-term follow-up studies are needed to assess possible long-term complications in untreated, nonsymptomatic celiac disease.",
"title": "Long-term health and quality-of-life consequences of mass screening for childhood celiac disease: a 10-year follow-up study."
},
{
"docid": "MED-4698",
"text": "Females live longer than males. Work from our laboratory has shown that this may be due to the up-regulation of longevity-associated genes by estrogens. Estrogens bind to the estrogen receptors and subsequently activate the mitogen activated protein kinase and nuclear factor kappa B signalling pathways, resulting in an up-regulation of antioxidant enzymes. Estrogen administration, however, has serious undesirable effects and of course, cannot be administered to males because of its powerful feminizing effects. Thus, we tested the effect of genistein, a phytoestrogen of high nutritional importance whose structure is similar to estradiol, on the regulation of the expression of antioxidant, longevity-related genes and consequently on oxidant levels in mammary gland tumour cells in culture. Phytoestrogens mimic the protective effect of oestradiol using the same signalling pathway. The critical importance of up-regulating antioxidant genes, by hormonal and dietary manipulations, to increase longevity is discussed.",
"title": "Role of mitochondrial oxidative stress to explain the different longevity between genders: protective effect of estrogens."
},
{
"docid": "MED-1018",
"text": "OBJECTIVE: To determine the magnitude of the decrease in the risk of retinopathy progression observed with intensive treatment and its relationship to baseline retinopathy severity and duration of follow-up. DESIGN: Randomized clinical trial, with 3 to 9 years of follow-up. SETTING AND PATIENTS: Between 1983 and 1989, 29 centers enrolled 1441 patients with insulin-dependent diabetes mellitus aged 13 to 39 years, including 726 patients with no retinopathy and a duration of diabetes of 1 to 5 years (primary prevention cohort) and 715 patients with very mild to moderate nonproliferative diabetic retinopathy and a duration of diabetes of 1 to 15 years (secondary intervention cohort). Ninety-five percent of all scheduled examinations were completed. INTERVENTIONS: Intensive treatment consisted of the administration of insulin at least three times a day by injection or pump, with doses adjusted based on self-blood glucose monitoring and with the goal of normoglycemia. Conventional treatment consisted of one or two daily insulin injections. OUTCOME MEASURES: Change between baseline and follow-up visits on the Early Treatment Diabetic Retinopathy Study retinopathy severity scale, assessed with masked gradings of stereoscopic color fundus photographs obtained every 6 months. RESULTS: Cumulative 8.5-year rates of retinopathy progression by three or more steps at two consecutive visits were 54.1% with conventional treatment and 11.5% with intensive treatment in the primary prevention cohort and 49.2% and 17.1% in the secondary intervention cohort. At the 6- and 12-month visits, a small adverse effect of intensive treatment was noted (\"early worsening\"), followed by a beneficial effect that increased in magnitude with time. Beyond 3.5 years of follow-up, the risk of progression was five or more times lower with intensive treatment than with conventional treatment. Once progression occurred, subsequent recovery was at least two times more likely with intensive treatment than with conventional treatment. Treatment effects were similar in all baseline retinopathy severity subgroups. CONCLUSIONS: The results of the Diabetes Control and Complications Trial strongly support the recommendation that most patients with insulin-dependent diabetes mellitus use intensive treatment, aiming for levels of glycemia as close to the nondiabetic range as is safely possible.",
"title": "The effect of intensive diabetes treatment on the progression of diabetic retinopathy in insulin-dependent diabetes mellitus. The Diabetes Control ..."
},
{
"docid": "MED-1838",
"text": "The determination of Al, B, Cu, Fe, Mn, Ni, P, Zn and Ca, K, Mg by inductively coupled plasma optical emission spectrometry (ICP-OES) and flame atomic absorption spectroscopy (FAAS), respectively, in digests and infusions of Hibiscus sabdariffa (petals), Rosa canina (receptacles), Ginkgo biloba (leaves), Cymbopogon citratus (leaves), Aloe vera (leaves) and Panax ginseng (roots) was carried out in this study. Particular attention has been given to Al and heavy metals for the identification of possible raw material contaminants, their transformation into the infusion and for predicting their eventual role in the human diet during daily consumption. Additionally, Ion Chromatography (IC) speciation of Al in the leachates was carried out. In dry herbs, hibiscus and ginkgo appeared to contain the greatest contents of Al, Fe, K, Mn, Ni, Zn and B, Mg, P, respectively. A. vera contained the highest amount of Ca and highest values of Cu and P were observed in ginseng. In infusions, the topmost concentrations of Al, B, Cu, Fe, P, K, Mn, Ni, Zn were detected in those prepared from hibiscus petals, Ca from aloe leaves and Mg from leaves of ginkgo. According to a possible daily consumption exceeding 1 L, hibiscus decoction was identified as potentially dietetically significant in the content of certain elements. It seems to be possibly one of the top contributors of B from food (up to 5.5±0.2 mg/L). The Mg contained in the infusion (up to 106±5 mg/L) may be a contributor in the attenuation of blood pressure. A high amount of accessible Mn (up to 17.4±1.1 mg/L) can probably have an adverse effect in humans. The total Al allowance (up to 1.2±0.1 mg/L) suggests that no more than 1 L of the hibiscus infusion should be consumed per day by sensitive individuals including pregnant women and should be completely excluded from the diet of children under 6 months of age and children with chronic renal failure. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Aluminium and other elements in selected herbal tea plant species and their infusions."
},
{
"docid": "MED-4980",
"text": "Feasibility of fluorescence imaging technique for the detection of diluted fecal matters from various parts of the digestive tract, including colon, ceca, small intestine, and duodenum, on poultry carcasses was investigated. One of the challenges for using fluorescence imaging for inspection of agricultural material is the low fluorescence yield in that fluorescence can be masked by ambient light. A laser-induced fluorescence imaging system (LIFIS) developed by our group allowed acquisition of fluorescence from feces-contaminated poultry carcasses in ambient light. Fluorescence emission images at 630 nm were captured with 415-nm laser excitation. Image processing algorithms including threshold and image erosion were used to identify fecal spots diluted up to 1: 10 by weight with double distilled water. Feces spots on the carcasses, without dilution and up to 1: 5 dilutions, could be detected with 100% accuracy regardless of feces type. Detection accuracy for fecal matters diluted up to 1: 10 was 96.6%. The results demonstrated good potential of the LIFIS for detection of diluted poultry fecal matter, which can harbor pathogens, on poultry carcasses.",
"title": "Detection of fecal residue on poultry carcasses by laser-induced fluorescence imaging."
},
{
"docid": "MED-4243",
"text": "CONTEXT: The Lifestyle Heart Trial demonstrated that intensive lifestyle changes may lead to regression of coronary atherosclerosis after 1 year. OBJECTIVES: To determine the feasibility of patients to sustain intensive lifestyle changes for a total of 5 years and the effects of these lifestyle changes (without lipid-lowering drugs) on coronary heart disease. DESIGN: Randomized controlled trial conducted from 1986 to 1992 using a randomized invitational design. PATIENTS: Forty-eight patients with moderate to severe coronary heart disease were randomized to an intensive lifestyle change group or to a usual-care control group, and 35 completed the 5-year follow-up quantitative coronary arteriography. SETTING: Two tertiary care university medical centers. INTERVENTION: Intensive lifestyle changes (10% fat whole foods vegetarian diet, aerobic exercise, stress management training, smoking cessation, group psychosocial support) for 5 years. MAIN OUTCOME MEASURES: Adherence to intensive lifestyle changes, changes in coronary artery percent diameter stenosis, and cardiac events. RESULTS: Experimental group patients (20 [71%] of 28 patients completed 5-year follow-up) made and maintained comprehensive lifestyle changes for 5 years, whereas control group patients (15 [75%] of 20 patients completed 5-year follow-up) made more moderate changes. In the experimental group, the average percent diameter stenosis at baseline decreased 1.75 absolute percentage points after 1 year (a 4.5% relative improvement) and by 3.1 absolute percentage points after 5 years (a 7.9% relative improvement). In contrast, the average percent diameter stenosis in the control group increased by 2.3 percentage points after 1 year (a 5.4% relative worsening) and by 11.8 percentage points after 5 years (a 27.7% relative worsening) (P=.001 between groups. Twenty-five cardiac events occurred in 28 experimental group patients vs 45 events in 20 control group patients during the 5-year follow-up (risk ratio for any event for the control group, 2.47 [95% confidence interval, 1.48-4.20]). CONCLUSIONS: More regression of coronary atherosclerosis occurred after 5 years than after 1 year in the experimental group. In contrast, in the control group, coronary atherosclerosis continued to progress and more than twice as many cardiac events occurred.",
"title": "Intensive lifestyle changes for reversal of coronary heart disease."
},
{
"docid": "MED-1201",
"text": "BACKGROUND: Several cross-sectional studies have focused on the low blood folate levels of depressive patients. Nevertheless, no prospective studies have been published on the association between dietary folate and depression. METHODS: We studied the association between dietary folate and cobalamin and receiving a discharge diagnosis of depression in a prospective follow-up setting. Our cohort was recruited between 1984 and 1989 and followed until the end of 2000, and it consisted of 2,313 men aged between 42 and 60 years from eastern Finland. RESULTS: The mean intake of folate in the whole cohort was 256 microg/day (SD=76). Those below the median of energy-adjusted folate intake had higher risk of getting discharge diagnosis of depression (RR 3.04, 95% CI: 1.58, 5.86) during the follow-up period than those who had a folate intake above the median. This excess risk remained significant after adjustment for current socioeconomic status, the baseline HPL depression score, the energy-adjusted daily intake of fibre and vitamin C, and the total fat intake. CONCLUSIONS: A low dietary intake of folate may be a risk factor for severe depression. This also indicates that nutrition may have a role in the prevention of depression.",
"title": "Dietary folate and the risk of depression in Finnish middle-aged men. A prospective follow-up study."
},
{
"docid": "MED-3766",
"text": "AIMS: To update epidemiological data on alcohol and breast cancer, with special emphasis on light alcohol consumption, and to review mechanisms of alcohol mediated mammary carcinogenesis. METHODS: For epidemiological data, in November 2011 we performed a literature search in various bibliographic databases, and we conducted a meta-analysis of data on light alcohol drinking. Relevant mechanistic studies were also reviewed to November 2011. RESULTS: A significant increase of the order of 4% in the risk of breast cancer is already present at intakes of up to one alcoholic drink/day. Heavy alcohol consumption, defined as three or more drinks/day, is associated with an increased risk by 40-50%. This translates into up to 5% of breast cancers attributable to alcohol in northern Europe and North America for a total of approximately 50,000 alcohol-attributable cases of breast cancer worldwide. Up to 1-2% of breast cancers in Europe and North America are attributable to light drinking alone, given its larger prevalence in most female populations when compared with heavy drinking. Alcohol increases estrogen levels, and estrogens may exert its carcinogenic effect on breast tissue either via the ER or directly. Other mechanisms may include acetaldehyde, oxidative stress, epigenetic changes due to a disturbed methyl transfer and decreased retinoic acid concentrations associated with an altered cell cycle. CONCLUSIONS: Women should not exceed one drink/day, and women at elevated risk for breast cancer should avoid alcohol or consume alcohol occasionally only.",
"title": "Epidemiology and pathophysiology of alcohol and breast cancer: Update 2012."
},
{
"docid": "MED-3844",
"text": "Low lignan status has been reported to be related to an elevated risk of breast cancer. Since lignan status is reduced by antibacterial medications, it is plausible to hypothesize that repeated use of antibiotics may also be a risk factor for breast cancer. History of treatment for urinary tract infection was studied for its prediction of breast cancer among 9461 Finnish women 19–89 years of age and initially cancer-free. During a follow-up in 1973–1991, a total of 157 breast cancer cases were diagnosed. Women reporting previous or present medication for urinary tract infection at baseline showed an elevated breast cancer risk in comparison with other women. The age-adjusted relative risk was 1.34 (95% confidence interval (CI) = 0.98–1.83). The association was concentrated to women under 50 years of age. The relative risk for these women was 1.74 (95% CI 1.13–2.68), whereas it was 0.97 (95% CI 0.59–1.58) for older women. The relative risk in the younger age-group was 1.47 (95% CI 0.73–2.97) during the first 10 years of follow-up, and 1.93 (95% CI 1.11–3.37) for follow-up times longer than 10 years. These data suggest that premenopausal women using long-term medication for urinary tract infections show a possible elevated risk of future breast cancer. The results are, however, still inconclusive and the hypothesis needs to be tested by other studies. © 2000 Cancer ResearchCampaign",
"title": "Does antibacterial treatment for urinary tract infection contribute to the risk of breast cancer?"
},
{
"docid": "MED-4291",
"text": "BACKGROUND AND AIMS: Short-term trials support that adding tree nuts or peanuts to usual diets does not induce weight gain. We reviewed the available epidemiological evidence on long-term nut consumption and body weight changes. We also report new results from the SUN (\"Seguimiento Universidad de Navarra\") cohort. METHODS AND RESULTS: Published epidemiologic studies with ≥1-yr follow-up were located. Two published reports from large cohorts (SUN and Nurses Health Study-2) showed inverse associations between frequency of nut consumption and long-term weight changes. A beneficial effect of a Mediterranean diet supplemented with tree nuts on waist circumference was reported after 1-yr follow-up in the first 1224 high-risk participants in the PREDIMED (\"PREvencion DIeta MEDiterranea\") trial. After assessing 11,895 participants of the SUN cohort, a borderline significant (p value for trend = 0.09) inverse association between baseline nut consumption and average yearly weight gain (multivariate-adjusted means = 0.32 kg/yr (95% confidence interval: 0.22-0.42) and 0.24 (0.11-0.37) kg/yr for participants with no consumption and >4 servings/week, respectively) was found after a 6-yr follow-up. CONCLUSIONS: Consumption of nuts was not associated with a higher risk of weight gain in long-term epidemiologic studies and clinical trials. Copyright © 2010 Elsevier B.V. All rights reserved.",
"title": "Nut consumption, weight gain and obesity: Epidemiological evidence."
},
{
"docid": "MED-5367",
"text": "Objective We examined the cross-sectional and longitudinal relationship between plasma carotenoids and depressive symptoms over a six-year follow-up in older persons. Methods and Materials This research is part of the InCHIANTI Study, a prospective population-based study of older persons in Tuscany, Italy. The sample for this analysis included 958 women and men aged 65 years and older. Plasma total carotenoids were assessed at baseline. Depressive symptoms were assessed at baseline and at the 3- and 6-year follow-up using the Center for Epidemiological Studies-Depression Scale (CES-D). Depressed mood was defined as CES-D≥20. Results At baseline, higher total carotenoids level were associated with lower probability of depressed mood (OR=0.82, 95%CI=0.68–0.99, p=0.04) after adjustment for sociodemographic, health and inflammation. After the exclusion of participants with baseline depressed mood and use of antidepressants, higher total carotenoids level were associated with lower risk of incident depressed mood (OR=0.72, 95%CI=0.52–0.99, p=0.04) at 6-year follow-up, after adjustment for confounders plus baseline CES-D. Inflammatory marker Interleukin-1 receptor antagonist partially mediated this association. Discussion Low plasma concentrations of carotenoids are associated with depressive symptoms and predict the development of new depressive symptoms in older persons. Understanding the mechanism of this association may reveal potential targets for prevention and treatment.",
"title": "The relationship between plasma carotenoids and depressive symptoms in older persons"
},
{
"docid": "MED-2287",
"text": "A complex system of interacting mediators exists in the gastric mucosa to strengthen its resistance against injury. In this system prostaglandins play an important role. Prostaglandin biosynthesis is catalysed by the enzyme cyclooxygenase (COX), which exists in two isoforms, COX-1 and COX-2. Initially the concept was developed that COX-1 functions as housekeeping enzyme, whereas COX-2 yields prostaglandins involved in pathophysiological reactions such as inflammation. In the gastrointestinal tract, the maintenance of mucosal integrity was attributed exclusively to COX-1 without a contribution of COX-2 and ulcerogenic effects of non-steroidal anti-inflammatory drugs (NSAIDs) were believed to be the consequence of inhibition of COX-1. Recent findings, however, indicate that both COX-1 and COX-2 either alone or in concert contribute to gastric mucosal defence. Thus, in normal rat gastric mucosa specific inhibition of COX-1 does not elicit mucosal lesions despite near-maximal suppression of gastric prostaglandin formation. When a selective COX-2 inhibitor which is not ulcerogenic when given alone is added to the COX-1 inhibitor, severe gastric damage develops. In contrast to normal gastric mucosa which requires simultaneous inhibition of COX-1 and COX-2 for breakdown of mucosal resistance, in the acid-challenged rat stomach inhibition of COX-1 alone results in dose-dependent injury which is further increased by additional inhibition of COX-2 enzyme activity or prevention of acid-induced up-regulation of COX-2 expression by dexamethasone. COX-2 inhibitors do not damage the normal or acid-challenged gastric mucosa when given alone. However, when nitric oxide formation is suppressed or afferent nerves are defunctionalized, specific inhibition of COX-2 induces severe gastric damage. Ischemia-reperfusion of the gastric artery is associated with up-regulation of COX-2 but not COX-1 mRNA. COX-2 inhibitors or dexamethasone augment ischemia-reperfusion-induced gastric damage up to four-fold, an effect abolished by concurrent administration of 16,16-dimethyl-PGE(2). Selective inhibition of COX-1 is less effective. Furthermore, COX-2 inhibitors antagonize the protective effect of a mild irritant or intragastric peptone perfusion in the rat stomach, whereas the protection induced by chronic administration of endotoxin is mediated by COX-1. Finally, an important function of COX-2 is the acceleration of ulcer healing. COX-2 is up-regulated in chronic gastric ulcers and inhibitors of COX-2 impair the healing of ulcers to the same extent as non-selective NSAIDs. Taken together, these observations show that both COX isoenzymes are essential factors in mucosal defence with specific contributions in various physiological and pathophysiological situations.",
"title": "Role of cyclooxygenase isoforms in gastric mucosal defence."
},
{
"docid": "MED-3141",
"text": "OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.",
"title": "A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome."
},
{
"docid": "MED-3789",
"text": "Background: Meat, milk, and eggs have been inconsistently associated with the risk of advanced prostate cancer. These foods are sources of choline—a nutrient that may affect prostate cancer progression through cell membrane function and one-carbon metabolism. No study has examined dietary choline and the risk of lethal prostate cancer. Objective: Our objective was to examine whether dietary choline, choline-containing compounds, and betaine (a choline metabolite) increase the risk of lethal prostate cancer. Design: We prospectively examined the intake of these nutrients and the risk of lethal prostate cancer among 47,896 men in the Health Professionals Follow-Up Study. In a case-only survival analysis, we examined the postdiagnostic intake of these nutrients and the risk of lethal prostate cancer among 4282 men with an initial diagnosis of nonmetastatic disease during follow-up. Diet was assessed with a validated questionnaire 6 times during 22 y of follow-up. Results: In the incidence analysis, we observed 695 lethal prostate cancers during 879,627 person-years. Men in the highest quintile of choline intake had a 70% increased risk of lethal prostate cancer (HR: 1.70; 95% CI: 1.18, 2.45; P-trend = 0.005). In the case-only survival analysis, we observed 271 lethal cases during 33,679 person-years. Postdiagnostic choline intake was not statistically significantly associated with the risk of lethal prostate cancer (HR for quintile 5 compared with quintile 1: 1.69; 95% CI: 0.93, 3.09; P-trend = 0.20). Conclusion: Of the 47,896 men in our study population, choline intake was associated with an increased risk of lethal prostate cancer.",
"title": "Choline intake and risk of lethal prostate cancer: incidence and survival"
},
{
"docid": "MED-4027",
"text": "Objectives To study the dietary behavior and knowledge about dental erosion and self-reported symptoms that can be related to dental erosion among Chinese adults in Hong Kong. Methods Chinese adults aged 25-45 years were randomly selected from a list of registered telephone numbers generated by computer. A telephone survey was administered to obtain information on demographic characteristics, dietary habits, dental visits, and knowledge of and presence of self-reported symptoms that can be related to dental erosion. Results A total of 520 participants were interviewed (response rate, 75%; sampling error, ± 4.4%) and their mean age was 37. Most respondents (79%) had ever had caries, and about two thirds (64%) attended dental check-ups at least once a year. Respondents had a mean of 5.4 meals per day and 36% had at least 6 meals per day. Fruit (89%) and lemon tea/water (41%) were the most commonly consumed acidic food and beverage. When asked if they ever noticed changes in their teeth, most respondents (92%) said they had experienced change that can be related to erosion. However, many (71%) had never heard about dental erosion and 53% mixed up dental erosion with dental caries. Conclusion Hong Kong Chinese adults have frequent intake of food and many have experienced symptoms that can be related to dental erosion. Their level of awareness of and knowledge about dental erosion is generally low, despite most of them have regular dental check-ups. Dental health education is essential to help the public understand dental erosion and its damaging effects.",
"title": "Dietary behavior and knowledge of dental erosion among Chinese adults"
},
{
"docid": "MED-4918",
"text": "Background & Aims The historical prevalence and long-term outcome of undiagnosed celiac disease (CD) are unknown. We investigated the long-term outcome of undiagnosed CD and whether the prevalence of undiagnosed CD has changed during the past 50 years. Methods This study included 9,133 healthy young adults at Warren Air Force Base (sera were collected between 1948 and 1954) and 12,768 sex-matched subjects from 2 recent cohorts from Olmsted County, Minnesota, with either similar years of birth (n=5,558) or age at sampling (n=7,210) to that of the Air Force cohort. Sera were tested for tissue transglutaminase and, if abnormal, for endomysial antibodies. Survival was measured during a follow-up period of 45 years in the Air Force cohort. The prevalence of undiagnosed CD between the Air Force cohort and recent cohorts was compared. Results Of 9,133 persons from the Air Force cohort, 14 (0.2%) had undiagnosed CD. In this cohort, during 45 years of follow-up, all-cause mortality was greater in persons with undiagnosed CD than among those who were seronegative (hazard ratio=3.9; 95% CI, 2.0–7.5; P<.001). Undiagnosed CD was found in 68 (0.9%) persons with similar age at sampling and 46 (0.8%) persons with similar years of birth. The rate of undiagnosed CD was 4.5-fold and 4-fold greater in the recent cohorts (respectively) than in the Air Force cohort (both P ≤ .0001). Conclusions During 45 years of follow-up, undiagnosed CD was associated with a nearly 4-fold increased risk of death. The prevalence of undiagnosed CD appears to have increased dramatically in the United States during the past 50 years.",
"title": "Increased Prevalence and Mortality in Undiagnosed Celiac Disease"
},
{
"docid": "MED-1323",
"text": "Background: Fat and protein sources may influence whether low-carbohydrate diets are associated with type 2 diabetes (T2D). Objective: The objective was to compare the associations of 3 low-carbohydrate diet scores with incident T2D. Design: A prospective cohort study was conducted in participants from the Health Professionals Follow-Up Study who were free of T2D, cardiovascular disease, or cancer at baseline (n = 40,475) for up to 20 y. Cumulative averages of 3 low-carbohydrate diet scores (high total protein and fat, high animal protein and fat, and high vegetable protein and fat) were calculated every 4 y from food-frequency questionnaires and were associated with incident T2D by using Cox models. Results: We documented 2689 cases of T2D during follow-up. After adjustments for age, smoking, physical activity, coffee intake, alcohol intake, family history of T2D, total energy intake, and body mass index, the score for high animal protein and fat was associated with an increased risk of T2D [top compared with bottom quintile; hazard ratio (HR): 1.37; 95% CI: 1.20, 1.58; P for trend < 0.01]. Adjustment for red and processed meat attenuated this association (HR: 1.11; 95% CI: 0.95, 1.30; P for trend = 0.20). A high score for vegetable protein and fat was not significantly associated with the risk of T2D overall but was inversely associated with T2D in men aged <65 y (HR: 0.78; 95% CI: 0.66, 0.92; P for trend = 0.01, P for interaction = 0.01). Conclusions: A score representing a low-carbohydrate diet high in animal protein and fat was positively associated with the risk of T2D in men. Low-carbohydrate diets should obtain protein and fat from foods other than red and processed meat.",
"title": "Low-carbohydrate diet scores and risk of type 2 diabetes in men"
},
{
"docid": "MED-5366",
"text": "CONTEXT: Adherence to the Mediterranean dietary pattern (MDP) is thought to reduce inflammatory, vascular, and metabolic processes that may be involved in the risk of clinical depression. OBJECTIVE: To assess the association between adherence to the MDP and the incidence of clinical depression. DESIGN: Prospective study that uses a validated 136-item food frequency questionnaire to assess adherence to the MDP. The MDP score positively weighted the consumption of vegetables, fruit and nuts, cereal, legumes, and fish; the monounsaturated- to saturated-fatty-acids ratio; and moderate alcohol consumption, whereas meat or meat products and whole-fat dairy were negatively weighted. SETTING: A dynamic cohort of university graduates (Seguimiento Universidad de Navarra/University of Navarra Follow-up [SUN] Project). PARTICIPANTS: A total of 10 094 initially healthy Spanish participants from the SUN Project participated in the study. Recruitment began on December 21, 1999, and is ongoing. MAIN OUTCOME MEASURE: Participants were classified as having incident depression if they were free of depression and antidepressant medication at baseline and reported a physician-made diagnosis of clinical depression and/or antidepressant medication use during follow-up. RESULTS: After a median follow-up of 4.4 years, 480 new cases of depression were identified. The multiple adjusted hazard ratios (95% confidence intervals) of depression for the 4 upper successive categories of adherence to the MDP (taking the category of lowest adherence as reference) were 0.74 (0.57-0.98), 0.66 (0.50-0.86), 0.49 (0.36-0.67), and 0.58 (0.44-0.77) (P for trend <.001). Inverse dose-response relationships were found for fruit and nuts, the monounsaturated- to saturated-fatty-acids ratio, and legumes. CONCLUSIONS: Our results suggest a potential protective role of the MDP with regard to the prevention of depressive disorders; additional longitudinal studies and trials are needed to confirm these findings.",
"title": "Association of the Mediterranean dietary pattern with the incidence of depression: the Seguimiento Universidad de Navarra/University of Navarra fol..."
}
] |
10102
|
Cons of withdrawing money from an Roth IRA account?
|
[
{
"docid": "595042",
"text": "\"One \"\"con\"\" I have not yet seen mentioned: retirement accounts are generally protected from creditors in a bankruptcy. There are limits and exceptions, Roth has a 1.2 million dollar limit and can be split by a divorce QDRO for instance. Link Since it seems you have no income this year, you may may be raiding your IRA for living expenses. If there is a chance you may declare bankruptcy in the next year or so, consider doing that first and raid the IRA for seed money after.\"",
"title": ""
},
{
"docid": "84334",
"text": "First thing to note is that contributions (i.e. the total of all the amounts that you directly contributed into Roth IRA at any point in time) to a Roth IRA can be withdrawn at any time, without needing any reason, without any tax or penalty. Early withdrawal (early because you are under 59.5) of earnings, on the other hand, will incur tax and penalty. (I didn't go into withdrawal of conversions as those are a little more complex.) When you withdraw, contributions come out first, so as long as you don't withdraw more than the amount of past contributions, you won't have any tax or penalty. And if it's not going to have tax, it doesn't really matter if you do it this year or next year. If you need to dip into the earnings, however, then maybe it would be better to do this year so it will be taxed at lower rates.",
"title": ""
},
{
"docid": "122404",
"text": "In a year with no income, the best advice is to convert existing IRA money to Roth. This lets you take advantage of the 'zero' bracket, the combination of your exemption and standard deduction. This adds to $10,300 for a single person. Other than that, if you are determined to take the money out, just do it. There would be a 10% penalty of the growth, but the original deposit comes out tax free anyway. Edit - There's a rule that if you sell your entire Roth account (i.e. all Roth accounts, you can't pick one of a few) and have a loss, you can take that loss. (Per Dilip's comment, this strategy is pretty moot, it's not a loss taken against other income as a stock loss would potentially be))",
"title": ""
}
] |
[
{
"docid": "398520",
"text": "Don’t take the cash deposit whatever you do. This is a retirement savings vehicle after all and you want to keep this money designated as such. You have 3 options: 1) Rollover the old 401k to the new 401k. Once Your new plan is setup you can call who ever runs that plan and ask them how to get started. It will require you filling out a form with the old 401k provider and they’ll transfer the balance of your account directly to the new 401k. 2) Rollover the old 401k to a Traditional IRA. This involves opening a new traditional IRA if you don’t already have one (I assume you don’t). Vanguard is a reddit favorite and I can vouch for them as Well. Other shops like Fidelity and Schwab are also good but since Vanguard is very low cost and has great service it’s usually a good choice especially for beginners. 3) Convert the old 401k to a ROTH IRA. This is essentially the same as Step 2, the difference is you’ll owe taxes on the balance you convert. Why would you voluntarily want to pay taxes f you can avoid them with options 1 or 2? The beauty of the ROTH is you only pay taxes on the money you contribute to the ROTH, then it grows tax free and when you’re retired you get to withdraw it tax free as well. (The money contained in a 401k or a traditional IRA is taxed when you withdraw in retirement). My $.02. 401k accounts typically have higher fees than IRAs, even if they own the same mutual funds the expense ratios are usually more in the 401k. The last 2 times I’ve changed jobs I’ve converted the 401k money into my ROTH IRA. If it’s a small sum of money and/or you can afford to pay the taxes on the money I’d suggest doing the same. You can read up heavily on the pros/cons of ROTH vs Traditional but My personal strategy is to have 2 “buckets” or money when I retire (some in ROTH and some in Traditional). I can withdraw as much money from the Traditional account until I Max out the lowest Tax bracket and then pull any other money I need from the ROTH accounts that are tax free.This allows you to keep taxes fairly low in retirement. If you don’t have a ROTH now this is a great way to start one.",
"title": ""
},
{
"docid": "252373",
"text": "\"Yes, it is possible to withdraw money from your Roth IRA before retirement (but I wouldn't necessarily advise you to do so.) Here's the good news, and the bad news: The good news: Unlike a traditional IRA, money contributed to a Roth IRA is done so on an after-tax basis, meaning you don't benefit from a tax deduction on contributions. So, the money you withdraw from your Roth IRA will not be taxed entirely as ordinary income. In fact, you are allowed to withdraw the amount of your original contributions (also known as basis) without any taxes or penalties. Let's imagine you originally deposited $9000 of that current $10K total value – then in such a case, $9000 could be withdrawn tax and penalty free. The bad news: When it comes to the investment earnings – the other $1000 in my example – it's a different story: Since you wouldn't be age 59 1/2 at the time of withdrawal, any money taken out beyond your original contributions would be considered a non-qualified withdrawal and subject to both ordinary income taxes plus a 10% early withdrawal penalty. Ouch! Perhaps you might want to restrict your withdrawal to your original contributions. I would imagine if you've had the account for such a short period of time that much or all of your account value is original contributions anyway. A good article about the rules for early IRA withdrawals is About.com's Tax Penalty for Early Distribution of Retirement Funds. Note: If your Roth IRA funds were the result of a rollover from another account type, other rules may apply. See Roth IRA (Wikipedia) for more detail; search for \"\"rollover\"\". Regarding the withdrawal process itself and the timing, you should check with your account custodian on how to proceed.\"",
"title": ""
},
{
"docid": "2128",
"text": "If the IRA is costing you $100 a year, you should almost certainly transfer it to a cheaper provider, regardless of whether you're going to withdraw anything. You can transfer the IRA to another provider that doesn't charge you the fees. Or you can convert it to Roth and combine it with your existing Roth. Either way, you will keep all the money, and save $100 per year in the future. If you want to take money out of your retirement accounts, you should take it out of your Roth IRA, because you can withdraw contributions (i.e., up to the amount you contributed) from the Roth without tax or penalty. Whether you should withdraw anything from your retirement accounts is a different question. If you're already maxing out your Roth IRA, and you have sufficient retirement savings, you could just instead plow that $5500 into your student loans. (If you can afford it, of course, it'd be better to just pay the $7500 from your income and still contribute to the retirement accounts.) There's no reason to withdraw from retirement accounts to pay loans when you could just divert current income for that purpose instead.",
"title": ""
},
{
"docid": "144751",
"text": "\"There's currently not much reason to keep around a long-term non-deductible Traditional IRA in my opinion -- a Roth IRA is almost strictly better. Think about it: a non-deductible Traditional IRA vs. a Roth IRA of the same amount. In both cases, contributions are after-tax (so no tax deduction). But when you withdraw, for the Roth IRA you don't have to pay tax, and for the non-deductible Traditional IRA, you have to pay tax on the \"\"earnings\"\". A Roth IRA can be contributed to at pretty much any income level, thanks to the backdoor Roth IRA process (which uses a temporary non-deductible Traditional IRA in the process). So there is not much reason for a long-term non-deductible Traditional IRA. As for your question, a non-deductible Traditional IRA vs. a taxable account. Well, a non-deductible Traditional IRA is contributed to with after-tax money, and taxed on the earnings only on withdrawal. So the taxation is almost identical to things like stocks and homes, where the gain is not realized until the thing is sold. However, compared to things like savings accounts and bonds, where you get taxed on the interest yearly, it is much better. Every time you get taxed on gains like this, it is taxing gains earned from after-tax money, so if you think of an amount of money as being equivalent to the amount of money it grows to over time (time value of money), then it is taxing money that is (or grown from money that is) already taxed. So it is better to have this only happen at the end at withdrawal than every year.\"",
"title": ""
},
{
"docid": "561636",
"text": "You're misunderstanding the concept of retirement savings. IRA distributions are taxed, in their entirety, as ordinary income. If you withdraw before the retirement age, additional 10% penalty is added. Investment income has preferential treatment - long term capital gains and qualified dividends are taxed at lower rates than ordinary income. However, IRA contributions are tax deductible. I.e.: you don't pay taxes on the amounts contributed to the IRA when you earned the money, only when you withdraw. In the mean time, the money is growing, tax free, based on your investments. Anything inside the IRA is tax free, including dividends, distributions (from funds to your IRA, not from IRA to you), capital gains, etc. This is very powerful, when taking into account the compounding effect of reinvesting your dividends/sale proceeds without taking a chunk out for taxes. Consider you make an investment in a fund that appreciated 100% in half a year. You cash out to reinvest in something less volatile to lock the gains. In a regular account - you pay taxes when you sell, based on your brackets. In the IRA you reinvest all of your sale proceeds. That would be ~25-35% more of the gains to reinvest and continue working for you! However, if you decide to withdraw - you pay ordinary rate taxes on the whole amount. If you would invest in a single fund for 30 years in a regular account - you'd pay 20% capital gains tax (on the appreciation, not the dividends). In the IRA, if you invest in the same fund for the same period - you'll pay your ordinary income rates. However, the benefit of reinvesting dividends tax-free softens the blow somewhat, but that's much harder to quantify. Bottom line: if you want to plan for retirement - plan for retirment. Otherwise - IRA is not an investment vehicle. Also consider Roth IRA/conversions. Roth IRA has the benefit of tax free distributions at retirement. If your current tax bracket is at 20%, for example, contributing $5K to Roth IRA instead of a traditional will cost you $1K of taxes now, but will save you all the taxes during the retirement (for the distributions from the Roth IRA). It may be very much worth your while, especially if you can contribute directly to Roth IRA (there are some income limitations and phaseouts). You can withdraw contributions (but not earnings) from Roth IRA - something you cannot do with a traditional IRA.",
"title": ""
},
{
"docid": "545184",
"text": "As far as I know, there is no direct equivalent. An IRA is subject to many rules. Not only are there early withdrawal penalties, but the ability to deduct contributions to an IRA phases out with one's income level. Qualified withdrawals from an IRA won't have penalties, but they will be taxed as income. Contributions to a Roth IRA can be made post-tax and the resulting gains will be tax free, but they cannot be withdrawn early. Another tax-deductable investment is a 529 plan. These can be withdrawn from at any time, but there is a penalty if the money is not used for educational purposes. A 401K or similar employer-sponsored fund is made with pre-tax dollars unless it is designated as a Roth 401K. These plans also require money to be withdrawn specifically for retirement, with a 10% penalty for early withdrawal. Qualifying withdrawals from a regular retirement plan are taxed as income, those from a Roth plan are not (as with an IRA). Money can be made harder to get at by investing in all of the types of funds you can invest in using an IRA through the same brokers under a different type of account, but the contribution will be made with post-tax, non-deductable dollars and the gains will be taxed.",
"title": ""
},
{
"docid": "175968",
"text": "\"In a Roth IRA scenario, this $5,000 would be reduced to $3,750 if we assume a (nice and round) 25% tax rate. For the Traditional IRA, the full $5,000 would be invested. No, that's not how it works. Taxes aren't removed from your Roth account. You'll have $5,000 invested either way. The difference is that you'll have a tax deduction if you invest in a traditional IRA, but not a Roth. So you'll \"\"save\"\" $1,250 in taxes up front if you invest in a traditional IRA versus a Roth. The flip side is when you withdraw the money. Since you've already paid tax on the Roth investment, and it grows tax free, you'll pay no tax when you withdraw it. But you'll pay tax on the investment and the gains when you withdraw from a traditional IRA. Using your numbers, you'd pay tax on $2.2MM from the traditional IRA, but NO TAX on $2.2MM from the Roth. At that point, you've saved over $500,000 in taxes. Now if you invested the tax savings from the traditional IRA and it earned the same amount, then yes, you'd end up in the same place in the end, provided you have the same marginal tax rate. But I suspect that most don't invest that savings, and if you withdraw significant amount, you'll likely move into higher tax brackets. In your example, suppose you only had $3,750 of \"\"discretionary\"\" income that you could put toward retirement. You could put $5,000 in a traditional IRA (since you'll get a $1,250 tax deduction), or $3,750 in a Roth. Then your math works out the same. If you invest the same amount in either, though, the math on the Roth is a no-brainer.\"",
"title": ""
},
{
"docid": "403103",
"text": "The primary advantage of an IRA or 401k is you get taxed effectively one time on the money (when you contribute for Roth, or when you withdraw for Traditional), whereas you get taxed effectively multiple times on some of the money in a taxable account (on all the money when you contribute, plus on the earnings part when you withdraw). Of course, you have to be able to withdraw without penalty for it to be optimally advantageous. And you said you want to retire decades early, so that is probably not retirement age. However, withdrawing early does not necessarily mean you have a penalty. For example: you can withdraw contributions to a Roth IRA at any time without tax or penalty; Roth 401k can be rolled over into Roth IRA; other types of accounts can be converted to Roth IRA and the principal of the conversion can be withdrawn after 5 years without penalty.",
"title": ""
},
{
"docid": "168530",
"text": "\"I spent some time searching, and couldn't find the answer written explicitly in IRS regulations. What I did find was this chart from the irs showing that nonqualified distributions from a Roth 401k are pro-rated between contributions and earnings. It is well documented that you can't withdraw any money early or tax free (even contributions) from a Roth 401k (\"\"Designated Roth Account\"\" in IRS parlance) that has made any money. source You can do a direct rollover from a \"\"Designated Roth Account\"\" to a Roth IRA and the basis describing contributions vs. earnings is preserved. source And there is plenty of evidence showing you can withdraw contributions from a Roth IRA without penalty. source All that being said, I can't find anything from the IRS that says this is a legitimate strategy.\"",
"title": ""
},
{
"docid": "59600",
"text": "It is really hard to tell where you should withdraw money from. So instead, I'll give you some pointers to make it easier for you to make the decision for yourself, while keeping the answer useful to others as well. I have 3 401ks, ... and some has post tax, non Roth money Why keeping 3 401ks? You can roll them over into an IRA or the one 401k which is still active (I assume here you're not currently employed with 3 different employers). This will also help you avoiding fees for too low balances on your IRAs. However, for the 401k with after tax (not Roth) balance - read the next part carefully. Post tax amounts are your basis. Generally, it is not a good idea to keep post-tax amounts in 401k/IRA, you usually do post-tax contributions to convert them to Roth ASAP. Withdrawing from 401k with basis may become a mess since you'll have to account for the basis portion of each withdrawal. Especially if you pool it with IRAs, so that one - don't rollover, keep it separately to make that accounting easier. I also have several smaller IRAs and Roth IRAs, Keep in mind the RMD requirements. Roth IRAs don't have those, and are non-taxable income, so you would probably want to keep them as long as possible. This is relevant for 401k as well. Again, consolidating will help you with the fees. I'm concerned about having easily accessible cash for emergencies. I suggest keeping Roth amounts for this purpose as they're easily accessible and bear no taxable consequence. Other than emergencies don't touch them for as long as you can. I do have some other money in taxable investments For those, consider re-balancing to a more conservative style, but beware of the capital gains taxes if you have a lot of gains accumulated. You may want consider loss-harvesting (selling the positions in the red) to liquidate investments without adverse tax consequences while getting some of your cash back into the checking account. In any case, depending on your tax bracket, capital gains taxes are generally lower (down to 0%) than ordinary income taxes (which is what you pay for IRA/401k withdrawals), so you would probably want to start with these, after careful planning and taking the RMD and the Social Security (if you're getting any) into account.",
"title": ""
},
{
"docid": "305855",
"text": "I think you're missing several key issues here. First for the facts: IRA contributions are $5500 a year maximum (currently, it changes with inflation), i.e.: you cannot deposit $10K in an IRA account in a single year. IRA withdrawals can only be made if you have something liquid in the IRA. You cannot withdraw from Lending Club IRA unless you manage to sell the notes currently held by you there. Roth IRA is funded with after-tax money, and you can withdraw your deposits in Roth IRA any time for any reason. No 10K limit there, only limited by what you deposited. However the main thing you're missing is this: You can withdraw up to $10K from your IRA for first home purchase without penalty. Pay attention: not without tax but without penalty. So what is the point in depositing $10k into IRA just to withdraw it the next year?",
"title": ""
},
{
"docid": "32671",
"text": "\"The receiving Roth IRA custodian will almost certainly not charge you anything; they are eager to get their hands on the money. In fact, the easiest and most efficient way is to fill out the forms for opening a Roth IRA account with the new custodian (most of this can be done online, but it might be necessary to print out a paper form, sign it and send/fax it to the company), tell them that the Roth IRA will be funded by a trustee-to-trustee transfer from the current custodian, and tell them to go get the money from the online bank who is the current custodian of your Roth IRA account. Don't approach your online bank and tell them to send the money to your new Roth IRA custodian; it will cost money and take more time and the likelihood of a screw-up is way too high. The current custodian might charge you a fee for closing the account, or for \"\"breaking a CD\"\" if that savings account is a CD and you are withdrawing the money before the maturity date of the CD. This will be spelled out in the Roth IRA custodial agreement that you accepted when you opened the account (but most likely did not read in full when you received it, and might even have discarded). One final note: with just $11K, please do not open a brokerage account for your Roth IRA and invest in stocks, bonds etc. For now, invest all your Roth IRA in a single low-cost mutual fund (preferably an index fund such as the Vanguard S&P 500 Index fund or Fidelity Spartan 500 fund); you can branch out into more funds when you have more money in your Roth IRA. Investing in these funds does not need you to have a brokerage account; you can do it directly on the fund's website. Avoid (for now) the siren song of Exchange-Traded Funds (ETFs) because you need to have a brokerage account to buy and sell them. When you have more money in your Roth IRA account, say in ten years' time, you can start investing in individual stocks, ETFs and the like through a brokerage account, but don't do it now.\"",
"title": ""
},
{
"docid": "585422",
"text": "\"The different things in each calculator are showing you a bunch of different things. In the \"\"Roth IRA calculator\"\", it is comparing what you would have in the end after contributing and withdrawing from a Roth IRA, with what you would have in the end with a taxable account (i.e. an investment outside of any IRAs). In the \"\"Traditional IRA calculator\"\", the \"\"IRA after taxes\"\" shows you what you would have in the end after contributing and withdrawing from a pre-tax Traditional IRA. The \"\"IRA before taxes\"\" simply shows the same amount before you pay the taxes on withdrawal, which is not a useful number. So if you want to compare Roth IRA vs. Traditional IRA, you want to compare the \"\"Roth IRA\"\" from the Roth IRA Calculator and the \"\"IRA after taxes\"\" from the Traditional IRA calculator, but there are some things you need to be aware of to make a fair comparison, because if you just plug in the same numbers you are going to get a very unfair comparison (it will look like Roth IRA is a lot \"\"better\"\" even though it's not). The Roth IRA contribution is after-tax, whereas a (pre-tax) Traditional IRA contribution is pre-tax, and an after-tax dollar is much more than a pre-tax dollar, so if you put in the same nominal contribution amount, you are actually contributing much \"\"more\"\" from your wallet in the Roth IRA case. To make a fair comparison, you would need to start with the same pre-tax amount, and put in a Roth IRA contribution amount that corresponds to the equivalent amount after taxes. So for example, a $5000 pre-tax amount with 25% taxes is equivalent to $5000 * 0.75 = $3750, so you would put in $5000 for Traditional IRA contribution vs. $3750 for Roth IRA contribution. Note that if you have the same flat tax rate at contribution and at withdrawal, (pre-tax) Traditional IRA and Roth IRA are exactly the same, and you can see this by putting in 25% for the \"\"Retirement tax rate\"\" in the Traditional IRA calculator (we already assumed 25% tax rate for Roth IRA when calculating the contribution). You will see that Traditional IRA would be better in a lower retirement tax rate (e.g. 15%), whereas Roth IRA would be higher in a higher retirement tax rate.\"",
"title": ""
},
{
"docid": "67410",
"text": "\"The tax code is a hodgepodge of rules that are often tough to explain. The reality is that it's our Congress that writes the tax code, and they often have conflicting goals among themselves. In theory, someone said \"\"How about we force withdrawals at some point. After all, these are retirement accounts, not 'give your kid a huge inheritance account'.\"\" And the discussion continued from there. The age 70-1/2 was arbitrary. 70 happens to be the age for maximum Social Security benefits. But the average retirement age is 63. To make things more confusing, one can easily start taking IRA or 401(k) withdrawals at age 59-1/2, but for 401(k) as early as 55 if you separate from the job at 55 or later. One can also take withdrawals earlier from an IRA with tax, but no penalty using Sec 72(t) rules (such as 72(t)(2)(A)(iv) on Substantially Equal Periodic Payments). To add to the confusion, Roth IRA? No RMDs. Roth 401(k), RMDs once separated from service. Since the money has already been taxed, it's the tax on the growth the government loses. My advice to the reader would be to move the Roth 401(k) to a Roth IRA before 70-1/2. My advice to congress would be to change the code to have the same rules for both accounts. Whether one agrees that a certain rule is 'fair' to them or others is up to them. I think we can agree that the rules are remarkably complex, from origin to execution. And a moving target. You can see just from the history of this site how older questions are often revisited as code changes occur.\"",
"title": ""
},
{
"docid": "202140",
"text": "Is it worth saving HSA funds until retirement? Yes Are there pros and cons from a tax perspective? Mostly pros. This has all of the benefits of an IRA, but if you use it for medical expenses then you get to use the money tax free on the other side. Retirement seems to be the time you are most likely to need money for medical expenses. So why wouldn't you want to start saving tax free to cover those expenses? The cons are similar to other tax advantaged retirement accounts. If you withdraw before retirement time for non-medical purposes, you will pay penalties, but if you withdraw at retirement time, you will pay the same taxes you would pay on an IRA. I should note that I put my money where my mouth is and I max out my contribution to my HSA every year.",
"title": ""
},
{
"docid": "587727",
"text": "\"IRAs have huge tax-advantages. You'll pay taxes when you liquidate gold and silver. While volatile, \"\"the stock market has never produced a loss during any rolling 15-year period (1926-2009)\"\" [PDF]. This is perhaps the most convincing article for retirement accounts over at I Will Teach You To Be Rich. An IRA is just a container for your money and you may invest the money however you like (cash, stocks, funds, etc). A typical investment is the purchase of stocks, bonds, and/or funds containing either or both. Stocks may pay dividends and bonds pay yields. Transactions of these things trigger capital gains (or losses). This happens if you sell or if the fund manager sells pieces of the fund to buy something in its place (i.e. transactions happen without your decision and high turnover can result in huge capital gains). In a taxable account you will pay taxes on dividends and capital gains. In an IRA you don't ever pay taxes on dividends and capital gains. Over the life of the IRA (30+ years) this can be a huge ton of savings. A traditional IRA is funded with pre-tax money and you only pay tax on the withdrawal. Therefore you get more money upfront to invest and more money compounds into greater amounts faster. A Roth IRA you fund with after-tax dollars, but your withdrawals are tax free. Traditional versus Roth comparison calculator. Here are a bunch more IRA and 401k calculators. Take a look at the IRA tax savings for various amounts compared to the same money in a taxable account. Compounding over time will make you rich and there's your reason for starting young. Increases in the value of gold and silver will never touch compounded gains. So tax savings are a huge reason to stash your money in an IRA. You trade liquidity (having to wait until age 59.5) for a heck of a lot more money. Though isn't it nice to be assured that you will have money when you retire? If you aren't going to earn it then, you'll have to earn it now. If you are going to earn it now, you may as well put it in a place that earns you even more. A traditional IRA has penalties for withdrawing before retirement age. With a Roth you can withdraw the principal at anytime without penalty as long as the account has been open 5 years. A traditional IRA requires you take out a certain amount once you reach retirement. A Roth doesn't, which means you can leave money in the account to grow even more. A Roth can be passed on to a spouse after death, and after the spouse's death onto another beneficiary. more on IRA Required Minimum Distributions.\"",
"title": ""
},
{
"docid": "94496",
"text": "First of all, there are some differences between the retirement accounts that you mentioned regarding taxes. Traditional IRA and 401(k) accounts allow you to make pre-tax contributions, giving you an immediate tax deduction when you contribute. Roth IRA, Roth 401(k) are funded with after tax money, and a non-retirement account is, of course, also funded with after tax money. So if you are looking for the immediate tax deduction, this is a point in favor of the retirement accounts. Roth IRA & Roth 401(k) accounts allow the investment to grow tax-free, which means that the growth is not taxed, even when taking the investment out at retirement. With Traditional IRA and 401(k) accounts, you need to pay tax on the gains realized in the account when you withdraw the money, just as you do with a non-retirement account. This is a point in favor of the Roth retirement accounts. To answer your question about capital gains, yes, it is true that you do not have a capital gain until an investment is sold. So, discounting the contribution tax deductions of the retirement accounts, if you only bought individual stocks that never paid a dividend, and never sold them until retirement, you are correct that it really wouldn't matter if you had it in a regular brokerage account or in a traditional IRA. However, even people dedicated to buy-and-hold rarely actually buy only individual stocks and hold them for 30 years. There are several different circumstances that will generally happen in the time between now and when you want to withdraw the money in retirement that would be taxable events if you are not in a retirement account: If you sell an investment and buy a different one, the gains would be taxable. If you want to rebalance your holdings, this also involves selling a portion of your investments. For example, if you want to maintain an 80% stock/20% bond ratio, and your stock values have gone up to 90%, you might want to sell some stock and buy bonds. Or if you are getting closer to retirement, you might decide to go with a higher percentage of bonds. This would trigger capital gains. Inside a mutual fund, anytime the management sells investments inside the fund and realizes capital gains, these gains are passed on to the investors, and are taxable. (This happens more often with managed funds than index funds, but still happens occasionally with index funds.) Dividends earned by the investments are taxable. Any of these events in a non-retirement account would trigger taxes that need to be paid immediately, even if you don't withdraw a cent from your account.",
"title": ""
},
{
"docid": "508219",
"text": "\"Basically, the idea of an IRA is that the money is earned by you and would normally be taxed at the individual rate, but the government is allowing you to avoid paying the taxes on it now by instead putting it in the account. This \"\"tax deferral\"\" encourages retirement savings by reducing your current taxable income (providing a short-term \"\"carrot\"\"). However, the government will want their cut; specifically, when you begin withdrawing from that account, the principal which wasn't taxed when you put it in will be taxed at the current individual rate when you take it out. When you think about it, that's only fair; you didn't pay taxes on it when it came out of your paycheck, so you should pay that tax once you're withdrawing it to live on. Here's the rub; the interest is also taxed at the individual rate. At the time, that was a good thing; the capital gains rate in 1976 (when the Regular IRA was established) was 35%, the highest it's ever been. Now, that's not looking so good because the current cap gains rate is only 15%. However, these rates rise and fall, cap gains more than individual rates, and so by contributing to a Traditional IRA you simplify your tax bill; the principal and interest is taxed at the individual rate as if you were still making a paycheck. A Roth IRA is basically the government trying to get money now by giving up money later. You pay the marginal individual rate on the contributions as you earn them (it becomes a \"\"post-tax deduction\"\") but then that money is completely yours, and the kicker is that the government won't tax the interest on it if you don't withdraw it before retirement age. This makes Roths very attractive to retirement investors as a hedge against higher overall tax rates later in life. If you think that, for any reason, you'll be paying more taxes in 30 years than you would be paying for the same money now, you should be investing in a Roth. A normal (non-IRA) investment account, at first, seems to be the worst of both worlds; you pay individual tax on all earned wages that you invest, then capital gains on the money your investment earns (stock gains and dividends, bond interest, etc) whenever you cash out. However, a traditional account has the most flexibility; you can keep your money in and take your money out on a timeline you choose. This means you can react both to market moves AND to tax changes; when a conservative administration slashes tax rates on capital gains, you can cash out, pay that low rate on the money you made from your account, and then the money's yours to spend or to reinvest. You can, if you're market- and tax-savvy, use all three of these instruments to your overall advantage. When tax rates are high now, contribute to a traditional IRA, and then withdraw the money during your retirement in times where individual tax rates are low. When tax rates are low (like right now), max out your Roth contributions, and use that money after retirement when tax rates are high. Use a regular investment account as an overage to Roth contributions when taxes are low; contribute when the individual rate is low, then capitalize and reinvest during times when capital gains taxes are low (perhaps replacing a paycheck deduction in annual contributions to a Roth, or you can simply fold it back into the investment account). This isn't as good as a Roth but is better than a Traditional; by capitalizing at an advantageous time, you turn interest earned into principal invested and pay a low tax on it at that time to avoid a higher tax later. However, the market and the tax structure have to coincide to make ordinary investing pay off; you may have bought in in the early 90s, taking advantage of the lowest individual rates since the Great Depression. While now, capital gains taxes are the lowest they've ever been, if you cash out you may not be realizing much of a gain in the first place.\"",
"title": ""
},
{
"docid": "298108",
"text": "\"If you have maxed out your IRA contribution for 2017 already (and it all went into your Roth IRA), then, until the 2017 Tax Day in April 2018, you can remove any part of this contribution (and the earnings therefrom) from your Roth IRA without any tax consequences or penalties. If you discover in early 2018 that you are not eligible (or only partially eligible) to contribute to a Roth IRA, then of course you must remove all (or part) of your 2017 contributions (and the earnings therefrom) from your Roth IRA by the 2017 Tax Day in April 2018. Indeed, if you have filed for an extension of time to submit your 2017 tax return, then you have until the extended due date to make the withdrawal. As NathanL's answer points out, for 2017, you and withdraw and re-contribute \"\"as many times as you like\"\" though if you push this idea to excess with the same IRA custodian, the custodian may start charging fees. Note that IRS Publication 590b says in the Roth IRA section, Withdrawals of contributions by due date. If you withdraw contributions (including any net earnings on the contributions) by the due date of your return for the year in which you made the contribution, the contributions are treated as if you never made them. If you have an extension of time to file your return, you can withdraw the contributions and earnings by the extended due date. The withdrawal of contributions is tax free, but you must include the earnings on the contributions in income for the year in which you made the contributions. Now, if in the middle of all these transactions, you need to take a distribution from your Roth IRA during 2017 (say because you have a cash flow problem), then it makes a lot of sense to first withdraw all your 2017 contributions and the earnings therefrom. If more money is needed, than you can take a distribution from your Roth IRA. What the distribution consists of is described in great detail in Publication 590b and you might have to pay a tax penalty for a premature distribution depending on how much the distribution is. (The first dollars coming are assumed to be previous contributions in the order in which you made them and these are tax-free and penalty-free; after that the rollover and conversion amounts start to come out and are penalized if they have not spent 5 years in the IRA etc) But you can put the money back into your Roth IRA within 60 days and avoid penalties. Important Notes regarding rollover transactions:\"",
"title": ""
},
{
"docid": "399564",
"text": "Your best bets are a Roth IRA or traditional IRA. If you roll it to a Roth, you will have to pay taxes on the amount you roll over (unless it was a Roth 401k), however what is in the Roth will grow tax free and it will be tax free when you withdraw. With a traditional IRA, you won't owe taxes on the money now but will pay taxes when you withdraw. You won't be able to withdraw this money until 59 1/2 years of age without paying a penalty, the same goes for your current 401k. If you take the money (for mortgage, other investment, etc.) and don't roll it over to a qualified account, you will owe taxes on it plus a 10% penalty. So you will only get between 60% and 70% of its value.",
"title": ""
},
{
"docid": "159197",
"text": ">I could be wrong but you will still get tax at 10% This isn't true for Roths. If I put 5k (post tax of course) money into a Roth 401k or a Roth IRA I can withdraw that 5k whenever I want penalty and tax free. Now lets say that 5k has grown to 7k and I take out all 7k the first 5k is penalty and tax free but the extra 2k is taxed (with the extra 10% penalty added on). So as long as you don't touch any growth in your roth accounts you can withdraw the principal amount with the same consequences you would experience if you were to take money out of your checking account at your bank. Also money in and IRA does not have to be invested it could be in a liquid position. Now a pre tax retirement account doesn't have the same luxury. If I stick 5k into a traditional IRA and it grows to 7k and I pull that money out the entire ammount gets taxed AND penalized (even the principal amount is subject the 10% penalty). Now if you do a Roth conversion (pre-tax to post-tax retirment account conversion) the principal ammount (the amount you paid taxes on) is still subject to the 10% penalty for 5 years. After the 5 years you can withdraw the converted ammount tax and penalty free (well you already paid the taxes) it would just be the growth that is subject to the penalty.",
"title": ""
},
{
"docid": "41417",
"text": "\"1) Usually, the choice between Traditional vs. Roth is whether you believe that your tax rate will be higher or lower in the future than it is now. Your income is probably in the 25% bracket now. It's hard to say whether that should be considered \"\"high\"\" or \"\"low\"\". Some people advocate Roth only for 15% bracket; but your income would probably go into higher brackets in the future, so Roth may be preferable from this point of view. Roth IRA also has another advantage that the principal of contributions can be taken out at any time without tax or penalty, so it can serve as an emergency fund just as well as money in taxable accounts. Given that you may not have a lot of money saved up right now, this is useful. 2) In a sense, it's nice to have a mix of Traditional and Roth when you withdraw to hedge against uncertainty in future tax rates and have the option of choosing whichever one is advantageous to withdraw when you need to withdraw. That said, you will likely have many years of access to a 401k and high income in your future working years, in which you can contribute to a Traditional 401k (or if no access to 401k, then Traditional IRA), so a mix will almost certainly happen even if you go all Roth IRA now. 3) I think that depends on you, whether you are a hands-on or hands-off kind of investor.\"",
"title": ""
},
{
"docid": "92442",
"text": "Is there any benefit to investing in a Roth 401(k) plan, as opposed to a Roth IRA? They have separate contribution limits, so how much you contribute to one does not change the amount you can contribute to the other. Which is relevant to your question because you said the earnings on that account compounded over the next 40 years growing tax-free will be much higher than what I'd save on current taxes on a traditional 401(k). This is only true if you max out your contribution limits. If you start with the same amount of money and have the same marginal tax rate in both years, it doesn't matter which one you pick. Start with $10,000 to invest. With the traditional, you can invest all $10,000. With the Roth, you pay taxes on it and then invest it. Let's assume a tax rate of 25%. So invest $7500. Let's assume that you invest either amount long enough to double four times (forty years at 7% return after inflation is about right). So the traditional has $160,000 and the Roth has $120,000. Now you withdraw them. For simplicity's sake, we'll pretend it's all one year. It's probably over several years, but the math is easier in a single year. With the Roth, you have $120,000. With the traditional, you have to pay tax. Again, let's assume 25%. So that's $40,000, leaving you with $120,000 from the traditional. That is the same amount as the Roth! So it would make sense to If you can max out both, great. You do that for forty years and your retirement will be as financially secure as you can make it. If you can't max them out, the most important thing is the employer match. That's free money. Then you may prefer your Roth IRA to the 401k. Note that you can also roll over your Roth 401k to a Roth IRA. Then you can withdraw your contributions from the Roth IRA without penalty or additional tax. Alternate source. Beyond answering your question, I would still like to reiterate that Roth or traditional does not have a big effect on your investment unless you max them out or you have different tax rates now versus in retirement. It may change other things. For example, you can roll over a Roth 401k to a Roth IRA without paying taxes. And the Roth IRA will act like it was contributed directly. You have to check with your employer what their rollover rules are. They may allow it any time or only at employment separation (when you leave the job). If you do max out your Roth accounts, then they will perform better than the traditional accounts at the same nominal contribution. This is because they are tax free while your returns in the other accounts will have to pay taxes. But it doesn't matter until you hit the limits. Until then, you could just invest the tax savings of the traditional as well as the money you could invest in a Roth.",
"title": ""
},
{
"docid": "482768",
"text": "There are a few incorrect assumptions in your question but the TL;DR version is: All, or most, of the withdrawal is taxable income that is reported on Lines 15a (total distribution) and 15b (taxable amount) of Form 1040. None of the distribution is given special treatment as Qualified Dividends or Capital Gains regardless of what happened inside the IRA, and none of the distribution is subject to the 3.8% Net Investment Income Tax that some high-income people need to compute on Form 8960. If the withdrawal is not a Qualified Distribution, it will be subject to a 10% excise tax (tax penalty on premature withdrawal). Not all contributions to Traditional IRAs are deductible from income for the year for which the contribution was made. People with high income and/or coverage by a workplace retirement plan (pension plan, 401(k) plan, 403(b) plan, etc) cannot deduct any contributions that they choose to make to a Traditional IRA. Such people can always make a contribution (subject to them having compensation (earned income such as salary or wages, self-employment income, commissions on sales, etc), but they don't get a tax deduction for it (just as contributions to Roth IRAs are not deductible). Whether it is wise to make such nondeductible contributions to a Traditional IRA is a question on which reasonable people can hold different opinions. Be that as it may, nondeductible contributions to a Traditional IRA create (or add to) what is called the basis of an IRA. They are reported to the IRS on Form 8606 which is attached to the Federal Form 1040. Note that the IRA custodian or trustee is not told that the contributions are not deductible. Earnings on the basis accumulate tax-deferred within the IRA just as do the earnings on the deductible contributions. Now, when you make a withdrawal from your Traditional IRA, no matter which of your various IRA accounts you take the money from, part of the money is deemed to be taken from the basis (and is not subject to income tax) while the rest is pure taxable income. That is, none of the rest is eligible for the reduced taxation rates for Qualified Dividends or Capital Gains and since it does not count as investment income, it is not subject to the 3.8% Net Investment Tax of Form 8960 either. Computation of how much of your withdrawal is nontaxable basis and how much is taxable income is done on Form 8606. Note that you don't get to withdraw your entire basis until such time as when you close all your Traditional IRA accounts. How is all this reported? Well, your IRA custodian(s) will send you Form 1099-R reporting the total amount of the withdrawal, what income tax, if any, was withheld, etc. The custodian(s) don't know what your basis is, and so Box 2b will say that the taxable amount is not determined. You need to fill out Form 8606 to figure out what the taxable amount is, and then report the taxable amount on Line 15b of Form 1040. (The total withdrawal is reported on Line 15a which is not included in the AGI computations). Note that as far as the IRS is concerned, you have only one Traditional IRA. The A in IRA stands for Arrangement, not Account as most everybody thinks, and your Traditional IRA can invest in many different things, stocks, bonds, mutual funds, etc with different custodians if you choose, but your basis is in the IRA, not the specific investment that you made with your nondeductible contribution. That's why the total IRA contribution is limited, not the per-account contribution, and why you need to look that the total value of your IRA in determining the taxable portion, not the specific account(s) from which you withdrew the money. So, how much basis did you withdraw? Well, if you withdrew $W during 2016 and the total value of all your Traditional IRA accounts was $X at the end of 2016 and your total basis in your Traditional IRA is $B, then (assuming that you did not indulge in any Traditional-to-Roth rollovers for 2016), multiply W by B/(W+X) to get the amount of nontaxable basis in the withdrawal. B thus gets reduced for 2017 by amount of basis withdrawal. What if you never made a nondeductible contribution to your Traditional IRA, or you made some nondeductible contributions many years ago and have forgotten about them? Well, you could still fill out Form 8606 reporting a zero basis, but it will just tell you that your basis continues $0. Or, you could just enter the total amount of your withdrawal in Lines 15a and 15b, effectively saying that all of the withdrawal is taxable income to you. The IRS does not care if you choose to pay taxes on nontaxable income.",
"title": ""
},
{
"docid": "214174",
"text": "\"A Roth IRA is simply a tax-sheltered account that you deposit funds into, and then invest however you choose (within the limits of the firm you deposit the funds with). For example, you could open a Roth IRA account with Vanguard. You could then invest the $3000 by purchasing shares of VOO, which tracks the S&P 500 index and has a very low expense ratio (0.04 as of last time I checked). Fidelity has a similar option, or Schwab, or whatever brokerage firm you prefer. IRAs are basically just normal investment accounts, except they don't owe taxes until you withdraw them (and Roth don't even owe them then, though you paid taxes on the funds you deposit). They have some limitations regarding options trading and such, but if you're a novice investor just looking to do basic investments, you'll not notice. Then, your IRA would go up or down in value as the market went up or down in value. You do have some restrictions on when you can withdraw the funds; Roth IRA has fewer than a normal IRA, as you can withdraw the capital (the amount you deposited) without penalty, but the profits cannot be withdrawn until you're retirement age (I won't put an actual year, as I suspect that actual year will change by the time you're that old; but think 60s). The reason not to invest in an IRA is if you plan on using the money in the near future - even as an \"\"emergency fund\"\". You should have some money that is not invested aggressively, that is in something very safe and very accessible, for your emergency fund; and if you plan to buy a house or whatever with the funds, don't start an IRA. But if this is truly money you want to save for retirement, that's the best place to start. **Note, this is not investment advice, and you should do your own homework prior to making any investment. You can lose some or all of the value of your account while investing.\"",
"title": ""
},
{
"docid": "461084",
"text": "Why shouldn't I just keep my money in the savings account and earn the same amount (both accounts have the same APY in this case)? I will assume that you are transferring money from your savings account into a Traditional IRA and deducting the contribution from your income. While you may think that the money that is being transferred is yours already -- it is sitting in your savings account, for Pete's sake! -- you are deducting that amount in getting to your taxable income, and so you are effectively contributing it from current income and not paying taxes on the amount contributed. So, consider the same amount of money sitting in your savings account versus the same amount of money sitting in your Traditional IRA account. While you will earn the same amount of interest in both accounts, you will have to pay taxes each year on the interest earned in the savings account. You might choose, as most people do, to not take money out of the savings account to pay theses taxes but just pay them from ready cash/checking account/current income etc., or these taxes might just reduce the refund that you will getting from the IRS and your State income tax authority, but in either case, you have paid taxes on the interest earned in your non-IRA savings account, and of course, long ago, you also paid taxes on the original amount in the non-IRA savings account. So, if you take any money out of the non-IRA savings account, you don't pay any taxes on the amount withdrawn except possibly for the interest earned from January 1 till the date of withdrawal (which you are paying from ready cash). On the other hand, consider the Traditional IRA. The original deposit was not taxed in the sense that you got a deduction (reduced tax or increased refund) when you made the contribution. The annual interest earned was not taxed each year either. So when you make a qualified withdrawal (after age 59.5 or by meeting one of the other exceptions allowing withdrawal before age 59.5), you are taking money on which you have not paid any taxes at all, and the IRS wants its cut. The money withdrawn is taxable income to you. Furthermore, the money withdrawn is not eligible for any kind of favorable treatment such as having it count as qualified dividends or as long-term capital gains even if your IRA was invested in stocks and the money in the account is all qualified dividends or long-term capital gains. If you make an unqualified withdrawal, you owe a penalty (technically named an excise tax) in addition to income tax on the amount withdrawn. If you are investing in a Roth IRA, you will not be getting a deduction when you make the contribution, and qualified withdrawals are completely tax-free, and so the answer is completely different from the above.",
"title": ""
},
{
"docid": "452870",
"text": "\"The IRA contribution limit is a limit on the total amount you can contribute to all of your Roth and traditional IRAs. It's not a per-account limit. (See here and here.) Once you've hit the contribution limit on one account, you've hit it on all of them. Even so, supposing you had a reason with try to take money out of one of the accounts, the answer to your question is \"\"sort of\"\". The limit is a limit on your gross contributions, not your net contributions. It is possible to withdraw Roth contributions if you do so before the tax filing deadline for that year, but you must also withdraw (and pay taxes on) any earnings accured during the time the money was in the Roth (see here). In addition, doing this may not be as simple as just taking the money out of your account; you should probably ask your bank about it and let them know you're \"\"undoing\"\" the contribution, since they may otherwise still record the amount as a real contribution and the withdrawal as unqualified early withdrawal (subject to penalties, etc.).\"",
"title": ""
},
{
"docid": "598378",
"text": "\"For 401(k) and regular IRA, you pay income tax on withdrawals from the account. At a certain age, there is a \"\"required minimum distribution\"\". This is an amount you must withdraw from the account or you face penalties. I've also read about, but am not familiar with, mechanisms by which you can retire early and start taking withdrawals before the regular official retirement age. (These may or may not be legit, I didn't do any research on it.) A Roth IRA, which is not \"\"tax deferred\"\" and thus not technically covered by your question, there is no tax on withdrawals (assuming you are at retirement age) and no required minimum distribution. Something to watch out for on your accounts are fees that they charge for withdrawals. I was in a 401(k) once that had a $50 fee per-withdrawal. A monthly check from this account would eat your money! I paid the fee once, when I rolled it into an account at a brokerage after leaving the company.\"",
"title": ""
},
{
"docid": "308150",
"text": "\"If I understand correctly, the Traditional IRA, if you have 401k with an employer already, has the following features: Actually, #1 and #2 are characteristics of Roth IRAs, not Traditional IRAs. Only #3 is a characteristic of a Traditional IRA. Whether you have a 401(k) with your employer or not makes absolutely no difference in how your IRAs are taxed for the vast majority of people. (The rules for IRAs are different if you have a very high income, though). You're allowed to have and contribute to both kinds of accounts. (In fact, I personally have both). Traditional IRAs are tax deferred (not tax-free as people sometimes mistakenly call them - they're very different), meaning that you don't have to pay taxes on the contributions or profits you make inside the account (e.g. from dividends, interest, profits from stock you sell, etc.). Rather, you pay taxes on any money you withdraw. For Roth IRAs, the contributions are taxed, but you never have to pay taxes on the money inside the account again. That means that any money you get over and above the contributions (e.g. through interest, trading profits, dividends, etc.) are genuinely tax-free. Also, if you leave any of the money to people, they don't have to pay any taxes, either. Important point: There are no tax-free retirement accounts in the U.S. The distinction between different kinds of IRAs basically boils down to \"\"pay now or pay later.\"\" Many people make expensive mistakes in their retirement strategy by not understanding that point. Please note that this applies equally to Traditional and Roth 401(k)s as well. You can have Roth 401(k)s and Traditional 401(k)s just like you can have Roth IRAs and Traditional IRAs. The same terminology and logic applies to both kinds of accounts. As far as I know, there aren't major differences tax-wise between them, with two exceptions - you're allowed to contribute more money to a 401(k) per year, and you're allowed to have a 401(k) even if you have a high income. (By way of contrast, people with very high incomes generally aren't allowed to open IRAs). A primary advantage of a Traditional IRA is that you can (in theory, at least) afford to contribute more money to it due to the tax break you're getting. Also, you can defer taxes on any profits you make (e.g. through dividends or selling stock at a profit), so you can grow your money faster.\"",
"title": ""
},
{
"docid": "461933",
"text": "\"So you are paying taxes on your contributions regardless, the timing is just different. I am failing to see why would a person get an IRA, instead of just putting the same amount of money into a mutual fund (like Vanguard) or something like that. What am I missing? You are failing to consider the time value of money. Getting $1 now is more valuable to you than a promise to get $1 in a year, even though the nominal amount is the same. With a certain amount of principal now, you can invest it and it will (likely) grow into a bigger amount of money (principal + earnings) at a later time, and we can consider the two to have approximately equivalent value (the principal now has the same value as the principal + earnings later). With pre-tax money in Traditional IRA, the principal + earnings are taxed once at the time of withdrawal. Assuming the same flat rate of tax at contribution and withdrawal, this is equivalent to Roth IRA, where the principal is taxed at the time of contribution, because the principal now has the same value as the principal + earnings later, so the same rate of tax on the two have the same value of tax, even though when you look at nominal amounts, it might seem you are paying a lot less tax with Roth IRA (since the earnings are never \"\"taxed\"\"). With actual numbers, if we take a $1000 pre-tax contribution to Traditional IRA, it grows at 5% for 10 years, and a 25% flat rate tax, we are left with $1000 * 1.05^10 * 0.75 = $1221.67. With the same $1000 pre-tax contribution (so after 25% tax it's a $750 after-tax contribution) to a Roth IRA, growing at the same 5% for 10 years, and no tax at withdrawal, we are left with $1000 * 0.75 * 1.05^10 = $1221.67. You can see they are equivalent even though the nominal amount of tax is different (the lower amount of tax paid now is equivalent to the bigger amount of tax later). With a taxable investment which you will not buy and sell until you take it out, you contribute with after-tax money, and when you take it out, the \"\"earnings\"\" portion is subject to capital-gains tax. But remember that the principal + earnings later is equivalent to the principal now, which is already all taxed once, and if we tax the \"\"earnings\"\" portion later, that is effectively taxing a portion of the money again. Another way to look at it is the contribution is just like the Roth IRA, but the withdrawal is worse because you have to pay capital-gains tax instead of no tax. You can take the same numbers as for the Roth IRA, $1000 * 0.75 * 1.05^10 = $1221.67, but where the $1221.67 - $750 = $471.67 is \"\"earnings\"\" and is taxed again at, say, a 15% capital-gains rate, so you lose another $70.75 in tax and are left with $1150.92. You would need a capital-gains tax rate of 0% to match the advantage of the pre-tax Traditional IRA or Roth IRA. After-tax money in Traditional IRA has a similar problem -- the contribution is after tax, but after it grows into principal + earnings, the \"\"earnings\"\" part is taxed again, except it is worse than the capital-gains case because it is taxed as regular income. Like above, you can take the same numbers as for the Roth IRA, $1000 * 0.75 * 1.05^10 = $1221.67, but where the $471.67 \"\"earnings\"\" is taxed again at 25%, so you lose another $117.92 in tax and are left with $1103.75. So although the nominal amount of tax paid is the same as for pre-tax money in Traditional IRA, it ends up being a lot worse. (Everything I said above about pre-tax money in Traditional IRA, after-tax money in Traditional IRA, and Roth IRA, also applies to pre-tax money in Traditional 401(k), after-tax money in Traditional 401(k), and Roth 401(k), respectively.) Regarding the question you raise in the title of your question, why someone would get contribute to a Traditional IRA if they already have a 401(k), the answer is, mostly, they wouldn't. First, note that if you merely have a 401(k) account but neither you nor your employer contributes to it during the year, then that doesn't prevent you from deducting Traditional IRA contributions for that year, so basically you can contribute to one or the other; so if you only want to contribute below the IRA contribution limit, and don't need the bigger 401(k) contribution limit, and the IRA's investment options are more attractive to you than your 401(k)'s, then it might make sense for you to contribute to only Traditional IRA. If you or your employer is already contributing to your 401(k) during the year, then you cannot deduct your Traditional IRA contributions unless your income is very low, and if your income is really that low, you are in such a low tax bracket that Roth IRA may be more advantageous for you. If you make a Traditional IRA contribution but cannot deduct it, it is a non-deductible Traditional IRA contribution, i.e. it becomes after-tax money in a Traditional IRA, which as I showed in the section above has much worse tax situation in the long run because its earnings are pre-tax and thus taxed again. However, there is one good use for non-deductible Traditional IRA contributions, and that is as one step in a \"\"backdoor Roth IRA contribution\"\". Basically, there is an income limit for being able to make Roth IRA contributions, but there is no income limit for being able to make Traditional IRA contributions or for being able to convert money from Traditional IRA to Roth IRA. So what you can do is make a (non-deductible) Traditional IRA contribution, and then immediately convert it to Roth IRA, and if you did not previously have any pre-tax money in Traditional IRAs, this achieves the same as a regular Roth IRA contribution, with the same tax treatment, but you can do it at any income level.\"",
"title": ""
}
] |
572
|
In chronic viral infections or tumors, peptides that selectively inhibit PTPRS can be utilized to boost insufficient activity of pDCs.
|
[
{
"docid": "4447055",
"text": "Contusive spinal cord injury leads to a variety of disabilities owing to limited neuronal regeneration and functional plasticity. It is well established that an upregulation of glial-derived chondroitin sulphate proteoglycans (CSPGs) within the glial scar and perineuronal net creates a barrier to axonal regrowth and sprouting. Protein tyrosine phosphatase σ (PTPσ), along with its sister phosphatase leukocyte common antigen-related (LAR) and the nogo receptors 1 and 3 (NgR), have recently been identified as receptors for the inhibitory glycosylated side chains of CSPGs. Here we find in rats that PTPσ has a critical role in converting growth cones into a dystrophic state by tightly stabilizing them within CSPG-rich substrates. We generated a membrane-permeable peptide mimetic of the PTPσ wedge domain that binds to PTPσ and relieves CSPG-mediated inhibition. Systemic delivery of this peptide over weeks restored substantial serotonergic innervation to the spinal cord below the level of injury and facilitated functional recovery of both locomotor and urinary systems. Our results add a new layer of understanding to the critical role of PTPσ in mediating the growth-inhibited state of neurons due to CSPGs within the injured adult spinal cord.",
"title": "Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury"
}
] |
[
{
"docid": "8596357",
"text": "Functional disruption of dendritic cells (DC) is an important strategy for viral pathogens to evade host defences. In this context, porcine circovirus type 2 (PCV2), a single-stranded DNA virus, impairs plasmacytoid DC (pDC) and conventional DC activation by certain viruses or Toll-like receptor (TLR) ligands. This inhibitory capacity is associated with the viral DNA, but the impairment does not affect all signalling cascades; TLR7 ligation by small chemical molecules will still induce interleukin-6 (IL-6) and tumour necrosis factor-α secretion, but not interferon-α or IL-12. In this study, the molecular mechanisms by which silencing occurs were investigated. PP2, a potent inhibitor of the Lyn and Hck kinases, produced a similar profile to the PCV2 DNA interference with cytokine secretion by pDC, efficiently inhibiting cell activation induced through TLR9, but not TLR7, ligation. Confocal microscopy and cytometry analysis strongly suggested that PCV2 DNA impairs actin polymerization and endocytosis in pDC and monocyte-derived DC, respectively. Altogether, this study delineates for the first time particular molecular mechanisms involved in PCV2 interference with DC danger recognition, which may be responsible for the virus-induced immunosuppression observed in infected pigs.",
"title": "Porcine circovirus type 2 DNA influences cytoskeleton rearrangements in plasmacytoid and monocyte-derived dendritic cells."
},
{
"docid": "72159",
"text": "On recognition of influenza virus (Flu) by TLR7, plasmacytoid dendritic cells (pDCs) produce type I IFN in significant amounts. Synthetic TLR7 ligands induce the maturation of pDCs, as evidenced by the expression of costimulatory molecules and the production of proinflammatory cytokines; however, they induce only low-level production of IFN-alpha. To dissect the TLR7 signaling in pDCs and how these different profiles are induced, we studied the effects of 2 TLR7 ligands (Flu and CL097) on the activation of blood-isolated pDCs and the human GEN2.2 pDC cell line. Type I IFN production by pDCs correlates with differential interferon regulatory factor 7 (IRF7) translocation into the nucleus induced by the 2 TLR7 ligands. Surprisingly, with both activators we nevertheless observed the rapid expression of the IFN-inducible genes mxa, cxcl10, and trail within 4 hours of stimulation. This expression, controlled by STAT1 phosphorylation, was independent of type I IFN. STAT1 activation was found to be strictly dependent on the PI3K-p38MAPK pathway, showing a new signaling pathway leading to rapid expression of IFN-inducible genes after TLR7 triggering. Thus, pDCs, through this unusual TLR7 signaling, have the capacity to promptly respond to viral infection during the early phases of the innate immune response.",
"title": "induction of early IFN-inducible genes in the absence of type"
},
{
"docid": "20960682",
"text": "BACKGROUND & AIMS GS-9620, an oral agonist of toll-like receptor 7 (TLR7), is in clinical development for the treatment of chronic hepatitis B (CHB). GS-9620 was previously shown to induce prolonged suppression of serum viral DNA and antigens in the woodchuck and chimpanzee models of CHB. Herein, we investigated the molecular mechanisms that contribute to the antiviral response to GS-9620 using in vitro models of hepatitis B virus (HBV) infection. METHODS Cryopreserved primary human hepatocytes (PHH) and differentiated HepaRG (dHepaRG) cells were infected with HBV and treated with GS-9620, conditioned media from human peripheral blood mononuclear cells treated with GS-9620 (GS-9620 conditioned media [GS-9620-CM]), or other innate immune stimuli. The antiviral and transcriptional response to these agents was determined. RESULTS GS-9620 had no antiviral activity in HBV-infected PHH, consistent with low level TLR7 mRNA expression in human hepatocytes. In contrast, GS-9620-CM induced prolonged reduction of HBV DNA, RNA, and antigen levels in PHH and dHepaRG cells via a type I interferon (IFN)-dependent mechanism. GS-9620-CM did not reduce covalently closed circular DNA (cccDNA) levels in either cell type. Transcriptional profiling demonstrated that GS-9620-CM strongly induced various HBV restriction factors - although not APOBEC3A or the Smc5/6 complex - and indicated that established HBV infection does not modulate innate immune sensing or signaling in cryopreserved PHH. GS-9620-CM also induced expression of immunoproteasome subunits and enhanced presentation of an immunodominant viral peptide in HBV-infected PHH. CONCLUSIONS Type I IFN induced by GS-9620 durably suppressed HBV in human hepatocytes without reducing cccDNA levels. Moreover, HBV antigen presentation was enhanced, suggesting additional components of the TLR7-induced immune response played a role in the antiviral response to GS-9620 in animal models of CHB. LAY SUMMARY GS-9620 is a drug currently being tested in clinical trials for the treatment of chronic hepatitis B virus (HBV) infection. GS-9620 has previously been shown to suppress HBV in various animal models, but the underlying antiviral mechanisms were not completely understood. In this study, we determined that GS-9620 does not directly activate antiviral pathways in human liver cells, but can induce prolonged suppression of HBV via induction of an antiviral cytokine called interferon. However, interferon did not destroy the HBV genome, suggesting that other parts of the immune response (e.g. activation of immune cells that kill infected cells) also play an important role in the antiviral response to GS-9620.",
"title": "Toll-like receptor 7 agonist GS-9620 induces prolonged inhibition of HBV via a type I interferon-dependent mechanism."
},
{
"docid": "11784947",
"text": "Short interfering RNAs (siRNAs) have been used to inhibit HIV-1 replication. The durable inhibition of HIV-1 replication by RNA interference has been impeded, however, by a high mutation rate when viral sequences are targeted and by cytotoxicity when cellular genes are knocked down. To identify cellular proteins that contribute to HIV-1 replication that can be chronically silenced without significant cytotoxicity, we employed a shRNA library that targets 54,509 human transcripts. We used this library to select a comprehensive population of Jurkat T-cell clones, each expressing a single discrete shRNA. The Jurkat clones were then infected with HIV-1. Clones that survived viral infection represent moieties silenced for a human mRNA needed for virus replication, but whose chronic knockdown did not cause cytotoxicity. Overall, 252 individual Jurkat mRNAs were identified. Twenty-two of these mRNAs were secondarily verified for their contributions to HIV-1 replication. Five mRNAs, NRF1, STXBP2, NCOA3, PRDM2, and EXOSC5, were studied for their effect on steps of the HIV-1 life cycle. We discuss the similarities and differences between our shRNA findings for HIV-1 using a spreading infection assay in human Jurkat T-cells and results from other investigators who used siRNA-based screenings in HeLa or 293T cells.",
"title": "A genome-wide short hairpin RNA screening of jurkat T-cells for human proteins contributing to productive HIV-1 replication."
},
{
"docid": "13231899",
"text": "Vaccines are largely ineffective for patients with established cancer, as advanced disease requires potent and sustained activation of CD8(+) cytotoxic T lymphocytes (CTLs) to kill tumor cells and clear the disease. Recent studies have found that subsets of dendritic cells (DCs) specialize in antigen cross-presentation and in the production of cytokines, which regulate both CTLs and T regulatory (Treg) cells that shut down effector T cell responses. Here, we addressed the hypothesis that coordinated regulation of a DC network, and plasmacytoid DCs (pDCs) and CD8(+) DCs in particular, could enhance host immunity in mice. We used functionalized biomaterials incorporating various combinations of an inflammatory cytokine, immune danger signal, and tumor lysates to control the activation and localization of host DC populations in situ. The numbers of pDCs and CD8(+) DCs, and the endogenous production of interleukin-12, all correlated strongly with the magnitude of protective antitumor immunity and the generation of potent CD8(+) CTLs. Vaccination by this method maintained local and systemic CTL responses for extended periods while inhibiting FoxP3 Treg activity during antigen clearance, resulting in complete regression of distant and established melanoma tumors. The efficacy of this vaccine as a monotherapy against large invasive tumors may be a result of the local activity of pDCs and CD8(+) DCs induced by persistent danger and antigen signaling at the vaccine site. These results indicate that a critical pattern of DC subsets correlates with the evolution of therapeutic antitumor responses and provide a template for future vaccine design.",
"title": "In situ regulation of DC subsets and T cells mediates tumor regression in mice."
},
{
"docid": "7224723",
"text": "HIV causes a chronic infection characterized by depletion of CD4(+) T lymphocytes and the development of opportunistic infections. Despite drugs that inhibit viral spread, HIV infection has been difficult to cure because of uncharacterized reservoirs of infected cells that are resistant to highly active antiretroviral therapy (HAART) and the immune response. Here we used CD34(+) cells from infected people as well as in vitro studies of wild-type HIV to show infection and killing of CD34(+) multipotent hematopoietic progenitor cells (HPCs). In some HPCs, we detected latent infection that stably persisted in cell culture until viral gene expression was activated by differentiation factors. A unique reporter HIV that directly detects latently infected cells in vitro confirmed the presence of distinct populations of active and latently infected HPCs. These findings have major implications for understanding HIV bone marrow pathology and the mechanisms by which HIV causes persistent infection.",
"title": "HIV–1 Infects Multipotent Progenitor Cells Causing Cell Death and Establishing Latent Cellular Reservoirs"
},
{
"docid": "10648422",
"text": "Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4+ T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interactions between PD-1 and programmed death ligand-1 (PD-L1) and between IL-10 and IL-10 receptor (IL-10R) results in viral clearance and improves T cell function in animal models of chronic viral infections. Here we show that high amounts of microbial products and inflammatory cytokines in the plasma of HIV-infected subjects lead to upregulation of PD-1 expression on monocytes that correlates with high plasma concentrations of IL-10. Triggering of PD-1 expressed on monocytes by PD-L1 expressed on various cell types induced IL-10 production and led to reversible CD4+ T cell dysfunction. We describe a new function for PD-1 whereby microbial products inhibit T cell expansion and function by upregulating PD-1 levels and IL-10 production by monocytes after binding of PD-1 by PD-L1.",
"title": "Programmed death-1–induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection"
},
{
"docid": "23420807",
"text": "Angiogenesis, the formation of new blood vessels from an existing vasculature, is requisite for tumor growth. It entails intercellular coordination of endothelial and tumor cells through angiogenic growth factor signaling. Interruption of these events has implications in the suppression of tumor growth. PD166285, a broad-spectrum receptor tyrosine kinase (RTK) inhibitor, and PD173074, a selective FGFR1TK inhibitor, were evaluated for their anti-angiogenic activity and anti-tumor efficacy in combination with photodynamic therapy (PDT). To evaluate the anti-angiogenic and anti-tumor activities of these compounds, RTK assays, in vitro tumor cell growth and microcapillary formation assays, in vivo murine angiogenesis and anti-tumor efficacy studies utilizing RTK inhibitors in combination with photodynamic therapy were performed. PD166285 inhibited PDGFR-β-, EGFR-, and FGFR1TKs and c-src TK by 50% (IC50) at concentrations between 7−85nM. PD173074 displayed selective inhibitory activity towards FGFR1TK at 26nM. PD173074 demonstrated (>100 fold) selective growth inhibitory action towards human umbilical vein endothelial cells compared with a panel of tumor cell lines. Both PD166285 and PD173074 (at 10nM) inhibited the formation of microcapillaries on Matrigel-coated plastic. In vivo anti-angiogenesis studies in mice revealed that oral administration (p.o.) of either PD166285 (1−25 mg/kg) or PD173074 (25−100 mg/kg) generated dose dependent inhibition of angiogenesis. Against a murine mammary 16c tumor, significantly prolonged tumor regressions were achieved with daily p.o. doses of PD166285 (5−10 mg/kg) or PD173074 (30−60 mg/kg) following PDT compared with PDT alone (p<0.001). Many long-term survivors were also noted in combination treatment groups. PD166285 and PD173074 displayed potent anti-angiogenic and anti-tumor activity and prolonged the duration of anti-tumor response to PDT. Interference in membrane signal transduction by inhibitors of specific RTKs (e.g. FGFR1TK) should result in new chemotherapeutic agents having the ability to limit tumor angiogenesis and regrowth following cytoreductive treatments such as PDT.",
"title": "Anti-Angiogenic Activity of Selected Receptor Tyrosine Kinase Inhibitors, PD166285 and PD173074: Implications for Combination Treatment with Photodynamic Therapy"
},
{
"docid": "27240699",
"text": "The human adenovirus E1B gene encodes a 55-kilodalton protein that inactivates the cellular tumor suppressor protein p53. Here it is shown that a mutant adenovirus that does not express this viral protein can replicate in and lyse p53-deficient human tumor cells but not cells with functional p53. Ectopic expression of the 55-kilodalton EIB protein in the latter cells rendered them sensitive to infection with the mutant virus. Injection of the mutant virus into p53-deficient human cervical carcinomas grown in nude mice caused a significant reduction in tumor size and caused complete regression of 60 percent of the tumors. These data raise the possibility that mutant adenoviruses can be used to treat certain human tumors.",
"title": "An adenovirus mutant that replicates selectively in p53-deficient human tumor cells."
},
{
"docid": "7451018",
"text": "Cancer has been recognized for thousands of years. Egyptians believed that cancer occurred at the will of the gods. Hippocrates believed human disease resulted from an imbalance of the four humors: blood, phlegm, yellow bile, and black bile with cancer being caused by excess black bile. The lymph theory of cancer replaced the humoral theory and the blastema theory replaced the lymph theory. Rudolph Virchow was the first to recognize that cancer cells like all cells came from other cells and believed chronic irritation caused cancer. At the same time there was a belief that trauma caused cancer, though it never evolved after many experiments inducing trauma. The birth of virology occurred in 1892 when Dimitri Ivanofsky demonstrated that diseased tobacco plants remained infective after filtering their sap through a filter that trapped bacteria. Martinus Beijerinck would call the tiny infective agent a virus and both Dimitri Ivanofsky and Marinus Beijerinck would become the fathers of virology. Not to long thereafter, Payton Rous founded the field of tumor virology in 1911 with his discovery of a transmittable sarcoma of chickens by what would come to be called Rous sarcoma virus or RSV for short. The first identified human tumor virus was the Epstein-Barr virus (EBV), named after Tony Epstein and Yvonne Barr who visualized the virus particles in Burkitt's lymphoma cells by electron microscopy in 1965. Since that time, many viruses have been associated with carcinogenesis including the most studied, human papilloma virus associated with cervical carcinoma, many other anogenital carcinomas, and oropharyngeal carcinoma. The World Health Organization currently estimates that approximately 22% of worldwide cancers are attributable to infectious etiologies, of which viral etiologies is estimated at 15-20%. The field of tumor virology/viral carcinogenesis has not only identified viruses as etiologic agents of human cancers, but has also given molecular insights to all human cancers including the oncogene activation and tumor suppressor gene inactivation.",
"title": "Viral Carcinogenesis."
},
{
"docid": "1574014",
"text": "Open reading frame 74 (ORF74) encoded by human herpesvirus 8 is a highly constitutively active seven transmembrane (7TM) receptor stimulated by angiogenic chemokines, e.g. growth-related oncogene-alpha, and inhibited by angiostatic chemokines e.g. interferon-gamma-inducible protein. Transgenic mice expressing ORF74 under control of the CD2 promoter develop highly vascularized Kaposi's sarcoma-like tumors. Through targeted mutagenesis we here create three distinct phenotypes of ORF74: a receptor with normal, high constitutive signaling through the phospholipase C pathway but deprived of binding and action of chemokines obtained through deletion of 22 amino acids from the N-terminal extension; an ORF74 with high constitutive activity but with selective elimination of stimulatory regulation by angiogenic chemokines obtained through substitution of basic residues at the extracellular ends of TM-V or TM-VI; and an ORF74 lacking constitutive activity but with preserved ability to be stimulated by agonist chemokines obtained through introduction of an Asp residue on the hydrophobic, presumed membrane-exposed face of TM-II. It is concluded that careful molecular dissection can selectively eliminate either agonist or inverse agonist modulation as well as high constitutive activity of the virally encoded oncogene ORF74 and that these mutant forms presumably can be used in transgenic animals to identify the molecular mechanism of its transforming activity.",
"title": "Selective elimination of high constitutive activity or chemokine binding in the human herpesvirus 8 encoded seven transmembrane oncogene ORF74."
},
{
"docid": "32556431",
"text": "MicroRNAs (miRNAs) are the subject of enormous interest. They are small non-coding RNAs that play a regulatory role in numerous and diverse cellular processes such as immune function, apoptosis and tumorigenesis. Several virus families have been shown to encode miRNAs, and an appreciation for their roles in the viral infectious cycle continues to grow. Despite the identification of numerous (>225) viral miRNAs, an in depth functional understanding of most virus-encoded miRNAs is lacking. Here we focus on a few viral miRNAs with well-defined functions. We use these examples to extrapolate general themes of viral miRNA activities including autoregulation of viral gene expression, avoidance of host defenses, and a likely important role in maintaining latent and persistent infections. We hypothesize that although the molecular mechanisms and machinery are similar, the majority of viral miRNAs may utilize a target strategy that differs from host miRNAs. That is, many viral miRNAs may have evolved to regulate viral-encoded transcripts or networks of host genes that are unique to viral miRNAs. Included in this latter category is a likely abundant class of viral miRNAs that may regulate only one or a few principal host genes. Key steps forward for the field are discussed, including the need for additional functional studies that utilize surgical viral miRNA mutants combined with relevant models of infection.",
"title": "Virus-encoded microRNAs."
},
{
"docid": "15425958",
"text": "Interleukin-10 (IL-10) suppresses the maturation and cytokine production of dendritic cells (DCs), key regulators of adaptive immunity, and prevents the activation and polarization of naïve T cells towards protective gamma interferon-producing effectors. We hypothesized that human cytomegalovirus (HCMV) utilizes its viral IL-10 homolog (cmvIL-10) to attenuate DC functionality, thereby subverting the efficient induction of antiviral immune responses. RNA and protein analyses demonstrated that the cmvIL-10 gene was expressed with late gene kinetics. Treatment of immature DCs (iDCs) with supernatant from HCMV-infected cultures inhibited both the lipopolysaccharide-induced DC maturation and proinflammatory cytokine production. These inhibitory effects were specifically mediated through the IL-10 receptor and were not observed when DCs were treated with supernatant of cells infected with a cmvIL-10-knockout mutant. Incubation of iDCs with recombinant cmvIL-10 recapitulated the inhibition of maturation. Furthermore, cmvIL-10 had pronounced long-term effects on those DCs that could overcome this inhibition of maturation. It enhanced the migration of mature DCs (mDCs) towards the lymph node homing chemokine but greatly reduced their cytokine production. The inability of mDCs to secrete IL-12 was maintained, even when they were restimulated by the activated T-cell signal CD40 ligand in the absence of cmvIL-10. Importantly, cmvIL-10 potentiates these anti-inflammatory effects, at least partially, by inducing endogenous cellular IL-10 expression in DCs. Collectively, we show that cmvIL-10 causes long-term functional alterations at all stages of DC activation.",
"title": "Human Cytomegalovirus-Encoded Interleukin-10 Homolog Inhibits Maturation of Dendritic Cells and Alters Their Functionality"
},
{
"docid": "26047921",
"text": "Cells can respond to mechanical stress by gating mechanosensitive ion channels (MSCs). The cloning of Piezo1, a eukaryotic cation selective MSC, defines a new system for studying mechanical transduction at the cellular level. Because Piezo1 has electrophysiological properties similar to those of endogenous cationic MSCs that are selectively inhibited by the peptide GsMTx4, we tested whether the peptide targets Piezo1 activity. Extracellular GsMTx4 at micromolar concentrations reversibly inhibited ∼80% of the mechanically induced current of outside-out patches from transfected HEK293 cells. The inhibition was voltage insensitive, and as seen with endogenous MSCs, the mirror image d enantiomer inhibited like the l. The rate constants for binding and unbinding based on Piezo1 current kinetics provided association and dissociation rates of 7.0 × 10(5) M(-1) s(-1) and 0.11 s(-1), respectively, and a K(D) of ∼155 nM, similar to values previously reported for endogenous MSCs. Consistent with predicted gating modifier behavior, GsMTx4 produced an ∼30 mmHg rightward shift in the pressure-gating curve and was active on closed channels. In contrast, streptomycin, a nonspecific inhibitor of cationic MSCs, showed the use-dependent inhibition characteristic of open channel block. The peptide did not block currents of the mechanical channel TREK-1 on outside-out patches. Whole-cell Piezo1 currents were also reversibly inhibited by GsMTx4, and although the off rate was nearly identical to that of outside-out patches, differences were observed for the on rate. The ability of GsMTx4 to target the mechanosensitivity of Piezo1 supports the use of this channel in high-throughput screens for pharmacological agents and diagnostic assays.",
"title": "The mechanosensitive ion channel Piezo1 is inhibited by the peptide GsMTx4."
},
{
"docid": "20357868",
"text": "Primary simian immunodeficiency virus (SIV) isolated from sooty mangabey (SIVsm [n = 6]), stumptail (SIVstm [n = 1]), mandrill (SIVmnd [n = 1]), and African green (SIVagm [n = 1]) primates were examined for their ability to infect human cells and for their coreceptor requirements. All isolates infected human peripheral blood mononuclear cells (PBMCs) from a CCR5(+/+) donor, and seven of eight isolates tested also infected CCR5(-/-) PBMCs. Analysis of coreceptor utilization using GHOST and U87 cell lines revealed that all of the isolates tested used CCR5 and the orphan receptors STRL33 and GPR15. Coreceptors such as CCR2b, CCR3, CCR8, and CX3CR1 were also utilized by some primary SIV isolates. More importantly, we found that CXCR4 was used as a coreceptor by the SIVstm, the SIVagm, and four of the SIVsm isolates in GHOST and U87 cells. These data suggest that primary SIV isolates from diverse primate species can utilize CXCR4 for viral entry, similar to what has been described for human immunodeficiency viruses.",
"title": "Simian immunodeficiency viruses of diverse origin can use CXCR4 as a coreceptor for entry into human cells."
},
{
"docid": "8671456",
"text": "BACKGROUND Interleukin-24 (IL-24) is a cytokine that belongs to the IL-10 family. It can selectively induce cancer cell apoptosis which has been utilized as a cancer gene therapy strategy. METHODS A recombinant type five adenovirus containing IL-24 gene (designated CNHK600-IL24) was constructed, whose replication is activated only in tumor cells. The replication of CNHK600-IL24 in breast tumor cells and fibroblasts were assessed by TCID50 and MTT assay; the secretion of IL-24 was measured by ELISA and western blotting. The in vivo anti-tumor effect of CNHK600-IL24 was investigated in nude mice carrying orthotopic or metastatic breast tumor. RESULTS We observed that CNHK600-IL24 could replicate efficiently and resulted in high level IL-24 expression and massive cell death in human breast cancer cell MDA-MB-231 but not in normal fibroblast cell MRC-5. In addition, orthotopic breast tumor growth in the nude mice model was significantly suppressed when CNHK600-IL24 was administered. In the metastatic model generated by tail vein injection, CNHK600-IL24 virotherapy significantly improved survival compared with the same virus expressing EGFP (median survival CNHK600-IL24, 55 days vs. CNHK600-EGFP, 41 day, p < 0.05 Mantal-Cox test). A similar phenomenon was observed in the metastatic model achieved by left ventricular injection as suggested by in vivo luminescence imaging of tumor growth. CONCLUSION The oncolytic adenovirus armed with IL-24, which exhibited enhanced anti-tumor activity and improved survival, is a promising candidate for virotherapy of breast cancer.",
"title": "Oncolytic adenovirus armed with IL-24 Inhibits the growth of breast cancer in vitro and in vivo"
},
{
"docid": "3829232",
"text": "BACKGROUND The Polycomb group (PcG) of proteins is a family of important developmental regulators. The respective members function as large protein complexes involved in establishment and maintenance of transcriptional repression of developmental control genes. MBTD1, Malignant Brain Tumor domain-containing protein 1, is one such PcG protein. MBTD1 contains four MBT repeats. METHODOLOGY/PRINCIPAL FINDINGS We have determined the crystal structure of MBTD1 (residues 130-566aa covering the 4 MBT repeats) at 2.5 A resolution by X-ray crystallography. The crystal structure of MBTD1 reveals its similarity to another four-MBT-repeat protein L3MBTL2, which binds lower methylated lysine histones. Fluorescence polarization experiments confirmed that MBTD1 preferentially binds mono- and di-methyllysine histone peptides, like L3MBTL1 and L3MBTL2. All known MBT-peptide complex structures characterized to date do not exhibit strong histone peptide sequence selectivity, and use a \"cavity insertion recognition mode\" to recognize the methylated lysine with the deeply buried methyl-lysine forming extensive interactions with the protein while the peptide residues flanking methyl-lysine forming very few contacts [1]. Nevertheless, our mutagenesis data based on L3MBTL1 suggested that the histone peptides could not bind to MBT repeats in any orientation. CONCLUSIONS The four MBT repeats in MBTD1 exhibits an asymmetric rhomboid architecture. Like other MBT repeat proteins characterized so far, MBTD1 binds mono- or dimethylated lysine histones through one of its four MBT repeats utilizing a semi-aromatic cage. ENHANCED VERSION This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.",
"title": "Structural Studies of a Four-MBT Repeat Protein MBTD1"
},
{
"docid": "3756384",
"text": "BACKGROUND & AIMS Hepatocytes in which the hepatitis B virus (HBV) is replicating exhibit loss of the chromatin modifying polycomb repressive complex 2 (PRC2), resulting in re-expression of specific, cellular PRC2-repressed genes. Epithelial cell adhesion molecule (EpCAM) is a PRC2-repressed gene, normally expressed in hepatic progenitors, but re-expressed in hepatic cancer stem cells (hCSCs). Herein, we investigated the functional significance of EpCAM re-expression in HBV-mediated hepatocarcinogenesis. METHODS Employing molecular approaches (transfections, fluorescence-activated cell sorting, immunoblotting, qRT-PCR), we investigated the role of EpCAM-regulated intramembrane proteolysis (RIP) in HBV replicating cells in vitro, and in liver tumors from HBV X/c-myc mice and chronically HBV infected patients. RESULTS EpCAM undergoes RIP in HBV replicating cells, activating canonical Wnt signaling. Transfection of Wnt-responsive plasmid expressing green fluorescent protein (GFP) identified a GFP + population of HBV replicating cells. These GFP+/Wnt+ cells exhibited cisplatin- and sorafenib-resistant growth resembling hCSCs, and increased expression of pluripotency genes NANOG, OCT4, SOX2, and hCSC markers BAMBI, CD44 and CD133. These genes are referred as EpCAM RIP and Wnt-induced hCSC-like gene signature. Interestingly, this gene signature is also overexpressed in liver tumors of X/c-myc bitransgenic mice. Clinically, a group of HBV-associated hepatocellular carcinomas was identified, exhibiting elevated expression of the hCSC-like gene signature and associated with reduced overall survival post-surgical resection. CONCLUSIONS The hCSC-like gene signature offers promise as prognostic tool for classifying subtypes of HBV-induced HCCs. Since EpCAM RIP and Wnt signaling drive expression of this hCSC-like signature, inhibition of these pathways can be explored as therapeutic strategy for this subtype of HBV-associated HCCs. LAY SUMMARY In this study, we provide evidence for a molecular mechanism by which chronic infection by the hepatitis B virus results in the development of poor prognosis liver cancer. Based on this mechanism our results suggest possible therapeutic interventions.",
"title": "EpCAM-regulated intramembrane proteolysis induces a cancer stem cell-like gene signature in hepatitis B virus-infected hepatocytes."
},
{
"docid": "14819804",
"text": "The novel phosphatidylinositol-3-kinase (PI3K) inhibitor PX-866 was tested against 13 experimental human tumor xenografts derived from cell lines of various tissue origins. Mutant PI3K (PIK3CA) and loss of PTEN activity were sufficient, but not necessary, as predictors of sensitivity to the antitumor activity of the PI3K inhibitor PX-866 in the presence of wild-type Ras, whereas mutant oncogenic Ras was a dominant determinant of resistance, even in tumors with coexisting mutations in PIK3CA. The level of activation of PI3K signaling measured by tumor phosphorylated Ser(473)-Akt was insufficient to predict in vivo antitumor response to PX-866. Reverse-phase protein array revealed that the Ras-dependent downstream targets c-Myc and cyclin B were elevated in cell lines resistant to PX-866 in vivo. Studies using an H-Ras construct to constitutively and preferentially activate the three best-defined downstream targets of Ras, i.e., Raf, RalGDS, and PI3K, showed that mutant Ras mediates resistance through its ability to use multiple pathways for tumorigenesis. The identification of Ras and downstream signaling pathways driving resistance to PI3K inhibition might serve as an important guide for patient selection as inhibitors enter clinical trials and for the development of rational combinations with other molecularly targeted agents.",
"title": "Mutations in the phosphatidylinositol-3-kinase pathway predict for antitumor activity of the inhibitor PX-866 whereas oncogenic Ras is a dominant predictor for resistance."
},
{
"docid": "4391121",
"text": "Half a century ago, chronic granulomatous disease (CGD) was first described as a disease fatally affecting the ability of children to survive infections. Various milestone discoveries have since been made, from an insufficient ability of patients’ leucocytes to kill microbes to the underlying genetic abnormalities. In this inherited disorder, phagocytes lack NADPH oxidase activity and do not generate reactive oxygen species, most notably superoxide anion, causing recurrent bacterial and fungal infections. Patients with CGD also suffer from chronic inflammatory conditions, most prominently granuloma formation in hollow viscera. The precise mechanisms of the increased microbial pathogenicity have been unclear, and more so the reasons for the exaggerated inflammatory response. Here we show that a superoxide-dependent step in tryptophan metabolism along the kynurenine pathway is blocked in CGD mice with lethal pulmonary aspergillosis, leading to unrestrained Vγ1+ γδ T-cell reactivity, dominant production of interleukin (IL)-17, defective regulatory T-cell activity and acute inflammatory lung injury. Although beneficial effects are induced by IL-17 neutralization or γδ T-cell contraction, complete cure and reversal of the hyperinflammatory phenotype are achieved by replacement therapy with a natural kynurenine distal to the blockade in the pathway. Effective therapy, which includes co-administration of recombinant interferon-γ (IFN-γ), restores production of downstream immunoactive metabolites and enables the emergence of regulatory Vγ4+ γδ and Foxp3+ αβ T cells. Therefore, paradoxically, the lack of reactive oxygen species contributes to the hyperinflammatory phenotype associated with NADPH oxidase deficiencies, through a dysfunctional kynurenine pathway of tryptophan catabolism. Yet, this condition can be reverted by reactivating the pathway downstream of the superoxide-dependent step.",
"title": "Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease"
},
{
"docid": "6559701",
"text": "Epstein-Barr virus (EBV) infection contributes to the development of several different types of human malignancy, including Burkitt lymphoma, Hodgkin lymphoma, and nasopharyngeal carcinoma. As a herpesvirus, EBV can establish latent or lytic infection in cells. EBV-positive tumors are composed almost exclusively of cells with latent EBV infection. Strategies for inducing the lytic form of EBV infection in tumor cells are being investigated as a potential therapy for EBV-positive tumors. In this article, we review how cellular and viral proteins regulate the latent-lytic EBV switch in infected B cells and epithelial cells, and discuss how harnessing lytic viral reactivation might be used therapeutically.",
"title": "Regulation of the latent-lytic switch in Epstein-Barr virus."
},
{
"docid": "9278263",
"text": "The cell surface display of peptides by MHC class I molecules to lymphocytes provides the host with an important surveillance mechanism to protect against invading pathogens. However, in turn, viruses have evolved elegant strategies to inhibit various stages of the MHC class I antigen presentation pathway and prevent the display of viral peptides. This Review highlights how the elucidation of mechanisms of viral immune evasion is important for advancing our understanding of virus–host interactions and can further our knowledge of the MHC class I presentation pathway as well as other cellular pathways.",
"title": "MHC class I antigen presentation: learning from viral evasion strategies"
},
{
"docid": "21868715",
"text": "Molecular mechanisms leading to myocardial injury during warm or cold ischemia are insufficiently understood. Although proteasomes are thought to contribute to myocardial ischemia-reperfusion injury, their roles during the ischemic period remain elusive. Because donor hearts are commonly exposed to prolonged global cold ischemia prior to cardiac transplantation, we evaluated the role and regulation of the proteasome during cold ischemic storage of rat hearts in context of the myocardial ATP content. When measured at the actual tissue ATP concentration, cardiac proteasome peptidase activity increased by 225% as ATP declined during cold ischemic storage of hearts in University of Wisconsin (UW) solution for up to 48h. Addition of the specific proteasome inhibitor epoxomicin to the UW solution inhibited proteasome activity in the cardiac extracts, significantly reduced edema formation and preserved the ultrastructural integrity of the cardiomyocyte. Utilizing purified 20S/26S proteasome enzyme preparations, we demonstrate that this activation can be attributed to a subset of 26S proteasomes which are stable at ATP concentrations far below physiological levels, that ATP negatively regulates its activity and that maximal activation occurs at ATP concentrations in the low mumol/L range. These data suggest that proteasome activation is a pathophysiologically relevant mechanism of cold ischemic myocardial injury. A subset of 26S proteasomes appears to be a cell-destructive protease that is activated as ATP levels decline. Proteasome inhibition during cold ischemia preserves the ultrastructural integrity of the cardiomyocyte.",
"title": "A subset of 26S proteasomes is activated at critically low ATP concentrations and contributes to myocardial injury during cold ischemia."
},
{
"docid": "6404801",
"text": "Micro (mi)RNAs are small non-coding RNAs that regulate the expression of their targets' messenger RNAs through both translational inhibition and regulation of target RNA stability. Recently, a number of viruses, particularly of the herpesvirus family, have been shown to express their own miRNAs to control both viral and cellular transcripts. Although some targets of viral miRNAs are known, their function in a physiologically relevant infection remains to be elucidated. As such, no in vivo phenotype of a viral miRNA knock-out mutant has been described so far. Here, we report on the first functional phenotype of a miRNA knock-out virus in vivo. During subacute infection of a mutant mouse cytomegalovirus lacking two viral miRNAs, virus production is selectively reduced in salivary glands, an organ essential for virus persistence and horizontal transmission. This phenotype depends on several parameters including viral load and mouse genetic background, and is abolished by combined but not single depletion of natural killer (NK) and CD4+ T cells. Together, our results point towards a miRNA-based immunoevasion mechanism important for long-term virus persistence.",
"title": "Cytomegalovirus microRNAs Facilitate Persistent Virus Infection in Salivary Glands"
},
{
"docid": "18938992",
"text": "Virally infected cells degrade intracellular viral proteins proteolytically and present the resulting peptides in association with major histocompatibility complex (MHC) class I molecules to CD8+ cytotoxic T lymphocytes (CTLs). These cells are normally prone to CTL-mediated elimination. However, several viruses have evolved strategies to avoid detection by the immune system that interfere with the pathway of antigen presentation. Epstein-Barr virus (EBV) expresses a predominantly late protein, the BCRF1 gene product vIL-10, that is similar in sequence to the human interleukin-10 (hIL-10). We show here that vIL-10 affects the expression of one of the two transporter proteins (TAPs) associated with antigen presentation. Similarly, hIL-10 showed the same activity. Expression of the LMP2 and TAP1 genes but not expression of TAP2 or LMP7 is efficiently downregulated, indicating a specific IL-10 effect on the two divergently transcribed TAP1 and LMP2 genes. Downregulation of TAP1 by IL-10 hampers the transport of peptide antigens into the endoplasmatic reticulum, as shown in the TAP-specific peptide transporter assay, their loading onto empty MHC I molecules, and the subsequent translocation to the cell surface. As a consequence, IL-10 causes a general reduction of surface MHC I molecules on B lymphocytes that might also affect the recognition of EBV-infected cells by cytotoxic T cells.",
"title": "Downregulation of TAP1 in B lymphocytes by cellular and Epstein-Barr virus-encoded interleukin-10."
},
{
"docid": "15997009",
"text": "BACKGROUND Treatment regimens for active tuberculosis (TB) that are intermittent, or use rifampin during only the initial phase, offer practical advantages, but their efficacy has been questioned. We conducted a systematic review of treatment regimens for active TB, to assess the effect of duration and intermittency of rifampin use on TB treatment outcomes. METHODS AND FINDINGS PubMed, Embase, and the Cochrane CENTRAL database for clinical trials were searched for randomized controlled trials, published in English, French, or Spanish, between 1965 and June 2008. Selected studies utilized standardized treatment with rifampin-containing regimens. Studies reported bacteriologically confirmed failure and/or relapse in previously untreated patients with bacteriologically confirmed pulmonary TB. Pooled cumulative incidences of treatment outcomes and association with risk factors were computed with stratified random effects meta-analyses. Meta-regression was performed using a negative binomial regression model. A total of 57 trials with 312 arms and 21,472 participants were included in the analysis. Regimens utilizing rifampin only for the first 1-2 mo had significantly higher rates of failure, relapse, and acquired drug resistance, as compared to regimens that used rifampin for 6 mo. This was particularly evident when there was initial drug resistance to isoniazid, streptomycin, or both. On the other hand, there was little evidence of difference in failure or relapse with daily or intermittent schedules of treatment administration, although there was insufficient published evidence of the efficacy of twice-weekly rifampin administration throughout therapy. CONCLUSIONS TB treatment outcomes were significantly worse with shorter duration of rifampin, or with initial drug resistance to isoniazid and/or streptomycin. Treatment outcomes were similar with all intermittent schedules evaluated, but there is insufficient evidence to support administration of treatment twice weekly throughout therapy.",
"title": "Effect of Duration and Intermittency of Rifampin on Tuberculosis Treatment Outcomes: A Systematic Review and Meta-Analysis"
},
{
"docid": "42489926",
"text": "p53 regulates a key pathway which protects normal tissues from tumor development that may result from diverse forms of stress. In the absence of stress, growth suppressive and proapoptotic activity of p53 is inhibited by MDM2 which binds p53 and negatively regulates its activity and stability. MDM2 antagonists could activate p53 and may offer a novel therapeutic approach to cancer. Recently, we identified the first potent and selective low molecular weight inhibitors of MDM2-p53 binding, the Nutlins. These molecules activate the p53 pathway and suppress tumor growth in vitro and in vivo. They represent valuable new tools for studying the p53 pathway and its defects in cancer. Nutlins induce p53-dependent apoptosis in human cancer cells but appear cytostatic to proliferating normal cells. Their potent activity against osteosarcoma xenografts suggests that MDM2 antagonists may have clinical utility in the treatment of tumors with wild-type p53.",
"title": "Small-molecule antagonists of p53-MDM2 binding: research tools and potential therapeutics."
},
{
"docid": "20261352",
"text": "OBJECTIVE To define the impact of chronic viremia and associated immune activation on B-cell exhaustion in HIV infection. DESIGN Progressive HIV infection is marked by B-cell anergy and exhaustion coupled with dramatic hypergammaglobulinemia. Although both upregulation of CD95 and loss of CD21 have been used as markers of infection-associated B-cell dysfunction, little is known regarding the specific profiles of dysfunctional B cells and whether persistent viral replication and its associated immune activation play a central role in driving B-cell dysfunction. METHODS Multiparameter flow cytometry was used to define the profile of dysfunctional B cells. The changes in the expression of CD21 and CD95 were tracked on B-cell subpopulations in patients with differential control of viral replication. RESULTS : Although the emergence of exhausted, CD21 tissue-like memory B cells followed similar patterns in both progressors and controllers, the frequency of CD21 activated memory B cells was lower in spontaneous controllers. CONCLUSION Our results suggest that the loss of CD21 and the upregulation of CD95 occur as separate events during the development of B-cell dysfunction. The loss of CD21 is a marker of B-cell exhaustion induced in the absence of appreciable viral replication, whereas the upregulation of CD95 is tightly linked to persistent viral replication and its associated immune activation. Thus, these dysfunctional profiles potentially represent two functionally distinct states within the B-cell compartment.",
"title": "Decoupling activation and exhaustion of B cells in spontaneous controllers of HIV infection."
},
{
"docid": "45287266",
"text": "Hepatitis C virus (HCV) nonstructural protein 3-4A (NS3-4A) is a complex composed of NS3 and its cofactor NS4A. It harbours serine protease as well as NTPase/RNA helicase activities and is essential for viral polyprotein processing, RNA replication and virion formation. Specific inhibitors of the NS3-4A protease significantly improve sustained virological response rates in patients with chronic hepatitis C when combined with pegylated interferon-α and ribavirin. The NS3-4A protease can also target selected cellular proteins, thereby blocking innate immune pathways and modulating growth factor signalling. Hence, NS3-4A is not only an essential component of the viral replication complex and prime target for antiviral intervention but also a key player in the persistence and pathogenesis of HCV. This review provides a concise update on the biochemical and structural aspects of NS3-4A, its role in the pathogenesis of chronic hepatitis C and the clinical development of NS3-4A protease inhibitors.",
"title": "Nonstructural protein 3-4A: the Swiss army knife of hepatitis C virus."
},
{
"docid": "16172576",
"text": "BACKGROUND High genetic diversity at both inter- and intra-host level are hallmarks of RNA viruses due to the error-prone nature of their genome replication. Several groups have evaluated the extent of viral variability using different RNA virus deep sequencing methods. Although much of this effort has been dedicated to pathogens that cause chronic infections in humans, few studies investigated arthropod-borne, acute viral infections. METHODS AND PRINCIPAL FINDINGS We deep sequenced the complete genome of ten DENV2 isolates from representative classical and severe cases sampled in a large outbreak in Brazil using two different approaches. Analysis of the consensus genomes confirmed the larger extent of the 2010 epidemic in comparison to a previous epidemic caused by the same viruses in another city two years before (genetic distance = 0.002 and 0.0008 respectively). Analysis of viral populations within the host revealed a high level of conservation. After excluding homopolymer regions of 454/Roche generated sequences, we found 10 to 44 variable sites per genome population at a frequency of >1%, resulting in very low intra-host genetic diversity. While up to 60% of all variable sites at intra-host level were non-synonymous changes, only 10% of inter-host variability resulted from non-synonymous mutations, indicative of purifying selection at the population level. CONCLUSIONS AND SIGNIFICANCE Despite the error-prone nature of RNA-dependent RNA-polymerase, dengue viruses maintain low levels of intra-host variability.",
"title": "Inter- and Intra-Host Viral Diversity in a Large Seasonal DENV2 Outbreak"
}
] |
6029
|
Richard Branson founded a chain of record stores.
|
[
{
"docid": "Richard_Branson",
"text": "Sir Richard Charles Nicholas Branson ( born 18 July 1950 ) is an English business magnate , investor and philanthropist . He founded the Virgin Group , which controls more than 400 companies . Branson expressed his desire to become an entrepreneur at a young age . At the age of sixteen his first business venture was a magazine called Student . In 1970 , he set up a mail-order record business . In 1972 , he opened a chain of record stores , Virgin Records , later known as Virgin Megastores . Branson 's Virgin brand grew rapidly during the 1980s , as he set up Virgin Atlantic airline and expanded the Virgin Records music label . In March 2000 , Branson was knighted at Buckingham Palace for `` services to entrepreneurship '' . For his work in retail , music and transport ( with interests in land , air , sea and space travel ) , his taste for adventure , and for his humanitarian work , he became one of the most prominent figures in British culture . In 2002 he was named in the BBC 's poll of the 100 Greatest Britons . In January 2016 , Forbes listed Branson 's estimated net worth at $ 5.2 billion .",
"title": ""
},
{
"docid": "Virgin_Records",
"text": "Virgin Records is a British-founded record label founded by English entrepreneurs Richard Branson , Simon Draper , Nik Powell , and musician Tom Newman in 1972 . The company grew to be a worldwide phenomenon over time , with the success of its platinum performers such as Janet Jackson , Roy Orbison , Devo , Genesis , Keith Richards , the Human League , Culture Club , Simple Minds , Lenny Kravitz , dc Talk , the Smashing Pumpkins , Mike Oldfield , Spice Girls and more on their list of artists . It was later sold to Thorn EMI in 1992 . Currently wholly owned by Universal Music Group after its purchase of EMI in 2012 , UMG absorbed Virgin 's British operations , Virgin Records , Ltd. , to create Virgin EMI Records in March 2013 , which in turn absorbed Mercury Records ' UK operations . Today , the operations of Virgin Records America , Inc. ( a unit of Virgin Records , Ltd. ) are still active and headquartered in Hollywood , California , as it operates exclusively under the Capitol Music Group since 2007 . A heavily minor amount of artists remain on Virgin Records America 's roster , which today is mostly occupied with European artists such as Bastille , Circa Waves , Corinne Bailey Rae , Ella Eyre , Grizfolk , Walking on Cars , Seinabo Sey , and Prides . US artists include Knox Hamilton , L'Tric and Rise Against .",
"title": ""
}
] |
[
{
"docid": "Virgin_Megastores",
"text": "Virgin Megastores is an international entertainment retailing chain , founded by Sir Richard Branson as a record shop on London 's Oxford Street in early 1976 . In 1979 the company opened their first Megastore at the end of Oxford Street and Tottenham Court Road . The company expanded to hundreds of stores worldwide in the 1990s , but has lost a large number of stores in recent years , largely with the sale and eventual closing of the UK , US , Irish , Canadian , Australian , Italian , Spanish , French , Greek and Japanese stores . By 2015 , current operations are exclusively in the Middle East and in North Africa , consisting of approximately 40 stores .",
"title": ""
},
{
"docid": "Zavvi_(retailer)",
"text": "Zavvi was an entertainment retail chain in the United Kingdom and Ireland , originally Virgin Megastores . Zavvi was formed in September 2007 when a management buy-out team purchased the company from Richard Branson 's Virgin Group . It was the UK 's largest independent entertainment retailer before being placed in administration on 24 December 2008 . Store closures took place from January 2009 , with the last to cease trading on 20 February . HMV purchased 19 Zavvi stores to be merged into the HMV chain . Former managing director Simon Douglas and business partner Les Whitfield purchased five of the stores to form Head Entertainment , all of which eventually closed in early 2009 after less than a year of trading . On 2 March 2009 , The Hut Group purchased the rights to the Zavvi brand online , and relaunched the Zavvi website with an increased range .",
"title": ""
},
{
"docid": "Virgin_Megastores_UK",
"text": "Virgin Megastores was a retail chain that operated in the United Kingdom from 1971 to 2007 . The company was established by Richard Branson , originally as a small record shop , and became a national chain . In 2007 , the company was sold to management , and was rebranded as Zavvi . Zavvi entered administration in 2008 and subsequently closed .",
"title": ""
},
{
"docid": "Reynolds_and_Branson",
"text": "Reynolds & Branson Leeds was a business based at 13 Briggate and 14 Commercial Street in Leeds , England . The business lasted from 1816 to 1972 . Edward Matterson managed the company in 1822 , and William West F.R.S. took over the in 1833 . The National Archives Records about the company include a day book , sales ledger , and prescription books . The records were created by Reynolds & Branson Ltd. . Reynolds & Branson was registered in July 1898 as a limited corporation with a capital of # 34,000 in shares of # 10 each by Messrs. R. Reynolds , F. W. Branson . No remuneration was given to Mr. R. Reynolds , but a # 700 per annum was given to each of the others . In 1890 , Richard Reynold 's son , Richard Freshfield ( Fred ) Reynolds was made a partner . The firm was in the business of wholesale and retail for chemists and surgical instrument makers .",
"title": ""
},
{
"docid": "National_Record_Mart",
"text": "National Record Mart , known as NRM for short , was an American music store chain . The first music store chain in the United States , it was founded in 1937 in Pittsburgh , Pennsylvania , and operated more than 130 locations at its peak . Other stores under its ownership included Oasis , Music X , Waves Music , and Vibes . The chain filed for bankruptcy in 2001 and closed the last of its stores in 2002 .",
"title": ""
},
{
"docid": "Rock_the_Kasbah",
"text": "Rock the Kasbah is an annual gala fundraiser co-hosted by Sir Richard Branson and his mother Eve Branson . Funds raised go to Richard Branson 's Virgin Unite foundation and also to The Eve Branson Foundation . The first Rock the Kasbah event was held on July 2 , 2007 at the Hollywood Roosevelt Hotel in Los Angeles , California . Richard Branson attended the event in formal Moroccan wear and arrived at the event by way of horseback . Branson described the first Rock the Kasbah event as `` one of the best parties I 've ever been to '' and musical guest Jewel performed . Funds raised at this event , via ticket sales and live and silent auctions , went to help build schools in the Atlas Mountains of Morocco , as well as three villages near Kasbah Tamadot . Celebrity guests included Buzz Aldrin and Rachel Hunter . The 2008 Rock the Kasbah event was also held at the Hollywood Roosevelt Hotel on October 23 in Los Angeles , California . Celebrity guests at that year 's gala included Salma Hayek and Charlize Theron . While at the event , Theron said that Richard Branson `` is an incredibly compassionate human being and is coming up with really innovative ways , under this umbrella of this foundation that he has , to really give back . '' Also in attendance were Neve Campbell and Natalie Imbruglia . Richard Branson was unable to attend the 2008 event due to being at sea in an attempt to set a transatlantic sailing record . In 2009 , Rock the Kasbah was held at Vibiana on October 26 in Los Angeles , California , with a mix of Moroccan and Hollywood theme . Gavin Rossdale performed and some of the celebrities in attendance were Paula Abdul , Lindsay Lohan , Sharon Stone , and Estelle . The 2010 event took place on November 11 at the Dorothy Chandler Pavilion in Los Angeles , California , with the goal to raise at minimum $ 500,000 . At the event , Colbie Caillat and Common performed together on stage . Sam Branson , son of Richard Branson , also performed at the event with his band Delilah . Items up for auction included a 7-night stay on Branson 's own Necker Island , and a Triumph Daytona 675 World Supersport motorcycle . Celebrity guests included Jennifer Love Hewitt , Justin Long , and musician Yoshiki . The fifth annual Rock the Kasbah event took place on November 16 , 2011 and was held at Boulevard3 in Los Angeles , California . Performers playing at the 2011 Rock the Kasbah event included O.A.R. , The Pussycat Dolls , and Mary J. Blige . Celebrities in attendance included Richard Branson and his mother , Eve Branson , Paris Hilton , Geena Davis , Stan Lee , will.i.am , and others . Items up for bid during the live auction included the opportunity to name a Virgin America airplane , a trip to meet Ben and Jerry and create a Ben and Jerry 's ice cream flavor , an opportunity to swim with the sharks and Richard Branson , and more . Prior to the event , on 1 November 2011 , a full-page ad on the back cover of Daily Variety magazine listed over 50 logos of the apparent partners in this event , including Virgin America , Virgin Atlantic , Virgin Galactic , Livestream , Tiffany & Co. , Harry Winston , Gilt , Charitybuzz , and many others . Rock the Kasbah 2011 was broadcast live ( for the first time ) on Livestream.com , an internet streaming channel .",
"title": ""
},
{
"docid": "Buy_Buy_Baby",
"text": "Buy Buy Baby , Inc. ( stylized : buybuy BABY ) is a chain of stores that sell clothing , strollers and other items for use with infants and young children . It operates 135 stores across the United States . The chain was founded in 1996 by brothers Richard and Jeffrey Feinstein . It consisted of eight stores when it was acquired by Bed Bath & Beyond in 2007 . Its primary competitor is Babies `` R '' Us .",
"title": ""
},
{
"docid": "Record_Bar",
"text": "The Record Bar is a former U.S. retail music/entertainment store chain founded in Durham , NC . The company eventually grew from a single location to 180 stores . One of the largest music retailing chains , it was located primarily in the Southeastern United States . From 1960 until the late 1980s the owners of Record Bar were the Bergman family of Durham , NC . In the mid-to-late 1980s Record Bar began opening large new stores and remodeled Record Bar stores under the Tracks name , to better reflect the changes taking place in retail music merchandising ( e.g. - large freestanding `` super '' stores like Peaches and Tower ) . In October 1989 the company was sold to Super Club N.V. , a Brussels , Belgium video distribution company , by Barrie and his partners for $ 92 million . At that time the Record Bar operated 167 stores in the southeastern United States and middle Atlantic states . In the early 1990s Super Club sold Record Bar , Turtle 's Records & Tapes and its other U.S. music and video rental acquisitions to Blockbuster Video . Blockbuster converted its music retail outlets to Blockbuster Music stores , ending the Record Bar chain . As of 2007 , no entity using the Record Bar name had a previous affiliation with the Durham NC based chain . After selling Record Bar , Barrie Bergman and John Hansen purchased Bare Escentuals which was bankrupt . This four store skin care company was consolidated into two stores . Mineral makeup became the focus instead of body lotions . Featured on QVC and twenty-four stores later , Bare Escentuals was rescued from economic ruin and recapitalized for over $ 200 million 14 years later .",
"title": ""
},
{
"docid": "Tom_Newman_(musician)",
"text": "Not to be confused with Thomas Newman . Thomas Dennis `` Tom '' Newman ( born 11 July 1943 in Perivale ) is an English record producer and musician ( rhythm guitar ) . In 1970 he began working with Richard Branson and helped to found The Manor Studio in Oxford for the nascent Virgin Records . There , he produced the recording of Mike Oldfield 's Tubular Bells .",
"title": ""
},
{
"docid": "Sears",
"text": "Sears , Roebuck & Company , also known simply as Sears , is an American chain of department stores founded by Richard Warren Sears and Alvah Curtis Roebuck in 1886 . Formerly based at the Sears Tower in Chicago and currently headquartered in Hoffman Estates , Illinois , it began as a mail ordering catalog company and began opening retail locations in 1925 . The company was bought by the American big box chain Kmart in 2005 , which had just emerged from bankruptcy at the time and renamed itself Sears Holdings upon completion of the merger . In terms of domestic revenue , Sears was the largest retailer in the United States until October 1989 , when Walmart surpassed the record . It is currently the fifth-largest American department store company by sales as of October 2013 ( behind Walmart , Target , Best Buy , and The Home Depot ) , and the twelfth-largest retailer in the country overall . Sears operates divisions in Canada and Mexico , as well as several other subsidiaries within its brand .",
"title": ""
},
{
"docid": "United_We_Stand_(Debby_and_Glen_Campbell_album)",
"text": "United We Stand is a release by Glen Campbell 's eldest daughter Debby . Debby Campbell has been performing with her father since 1987 . She was a featured vocalist on the Glen Campbell Goodtime Theater shows in Branson , MO during the mid 90s . United We Stand was released as a cassette only . It was sold in record stores and the Goodtime Theatre in Branson and after concerts during tours . Next to solo recordings , it contains four duets with Glen Campbell , two of which were recorded live at the shows .",
"title": ""
},
{
"docid": "Dick's_Sporting_Goods",
"text": "Dick 's Sporting Goods , Inc. , sometimes shortened to Dick 's , is a Fortune 500 American sporting goods retailing corporation headquartered in Coraopolis , Pennsylvania in Greater Pittsburgh . Dick 's has 610 stores in 47 states ( no stores in Alaska , Hawaii , and Montana ) , primarily in the Eastern United States . The company also owns Golf Galaxy , Inc. , a golf specialty retailer , with 82 stores in 30 states . The company also operates specialty chains True Runner and Field & Stream . Founded in 1948 by Richard `` Dick '' Stack , the chain has expanded to become one of the largest sporting goods retailers in the world .",
"title": ""
},
{
"docid": "Turtle's_Records_&_Tapes",
"text": "Turtle 's Records and Tapes was a Southern USA retail chain , based in Atlanta , that specialized in selling cassettes , records , and concert tickets ; in the latter years of the chain 's existence , it also rented movies in VHS format . Turtle 's was recognized for its trademark logo , an upright standing turtle with its neck twisted around in several coils as he attempts to look backwards . It was known for its deep selection and one of the most varied video rental offerings in its markets before the arrival of the big chains such as Blockbuster Inc. . Small gold coins with a turtle on one side and a record on the other were issued by the stores for gift certificates . Owned and incorporated by Al Levenson in 1977 , the chain was regional in nature , concentrated in Georgia and Florida . Levenson sold the chain to Clinton Holding Co. of White Plains , New York around 1983 although he still remained in charge of its operations . At the time of the sale the chain consisted of 26 stores in the Atlanta metro area , but by October 1986 the business had expanded to 70 stores with locations in cities such as Birmingham , Alabama , Tallahassee , Jacksonville and Macon . Blockbuster purchased Super Club Retail Entertainment Corp. , including the Turtle 's Records chain , in 1993 . Over the succeeding four years , Turtle 's stores were converted into Blockbuster Music stores or merged with stores that Blockbuster owned at the time of the purchase of the regional record seller .",
"title": ""
},
{
"docid": "Free_Record_Shop",
"text": "Free Record Shop was a chain of home entertainment stores selling products such as CDs , DVDs and video games , founded by Hans Breukhoven . Its first store opened on October 15 , 1971 in Schiedam , Netherlands . At its peak , the franchise had more than 200 stores in the Netherlands and Belgium , but online available music and media supplanted the sale of physical media carriers . Free Record Shop is now only present in Luxembourg ( 3 shops ) and 36 in the Netherlands ( shop-in-shop in `` Boekenvoordeel '' book shops ) . It owned the entertainment products retail chain vanLeest , an Amsterdam-based flagship entertainment store called FAME , a gamestore chain called GameMania and several Build-a-Bear Workshop stores . The company operated multiple online stores using the different brand names . In March 2008 the company announced that it has sold off its Norway and Finland operations to concentrate on the Benelux market . In January 2012 the company licensed its websites to be fully managed and run by ECI Nederland BV , known for its labels ECI and Cosmox , making ECI the 2nd biggest online retailer in books and home entertainment in the Benelux . On May 24 , 2013 staff and personnel were informed that Free Record Shop had declared bankruptcy . On May 28 , the bankruptcy was accepted by a Dutch court . On April 22 , 2014 Free Record Shop was finally declared bankrupt . The three shops in Luxembourg , however , have remained open and are now run by a separate management .",
"title": ""
},
{
"docid": "Rosa_Branson",
"text": "Rosa Branson MBE ( born 1933 ) is a British painter and fabric designer , living in Highgate , London . She is the daughter of Clive Branson and Noreen Branson , and a second cousin of Richard Branson .",
"title": ""
},
{
"docid": "Richard_Jones_(department_store)",
"text": "Richard Jones was a department store in the town of Chester , England before being bought out by defunct department store chain Owen Owen .",
"title": ""
},
{
"docid": "Record_shop",
"text": "A record shop or record store is a retail outlet that sells recorded music . In the late 19th century and the early 20th century , record shops only sold gramophone records , but over the 20th century , record shops sold the new formats that were developed , such as eight track tapes , compact cassettes and compact discs ( CDs ) . Today in the 21st century , record stores sell CDs , vinyl records and in some cases , DVDs of movies , TV shows , cartoons and concerts . Some record stores also sell music-related items such as posters of bands or singers and even clothing and items such as bags and coffee mugs . Even in the heyday of the CD during the 1990s , people in English-speaking countries still used the term `` record shop '' to describe a shop selling sound recordings such as CDs . Now that vinyl records have had a resurgence in the 21st century , often generating more income than CDs , the name has come full circle and is relevant once more . Prior to the 2000s , more record shops were privately run , independent businesses , meaning that prices could differ from town to town and store to store . In the 2000s , record shops are largely chain-owned and thus prices are fairly similar in different towns . In the United Kingdom the national chain style of selling records and tapes developed with Our Price , itself originally a small independent business founded in the early 1970s that expanded nationwide . Current major chains around the world include HMV , Fopp , Rough Trade , Virgin Megastores , Tower Records , FYE , Sam Goody , Velvet Music , Sunrise Records , Plato , Amoeba Music and Rasputin Music . The enormous increase in sales of vinyl records in the 2000s has provided an opportunity for growth in some sectors . The flagship HMV store at 363 Oxford Street in London , for example , has a whole department for new vinyl LPs and singles .",
"title": ""
},
{
"docid": "Chain_Reaction_(record_label)",
"text": "Chain Reaction was a German record label founded in 1995 by Basic Channel members Moritz Von Oswald and Mark Ernestus . The label 's output consisted of the extended friends and family of the Basic Channel duo , which centered on the Hard Wax record store in Berlin . The label 's sound focused on a similar minimal and dub techno style as that of Basic Channel , rooted in atmospherics and minimalism , but some have found Chain Reaction 's output to be `` more avant-experimental '' . Notable artists that have released records on the label include Monolake , Porter Ricks , Vainqueur and Fluxion . The last record on the label was released in 2003 .",
"title": ""
},
{
"docid": "Arbor_Drugs",
"text": "Arbor Drugs was a chain of drug stores based in Troy , Michigan . It was founded by Eugene Applebaum when merging five stores and incorporating the chain under the Arbor name . In 1986 , the chain went public , opening on NASDAQ under the stock symbol ARBR . Through the years , the chain grew , by opening stores and acquiring rival chains , such as Sentry Drugs in 1986 and M&R in 1994 . By 1992 the chain held a 27.6 % market share in the Detroit area . In 1979 , the chain was one of the first to offer computerized prescriptions , and by 1989 , the entire chain 's records were linked together . By 1994 , half the chain 's sales were pharmacy-related . A scandal broke out in July 1993 when it was revealed that the chain had overcharged the health insurance company Blue Cross and Blue Shield Association at least $ 17 million in prescriptions since 1988 . The two sides later settled for $ 15 million , but only one year later , Arbor was once again involved in a controversy over overcharging Medicaid claims . Eventually , all charges , both criminal and civil , were dropped . By 1997 , the drug store chain was the nation 's eighth largest , having 207 locations throughout southeastern Michigan . Year 1997 revenues totaled $ 962.8 million . CVS Corporation announced on February 9 , 1998 that it would be purchasing Arbor Drugs in a transaction estimated at $ 1.48 billion , and creating the largest chain drug retailer in the process . Although most Arbor Drug locations were converted to CVS , several of these stores were later shuttered by the CVS Corporation . ``",
"title": ""
},
{
"docid": "Makepeace_Island",
"text": "Makepeace Island is a small heart shaped island resort located in the Noosa River on Australia 's Sunshine Coast . The island is currently owned by Virgin Australia ( formerly known as Virgin Blue ) founding partners , Brett Godfrey and Sir Richard Branson . The island is Sir Richard Branson 's Australian home and can hold up to 22 guests accommodated in three 2-bedroom villas and a 4 bedroom Bali House wing . The property has a tennis court , theatre , two-storey Balinese wantilan , 500,000-litre pool and indoor bar and dining area .",
"title": ""
},
{
"docid": "The_Nature_Company",
"text": "The Nature Company was a Berkeley , California based chain of retail stores that sold scientific toys , telescopes , artwork , fossils , minerals and gems , and music CDs . The Nature Company was founded in 1972 by Priscilla and Tom Wrubel . Starting from its flagship store on Berkeley 's 4th Street , it expanded throughout the United States , and had stores in Canada and the United Kingdom . In 1996 , it was purchased by Discovery Channel , at a price of $ 40 million . At the time , it had 114 stores in malls , airports , and on shopping streets . Prior to the sale it was owned by CML Group , the holding company for NordicTrack ( fitness equipment ) , Boston Whaler and Smith & Hawken ( gardening equipment ) . From 1996 to 2000 , approximately 75 % of The Nature Co. stores were converted into Discovery Channel stores . By the end of 2001 , all of the Nature Co. stores were closed or converted . Nature Company Stores were recognizable by their stone entranceway arch and water feature , customized to each location . All stores had extravagantly built custom cabinetry to showcase the maps , fossils , minerals and gems that were sold . The original store concept was designed by the San Francisco office of the award-winning retail architect Richard Altuna . Later stores in the chain were designed and rolled out by the San Francisco office of the firm NBBJ .",
"title": ""
},
{
"docid": "Virgin_Cinemas",
"text": "Virgin Cinemas was founded in 1995 when Sir Richard Branson 's Virgin Group acquired MGM Cinemas , the largest movie theatre operator in the United Kingdom . Virgin Group bought the cinemas for # 195m , and subsequently sold 90 of the chain 's smallest cinemas to Cinven and ABC for # 70m to concentrate on multiplexes . In late 1999 Virgin announced that it would sell its cinema interests in Britain and Ireland to UGC , in which French entertainment and utilities giant Vivendi has a 38 % controlling share . Virgin sold the chain for # 215m , making them a profit of # 90m , and all the cinemas were to be rebranded to UGC . The company did strike a long term deal , however , for UGC to continue to sell Virgin Cola . The group continued to operate a Virgin Cinemas Japan unit , and announced , also in late 1999 , that it would spend up to US$ 200 million to develop 20 multiplexes in Japan by the early 21st century ; a number of Virgin multiplexes in the United States were also under consideration . Despite this , the company closed down in late 2002 .",
"title": ""
},
{
"docid": "Richard_Tompkins",
"text": "Granville Richard Francis Tompkins CBE ( 15 May 1918 -- 6 December 1992 ) was a print , advertising and retail entrepreneur , best known for founding the Green Shield Stamps company , as well as the Argos chain of catalogue stores which became one of the largest retailers in the United Kingdom , and a constituent of the FTSE 100 Index .",
"title": ""
},
{
"docid": "Woolworths_(South_Africa)",
"text": "Woolworths Holdings Limited is a South African chain of retail stores and one of the largest in the country , modelled on Marks & Spencer of the United Kingdom . This relationship with Britain 's Marks and Spencer was formed after the Second World War , which led to the retailer buying all of the unissued share capital of Woolworths in 1947 . These shares were later sold , but close ties still remain . The first Woolworths store opened in The Old Royal Hotel in Cape Town in October 1931 . It was founded by Max Sonnenberg assisted by his son Richard and Fred Kossuth . The Woolworths brand incorporates a series of food stores , some of which are attached to department stores , while others stand alone or are attached to Engen petrol stations in prosperous urban areas . Some branches include an in-store restaurant , branded as `` Cafe W '' . Woolworths goods are sold at 149 corporate stores , 51 international franchise stores throughout the rest of Africa and the Middle East and 69 South African franchise stores nationwide . Woolworths sells clothing and accessory items under a number of premium brands , namely Country Road , Witchery , Mimco and Trenery . The chain was named after the United States chain F. W. Woolworth Company but , because of the contemporary trademark laws , the name was legally used without permission . No financial connection ever existed between the companies . Similarly , Woolworths Holdings Limited is not to be confused with Woolworths Limited , an Australian retail company .",
"title": ""
},
{
"docid": "Max_Handley",
"text": "Max Handley ( 1945 -- 1990 ) was a British comedy writer . He worked on Radio Four 's Week Ending and other programmes often with Tony Allen . In 1988 he wrote the script for the comedy musical Quasimodo with music by Richard Rowland . Between 1971 and 1974 he recorded songs at Richard Branson 's Manor Studio and these were issued in 1974 on an LP , titled `` Max '' , on Virgin 's budget Caroline label imprint . A single , `` Stephanie '' ( B-side `` All I Know '' ) , was taken from the LP and released on the Virgin label proper ( as was normal for those Caroline artists that got to release singles ) . The album and single were credited to `` Max '' with the surname dropped . The Virgin label connection came about because Handley had been on the production team for Richard Branson 's `` Student '' magazine .",
"title": ""
},
{
"docid": "A&A_Records",
"text": "A&A Records was a Canadian record store chain , which filed for bankruptcy in 1991 . Prior to the expansion of Sam the Record Man in the early 1960s , A&A was the dominant record store chain in Canada . It was acquired by CBS Records after it lost the dominant market position to the Sam 's chain , but was reacquired by a Toronto investment group in 1981 .",
"title": ""
},
{
"docid": "Branson_(surname)",
"text": "Branson is a surname . Notable people with the surname include : Brad Branson ( born 1958 ) , retired American professional basketball player Catherine Branson , Australian human rights commissioner Clive Branson ( 1907 -- 44 ) , British artist and poet David Branson ( 1963 -- 2001 ) , Australian theatre director Don Branson ( 1920 -- 66 ) , American racecar driver Edward Branson , an American geologist and paleontologist Frederick Woodward Branson ( 1851-1933 ) , British chemist , glassblower , instrument maker and X-ray pioneer G. A. H. Branson ( 1871 -- 1951 ) , judge of the High Court of England and Wales George Branson ( 1918 -- 99 ) , Australian politician Herman Branson ( 1914 -- 95 ) , African-American physicist Jeff Branson ( born 1977 ) , American actor Jeff Branson ( baseball player ) ( born 1967 ) , former American Major League baseball player Jesse Branson ( born 1942 ) , retired American basketball player Noreen Branson ( 1910 -- 2003 ) , British Communist activist Richard Branson ( born 1950 ) , British entrepreneur Tony Branson ( born 1947 ) , Australian rugby league footballer William Henry Branson ( 1887 -- 1961 ) , American Seventh-day Adventist",
"title": ""
},
{
"docid": "G._A._H._Branson",
"text": "Sir George Arthur Harwin Branson PC ( 11 July 1871 -- 23 April 1951 ) , known professionally as G. A. H. Branson , was an English barrister who became a judge of the High Court of Justice . In that role he was known as Mr Justice Branson . In his youth Branson was notable as an oarsman and rowed in the University of Cambridge boat for the Oxford and Cambridge Boat Race of 1893 . He is the grandfather of Richard Branson .",
"title": ""
},
{
"docid": "Virgin_Classics",
"text": "Virgin Classics was a record label founded in 1988 as part of Richard Branson 's Virgin Records . The unit , along with EMI Classics , was acquired by Universal Music in 2012 as part of the takeover of the EMI Group , however the terms of the European Commission 's September 2012 approval of the takeover requires divestment of the classical labels which were sold on 7 February 2013 to Warner Music Group . The European Union approved the deal on May 2013 . Warner Music 's Warner Classics unit absorbed the Virgin Classics artists roster and catalogue into Erato Records but lost the rights to use either EMI or Virgin names .",
"title": ""
},
{
"docid": "The_MarketPlace",
"text": "The MarketPlace Limited is a grocery store chain in Bermuda . the chain had eight locations . The corporate headquarters is located within the chain 's Hamilton MarketPlace location , the largest grocery store in Bermuda . The MarketPlace caters to both Bermuda residents and to vacationers . The chain was founded by the Crisson Family in 1939 , and was originally called Piggly Wiggly Limited , with each store having the name `` Piggly Wiggly . '' In 1946 the company was purchased by the Pimental Family , and in 1950 was purchased by Mr. Fernance Perry . In March 1979 Alvin Ferreira purchased the operations of the Piggly Wiggly Limited chain ; since he already operated another store , the Modern Mart , the Piggly Wiggly Limited chain was expanded to five stores . In 1981 the chain was renamed The MarketPlace Ltd. , with the five stores following suit . In 1987 the chain acquired the A-1 Paget and A-1 Smith stores , so the chain now had seven stores . In 1994 the chain acquired the Shopping Centre Limited grocery store .",
"title": ""
}
] |
91252
|
Bonnie Hunt was in a movie.
|
[
{
"docid": "Cars_(film)",
"text": "Cars is a 2006 American computer-animated comedy-adventure film produced by Pixar Animation Studios and released by Walt Disney Pictures . Directed and co-written by John Lasseter , it is Pixar 's final independently-produced motion picture before its purchase by Disney in May 2006 . Set in a world populated entirely by anthropomorphic cars and other vehicles , the film stars the voices of Owen Wilson , Paul Newman ( in his final acting role ) , Bonnie Hunt , Larry the Cable Guy , Tony Shalhoub , Cheech Marin , Michael Wallis , George Carlin , Paul Dooley , Jenifer Lewis , Guido Quaroni , Michael Keaton , Katherine Helmond and John Ratzenberger . Race car drivers Dale Earnhardt , Jr. , Mario Andretti , Michael Schumacher and car enthusiast Jay Leno ( as `` Jay Limo '' ) voice themselves . Cars premiered on May 26 , 2006 at Lowe 's Motor Speedway in Concord , North Carolina , and was theatrically released on June 9 , 2006 to mostly positive reviews from critics . It was nominated for two Academy Awards including Best Animated Feature , and won the Golden Globe Award for Best Animated Feature Film . The film was released on DVD on November 7 , 2006 and on Blu-ray in 2007 . The film was accompanied by the short One Man Band for its theatrical and home media releases . Merchandise based on the film ( including scale models of several of the cars ) broke records for retail sales of merchandise based on a Disney/Pixar film , bringing an estimated $ 10 billion for 5 years after the film 's release . The film was dedicated to Joe Ranft , who was killed in a car accident during the film 's production . A sequel , titled Cars 2 , was released on June 24 , 2011 , and a spin-off film titled Planes , produced by DisneyToon Studios , was released on August 9 , 2013 , which was followed by its own sequel , Planes : Fire & Rescue , released on July 18 , 2014 . A series of short animated films titled Cars Toons debuted in 2008 on Disney Channel and Disney XD . A second sequel , Cars 3 , is scheduled for release on June 16 , 2017 .",
"title": ""
},
{
"docid": "Bonnie_Hunt",
"text": "Bonnie Lynne Hunt ( born September 22 , 1961 ) is an American stand-up comedian , actress , director , producer , writer and host . She has appeared in films , such as Rain Man , Beethoven , Beethoven 's 2nd , Jumanji , Jerry Maguire , The Green Mile , Cheaper by the Dozen and Cheaper by the Dozen 2 . Hunt has done voice work in A Bug 's Life , Monsters , Inc. , Cars , Toy Story 3 , Cars 2 , Monsters University , and Zootopia . She starred in Grand and Davis Rules , as well as creating , producing , writing , and starring in The Building , Bonnie , and Life with Bonnie . From 2008 to 2010 , she hosted The Bonnie Hunt Show .",
"title": ""
}
] |
[
{
"docid": "Don_Lake",
"text": "Don Lake ( born November 26 , 1956 ) is a Canadian actor , film and television writer , and television producer . He is frequently cast by director Christopher Guest , and is also a close friend and the collaborative partner of Bonnie Hunt . He had a role in The Bonnie Hunt Show , which he received comedic praise . He also had roles in the comedy films Police Academy , Hot Shots ! , Dumb & Dumber To , and Corner Gas : The Movie . He played more serious roles in Terminator 2 : Judgment Day , and Super Mario Bros. , along with a voice role in as Stu Hopps in Zootopia . He is also known as Dr. Carl Whitehorn on The Fresh Prince of Bel-Air .",
"title": ""
},
{
"docid": "The_Bonnie_Hunt_Show",
"text": "The Bonnie Hunt Show was an American syndicated talk show hosted by Bonnie Hunt . It premiered on September 8 , 2008 . The show 's second and final season premiered on September 8 , 2009 . It was announced on December 7 , 2009 that The Bonnie Hunt Show would not return for a third season and its final episode aired on May 26 , 2010 with reruns airing through September 3 .",
"title": ""
},
{
"docid": "Bonnie_(TV_series)",
"text": "Bonnie ( originally titled The Bonnie Hunt Show ) is an American CBS television comedy that aired from 1995 to 1996 . Bonnie Hunt played Bonnie Kelly , a television reporter who moves from Wisconsin to take a job in Chicago . There she encounters an eclectic group of coworkers . Each episode had parts where Bonnie would interview real people , asking ridiculous questions . These scenes were improvised . The show bore similarities to another series produced by David Letterman , Welcome to New York .",
"title": ""
},
{
"docid": "Bonnie_(disambiguation)",
"text": "Bonnie is a given name , predominantly but not always feminine . Bonnie may also refer to : Places : Bonnie , Illinois , a village Bonnie , West Virginia , an unincorporated community Bonnie Lake ( Alberta ) , Canada Other uses : Tropical Storm Bonnie ( disambiguation ) , various hurricanes , cyclones and tropical storms Triumph Bonneville , a British motorcycle also nicknamed `` Bonnie '' Bonnie ( TV series ) ( 1995-1996 ) , an American sitcom starring Bonnie Hunt Bonnie Field , a privately owned public airport in Marquette County , Michigan bonnie and bonnie + + , free ( open-source ) file system benchmarking tools for Unix-like operating systems Buddleja davidii ` Bonnie ' , a cultivar Bonnie , an animatronic character from Five Nights at Freddy 's",
"title": ""
},
{
"docid": "Sarah_Rose_Karr",
"text": "Sarah Rose Karr ( born November 13 , 1984 ) is an American former child actress . She is best known for her roles in the movies Beethoven and Beethoven 's 2nd as Emily Newton ( the youngest daughter of the characters played by Charles Grodin and Bonnie Hunt ) , and Kindergarten Cop ( 1990 ) , where she played a pupil of the kindergarten teacher Arnold Schwarzenegger . As a very short cameo , she also appeared as a young Annie Banks in the film Father of the Bride .",
"title": ""
},
{
"docid": "Life_with_Bonnie",
"text": "Life with Bonnie is an ABC television sitcom that originally aired from 2002 to 2004 . The show outlined the life of character Bonnie Malloy , who juggled her personal life and her job as a daytime TV talk show host . The series was created by Bonnie Hunt and Don Lake and produced by Bob & Alice Productions , in association with Touchstone Television The series had fair ratings in the first season , but struggled in the second season , resulting in its cancellation . Life With Bonnie was also shown on Living TV during ABC 's airings .",
"title": ""
},
{
"docid": "Eve_Duncan",
"text": "Eve Duncan is a fictional forensic sculptor in a series of suspense thriller novels by Iris Johansen . The series includes sub-series : the Eve , Quinn , and Bonnie trilogy and the Taking Eve , Hunting Eve , and Silencing Eve trilogy . These trilogies incorporate the familiar characters from the rest of the series while standing on their own . Several of the books have been New York Times bestsellers . One book in the series , The Killing Game , was adapted as a 2011 television movie on Lifetime . The film stars Laura Prepon as Eve Duncan and Naomi Judd as her mother , Sandra Duncan .",
"title": ""
},
{
"docid": "Cheaper_by_the_Dozen_2",
"text": "Cheaper by the Dozen 2 is a 2005 American comedy film produced by 20th Century Fox . It is the sequel to the family comedy film Cheaper by the Dozen ( 2003 ) . Shawn Levy , the director of the first film , did not return as director for this sequel , which was instead directed by Adam Shankman ( The Pacifier ) . Levy was a producer of the film and made an appearance as a hospital intern in the movie . Steve Martin , Bonnie Hunt , Hilary Duff , Piper Perabo , Alyson Stoner , and Tom Welling reprise their roles as members of the twelve-child Baker family . Eugene Levy co-stars as the patriarch of a rival family of eight children . Carmen Electra portrays Levy 's wife . The film was shot in Toronto and Eugene Levy 's hometown of Hamilton , Ontario , Canada and on Stoney Lake in Burleigh Falls , Ontario .",
"title": ""
},
{
"docid": "Bonnie_Bo",
"text": "Bonnie Bo ( also can be read as Bonnie Bai ; traditional Chinese : 柏邦妮 ; simplified Chinese : 柏邦妮 ; form name : 张珊珊 ) was born on 1982 . She is an author and screenwriter . Bonnie graduated in Literature and reading from Beijing Film Academy . In 2005 she published a personal collection of essays known as `` The Same As Bonnie Love You . '' Bo writes for fashion magazine , Interview , and worked as a film critic and columnist from 2003 . She interviewed Maggie Cheung , Gong Li , Ang Lee , Hou Hsiao-hsien and other celebrities . She worked as a screenwriter for the TV shows Yan Qing prodigal son , Flea on the drum when the move and Than I love my . She wrote the screenplay for the movie Ballad of loess and part of the 2008 remake of Dream of Red Mansions .",
"title": ""
},
{
"docid": "'03_Bonnie_&_Clyde",
"text": "`` 03 Bonnie & Clyde '' is a song recorded by American rapper Jay-Z featuring his then-girlfriend , American singer Beyoncé . It was composed by Shawn Carter , Kanye West , Prince Nelson , Tupac Shakur , Darryl Harper , Ricky Rouse and Tyrone Wrice for Jay-Z 's seventh studio album The Blueprint 2 : The Gift & The Curse and the soundtrack album to the Nickelodeon Movies film Hey Arnold ! : The Movie ( 2002 ) . The song was released as the album 's lead single on October 10 , 2002 . An East Coast hip hop and R&B song , '' '03 Bonnie & Clyde '' sampled its beat from American rapper Tupac Shakur 's 1996 song `` Me and My Girlfriend '' , and was inspired by the crime film Bonnie and Clyde . The instrumentation is based on programmed drums , bass instruments , and a flamenco guitar , accompanied by Puerto Rican singer Ricky Martin . '' '03 Bonnie & Clyde '' was generally received with favorable reviews by music critics , who complimented the combination of Jay-Z 's and Beyoncé 's musical styles , their collaboration and the song 's production . The single reached number four on the Billboard Hot 100 , becoming Jay-Z 's second top ten single and Beyoncé 's first as a solo artist . It charted at number two in the United Kingdom and peaked in the top twenty in other European territories . '' '03 Bonnie & Clyde '' was certified gold by the Recording Industry Association of America ( RIAA ) and platinum by the Australian Recording Industry Association ( ARIA ) . The accompanying music video was directed by Chris Robinson , and features Jay-Z and Beyoncé playing a modern-day version of the 1920s bank robbers Clyde Barrow and Bonnie Parker . It was nominated for Best Hip-Hop Video at the 2003 MTV Video Music Awards . '' '03 Bonnie & Clyde '' spawned a feud with American recording artist Toni Braxton , who had also sampled `` Me and My Girlfriend '' in her 2002 song `` Me & My Boyfriend '' . She accused West and Jay-Z of stealing the idea of using the song as a sample , which was later denied by both of them . `` 03 Bonnie & Clyde '' was performed by Jay-Z and Beyoncé on several television shows and was later included on the set list of their concert performances and tours , most notably on their co-headlining On the Run Tour ( 2014 ) .",
"title": ""
},
{
"docid": "Charlie_Stewart",
"text": "Charlie Stewart ( born September 9 , 1993 ) is an American actor . He is of Irish descent . He had appeared in many popular tv shows . Stewart played the role of Bob in The Suite Life of Zack & Cody and guest starred on its sequel The Suite Life on Deck in Flowers and Chocolate . Stewart also starred in Life With Bonnie with Bonnie Hunt , as her son . He has appeared in several commercials , for products such as Leapfrog , Twister , and Toys `` R '' Us .",
"title": ""
},
{
"docid": "Bonnie_Chakraborty",
"text": "Bonnie Chakraborty was the lead vocalist of Kolkata based band Krosswindz until 1998 . He has sung many songs in several languages including Hindi , Tamil and Bengali movies . He did four Bengali albums till date .",
"title": ""
},
{
"docid": "Bonnie_Bedelia",
"text": "Bonnie Bedelia ( born Bonnie Bedelia Culkin , March 25 , 1948 ) is an American actress . She began her career in theatre and during 1960s starred in the CBS daytime soap opera , Love of Life ( 1961 -- 67 ) , before making her movie debut in The Gypsy Moths ( 1969 ) . Bedelia was nominated for a Golden Globe Award for her performance in 1983 film Heart Like a Wheel , and for an Independent Spirit Award for The Prince of Pennsylvania ( 1988 ) . She is best known for her role as Holly Gennero McClane in the action films Die Hard ( 1988 ) and Die Hard 2 ( 1990 ) , as well as the movies They Shoot Horses , Do n't They ? ( 1969 ) , Lovers and Other Strangers ( 1970 ) , Presumed Innocent ( 1990 ) , and Needful Things ( 1993 ) . Bedelia also had many other leading and supporting roles , and has worked regularly on television . For her television work , Bedelia received two Emmy Awards nominations . From 2001 to 2004 , Bedelia played the lead role in the Lifetime television drama series , The Division , and later starred as family matriarch Camille Braverman in the NBC drama series , Parenthood ( 2010 -- 2015 ) .",
"title": ""
},
{
"docid": "The_Building_(TV_series)",
"text": "The Building is an American sitcom , which aired on CBS in 1993 . The series ran for five episodes . It starred Bonnie Hunt .",
"title": ""
},
{
"docid": "Bonnie_Somerville",
"text": "Bonnie Somerville ( born February 24 , 1974 ) is an American actress and singer . She has had roles in a number of movies and television series , most notably NYPD Blue , Grosse Pointe , Friends , The O.C. , Cashmere Mafia , and Golden Boy . She starred as Dr. Christa Lorenson in season one of the CBS medical drama Code Black .",
"title": ""
},
{
"docid": "Now_and_Then_(film)",
"text": "Now and Then is a 1995 American coming-of-age film directed by Lesli Linka Glatter and starring Christina Ricci , Rosie O'Donnell , Thora Birch , Melanie Griffith , Gaby Hoffmann , Demi Moore , Ashleigh Aston Moore and Rita Wilson . The supporting cast features Hank Azaria , Janeane Garofalo , Cloris Leachman , and Bonnie Hunt , among many others . The plot follows four women who recount a pivotal summer they shared together as adolescents in 1970 . It was filmed largely in Savannah , Georgia , although called Shelby , Indiana in the movie , using the Gaslight Addition and Old Town Cemetery , highlighting the downtown area . Additional filming was done in Statesboro , Georgia in locations including the Bulloch County Court House ( also featured in the film `` 1969 '' ) and the building now housing the Averitt Center for the Arts . On July 18 , 2012 , it was announced that ABC Family would develop the film into a television series by I. Marlene King , who wrote the film and adapted Pretty Little Liars . However , the project did not move past the development stage .",
"title": ""
},
{
"docid": "Sally_Carrera",
"text": "Sally Carrera is a fictional character In the Pixar computer animated film Cars . She is Radiator Springs 's town attorney and protagonist Lightning McQueen 's love interest . She is voiced by Bonnie Hunt .",
"title": ""
},
{
"docid": "Angel_Heart_(disambiguation)",
"text": "Angel Heart is a 1987 horror movie , written and directed by Alan Parker . Angel Heart may also refer to : Angel Heart ( manga ) , comic series by Tsukasa Hōjō Angel Heart ( 2015 TV series ) , a series of Japanese drama based on the manga by Tsukasa Hōjō Angel Heart ( Bonnie Tyler album ) , 1992 release by singer Bonnie Tyler Angel Heart ( Jimmy Webb album ) , 1982 release by the American songwriter `` Angel Heart '' , a song on this album",
"title": ""
},
{
"docid": "The_Bonnie_Sisters",
"text": "The Bonnie Sisters were an American pop group from New York City . The three members were all nurses at Bellevue Hospital . After hearing The DeJohn Sisters on the radio , they began singing together at work , calling themselves The Belle Aimes initially . After performing on Arthur Godfrey 's television show , they were signed by Mickey Baker to Rainbow Records and changed their name to The Bonnie Sisters at the behest of Rainbow owner Eddie Heller . Their first recording was `` Cry Baby '' , originally a B-side recorded by The Scarlets . The tune became a hit in the U.S. , peaking at # 18 on the Billboard Hot 100 in 1956 . Follow-up singles `` Track That Cat '' , `` Wandering Heart '' , and `` Confess '' failed to chart , and the group returned to nursing . The 1990 John Waters movie , Cry-Baby , is named after the group 's lone hit .",
"title": ""
},
{
"docid": "Nicholas_Pike",
"text": "Nicholas Pike is an Emmy Award-winning Hollywood film and television composer . He was born in Water Orton , Warwickshire , England and is known for featuring unique sounds and instrumentation . He started his music career at the age of 7 at the prestigious Canterbury Choir School and subsequently moved to Cape Town , South Africa at the age of 10 where he continued in music becoming Head Chorister at St George 's Cathedral as well as playing the flute with the Cape Town Symphony Orchestra at the age of 15 . He was also a member of the iconic rock band HAMMAK and toured the country with this and other bands . At age 17 he left to study flute and composition in Boston at the Berklee School of Music after which he moved to New York City where he recorded and performed with his band FLUTEJUICE featuring Bill Frisell , Billy Hart , Kenny Werner , Hank Roberts among many others . He also recorded and released the album WATERLILIES with legendary Brazilian percussionist Nana Vasconcelos and guitar virtuoso Bill Connors . Prior to embarking on his film scoring career he conducted and recorded his suite `` Master Harold and the Boys '' with the London Symphony Orchestra which was based on Athol Fugard 's apartheid era play of the same name . As a film composer he has written for projects ranging from Stephen King 's The Shining to Disney 's Captain Ron as well as animated films like Disney 's `` The Prince and the Pauper '' . Awards include the Elmer Bernstein Award for his score to Love Object at the Woodstock Film Festival , the Best Music Award from the Sitges Cinema Fantastic Festival for his score to Critters 2 and the Emmy for original music for the HBO documentary `` In Tahrir Square '' about the beginnings of the Arab Spring . He has also written music for large scale music videos like Michael Jackson 's `` Ghost '' and `` You Rock My World '' , MC Hammer 's `` Too Legit To Quit '' and `` Here Comes The Hammer '' and Will Smith 's `` Wild Wild West '' . He was recently hand-picked by actress/comedian and talk show host Bonnie Hunt to create and lead the first-ever daytime talk show live band for The Bonnie Hunt Show which aired on the NBC network . Nicholas Pike also composed and scored The Bonnie Hunt Show theme . He recently wrote and produced the song `` On Ghost Ridge '' for the documentary 100 Years chronicling the epic battle between Blackfeet Indian Elouise Cobell and the US government . The song is sung by pop star Yuna and is currently under consideration for an Academy Award Nomination .",
"title": ""
},
{
"docid": "Joel_Ward_(magician)",
"text": "Joel Ward ( born September 27 , 1983 ) is an American magician , actor , comedian , and TV personality . Ward has been a guest on `` The Tonight Show '' and `` The Bonnie Hunt Show '' . He also tours regularly with a comedy & magic show . He lives in Hollywood , CA .",
"title": ""
},
{
"docid": "Getting_Away_with_Murder_(film)",
"text": "Getting Away with Murder is a 1996 American comedy film written and directed by Harvey Miller . The film stars Dan Aykroyd , Jack Lemmon , Lily Tomlin and Bonnie Hunt . This was the final project for veteran writer and director Harvey Miller . It received poor reviews and was panned by critics .",
"title": ""
},
{
"docid": "Return_to_Me",
"text": "Return to Me is a 2000 American romantic comedy-drama film directed by Bonnie Hunt and starring David Duchovny and Minnie Driver . It was filmed in Chicago , Illinois and was released on April 7 , 2000 by Metro-Goldwyn-Mayer . It was Carroll O'Connor 's final film before his death the following year .",
"title": ""
},
{
"docid": "Bonnie_and_Terry_Turner",
"text": "Bonnie and Terry Turner are a husband-and-wife writing team , best known for creating the sitcoms 3rd Rock from the Sun ( 1996 -- 2001 ) and That '70s Show ( 1998 -- 2006 ) , for NBC and FOX respectively , as well as That '80s Show for FOX in 2002 , and Normal , Ohio starring John Goodman in 2000 . From 1986 until 1992 , the team were staff writers for Saturday Night Live . Between 1987 and 1995 , they were responsible for authoring or screenwriting six films , including Coneheads , Wayne 's World , Wayne 's World 2 , Tommy Boy , and The Brady Bunch Movie .",
"title": ""
},
{
"docid": "Escanaba_in_da_Moonlight",
"text": "Escanaba in da Moonlight ( `` da '' is Yooper for `` the '' ) is a 2001 movie starring Jeff Daniels . It is a comedy about hunting and hunting traditions and is set ( and filmed ) in the Escanaba , Michigan area . The movie is the film adaptation of the play of the same name , which premiered at Jeff Daniels ' Purple Rose Theatre in Chelsea , Michigan .",
"title": ""
},
{
"docid": "Grand_(TV_series)",
"text": "Grand is an American sitcom that aired on NBC from January 18 to December 27 , 1990 . The series featured an ensemble cast including Pamela Reed , Bonnie Hunt , Michael McKean , John Randolph , Andrew Lauer , John Neville , Joel Murray and Sara Rue . It was created by Michael Leeson , executive produced by Leeson , Marcy Carsey and Tom Werner .",
"title": ""
},
{
"docid": "Love_and_a_.45",
"text": "Love and a .45 is a 1994 Bonnie and Clyde-esque road movie starring Gil Bellows and Renée Zellweger . The film was originally released by Lions Gate Entertainment .",
"title": ""
},
{
"docid": "Bonnie_Zacherle",
"text": "Bonnie D. Zacherle ( born November 14 , 1946 ) is an American illustrator and designer who now resides in Warrenton , Virginia . Zacherle is best known as the original creator of the best-selling My Little Pony toy line . She is also the creator of Nerfuls . Zacherle has done some outside consulting for Bliss House , an American licensing consultancy , on the graphics and product development side . In 2003 , she became a member of ` Women In Toys ' . Her uncle , John Zacherle was an American television host , radio personality and voice actor known for his long career as a television horror host broadcasting horror movies in Philadelphia and New York City in the 1950s and 1960s .",
"title": ""
},
{
"docid": "BroadwayHD",
"text": "BroadwayHD is a live theater to digital platforms company , founded in 2013 by Stewart F. Lane and Bonnie Comley . Based out of New York City , the company records live theater performances to be made available through other platforms such as movie theaters , television , and DVDs . The first production recorded by BroadwayHD was Romeo and Juliet which had a limited run engagement on Broadway from September 19 , 2013 to December 8 , 2013 . The show starred movie actor Orlando Bloom and two time Tony-nominated actress Condola Rashad . The digital recording was released in movie theaters across the U.S. in February 2014 . It screened internationally in April 2014 .",
"title": ""
},
{
"docid": "The_Hunt_for_Red_October_(console_game)",
"text": "The Hunt for Red October is a video game based on the movie The Hunt for Red October . It was first released in 1991 for the Nintendo Entertainment System . Versions for the Game Boy and Super NES were subsequently released .",
"title": ""
}
] |
751
|
Major vault protein (MVP) leads to more aggressive tumors by regulating the sorting of tumor suppressive miR-193a into extracellular vesicles (EVs).
|
[
{
"docid": "19800147",
"text": "Exosomes are emerging mediators of intercellular communication; whether the release of exosomes has an effect on the exosome donor cells in addition to the recipient cells has not been investigated to any extent. Here, we examine different exosomal miRNA expression profiles in primary mouse colon tumour, liver metastasis of colon cancer and naive colon tissues. In more advanced disease, higher levels of tumour suppressor miRNAs are encapsulated in the exosomes. miR-193a interacts with major vault protein (MVP). Knockout of MVP leads to miR-193a accumulation in the exosomal donor cells instead of exosomes, inhibiting tumour progression. Furthermore, miR-193a causes cell cycle G1 arrest and cell proliferation repression through targeting of Caprin1, which upregulates Ccnd2 and c-Myc. Human colon cancer patients with more advanced disease show higher levels of circulating exosomal miR-193a. In summary, our data demonstrate that MVP-mediated selective sorting of tumour suppressor miRNA into exosomes promotes tumour progression.",
"title": "MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression"
}
] |
[
{
"docid": "1905095",
"text": "AIMS Recent evidence suggests that cardiac progenitor cells (CPCs) may improve cardiac function after injury. The underlying mechanisms are indirect, but their mediators remain unidentified. Exosomes and other secreted membrane vesicles, hereafter collectively referred to as extracellular vesicles (EVs), act as paracrine signalling mediators. Here, we report that EVs secreted by human CPCs are crucial cardioprotective agents. METHODS AND RESULTS CPCs were derived from atrial appendage explants from patients who underwent heart valve surgery. CPC-conditioned medium (CM) inhibited apoptosis in mouse HL-1 cardiomyocytic cells, while enhancing tube formation in human umbilical vein endothelial cells. These effects were abrogated by depleting CM of EVs. They were reproduced by EVs secreted by CPCs, but not by those secreted by human dermal fibroblasts. Transmission electron microscopy and nanoparticle tracking analysis showed most EVs to be 30-90 nm in diameter, the size of exosomes, although smaller and larger vesicles were also present. MicroRNAs most highly enriched in EVs secreted by CPCs compared with fibroblasts included miR-210, miR-132, and miR-146a-3p. miR-210 down-regulated its known targets, ephrin A3 and PTP1b, inhibiting apoptosis in cardiomyocytic cells. miR-132 down-regulated its target, RasGAP-p120, enhancing tube formation in endothelial cells. Infarcted hearts injected with EVs from CPCs, but not from fibroblasts, exhibited less cardiomyocyte apoptosis, enhanced angiogenesis, and improved LV ejection fraction (0.8 ± 6.8 vs. -21.3 ± 4.5%; P < 0.05) compared with those injected with control medium. CONCLUSION EVs are the active component of the paracrine secretion by human CPCs. As a cell-free approach, EVs could circumvent many of the limitations of cell transplantation.",
"title": "Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction."
},
{
"docid": "14768471",
"text": "Renal carcinomas have been shown to contain a population of cancer stem cells (CSCs) that present self-renewing capacity and support tumor growth and metastasis. CSCs were shown to secrete large amount of extracellular vesicles (EVs) that can transfer several molecules (proteins, lipids and nucleic acids) and induce epigenetic changes in target cells. Mesenchymal Stromal Cells (MSCs) are susceptible to tumor signalling and can be recruited to tumor regions. The precise role of MSCs in tumor development is still under debate since both pro- and anti-tumorigenic effects have been reported. In this study we analysed the participation of renal CSC-derived EVs in the interaction between tumor and MSCs. We found that CSC-derived EVs promoted persistent phenotypical changes in MSCs characterized by an increased expression of genes associated with cell migration (CXCR4, CXCR7), matrix remodeling (COL4A3), angiogenesis and tumor growth (IL-8, Osteopontin and Myeloperoxidase). EV-stimulated MSCs exhibited in vitro an enhancement of migration toward the tumor conditioned medium. Moreover, EV-stimulated MSCs enhanced migration of renal tumor cells and induced vessel-like formation. In vivo, EV-stimulated MSCs supported tumor development and vascularization, when co-injected with renal tumor cells. In conclusion, CSC-derived EVs induced phenotypical changes in MSCs that are associated with tumor growth.",
"title": "Extracellular vesicles derived from renal cancer stem cells induce a pro-tumorigenic phenotype in mesenchymal stromal cells"
},
{
"docid": "654735",
"text": "Glioma is a most common type of primary brain tumors. Extracellular vesicles, in the form of exosomes, are known to mediate cell-cell communication by transporting cell-derived proteins and nucleic acids, including various microRNAs (miRNAs). Here we examined the cerebrospinal fluid (CSF) from patients with recurrent glioma for the levels of cancer-related miRNAs, and evaluated the values for prognosis by comparing the measures of CSF-, serum-, and exosome-contained miR-21 levels. Samples from seventy glioma patients following surgery were compared with those from brain trauma patients as a non-tumor control group. Exosomal miR-21 levels in the CSF of glioma patients were found significantly higher than in the controls; whereas no difference was detected in serum-derived exosomal miR-21 expression. The CSF-derived exosomal miR-21 levels correlated with tumor spinal/ventricle metastasis and the recurrence with anatomical site preference. From additional 198 glioma tissue samples, we verified that miR-21 levels associated with tumor grade of diagnosis and negatively correlated with the median values of patient overall survival time. We further used a lentiviral inhibitor to suppress miR-21 expression in U251 cells. The results showed that the levels of miR-21 target genes of PTEN, RECK and PDCD4 were up-regulated at protein levels. Therefore, we concluded that the exosomal miR-21 levels could be demonstrated as a promising indicator for glioma diagnosis and prognosis, particularly with values to predict tumor recurrence or metastasis.",
"title": "Exosomal levels of miRNA-21 from cerebrospinal fluids associated with poor prognosis and tumor recurrence of glioma patients"
},
{
"docid": "3588621",
"text": "Two broad categories of extracellular vesicles (EVs), exosomes and shed microvesicles (sMVs), which differ in size distribution as well as protein and RNA profiles, have been described. EVs are known to play key roles in cell-cell communication, acting proximally as well as systemically. This Review discusses the nature of EV subtypes, strategies for isolating EVs from both cell-culture media and body fluids, and procedures for quantifying EVs. We also discuss proteins selectively enriched in exosomes and sMVs that have the potential for use as markers to discriminate between EV subtypes, as well as various applications of EVs in clinical diagnosis.",
"title": "Extracellular vesicle isolation and characterization: toward clinical application."
},
{
"docid": "4435369",
"text": "Extracellular vesicles (EVs) are cell-derived membrane vesicles, and represent an endogenous mechanism for intercellular communication. Since the discovery that EVs are capable of functionally transferring biological information, the potential use of EVs as drug delivery vehicles has gained considerable scientific interest. EVs may have multiple advantages over currently available drug delivery vehicles, such as their ability to overcome natural barriers, their intrinsic cell targeting properties, and stability in the circulation. However, therapeutic applications of EVs as drug delivery systems have been limited due to a lack of methods for scalable EV isolation and efficient drug loading. Furthermore, in order to achieve targeted drug delivery, their intrinsic cell targeting properties should be tuned through EV engineering. Here, we review and discuss recent progress and remaining challenges in the development of EVs as drug delivery vehicles.",
"title": "Extracellular vesicles for drug delivery."
},
{
"docid": "982650",
"text": "BACKGROUND & AIMS Tumor cells survive hypoxic conditions by inducing autophagy. We investigated the roles of microRNAs (miRNAs) in regulating autophagy of hepatocellular carcinoma (HCC) cells under hypoxic conditions. METHODS We used gain- and loss-of-function methods to evaluate the effect of miRNAs on autophagy in human HCC cell lines (Huh7 and Hep3B) under hypoxic conditions. Autophagy was quantified by immunoblot, immunofluoresence, and transmission electron microscopy analyses, and after incubation of cells with bafilomycin A1. We used a luciferase reporter assay to confirm associations between miRNAs and their targets. We analyzed growth of HCC xenograft tumors in nude mice. RESULTS miR-375 was down-regulated in HCC cells and tissues; it inhibited autophagy under hypoxic conditions by suppressing the conversion of LC3I to LC3II and thereby autophagic flux. The ability of miR-375 to inhibit autophagy was independent of its ability to regulate 3'-phosphoinositide-dependent protein kinase-1-AKT-mammalian target of rapamycin signaling, but instead involved suppression of ATG7, an autophagy-associated gene. miR-375 bound directly to a predicted site in the 3' untranslated region of ATG7. Up-regulating miR-375 or down-regulating ATG7 inhibited mitochondrial autophagy of HCC cells, reduced the elimination of damaged mitochondria under hypoxia, increased release of mitochondrial apoptotic proteins, and reduced viability of HCC cells. In mice, xenograft tumors that expressed miR-375 had fewer autophagic cells, larger areas of necrosis, and grew more slowly than tumors from HCC cells that expressed lower levels of miR-375. CONCLUSIONS miR-375 inhibits autophagy by reducing expression of ATG7 and impairs viability of HCC cells under hypoxic conditions in culture and in mice. miRNAs that inhibit autophagy of cancer cells might be developed as therapeutics.",
"title": "miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions."
},
{
"docid": "17209919",
"text": "Cilia are sensory organelles that protrude from cell surfaces to monitor the surrounding environment. In addition to its role as sensory receiver, the cilium also releases extracellular vesicles (EVs). The release of sub-micron sized EVs is a conserved form of intercellular communication used by all three kingdoms of life. These extracellular organelles play important roles in both short and long range signaling between donor and target cells and may coordinate systemic responses within an organism in normal and diseased states. EV shedding from ciliated cells and EV–cilia interactions are evolutionarily conserved phenomena, yet remarkably little is known about the relationship between the cilia and EVs and the fundamental biology of EVs. Studies in the model organisms Chlamydomonas and Caenorhabditis elegans have begun to shed light on ciliary EVs. Chlamydomonas EVs are shed from tips of flagella and are bioactive. Caenorhabditis elegans EVs are shed and released by ciliated sensory neurons in an intraflagellar transport-dependent manner. Caenorhabditis elegans EVs play a role in modulating animal-to-animal communication, and this EV bioactivity is dependent on EV cargo content. Some ciliary pathologies, or ciliopathies, are associated with abnormal EV shedding or with abnormal cilia–EV interactions. Until the 21st century, both cilia and EVs were ignored as vestigial or cellular junk. As research interest in these two organelles continues to gain momentum, we envision a new field of cell biology emerging. Here, we propose that the cilium is a dedicated organelle for EV biogenesis and EV reception. We will also discuss possible mechanisms by which EVs exert bioactivity and explain how what is learned in model organisms regarding EV biogenesis and function may provide insight to human ciliopathies.",
"title": "Ciliary Extracellular Vesicles: Txt Msg Organelles"
},
{
"docid": "8702697",
"text": "AIMS Tumor microenvironment is a strong determinant for the acquisition of metastatic potential of cancer cells. We have recently demonstrated that cancer-associated fibroblasts (CAFs) elicit a redox-dependent epithelial-mesenchymal transition (EMT) in prostate cancer (PCa) cells, driven by cycloxygenase-2/hypoxia-inducible factor-1 (HIF-1)/nuclear factor-κB pathway and enhancing tumor aggressiveness. Here, we investigated the involvement of microRNAs (miRNAs) in tumor-stroma interplay to identify possible tools to counteract oxidative stress and metastasis dissemination. RESULTS We found that miR-205 is the most downmodulated miRNA in PCa cells upon CAF stimulation, due to direct transcriptional repression by HIF-1, a known redox-sensitive transcription factor. Rescue experiments demonstrated that ectopic miR-205 overexpression in PCa cells counteracts CAF-induced EMT, thus impairing enhancement of cell invasion, acquisition of stem cell traits, tumorigenicity, and metastatic dissemination. In addition, miR-205 blocks tumor-driven activation of surrounding fibroblasts by reducing pro-inflammatory cytokine secretion. INNOVATION Overall, such findings suggest miR-205 as a brake against PCa metastasis by blocking both the afferent and efferent arms of the circuit between tumor cells and associated fibroblasts, thus interrupting the pro-oxidant and pro-inflammatory circuitries engaged by reactive stroma. CONCLUSION The evidence that miR-205 replacement in PCa cells is able not only to prevent but also to revert the oxidative/pro-inflammatory axis leading to EMT induced by CAFs sets the rationale for developing miRNA-based approaches to prevent and treat metastatic disease.",
"title": "miR-205 hinders the malignant interplay between prostate cancer cells and associated fibroblasts."
},
{
"docid": "16532419",
"text": "BACKGROUND Carbon nanotubes (CNT) hold great promise to create new and better products for commercial and biomedical applications, but their long-term adverse health effects are a major concern. The objective of this study was to address human lung cancer risks associated with chronic pulmonary exposure to single-walled (SW) CNT through the fundamental understanding of cellular and molecular processes leading to carcinogenesis. We hypothesized that the acquisition of cancer stem cells (CSC), a subpopulation that drive tumor initiation and progression, may contribute to CNT carcinogenesis. METHODS Non-tumorigenic human lung epithelial cells were chronically exposed to well-dispersed SWCNT for a period of 6 months at the physiologically relevant concentration of 0.02 μg/cm2 surface area dose. Chronic SWCNT-exposed cells were evaluated for the presence of CSC-like cells under CSC-selective conditions of tumor spheres and side population (SP). CSC-like cells were isolated using fluorescence-activated cell sorting and were assessed for aggressive behaviors, including acquired apoptosis resistance and increased cell migration and invasion in vitro, and tumor-initiating capability in vivo. Non-small cell lung cancer cells served as a positive control. RESULTS We demonstrated for the first time the existence of CSC-like cells in all clones of chronic SWCNT-exposed lung epithelial cells. These CSC-like cells, in contrary to their non-CSC counterpart, possessed all biological features of lung CSC that are central to irreversible malignant transformation, self-renewal, aggressive cancer behaviors, and in vivo tumorigenesis. These cells also displayed aberrant stem cell markers, notably Nanog, SOX-2, SOX-17 and E-cadherin. Restored expression of tumor suppressor p53 abrogated CSC properties of CSC-like cells. Furthermore, we identified specific stem cell surface markers CD24low and CD133high that are associated with SWCNT-induced CSC formation and tumorigenesis. CONCLUSIONS Our findings provide new and compelling evidence for the acquisition of CSC-like cells induced by chronic SWCNT exposure, which are likely to be a major driving force for SWCNT tumorigenesis. Thus, our study supports prudent adoption of prevention strategies and implementation of exposure control for SWCNT. We also suggest that the detection of CSC and associated surface markers may provide an effective screening tool for prediction of the carcinogenic potential of SWCNT and related nanoparticles.",
"title": "Induction of stem-like cells with malignant properties by chronic exposure of human lung epithelial cells to single-walled carbon nanotubes"
},
{
"docid": "53211308",
"text": "BACKGROUND microRNAs (miRNAs) stably exist in circulating blood and are encapsulated in extracellular vesicles such as exosomes. The aims of this study were to identify which exosomal miRNAs are highly produced from epithelial ovarian cancer (EOC) cells, to analyze whether serum miRNA can be used to discriminate patients with EOC from healthy volunteers, and to investigate the functional role of exosomal miRNAs in ovarian cancer progression. METHODS Exosomes were collected from the culture media of serous ovarian cancer cell lines, namely TYK-nu and HeyA8 cells. An exosomal miRNA microarray revealed that several miRNAs including miR-99a-5p were specifically elevated in EOC-derived exosomes. Expression levels of serum miR-99a-5p in 62 patients with EOC, 26 patients with benign ovarian tumors, and 20 healthy volunteers were determined by miRNA quantitative reverse transcription-polymerase chain reaction. To investigate the role of exosomal miR-99a-5p in peritoneal dissemination, neighboring human peritoneal mesothelial cells (HPMCs) were treated with EOC-derived exosomes and then expression levels of miR-99a-5p were examined. Furthermore, mimics of miR-99a-5p were transfected into HPMCs and the effect of miR-99a-5p on cancer invasion was analyzed using a 3D culture model. Proteomic analysis with the tandem mass tag method was performed on HPMCs transfected with miR-99a-5p and then potential target genes of miR-99a-5p were examined. RESULTS The serum miR-99a-5p levels were significantly increased in patients with EOC, compared with those in benign tumor patients and healthy volunteers (1.7-fold and 2.8-fold, respectively). A receiver operating characteristic curve analysis showed with a cut-off of 1.41 showed sensitivity and specificity of 0.85 and 0.75, respectively, for detecting EOC (area under the curve = 0.88). Serum miR-99a-5p expression levels were significantly decreased after EOC surgeries (1.8 to 1.3, p = 0.002), indicating that miR-99a-5p reflects tumor burden. Treatment with EOC-derived exosomes significantly increased miR-99a-5p expression in HPMCs. HPMCs transfected with miR-99a-5p promoted ovarian cancer invasion and exhibited increased expression levels of fibronectin and vitronectin. CONCLUSIONS Serum miR-99a-5p is significantly elevated in ovarian cancer patients. Exosomal miR-99a-5p from EOC cells promotes cell invasion by affecting HPMCs through fibronectin and vitronectin upregulation and may serve as a target for inhibiting ovarian cancer progression.",
"title": "Exosomal miR-99a-5p is elevated in sera of ovarian cancer patients and promotes cancer cell invasion by increasing fibronectin and vitronectin expression in neighboring peritoneal mesothelial cells"
},
{
"docid": "19358586",
"text": "The myc oncogene is overexpressed in almost half of all breast and ovarian cancers, but attempts at therapeutic interventions against myc have proven to be challenging. Myc regulates multiple biological processes, including the cell cycle, and as such is associated with cell proliferation and tumor progression. We identified a protein signature of high myc, low p27 and high phospho-Rb significantly correlated with poor patient survival in breast and ovarian cancers. Screening of a miRNA library by functional proteomics in multiple cell lines and integration of data from patient tumors revealed a panel of five microRNAs (miRNAs) (miR-124, miR-365, miR-34b*, miR-18a and miR-506) as potential tumor suppressors capable of reversing the p27/myc/phospho-Rb protein signature. Mechanistic studies revealed an RNA-activation function of miR-124 resulting in direct induction of p27 protein levels by binding to and inducing transcription on the p27 promoter region leading to a subsequent G1 arrest. Additionally, in vivo studies utilizing a xenograft model demonstrated that nanoparticle-mediated delivery of miR-124 could reduce tumor growth and sensitize cells to etoposide, suggesting a clinical application of miRNAs as therapeutics to target the functional effect of myc on tumor growth.",
"title": "Functional proteomics identifies miRNAs to target a p27/Myc/phospho-Rb signature in breast and ovarian cancer"
},
{
"docid": "15521377",
"text": "Cellular senescence is a stable form of cell-cycle arrest which is thought to limit the proliferative potential of premalignant cells [1]. The senescence phenotype was initially described by Hayflick and Moorhead in 1961 on human fibroblasts undergoing replicative exhaustion in culture [2]. It has been shown that senescence can be triggered in different cell types in response to diverse forms of cellular damage or stress (for review see [1]). Importantly, while senescence was denounced as a tissue culture phenomenon for many years, recent in vivo studies demonstrated that cellular senescence represents a potent failsafe mechanism against tumorigenesis and contributes to the cytotoxicity of certain anticancer agents (see for example [3-7]). Interestingly, senescent cells have also been observed in certain aged or damaged tissues and there is growing evidence that senescence checkpoints can affect the regenerative reserve of tissues and organismal aging [8-11]. However, senescence may also have positive effects on organ maintenance by limiting pathological responses to acute forms of injury such as fibrotic scarring in response to chemical induced liver injury [12]. Over the past years it was also shown that senescent cells can communicate with their environment by secreting a myriad of cytokines and growth factors. Interestingly, this \"senescence associated secretory phenotype (SASP)\" seems to be a double edged sword regarding tumor initiation and maintenance: i) On the one hand, it has been shown that the SASP can have pro-tumorigenic effects. In an experimental system it was shown that senescent mesenchymal cells can enhance the tumorigenicity of surrounding breast cancer cells [13]. ii) Similarly, it is possible that the SASP enhances selection of transformed cell clones in aged organ systems. It has been shown that loss of proliferative competition of non-transformed cells can accelerate leukemogenesis [14]. It remains to be seen whether aberrant secretion of cytokines and growth factors by the SASP can accelerated this process in aged and chronically damage organ systems. iii) In contrast to its pro-tumorigenic aspect, the SASP could also have anti-tumor effects. A recent study showed that in a mosaic liver cancer mouse model the activation of p53 induced senescence, an upregulation of inflammatory cytokines, and activation of innate immune responses leading to tumour cell clearance [15]. iv) In further support that the SASP could have anti-tumor activities, a series of recent papers showed that components of the SASP can stabilize the senescence cell cycle arrest via an autoregulatory feedback loop [16,17] or induces apoptosis of tumor cells [18]. In addition to its effects on tumorigenesis, the SASP could also influence tissue aging. Studies on aging telomere dysfunctional mice have provided direct experimental evidence for an in vivo activation of the SASP in response to telomere dysfunction [19]. Interestingly, this in vivo SASP provoked alterations in stem cell differentiation (skewing of hematopoiesis towards reduction in lymphopoiesis and enhancement of myelopoiesis) that are also characteristic signs of human aging. Figure 1. Different cellular stresses can induce senescence including telomere shortening, DNA damage, and oncogene activation. Senescence of tumor cells ... In light of the many possible roles o the SASP in aging and carcinogenesis, it appears to be of utmost importance to decipher regulatory pathways controlling the SASP. In a current publication, Bhaumik et al. have identified 2 microRNAs (miR-146a/b) that negatively regulate the secretion of IL-6 and IL-8 - two of the SASP [20]. The authors show that these microRNAs are up-regulated at late stages of senescence, many days after a permanent cell cycle arrest has been established. Interestingly, the inhibitory miRs are most strongly up-regulated in senescence of cell lines that show a strong SASP but not in cell lines characterized by a weak SASP. The authors propose a new concept indicating that miRs 146a and b function in a negative feedback loop preventing an over-activation of the SASP in senescent cells. The authors present some initial data suggesting that activation of this negative feedback loop involves IL-1 receptor, IRAK-1, and NFκB signalling leading to an up-regulation of miRs-146a and b. A direct proof that this proposed feedback loop suppresses over-activation of the SASP remains to be demonstrated in future studies. The authors show that blockage of IL-1-receptor signalling prevents both the up-regulation of miRs-146a and b as well as Il-6 secretion. To confirm their new concept, it would be important to show that a selective blockage of miRs-146a and b results in over-activation of the SASP. The work by Bhaumik et al. places mir-146a/b as central players to control IL-6 and IL-8 expression within the SASP. MicroRNAs are emerging therapeutic targets because their expression levels can be effectively modulated via the use of antagomirs (see for example [21]). Also, for increasing microRNA expression, microRNAs can be delivered into cellsin vivo (see for example [22]). Therefore, it will be interesting to functionally test the impact of mir-146 inhibition on tumorigenesis and aging in relevant mouse models. Such studies will be of particular interest, as recent work showed that IL-6 secretion by senescent cells is relevant for initiating and maintaining the senescene response via an autocrine loop [17]. A reduction of miR-146 could increase IL-6 levels in senescent cells, which should stabilize the senescence program and reduce the risk of malignant transformation. Furthermore, it can be speculated that reduction of mir-146 a/b will increase NfκB activation via IRAK1. As NfκB is modulating the expression of various inflammation associated genes, this may also lead to increased clearance of senescent tumor cells by the innate immune system. However, it should be mentioned that Il-6 secreted by senescent cells can also act as a mitogen for surrounding cells, thus potentially increasing the risk of malignant transformation [13,17]. Besides its function in SASP modulation, miR-146 was also reported to target the mRNAs of the BRCA1 and BRCA2 tumor suppressors. In a recent study a G to C polymorphism in miR-146, which leads to an increased processing and release of the mature microRNA, can predict an early onset of breast cancer [23]. Taken together, the study of Bhaumik et al. opens an interesting new research area dealing with the gene regulatory mechanisms that control activation of the SASP. Given the diverse roles of the SASP in modulating tumor progression, immune surveillance of damaged cells, and the stabilization of the senescence arrest itself, it will be of great interest to analyse the influence of SASP regulatory pathways during aging and cancer.",
"title": "Keeping your senescent cells under control"
},
{
"docid": "10024681",
"text": "Deregulation of microRNA (miRNA) expression can have a critical role in carcinogenesis. Here we show in prostate cancer that miRNA-205 (miR-205) transcription is commonly repressed and the MIR-205 locus is hypermethylated. LOC642587, the MIR-205 host gene of unknown function, is also concordantly inactivated. We show that miR-205 targets mediator 1 (MED1, also called TRAP220 and PPARBP) for transcriptional silencing in normal prostate cells, leading to reduction in MED1 mRNA levels, and in total and active phospho-MED1 protein. Overexpression of miR-205 in prostate cancer cells negatively affects cell viability, consistent with a tumor suppressor function. We found that hypermethylation of the MIR-205 locus was strongly related with a decrease in miR-205 expression and an increase in MED1 expression in primary tumor samples (n=14), when compared with matched normal prostate (n=7). An expanded patient cohort (tumor n=149, matched normal n=30) also showed significant MIR-205 DNA methylation in tumors compared with normal, and MIR-205 hypermethylation is significantly associated with biochemical recurrence (hazard ratio=2.005, 95% confidence interval (1.109, 3.625), P=0.02), in patients with low preoperative prostate specific antigen. In summary, these results suggest that miR-205 is an epigenetically regulated tumor suppressor that targets MED1 and may provide a potential biomarker in prostate cancer management.",
"title": "Epigenetic-induced repression of microRNA-205 is associated with MED1 activation and a poorer prognosis in localized prostate cancer"
},
{
"docid": "5783785",
"text": "The discovery of microRNAs (miRNAs) provides a new and powerful tool for studying the mechanism, diagnosis and treatment of human cancers. Currently, down-regulation of tumor suppressive miRNAs by CpG island hypermethylation is emerging as a common hallmark of cancer. Here, we reported that the down-regulation of miR-33b was associated with pM stage of gastric cancer (GC) patients. Ectopic expression of miR-33b in HGC-27 and MGC-803 cells inhibited cell proliferation, migration and invasion, which might be due to miR-33b targeting oncogene c-Myc. Moreover, enhanced methylation level of the CpG island upstream of miR-33b in GC patients with down-regulated miR-33b was confirmed by methylation-specific PCR (MSP) amplification. Furthermore, re-introduction of miR-33b significantly suppressed tumorigenesis of GC cells in the nude mice. In conclusion, miR-33b acts as a tumor suppressor and hypermethylation of the CpG island upstream of miR-33b is responsible for its down-regulation in gastric cancer.",
"title": "DNA Methylation mediated down-regulating of MicroRNA-33b and its role in gastric cancer"
},
{
"docid": "1782201",
"text": "Integrins regulate adhesion-dependent growth, survival and invasion of tumor cells. In particular, expression of integrin alpha(v)beta(3) is associated with progression of a variety of human tumors. Here we reveal a previously undescribed adhesion-independent role for integrin alpha(v)beta(3) in pancreatic cancer and other carcinomas. Specifically, alpha(v)beta(3) expressed in carcinoma cells enhanced anchorage-independent tumor growth in vitro and increased lymph node metastases in vivo. These effects required recruitment of c-Src to the beta(3) integrin cytoplasmic tail, leading to c-Src activation, Crk-associated substrate (CAS) phosphorylation and tumor cell survival that, unexpectedly, was independent of cell adhesion or focal adhesion kinase (FAK) activation. Pharmacological blockade of c-Src kinase activity or decreased expression of endogenous alpha(v)beta(3) integrin or c-Src not only inhibited anchorage-independent growth but also suppressed metastasis in vivo, yet these manipulations did not affect tumor cell migration or invasion. These data define an unexpected role for an integrin as a mediator of anchorage independence, suggesting that an alpha(v)beta(3)-c-Src signaling module may account for the aggressive behavior of integrin alpha(v)beta(3)-expressing tumors in humans.",
"title": "Integrin αvβ3/c-src “Oncogenic Unit” Promotes Anchorage-independence and Tumor Progression"
},
{
"docid": "12887068",
"text": "Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail of histone H3.3. The role of the H3.3K27M mutation in tumorigenesis is not fully understood. Here, we use a human embryonic stem cell system to model this tumor. We show that H3.3K27M expression synergizes with p53 loss and PDGFRA activation in neural progenitor cells derived from human embryonic stem cells, resulting in neoplastic transformation. Genome-wide analyses indicate a resetting of the transformed precursors to a developmentally more primitive stem cell state, with evidence of major modifications of histone marks at several master regulator genes. Drug screening assays identified a compound targeting the protein menin as an inhibitor of tumor cell growth in vitro and in mice.",
"title": "Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation"
},
{
"docid": "2260571",
"text": "RATIONALE Matrix vesicles (MVs), secreted by vascular smooth muscle cells (VSMCs), form the first nidus for mineralization and fetuin-A, a potent circulating inhibitor of calcification, is specifically loaded into MVs. However, the processes of fetuin-A intracellular trafficking and MV biogenesis are poorly understood. OBJECTIVE The objective of this study is to investigate the regulation, and role, of MV biogenesis in VSMC calcification. METHODS AND RESULTS Alexa488-labeled fetuin-A was internalized by human VSMCs, trafficked via the endosomal system, and exocytosed from multivesicular bodies via exosome release. VSMC-derived exosomes were enriched with the tetraspanins CD9, CD63, and CD81, and their release was regulated by sphingomyelin phosphodiesterase 3. Comparative proteomics showed that VSMC-derived exosomes were compositionally similar to exosomes from other cell sources but also shared components with osteoblast-derived MVs including calcium-binding and extracellular matrix proteins. Elevated extracellular calcium was found to induce sphingomyelin phosphodiesterase 3 expression and the secretion of calcifying exosomes from VSMCs in vitro, and chemical inhibition of sphingomyelin phosphodiesterase 3 prevented VSMC calcification. In vivo, multivesicular bodies containing exosomes were observed in vessels from chronic kidney disease patients on dialysis, and CD63 was found to colocalize with calcification. Importantly, factors such as tumor necrosis factor-α and platelet derived growth factor-BB were also found to increase exosome production, leading to increased calcification of VSMCs in response to calcifying conditions. CONCLUSIONS This study identifies MVs as exosomes and shows that factors that can increase exosome release can promote vascular calcification in response to environmental calcium stress. Modulation of the exosome release pathway may be as a novel therapeutic target for prevention.",
"title": "Vascular smooth muscle cell calcification is mediated by regulated exosome secretion."
},
{
"docid": "13964633",
"text": "BACKGROUND Mature microRNAs (miRNAs) are single-stranded RNAs that regulate post-transcriptional gene expression. In our previous study, we have shown that versican 3'UTR, a fragment of non-coding transcript, has the ability to antagonize miR-199a-3p function thereby regulating expression of the matrix proteins versican and fibronectin, and thus resulting in enhanced cell-cell adhesion and organ adhesion. However, the impact of this non-coding fragment on tumorigenesis is yet to be determined. METHODS AND FINDINGS Using computational prediction confirmed with in vitro and in vivo experiments, we report that the expression of versican 3'UTR not only antagonizes miR-199a-3p but can also lower its steady state expression. We found that expression of versican 3'UTR in a mouse breast carcinoma cell line, 4T1, decreased miR-199a-3p levels. The decrease in miRNA activity consequently translated into differences in tumor growth. Computational analysis indicated that both miR-199a-3p and miR-144 targeted a cell cycle regulator, Rb1. In addition, miR-144 and miR-136, which have also been shown to interact with versican 3'UTR, was found to target PTEN. Expression of Rb1 and PTEN were up-regulated synergistically in vitro and in vivo, suggesting that the 3'UTR binds and modulates miRNA activities, freeing Rb1 and PTEN mRNAs for translation. In tumor formation assays, cells transfected with the 3'UTR formed smaller tumors compared with cells transfected with a control vector. CONCLUSION Our results demonstrated that a 3'UTR fragment can be used to modulate miRNA functions. Our study also suggests that miRNAs in the cancer cells are more susceptible to degradation, due to its interaction with a non-coding 3'UTR. This non-coding component of mRNA may be used retrospectively to modulate miRNA activities.",
"title": "Expression of Versican 3′-Untranslated Region Modulates Endogenous MicroRNA Functions"
},
{
"docid": "7764903",
"text": "Both eukaryotic and prokaryotic cells release small, phospholipid-enclosed vesicles into their environment. Why do cells release vesicles? Initial studies showed that eukaryotic vesicles are used to remove obsolete cellular molecules. Although this release of vesicles is beneficial to the cell, the vesicles can also be a danger to their environment, for instance in blood, where vesicles can provide a surface supporting coagulation. Evidence is accumulating that vesicles are cargo containers used by eukaryotic cells to exchange biomolecules as transmembrane receptors and genetic information. Because also bacteria communicate to each other via extracellular vesicles, the intercellular communication via extracellular cargo carriers seems to be conserved throughout evolution, and therefore vesicles are likely to be a highly efficient, robust, and economic manner of exchanging information between cells. Furthermore, vesicles protect cells from accumulation of waste or drugs, they contribute to physiology and pathology, and they have a myriad of potential clinical applications, ranging from biomarkers to anticancer therapy. Because vesicles may pass the blood-brain barrier, they can perhaps even be considered naturally occurring liposomes. Unfortunately, pathways of vesicle release and vesicles themselves are also being used by tumors and infectious diseases to facilitate spreading, and to escape from immune surveillance. In this review, the different types, nomenclature, functions, and clinical relevance of vesicles will be discussed.",
"title": "Classification, functions, and clinical relevance of extracellular vesicles."
},
{
"docid": "14692646",
"text": "Extracellular vesicles, including exosomes, are small membrane vesicles derived from multivesicular bodies or from the plasma membrane. Most, if not all, cell types release extracellular vesicles, which then enter the bodily fluids. These vesicles contain a subset of proteins, lipids and nucleic acids that are derived from the parent cell. It is thought that extracellular vesicles have important roles in intercellular communication, both locally and systemically, as they transfer their contents, including proteins, lipids and RNAs, between cells. Extracellular vesicles are involved in numerous physiological processes, and vesicles from both non-immune and immune cells have important roles in immune regulation. Moreover, extracellular vesicle-based therapeutics are being developed and clinically tested for the treatment of inflammatory diseases, autoimmune disorders and cancer. Given the tremendous therapeutic potential of extracellular vesicles, this Review focuses on their role in modulating immune responses, as well as their potential therapeutic applications.",
"title": "Regulation of immune responses by extracellular vesicles"
},
{
"docid": "4583180",
"text": "Conditions of the tumor microenvironment, such as hypoxia and nutrient starvation, play critical roles in cancer progression. However, the role of acidic extracellular pH in cancer progression is not studied as extensively as that of hypoxia. Here, we show that extracellular acidic pH (pH 6.8) triggered activation of sterol regulatory element-binding protein 2 (SREBP2) by stimulating nuclear translocation and promoter binding to its targets, along with intracellular acidification. Interestingly, inhibition of SREBP2, but not SREBP1, suppressed the upregulation of low pH-induced cholesterol biosynthesis-related genes. Moreover, acyl-CoA synthetase short-chain family member 2 (ACSS2), a direct SREBP2 target, provided a growth advantage to cancer cells under acidic pH. Furthermore, acidic pH-responsive SREBP2 target genes were associated with reduced overall survival of cancer patients. Thus, our findings show that SREBP2 is a key transcriptional regulator of metabolic genes and progression of cancer cells, partly in response to extracellular acidification.",
"title": "Extracellular Acidic pH Activates the Sterol Regulatory Element-Binding Protein 2 to Promote Tumor Progression."
},
{
"docid": "41548287",
"text": "Pancreatic ductal adenocarcinoma (PDAC) and other carcinomas are hierarchically organized, with cancer stem cells (CSC) residing at the top of the hierarchy, where they drive tumor progression, metastasis, and chemoresistance. As CSC and non-CSC share an identical genetic background, we hypothesize that differences in epigenetics account for the striking functional differences between these two cell populations. Epigenetic mechanisms, such as DNA methylation, play an important role in maintaining pluripotency and regulating the differentiation of stem cells, but the role of DNA methylation in pancreatic CSC is obscure. In this study, we investigated the genome-wide DNA methylation profile of PDAC CSC, and we determined the importance of DNA methyltransferases for CSC maintenance and tumorigenicity. Using high-throughput methylation analysis, we discovered that sorted CSCs have a higher level of DNA methylation, regardless of the heterogeneity or polyclonality of the CSC populations present in the tumors analyzed. Mechanistically, CSC expressed higher DNMT1 levels than non-CSC. Pharmacologic or genetic targeting of DNMT1 in CSCs reduced their self-renewal and in vivo tumorigenic potential, defining DNMT1 as a candidate CSC therapeutic target. The inhibitory effect we observed was mediated in part through epigenetic reactivation of previously silenced miRNAs, in particular the miR-17-92 cluster. Together, our findings indicate that DNA methylation plays an important role in CSC biology and also provide a rationale to develop epigenetic modulators to target CSC plasticity and improve the poor outcome of PDAC patients. Cancer Res; 76(15); 4546-58. ©2016 AACR.",
"title": "DNMT1 Inhibition Reprograms Pancreatic Cancer Stem Cells via Upregulation of the miR-17-92 Cluster."
},
{
"docid": "32721137",
"text": "Although 75% of endometrial cancers are treated at an early stage, 15% to 20% of these recur. We performed an integrated analysis of genome-wide expression and copy-number data for primary endometrial carcinomas with extensive clinical and histopathological data to detect features predictive of recurrent disease. Unsupervised analysis of the expression data distinguished 2 major clusters with strikingly different phenotypes, including significant differences in disease-free survival. To identify possible mechanisms for these differences, we performed a global genomic survey of amplifications, deletions, and loss of heterozygosity, which identified 11 significantly amplified and 13 significantly deleted regions. Amplifications of 3q26.32 harboring the oncogene PIK3CA were associated with poor prognosis and segregated with the aggressive transcriptional cluster. Moreover, samples with PIK3CA amplification carried signatures associated with in vitro activation of PI3 kinase (PI3K), a signature that was shared by aggressive tumors without PIK3CA amplification. Tumors with loss of PTEN expression or PIK3CA overexpression that did not have PIK3CA amplification also shared the PI3K activation signature, high protein expression of the PI3K pathway member STMN1, and an aggressive phenotype in test and validation datasets. However, mutations of PTEN or PIK3CA were not associated with the same expression profile or aggressive phenotype. STMN1 expression had independent prognostic value. The results affirm the utility of systematic characterization of the cancer genome in clinically annotated specimens and suggest the particular importance of the PI3K pathway in patients who have aggressive endometrial cancer.",
"title": "Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation."
},
{
"docid": "51706771",
"text": "Glioblastoma (GBM) is the most aggressive and common form of brain cancer in adults. GBM is characterized by poor survival and remarkably high tumors heterogeneity (both intertumoral and intratumoral), and lack of effective therapies. Recent high-throughput data revealed heterogeneous genetic/genomic/epigenetic features and led to multiple methods aiming to classify tumors according to the key molecular events that drive the most aggressive cellular components so that targeted therapies can be developed for individual subtypes. However, GBM molecular subtypes have not led to improvement of patients outcomes. Targeted or tailored therapies for specific mutations or subtypes largely failed due to the complexities arising from intratumoral molecular heterogeneity. Most tumors develop resistance to treatment and soon recur. GBM stem cells (GSCs) have been identified. Recent single cell sequencing studies of GBM suggest that intratumoral cellular heterogeneity can be partially explained by tumor cell hierarchy arising from GBM stem cells. Therefore, the molecular subtypes based on patient derived GSCs may potentially lead to more effective subtype-specific treatments. In this paper, we review the molecular alterations of GBM and molecular subtyping methods as well as subtype plasticity in primary and recurrent tumors emphasizing the clinical relevance of potential targets for further drug development.",
"title": "Comparison of glioblastoma (GBM) molecular classification methods."
},
{
"docid": "52925737",
"text": "BACKGROUND Exosomes are extracellular vesicles that mediate cellular communication in health and diseases. Neutrophils could be polarized to a pro-tumor phenotype by tumor. The function of tumor-derived exosomes in neutrophil regulation remains unclear. METHODS We investigated the effects of gastric cancer cell-derived exosomes (GC-Ex) on the pro-tumor activation of neutrophils and elucidated the underlying mechanisms. RESULTS GC-Ex prolonged neutrophil survival and induced expression of inflammatory factors in neutrophils. GC-Ex-activated neutrophils, in turn, promoted gastric cancer cell migration. GC-Ex transported high mobility group box-1 (HMGB1) that activated NF-κB pathway through interaction with TLR4, resulting in an increased autophagic response in neutrophils. Blocking HMGB1/TLR4 interaction, NF-κB pathway, and autophagy reversed GC-Ex-induced neutrophil activation. Silencing HMGB1 in gastric cancer cells confirmed HMGB1 as a key factor for GC-Ex-mediated neutrophil activation. Furthermore, HMGB1 expression was upregulated in gastric cancer tissues. Increased HMGB1 expression was associated with poor prognosis in patients with gastric cancer. Finally, gastric cancer tissue-derived exosomes acted similarly as exosomes derived from gastric cancer cell lines in neutrophil activation. CONCLUSION We demonstrate that gastric cancer cell-derived exosomes induce autophagy and pro-tumor activation of neutrophils via HMGB1/TLR4/NF-κB signaling, which provides new insights into mechanisms for neutrophil regulation in cancer and sheds lights on the multifaceted role of exosomes in reshaping tumor microenvironment.",
"title": "Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration"
},
{
"docid": "16364639",
"text": "By analyzing gene expression data in glioblastoma in combination with matched microRNA profiles, we have uncovered a posttranscriptional regulation layer of surprising magnitude, comprising more than 248,000 microRNA (miR)-mediated interactions. These include ∼7,000 genes whose transcripts act as miR \"sponges\" and 148 genes that act through alternative, nonsponge interactions. Biochemical analyses in cell lines confirmed that this network regulates established drivers of tumor initiation and subtype implementation, including PTEN, PDGFRA, RB1, VEGFA, STAT3, and RUNX1, suggesting that these interactions mediate crosstalk between canonical oncogenic pathways. siRNA silencing of 13 miR-mediated PTEN regulators, whose locus deletions are predictive of PTEN expression variability, was sufficient to downregulate PTEN in a 3'UTR-dependent manner and to increase tumor cell growth rates. Thus, miR-mediated interactions provide a mechanistic, experimentally validated rationale for the loss of PTEN expression in a large number of glioma samples with an intact PTEN locus.",
"title": "An Extensive MicroRNA-Mediated Network of RNA-RNA Interactions Regulates Established Oncogenic Pathways in Glioblastoma"
},
{
"docid": "4653837",
"text": "The mechanisms underlying the development of aging-induced muscle atrophy are unclear. By microRNA array and individual qPCR analyses, we found significant up-regulation of miR-29 in muscles of aged rodents vs. results in young. With aging, p85α, IGF-1 and B-myb muscle levels were lower while the expression of certain cell arrest proteins (p53, p16 and pRB) increased. When miR-29 was expressed in muscle progenitor cells (MPC), their proliferation was impaired while SA-βgal expression increased signifying the development of senescence. Impaired MPC proliferation resulted from interactions between miR-29 and the 3'-UTR of p85a, IGF-1 and B-myb, suppressing the translation of these mediators of myoblast proliferation. In vivo, electroporation of miR-29 into muscles of young mice suppressed the proliferation and increased levels of cellular arrest proteins, recapitulating aging-induced responses in muscle. A potential stimulus of miR-29 expression is Wnt-3a since we found that exogenous Wnt-3a stimulated miR-29 expression 2.7-fold in primary cultures of MPCs. Thus, aging-induced muscle senescence results from activation of miR-29 by Wnt-3a leading to suppressed expression of several signaling proteins (p85α, IGF-1 and B-myb) that act coordinately to impair the proliferation of MPCs contributing to muscle atrophy. The increase in miR-29 provides a potential mechanism for aging-induced sarcopenia.",
"title": "MicroRNA-29 induces cellular senescence in aging muscle through multiple signaling pathways"
},
{
"docid": "4020950",
"text": "Exosomes are extracellular vesicles of endosomal origin which have emerged as key mediators of intercellular communication. All major cardiac cell types-including cardiomyocytes, endothelial cells, and fibroblasts-release exosomes that modulate cellular functions. Exosomes released from human cardiac progenitor cells (CPCs) are cardioprotective and improve cardiac function after myocardial infarction to an extent comparable with that achieved by their parent cells. Cardiac progenitor cell-derived exosomes are enriched in cardioprotective microRNAs, particularly miR-146a-3p. Circulating exosomes mediate remote ischaemic preconditioning. Moreover, they currently are being investigated as diagnostic markers. The discovery that cell-derived extracellular signalling organelles mediate the paracrine effects of stem cells suggests that cell-free strategies could supplant cell transplantation. This review discusses emerging roles of exosomes in cardiovascular physiology, with a focus on cardioprotective activities of CPC-derived exosomes.",
"title": "Roles of exosomes in cardioprotection."
},
{
"docid": "16605494",
"text": "BACKGROUND Whereas many causes and mechanisms of neurodegenerative diseases have been identified, very few therapeutic strategies have emerged in parallel. One possible explanation is that successful treatment strategy may require simultaneous targeting of more than one molecule of pathway. A new therapeutic approach to have emerged recently is the engagement of microRNAs (miRNAs), which affords the opportunity to target multiple cellular pathways simultaneously using a single sequence. METHODOLOGY/PRINCIPAL FINDINGS We identified miR-22 as a potentially neuroprotective miRNA based on its predicted regulation of several targets implicated in Huntington's disease (histone deacetylase 4 (HDAC4), REST corepresor 1 (Rcor1) and regulator of G-protein signaling 2 (Rgs2)) and its diminished expression in Huntington's and Alzheimer's disease brains. We then tested the hypothesis that increasing cellular levels of miRNA-22 would achieve neuroprotection in in vitro models of neurodegeneration. As predicted, overexpression of miR-22 inhibited neurodegeneration in primary striatal and cortical cultures exposed to a mutated human huntingtin fragment (Htt171-82Q). Overexpression of miR-22 also decreased neurodegeneration in primary neuronal cultures exposed to 3-nitropropionic acid (3-NP), a mitochondrial complex II/III inhibitor. In addition, miR-22 improved neuronal viability in an in vitro model of brain aging. The mechanisms underlying the effects of miR-22 included a reduction in caspase activation, consistent with miR-22's targeting the pro-apoptotic activities of mitogen-activated protein kinase 14/p38 (MAPK14/p38) and tumor protein p53-inducible nuclear protein 1 (Tp53inp1). Moreover, HD-specific effects comprised not only targeting HDAC4, Rcor1 and Rgs2 mRNAs, but also decreasing focal accumulation of mutant Htt-positive foci, which occurred via an unknown mechanism. CONCLUSIONS These data show that miR-22 has multipartite anti-neurodegenerative activities including the inhibition of apoptosis and the targeting of mRNAs implicated in the etiology of HD. These results motivate additional studies to evaluate the feasibility and therapeutic efficacy of manipulating miR-22 in vivo.",
"title": "MicroRNA-22 (miR-22) Overexpression Is Neuroprotective via General Anti-Apoptotic Effects and May also Target Specific Huntington’s Disease-Related Mechanisms"
},
{
"docid": "13070316",
"text": "Tumor angiogenesis is an essential process for supplying rapidly growing malignant tissues with essential nutrients and oxygen. An angiogenic switch allows tumor cells to survive and grow, and provides them access to vasculature resulting in metastatic disease. Monocyte-derived macrophages recruited and reprogrammed by tumor cells serve as a major source of angiogenic factors boosting the angiogenic switch. Tumor endothelium releases angiopoietin-2 and further facilitates recruitment of TIE2 receptor expressing monocytes (TEM) into tumor sites. Tumor-associated macrophages (TAM) sense hypoxia in avascular areas of tumors, and react by production of angiogenic factors such as VEGFA. VEGFA stimulates chemotaxis of endothelial cells (EC) and macrophages. In some tumors, TAM appeared to be a major source of MMP9. Elevated expression of MMP9 by TAM mediates extracellular matrix (ECM) degradation and the release of bioactive VEGFA. Other angiogenic factors released by TAM include basic fibroblast growth factor (bFGF), thymidine phosphorylase (TP), urokinase-type plasminogen activator (uPA), and adrenomedullin (ADM). The same factors used by macrophages for the induction of angiogenesis [like vascular endothelial growth factor A (VEGF-A) and MMP9] support lymphangiogenesis. TAM can express LYVE-1, one of the established markers of lymphatic endothelium. TAM support tumor lymphangiogenesis not only by secretion of pro-lymphangiogenic factors but also by trans-differentiation into lymphatic EC. New pro-angiogenic factor YKL-40 belongs to a family of mammalian chitinase-like proteins (CLP) that act as cytokines or growth factors. Human CLP family comprises YKL-40, YKL-39, and SI-CLP. Production of all three CLP in macrophages is antagonistically regulated by cytokines. It was recently established that YKL-40 induces angiogenesis in vitro and in animal tumor models. YKL-40-neutralizing monoclonal antibody blocks tumor angiogenesis and progression. The role of YKL-39 and SI-CLP in tumor angiogenesis and lymphangiogenesis remains to be investigated.",
"title": "Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis"
}
] |
PLAIN-2936
|
Antimutagenic Activity of Green Versus White Tea
|
[
{
"docid": "MED-4472",
"text": "N-Nitroso compounds were known almost 40 years ago to be present in food treated with sodium nitrite, which made fish meal hepatotoxic to animals through formation of nitrosodimethylamine (NDMA). Since that time, N-nitroso compounds have been shown in animal experiments to be the most broadly acting and the most potent group of carcinogens. The key role of nitrite and nitrogen oxides in forming N-nitroso compounds by interaction with secondary and tertiary amino compounds has led to the examination worldwide of foods for the presence of N-nitroso compounds, which have been found almost exclusively in those foods containing nitrite or which have become exposed to nitrogen oxides. Among these are cured meats, especially bacon-and especially when cooked; concentrations of 100 micrograms kg(-1) have been found or, more usually, near 10 micrograms kg(-1). This would correspond to consumption of 1 microgram of NDMA in a 100-g portion. Much higher concentrations of NDMA (but lower ones of other nitrosamines) have been found in Japanese smoked and cured fish (more than 100 micrograms kg(-1)). Beer is one source of NDMA, in which as much as 70 micrograms l(-1) has been reported in some types of German beer, although usual levels are much lower (10 or 5 micrograms l(-1)); this could mean a considerable intake for a heavy beer drinker of several liters per day. Levels of nitrosamines have been declining during the past three decades, concurrent with a lowering of the nitrite used in food and greater control of exposure of malt to nitrogen oxides in beer making. There have been declines of N-nitroso compound concentrations in many foods during the past two decades. The small amounts of nitrosamines in food are nonetheless significant because of the possibility-even likelihood-that humans are more sensitive to these carcinogens than are laboratory rodents. Although it is probable that alkylnitrosamides (which induce brain tumors in rodents) are present in cured meats and other potentially nitrosated products in spite of much searching, there has been only limited indirect evidence of their presence. Copyright 1999 Elsevier Science B.V.",
"title": "N-Nitroso compounds in the diet."
},
{
"docid": "MED-4720",
"text": "Tritiated naloxone, a powerful opiate antagonist, specifically binds to an opiate receptor of mammalian brain and guinea pig intestine. Competition for the opiate receptor by various opiates and their antagonists closely parallels their pharmacological potency. The opiate receptor is confined to nervous tissue.",
"title": "Opiate receptor: demonstration in nervous tissue."
},
{
"docid": "MED-4869",
"text": "This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, including flavouring agents, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives (in particular, flavouring agents). A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives (asparaginase from Aspergillus niger expressed in A. niger, calcium lignosulfonate (40-65), ethyl lauroyl arginate, paprika extract, phospholipase C expressed in Pichia pastoris, phytosterols, phytostanols and their esters, polydimethylsiloxane, steviol glycosides and sulfites [assessment of dietary exposure]) and 10 groups of related flavouring agents (aliphatic branched-chain saturated and unsaturated alcohols, aldehydes, acids and related esters; aliphatic linear alpha,beta-unsaturated aldehydes, acids and related alcohols, acetals and esters; aliphatic secondary alcohols, ketones and related esters; alkoxy-substituted allylbenzenes present in foods and essential oils and used as flavouring agents; esters of aliphatic acyclic primary alcohols with aliphatic linear saturated carboxylic acids; furan-substituted aliphatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids and related esters, sulfides, disulfides and ethers; miscellaneous nitrogen-containing substances; monocyclic and bicyclic secondary alcohols, ketones and related esters; hydroxy- and alkoxy-substituted benzyl derivatives; and substances structurally related to menthol). Specifications for the following food additives were revised: canthaxanthin; carob bean gum and carob bean gum (clarified); chlorophyllin copper complexes, sodium and potassium salts; Fast Green FCF; guar gum and guar gum (clarified); iron oxides; isomalt; monomagnesium phosphate; Patent Blue V; Sunset Yellow FCF; and trisodium diphosphate. Re-evaluation of flavouring agents for which estimated intake was based on anticipated poundage data was carried out for 2-isopropyl- N,2,3-trimethylbutyramide (No. 1595) and L-monomenthyl glutarate (No. 1414). Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives considered.",
"title": "Evaluation of certain food additives."
},
{
"docid": "MED-4878",
"text": "Background Telomere length reflects biological aging and may be influenced by environmental factors, including those that affect inflammatory processes. Objective With data from 840 white, black, and Hispanic adults from the Multi-Ethnic Study of Atherosclerosis, we studied cross-sectional associations between telomere length and dietary patterns and foods and beverages that were associated with markers of inflammation. Design Leukocyte telomere length was measured by quantitative polymerase chain reaction. Length was calculated as the amount of telomeric DNA (T) divided by the amount of a single-copy control DNA (S) (T/S ratio). Intake of whole grains, fruit and vegetables, low-fat dairy, nuts or seeds, nonfried fish, coffee, refined grains, fried foods, red meat, processed meat, and sugar-sweetened soda were computed with responses to a 120-item food-frequency questionnaire completed at baseline. Scores on 2 previously defined empirical dietary patterns were also computed for each participant. Results After adjustment for age, other demographics, lifestyle factors, and intakes of other foods or beverages, only processed meat intake was associated with telomere length. For every 1 serving/d greater intake of processed meat, the T/S ratio was 0.07 smaller (β ± SE: −0.07 ± 0.03, P = 0.006). Categorical analysis showed that participants consuming ≥1 serving of processed meat each week had 0.017 smaller T/S ratios than did nonconsumers. Other foods or beverages and the 2 dietary patterns were not associated with telomere length. Conclusions Processed meat intake showed an expected inverse association with telomere length, but other diet features did not show their expected associations.",
"title": "Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA)"
},
{
"docid": "MED-4976",
"text": "Airborne cooking by-products from frying beef (hamburgers), pork (bacon strips) and soybean-based food (tempeh burgers) were collected, extracted, tested for mutagenicity and chemically analysed. The fumes generated by frying pork and beef were mutagenic, with 4900 and 1300 revertants/g of food cooked, respectively. No mutagenicity was detected in fumes from frying tempeh burgers. Bacon fried to a well-done but non-charred state was eight times more mutagenic in a microsuspension Ames/Salmonella test (TA98 with S-9) than hamburgers and about 350 times more mutagenic than tempeh burgers. Among food samples cooked to a well-done, non-charred state, bacon strips had almost 15-fold more mass (109.5 ng/g) than that of the beef, whereas no heterocyclic amine (HCA) was detected in the fried tempeh burgers. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was the most abundant HCA, followed by 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx). No 2-amino-9H-pyrido[2,3-b]indole (A alpha C) was detected in the food samples fried at about 200 degrees C, although it was present in the collected airborne products. The total amounts of HCAs in the smoke condensates were 3 ng/g from fried bacon, 0.37 ng/g from fried beef and 0.177 ng/g from fried soy-based food. This study indicates that cooks are potentially exposed to relatively high levels of airborne mutagens and carcinogens and that long-term sampling inside restaurants and kitchens may be warranted in order to assess the potential risk of prolonged exposure.",
"title": "Airborne mutagens produced by frying beef, pork and a soy-based food."
},
{
"docid": "MED-4868",
"text": "Studies revealed that Stevia has been used throughout the world since ancient times for various purposes; for example, as a sweetener and a medicine. We conducted a systematic literature review to summarize and quantify the past and current evidence for Stevia. We searched relevant papers up to 2007 in various databases. As we know that the leaves of Stevia plants have functional and sensory properties superior to those of many other high-potency sweeteners, Stevia is likely to become a major source of high-potency sweetener for the growing natural food market in the future. Although Stevia can be helpful to anyone, there are certain groups who are more likely to benefit from its remarkable sweetening potential. These include diabetic patients, those interested in decreasing caloric intake, and children. Stevia is a small perennial shrub that has been used for centuries as a bio-sweetener and for other medicinal uses such as to lower blood sugar. Its white crystalline compound (stevioside) is the natural herbal sweetener with no calories and is over 100-300 times sweeter than table sugar.",
"title": "Stevia (Stevia rebaudiana) a bio-sweetener: a review."
},
{
"docid": "MED-4877",
"text": "BACKGROUND: Telomeres are protective DNA-protein complexes at the end of linear chromosomes that promote chromosomal stability. Telomere shortness in human beings is emerging as a prognostic marker of disease risk, progression, and premature mortality in many types of cancer, including breast, prostate, colorectal, bladder, head and neck, lung, and renal cell. Telomere shortening is counteracted by the cellular enzyme telomerase. Lifestyle factors known to promote cancer and cardiovascular disease might also adversely affect telomerase function. However, previous studies have not addressed whether improvements in nutrition and lifestyle are associated with increases in telomerase activity. We aimed to assess whether 3 months of intensive lifestyle changes increased telomerase activity in peripheral blood mononuclear cells (PBMC). METHODS: 30 men with biopsy-diagnosed low-risk prostate cancer were asked to make comprehensive lifestyle changes. The primary endpoint was telomerase enzymatic activity per viable cell, measured at baseline and after 3 months. 24 patients had sufficient PBMCs needed for longitudinal analysis. This study is registered on the ClinicalTrials.gov website, number NCT00739791. FINDINGS: PBMC telomerase activity expressed as natural logarithms increased from 2.00 (SD 0.44) to 2.22 (SD 0.49; p=0.031). Raw values of telomerase increased from 8.05 (SD 3.50) standard arbitrary units to 10.38 (SD 6.01) standard arbitrary units. The increases in telomerase activity were significantly associated with decreases in low-density lipoprotein (LDL) cholesterol (r=-0.36, p=0.041) and decreases in psychological distress (r=-0.35, p=0.047). INTERPRETATION: Comprehensive lifestyle changes significantly increase telomerase activity and consequently telomere maintenance capacity in human immune-system cells. Given this finding and the pilot nature of this study, we report these increases in telomerase activity as a significant association rather than inferring causation. Larger randomised controlled trials are warranted to confirm the findings of this study.",
"title": "Increased telomerase activity and comprehensive lifestyle changes: a pilot study."
},
{
"docid": "MED-4332",
"text": "There is growing interest in the potential health benefits of tea, including the antimutagenic properties. Four varieties of white tea, which represent the least processed form of tea, were shown to have marked antimutagenic activity in the Salmonella assay, particularly in the presence of S9. The most active of these teas, Exotica China white tea, was significantly more effective than Premium green tea (Dragonwell special grade) against 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and four other heterocyclic amine mutagens, namely 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Mechanism studies were performed using rat liver S9 in assays for methoxyresorufin O-demethylase (MROD), a marker for the enzyme cytochrome P4501A2 that activates heterocyclic amines, as well as Salmonella assays with the direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). White tea at low concentrations in the assay inhibited MROD activity, and attenuated the mutagenic activity of N-hydroxy-IQ in the absence of S9. Nine of the major constituents found in green tea also were detected in white tea, including high levels of epigallocatechin-3-gallate (EGCG) and several other polyphenols. When these major constituents were mixed to produce \"artificial\" teas, according to their relative levels in white and green teas, the complete tea exhibited higher antimutagenic potency compared with the corresponding artificial tea. The results suggest that the greater inhibitory potency of white versus green tea in the Salmonella assay might be related to the relative levels of the nine major constituents, perhaps acting synergistically with other (minor) constituents, to inhibit mutagen activation as well as \"scavenging\" the reactive intermediate(s).",
"title": "Potent antimutagenic activity of white tea in comparison with green tea in the Salmonella assay."
},
{
"docid": "MED-5047",
"text": "Our objective was to examine whether habitual green tea consumption is associated with blood glucose levels and other biomarkers of glucose metabolism. We conducted a cross-sectional study of 35 male volunteers, 23–63 years old and residing in Shizuoka Prefecture in Japan. Biochemical data were measured and we conducted a questionnaire survey on health, lifestyle, and nutrition, as well as frequency of consumption and concentrations (1%, 2%, and 3%) of green tea. Men who consumed a 3% concentration of green tea showed lower mean values of fasting blood glucose and fructosamine than those who consumed a 1% concentration. Fasting blood glucose levels were found to be significantly associated with green tea concentration (β = −0.14, p = 0.03). However, green tea consumption frequency showed no significant differences in mean levels of blood glucose, fructosamine and hemoglobin A1c. In conclusion, our findings suggest that the consumption of green tea at a high concentration has the potential to reduce blood glucose levels.",
"title": "The Association between Concentrations of Green Tea and Blood Glucose Levels"
},
{
"docid": "MED-5065",
"text": "Anthocyanins, belonging to the flavonoid family of phytochemicals, have received attention as agents that may have potential in preventing chronic diseases such as cardiovascular diseases and certain cancers. In the present study, an anthocyanin-rich extract from Concord grapes [referred to as Concord grape extract (CGE)] and the anthocyanin delphinidin were evaluated for their capacity to inhibit DNA adduct formation due to the environmental carcinogen benzo[a]pyrene (BP) in MCF-10F cells, a noncancerous, immortalized human breast epithelial cell line. CGE at 10 and 20 microg/mL and delphinidin at 0.6 microM concentrations significantly inhibited BP-DNA adduct formation. This was associated with a significant increase in activities of the phase II detoxification enzymes glutathione S-transferase and NAD(P)H:quinone reductase 1. In addition, these grape components also suppressed reactive oxygen species (ROS) formation, but did not induce antioxidant response element-dependent transcription. Taken together, these data suggest that CGE and a component grape anthocyanin have breast cancer chemopreventive potential due in part to their capacity to block carcinogen-DNA adduct formation, modulate activities of carcinogen-metabolizing enzymes, and suppress ROS in these noncancerous human breast cells.",
"title": "Anthocyanin-rich grape extract blocks breast cell DNA damage."
},
{
"docid": "MED-5046",
"text": "Epidemiological evidence suggests a role for tea catechins in reduction of chronic disease risk. However, stability of catechins under digestive conditions is poorly understood. The objective of this study was to characterize the effect of common food additives on digestive recovery of tea catechins. Green tea water extracts were formulated in beverages providing 4.5, 18, 23, and 3.5 mg per 100 mL epicatechin (EC), epigallocatechin (EGC), epigallocatechin-gallate (EGCG), and epicatechin-gallate (ECG), respectively. Common commercial beverage additives; citric acid (CA), BHT, EDTA, ascorbic acid (AA), milk (bovine, soy, and rice), and citrus juice (orange, grapefruit, lemon, and lime) were formulated into finished tea beverages at incremental dosages. Samples were then subjected to in vitro digestion simulating gastric and small intestinal conditions with pre- and post-digestion catechin profiles assessed by HPLC. Catechin stability in green tea was poor with <20% total catechins remaining post-digestion. EGC and EGCG were most sensitive with less, not double equals 10% recovery. Teas formulated with 50% bovine, soy, and rice milk increased total catechin recovery significantly to 52, 55, and 69% respectively. Including 30 mg AA in 250 mL of tea beverage significantly (p<0.05) increased catechin recovery of EGC, EGCG, EC, and ECG to 74, 54, 82, and 45% respectively. Juice preparation resulted in the highest recovery of any formulation for EGC (81-98%), EGCG (56-76%), EC (86-95%), and ECG (30-55%). These data provide evidence that tea consumption practices and formulation factors likely impact catechin digestive recovery and may result in diverse physiological profiles.",
"title": "Common tea formulations modulate in vitro digestive recovery of green tea catechins."
},
{
"docid": "MED-5064",
"text": "To find out if the cancer protective effects of Brussels sprouts seen in epidemiological studies are due to protection against DNA-damage, an intervention trial was conducted in which the impact of vegetable consumption on DNA-stability was monitored in lymphocytes with the comet assay. After consumption of the sprouts (300 g/p/d, n = 8), a reduction of DNA-migration (97%) induced by the heterocyclic aromatic amine 2-amino-1-methyl-6-phenyl-imidazo-[4,5-b]pyridine (PhIP) was observed whereas no effect was seen with 3-amino-1-methyl-5H-pyrido[4,3-b]-indole (Trp-P-2). This effect protection may be due to inhibition of sulfotransferase 1A1, which plays a key role in the activation of PhIP. In addition, a decrease of the endogenous formation of oxidized bases was observed and DNA-damage caused by hydrogen peroxide was significantly (39%) lower after the intervention. These effects could not be explained by induction of antioxidant enzymes glutathione peroxidase and superoxide dismutase, but in vitro experiments indicate that sprouts contain compounds, which act as direct scavengers of reactive oxygen species. Serum vitamin C levels were increased by 37% after sprout consumption but no correlations were seen between prevention of DNA-damage and individual alterations of the vitamin levels. Our study shows for the first time that sprout consumption leads to inhibition of sulfotransferases in humans and to protection against PhIP and oxidative DNA-damage.",
"title": "Consumption of Brussels sprouts protects peripheral human lymphocytes against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and oxidative ..."
},
{
"docid": "MED-4775",
"text": "PURPOSE: To investigate the association between green tea consumption and mortality from all causes, cancer, and cardiovascular disease (CVD) among elderly people. METHODS: In a population-based, prospective cohort study, a total of 14,001 elderly residents (aged 65-84 years), randomly chosen from all 74 municipalities in Shizuoka, Japan, completed questionnaires that included items about frequency of green tea consumption. They were followed for up to 6 years, from December 1999 to March 2006. Consequently, 12,251 subjects were analyzed to estimate the hazard ratios (HRs) for all-cause mortality, cancer, and CVD. RESULTS: Among 64,002 person-years, 1,224 deaths were identified (follow-up rate, 71.6%). The multivariate HRs and 95% confidence intervals (CIs) for CVD mortality compared those who consumed seven or more cups per day with those who consumed less than one cup per day, were 0.24 (0.14-0.40), 0.30 (0.15-0.61), and 0.18 (0.08-0.40) for total participants, men, and women, respectively. Although green tea consumption was not inversely associated with cancer mortality, green tea consumption and colorectal cancer mortality were inversely associated with a moderate dose-response relationship. CONCLUSIONS: Green tea consumption is associated with reduced mortality from all causes and CVD. This study also suggests that green tea could have protective effects against colorectal cancer.",
"title": "Green tea consumption and mortality among Japanese elderly people: the prospective Shizuoka elderly cohort."
},
{
"docid": "MED-4471",
"text": "Some indoor activities increase the number concentration of small particles and, hence, enhance the dose delivered to the lungs. The received particle dose indoors may exceed noticeably the dose from ambient air under routine in-house activities like cooking. In the present work, the internal dose by inhalation of ultrafine and fine particles is assessed, using an appropriate mechanistic model of lung deposition, accommodating aerosol, and inhalation dynamics. The analysis is based on size distribution measurements (10-350 nm) of indoor and outdoor aerosol number concentrations in a typical residence in Athens, Greece. Four different cases are examined, namely, a cooking event, a no activity period indoors and the equivalent time periods outdoors. When the cooking event (frying of bacon-eggs with a gas fire) occurred, the amount of deposited particles deep into the lung of an individual indoors exceeded by up to 10 times the amount received by an individual at the same time period outdoors. The fine particle deposition depends on the level of physical exertion and the hygroscopic properties of the inhaled aerosol. The dose is not found linearly dependant on the indoor/outdoor concentrations during the cooking event, whereas it is during the no activity period. PRACTICAL IMPLICATIONS: The necessity for determining the dose in specific regions of the human lung, as well as the non-linear relationship between aerosol concentration and internal dose makes the application of dosimetry models important. Lung dose of fine and ultrafine particles, during a cooking event, is compared with the dose at no indoor activity and the dose received under outdoor exposure conditions. The dose is expressed in terms of number or surface of deposited particles. This permits to address the dosimetry of very small particles, which are released by many indoor sources but represent a slight fraction of the particulate matter mass. The enhancement of the internal dose resulting from fine and ultrafine particles generated during the cooking event vs. the dose when no indoor source is active is assessed. The results for those cases are also compared with the dose calculated for the measured aerosol outdoors.",
"title": "Lung deposition of fine and ultrafine particles outdoors and indoors during a cooking event and a no activity period."
},
{
"docid": "MED-4867",
"text": "Stevioside, a constituent of Stevia rebaudiana, is commonly used as a non-caloric sugar substitute in Japan. The genetic toxicities of stevioside and its aglycone, steviol, were examined with seven mutagenicity tests using bacteria (reverse mutation assay, forward mutation assay, umu test and rec assay), cultured mammalian cells (chromosomal aberration test and gene mutation assay) and mice (micronucleus test). Stevioside was not mutagenic in any of the assays examined. The aglycone, steviol, however, produced dose-related positive responses in some mutagenicity tests, i.e. the forward mutation assay using Salmonella typhimurium TM677, the chromosomal aberration test using Chinese hamster lung fibroblast cell line (CHL) and the gene mutation assay using CHL. Metabolic activation systems containing 9000 g supernatant fraction (S9) of liver homogenates prepared from polychlorinated biphenyl or phenobarbital plus 5,6-benzoflavone-pretreated rats were required for mutagenesis and clastogenesis. Steviol was weakly positive in the umu test using S.typhimurium TA1535/pSK1002 either with or without the metabolic activation system. Steviol, even in the presence of the S9 activation system, was negative in other assays, i.e. the reverse mutation assays using S.typhimurium TA97, TA98, TA100, TA102, TA104, TA1535, TA1537 and Escherichia coli WP2 uvrA/pKM101 and the rec-assay using Bacillus subtilis. Steviol was negative in the mouse micronucleus test. The genotoxic risk of steviol to humans is discussed.",
"title": "Evaluation of the genotoxicity of stevioside and steviol using six in vitro and one in vivo mutagenicity assays."
},
{
"docid": "MED-5048",
"text": "Despite the continuing reports supporting the hepatoprotective effects of green tea against ethanol intoxication, there remain controversies regarding the active compound(s) and molecular mechanism. These issues were addressed in the present study using cultured HepG2 cells exposed to a lethal dose of ethanol. Gamma-glutamyl transferase (GGT) was chosen as a marker of ethanol toxicity because it is widely used in clinics. When the cells were treated with ethanol at various concentrations, there was a dose-dependent increase of GGT activity in the culture media and loss of cell viability. Pretreatment of the cells with green tea extract attenuated the changes significantly. Among the green tea constituents, (-)-epigallocatechin gallate (EGCG) attenuated the ethanol cytotoxicity effectively, whereas L-theanine and caffeine had no effects. The ethanol cytotoxicity was also attenuated by alcohol dehydrogenase inhibitor 4-methyl pyrazol and GGT inhibitor acivicin as well as by thiol modulators such as S-adenosyl-L-methionine, N-acetyl-L-cysteine and glutathione. EGCG failed to prevent the intracellular glutathione loss caused by ethanol, but it appeared to be a strong GGT inhibitor. Therefore the cytoprotective effects of green tea could be attributed to the inhibition of GGT activity by EGCG. This study suggests that GGT inhibitors including EGCG may provide a novel strategy for attenuating ethanol-induced liver damage.",
"title": "Effect of green tea and (-)-epigallocatechin gallate on ethanol-induced toxicity in HepG2 cells."
},
{
"docid": "MED-4719",
"text": "Among the many known health benefits of tea catechins count anti-inflammatory and neuroprotective activities, as well as effects on the regulation of food intake. Here we address cannabimimetic bioactivity of catechin derivatives occurring in tea leaves as a possible cellular effector of these functionalities. Competitive radioligand binding assays using recombinant human cannabinoid receptors expressed in Chem-1 and CHO cells identified (-)-epigallocatechin-3-O-gallate, EGCG (K(i)=33.6 microM), (-)-epigallocatechin, EGC (K(i)=35.7 microM), and (-)-epicatechin-3-O-gallate, ECG (K(i)=47.3 microM) as ligands with moderate affinity for type 1 cannabinoid receptors, CB1. Binding to CB2 was weaker with inhibition constants exceeding 50 microM for EGC and ECG. The epimers (+)-catechin and (-)-epicatechin exhibited negligible affinities for both CB1 and CB2. It can be concluded that central nervous cannabinoid receptors may be targeted by selected tea catechins but signaling via peripheral type receptors is less likely to play a major role in vivo.",
"title": "Tea catechins' affinity for human cannabinoid receptors."
},
{
"docid": "MED-5049",
"text": "OBJECTIVE: To evaluate the hypolipemic and antioxidant effects of soy and green tea alone and/or in association in dyslipidemic subjects. METHODS: One hundred dyslipidemic individuals were allocated into four groups. The soy group ingested 50 g of soy (kinako) daily, and the green tea group ingested 3 g of green tea in 500 mL of water per day. A third group ingested 50 g of soy and 3 g of green tea daily, and the control group had a hypocholesterolemic diet. Evaluations were performed at baseline and after 45 and 90 d. Plasma levels of total cholesterol, high-density lipoprotein, and triacylglycerols were evaluated by automated methods. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. LDL was isolated by ultracentrifugation. Total plasma antioxidant capacity and plasma levels of total lipid hydroperoxides and those linked to LDL were evaluated by chemiluminescence. The results were expressed as median values and their 25th to 75th percentiles, with a 5% level of significance. RESULTS: No significant difference occurred in LDL, high-density lipoprotein cholesterol, and triacylglycerol levels across groups. However, a statistically significant difference in total cholesterol occurred within the soy/green tea group 45 and 90 d after intervention. No statistically significant difference occurred in plasma levels of lipid hydroperoxides or those linked to LDL in any of the groups studied. All the groups that used soy and/or green tea presented increased total plasma antioxidant potential. CONCLUSION: Soy and green tea, alone or in combination, increased the total antioxidant potential of hypercholesterolemic patients, whereas only the combination decreased total cholesterol levels.",
"title": "Association between soy and green tea (Camellia sinensis) diminishes hypercholesterolemia and increases total plasma antioxidant potential in dysli..."
},
{
"docid": "MED-4721",
"text": "[3H]CP 55,940, a radiolabeled synthetic cannabinoid, which is 10-100 times more potent in vivo than delta 9-tetrahydrocannabinol, was used to characterize and localize a specific cannabinoid receptor in brain sections. The potencies of a series of natural and synthetic cannabinoids as competitors of [3H]CP 55,940 binding correlated closely with their relative potencies in several biological assays, suggesting that the receptor characterized in our in vitro assay is the same receptor that mediates behavioral and pharmacological effects of cannabinoids, including human subjective experience. Autoradiography of cannabinoid receptors in brain sections from several mammalian species, including human, reveals a unique and conserved distribution; binding is most dense in outflow nuclei of the basal ganglia--the substantia nigra pars reticulata and globus pallidus--and in the hippocampus and cerebellum. Generally high densities in forebrain and cerebellum implicate roles for cannabinoids in cognition and movement. Sparse densities in lower brainstem areas controlling cardiovascular and respiratory functions may explain why high doses of delta 9-tetrahydrocannabinol are not lethal.",
"title": "Cannabinoid receptor localization in brain."
},
{
"docid": "MED-4879",
"text": "To estimate age using DNA based on telomere shortening, we determined the terminal restriction fragment (TRF) length, as telomere length, using Southern blot analysis of peripheral human blood and blood stains. All blood stains had been stored at room temperature for 5 months. The average TRF length clearly showed a tendency to shortening with aging. The formula for age estimation was based on a correlation between average TRF length and age of the subjects. The estimated age calculated from TRF length widely depends on environmental and genetic factors. However, as long as the DNA is well preserved, use of our method is feasible regardless of age of the subject and can give a rough estimation of age of subjects in forensic samples that carry no morphological information. Copyright 2002 Elsevier Science Ireland Ltd.",
"title": "Estimating age of humans based on telomere shortening."
},
{
"docid": "MED-5050",
"text": "Tea is the most widely consumed beverage in the world after water. Tea is known to be a rich source of flavonoid antioxidants. However tea also contains a unique amino acid, L-theanine that may modulate aspects of brain function in humans. Evidence from human electroencephalograph (EEG) studies show that it has a direct effect on the brain (Juneja et al. Trends in Food Science & Tech 1999;10;199-204). L-theanine significantly increases activity in the alpha frequency band which indicates that it relaxes the mind without inducing drowsiness. However, this effect has only been established at higher doses than that typically found in a cup of black tea (approximately 20mg). The aim of the current research was to establish this effect at more realistic dietary levels. EEG was measured in healthy, young participants at baseline and 45, 60, 75, 90 and 105 minutes after ingestion of 50mg L-theanine (n=16) or placebo (n=19). Participants were resting with their eyes closed during EEG recording. There was a greater increase in alpha activity across time in the L-theanine condition (relative to placebo (p+0.05). A second study replicated this effect in participants engaged in passive activity. These data indicate that L-theanine, at realistic dietary levels, has a significant effect on the general state of mental alertness or arousal. Furthermore, alpha activity is known to play an important role in critical aspects of attention, and further research is therefore focussed on understanding the effect of L-theanine on attentional processes.",
"title": "L-theanine, a natural constituent in tea, and its effect on mental state."
}
] |
[
{
"docid": "MED-870",
"text": "Ilex paraguariensis dried and minced leaves are made into a brewed tea, prepared in a sui generis manner by large populations in South America, having evolved from a tea drunk by the Guarani ethnic group to a beverage that has a social and almost ritualistic role in some South American modern societies. It is used both as a source of caffeine, in lieu or in parallel with tea and coffee, but also as a therapeutic agent for its alleged pharmacological properties. Although with some exceptions, research on biomedical properties of this herb has had a late start and strongly lags behind the impressive amount of literature on green tea and coffee. However, in the past 15 years, there was a several-fold increase in the literature studying Ilex paraguariensis properties showing effects such as antioxidant properties in chemical models and ex vivo lipoprotein studies, vaso-dilating and lipid reduction properties, antimutagenic effects, controversial association with oropharyngeal cancer, anti-glycation effects and weight reduction properties. Lately, promising results from human intervention studies have surfaced and the literature offers several developments on this area. The aim of this review is to provide a concise summary of the research published in the past three years, with an emphasis on translational studies, inflammation and lipid metabolism. Ilex paraguariensis reduces LDL-cholesterol levels in humans with Ilex paraguariensis dyslipoproteinemia and the effect is synergic with that of statins. Plasma antioxidant capacity as well as expression of antioxidant enzymes is positively modulated by intervention with Ilex paraguariensis in human cohorts. A review on the evidence implicating Ilex paraguariensis heavy consumption with some neoplasias show data that are inconclusive but indicate that contamination with alkylating agents during the drying process of the leaves should be avoided. On the other hand, several new studies confirm the antimutagenic effects of Ilex paraguariensis in different models, from DNA double breaks in cell culture models to mice studies. Novel interesting work has emerged showing significant effect on weight reduction both in mice and in rat models. Some mechanisms involved are inhibition of pancreatic lipase, activation of AMPK and uncoupling of electron transport. Intervention studies in animals have provided strong evidence of anti-inflammatory effects of Ilex paraguariensis, notably protecting cigarette-induced lung inflammation acting on macrophage migration and inactivating matrix-metalloproteinase. Research on the effects of Ilex paraguariensis in health and disease has confirmed its antioxidant, anti-inflammatory, antimutagenic and lipid-lowering activities. Although we are still waiting for the double-blind, randomized prospective clinical trial, the evidence seems to provide support for beneficial effects of mate drinking on chronic diseases with inflammatory component and lipid metabolism disorders. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.",
"title": "Recent advances on Ilex paraguariensis research: minireview."
},
{
"docid": "MED-4777",
"text": "The current practice of introducing phytochemicals to support the immune system or fight against diseases is based on centuries old traditions. Nutritional support is a recent advancement in the domain of diet-based therapies; green tea and its constituents are one of the important components of these strategies to prevent and cure various malignancies. The anti-carcinogenic and anti-mutagenic activities of green tea were highlighted some years ago suggesting that it could reduce the prevalence of cancer and even provide protection. The pharmacological actions of green tea are mainly attributed to polyphenols that includes epigallocatechin-3-gallate (EGCG), epicatechin, epicatechin-3-gallate, epigallocatechin. Green tea and its components effectively mitigate cellular damage arising due to oxidative stress. Green tea is supposed to enhance humoral and cell-mediated immunity, decreasing the risk of certain cancers, and may have certain advantage in treating inflammatory disorders. Much of the cancer chemopreventive properties of green tea are mediated by EGCG that induces apoptosis and promotes cell growth arrest, by altering the expression of cell cycle regulatory proteins, activating killer caspases, and suppressing nuclear factor kappa-B activation. Besides, it regulates and promotes IL-23 dependent DNA repair and stimulates cytotoxic T cells activities in a tumor microenvironment. It also blocks carcinogenesis by modulating the signal transduction pathways involved in cell proliferation, transformation, inflammation and metastasis. The review is intended to highlight the chemistry of green tea, its antioxidant potential, its immunopotentiating properties and mode of action against various cancer cell lines that showed its potential as a chemopreventive agent against colon, skin, lung, prostate, and breast cancer.",
"title": "Green tea: nature's defense against malignancies."
},
{
"docid": "MED-4330",
"text": "Scope Observational studies have evaluated the relationship between green tea intake and cancers of the ovary and endometrium, but we are not aware of the published studies on green tea intake and risk of human papillomavirus (HPV)-related cancers of the cervix, vagina, or vulva. Methods and results A critical review of the published literature on tea intake and risk of ovarian and endometrial cancers was conducted. In meta-analyses, we report inverse associations for green tea intake and risk of ovarian cancer (odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.54, 0.80), and for green tea and risk of endometrial cancer (OR = 0.78, 95% CI: 0.62, 0.98). There was no association for black tea and ovarian cancer risk (OR = 0.94, 95% CI: 0.87, 1.02) and a positive association with endometrial cancer risk (OR = 1.20, 95% CI: 1.05, 1.38). We summarized the experimental evidence supporting the antiviral and immunomodulatory activities of green tea catechins, and results from randomized clinical trials that demonstrated green tea catechin efficacy on treatment of cervical lesions and external genital warts. Conclusion Observational data support a protective role of green tea on risk of ovarian and endometrial cancers. Observational data are needed to evaluate whether green tea reduces risk of human papillomavirus-related cancers.",
"title": "Green and black tea in relation to gynecologic cancers"
},
{
"docid": "MED-2094",
"text": "INTRODUCTION: An increasing number of people all around the world are turning to the nature by using the natural herbal products in both prophylaxes and treatment of different diseases. Green tea with active chemical ingredients posses diverse pharmacological properties that include anti-inflammatory, anticariogenic, antioxidant and antibacterial effects. AIMS: To assess the possible protective properties of green tea on oral health. METHODS: The researchers used the following measurements: Streptococcus mutans count in saliva and plaque, Salivary and plaque pH values, Gingival Bleeding Index (GBI). The above-mentioned measurements were applied to a sample consists of 25 subjects before and after rinsing with green tea for 5 min (short-term study). While, S. mutans count for saliva and plaque and GBI measurements, this experimental intervention study was carried out in the El-Azhar University dental clinic. RESULTS: The results of this study showed that there was a statistically significant difference among subjects pre- and post-rinsing with 2% green tea for 5 min concerning S. mutans count in saliva and plaque, salivary and plaque pH values and GBI. CONCLUSION: This study supports the effectiveness of local application of green tea as antibacterial and anticariogenic material as it decreases the acidity of the saliva and plaque, so it is a cost-effective caries prevention measures especially in developing countries. © 2009 John Wiley & Sons A/S.",
"title": "A pilot study of the role of green tea use on oral health."
},
{
"docid": "MED-4864",
"text": "To elucidate the health benefit of herbal teas on the cytotoxicity induced by H(2)O(2) in V79-4 cells, herbal extracts and its flavonoids were tested using lactate dehydrogenase release and determining intracellular reactive oxygen species generation and antioxidant activity with superoxide radical scavenging assay. Significant decrease in cell viability was observed on V79-4 cells treated with H(2)O(2) (1 mM), while herbal extracts and its flavonoids including catechin and epigallocatechin gallate prevented the LDH release from H(2)O(2) cytotoxicity. Total catechin contents of green tea (65.6 mg/g of dry matter) were significantly higher than other herbal teas (35.8 to 1.2 mg/g of DM). The relative concentration of the 4 major tea catechins ranked EGCG > EGC > EC > C. Green tea exhibited the lowest IC(50) values (2 g fresh herb/100 mL) of superoxide radical scavenging activity among the tested herbal tea, which indicates powerful antioxidant activity in O(2)(*-) radicals scavenging, followed by black tea, dandelion, hawthorn, rose hip, chamomile.",
"title": "Comparative flavonoids contents of selected herbs and associations of their radical scavenging activity with antiproliferative actions in V79-4 cells."
},
{
"docid": "MED-4365",
"text": "A myriad of health claims are being made in favor of the consumption of green tea. However, mostly due to the easy availability and greater than ever popularity of highly concentrated green tea extracts, sometimes combined with an attitude of more-is-better, certain health risks of green tea consumption have begun to emerge. Among such risks are the possibility of liver damage, the potential to interact with prescription drugs to alter their therapeutic efficacy, and the chance to cause harm when combined with other highly popular herbal remedies. This review will summarize documented examples of adverse effects of green tea in humans, and will discuss risks of copious consumption of highly concentrated green tea extracts as indicated by studies in animals. While there is no intention to minimize any of the scientifically established benefits of the use of green tea, the purpose of this review is to focus primarily on the potential for adverse effects and raise awareness of the rare, yet under-appreciated risks. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Adverse effects of concentrated green tea extracts."
},
{
"docid": "MED-5052",
"text": "OBJECTIVE: Habitual green tea consumption has long been associated with health benefits including chemoprevention and cardiovascular protection. This non-systematic literature review presents the clinical evidence to date. METHOD: A literature review of peer-reviewed articles on observational and interventional studies was conducted to include green tea, its extract or its purified polyphenol (-)-epigallocatechin-3-gallate (EGCG). Electronic databases searched included PubMed (1966-2009) and the Cochrane Library (Issue 4, 2008). RESULTS: Observational studies are inconclusive on the benefits of habitual consumption of green tea in the prevention of most cancers. However, there are trends towards prevention in breast and prostate cancers. Interventional studies have demonstrated reduction in relapses following surgical resection in colorectal adenomas and increased survival rates in epithelial ovarian cancer. Observational studies indicate that green tea may provide protection against hypertension and reduce the risk for stroke, and interventional studies are providing biochemical and physiological evidence. CONCLUSION: Although the overall clinical evidence is inconclusive, habitual green tea consumption may be providing some level of chemoprevention in prostate and breast cancer. Green tea may also attenuate the risk factors association with the development of atherosclerosis thus reducing the incidence of cardiovascular events and stoke.",
"title": "Can green tea do that? A literature review of the clinical evidence."
},
{
"docid": "MED-4780",
"text": "OBJECTIVE: To examine the association between green tea consumption and tooth loss. METHODS: We analyzed cross-sectional data from the Ohsaki Cohort 2006 Study. Usable self-administered questionnaires about green tea consumption and tooth loss were returned from 25,078 persons (12,019 men and 13,059 women) aged 40 to 64 years in Japan. Multivariate logistic regression analysis was used to calculate odds ratios (ORs) for tooth loss using 3 cut-off points of 10, 20, and 25 teeth relative to each category of green tea consumption. RESULTS: Consumption of > or = 1 cup/day of green tea was significantly associated with decreased odds for tooth loss, and the association appeared to fit a threshold model. In men, the multivariate-adjusted ORs for tooth loss with a cut-off point of <20 teeth associated with different frequencies of green tea consumption were 1.00 (reference) for <1 cup/day, 0.82 (95% CI, 0.74-0.91) for 1-2 cups/day, 0.82 (95% CI, 0.73-0.92) for 3-4 cups/day, and 0.77 (95% CI, 0.66-0.89) for > or = 5 cups/day. The corresponding data for women and the results for cut-off points of 10 and 25 teeth were essentially the same. CONCLUSIONS: The present findings indicate an association of green tea consumption with decreased odds for tooth loss. Copyright 2010 Elsevier Inc. All rights reserved.",
"title": "Association between green tea consumption and tooth loss: cross-sectional results from the Ohsaki Cohort 2006 Study."
},
{
"docid": "MED-5156",
"text": "Tea leaves produce organic compounds that may be involved in the defense of the plants against invading pathogens including insects, bacteria, fungi, and viruses. These metabolites include polyphenolic compounds, the six so-called catechins, and the methyl-xanthine alkaloids caffeine, theobromine, and theophylline. Postharvest inactivation of phenol oxidases in green tea leaves prevents oxidation of the catechins, whereas postharvest enzyme-catalyzed oxidation (fermentation) of catechins in tea leaves results in the formation of four theaflavins as well as polymeric thearubigins. These substances impart the black color to black teas. Black and partly fermented oolong teas contain both classes of phenolic compounds. A need exists to develop a better understanding of the roles of polyphenolic tea compounds in food and medical microbiology. This overview surveys and interprets our present knowledge of activities of tea flavonoids and teas against foodborne and other pathogenic bacteria, virulent protein toxins produced by some of the bacteria, virulent bacteriophages, pathogenic viruses and fungi. Also covered are synergistic, mechanistic, and bioavailability aspects of the antimicrobial effects. Further research is suggested for each of these categories. The herein described findings are not only of fundamental interest, but also have practical implications for nutrition, food safety, and animal and human health.",
"title": "Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas."
},
{
"docid": "MED-3920",
"text": "Green tea is reported to have wide ranging beneficial health outcomes across epidemiological studies, which have been attributed to its flavonoid content. We investigated whether the flavonoid epigallocatechin gallate (EGCG) modulates brain activity and self-reported mood in a double-blind, placebo controlled crossover study. Participants completed baseline assessments of cognitive and cardiovascular functioning, mood and a resting state electroencephalogram (EEG) before and then 120 min following administration of 300 mg EGCG or matched placebo. EGCG administration was associated with a significant overall increase in alpha, beta and theta activity, also reflected in overall EEG activity, more dominant in midline frontal and central regions, specifically in the frontal gyrus and medial frontal gyrus. In comparison to placebo the EGCG treatment also increased self-rated calmness and reduced self rated stress. This pattern of results suggests that participants in the EGCG condition may have been in a more relaxed and attentive state after consuming EGCG. This is in keeping with the widespread consumption of green tea for its purported relaxing/refreshing properties. The modulation of brain function due to EGCG is deserving of further controlled human studies. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Acute neurocognitive effects of epigallocatechin gallate (EGCG)."
},
{
"docid": "MED-4050",
"text": "Green tea is a commonly consumed beverage in Asia and has been suggested to have anti-inflammatory and possible anti-carcinogenic properties in laboratory studies. We sought to examine the association between green tea consumption and risk of breast cancer incidence or recurrence, using all available epidemiologic evidence to date. We conducted a systematic search of five databases and performed a meta-analysis of studies of breast cancer risk and recurrence published between 1998 and 2009, encompassing 5,617 cases of breast cancer. Summary relative risks (RR) were calculated using a fixed effects model, and tests of heterogeneity across combined studies were conducted. We identified two studies of breast cancer recurrence and seven studies of breast cancer incidence. Increased green tea consumption (more than three cups a day) was inversely associated with breast cancer recurrence (Pooled RR = 0.73, 95% CI: 0.56-0.96). An analysis of case-control studies of breast cancer incidence suggested an inverse association with a pooled RR of 0.81 (95% CI: 0.75, 0.88) while no association was found among cohort studies of breast cancer incidence. Combining all studies of breast cancer incidence resulted in significant heterogeneity. Available epidemiologic evidence supports the hypothesis that increased green tea consumption may be inversely associated with risk of breast cancer recurrence. The association between green tea consumption and breast cancer incidence remains unclear based on the current evidence.",
"title": "Green tea consumption and breast cancer risk or recurrence: a meta-analysis."
},
{
"docid": "MED-4468",
"text": "Many constituents present in the human diet may inhibit endogenous formation of N-nitroso compounds (NOC). Studies with human volunteers showed inhibiting effects of intake of ascorbic acid and green tea consumption on nitrosation using the N-nitrosoproline test. The aim of the present study was to evaluate the effects of ascorbic acid and green tea on urinary excretion of carcinogenic N-nitrosodimethylamine (NDMA) and N-nitrosopiperidine (NPIP) in humans. Twenty-five healthy female volunteers consumed a fish meal rich in amines as nitrosatable precursors in combination with intake of nitrate-containing drinking water at the Acceptable Daily Intake level during 7 consecutive days. During 1 week before and after nitrate intake a diet low in nitrate was consumed. Using the same protocol, the effect of two different doses of ascorbic acid (250 mg and 1 g/day) and two different doses of green tea (2 g and 4 g/day) on formation of NDMA and NPIP was studied. Mean nitrate excretion in urine significantly increased from control (76+/-24) to 167+/-25 mg/24 h. Intake of nitrate and fish resulted in a significant increase in mean urinary excretion of NDMA compared with the control weeks: 871+/-430 and 640+/-277 ng/24 h during days 1-3 and 4-7, respectively, compared with 385+/-196 ng/24 h (p<0.0002). Excretion of NPIP in urine was not related to nitrate intake and composition of the diet. Intake of 250 mg and 1 g of ascorbic acid per day resulted in a significant decrease in urinary NDMA excretion during days 4-7 (p=0.0001), but not during days 1-3. Also, consumption of four cups of green tea per day (2 g) significantly decreased excretion of NDMA during days 4-7 (p=0.0035), but not during days 1-3. Surprisingly, consumption of eight cups of green tea per day (4 g) significantly increased NDMA excretion during days 4-7 (p=0.0001), again not during days 1-3. This increase is probably a result of catalytic effects of tea polyphenols on nitrosation, or of another, yet unknown, mechanism. These results suggest that intake of ascorbic acid and moderate consumption of green tea can reduce endogenous NDMA formation.",
"title": "Effect of ascorbic acid and green tea on endogenous formation of N-nitrosodimethylamine and N-nitrosopiperidine in humans."
},
{
"docid": "MED-4097",
"text": "The identification of modifiable lifestyle factors that could reduce the risk of breast cancer is a research priority. Despite the enormous chemo preventive potential of green tea and compelling evidence from animal studies, its role in breast cancer development in humans is still unclear. Part of the uncertainty is related to the relatively small number of epidemiological studies on green tea and breast cancer and that the overall results from case-control studies and prospective cohort studies are discordant. In addition, the mechanisms by which green tea intake may influence risk of breast cancer in humans remains not well studied. We review the human studies that have evaluated the relationship between green tea intake and four biomarkers (sex steroid hormones, mammographic density, insulin-like growth factor, adiponectin) that are believed to be important in breast cancer development. Results from these biomarker studies are also inconclusive. Limitations of human studies and areas of further investigations are discussed.",
"title": "Green Tea and Breast Cancer"
},
{
"docid": "MED-1645",
"text": "BACKGROUND: Tea consumption is associated with decreased cardiovascular risk. Flow-mediated dilatation (FMD) of the brachial artery is related to coronary endothelial function and it is an independent predictor of cardiovascular risk. Black tea has a beneficial effect on endothelial function; the effect, however, of green tea on brachial artery reactivity has not been defined yet. DESIGN AND METHODS: We studied 14 healthy individuals (age 30+/-3 years) with no cardiovascular risk factors except from smoking (50%) on three separate occasions on which they took: (a) 6 g of green tea, (b) 125 mg of caffeine (the amount contained in 6 g of tea), or (c) hot water. FMD of the brachial artery was measured before each intervention and 30, 90, and 120 min afterward. High-sensitivity C-reactive protein, interleukins 6 (Il-6) and 1b (Il-1b), total plasma antioxidative capacity, and total plasma oxidative status/stress were measured at baseline and at 120 min after each intervention. RESULTS: Resting and hyperemic brachial artery diameter did not change either with tea or with caffeine. FMD increased significantly with tea (by 3.69%, peak at 30 min, P<0.02), whereas it did not change significantly with caffeine (increase by 1.72%, peak at 30 min, P=NS). Neither tea nor caffeine had any effect on high-sensitivity C-reactive protein, Il-6, Il-1b, total plasma antioxidative capacity, or total plasma oxidative status/stress. CONCLUSION: Green tea consumption has an acute beneficial effect on endothelial function, assessed with FMD of the brachial artery, in healthy individuals. This may be involved in the beneficial effect of tea on cardiovascular risk.",
"title": "The acute effect of green tea consumption on endothelial function in healthy individuals."
},
{
"docid": "MED-4098",
"text": "To investigate effects of dietary mushrooms and joint effects of mushrooms and green tea on breast cancer, a case-control study was conducted in southeast China in 2004-2005. The incident cases were 1,009 female patients aged 20-87 years with histologically confirmed breast cancer. The 1,009 age-matched controls were healthy women randomly recruited from outpatient breast clinics. Information on frequency and quantity of dietary intake of mushrooms and tea consumption, usual diet, and lifestyle were collected by face-to-face interview using a validated and reliable questionnaire. Compared with nonconsumers, the Odds ratios (Ors) were 0.36 (95% CI = 0.25-0.51) and 0.53 (0.38-0.73) for daily intake of >or=10 g fresh mushrooms and >or=4 g dried mushrooms, based on multivariate logistic regression analysis adjusting for established and potential confounders. There were dose-response relationships with significant tests for trend (p < 0.001). The inverse association was found in both pre- and postmenopausal women. Compared with those who consumed neither mushrooms nor green tea, the ORs were 0.11 (0.06-0.20) and 0.18 (0.11-0.29) for daily high intake of fresh and dried mushrooms combined with consuming beverages made from >or=1.05 g dried green tea leaves per day. The corresponding linear trends were statistically significant for joint effect (p < 0.001). We conclude that higher dietary intake of mushrooms decreased breast cancer risk in pre- and postmenopausal Chinese women and an additional decreased risk of breast cancer from joint effect of mushrooms and green tea was observed. More research is warranted to examine the effects of dietary mushrooms and mechanism of joint effects of phytochemicals on breast cancer.",
"title": "Dietary intakes of mushrooms and green tea combine to reduce the risk of breast cancer in Chinese women."
},
{
"docid": "MED-4329",
"text": "We investigated clinical efficacy of green tea extracts (polyphenon E; poly E and (-)-epigallocatechin-3-gallate [EGCG]) delivered in a form of ointment or capsule in patients with human papilloma virus (HPV) infected cervical lesions. Fifty-one patients with cervical lesions (chronic cervicitis, mild dysplasia, moderate dysplasia and severe dysplasia) were divided into four groups, as compared with 39 untreated patients as a control. Poly E ointment was applied locally to 27 patients twice a week. For oral delivery, a 200 mg of poly E or EGCG capsule was taken orally every day for eight to 12 weeks. In the study, 20 out of 27 patients (74%) under poly E ointment therapy showed a response. Six out of eight patients under poly E ointment plus poly E capsule therapy (75%) showed a response, and three out of six patients (50%) under poly E capsule therapy showed a response. Six out of 10 patients (60%) under EGCG capsule therapy showed a response. Overall, a 69% response rate (35/51) was noted for treatment with green tea extracts, as compared with a 10% response rate (4/39) in untreated controls (P<0.05). Thus, the data collected here demonstrated that green tea extracts in a form of ointment and capsule are effective for treating cervical lesions, suggesting that green tea extracts can be a potential therapy regimen for patients with HPV infected cervical lesions.",
"title": "Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions."
},
{
"docid": "MED-1844",
"text": "Total aluminum, chromium, copper, iron, manganese, and nickel were determined in black tea, green tea, Hibiscus sabdariffa, and Ilex paraguariensis (mate) by electrothermal atomic absorption spectrometry after nitric/perchloric acid digestion. In each case, one ground sample of commercially available leafy material was prepared and three 0.5-g subsamples were run in parallel. The infusions were also analyzed and the percentage of each element leached into the liquor was evaluated. The obtained results indicated that hibiscus and mate contained lower levels of aluminum (272+/-19 microg/g and 369+/-22 microg/g, respectively) as referred to black tea (759+/-31 microg/g) or green tea (919micro29 microg/g) and suggested that mate drinking could be a good dietary source of essential micronutrient manganese (total content 2223+/-110 microg/g, 48.1% leached to the infusion). It was also found that the infusion of hibiscus could supply greater amounts of iron (111+/-5 microg/g total, 40.5% leached) and copper (5.9+/-0.3 microg/g total, 93.4% leached) as compared to other infusions. Moreover, it was found that the percentage of element leached to the infusion was strongly related to the tannins content in the beverage (correlation coefficients > 0.82 with the exception for nickel); for lower tannins level, better leaching was observed.",
"title": "Determination of total aluminum, chromium, copper, iron, manganese, and nickel and their fractions leached to the infusions of black tea, green tea..."
},
{
"docid": "MED-3554",
"text": "A great deal of effort is now being devoted to the development of new drugs that hopefully will control the spread of inoperable cancer by safely inhibiting tumor-evoked angiogenesis. However, there is growing evidence that certain practical nutritional measures have the potential to slow tumor angiogenesis, and it is reasonable to anticipate that, by combining several measures that work in distinct but complementary ways to impede the angiogenic process, a clinically useful 'multifocal angiostatic therapy' (MAT) might be devised. Several measures which might reasonably be included in such a protocol are discussed below, and include: a low-fat, low-glycemic index vegan diet, which may down-regulate the systemic IGF-I activity that supports angiogenesis; supplemental omega-3-rich fish oil, which has been shown to inhibit endothelial expression of Flk-1, a functionally crucial receptor for VEGF, and also can suppress tumor production of pro-angiogenic eicosanoids; high-dose selenium, which has recently been shown to inhibit tumor production of VEGF; green tea polyphenols, which can suppress endothelial responsiveness to both VEGF and fibroblast growth factor; and high-dose glycine, whose recently reported angiostatic activity may reflect inhibition of endothelial cell mitosis, possibly mediated by activation of glycine-gated chloride channels. In light of evidence that tumor-evoked angiogenesis has a high requirement for copper, copper depletion may have exceptional potential as an angiostatic measure, and is most efficiently achieved with the copper-chelating drug tetrathiomolybdate. If logistical difficulties make it difficult to acquire this experimental drug, high-dose zinc supplementation can achieve a slower depletion of the body's copper pool, and in any case can be used as maintenance therapy to maintain an adequate level of copper depletion. A provisional protocol is offered for a nutritionally based MAT entailing a vegan diet and supplemental intakes of fish oil, selenium, green tea polyphenols, glycine, and zinc. Inasmuch as cox-2 is overexpressed in many cancers, and cAMP can boost tumor production of various angiogenic factors as well as autogenous growth factors, adjunctive use of cox-2-specific NSAIDS may be warranted in some cases.",
"title": "A wholly nutritional 'multifocal angiostatic therapy' for control of disseminated cancer."
},
{
"docid": "MED-1853",
"text": "PURPOSE: To measure the pH, titratable acidity, fluoride concentration and erosive potential of brewed teas. METHODS: Bag teas were purchased to represent black, green, citrus, fruity, and floral tea flavors from Tulsi, Bigelow, HyVee, Tazo, and Yogi brands and brewed (1 bag/240 ml) in boiling water for 3 minutes. The pH, titratable acidity, and fluoride concentrations were measured. Following these measurements, a representative tea from each flavor was selected for investigation of erosion potential. Six extracted human molars were randomly assigned to each tea. Teeth were painted with fingernail polish to expose a 1 x 4 mm window and then soaked in tea for a total of 25 hours with teas refreshed every 5 hours. Teeth were then sectioned using a microtome and photographed using a polarized light microscope. Lesion depths (i.e., eroded surfaces) were measured using Image Pro Plus software. Differences in physiochemical properties and lesion depths between beverages were investigated using one-way ANOVA with post-hoc Tukey's HSD test. Relationships among lesion depths and physiochemical properties were evaluated using the Pearson correlation test. RESULTS: pH, titratable acidity and fluoride concentrations differed between tea flavors (P < 0.05) and between brands (P < 0.05). Lesion depths produced by the citrus tea (83.1 +/- 10.3 microm) were greater than those produced by the fruity tea (56.5 +/- 6.1 microm); both teas produced greater depths than black (30.1 +/- 7.4 microm), floral (25.0 +/- 3.2 microm) or green (22.3 +/- 6.3 microm) teas (P < 0.05). pH (r = -0.96; P = 0.009) was inversely and titratable acidity (r = 0.97; P = 0.006) was positively associated with lesion depths.",
"title": "Erosive potentials of brewed teas."
},
{
"docid": "MED-2677",
"text": "Population differences in age-related diseases and cancer could stem from differences in diet. To characterize DNA strand-breaking activities in selected foods/beverages, flavorings, and some of their constituent chemicals, we used p53R cells, a cellular assay sensitive to such breaks. Substances testing positive included reference chemicals: quinacrine (peak response, 51X) and etoposide (33X); flavonoids: EGCG (19X), curcumin (12X), apigenin (9X), and quercetin (7X); beverages: chamomile (11X), green (21X), and black tea (26X) and coffee (3 to 29X); and liquid smoke (4 to 28X). Damage occurred at dietary concentrations: etoposide near 5 μg/ml produced responses similar to a 1:1000 dilution of liquid smoke, a 1:20 dilution of coffee, and a 1:5 dilution of tea. Pyrogallol-related chemicals and tannins are present in dietary sources and individually produced strong activity: pyrogallol (30X), 3-methoxycatechol (25X), gallic acid (21X), and 1,2,4-benzenetriol (21X). From structure-activity relationships, high activities depended on specific orientations of hydroxyls on the benzene ring. Responses accompanied cellular signals characteristic of DNA breaks such as H2AX phosphorylation. Breaks were also directly detected by comet assay. Cellular toxicological effects of foods and flavorings could guide epidemiologic and experimental studies of potential disease risks from DNA strand-breaking chemicals in diets.",
"title": "Biological Clues to Potent DNA-Damaging Activities in Food and Flavoring"
},
{
"docid": "MED-1627",
"text": "Sweetened beverages, coffee, and tea are the most consumed non-alcoholic beverages and may have important health consequences. We prospectively evaluated the consumption of various types of beverages assessed in 1995–1996 in relation to self-reported depression diagnosis after 2000 among 263,923 participants of the NIH-AARP Diet and Health Study. Odds ratios (OR) and 95% confidence intervals (CI) were derived from multivariate logistic regressions. The OR (95% CI) comparing ≥4 cans/cups per day with none were 1.30 (95%CI: 1.17–1.44) for soft drinks, 1.38 (1.15–1.65) for fruit drinks, and 0.91 (0.84–0.98) for coffee (all P for trend<0.0001). Null associations were observed for iced-tea and hot tea. In stratified analyses by drinkers of primarily diet versus regular beverages, the ORs were 1.31 (1.16–1.47) for diet versus 1.22 (1.03–1.45) for regular soft drinks, 1.51 (1.18–1.92) for diet versus 1.08 (0.79–1.46) for regular fruit drinks, and 1.25 (1.10–1.41) for diet versus 0.94 (0.83–1.08) for regular sweetened iced-tea. Finally, compared to nondrinkers, drinking coffee or tea without any sweetener was associated with a lower risk for depression, adding artificial sweeteners, but not sugar or honey, was associated with higher risks. Frequent consumption of sweetened beverages, especially diet drinks, may increase depression risk among older adults, whereas coffee consumption may lower the risk.",
"title": "Sweetened Beverages, Coffee, and Tea and Depression Risk among Older US Adults"
},
{
"docid": "MED-1109",
"text": "BACKGROUND: The distinctive racial/ethnic and geographic distribution of multiple myeloma (MM) suggests that both family history and environmental factors may contribute to its development. METHODS: A hospital-based case-control study consisting of 220 confirmed MM cases and 220 individually matched patient controls, by sex, age and hospital was carried out at 5 major hospitals in Northwest China. A questionnaire was used to obtain information on demographics, family history, and the frequency of food items consumed. RESULTS: Based on multivariate analysis, a significant association between the risk of MM and family history of cancers in first degree relatives was observed (OR=4.03, 95% CI: 2.50-6.52). Fried food, cured/smoked food, black tea, and fish were not significantly associated with the risk of MM. Intake of shallot and garlic (OR=0.60, 95% CI: 0.43-0.85), soy food (OR=0.52, 95% CI: 0.36-0.75) and green tea (OR=0.38, 95% CI: 0.27-0.53) was significantly associated with a reduced risk of MM. In contrast, intake of brined vegetables and pickle was significantly associated with an increased risk (OR=2.03, 95% CI: 1.41-2.93). A more than multiplicative interaction on the decreased risk of MM was found between shallot/garlic and soy food. CONCLUSION: Our study in Northwest China found an increased risk of MM with a family history of cancer, a diet characterized by low consumption of garlic, green tea and soy foods, and high consumption of pickled vegetables. The effect of green tea in reducing the risk of MM is an interesting new finding which should be further confirmed. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Risk factors for multiple myeloma: a hospital-based case-control study in Northwest China."
},
{
"docid": "MED-5078",
"text": "In this study, solid fermentation of steamed black soybean with various GRAS (Generally recognized as safe) filamentious-fungi including Aspergillus awamori, Aspergillus oryzae BCRC 30222, Aspergillus sojae BCRC 30103, Rhizopus azygosporus BCRC 31158 and Rhizopus sp. No. 2 was performed. Mutagenicity and antimutagenicity of the methanol extracts of unfermented and fermented steamed black soybeans against 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen and Benzo[a]pyrene (B[a]P), an indirect mutagen, on Salmonella Typhimurium TA100 and TA 98, were examined. The methanol extracts of unfermented and fermented steamed black soybeans show no mutagenic activity for either test strains at the doses tested. The extracts inhibited mutagenesis by either 4-NQO or B[a]P in S. Typhimurium TA100 and TA98. Fermentation with fungi also enhanced the antimutagenic effect of black soybean while the antimutagenic effect of the fermented black soybeans extract varied with the starter organism, mutagen, and test strain of S. Typhimurium examined. Generally, the extracts of A. awamori-fermented black soybean exhibited the highest antimutagenic effect. With strain TA100, the inhibitory effects of 5.0 mg of A. awamori-fermented black soybean extract per plate on the mutagenic effects of 4-NQO and B[a]P were 92% and 89%, respectively, while the corresponding rates for extract of unfermented were 41% and 63%, respectively. With strain 98, the inhibition rates were 94 and 81% for the fermented bean extract and 58% and 44% for the unfermented bean extracts. Testing of extracts prepared from black soybean by A. awamori at temperatures 25, 30 and 35 degrees C and for times of 1-5 days revealed that, generally, the extract prepared from beans fermented at 30 degrees C for 3 days exhibited the greatest inhibition against the mutagenic effects of 4-NQO and B[a]P.",
"title": "Mutagenic and antimutagenic effects of methanol extracts of unfermented and fermented black soybeans."
},
{
"docid": "MED-945",
"text": "We assess the evidence for health benefits of three commonly consumed plant food supplements (PFS), green tea, isoflavone and aloe vera, based on published systematic reviews of randomised controlled trials (RCTs). Whilst the potential benefits of green tea have been reported in a wide range of health areas, it is only in the area of the metabolic syndrome that the number of RCTs is approaching sufficient to judge such efficacy. Isoflavone supplements are widely used, and RCTs indicate that they affect bone resorption at lower doses in postmenopausal women undergoing estrogen-related bone loss, but this is only translated to attenuation of bone loss at higher doses of isoflavones. A systematic review on RCTs concluded that the effects of isoflavones on hot flashes in postmenopausal women were highly variable and no conclusions could be drawn. Despite the popularity of aloe vera as a PFS, the evaluation of its efficacy as a coadjuvant therapy for certain metabolic or digestive pathologies remains scarce; it constitutes a typical example of a naturally occurring ingredient whose efficacy in topical applications presupposes its efficacy in systemic applications. Nevertheless, its possible toxic effects on oral consumption call for caution in its utility as a PFS. Since 2007, efficacy evaluation of PFS in Europe has been covered by European Union Nutrition and Health Claims legislation. The European Food Safety Authority has adopted an approach relying on RCTs, while medicinal effects are accepted based on traditional use. In general, there are insufficient RCTs for claims to be made, and conclusive results on PFS should be obtained in the future by conducting studies with more homogeneous populations, by using supplements with optimised and measured bioavailability, and by conducting larger RCTs.",
"title": "Review of the efficacy of green tea, isoflavones and aloe vera supplements based on randomised controlled trials."
},
{
"docid": "MED-5160",
"text": "Pine needles (Pinus densiflora Siebold et Zuccarini) have long been used as a traditional health-promoting medicinal food in Korea. To investigate their potential anticancer effects, antioxidant, antimutagenic, and antitumor activities were assessed in vitro and/or in vivo. Pine needle ethanol extract (PNE) significantly inhibited Fe(2+)-induced lipid peroxidation and scavenged 1,1-diphenyl- 2-picrylhydrazyl radical in vitro. PNE markedly inhibited mutagenicity of 2-anthramine, 2-nitrofluorene, or sodium azide in Salmonella typhimurium TA98 or TA100 in Ames tests. PNE exposure effectively inhibited the growth of cancer cells (MCF-7, SNU-638, and HL-60) compared with normal cell (HDF) in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In in vivo antitumor studies, freeze-dried pine needle powder supplemented (5%, wt/wt) diet was fed to mice inoculated with Sarcoma-180 cells or rats treated with mammary carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA, 50 mg/kg body weight). Tumorigenesis was suppressed by pine needle supplementation in the two model systems. Moreover, blood urea nitrogen and aspartate aminotransferase levels were significantly lower in pine needle-supplemented rats in the DMBA-induced mammary tumor model. These results demonstrate that pine needles exhibit strong antioxidant, antimutagenic, and antiproliferative effects on cancer cells and also antitumor effects in vivo and point to their potential usefulness in cancer prevention.",
"title": "Antioxidant, antimutagenic, and antitumor effects of pine needles (Pinus densiflora)."
},
{
"docid": "MED-4413",
"text": "Estimation of total antioxidant intake is the first step to investigate the protective effects of antioxidants on oxidative stress-mediated disease. The present study was designed to develop an algorithm to estimate total antioxidant capacity (TAC) of the US diet. TAC of individual antioxidants and 50 popular antioxidant-rich food items in the US diet were determined by 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) assay and the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Theoretical TAC of foods was calculated as the sum of individual antioxidant capacities of compounds. The top 10 TAC food items in the US diet according to standard serving size were blueberry > plum > green tea > strawberry > green tea (decaffeinated) > red wine > grape juice > black tea > cherry > grape. Major contributors to TAC were the total phenolic content (r = 0.952, P < 0.001) and flavonoid content (r = 0.827, P < 0.001) of 50 foods. Theoretical TAC was positively correlated to experimental TAC of 50 foods determined by the ABTS assay (r = 0.833, P < 0.001) and the DPPH assay (r = 0.696, P < 0.001), and to TAC from the USDA database for the oxygen radical absorbance capacity (r = 0.484, P = 0.001, n = 44). The TAC database of the US diet has been established and validated. In future studies, TAC of the US diet can be linked to biomarkers of chronic disease.",
"title": "Development and validation of an algorithm to establish a total antioxidant capacity database of the US diet."
},
{
"docid": "MED-4776",
"text": "Tea (Camellia sinensis, Theaceae) and tea polyphenols have been studied for the prevention of chronic diseases, including obesity. Obesity currently affects >20% of adults in the United States and is a risk factor for chronic diseases such as type II diabetes, cardiovascular disease, and cancer. Given this increasing public health concern, the use of dietary agents for the prevention of obesity would be of tremendous benefit. Whereas many laboratory studies have demonstrated the potential efficacy of green or black tea for the prevention of obesity, the underlying mechanisms remain unclear. The results of human intervention studies are mixed and the role of caffeine has not been clearly established. Finally, there is emerging evidence that high doses of tea polyphenols may have adverse side effects. Given that the results of scientific studies on dietary components, including tea polyphenols, are often translated into dietary supplements, understanding the potential toxicities of the tea polyphenols is critical to understanding their potential usefulness in preventing obesity. In this review, we will critically evaluate the evidence for the prevention of obesity by tea, discuss the relevance of proposed mechanisms in light of tea polyphenol bioavailability, and review the reports concerning the toxic effects of high doses of tea polyphenols and the implication that this has for the potential use of tea for the prevention of obesity. We hope that this review will expose areas for further study and encourage research on this important public health issue.",
"title": "Laboratory, Epidemiological, and Human Intervention Studies Show That Tea (Camellia sinensis) May Be Useful in the Prevention of Obesity"
},
{
"docid": "MED-4194",
"text": "In this review recent publications are cited for a number of antimutagens. The molecules surveyed are potential or proven \"desmutagens\" or \"interceptors.\" These are biologically prevalent or synthetic molecules that are most often small metabolites proficient in binding to, or reacting with, mutagenic chemicals and free radicals. Many of this class of \"blocking agents\" are \"soft\" and \"hard\" nucleophiles with consequently varying abilities to react with particular classes of electrophiles, the major classes of direct-acting mutagens. Although they serve as a first line of defense against mutagens and carcinogens, many interceptor molecules are under-investigated with regard to their spectra of activity and their possible relevance to prophylaxis or treatment of human disease states.",
"title": "Antimutagens and anticarcinogens: a survey of putative interceptor molecules."
},
{
"docid": "MED-1850",
"text": "A microwave-assisted acid digestion procedure coupled with a graphite furnace atomic absorption method has been applied in the determination of aluminum (Al) in urine to verify the correlation of free forms of Al in tea infusions and urinary excretion of Al. Significant urinary Al excretion has been found in 24-h urine of four volunteers after tea drinking. However, the difference in amount of Al excretion in urine between the consumption of Oolong (black tea) and Long-Jin (green tea), each of them with unique Al contents and species, was not significant. These findings indicated that the high levels of free Al species in tea infusions did not result in significant change in urinary excretion of the metal, possibly owing to the transformation by ligands present in food and the gastrointestinal tract (GIT). However, it could not be assumed that there was no big difference in absorption of the metal in the human body if fractions of consumed Al retained in the body or excreted by bile or feces were considered.",
"title": "Urine levels of aluminum after drinking tea."
},
{
"docid": "MED-4587",
"text": "A polyphenol-rich (P-R) juice drink was developed as a potential approach to increase intake of dietary polyphenols. Analysis of the beverage by HPLC with PDA, fluorescence, and MS detection facilitated the identification/partial identification of 40 flavonoids and related phenolic compounds. The main constituents were (-)-epigallocatechin and other green tea flavan-3-ols, phloretin-2'-O-glucoside, gallic acid, hesperetin-7-O-rutinoside, 5-O-caffeoylquinic acid, and procyanidins, with trace levels of several flavonols and purple grape juice anthocyanins also being present. Healthy human subjects (n = 10) consumed 350 mL of the P-R juice drink, after which plasma and urine samples were collected over a 0-24 h period. HPLC-MS analysis identified 13 metabolites in plasma and a further 20 in urine. Qualitatively, the profiles of the glucuronide, sulfated, and methylated metabolites were very similar to those detected in earlier investigations when the main components in the juice drink were consumed separately in feeding studies with coffee, green tea, orange juice, and apple cider.",
"title": "Identification of metabolites in human plasma and urine after consumption of a polyphenol-rich juice drink."
}
] |
167
|
Bariatric surgery leads to positive outcomes in mental health.
|
[
{
"docid": "18872233",
"text": "IMPORTANCE Bariatric surgery is associated with sustained weight loss and improved physical health status for severely obese individuals. Mental health conditions may be common among patients seeking bariatric surgery; however, the prevalence of these conditions and whether they are associated with postoperative outcomes remains unknown. OBJECTIVE To determine the prevalence of mental health conditions among bariatric surgery candidates and recipients, to evaluate the association between preoperative mental health conditions and health outcomes following bariatric surgery, and to evaluate the association between surgery and the clinical course of mental health conditions. DATA SOURCES We searched PubMed, MEDLINE on OVID, and PsycINFO for studies published between January 1988 and November 2015. Study quality was assessed using an adapted tool for risk of bias; quality of evidence was rated based on GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. FINDINGS We identified 68 publications meeting inclusion criteria: 59 reporting the prevalence of preoperative mental health conditions (65,363 patients) and 27 reporting associations between preoperative mental health conditions and postoperative outcomes (50,182 patients). Among patients seeking and undergoing bariatric surgery, the most common mental health conditions, based on random-effects estimates of prevalence, were depression (19% [95% CI, 14%-25%]) and binge eating disorder (17% [95% CI, 13%-21%]). There was conflicting evidence regarding the association between preoperative mental health conditions and postoperative weight loss. Neither depression nor binge eating disorder was consistently associated with differences in weight outcomes. Bariatric surgery was, however, consistently associated with postoperative decreases in the prevalence of depression (7 studies; 8%-74% decrease) and the severity of depressive symptoms (6 studies; 40%-70% decrease). CONCLUSIONS AND RELEVANCE Mental health conditions are common among bariatric surgery patients-in particular, depression and binge eating disorder. There is inconsistent evidence regarding the association between preoperative mental health conditions and postoperative weight loss. Moderate-quality evidence supports an association between bariatric surgery and lower rates of depression postoperatively.",
"title": "Mental Health Conditions Among Patients Seeking and Undergoing Bariatric Surgery: A Meta-analysis."
}
] |
[
{
"docid": "43220289",
"text": "Extreme obesity is associated with severe psychiatric and somatic comorbidity and impairment of psychosocial functioning. Bariatric surgery is the most effective treatment not only with regard to weight loss but also with obesity-associated illnesses. Health-related psychological and psychosocial variables have been increasingly considered as important outcome variables of bariatric surgery. However, the long-term impact of bariatric surgery on psychological and psychosocial functioning is largely unclear. The aim of this study was to evaluate the relationship between the course of weight and psychological variables including depression, anxiety, health-related quality of life (HRQOL), and self-esteem up to 4 years after obesity surgery. By standardized questionnaires prior to (T1) and 1 year (T2), 2 years (T3), and 4 years (T4) after surgery, 148 patients (47 males (31.8 %), 101 females (68.2 %), mean age 38.8 ± 10.2 years) were assessed. On average, participants lost 24.6 % of their initial weight 1 year after surgery, 25.1 % after 2 years, and 22.3 % after 4 years. Statistical analysis revealed significant improvements in depressive symptoms, physical dimension of quality of life, and self-esteem with peak improvements 1 year after surgery. These improvements were largely maintained. Significant correlations between weight loss and improvements in depression, physical aspects of HRQOL (T2, T3, and T4), and self-esteem (T3) were observed. Corresponding to the considerable weight loss after bariatric surgery, important aspects of mental health improved significantly during the 4-year follow-up period. However, parallel to weight regain, psychological improvements showed a slow but not significant decline over time.",
"title": "Psychological Outcome 4 Years after Restrictive Bariatric Surgery"
},
{
"docid": "19071857",
"text": "Pre-operative psychological assessment is recommended by international guidelines for bariatric surgery candidates. Thereby, service teams caring for bariatric patients should include at least one mental health provider (e.g., a psychologist or psychiatrist). The objective of this study was to evaluate the psychology and psychiatry resources and practices in the 37 specialized obesity centers (CSOs) created by the French Ministry of Health. CSO coordinators were contacted by e-mail to collect general information on the centers (e.g., number of bariatric operations). Secondly, psychologists and psychiatrists of each center completed an anonymous questionnaire assessing their professional practices and their organization of care pathways. The vast majority of CSO coordinators (81%, n = 26/32) answered our survey. These results show significant differences and shortages in terms of the psychology/psychiatry resources available. Most of the psychologists (n = 26/31) and psychiatrists (n = 10/10) stated that they systematically meet new patients only before surgery (56%) or both before and after the operation (30%); however, some psychologists and psychiatrists (14%) do not systematically meet all the patients (before and/or after surgery). Nevertheless, all the professionals provide psychology assessments, and about 75% of them offer a psychological follow-up, indicating a similarity regarding the practices of psychologists and psychiatrists. Our results highlight the place of psychological/psychiatric evaluations in French CSOs and emphasize the absence of mental health providers in several of these services. Post-operative psychological follow-up is not usually provided. It would be appropriate to create clear recommendations for post-operative psychological or psychiatric long-term follow-up.",
"title": "Mental Health Support Provided Throughout the Bariatric Surgery Clinical Pathway in French Specialized Care Centers for Obesity"
},
{
"docid": "5824985",
"text": "BACKGROUND Bariatric surgery is becoming a more widespread treatment for obesity. Comprehensive evidence of the long-term effects of contemporary surgery on a broad range of clinical outcomes in large populations treated in routine clinical practice is lacking. The objective of this study was to measure the association between bariatric surgery, weight, body mass index, and obesity-related co-morbidities. METHODS AND FINDINGS This was an observational retrospective cohort study using data from the United Kingdom Clinical Practice Research Datalink. All 3,882 patients registered in the database and with bariatric surgery on or before 31 December 2014 were included and matched by propensity score to 3,882 obese patients without surgery. The main outcome measures were change in weight and body mass index over 4 y; incident diagnoses of type 2 diabetes mellitus (T2DM), hypertension, angina, myocardial infarction (MI), stroke, fractures, obstructive sleep apnoea, and cancer; mortality; and resolution of hypertension and T2DM. Weight measures were available for 3,847 patients between 1 and 4 mo, 2,884 patients between 5 and 12 mo, and 2,258 patients between 13 and 48 mo post-procedure. Bariatric surgery patients exhibited rapid weight loss for the first four postoperative months, at a rate of 4.98 kg/mo (95% CI 4.88-5.08). Slower weight loss was sustained to the end of 4 y. Gastric bypass (6.56 kg/mo) and sleeve gastrectomy (6.29 kg/mo) were associated with greater initial weight reduction than gastric banding (2.77 kg/mo). Protective hazard ratios (HRs) were detected for bariatric surgery for incident T2DM, 0.68 (95% CI 0.55-0.83); hypertension, 0.35 (95% CI 0.27-0.45); angina, 0.59 (95% CI 0.40-0.87);MI, 0.28 (95% CI 0.10-0.74); and obstructive sleep apnoea, 0.55 (95% CI 0.40-0.87). Strong associations were found between bariatric surgery and the resolution of T2DM, with a HR of 9.29 (95% CI 6.84-12.62), and between bariatric surgery and the resolution of hypertension, with a HR of 5.64 (95% CI 2.65-11.99). No association was detected between bariatric surgery and fractures, cancer, or stroke. Effect estimates for mortality found no protective association with bariatric surgery overall, with a HR of 0.97 (95% CI 0.66-1.43). The data used were recorded for the management of patients in primary care and may be subject to inaccuracy, which would tend to lead to underestimates of true relative effect sizes. CONCLUSIONS Bariatric surgery as delivered in the UK healthcare system is associated with dramatic weight loss, sustained at least 4 y after surgery. This weight loss is accompanied by substantial improvements in pre-existing T2DM and hypertension, as well as a reduced risk of incident T2DM, hypertension, angina, MI, and obstructive sleep apnoea. Widening the availability of bariatric surgery could lead to substantial health benefits for many people who are morbidly obese.",
"title": "Bariatric Surgery in the United Kingdom: A Cohort Study of Weight Loss and Clinical Outcomes in Routine Clinical Care."
},
{
"docid": "29022271",
"text": "Psychosocial factors have significant potential to affect long-term outcomes of bariatric surgery, including emotional adjustment, adherence to the recommended postoperative lifestyle regimen, weight loss outcomes, and co-morbidity improvement and or resolution. Thus, it is recommended that bariatric behavioral health clinicians with specialized knowledge and experience be involved in the evaluation and care of patients both before and after surgery. The evaluating clinician plays a number of important roles in the multidisciplinary treatment of the bariatric patient. Central among these is the role of identifying factors that may pose challenges to optimal surgical outcome and providing recommendations to the patient and bariatric team on how to address these issues. This document outlines recommendations for the psychosocial evaluation of bariatric surgery patients, appropriate qualifications of those conducting these evaluations, communication of evaluation results and suggested treatment plan, and the extension of behavioral healthcare of the bariatric patient to the entire span of the surgical and postsurgical process.",
"title": "Recommendations for the presurgical psychosocial evaluation of bariatric surgery patients."
},
{
"docid": "7627167",
"text": "BACKGROUND The objective of this study was to evaluate the effectiveness of a brief, 4-session cognitive behavioral, group psychotherapy for binge eating among bariatric surgery candidates at an academic medical center. Binge eating behaviors have been linked to poorer outcomes among bariatric surgery patients, and binge eating disorder have be considered a contraindication in surgery programs, some of which have mandated preoperative binge eating treatment. However, no previous studies have examined whether a preoperative binge eating intervention could successfully reduce binge eating behaviors among severely obese bariatric surgery candidates. METHODS A total of 243 bariatric surgery candidates completed a brief cognitive behavioral group treatment for binge eating behaviors and were administered the Binge Eating Scale and reported the number of weekly binge eating episodes at the initial psychological evaluation and again after the group sessions. The study used a pre-post intervention design. RESULTS The results suggested significant reductions in both binge eating behaviors and cognitions and binge eating episodes after the group intervention. The intervention's effectiveness did not differ according to gender or ethnicity (black versus white). CONCLUSION A brief cognitive behavioral intervention can reduce binge eating behaviors among bariatric surgery candidates. Given the potential influence of binge eating on outcomes, bariatric surgery programs could benefit by treating binge eating before surgery.",
"title": "Brief, four-session group CBT reduces binge eating behaviors among bariatric surgery candidates."
},
{
"docid": "40949706",
"text": "Obesity affects 32% of adults in the USA. Surgery generates substantial weight loss, but 20–30% fails to achieve successful weight loss. Our objective was to identify preoperative psychosocial factors associated with weight loss following bariatric surgery. We performed a literature search of PubMed® and the Cochrane Database of Reviews of Effectiveness between 1988 and April 2010. Articles were screened for bariatric surgery and weight loss if they included a preoperative predictor of weight loss: body mass index (BMI), preoperative weight loss, eating disorders, or psychiatric disorder/substance abuse. One thousand seven titles were reviewed, 534 articles screened, and 115 included in the review. Factors that may be positively associated with weight loss after surgery include mandatory preoperative weight loss (7 of 14 studies with positive association). Factors that may be negatively associated with weight loss include preoperative BMI (37 out of 62 studies with negative association), super-obesity (24 out of 33 studies), and personality disorders (7 out of 14 studies). Meta-analysis revealed a decrease of 10.1% excess weight loss (EWL) for super-obese patients (95% confidence interval (CI) [3.7–16.5%]), though there was significant heterogeneity in the meta-analysis, and an increase of 5.9% EWL for patients with binge eating at 12 months after surgery (95% CI [1.9–9.8%]). Further studies are necessary to investigate whether preoperative factors can predict a clinically meaningful difference in weight loss after bariatric surgery. The identification of predictive factors may improve patient selection and help develop interventions targeting specific needs of patients.",
"title": "Preoperative Predictors of Weight Loss Following Bariatric Surgery: Systematic Review"
},
{
"docid": "31612088",
"text": "Efforts to improve the outcomes of patients with mental illness often have involved incorporating the skills of a variety of health care professionals into collaborative care models. For over 30 years, clinical pharmacists have contributed to these care models in capacities ranging from educator to consultant to provider. This systematic review evaluates the quantity and quality of medical literature examining the impact of pharmacists in mental health from 1972-2003. Although we identified approximately 35 publications describing the roles of clinical pharmacists in this regard, only 16 were of sufficient scientific rigor to permit evaluation and comparison. The 16 studies were divided equally between inpatient and outpatient settings and were conducted in a variety of health care organizations (e.g., Veterans Administration, health maintenance organizations, community mental health clinics, and nursing homes). Nine of the studies examined the role of pharmacists in providing treatment recommendations and patient education, five featured pharmacists as providers (with prescriptive authority), and the remaining two described the impact pharmacists have in delivering education to the psychiatric staff. Six of the 16 studies were prospective, but only three of these incorporated a randomization procedure for patients or facilities. Collectively, the results of the 16 studies were positive, demonstrating improvements in outcomes, prescribing practices, patient satisfaction, and resource use. Unfortunately, most of the investigations were small, and significant limitations in study design limited further comparison. Given the long history and anecdotal success of pharmacists in mental health care settings, additional multicenter cost-effectiveness trials are warranted to further support the role of the psychiatric pharmacist.",
"title": "Evaluating the impact of pharmacists in mental health: a systematic review."
},
{
"docid": "8529693",
"text": "In this paper we review the associations between maternal and child undernutrition with human capital and risk of adult diseases in low-income and middle-income countries. We analysed data from five long-standing prospective cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa and noted that indices of maternal and child undernutrition (maternal height, birthweight, intrauterine growth restriction, and weight, height, and body-mass index at 2 years according to the new WHO growth standards) were related to adult outcomes (height, schooling, income or assets, offspring birthweight, body-mass index, glucose concentrations, blood pressure). We undertook systematic reviews of studies from low-income and middle-income countries for these outcomes and for indicators related to blood lipids, cardiovascular disease, lung and immune function, cancers, osteoporosis, and mental illness. Undernutrition was strongly associated, both in the review of published work and in new analyses, with shorter adult height, less schooling, reduced economic productivity, and--for women--lower offspring birthweight. Associations with adult disease indicators were not so clear-cut. Increased size at birth and in childhood were positively associated with adult body-mass index and to a lesser extent with blood pressure values, but not with blood glucose concentrations. In our new analyses and in published work, lower birthweight and undernutrition in childhood were risk factors for high glucose concentrations, blood pressure, and harmful lipid profiles once adult body-mass index and height were adjusted for, suggesting that rapid postnatal weight gain--especially after infancy--is linked to these conditions. The review of published works indicates that there is insufficient information about long-term changes in immune function, blood lipids, or osteoporosis indicators. Birthweight is positively associated with lung function and with the incidence of some cancers, and undernutrition could be associated with mental illness. We noted that height-for-age at 2 years was the best predictor of human capital and that undernutrition is associated with lower human capital. We conclude that damage suffered in early life leads to permanent impairment, and might also affect future generations. Its prevention will probably bring about important health, educational, and economic benefits. Chronic diseases are especially common in undernourished children who experience rapid weight gain after infancy.",
"title": "Maternal and child undernutrition: consequences for adult health and human capital"
},
{
"docid": "20130904",
"text": "BACKGROUND Gastric bypass patients with a range of disturbed eating patterns before surgery may be at risk of returning to old patterns postoperatively. Recent research has shown that binge eating is common among the obese before surgery as well as in the postoperative maintenance phase and appears to be linked to poorer outcome. Although \"grazing\" behavior has not been specifically studied, it is also a high-risk pattern. This paper is a descriptive investigation summarizing postoperative eating patterns in a group of patients. METHODS Patients completed self-report questionnaires before surgery and were seen for a preoperative mental health evaluation with particular focus on assessing eating patterns. Patients with high-risk eating patterns, both binge eating and \"grazing\", were identified, invited to attend a post-surgery therapy group, and were given additional follow-up questionnaires regarding postoperative eating patterns. RESULTS Consistent with recent studies, many high-risk patients reported recurrent loss of control over eating and, in some cases, subsequent weight gain. Although no longer able to eat large amounts, \"grazing\" became a more common pattern, appearing >or=6 months following surgery. CONCLUSION Different forms of overeating need to be assessed in this population, focusing on the subjective loss of control rather than on the quantity consumed. Although many patients do not meet strict criteria for binge eating disorder before surgery, these \"grazers\" are also high-risk. Former binge eaters often turn into \"grazers\" following surgery. Interventions are needed for at-risk patients.",
"title": "\"Grazing\": a high-risk behavior."
},
{
"docid": "26199970",
"text": "Objective: It is unclear whether blockade of the angiotensin system has effects on mental health. Our objective was to determine the impact of angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor (AT1R) blockers on mental health domain of quality of life. Study design: Meta-analysis of published literature. Data sources: PubMed and clinicaltrials.gov databases. The last search was conducted in January 2017. Study selection: Randomized controlled trials comparing any angiotensin converting enzyme inhibitor or AT1R blocker versus placebo or non-angiotensin converting enzyme inhibitor or non-AT1R blocker were selected. Study participants were adults without any major physical symptoms. We adhered to meta-analysis reporting methods as per PRISMA and the Cochrane Collaboration. Data synthesis: Eleven studies were included in the analysis. When compared with placebo or other antihypertensive medications, AT1R blockers and angiotensin converting enzyme inhibitors were associated with improved overall quality of life (standard mean difference = 0.11, 95% confidence interval = [0.08, 0.14], p < 0.0001), positive wellbeing (standard mean difference = 0.11, 95% confidence interval = [0.05, 0.17], p < 0.0001), mental (standard mean difference = 0.15, 95% confidence interval = [0.06, 0.25], p < 0.0001), and anxiety (standard mean difference = 0.08, 95% confidence interval = [0.01, 0.16], p < 0.0001) domains of QoL. No significant difference was found for the depression domain (standard mean difference = 0.05, 95% confidence interval = [0.02, 0.12], p = 0.15). Conclusions: Use of angiotensin blockers and inhibitors for the treatment of hypertension in otherwise healthy adults is associated with improved mental health domains of quality of life. Mental health quality of life was a secondary outcome in the included studies. Research specifically designed to analyse the usefulness of drugs that block the angiotensin system is necessary to properly evaluate this novel psychiatric target.",
"title": "Blockade of the angiotensin system improves mental health domain of quality of life: A meta-analysis of randomized clinical trials"
},
{
"docid": "24988745",
"text": "This study aimed to compare the symptoms, unmet needs, and QoL reported by women at 6 months to <2 years and 2 to 5 years following surgery and adjuvant treatment for breast cancer. It also evaluated the relationships among symptoms, unmet needs, and QoL using structural equation modeling. In this study, 113 and 137 survivors following breast cancer treatment 6 months to <2 years and 2 to 5 years, respectively, completed the Memorial Symptom Assessment Scale, the Supportive Care Needs Survey-34, and the Medical Outcomes Study 12-item Short Form Health Survey version 2.0 during their medical follow-up. The mean numbers of symptoms and unmet needs were 5.43 and 3.0, respectively, for survivors at <2 years, and 5.24 and 2.42, respectively, for survivors at 2 to 5 years following treatment. The most common reported symptoms were related primarily to physical domains. No significant differences were found between the two survivor groups on the MSAS scores. Survivors at <2 years reported significantly higher scores in Psychological and Health Care System/Information needs (p < 0.01), and lower composite scores in physical and mental QoL (p < 0.05) than those at 2 to 5 years post-treatment. Significant direct and indirect effects were found of symptom burden through unmet needs on survivors’ physical and mental QoL after adjustment for survival time, and the models showed a good fit. Results suggest that breast cancer survivors continue to endure many symptoms independent of the survivorship period. The unmet needs mediate the relationship between symptom burden and survivors’ QoL.",
"title": "Unmet needs mediate the relationship between symptoms and quality of life in breast cancer survivors"
},
{
"docid": "44048701",
"text": "IMPORTANCE The need for surgery for the majority of patients with displaced proximal humeral fractures is unclear, but its use is increasing. OBJECTIVE To evaluate the clinical effectiveness of surgical vs nonsurgical treatment for adults with displaced fractures of the proximal humerus involving the surgical neck. DESIGN, SETTING, AND PARTICIPANTS A pragmatic, multicenter, parallel-group, randomized clinical trial, the Proximal Fracture of the Humerus Evaluation by Randomization (PROFHER) trial, recruited 250 patients aged 16 years or older (mean age, 66 years [range, 24-92 years]; 192 [77%] were female; and 249 [99.6%] were white) who presented at the orthopedic departments of 32 acute UK National Health Service hospitals between September 2008 and April 2011 within 3 weeks after sustaining a displaced fracture of the proximal humerus involving the surgical neck. Patients were followed up for 2 years (up to April 2013) and 215 had complete follow-up data. The data for 231 patients (114 in surgical group and 117 in nonsurgical group) were included in the primary analysis. INTERVENTIONS Fracture fixation or humeral head replacement were performed by surgeons experienced in these techniques. Nonsurgical treatment was sling immobilization. Standardized outpatient and community-based rehabilitation was provided to both groups. MAIN OUTCOMES AND MEASURES Primary outcome was the Oxford Shoulder Score (range, 0-48; higher scores indicate better outcomes) assessed during a 2-year period, with assessment and data collection at 6, 12, and 24 months. Sample size was based on a minimal clinically important difference of 5 points for the Oxford Shoulder Score. Secondary outcomes were the Short-Form 12 (SF-12), complications, subsequent therapy, and mortality. RESULTS There was no significant mean treatment group difference in the Oxford Shoulder Score averaged over 2 years (39.07 points for the surgical group vs 38.32 points for the nonsurgical group; difference of 0.75 points [95% CI, -1.33 to 2.84 points]; P = .48) or at individual time points. There were also no significant between-group differences over 2 years in the mean SF-12 physical component score (surgical group: 1.77 points higher [95% CI, -0.84 to 4.39 points]; P = .18); the mean SF-12 mental component score (surgical group: 1.28 points lower [95% CI, -3.80 to 1.23 points]; P = .32); complications related to surgery or shoulder fracture (30 patients in surgical group vs 23 patients in nonsurgical group; P = .28), requiring secondary surgery to the shoulder (11 patients in both groups), and increased or new shoulder-related therapy (7 patients vs 4 patients, respectively; P = .58); and mortality (9 patients vs 5 patients; P = .27). Ten medical complications (2 cardiovascular events, 2 respiratory events, 2 gastrointestinal events, and 4 others) occurred in the surgical group during the postoperative hospital stay. CONCLUSIONS AND RELEVANCE Among patients with displaced proximal humeral fractures involving the surgical neck, there was no significant difference between surgical treatment compared with nonsurgical treatment in patient-reported clinical outcomes over 2 years following fracture occurrence. These results do not support the trend of increased surgery for patients with displaced fractures of the proximal humerus. TRIAL REGISTRATION isrctn.com Identifier: ISRCTN50850043.",
"title": "Surgical vs nonsurgical treatment of adults with displaced fractures of the proximal humerus: the PROFHER randomized clinical trial."
},
{
"docid": "29845974",
"text": "Medicines are a major treatment modality for many mental illnesses, and with the growing burden of mental disorders worldwide pharmacists are ideally positioned to play a greater role in supporting people with a mental illness. This narrative review aims to describe the evidence for pharmacist-delivered services in mental health care and address the barriers and facilitators to increasing the uptake of pharmacist services as part of the broader mental health care team. This narrative review is divided into three main sections: (1) the role of the pharmacist in mental health care in multidisciplinary teams and in supporting early detection of mental illness; (2) the pharmacists' role in supporting quality use of medicines in medication review, strategies to improve medication adherence and antipsychotic polypharmacy, and shared decision making; and (3) barriers and facilitators to the implementation of mental health pharmacy services with a focus on organizational culture and mental health stigma. In the first section, the review presents new roles for pharmacists within multidisciplinary teams, such as in case conferencing or collaborative drug therapy management; and new roles that would benefit from increased pharmacist involvement, such as the early detection of mental health conditions, development of care plans and follow up of people with mental health problems. The second section describes the impact of medication review services and other pharmacist-led interventions designed to reduce inappropriate use of psychotropic medicines and improve medication adherence. Other new potential roles discussed include the management of antipsychotic polypharmacy and involvement in patient-centered care. Finally, barriers related to pharmacists' attitudes, stigma and skills in the care of patients with mental health problems and barriers affecting pharmacist-physician collaboration are described, along with strategies to reduce mental health stigma.",
"title": "New Roles for Pharmacists in Community Mental Health Care: A Narrative Review"
},
{
"docid": "17693849",
"text": "BACKGROUND Appropriate understanding of health information by patients with cardiovascular disease (CVD) is fundamental for better management of risk factors and improved morbidity, which can also benefit their quality of life. OBJECTIVES To assess the relationship between health literacy and health-related quality of life (HRQoL) in patients with ischaemic heart disease (IHD), and to investigate the role of sociodemographic and clinical variables as possible confounders. METHODS Cross-sectional study of patients with IHD recruited from a stratified sample of general practices in two Australian states (Queensland and South Australia) between 2007 and 2009. Health literacy was measured using a validated questionnaire and classified as inadequate, marginal, or adequate. Physical and mental components of HRQoL were assessed using the Medical Outcomes Study Short Form (SF12) questionnaire. Analyses were adjusted for confounders (sociodemographic variables, clinical history of IHD, number of CVD comorbidities, and CVD risk factors) using multiple linear regression. RESULTS A total sample of 587 patients with IHD (mean age 72.0±8.4 years) was evaluated: 76.8% males, 84.2% retired or pensioner, and 51.4% with up to secondary educational level. Health literacy showed a mean of 39.6±6.7 points, with 14.3% (95%CI 11.8-17.3) classified as inadequate. Scores of the physical component of HRQoL were 39.6 (95%CI 37.1-42.1), 42.1 (95%CI 40.8-43.3) and 44.8 (95%CI 43.3-46.2) for inadequate, marginal, and adequate health literacy, respectively (p-value for trend = 0.001). This association persisted after adjustment for confounders. Health literacy was not associated with the mental component of HRQoL (p-value = 0.482). Advanced age, lower educational level, disadvantaged socioeconomic position, and a larger number of CVD comorbidities adversely affected both, health literacy and HRQoL. CONCLUSION Inadequate health literacy is a contributing factor to poor physical functioning in patients with IHD. Increasing health literacy may improve HRQoL and reduce the impact of IHD among patients with this chronic CVD.",
"title": "Effect of Health Literacy on Quality of Life amongst Patients with Ischaemic Heart Disease in Australian General Practice"
},
{
"docid": "25649714",
"text": "OBJECTIVE To establish the mental health needs of homeless children and families before and after rehousing. DESIGN Cross sectional, longitudinal study. SETTING City of Birmingham. SUBJECTS 58 rehoused families with 103 children aged 2-16 years and 21 comparison families of low socioeconomic status in stable housing, with 54 children. MAIN OUTCOME MEASURES Children's mental health problems and level of communication; mothers' mental health problems and social support one year after rehousing. RESULTS Mental health problems remained significantly higher in rehoused mothers and their children than in the comparison group (mothers 26% v 5%, P = 0.04; children 39% v 11%, P = 0.0003). Homeless mothers continued to have significantly less social support at follow up. Mothers with a history of abuse and poor social integration were more likely to have children with persistent mental health problems. CONCLUSIONS Homeless families have a high level of complex needs that cannot be met by conventional health services and arrangements. Local strategies for rapid rehousing into permanent accommodation, effective social support and health care for parents and children, and protection from violence and intimidation should be developed and implemented.",
"title": "Mental health problems of homeless children and families: longitudinal study."
},
{
"docid": "6490571",
"text": "CONTEXT Little is known about the extent or severity of untreated mental disorders, especially in less-developed countries. OBJECTIVE To estimate prevalence, severity, and treatment of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders in 14 countries (6 less developed, 8 developed) in the World Health Organization (WHO) World Mental Health (WMH) Survey Initiative. DESIGN, SETTING, AND PARTICIPANTS Face-to-face household surveys of 60 463 community adults conducted from 2001-2003 in 14 countries in the Americas, Europe, the Middle East, Africa, and Asia. MAIN OUTCOME MEASURES The DSM-IV disorders, severity, and treatment were assessed with the WMH version of the WHO Composite International Diagnostic Interview (WMH-CIDI), a fully structured, lay-administered psychiatric diagnostic interview. RESULTS The prevalence of having any WMH-CIDI/DSM-IV disorder in the prior year varied widely, from 4.3% in Shanghai to 26.4% in the United States, with an interquartile range (IQR) of 9.1%-16.9%. Between 33.1% (Colombia) and 80.9% (Nigeria) of 12-month cases were mild (IQR, 40.2%-53.3%). Serious disorders were associated with substantial role disability. Although disorder severity was correlated with probability of treatment in almost all countries, 35.5% to 50.3% of serious cases in developed countries and 76.3% to 85.4% in less-developed countries received no treatment in the 12 months before the interview. Due to the high prevalence of mild and subthreshold cases, the number of those who received treatment far exceeds the number of untreated serious cases in every country. CONCLUSIONS Reallocation of treatment resources could substantially decrease the problem of unmet need for treatment of mental disorders among serious cases. Structural barriers exist to this reallocation. Careful consideration needs to be given to the value of treating some mild cases, especially those at risk for progressing to more serious disorders.",
"title": "Prevalence, severity, and unmet need for treatment of mental disorders in the World Health Organization World Mental Health Surveys."
},
{
"docid": "79447",
"text": "OBJECTIVE The purpose of this study was to characterize the relationship between adipose tissue phenotype and depot-specific microvascular function in fat. METHODS AND RESULTS In 30 obese subjects (age 42±11 years, body mass index 46±11 kg/m(2)) undergoing bariatric surgery, we intraoperatively collected visceral and subcutaneous adipose tissue and characterized depot-specific adipose phenotypes. We assessed vasomotor function of the adipose microvasculature using videomicroscopy of small arterioles (75-250 μm) isolated from different fat compartments. Endothelium-dependent, acetylcholine-mediated vasodilation was severely impaired in visceral arterioles, compared to the subcutaneous depot (P<0.001 by ANOVA). Nonendothelium dependent responses to papaverine and nitroprusside were similar. Endothelial nitric oxide synthase inhibition with N(ω)-nitro-l-arginine methyl ester reduced subcutaneous vasodilation but had no effect on severely blunted visceral arteriolar responses. Visceral fat exhibited greater expression of proinflammatory, oxidative stress-related, hypoxia-induced, and proangiogenic genes; increased activated macrophage populations; and had a higher capacity for cytokine production ex vivo. CONCLUSIONS Our findings provide clinical evidence that the visceral microenvironment may be intrinsically toxic to arterial health providing a potential mechanism by which visceral adiposity burden is linked to atherosclerotic vascular disease. Our findings also support the evolving concept that both adipose tissue quality and quantity may play significant roles in shaping cardiovascular phenotypes in human obesity.",
"title": "Arteriolar function in visceral adipose tissue is impaired in human obesity."
},
{
"docid": "57762078",
"text": "Background Compared to other European countries, Sweden's yearly sick leave expenditures are moderate. Common mental disorders (CMD) are important causes of sick leave, affecting 10-15% of the adult population. A Swedish register based study indicates that antidepressant therapy for patients on long-term sick leave for CMD leads to longer sick leave and higher frequency of non-time-limited sickness compensation as compared to psychotherapy, work oriented rehabilitation, and other therapies. Aim To verify if patients on antidepressant therapy and on long-term sick leave for depression, anxiety and stress-related mental disorders have a longer sick leave than patients treated with other therapies. Method Prospective, observational study at 28 primary health care centers in the Region Västra Götaland, Sweden, including 192 patients on sick leave for CMD. Outcome measures were gross and net sick leave days. Interpretation There were no significant differences in sick leave days (gross or net) due to CMD when comparing the patients treated and not treated with antidepressants during the 12 month observation period. The groups differed at baseline only concerning frequency of exhaustion disorder, with a higher frequency of exhaustion disorder in the group without antidepressants. Analysis of other possible factors associated with shorter or longer sick leave only showed associations with the patient's own perception of possibility of returning to work in near and distant future. An important factor associated with longer sick leave was the patient's own perception of possibility of return to present workplace. As CMD are important causes of sick leave and sick leave costs, this factor should be highlighted in future research on the rehabilitation process.",
"title": "Influence of antidepressant therapy on sick leave in primary care: ADAS, a comparative observational study"
},
{
"docid": "6767133",
"text": "STUDY DESIGN Prospective observational cohort. OBJECTIVE To describe the baseline characteristics of patients with a diagnosis of intervertebral disc herniation who had different treatment preferences and the relationship of specific expectations with those preferences. SUMMARY OF BACKGROUND DATA Data were gathered from the observational cohort of the Spine Patient Outcomes Research Trial (SPORT). Patients in the observational cohort met eligibility requirements identical to those of the randomized cohort, but declined randomization, receiving instead the treatment of their choice. METHODS Baseline preference and expectation data were acquired at the time of enrollment of the patient, before exposure to the informed consent process. Univariate analyses were performed using a t test for continuous variables and chi for categorical variables. Multivariate analyses were also performed with ANCOVA for continuous variables and logistic regression for categorical variables. Multiple logistic regression models were developed in a forward stepwise fashion using blocks of variables. RESULTS More patients preferred operative care: 67% preferred surgery, 28% preferred nonoperative treatment, and 6% were unsure; 53% of those preferring surgery stated a definite preference, whereas only 18% of those preferring nonoperative care had a definite preference. Patients preferring surgery were younger, had lower levels of education, and higher levels of unemployment/disability. This group also reported higher pain, worse physical and mental functioning, more back pain related disability, a longer duration of symptoms, and more opiate use. Gender, race, comorbidities, and use of other therapies did not differ significantly across preference groups. Patients' expectations regarding improvement with nonoperative care was the strongest predictor of preference. CONCLUSION Patient expectations, particularly regarding the benefit of nonoperative treatment, are the primary determinant of surgery preference among patients with lumbar intervertebral disc herniation. Demographic, functional status, and prior treatment experience had significant associations with patients' expectations and preferences.",
"title": "Patient preferences and expectations for care: determinants in patients with lumbar intervertebral disc herniation."
},
{
"docid": "463533",
"text": "INTRODUCTION The aim of this study was to examine health-related quality of life (HRQoL) as measured by EQ-5D and to investigate the influence of chronic conditions and other risk factors on HRQoL based on a distributed sample located in Shaanxi Province, China. METHODS A multi-stage stratified cluster sampling method was performed to select subjects. EQ-5D was employed to measure the HRQoL. The likelihood that individuals with selected chronic diseases would report any problem in the EQ-5D dimensions was calculated and tested relative to that of each of the two reference groups. Multivariable linear regression models were used to investigate factors associated with EQ VAS. RESULTS The most frequently reported problems involved pain/discomfort (8.8%) and anxiety/depression (7.6%). Nearly half of the respondents who reported problems in any of the five dimensions were chronic patients. Higher EQ VAS scores were associated with the male gender, higher level of education, employment, younger age, an urban area of residence, access to free medical service and higher levels of physical activity. Except for anemia, all the selected chronic diseases were indicative of a negative EQ VAS score. The three leading risk factors were cerebrovascular disease, cancer and mental disease. Increases in age, number of chronic conditions and frequency of physical activity were found to have a gradient effect. CONCLUSION The results of the present work add to the volume of knowledge regarding population health status in this area, apart from the known health status using mortality and morbidity data. Medical, policy, social and individual attention should be given to the management of chronic diseases and improvement of HRQoL. Longitudinal studies must be performed to monitor changes in HRQoL and to permit evaluation of the outcomes of chronic disease intervention programs.",
"title": "Health-Related Quality of Life as Measured with EQ-5D among Populations with and without Specific Chronic Conditions: A Population-Based Survey in Shaanxi Province, China"
},
{
"docid": "73473433",
"text": "BACKGROUND Over the past 20 years the prevalence of child and adolescent mental disorders in high-income countries has not changed despite increased investment in mental health services. Insufficient contact with mental health services may be a contributing factor; however, it is not known what proportion of children have sufficient contact with health professionals to allow delivery of treatment meeting minimal clinical practice guidelines, or how long children experience symptoms prior to receiving treatment. AimsTo investigate the level of mental healthcare received by Australian children from age 4 years to 14 years. METHOD Trajectories of mental health symptoms were mapped using the Strengths and Difficulties Questionnaire. Health professional attendances and psychotropic medications dispensed were identified from linked national Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme records. RESULTS Four trajectories of mental health symptoms were identified (low, high-decreasing, moderate-increasing and high-increasing). Most children with mental health symptoms had few MBS mental health attendances, and only a minority received care meeting study criteria for minimally adequate treatment. Children in the high-increasing and moderate-increasing trajectories were more likely to access care, yet there was no evidence of improvement in symptoms. CONCLUSIONS It is important that children and adolescents with mental health problems receive treatment that meets minimal practice guidelines. Further research is needed to identify the quality of care currently provided to children with mental health difficulties and how clinicians can be best funded and supported to provide care meeting minimal practice guidelines. Declaration of interestsNone.",
"title": "Mental health difficulties across childhood and mental health service use: findings from a longitudinal population-based study."
},
{
"docid": "45548062",
"text": "OBJECTIVE Policy discussions regarding the mental health needs of children and adolescents emphasize a lack of use of mental health services among youth, but few national estimates are available. The authors use three national data sets and examine ethnic disparities in unmet need (defined as having a need for mental health evaluation but not using any services in a 1-year period) to provide such estimates. METHOD The authors conducted secondary data analyses in three nationally representative household surveys fielded in 1996-1998: the National Health Interview Survey, the National Survey of American Families, and the Community Tracking Survey. They determined rates of mental health service use by children and adolescents 3-17 years of age and differences by ethnicity and insurance status. Among the children defined as in need of mental health services, defined by an estimator of mental health problems (selected items from the Child Behavior Checklist), they examined the association of unmet need with ethnicity and insurance status. RESULTS In a 12-month period, 2%-3% of children 3-5 years old and 6%-9% of children and adolescents 6-17 years old used mental health services. Of children and adolescents 6-17 years old who were defined as needing mental health services, nearly 80% did not receive mental health care. Controlling for other factors, the authors determined that the rate of unmet need was greater among Latino than white children and among uninsured than publicly insured children. CONCLUSIONS These findings reveal that most children who need a mental health evaluation do not receive services and that Latinos and the uninsured have especially high rates of unmet need relative to other children. Rates of use of mental health services are extremely low among preschool children. Research clarifying the reasons for high rates of unmet need in specific groups can help inform policy and clinical programs.",
"title": "Unmet need for mental health care among U.S. children: variation by ethnicity and insurance status."
},
{
"docid": "39187170",
"text": "Adipose tissue exerts important endocrine and metabolic functions in health and disease. Yet the bioenergetics of this tissue is not characterized in humans and possible regional differences are not elucidated. Using high resolution respirometry, mitochondrial respiration was quantified in human abdominal subcutaneous and intra-abdominal visceral (omentum majus) adipose tissue from biopsies obtained in 20 obese patients undergoing bariatric surgery. Mitochondrial DNA (mtDNA) and genomic DNA (gDNA) were determined by the PCR technique for estimation of mitochondrial density. Adipose tissue samples were permeabilized and respirometric measurements were performed in duplicate at 37 degrees C. Substrates (glutamate (G) + malate (M) + octanoyl carnitine (O) + succinate (S)) were added sequentially to provide electrons to complex I + II. ADP ((D)) for state 3 respiration was added after GM. Uncoupled respiration was measured after addition of FCCP. Visceral fat contained more mitochondria per milligram of tissue than subcutaneous fat, but the cells were smaller. Robust, stable oxygen fluxes were found in both tissues, and coupled state 3 (GMOS(D)) and uncoupled respiration were significantly (P < 0.05) higher in visceral (0.95 +/- 0.05 and 1.15 +/- 0.06 pmol O(2) s(1) mg(1), respectively) compared with subcutaneous (0.76 +/- 0.04 and 0.98 +/- 0.05 pmol O(2) s(1) mg(1), respectively) adipose tissue. Expressed per mtDNA, visceral adipose tissue had significantly (P < 0.05) lower mitochondrial respiration. Substrate control ratios were higher and uncoupling control ratio lower (P < 0.05) in visceral compared with subcutaneous adipose tissue. We conclude that visceral fat is bioenergetically more active and more sensitive to mitochondrial substrate supply than subcutaneous fat. Oxidative phosphorylation has a higher relative activity in visceral compared with subcutaneous adipose tissue.",
"title": "Mitochondrial respiration in subcutaneous and visceral adipose tissue from patients with morbid obesity."
},
{
"docid": "24318630",
"text": "Since 2008 the World Health Organization (WHO), through its mental health Gap Action Programme, has attempted to revitalize efforts to integrate mental health into non-specialized (e.g. primary) healthcare. While this has led to renewed interest in this potential method of mental health service delivery, it has also prompted criticism. Some concerns raised are that it would contribute to the medicalization of social and psychological problems, and narrowly focus on primary care without sufficient attention given to strengthening other levels of the healthcare system, notably community-based care and care on district levels. This paper discusses seven elements that may be critical to preventing inadvertently contributing to increasing a narrow biomedical approach to mental healthcare when integrating mental health into non-specialized healthcare: (1) using task shifting approaches within a system of stepped care, (2) ensuring primary mental healthcare also includes brief psychotherapeutic interventions, (3) promote community-based recovery-oriented interventions for people with disabling chronic mental disorders, (4) conceptualizing training as a continuous process of strengthening clinical competencies through supervision, (5) engaging communities as partners in psychosocial interventions, (6) embedding shifts to primary mental healthcare within wider health policy reforms, and (7) promoting inter-sectoral approaches to address social determinants of mental health.",
"title": "Integration of mental health into primary healthcare in low-income countries: avoiding medicalization."
},
{
"docid": "6129301",
"text": "AIMS To describe the characteristics of homeless children and families seen by the mental health outreach service (MHOS), to evaluate the impact of this service on the short term psychosocial functioning of children and parents, and to establish perceptions of, and satisfaction with, the service. METHODS Twenty seven children from 23 families who were in receipt of the MHOS and 27 children from 23 families residing in other hostels where no such service was available were studied. The MHOS was delivered by a clinical nurse specialist with expertise in child mental health, who offered the following interventions: assessment and brief treatment of mental health disorders in children; liaison with agencies; and training of homeless centre staff. RESULTS Children in the experimental group had a significantly higher decrease in Strengths and Difficulties Questionnaire (SDQ) total scores. Having received the intervention was the strongest predictor of improvement in SDQ total scores. There was no significant impact on parental mental health (General Health Questionnaire) scores. Homeless families and staff expressed high satisfaction with the MHOS. CONCLUSION This MHOS for homeless families is an innovative intervention which meets the complex and multiple needs of a vulnerable population unable to access mainstream mental health services. The primary objective of the service was to improve child mental health problems; however, the service developed in a responsive way by meeting social and practical needs of families in addition to its clinical role.",
"title": "Evaluation of a mental health outreach service for homeless families."
},
{
"docid": "58564850",
"text": "Background We aimed to determine the prevalence and gap in use of mental health services for late-life depression in four European regions (Western Europe, Scandinavia, Southern Europe and Central and Eastern Europe) and explore socio-demographic, social and health-related factors associated with it. Methods We conducted a cross-sectional study based on data from the Survey on Health, Ageing and Retirement in Europe. Participants were a population-based sample of 28 796 persons (53% women, mean age 74 years old) residing in Europe. Mental health service use was estimated using information about the diagnosis or treatment for depression. Results The prevalence of late-life depression was 29% in the whole sample and was highest in Southern Europe (35%), followed by Central and Eastern Europe (32%), Western Europe (26%) and lowest in Scandinavia (17%). Factors that had the strongest association with depression were total number of chronic diseases, pain, limitations in instrumental activities of daily living, grip strength and cognitive impairment. The gap in mental health service use was 79%. Conclusions We suggest that interventions to decrease the burden of late-life depression should be targeted at individuals that are affected by chronic somatic comorbidities and are limited in mental and physical functioning. Promotion of help-seeking of older adults, de-stigmatization of mental illness and education of general practitioners could help decrease the gap in mental health service utilization.",
"title": "Prevalence of late-life depression and gap in mental health service use across European regions."
},
{
"docid": "26067999",
"text": "The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms. It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment. The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms. Summary of Recommendation and Evidence The USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) See the Clinical Considerations section for suggestions for implementation in practice. See the Figure for a summary of the recommendation and suggestions for clinical practice. Figure. Screening for lung cancer: clinical summary of U.S. Preventive Services Task Force recommendation. Appendix Table 1 describes the USPSTF grades, and Appendix Table 2 describes the USPSTF classification of levels of certainty about net benefit. Appendix Table 1. What the USPSTF Grades Mean and Suggestions for Practice Appendix Table 2. USPSTF Levels of Certainty Regarding Net Benefit Supplement. Consumer Fact Sheet. Rationale Importance Lung cancer is the third most common cancer and the leading cause of cancer-related death in the United States (1). The most important risk factor for lung cancer is smoking, which results in approximately 85% of all U.S. lung cancer cases (2). Although the prevalence of smoking has decreased, approximately 37% of U.S. adults are current or former smokers (2). The incidence of lung cancer increases with age and occurs most commonly in persons aged 55 years or older. Increasing age and cumulative exposure to tobacco smoke are the 2 most common risk factors for lung cancer. Lung cancer has a poor prognosis, and nearly 90% of persons with lung cancer die of the disease. However, early-stage nonsmall cell lung cancer (NSCLC) has a better prognosis and can be treated with surgical resection. Detection Most lung cancer cases are NSCLC, and most screening programs focus on the detection and treatment of early-stage NSCLC. Although chest radiography and sputum cytologic evaluation have been used to screen for lung cancer, LDCT has greater sensitivity for detecting early-stage cancer (3). Benefits of Detection and Early Treatment Although lung cancer screening is not an alternative to smoking cessation, the USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancerrelated deaths. Direct evidence from a large, well-conducted, randomized, controlled trial (RCT) provides moderate certainty of the benefit of lung cancer screening with LDCT in this population (4). The magnitude of benefit to the person depends on that person's risk for lung cancer because those who are at highest risk are most likely to benefit. Screening cannot prevent most lung cancerrelated deaths, and smoking cessation remains essential. Harms of Detection and Early Intervention and Treatment The harms associated with LDCT screening include false-negative and false-positive results, incidental findings, overdiagnosis, and radiation exposure. False-positive LDCT results occur in a substantial proportion of screened persons; 95% of all positive results do not lead to a diagnosis of cancer. In a high-quality screening program, further imaging can resolve most false-positive results; however, some patients may require invasive procedures. The USPSTF found insufficient evidence on the harms associated with incidental findings. Overdiagnosis of lung cancer occurs, but its precise magnitude is uncertain. A modeling study performed for the USPSTF estimated that 10% to 12% of screen-detected cancer cases are overdiagnosedthat is, they would not have been detected in the patient's lifetime without screening. Radiation harms, including cancer resulting from cumulative exposure to radiation, vary depending on the age at the start of screening; the number of scans received; and the person's exposure to other sources of radiation, particularly other medical imaging. USPSTF Assessment The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT is of moderate net benefit in asymptomatic persons who are at high risk for lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. The moderate net benefit of screening depends on limiting screening to persons who are at high risk, the accuracy of image interpretation being similar to that found in the NLST (National Lung Screening Trial), and the resolution of most false-positive results without invasive procedures (4). Clinical Considerations Patient Population Under Consideration The risk for lung cancer increases with age and cumulative exposure to tobacco smoke and decreases with time since quitting smoking. The best evidence for the benefit of screening comes from the NLST, which enrolled adults aged 55 to 74 years who had at least a 30 pack-year smoking history and were current smokers or had quit within the past 15 years. As with all screening trials, the NLST tested a specific intervention over a finite period. Because initial eligibility extended through age 74 years and participants received 3 annual screening computed tomographic scans, the oldest participants in the trial were aged 77 years. The USPSTF used modeling studies to predict the benefits and harms of screening programs that use different screening intervals, age ranges, smoking histories, and times since quitting. A program that annually screens adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years is projected to have a reasonable balance of benefits and harms. The model assumes that persons who achieve 15 years of smoking cessation during the screening program discontinue screening. This model predicts the outcomes of continuing the screening program used in the NLST through age 80 years. Screening may not be appropriate for patients with substantial comorbid conditions, particularly those at the upper end of the screening age range. The NLST excluded persons who were unlikely to complete curative lung cancer surgery and those with medical conditions that posed a substantial risk for death during the 8-year trial. The baseline characteristics of the NLST showed a relatively healthy sample, and fewer than 10% of enrolled participants were older than 70 years (5). Persons with serious comorbid conditions may experience net harm, no net benefit, or at least substantially less net benefit. Similarly, persons who are unwilling to have curative lung surgery are unlikely to benefit from a screening program. Assessment of Risk Age, total exposure to tobacco smoke, and years since quitting smoking are important risk factors for lung cancer and were used to determine eligibility in the NLST. Other risk factors include specific occupational exposures, radon exposure, family history, and history of pulmonary fibrosis or chronic obstructive lung disease. The incidence of lung cancer is relatively low in persons younger than 50 years but increases with age, especially after age 60 years. In current and former smokers, age-specific incidence rates increase with age and cumulative exposure to tobacco smoke. Smoking cessation substantially reduces a person's risk for developing and dying of lung cancer. Among persons enrolled in the NLST, those who were at highest risk because of additional risk factors or a greater cumulative exposure to tobacco smoke experienced most of the benefit (6). A validated multivariate model showed that persons in the highest 60% of risk accounted for 88% of all deaths preventable by screening. Screening Tests Low-dose computed tomography has shown high sensitivity and acceptable specificity for the detection of lung cancer in high-risk persons. Chest radiography and sputum cytologic evaluation have not shown adequate sensitivity or specificity as screening tests. Therefore, LDCT is currently the only recommended screening test for lung cancer. Treatment Surgical resection is the current standard of care for localized NSCLC. This type of cancer is treated with surgical resection when possible and also with radiation and chemotherapy. Annual LDCT screening may not be useful for patients with life-limiting comorbid conditions or poor functional status who may not be candidates for surgery. Other Approaches to Prevention Smoking cessation is the most important intervention to prevent NSCLC. Advising smokers to stop smoking and preventing nonsmokers from being exposed to tobacco smoke are the most effective ways to decrease the morbidity and mortality associated with lung cancer. Current smokers should be informed of their continuing risk for lung cancer and offered cessation treatments. Screening with LDCT should be viewed as an adjunct to tobacco cessation interventions. Useful Resources Clinicians have many resources to help patients stop smoking. The Centers for Disease Control and Prevention has developed a Web site with many such resources, including information on tobacco quit lines, available in several languages (www.cdc.gov/tobacco/campaign/tips). Quit l",
"title": "Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation Statement"
},
{
"docid": "22467585",
"text": "Background: The loss of a child during pregnancy causes significant psychological distress for many women and their partners, and may lead to long-lasting psychiatric disorders. Internet-based interventions using exposure techniques and cognitive restructuring have proved effective for posttraumatic stress disorder (PTSD) and prolonged grief. This study compared the effects of an Internet-based intervention for parents after prenatal loss with a waiting list condition (WLC). Methods: The Impact of Event Scale - Revised assessed symptoms of PTSD; the Inventory of Complicated Grief and the Brief Symptom Inventory assessed depression, anxiety, and general mental health. The 228 participants (92% female) were randomly allocated to a treatment group (TG; n = 115) or a WLC group (n = 113). The TG received a 5-week cognitive behavioral intervention including (1) self-confrontation, (2) cognitive restructuring, and (3) social sharing. Results: The TG showed significantly reduced symptoms of posttraumatic stress, prolonged grief, depression, and anxiety relative to the WLC control group. Intention-to-treat analysis revealed treatment effects of between d = 0.84 and d = 1.02 for posttraumatic stress and prolonged grief from pre- to posttreatment time points. Further significant improvement in all symptoms of PTSD and prolonged grief was found from the posttreatment evaluation to the 12-month follow-up. The attrition rate of 14% was relatively low. Conclusions: The Internet-based intervention proved to be a feasible and cost-effective treatment, reducing symptoms of posttraumatic stress, grief, depression, anxiety, and general mental health after pregnancy loss. Low-threshold e-health interventions should be further evaluated and implemented routinely to improve psychological support after pregnancy loss.",
"title": "Brief Internet-Based Intervention Reduces Posttraumatic Stress and Prolonged Grief in Parents after the Loss of a Child during Pregnancy: A Randomized Controlled Trial"
},
{
"docid": "35022568",
"text": "Recent years have seen the emergence of a 'global mental health' agenda, focused on providing evidence-based interventions for mental illnesses in low- and middle-income countries. Anthropologists and cultural psychiatrists have engaged in vigorous debates about the appropriateness of this agenda. In this article, we reflect on these debates, drawing on ethnographic fieldwork on the management of substance use disorders in China, Russia, and the United States. We argue that the logic of 'treatment gaps,' which guides much research and intervention under the rubric of global mental health, partially obscures the complex assemblages of institutions, therapeutics, knowledges, and actors framing and managing addiction (as well as other mental health issues) in any particular setting.",
"title": "What's in the 'treatment gap'? Ethnographic perspectives on addiction and global mental health from China, Russia, and the United States."
},
{
"docid": "24159217",
"text": "CONTEXT No randomized controlled studies have been conducted to date on the effectiveness of psychological interventions for children with symptoms of posttraumatic stress disorder (PTSD) that has resulted from personally witnessing or being personally exposed to violence. OBJECTIVE To evaluate the effectiveness of a collaboratively designed school-based intervention for reducing children's symptoms of PTSD and depression that has resulted from exposure to violence. DESIGN A randomized controlled trial conducted during the 2001-2002 academic year. SETTING AND PARTICIPANTS Sixth-grade students at 2 large middle schools in Los Angeles who reported exposure to violence and had clinical levels of symptoms of PTSD. INTERVENTION Students were randomly assigned to a 10-session standardized cognitive-behavioral therapy (the Cognitive-Behavioral Intervention for Trauma in Schools) early intervention group (n = 61) or to a wait-list delayed intervention comparison group (n = 65) conducted by trained school mental health clinicians. MAIN OUTCOME MEASURES Students were assessed before the intervention and 3 months after the intervention on measures assessing child-reported symptoms of PTSD (Child PTSD Symptom Scale; range, 0-51 points) and depression (Child Depression Inventory; range, 0-52 points), parent-reported psychosocial dysfunction (Pediatric Symptom Checklist; range, 0-70 points), and teacher-reported classroom problems using the Teacher-Child Rating Scale (acting out, shyness/anxiousness, and learning problems; range of subscales, 6-30 points). RESULTS Compared with the wait-list delayed intervention group (no intervention), after 3 months of intervention students who were randomly assigned to the early intervention group had significantly lower scores on symptoms of PTSD (8.9 vs 15.5, adjusted mean difference, - 7.0; 95% confidence interval [CI], - 10.8 to - 3.2), depression (9.4 vs 12.7, adjusted mean difference, - 3.4; 95% CI, - 6.5 to - 0.4), and psychosocial dysfunction (12.5 vs 16.5, adjusted mean difference, - 6.4; 95% CI, -10.4 to -2.3). Adjusted mean differences between the 2 groups at 3 months did not show significant differences for teacher-reported classroom problems in acting out (-1.0; 95% CI, -2.5 to 0.5), shyness/anxiousness (0.1; 95% CI, -1.5 to 1.7), and learning (-1.1, 95% CI, -2.9 to 0.8). At 6 months, after both groups had received the intervention, the differences between the 2 groups were not significantly different for symptoms of PTSD and depression; showed similar ratings for psychosocial function; and teachers did not report significant differences in classroom behaviors. CONCLUSION A standardized 10-session cognitive-behavioral group intervention can significantly decrease symptoms of PTSD and depression in students who are exposed to violence and can be effectively delivered on school campuses by trained school-based mental health clinicians.",
"title": "A mental health intervention for schoolchildren exposed to violence: a randomized controlled trial."
}
] |
104595
|
All My Children is the slogan for the company of Sarah Michelle Gellar.
|
[
{
"docid": "Sarah_Michelle_Gellar",
"text": "Sarah Michelle Prinze ( née Gellar ; born April 14 , 1977 ) is an American actress , producer , and entrepreneur . After being spotted by an agent at the age of four in New York City , she made her acting debut in the made-for-TV movie An Invasion of Privacy ( 1983 ) . Gellar went on to appear in numerous television series and commercials . Her first leading part was in the 1992 miniseries Swans Crossing , for which she was nominated for two Young Artist Awards , and her television breakthrough came in 1993 , when she originated the role of Kendall Hart on the ABC daytime soap opera All My Children , winning the 1995 Daytime Emmy Award for Outstanding Younger Actress in a Drama Series . Gellar received widespread recognition for her portrayal of Buffy Summers on the WB series Buffy the Vampire Slayer ( 1997 -- 2003 ) , which earned her five Teen Choice Awards , a Saturn Award and a Golden Globe Award nomination . The character was widely popular during the airing of the show and became recognized as one of the 100 greatest female characters in U.S. television . Gellar also gained significant attention for her appearances in the slasher movies I Know What You Did Last Summer ( 1997 ) and Scream 2 ( 1997 ) , and for her portrayal of Kathryn Merteuil in Cruel Intentions ( 1999 ) . She appeared as Daphne Blake in Scooby-Doo ( 2002 ) , her biggest live action commercial success . In 2004 , Gellar reprised her role as Daphne in the sequel Scooby-Doo 2 : Monsters Unleashed and portrayed Karen Davis in the horror remake The Grudge , both of which grossed more than US$ 180 million worldwide . She subsequently appeared in smaller scale movies such as The Return ( 2006 ) and Southland Tales ( 2007 ) , and provided her voice for TMNT ( 2007 ) . Her later film credits include The Air I Breathe ( 2008 ) , Possession ( 2009 ) and Veronika Decides to Die ( 2009 ) . She headlined the short lived television series Ringer ( 2011 -- 2012 ) and The Crazy Ones ( 2013 -- 2014 ) , which co-starred Robin Williams . In October 2015 , Gellar co-founded Foodstirs , a food crafting brand and e-commerce startup selling baking kits for children .",
"title": ""
}
] |
[
{
"docid": "Kendall_Hart",
"text": "Kendall Hart is a fictional character from the American daytime drama All My Children . The character was portrayed by Sarah Michelle Gellar from 1993 to 1995 , and by Alicia Minshew from 2002 until the show 's series finale on September 23 , 2011 . On March 7 , 2013 , it was announced that Minshew would guest star on the Prospect Park 's continuation of All My Children . She appeared on the second July 8 episode , and exited the same day . Kendall is the daughter of Erica Kane , a child conceived when Erica was raped on the night of her 14th birthday by movie matinee idol Richard Fields . Emerging as one of daytime television 's most popular and layered characters , Kendall was originally written as a complex villain , described as a `` complicated bad girl '' and `` the scheming daughter of the biggest schemer of them all , Erica Kane , '' but was later reformed . The writers scripted her as a heroine , while keeping devious aspects of the character intact .",
"title": ""
},
{
"docid": "Justin_Bruening",
"text": "Justin Bruening ( born September 24 , 1979 ) is an American actor and former fashion model . In 2003 , his acting career began when he was cast in the role of Jamie Martin on the daytime drama All My Children , earning him a Soap Opera Digest Award in 2005 for the portrayal . In late 2007 , not long after leaving the role , Bruening was cast as Mike Traceur , the son of character Michael Knight , a new take on the original Knight Rider series . In 2011 , he was cast as Tyler Berrett , a recurring role on The CW series Ringer starring Sarah Michelle Gellar and in 2013 , he joined Ravenswood .",
"title": ""
},
{
"docid": "Gellar",
"text": "Gellar may refer to : Gellar-e Mohammad Hasan , a village in Ardabil Province , Iran Gellar-e Mohammad Taqi , a village in Ardabil Province , Iran Sarah Michelle Gellar , an American actress Caitlyn Gellar , a fictional character in Camp Rock James Gellar , a fictional character in Dexter",
"title": ""
},
{
"docid": "Foodstirs",
"text": "Foodstirs is an American cooking and lifestyle company that produces baking kits and mixes for sale online , by subscription , or in select stores . The kits contain only organic and non-GMO ingredients and are intended to be `` kid-friendly '' to prepare . One of the company 's co-founders is actress , Sarah Michelle Gellar . It is headquartered in Santa Monica , California . The company was named to the CNBC Upstart 25 list in February 2017 .",
"title": ""
},
{
"docid": "Becoming_(Buffy_the_Vampire_Slayer)",
"text": "`` Becoming '' is the season finale of the WB Television Network 's second season of the drama television series Buffy the Vampire Slayer , consisting of the twenty-first and twenty-second episodes . The two episodes were split into two broadcasts ; `` Part 1 '' first aired on May 12 , 1998 and `` Part 2 '' first aired on May 19 , 1998 . They were written and directed by series creator Joss Whedon . The narrative features vampire slayer Buffy Summers ( Sarah Michelle Gellar ) working to prevent Angelus ( David Boreanaz ) and fellow vampires Drusilla ( Juliet Landau ) and Spike ( James Marsters ) from awakening the demon Acathla . Production of `` Becoming '' was the first time that the show had been filmed outside of the usual warehouses or other locations . A studio was used for the flashback scenes set in New York and Ireland . Actors Sarah Michelle Gellar and David Boreanaz undertook training for their climactic sword fight .",
"title": ""
},
{
"docid": "The_Air_I_Breathe",
"text": "The Air I Breathe is the 2007 directorial film debut of Korean-American filmmaker Jieho Lee , who co-wrote the script with Bob DeRosa . It stars Kevin Bacon , Julie Delpy , Brendan Fraser , Andy Garcia , Sarah Michelle Gellar , Emile Hirsch , and Forest Whitaker . The film was financed by NALA Investments through its production company NALA Films , and was released on January 25 , 2008 in the United States . The concept of the film is based on an ancient Chinese proverb that breaks life down into four emotional cornerstones -- Happiness ( Whitaker ) , Pleasure ( Fraser ) , Sorrow ( Gellar ) , and Love ( Bacon ) . The proverb speaks of these emotions , not as isolated fragments of feelings , but as elements that make up the whole of the human existence . Each of the four protagonists is based on one of the four emotions ; and like the proverb their paths are inextricably linked to each other , akin to the Fingers ( Garcia ) of a hand . None of the four main characters ' actual names are mentioned in the whole film , although Gellar 's character 's stage name , `` Trista '' , is mentioned several times .",
"title": ""
},
{
"docid": "Possession_(2009_film)",
"text": "Possession is an 2009 American remake of the South Korean film Addicted . It is a psychological thriller film starring Sarah Michelle Gellar and Lee Pace .",
"title": ""
},
{
"docid": "Prinze",
"text": "Prinze is a surname . Notable people with the surname include : Freddie Prinze , American actor Freddie Prinze , Jr. , American actor Sarah Michelle Gellar Prinze , American actress",
"title": ""
},
{
"docid": "The_Wonderful_Maladys",
"text": "The Wonderful Maladys is a HBO television pilot written by Charles Randolph , directed by Alan Taylor and starring Sarah Michelle Gellar . HBO did not pick the series for their lineup .",
"title": ""
},
{
"docid": "Simply_Irresistible_(film)",
"text": "Simply Irresistible is a 1999 American romantic comedy film starring Sarah Michelle Gellar and Sean Patrick Flanery . It was directed by Mark Tarlov and was written by Judith Roberts .",
"title": ""
},
{
"docid": "Cruel_Intentions_(pilot)",
"text": "Cruel Intentions is an American drama pilot that was in production for NBC . It acted as a sequel to 1999 film of same name , with Sarah Michelle Gellar reprising her role of Kathryn Merteuil .",
"title": ""
},
{
"docid": "Harvard_Man",
"text": "Harvard Man is a 2001 crime comedy-drama thriller film written and directed by James Toback , and starring Adrian Grenier , Sarah Michelle Gellar , Joey Lauren Adams , Eric Stoltz , and Rebecca Gayheart .",
"title": ""
},
{
"docid": "Ringer_(TV_series)",
"text": "Ringer is an American television series that initially aired on The CW from September 13 , 2011 to April 17 , 2012 . The series stars Sarah Michelle Gellar , who plays twin sisters Bridget Kelly and Siobhan Martin . On May 13 , 2011 , it was reported that the project had been picked up to series by The CW . On October 12 , 2011 , The CW ordered a full first season of 22 episodes . Ringer received mixed reviews , though most critics praised Gellar 's performance . On May 11 , 2012 , The CW announced the cancellation of Ringer after one season .",
"title": ""
},
{
"docid": "Emily_Young_(film_director)",
"text": "Emily Young ( born 1970 ) is an award-winning English film director and screenwriter . Her film Veronika Decides to Die , an adaptation of the book by Paulo Coelho and starring Sarah Michelle Gellar was released in 2009 .",
"title": ""
},
{
"docid": "High_Stakes_(1989_film)",
"text": "High Stakes ( also known as Melanie Rose ) is a 1989 thriller-drama film starring Sally Kirkland , and features Sarah Michelle Gellar in a supporting role . Kathy Bates also has a minor role .",
"title": ""
},
{
"docid": "Simply_Irresistible",
"text": "Simply Irresistible may refer to : `` Simply Irresisitible '' ( song ) , a 1988 song by Robert Palmer Simply Irresistible ( film ) , a 1999 film starring Sarah Michelle Gellar `` Simply Irresistible '' , a story by Miranda Lee Simply Irresistible , a 2010 novel by Jill Shalvis",
"title": ""
},
{
"docid": "Moonshine_River",
"text": "`` Moonshine River '' is the first episode of The Simpsons twenty-fourth season . It originally aired on the Fox network in the United States on September 30 , 2012 . In the UK and Ireland , the episode aired on Sky 1 on 24 March 2013 with 1,295,000 viewers , making it the second most watched program that week . The episode has ten guest stars , Ken Burns , Zooey Deschanel , Sarah Michelle Gellar , Anne Hathaway , Maurice LaMarche , Don Pardo , Natalie Portman , Kevin Michael Richardson , Al Roker and Sarah Silverman . Deschanel , Gellar , Hathaway , Portman and Silverman reprise their roles as Bart 's previous love interests , Mary Spuckler ( from `` Apocalypse Cow '' ) , Gina Vendetti ( from `` The Wandering Juvie '' ) , Jenny ( from `` The Good , the Sad and the Drugly '' ) , Darcy ( from `` Little Big Girl '' ) and Nikki ( from `` Stealing First Base '' ) , respectively . This is the second episode in which the Simpsons go to New York City , the first episode being `` The City of New York vs. Homer Simpson '' . The title is a parody of the 1961 Academy Award-winning song , `` Moon River '' .",
"title": ""
},
{
"docid": "The_Return_(2006_film)",
"text": "The Return is a 2006 American horror thriller film directed by Asif Kapadia and starring Sarah Michelle Gellar , Kate Beahan , Peter O'Brien , and Sam Shepard . It was released theatrically on November 10 , 2006 , and on DVD on February 27 , 2007 . The Blu-ray was released on October 6 , 2009 .",
"title": ""
},
{
"docid": "Kathryn_Merteuil",
"text": "Kathryn Merteuil is a fictional character who appears in Cruel Intentions and Cruel Intentions 2 , portrayed by actresses Sarah Michelle Gellar and Amy Adams , respectively . Based on the Marquise Isabelle de Merteuil in Pierre Choderlos de Laclos 's Les Liaisons dangereuses , Kathryn serves as the primary antagonist of the series .",
"title": ""
},
{
"docid": "List_of_The_Grudge_characters",
"text": "The Grudge film series features a large cast of characters mainly created by screenwriter Stephen Susco and Takashi Shimizu . The film series focuses on people affected by a deadly curse that spreads like a virus and manifests itself in various ways , such as turning people homicidal or people being haunted , ultimately leading to their demise , if they come in contact with the curse in any way . All films in the series feature different protagonists , with the first being Karen Davis played by Sarah Michelle Gellar . The protagonist of the second installment and Karen 's younger sister Aubrey was played by Amber Tamblyn , while the protagonist of The Grudge 3 , Lisa , was portrayed by Johanna Braddy .",
"title": ""
},
{
"docid": "2001_Teen_Choice_Awards",
"text": "The 2001 Teen Choice Awards ceremony was held on August 12 , 2001 , at the Gibson Amphitheatre , Universal City , California . The event had no designated host but David Spade introduced the show with Aaron Carter and Nick Carter , Usher , Eve and Gwen Stefani and Shaggy as performers . Sarah Michelle Gellar received the Extraordinary Achievement Award .",
"title": ""
},
{
"docid": "Karen_Davis_(The_Grudge)",
"text": "Karen Davis ( portrayed by Sarah Michelle Gellar ) is a fictional character from The Grudge . Being the central character , she uncovers the Saeki house 's dark past and is the only one to survive the first film . She returns in The Grudge 2 and compels her sister , Aubrey , to put a stop to the curse . Her portrayal was met with critical acclaim by critics and the films crew .",
"title": ""
},
{
"docid": "Never_Kill_a_Boy_on_the_First_Date",
"text": "`` Never Kill a Boy on the First Date '' is the fifth episode of the first season of the television series Buffy the Vampire Slayer . The episode was written by story editors Rob Des Hotel and Dean Batali , and directed by David Semel . The narrative follows Buffy Summers ( Sarah Michelle Gellar ) , as she struggles to find a date and stop the rise of the Anointed One .",
"title": ""
},
{
"docid": "Prophecy_Girl",
"text": "`` Prophecy Girl '' is the season finale of the WB Television Network 's first season of the drama television series Buffy the Vampire Slayer , and the 12th episode of the series . It first aired on June 2 , 1997 . Series creator Joss Whedon wrote and directed the episode . The narrative features vampire Slayer Buffy Summers ( Sarah Michelle Gellar ) working to prevent vampire the Master ( Mark Metcalf ) from rising to power , despite a prophecy predicting her death at his hands . Due to the first season of the show acting as a midseason replacement for Savannah , all twelve episodes were produced before the first episode aired ( and as such , the conclusion of the episode serves to wrap the series up in case it were not renewed ) . All following seasons ran from September to May and received twenty-two episode pick-ups .",
"title": ""
},
{
"docid": "Beverly_Hills_Family_Robinson",
"text": "Beverly Hills Family Robinson is a 1997 American Walt Disney television film based on the novel Swiss Family Robinson by Johann David Wyss . The film features Dyan Cannon , Martin Mull , Sarah Michelle Gellar and Ryan O'Donohue as the main cast and was aired on ABC . This Disney film was shot in the Far North of Queensland , Australia from 25 January to 23 February 1996 .",
"title": ""
},
{
"docid": "Veronika_Decides_to_Die_(film)",
"text": "Veronika Decides to Die is a 2009 psychological drama film directed by Emily Young and starring Sarah Michelle Gellar , Jonathan Tucker , Melissa Leo , David Thewlis and Erika Christensen , . The film is written by Larry Gross and Roberta Hanley and is adapted from the best-selling novel of the same name by Paulo Coelho . The setting of the movie is New York instead of the original location of the novel in Ljubljana , Slovenia .",
"title": ""
},
{
"docid": "April_O'Neil",
"text": "April O'Neil is a fictional character from the Teenage Mutant Ninja Turtles comics and all related media . In all of the TMNT continuities , she is a good friend of the Turtles : Leonardo , Donatello , Raphael , and Michelangelo . April made her first appearance in the Mirage comic series in 1984 as a computer programmer . She was later portrayed as a strong-willed news reporter in the Turtles ' first animated series , as a warrior in the Teenage Mutant Ninja Turtles Adventures comic produced by Archie Comics , and various other personas in different TMNT media . April was later voiced by Renae Jacobs in the 1987 animated series , in the 2003 animated series by Veronica Taylor , and by Sarah Michelle Gellar in the 2007 film TMNT . In the 2012 animated series , April is voiced by Mae Whitman . In live-action media , she has been portrayed by Judith Hoag ( 1990 ) , Paige Turco ( 1991 and 1993 ) , and Megan Fox ( 2014 and 2016 ) .",
"title": ""
},
{
"docid": "The_Wandering_Juvie",
"text": "`` The Wandering Juvie '' is the sixteenth episode of The Simpsons ' fifteenth season . It originally aired on the Fox network in the United States on March 28 , 2004 . It guest-starred Sarah Michelle Gellar as Gina Vendetti . It also guest-starred Charles Napier and Jane Kaczmarek . Bart gets sent to juvenile hall after registering for gifts at a department store and having a fraudulent wedding to obtain gifts . This episode sees the first appearance of Gina Vendetti , who later appears in `` Moonshine River '' .",
"title": ""
},
{
"docid": "Angel_(Buffy_the_Vampire_Slayer_episode)",
"text": "`` Angel '' is the seventh episode of season 1 of the television series Buffy the Vampire Slayer . It was written by co-executive producer David Greenwalt and directed by Scott Brazil . The narrative follows Buffy Summers ( Sarah Michelle Gellar ) , vampire slayer , coming to terms with her feelings for Angel ( David Boreanaz ) , who is revealed to be a vampire cursed with a soul . However , Darla ( Julie Benz ) is playing a deadly game manipulating both Buffy and Angel to the Master 's ( Mark Metcalf ) will .",
"title": ""
},
{
"docid": "Sophia_Crawford",
"text": "Sophia Crawford ( born 19 May 1966 at Hammersmith , London , United Kingdom ) is an actress , stuntwoman and martial artist . She was Sarah Michelle Gellar 's stunt double on the first four seasons of Buffy the Vampire Slayer . She also married ` Buffy ' stunt Co-ordinator , Jeff Pruitt in 1998 . She is also known for her role as `` Chameleon '' , one of the fighters on WMAC Masters and performing on the TV series Mighty Morphin ' Power Rangers . She also doubled for Fergie in the 2006 movie Poseidon .",
"title": ""
}
] |
PLAIN-1648
|
monounsaturated fats
|
[
{
"docid": "MED-5333",
"text": "BACKGROUND/AIM: A vegetarian diet is known to prevent a series of diseases but may influence the balance of carbohydrate and fat metabolism as well as collagen synthesis. This study compares expression patterns of relevant genes in oral mucosa of omnivores and vegetarians. METHODS: Quantitative reverse transcriptase polymerase chain reaction was applied for analysis of mRNA levels from carnitine transporter OCTN2, hepatic CPT1A and nonhepatic CPT1B isoforms of carnitine palmitoyltransferase and collagen (CCOL2A1) in oral mucosa. RESULTS: Compared with volunteers with traditional eating habits, carbohydrate consumption was significantly higher (+22%) in vegetarians. This was associated with a significant stimulation of CPT1A (+50%) and OCTN2 (+10%) and a lowered collagen synthesis (-10%). CONCLUSION: These novel findings provide further insight into the association of a changed fat metabolism and reduced collagen synthesis in vegetarians, which could also play a role in the aging process. Copyright 2008 S. Karger AG, Basel.",
"title": "Vegetarian diet affects genes of oxidative metabolism and collagen synthesis."
},
{
"docid": "MED-1458",
"text": "BACKGROUND/OBJECTIVES: Vegans have a lower incidence of insulin resistance (IR)-associated diseases and a higher insulin sensitivity (IS) compared with omnivores. The aim of this study was to examine whether the higher IS in vegans relates to markers of mitochondrial biogenesis and to intramyocellular lipid (IMCL) content. SUBJECTS/METHODS: Eleven vegans and 10 matched (race, age, sex, body mass index, physical activity and energy intake) omnivorous controls were enrolled in a case-control study. Anthropometry, bioimpedance (BIA), ultrasound measurement of visceral and subcutaneous fat layer, parameters of glucose and lipid homeostasis, hyperinsulinemic euglycemic clamp and muscle biopsies were performed. Citrate synthase (CS) activity, mitochondrial DNA (mtDNA) and IMCL content were assessed in skeletal muscle samples. RESULTS: Both groups were comparable in anthropometric and BIA parameters, physical activity and protein-energy intake. Vegans had significantly higher glucose disposal (M-value, vegans 8.11±1.51 vs controls 6.31±1.57 mg/kg/min, 95% confidence interval: 0.402 to 3.212, P=0.014), slightly lower IMCL content (vegans 13.91 (7.8 to 44.0) vs controls 17.36 (12.4 to 78.5) mg/g of muscle, 95% confidence interval: -7.594 to 24.550, P=0.193) and slightly higher relative muscle mtDNA amount (vegans 1.36±0.31 vs controls 1.13±0.36, 95% confidence interval:-0.078 to 0.537, P=0.135). No significant differences were found in CS activity (vegans 18.43±5.05 vs controls 18.16±5.41 μmol/g/min, 95% confidence interval: -4.503 to 5.050, P=0.906). CONCLUSIONS: Vegans have a higher IS, but comparable mitochondrial density and IMCL content with omnivores. This suggests that a decrease in whole-body glucose disposal may precede muscle lipid accumulation and mitochondrial dysfunction in IR development.",
"title": "Higher insulin sensitivity in vegans is not associated with higher mitochondrial density."
},
{
"docid": "MED-1454",
"text": "AIMS/HYPOTHESIS: The amount and quality of fat in the diet could be of importance for development of insulin resistance and related metabolic disorders. Our aim was to determine whether a change in dietary fat quality alone could alter insulin action in humans. METHODS: The KANWU study included 162 healthy subjects chosen at random to receive a controlled, isoenergetic diet for 3 months containing either a high proportion of saturated (SAFA diet) or monounsaturated (MUFA diet) fatty acids. Within each group there was a second assignment at random to supplements with fish oil (3.6 g n-3 fatty acids/d) or placebo. RESULTS: Insulin sensitivity was significantly impaired on the saturated fatty acid diet (-10%, p = 0.03) but did not change on the monounsaturated fatty acid diet (+2%, NS) (p = 0.05 for difference between diets). Insulin secretion was not affected. The addition of n-3 fatty acids influenced neither insulin sensitivity nor insulin secretion. The favourable effects of substituting a monounsaturated fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only seen at a total fat intake below median (37E%). Here, insulin sensitivity was 12.5% lower and 8.8% higher on the saturated fatty acid diet and monounsaturated fatty acid diet respectively (p = 0.03). Low density lipoprotein cholesterol (LDL) increased on the saturated fatty acid diet (+4.1%, p < 0.01) but decreased on the monounsaturated fatty acid diet (MUFA) (-5.2, p < 0.001), whereas lipoprotein (a) [Lp(a)] increased on a monounsaturated fatty acid diet by 12% (p < 0.001). CONCLUSIONS/INTERPRETATION: A change of the proportions of dietary fatty acids, decreasing saturated fatty acid and increasing monounsaturated fatty acid, improves insulin sensitivity but has no effect on insulin secretion. A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake (> 37E%).",
"title": "Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study."
},
{
"docid": "MED-1456",
"text": "OBJECTIVE: To test the hypothesis that dietary factors in the vegan diet lead to improved insulin sensitivity and lower intramyocellular lipid (IMCL) storage. DESIGN: Case-control study. SETTING: Imperial College School of Medicine, Hammersmith Hospital Campus, London, UK. SUBJECTS: A total of 24 vegans and 25 omnivores participated in this study; three vegan subjects could not be matched therefore the matched results are shown for 21 vegans and 25 omnivores. The subjects were matched for gender, age and body mass index (BMI). INTERVENTIONS: Full anthropometry, 7-day dietary assessment and physical activity levels were obtained. Insulin sensitivity (%S) and beta-cell function (%B) were determined using the homeostatic model assessment (HOMA). IMCL levels were determined using in vivo proton magnetic resonance spectroscopy; total body fat content was assessed by bioelectrical impedance. RESULTS: There was no difference between the groups in sex, age, BMI, waist measurement, percentage body fat, activity levels and energy intake. Vegans had a significantly lower systolic blood pressure (-11.0 mmHg, CI -20.6 to -1.3, P=0.027) and higher dietary intake of carbohydrate (10.7%, CI 6.8-14.5, P<0.001), nonstarch polysaccharides (20.7 g, CI 15.8-25.6, P<0.001) and polyunsaturated fat (2.8%, CI 1.0-4.6, P=0.003), with a significantly lower glycaemic index (-3.7, CI -6.7 to -0.7, P=0.01). Also, vegans had lower fasting plasma triacylglycerol (-0.7 mmol/l, CI -0.9 to -0.4, P<0.001) and glucose (-0.4 mmol/l, CI -0.7 to -0.09, P=0.05) concentrations. There was no significant difference in HOMA %S but there was with HOMA %B (32.1%, CI 10.3-53.9, P=0.005), while IMCL levels were significantly lower in the soleus muscle (-9.7, CI -16.2 to -3.3, P=0.01). CONCLUSION: Vegans have a food intake and a biochemical profile that will be expected to be cardioprotective, with lower IMCL accumulation and beta-cell protective.",
"title": "Veganism and its relationship with insulin resistance and intramyocellular lipid."
},
{
"docid": "MED-1461",
"text": "Insulin resistance is the best prediction factor for the clinical onset of type 2 diabetes. It was suggested that intramuscular triglyceride store may be a primary pathogenic factor for its development. To test this hypothesis, 14 young lean offspring of type 2 diabetic parents, a model of in vivo insulin resistance with increased risk to develop diabetes, and 14 healthy subjects matched for anthropomorphic parameters and life habits were studied with 1) euglycemic-hyperinsulinemic clamp to assess whole body insulin sensitivity, 2) localized 1H nuclear magnetic resonance (NMR) spectroscopy of the soleus (higher content of fiber type I, insulin sensitive) and tibialis anterior (higher content of fiber type IIb, less insulin sensitive) muscles to assess intramyocellular triglyceride content, 3) 13C NMR of the calf subcutaneous adipose tissue to assess composition in saturated/unsaturated carbons of triglyceride fatty acid chains, and 4) dual X-ray energy absorption to assess body composition. Offspring of diabetic parents, notwithstanding normal fat content and distribution, were characterized by insulin resistance and increased intramyocellular triglyceride content in the soleus (P < 0.01) but not in the tibialis anterior (P = 0.19), but showed a normal content of saturated/unsaturated carbons in the fatty acid chain of subcutaneous adipocytes. Stepwise regression analysis selected intramyocellular triglyceride soleus content and plasma free fatty acid levels as the main predictors of whole body insulin sensitivity. In conclusion, 1H and 13C NMR spectroscopy revealed intramyocellular abnormalities of lipid metabolism associated with whole body insulin resistance in subjects at high risk of developing diabetes, and might be useful tools for noninvasively monitoring these alterations in diabetes and prediabetic states.",
"title": "Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy as..."
},
{
"docid": "MED-4619",
"text": "Avocados have a high content of phytochemicals with potential chemopreventive activity. Previously we reported that phytochemicals extracted from avocado meat into a chloroform partition (D003) selectively induced apoptosis in cancer but not normal, human oral epithelial cell lines. In the present study, we observed that treatment of human oral cancer cell lines containing high levels of reactive oxygen (ROS) with D003 increased ROS levels twofold to threefold and induced apoptosis. In contrast, ROS levels increased only 1.3-fold, and apoptosis was not induced in the normal cell lines containing much lower levels of basal ROS. When cellular ROS levels in the malignant cell lines were reduced by N-acetyl-l-cysteine (NAC), cells were resistant to D003 induced apoptosis. NAC also delayed the induction of apoptosis in dominant negative FADD-expressing malignant cell lines. D003 increased ROS levels via mitochondrial complex I in the electron transport chain to induce apoptosis. Normal human oral epithelial cell lines transformed with HPV16 E6 or E7 expressed higher basal levels of ROS and became sensitive to D003. These data suggest that perturbing the ROS levels in human oral cancer cell lines may be a key factor in selective apoptosis and molecular targeting for chemoprevention by phytochemicals.",
"title": "Selective induction of apoptosis of human oral cancer cell lines by avocado extracts via a ROS-mediated mechanism."
},
{
"docid": "MED-1455",
"text": "The ingestion of excessive amounts of saturated fatty acids (SFAs) and transfatty acids (TFAs) is considered to be a risk factor for cardiovascular diseases, insulin resistance, dyslipidemia, and obesity. The focus of this paper was to elucidate the influence of dietary SFA and TFA intake on the promotion of lipotoxicity to the liver and cardiovascular, endothelial, and gut microbiota systems, as well as on insulin resistance and endoplasmic reticulum stress. The saturated and transfatty acids favor a proinflammatory state leading to insulin resistance. These fatty acids can be involved in several inflammatory pathways, contributing to disease progression in chronic inflammation, autoimmunity, allergy, cancer, atherosclerosis, hypertension, and heart hypertrophy as well as other metabolic and degenerative diseases. As a consequence, lipotoxicity may occur in several target organs by direct effects, represented by inflammation pathways, and through indirect effects, including an important alteration in the gut microbiota associated with endotoxemia. Interactions between these pathways may perpetuate a feedback process that exacerbates an inflammatory state. The importance of lifestyle modification, including an improved diet, is recommended as a strategy for treatment of these diseases.",
"title": "Lipotoxicity: Effects of Dietary Saturated and Transfatty Acids"
},
{
"docid": "MED-1460",
"text": "Insulin resistance condition is associated to the development of several syndromes, such as obesity, type 2 diabetes mellitus and metabolic syndrome. Although the factors linking insulin resistance to these syndromes are not precisely defined yet, evidence suggests that the elevated plasma free fatty acid (FFA) level plays an important role in the development of skeletal muscle insulin resistance. Accordantly, in vivo and in vitro exposure of skeletal muscle and myocytes to physiological concentrations of saturated fatty acids is associated with insulin resistance condition. Several mechanisms have been postulated to account for fatty acids-induced muscle insulin resistance, including Randle cycle, oxidative stress, inflammation and mitochondrial dysfunction. Here we reviewed experimental evidence supporting the involvement of each of these propositions in the development of skeletal muscle insulin resistance induced by saturated fatty acids and propose an integrative model placing mitochondrial dysfunction as an important and common factor to the other mechanisms.",
"title": "Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: importance of the mitochondrial function"
},
{
"docid": "MED-4621",
"text": "The aqueous seed extract of Persea americana Mill (Lauraceae) is used by herbalists in Nigeria for the management of hypertension. As part of our on-going scientific evaluation of the extract, we designed the present study to assess its acute and sub-acute toxicity profiles in rats. Experiments were conducted to determine the oral median lethal dose (LD50) and other gross toxicological manifestations on acute basis. In the sub-acute experiments, the animals were administered 2.5 g/kg (p.o) per day of the extract for 28 consecutive days. Animal weight and fluid intake were recorded during the 28 days period. Terminally, kidneys, hearts, blood/sera were obtained for weight, haematological and biochemical markers of toxicity. Results show that the LD50 could not be determined after a maximum dose of 10 g/kg. Sub-acute treatment with the extract neither affected whole body weight nor organ-to-body weight ratios but significantly increased the fluid intake (P < 0.0001). Haematological parameters and the levels of ALT, AST, albumin and creatinine were not significantly altered. However, the concentration of total proteins was significantly increased in the treated group. In conclusion, the aqueous seed extract of P. americana is safe on sub-acute basis but extremely high doses may not be advisable.",
"title": "Acute and Sub-Acute Toxicological Assessment of the Aqueous Seed Extract of Persea Americana Mill (Lauraceae) in Rats"
},
{
"docid": "MED-1474",
"text": "PURPOSE OF REVIEW: Acute exposure to fatty acids causes insulin resistance in muscle, and excess dietary lipid and obesity are also strongly associated with muscle insulin resistance. Relevant mechanisms, however, are still not fully elucidated. Here we examine the latest evidence as to why lipids might accumulate in muscle and the possible mechanisms for lipid-induced insulin resistance. RECENT FINDINGS: Muscle lipid metabolites such as long chain fatty acid coenzyme As, diacylglycerol and ceramides may impair insulin signalling directly. Crosstalk between inflammatory signalling pathways and insulin signalling pathways, mitochondrial dysfunction and oxidative stress have also been put forward as major contributors to the development or maintenance of lipid-induced insulin resistance in muscle. Several animal models with gene deletions in pathways of fatty acid synthesis and storage also show increased metabolic rate, reduced intramuscular lipid storage and improved insulin action when challenged with a high lipid load. SUMMARY: Studies in genetic and dietary obese animal models, genetically modified animals and humans with obesity or type 2 diabetes suggest plausible mechanisms for effects of fatty acids, lipid metabolites, inflammatory pathways and mitochondrial dysfunction on insulin action in muscle. Many of these mechanisms, however, have been demonstrated in situations in which lipid accumulation (obesity) already exists. Whether the initial events leading to muscle insulin resistance are direct effects of fatty acids in muscle or are secondary to lipid accumulation in adipose tissue or liver remains to be clarified.",
"title": "Free fatty acids and skeletal muscle insulin resistance."
},
{
"docid": "MED-4620",
"text": "Phytochemicals are recognized as playing an important role in cancer prevention by fruits and vegetables. The avocado is a widely grown and consumed fruit that is high in nutrients and low in calories, sodium, and fats. Studies have shown that phytochemicals extracted from the avocado fruit selectively induce cell cycle arrest, inhibit growth, and induce apoptosis in precancerous and cancer cell lines. Our recent studies indicate that phytochemicals extracted with chloroform from avocado fruits target multiple signaling pathways and increase intracellular reactive oxygen leading to apoptosis. This review summarizes the reported phytochemicals in avocado fruit and discusses their molecular mechanisms and targets. These studies suggest that individual and combinations of phytochemicals from the avocado fruit may offer an advantageous dietary strategy in cancer prevention.",
"title": "Chemopreventive characteristics of avocado fruit."
},
{
"docid": "MED-5010",
"text": "Phytochemicals are recognized as playing an important role in cancer prevention by fruits and vegetables. The avocado is a widely grown and consumed fruit that is high in nutrients and low in calories, sodium, and fats. Studies have shown that phytochemicals extracted from the avocado fruit selectively induce cell cycle arrest, inhibit growth, and induce apoptosis in precancerous and cancer cell lines. Our recent studies indicate that phytochemicals extracted with chloroform from avocado fruits target multiple signaling pathways and increase intracellular reactive oxygen leading to apoptosis. This review summarizes the reported phytochemicals in avocado fruit and discusses their molecular mechanisms and targets. These studies suggest that individual and combinations of phytochemicals from the avocado fruit may offer an advantageous dietary strategy in cancer prevention.",
"title": "Chemopreventive characteristics of avocado fruit."
},
{
"docid": "MED-1463",
"text": "Insulin resistance is a pathophysiological link of obesity to type 2 diabetes. The initial cause of insulin resistance is critical for prevention and treatment of type 2 diabetes. Lipotoxicity is a well-known concept in the explanation of initiation of insulin resistance. Although there are several prevailing hypotheses about the cellular/molecular mechanisms of lipotoxicity, such as inflammation, oxidative stress, hyperinsulinemia, and ER stress, the relative importance of these hypothesized events remains to be determined. The role of hyperinsulinemia is relatively under documented in the literature for the initiation of insulin resistance. In this review, an interaction of fatty acid and beta-cells, and a synergy between free fatty acids (FFAs) and insulin are emphasized for the role of hyperinsulinemia. This article presents the evidence about FFA-induced insulin secretion in vitro and in vivo, recent advances in the molecular mechanism of FFA action in beta-cells, a role of GPR40 in the development of insulin resistance, and the negative feedback loop of the insulin receptor signal pathway. The negative feedback loop is discussed in detail with a focus on IRS-1 serine kinases. This article provides a substantial support for the role of insulin in the early stages of FFA-associated insulin resistance. The hypothesis of insulin's role in lipotoxicity is referred to as the \"insulin hypothesis\" in this review. According to this hypothesis, prevention of increased beta-cell response to glucose may be a potential approach for early intervention of metabolic syndrome.",
"title": "Role of insulin in the pathogenesis of free fatty acid-induced insulin resistance in skeletal muscle."
},
{
"docid": "MED-5011",
"text": "AV119 is a patented blend of two sugars from avocado that can induce human beta-defensin-2 production by normal human keratinocytes. In this study, we analysed the effect of AV119 on growth and invasiveness of Malassezia furfur, a dimorphic, lipid-dependent yeast that is part of the normal human cutaneous commensal flora. The ability to modulate the expression of the proinflammatory and immunomodulatory cytokines in normal human keratinocytes was also investigated. Microbiological assay demonstrated that this sugar induced the aggregation of yeast cells and inhibited the invasiveness of M. furfur, without affecting its growth. Real-time PCR analysis demonstrated that AV119 was able to modulate the HBD-2 response in treated keratinocytes, reaching a maximum after 48-h treatment, and to induce the recovery of a satisfactory proinflammatory response in human keratinocytes. As AV119 can induce aggregation of yeast cells, thus inhibiting their penetration into the keratinocytes, the sugar could be used in the preparation of cosmetics or pharmacological drugs to inhibit colonization of the skin by pathogenic strains of M. furfur.",
"title": "Effects of AV119, a natural sugar from avocado, on Malassezia furfur invasiveness and on the expression of HBD-2 and cytokines in human keratinocytes."
},
{
"docid": "MED-5009",
"text": "OBJECTIVE: To evaluate the efficacy of preparations with avocado-soybean unsaponifiables (ASUs) in osteoarthritis (OA) patients using meta-analysis on randomized controlled trials (RCTs). METHOD: RCTs from systematic searches were included if they explicitly stated that hip and/or knee OA patients were randomized to either ASU or placebo. The co-primary outcome was reduction in pain and Lequesne index, leading to effect size (ES), calculated as the standardized mean difference. As secondary analysis, the number of responders to therapy was analyzed as odds ratios (ORs). Restricted maximum likelihood methods were applied for the meta-analyses, using mixed effects models. RESULTS: Four trials--all supported by the manufacturer--were included, with 664 OA patients with either hip (41.4%) or knee (58.6%) OA allocated to either 300 mg ASU (336) or placebo (328). Average trial duration was 6 months (range: 3-12 months). Though based on heterogeneous results, the combined pain reduction favored ASU (I(2) = 83.5%, ES = 0.39 [95% confidence intervals: 0.01-0.76], P=0.04). Applying the Lequesne index also favored ASU (I(2) = 61.0%, ES = 0.45 [0.21-0.70], P = 0.0003). Secondarily, the number of responders following ASU compared to placebo (OR = 2.19, P = 0.007) corresponded to a number needed to treat of six (4-21) patients. CONCLUSIONS: Based on the available evidence, patients may be recommended to give ASU a chance for e.g., 3 months. Meta-analysis data support better chances of success in patients with knee OA than in those with hip OA.",
"title": "Symptomatic efficacy of avocado-soybean unsaponifiables (ASU) in osteoarthritis (OA) patients: a meta-analysis of randomized controlled trials."
},
{
"docid": "MED-1459",
"text": "Insulin resistance is a complex metabolic disorder that defies a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, may be a common pathway leading to impaired insulin signaling and insulin resistance.",
"title": "Integrating Mechanisms for Insulin Resistance: Common Threads and Missing Links"
},
{
"docid": "MED-1457",
"text": "Obesity and type 2 diabetes have been associated with a high-fat diet (HFD) and reduced mitochondrial mass and function. We hypothesized a HFD may affect expression of genes involved in mitochondrial function and biogenesis. To test this hypothesis, we fed 10 insulin-sensitive males an isoenergetic HFD for 3 days with muscle biopsies before and after intervention. Oligonucleotide microarray analysis revealed 297 genes were differentially regulated by the HFD (Bonferonni adjusted P < 0.001). Six genes involved in oxidative phosphorylation (OXPHOS) decreased. Four were members of mitochondrial complex I: NDUFB3, NDUFB5, NDUFS1, and NDUFV1; one was SDHB in complex II and a mitochondrial carrier protein SLC25A12. Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC1) alpha and PGC1beta mRNA were decreased by -20%, P < 0.01, and -25%, P < 0.01, respectively. In a separate experiment, we fed C57Bl/6J mice a HFD for 3 weeks and found that the same OXPHOS and PGC1 mRNAs were downregulated by approximately 90%, cytochrome C and PGC1alpha protein by approximately 40%. Combined, these results suggest a mechanism whereby HFD downregulates genes necessary for OXPHOS and mitochondrial biogenesis. These changes mimic those observed in diabetes and insulin resistance and, if sustained, may result in mitochondrial dysfunction in the prediabetic/insulin-resistant state.",
"title": "A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle."
}
] |
[
{
"docid": "MED-5267",
"text": "BACKGROUND: The regulatory function of the endothelium is altered in hypercholesterolemia, and the subsequent endothelial dysfunction plays a central role in the development of atherosclerosis. OBJECTIVE: To determine whether endothelial function in hypercholesterolemic patients is affected by replacing a saturated fat-enriched diet with a low-fat, low-saturated fat diet (the U.S. National Cholesterol Education Program stage 1 [NCEP-1] diet) or a diet rich in monounsaturated fat (such as that common in Mediterranean countries). DESIGN: Intervention dietary study with a baseline phase and two randomized crossover dietary periods. SETTING: Hospital Universitario Reina Sofía, Córdoba, Spain. PATIENTS: 22 hypercholesterolemic men. INTERVENTION: Patients followed a diet high in saturated fat, then were assigned in a crossover design to the NCEP-1 diet or a Mediterranean diet. Each dietary period lasted 28 days. MEASUREMENTS: Plasma P-selectin levels, lipid concentrations, and endothelial function. RESULTS: Compared with the saturated fat diet, flow-mediated dilatation increased during the Mediterranean diet but not during the NCEP-1 diet. In addition, levels of plasma cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and P-selectin decreased during the NCEP-1 and Mediterranean diets. CONCLUSION: In hypercholesterolemic men, diets low in fat (especially saturated fat) and diets rich in monounsaturated fats improve endothelial function.",
"title": "Mediterranean and low-fat diets improve endothelial function in hypercholesterolemic men."
},
{
"docid": "MED-963",
"text": "The public perceives that the nutritional quality of eggs produced as free range is superior to that of eggs produced in cages. Therefore, this study compared the nutrient content of free-range vs. cage-produced shell eggs by examining the effects of the laboratory, production environment, and hen age. A flock of 500 Hy-Line Brown layers were hatched simultaneously and received the same care (i.e., vaccination, lighting, and feeding regimen), with the only difference being access to the range. The nutrient content of the eggs was analyzed for cholesterol, n-3 fatty acids, saturated fat, monounsaturated fat, polyunsaturated fat, β-carotene, vitamin A, and vitamin E. The same egg pool was divided and sent to 4 different laboratories for analysis. The laboratory was found to have a significant effect on the content of all nutrients in the analysis except for cholesterol. Total fat content in the samples varied (P < 0.001) from a high of 8.88% to a low of 6.76% in laboratories D and C, respectively. Eggs from the range production environment had more total fat (P < 0.05), monounsaturated fat (P < 0.05), and polyunsaturated fat (P < 0.001) than eggs produced by caged hens. Levels of n-3 fatty acids were also higher (P < 0.05), at 0.17% in range eggs vs. 0.14% in cage eggs. The range environment had no effect on cholesterol (163.42 and 165.38 mg/50 g in eggs from caged and range hens, respectively). Vitamin A and E levels were not affected by the husbandry to which the hens were exposed but were lowest at 62 wk of age. The age of the hens did not influence the fat levels in the egg, but cholesterol levels were highest (P < 0.001) at 62 wk of age (172.54 mg/50 g). Although range production did not influence the cholesterol level in the egg, there was an increase in fat levels in eggs produced on the range.",
"title": "Comparison of fatty acid, cholesterol, and vitamin A and E composition in eggs from hens housed in conventional cage and range production facilities."
},
{
"docid": "MED-1410",
"text": "In 15 cohorts of the Seven Countries Study, comprising 11,579 men aged 40-59 years and \"healthy\" at entry, 2,288 died in 15 years. Death rates differed among cohorts. Differences in mean age, blood pressure, serum cholesterol, and smoking habits \"explained\" 46% of variance in death rate from all causes, 80% from coronary heart disease, 35% from cancer, and 45% from stroke. Death rate differences were unrelated to cohort differences in mean relative body weight, fatness, and physical activity. The cohorts differed in average diets. Death rates were related positively to average percentage of dietary energy from saturated fatty acids, negatively to dietary energy percentage from monounsaturated fatty acids, and were unrelated to dietary energy percentage from polyunsaturated fatty acids, proteins, carbohydrates, and alcohol. All death rates were negatively related to the ratio of monounsaturated to saturated fatty acids. Inclusion of that ratio with age, blood pressure, serum cholesterol, and smoking habits as independent variables accounted for 85% of variance in rates of deaths from all causes, 96% coronary heart disease, 55% cancer, and 66% stroke. Oleic acid accounted for almost all differences in monounsaturates among cohorts. All-cause and coronary heart disease death rates were low in cohorts with olive oil as the main fat. Causal relationships are not claimed but consideration of characteristics of populations as well as of individuals within populations is urged in evaluating risks.",
"title": "The diet and 15-year death rate in the seven countries study."
},
{
"docid": "MED-1069",
"text": "AIMS/HYPOTHESIS: Prolonged elevation of plasma specific fatty acids may exert differential effects on glucose-stimulated insulin secretion (GSIS), insulin sensitivity and clearance. SUBJECTS AND METHODS: We examined the effect of oral ingestion, at regular intervals for 24 h, of an emulsion containing either predominantly monounsaturated (MUFA), polyunsaturated (PUFA) or saturated (SFA) fat or water (control) on GSIS, insulin sensitivity and insulin clearance in seven overweight or obese, non-diabetic humans. Four studies were conducted in each individual in random order, 4-6 weeks apart. Twenty-four hours after initiation of oral ingestion, subjects underwent a 2 h, 20 mmol/l hyperglycaemic clamp to assess GSIS, insulin sensitivity and insulin clearance. RESULTS: Following oral ingestion of any of the three fat emulsions over 24 h, plasma NEFAs were elevated by approximately 1.5- to 2-fold over the basal level. Ingestion of any of the three fat emulsions resulted in reduction in insulin clearance, and SFA ingestion reduced insulin sensitivity. PUFA ingestion was associated with an absolute reduction in GSIS, whereas insulin secretion failed to compensate for insulin resistance in subjects who ingested SFA. CONCLUSIONS/INTERPRETATION: Oral ingestion of fats with differing degrees of saturation resulted in different effects on insulin secretion and action. PUFA ingestion resulted in an absolute reduction in insulin secretion and SFA ingestion induced insulin resistance. Failure of insulin secretion to compensate for insulin resistance implies impaired beta cell function in the SFA study.",
"title": "Differential effects of monounsaturated, polyunsaturated and saturated fat ingestion on glucose-stimulated insulin secretion, sensitivity and clear..."
},
{
"docid": "MED-1238",
"text": "The relationship between dietary fat and glucose metabolism has been recognized for at least 60 years. In experimental animals, high fat diets result in impaired glucose tolerance. This impairment is associated with decreased basal and insulin-stimulated glucose metabolism. Impaired insulin binding and/or glucose transporters has been related to changes in the fatty acid composition of the membrane induced by dietary fat modification. In humans, high-fat diets, independent of fatty acid profile, have been reported to result in decreased insulin sensitivity. Saturated fat, relative to monounsaturated and polyunsaturated fat, appears to be more deleterious with respect to fat-induced insulin insensitivity. Some of the adverse effects induced by fat feeding can be ameliorated with omega-3 fatty acid. Epidemiological data in humans suggest that subjects with higher intakes of fat are more prone to develop disturbances in glucose metabolism, type 2 diabetes or impaired glucose tolerance, than subjects with lower intakes of fat. Inconsistencies in the data may be attributable to clustering of high intakes of dietary fat (especially animal fat) with obesity and inactivity. Metabolic studies suggest that higher-fat diets containing a higher proportion of unsaturated fat result in better measures of glucose metabolism than high-carbohydrate diet. Clearly, the area of dietary fat and glucose metabolism has yet to be fully elucidated.",
"title": "Relationship of dietary fat to glucose metabolism."
},
{
"docid": "MED-5277",
"text": "Consumption of a meal high in monounsaturated fat was associated with acute impairment of endothelial function when compared with a carbohydrate-rich meal. Such a divergent response in endothelial function may be important in the modulation of vascular function in health and disease.",
"title": "Effect of fat and carbohydrate consumption on endothelial function."
},
{
"docid": "MED-5261",
"text": "OBJECTIVE—To examine the acute effects of consumption of monounsaturated (MUFAs) and saturated fatty acids (SAFAs) on endothelial function in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 33 participants were examined after consumption of two different isocaloric meals: one rich in MUFA and one rich in SAFA, in the form of extra-virgin olive oil and butter, respectively. Endothelial function was assessed by determination of flow-mediated dilatation (FMD). RESULTS—FMD did not change significantly after the MUFA-rich meal but declined after the SAFA-rich meal. The FMD during the experiment, expressed as incremental area under the curve, increased after the MUFA-rich meal by 5.2 ± 2.5% and decreased after the SAFA-rich meal by 16.7 ± 6.0% (Δ = −11.5 ± 6.4%; P = 0.008). CONCLUSIONS—Consumption of an SAFA-rich meal is harmful for the endothelium, while a MUFA-rich meal does not impair endothelial function in subjects with type 2 diabetes.",
"title": "Differential Effects of Two Isoenergetic Meals Rich in Saturated or Monounsaturated Fat on Endothelial Function in Subjects With Type 2 Diabetes"
},
{
"docid": "MED-2850",
"text": "Background: Fatty acids play a vital role in glucose homeostasis; however, studies on habitual dietary fat intakes and gestational diabetes mellitus (GDM) risk are limited and provide conflicting findings. Objective: We determined whether the total amount and the type and source of prepregnancy dietary fats are related to risk of GDM. Design: A prospective study was conducted in 13,475 women who reported a singleton pregnancy between 1991 and 2001 in the Nurses’ Health Study II. In these women, 860 incident GDM cases were reported. The adjusted RR of GDM was estimated for quintiles of total fat, specific fat, and the source of fat intakes by pooled logistic regression. Results: Higher animal fat and cholesterol intakes were significantly associated with increased GDM risk. Across increasing quintiles of animal fat, RRs (95% CIs) for GDM were 1.00 (reference), 1.55 (1.20, 1.98), 1.43 (1.09, 1.88), 1.40 (1.04, 1.89), and 1.88 (1.36, 2.60) (P-trend = 0.05). Corresponding RRs (95% CIs) for dietary cholesterol were 1.00 (reference), 1.08 (0.84, 1.32), 1.02 (0.78, 1.29), 1.20 (0.93, 1.55), and 1.45 (1.11, 1.89) (P-trend = 0.04). The substitution of 5% of energy from animal fat for an equal percentage of energy from carbohydrates was associated with significantly increased risk of GDM [RR (95% CI): 1.13 (1.08, 1.18); P < 0.0001]. No significant associations were observed between dietary polyunsaturated fat, monounsaturated fat, or trans fat intakes and GDM risk. Conclusion: Higher prepregnancy intakes of animal fat and cholesterol were associated with elevated GDM risk.",
"title": "A prospective study of prepregnancy dietary fat intake and risk of gestational diabetes"
},
{
"docid": "MED-4154",
"text": "Daily diet may have implications for skin ageing. However, data on the relationship between diet and the parameters of skin conditions are scarce. The present study aimed to examine the associations of biophysical properties of the skin of women with intakes of fats and antioxidant micronutrients as well as food groups as sources of these nutrients. In a cross-sectional study, we measured the hydration, surface lipids and elasticity of the skin of 716 Japanese women using non-invasive techniques. The extent of facial wrinkles in the crow's-foot area was determined by observation using the Daniell scale. Each subject's usual diet was determined with the use of a validated FFQ. After controlling for covariates including age, smoking status, BMI and lifetime sun exposure, the results showed that higher intakes of total fat, saturated fat and monounsaturated fat were significantly associated with increased skin elasticity. A higher intake of green and yellow vegetables was significantly associated with a decreased Daniell wrinkling score. Intake of saturated fat was significantly inversely associated with the Daniell wrinkling score after additional adjustment for green and yellow vegetable intake. Further studies with more accurate measurement methods are needed to investigate the role of daily diet in skin ageing.",
"title": "Association of dietary fat, vegetables and antioxidant micronutrients with skin ageing in Japanese women."
},
{
"docid": "MED-4211",
"text": "Circulating levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) have each been associated with premenopausal breast cancer risks. We analyzed data from a cross-sectional study of 261 premenopausal Japanese women aged 20-54 yr with adequate nutritional status to evaluate the relationships between concentrations of IGF-1 and IGFBP-3 in serum and dietary intakes of soy, fats and other nutrients. Diet was assessed by a semiquantitative food frequency questionnaire. There was no significant correlation between soy product as well as soy isoflavone intake and serum IGF-1 or IGFBP-3 levels after controlling for age, total energy, percent body fat, and education level. Total fat intake was significantly inversely correlated with serum IGFBP-3 level (r = -0.13, P = 0.04). The correlations of saturated and monounsaturated fats with serum IGFBP-3 were of borderline significance (r = -0.12, P = 0.06 and r = -0.11, P = 0.07, respectively).",
"title": "Dietary soy and fats in relation to serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels in premenopausal Jap..."
},
{
"docid": "MED-4481",
"text": "The aim of this study was to investigate whether dietary fat and meat intakes are associated with reflux esophagitis (RE), Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). In this all-Ireland case-control study, dietary intake data was collected using a food frequency questionnaire in 219 RE patients, 220 BE patients, 224 EAC patients, and 256 frequency-matched controls between 2002 and 2005. Unconditional multiple logistic regression analysis was used to examine the association between dietary variables and disease risk using quartiles of intake, to attain odds ratios (OR) and 95% confidence intervals (95%CI), while adjusting for potential confounders. Patients in the highest quartile of total fat intake had a higher risk of RE (OR=3.54; 95%CI=1.32–9.46) and EAC (OR=5.44; 95%CI=2.08–14.27). A higher risk of RE and EAC was also reported for patients in the highest quartile of saturated fat intake (OR=2.79; 95%CI=1.11–7.04; OR=2.41; 95%CI=1.14–5.08, respectively) and monounsaturated fat intake (OR=2.63; 95%CI=1.01–6.86; OR=5.35; 95%CI=2.14–13.34, respectively). Patients in the highest quartile of fresh red meat intake had a higher risk of EAC (OR=3.15; 95%CI=1.38–7.20). Patients in the highest category of processed meat intake had a higher risk of RE (OR=4.67; 95%CI=1.71–12.74). No consistent associations were seen for BE with either fat or meat intakes. Further studies, investigating the association between dietary fat and food sources of fat are needed to confirm these results.",
"title": "Dietary fat and meat intakes and risk of reflux esophagitis, Barrett’s esophagus and esophageal adenocarcinoma"
},
{
"docid": "MED-1552",
"text": "OBJECTIVE: To determine the quantitative importance of dietary fatty acids and dietary cholesterol to blood concentrations of total, low density lipoprotein, and high density lipoprotein cholesterol. DESIGN: Meta-analysis of metabolic ward studies of solid food diets in healthy volunteers. SUBJECTS: 395 dietary experiments (median duration 1 month) among 129 groups of individuals. RESULTS: Isocaloric replacement of saturated fats by complex carbohydrates for 10% of dietary calories resulted in blood total cholesterol falling by 0.52 (SE 0.03) mmol/l and low density lipoprotein cholesterol falling by 0.36 (0.05) mmol/l. Isocaloric replacement of complex carbohydrates by polyunsaturated fats for 5% of dietary calories resulted in total cholesterol falling by a further 0.13 (0.02) mmol/l and low density lipoprotein cholesterol falling by 0.11 (0.02) mmol/l. Similar replacement of carbohydrates by monounsaturated fats produced no significant effect on total or low density lipoprotein cholesterol. Avoiding 200 mg/day dietary cholesterol further decreased blood total cholesterol by 0.13 (0.02) mmol/l and low density lipoprotein cholesterol by 0.10 (0.02) mmol/l. CONCLUSIONS: In typical British diets replacing 60% of saturated fats by other fats and avoiding 60% of dietary cholesterol would reduce blood total cholesterol by about 0.8 mmol/l (that is, by 10-15%), with four fifths of this reduction being in low density lipoprotein cholesterol.",
"title": "Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies."
},
{
"docid": "MED-4004",
"text": "Evidence suggests that monounsaturated and polyunsaturated fats facilitate greater absorption of carotenoids than saturated fats. However, the comparison of consuming a polyunsaturated fat source versus a saturated fat source on tomato carotenoid bioaccumulation has not been examined. The goal of this study was to determine the influence of coconut oil and safflower oil on tomato carotenoid tissue accumulation in Mongolian gerbils ( Meriones unguiculatus ) fed a 20% fat diet. Coconut oil feeding increased carotenoid concentrations among many compartments including total carotenoids in the serum (p = 0.0003), adrenal glandular phytoene (p = 0.04), hepatic phytofluene (p = 0.0001), testicular all-trans-lycopene (p = 0.01), and cis-lycopene (p = 0.006) in the prostate-seminal vesicle complex compared to safflower oil. Safflower oil-fed gerbils had greater splenic lycopene concentrations (p = 0.006) compared to coconut oil-fed gerbils. Coconut oil feeding increased serum cholesterol (p = 0.0001) and decreased hepatic cholesterol (p = 0.0003) compared to safflower oil. In summary, coconut oil enhanced tissue uptake of tomato carotenoids to a greater degree than safflower oil. These results may have been due to the large proportion of medium-chain fatty acids in coconut oil, which might have caused a shift in cholesterol flux to favor extrahepatic carotenoid tissue deposition.",
"title": "Coconut oil enhances tomato carotenoid tissue accumulation compared to safflower oil in the Mongolian gerbil ( Meriones unguiculatus )."
},
{
"docid": "MED-4823",
"text": "Background Previous research relating dietary fat, a modifiable risk factor, to pancreatic cancer has been inconclusive. Methods We prospectively analyzed the association between intakes of fat, fat subtypes, and fat food sources and exocrine pancreatic cancer in the National Institutes of Health–AARP Diet and Health Study, a US cohort of 308 736 men and 216 737 women who completed a 124-item food frequency questionnaire in 1995–1996. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models, with adjustment for energy intake, smoking history, body mass index, and diabetes. Statistical tests were two-sided. Results Over an average follow-up of 6.3 years, 865 men and 472 women were diagnosed with exocrine pancreatic cancer (45.0 and 34.5 cases per 100 000 person-years, respectively). After multivariable adjustment and combination of data for men and women, pancreatic cancer risk was directly related to the intakes of total fat (highest vs lowest quintile, 46.8 vs 33.2 cases per 100 000 person-years, HR = 1.23, 95% CI = 1.03 to 1.46; Ptrend = .03), saturated fat (51.5 vs 33.1 cases per 100 000 person-years, HR = 1.36, 95% CI = 1.14 to 1.62; Ptrend < .001), and monounsaturated fat (46.2 vs 32.9 cases per 100 000 person-years, HR = 1.22, 95% CI = 1.02 to 1.46; Ptrend = .05) but not polyunsaturated fat. The associations were strongest for saturated fat from animal food sources (52.0 vs 32.2 cases per 100 000 person-years, HR = 1.43, 95% CI = 1.20 to 1.70; Ptrend < .001); specifically, intakes from red meat and dairy products were both statistically significantly associated with increased pancreatic cancer risk (HR = 1.27 and 1.19, respectively). Conclusion In this large prospective cohort with a wide range of intakes, dietary fat of animal origin was associated with increased pancreatic cancer risk.",
"title": "Dietary Fatty Acids and Pancreatic Cancer in the NIH-AARP Diet and Health Study"
},
{
"docid": "MED-5366",
"text": "CONTEXT: Adherence to the Mediterranean dietary pattern (MDP) is thought to reduce inflammatory, vascular, and metabolic processes that may be involved in the risk of clinical depression. OBJECTIVE: To assess the association between adherence to the MDP and the incidence of clinical depression. DESIGN: Prospective study that uses a validated 136-item food frequency questionnaire to assess adherence to the MDP. The MDP score positively weighted the consumption of vegetables, fruit and nuts, cereal, legumes, and fish; the monounsaturated- to saturated-fatty-acids ratio; and moderate alcohol consumption, whereas meat or meat products and whole-fat dairy were negatively weighted. SETTING: A dynamic cohort of university graduates (Seguimiento Universidad de Navarra/University of Navarra Follow-up [SUN] Project). PARTICIPANTS: A total of 10 094 initially healthy Spanish participants from the SUN Project participated in the study. Recruitment began on December 21, 1999, and is ongoing. MAIN OUTCOME MEASURE: Participants were classified as having incident depression if they were free of depression and antidepressant medication at baseline and reported a physician-made diagnosis of clinical depression and/or antidepressant medication use during follow-up. RESULTS: After a median follow-up of 4.4 years, 480 new cases of depression were identified. The multiple adjusted hazard ratios (95% confidence intervals) of depression for the 4 upper successive categories of adherence to the MDP (taking the category of lowest adherence as reference) were 0.74 (0.57-0.98), 0.66 (0.50-0.86), 0.49 (0.36-0.67), and 0.58 (0.44-0.77) (P for trend <.001). Inverse dose-response relationships were found for fruit and nuts, the monounsaturated- to saturated-fatty-acids ratio, and legumes. CONCLUSIONS: Our results suggest a potential protective role of the MDP with regard to the prevention of depressive disorders; additional longitudinal studies and trials are needed to confirm these findings.",
"title": "Association of the Mediterranean dietary pattern with the incidence of depression: the Seguimiento Universidad de Navarra/University of Navarra fol..."
},
{
"docid": "MED-4709",
"text": "BACKGROUND: Inflammation is crucial in all stages of atherosclerosis, and few studies have investigated the effect of dietary fat on markers of inflammation related to this disease during the postprandial period. OBJECTIVE: To evaluate the chronic effects of dietary fat on the postprandial expression of proinflammatory genes in peripheral blood mononuclear cells (PBMCs) in healthy subjects. DESIGN: 20 healthy men followed three different diets for 4 weeks each, according to a randomized crossover design: Western diet: 15% protein, 47% carbohydrates (CHO), 38% fat (22% saturated fatty acid (SFA)); Mediterranean diet: 15% protein, 47% CHO, 38% fat (24% monounsaturated fatty acid (MUFA)); CHO-rich and n-3 diet: 15% protein, 55% CHO, <30% fat (8% polyunsaturated fatty acid (PUFA)). After 12-h fast, volunteers were given a breakfast with a fat composition similar to that consumed in each of the diets-butter breakfast: 35% SFA; olive oil breakfast: 36% MUFA; walnut breakfast: 16% PUFA, 4% alpha-linolenic acid (LNA). RESULTS: The butter breakfast induced a higher increase in tumor necrosis factor (TNF)-alpha messenger RNA (mRNA) expression than the olive oil or walnut breakfasts (P=0.014) in PBMCs. Moreover, we found a higher postprandial response in the mRNA of interleukin (IL)-6 with the intake of butter and olive oil breakfasts than with the walnut breakfast (P=0.025) in these cells. However, the effects of the three fatty breakfasts on the plasma concentrations of these proinflammatory parameters showed no significant differences (P=N.S.). CONCLUSION: Consumption of a butter-enriched meal elicits greater postprandial expression of proinflammatory cytokine mRNA in PBMCs, compared to the olive oil and walnut breakfasts.",
"title": "Olive oil and walnut breakfasts reduce the postprandial inflammatory response in mononuclear cells compared with a butter breakfast in healthy men."
},
{
"docid": "MED-1447",
"text": "Background/objectives: To assess the effects on macro- and micronutrient intake of a nutrition intervention program in corporate settings across the United States. Subjects/methods: Two hundred and ninety-two individuals who were overweight or had type 2 diabetes were recruited from 10 sites of a US insurance company. Two hundred and seventy-one participants completed baseline diet recalls, and 183 participants completed dietary recalls at 18 weeks. Sites were randomly assigned to an intervention group (five sites) or to a control group (five sites) for 18 weeks. At intervention sites, participants were asked to follow a low-fat vegan diet and attend weekly group meetings. At control sites, participants continued their usual diets. At baseline and 18 weeks, participants completed 2-day diet recalls. Between-group differences in changes in nutrient intake were assessed using an analysis of covariance. Results: Compared with those in the control group, intervention-group participants significantly reduced the reported intake of total fat (P=0.02), saturated (P=0.006) and monounsaturated fats (P=0.01), cholesterol (P=0.009), protein (P=0.03) and calcium (P=0.02), and increased the intake of carbohydrate (P=0.006), fiber (P=0.002), β-carotene (P=0.01), vitamin C (P=0.003), magnesium (P=0.04) and potassium (P=0.002). Conclusions: An 18-week intervention program in a corporate setting reduces intake of total fat, saturated fat and cholesterol and increases the intake of protective nutrients, particularly fiber, β-carotene, vitamin C, magnesium and potassium. The reduction in calcium intake indicates the need for planning for this nutrient.",
"title": "Nutrient intake in the GEICO multicenter trial: the effects of a multicomponent worksite intervention"
},
{
"docid": "MED-1576",
"text": "OBJECTIVES: The incidence of inflammatory bowel disease (IBD) is increasing. Dietary factors such as the spread of the \"Western\" diet, high in fat and protein but low in fruits and vegetables, may be associated with the increase. Although many studies have evaluated the association between diet and IBD risk, there has been no systematic review. METHODS: We performed a systematic review using guideline-recommended methodology to evaluate the association between pre-illness intake of nutrients (fats, carbohydrates, protein) and food groups (fruits, vegetables, meats) and the risk of subsequent IBD diagnosis. Eligible studies were identified via structured keyword searches in PubMed and Google Scholar and manual searches. RESULTS: Nineteen studies were included, encompassing 2,609 IBD patients (1,269 Crohn's disease (CD) and 1,340 ulcerative colitis (UC) patients) and over 4,000 controls. Studies reported a positive association between high intake of saturated fats, monounsaturated fatty acids, total polyunsaturated fatty acids (PUFAs), total omega-3 fatty acids, omega-6 fatty acids, mono- and disaccharides, and meat and increased subsequent CD risk. Studies reported a negative association between dietary fiber and fruits and subsequent CD risk. High intakes of total fats, total PUFAs, omega-6 fatty acids, and meat were associated with an increased risk of UC. High vegetable intake was associated with a decreased risk of UC. CONCLUSIONS: High dietary intakes of total fats, PUFAs, omega-6 fatty acids, and meat were associated with an increased risk of CD and UC. High fiber and fruit intakes were associated with decreased CD risk, and high vegetable intake was associated with decreased UC risk.",
"title": "Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature."
},
{
"docid": "MED-5186",
"text": "We evaluated the role of dietary nutrients in the etiology of endometrial cancer in a population-based case-control study of 1,204 newly diagnosed endometrial cancer cases and 1,212 age frequency-matched controls. Information on usual dietary habits was collected during an in-person interview using a validated, quantitative food frequency questionnaire. Logistic regression analysis was conducted to evaluate the association of nutrients with endometrial cancer risk using an energy density method (e.g., nutrient intake/1,000 kilocalories of intake). Higher energy intake was associated with increased risk, which was attributable to animal source energy and a high proportion of energy from protein and fat. Odds ratios comparing highest versus lowest quintiles of intake were elevated for intake of animal protein (Odds ratio (OR) 5 2.0, 95% confidential interval: 1.5–2.7) and fat (OR 5 1.5, 1.2–2.0), but reduced for plant sources of these nutrients (OR 5 0.7, 0.5–0.9 for protein and OR 5 0.6, 0.5–0.8 for fat). Further analysis showed that saturated and monounsaturated fat intake was associated with elevated risk, while polyunsaturated fat intake was unrelated to risk. Dietary retinol, β-carotene, vitamin C, vitamin E, fiber, and vitamin supplements were inversely associated with risk. No significant association was observed for dietary vitamin B1 or vitamin B2. Our findings suggest that associations of dietary macronutrients with endometrial cancer risk may depend on their sources, with intake of animal origin nutrients being related to higher risk and intake of plant origin nutrients related to lower risk. Dietary fiber, retinol, β-carotene, vitamin C, vitamin E, and vitamin supplementation may decrease the risk of endometrial cancer.",
"title": "Nutritional factors in relation to endometrial cancer: A report from a population-based case-control study in Shanghai, China"
},
{
"docid": "MED-1921",
"text": "Dietary factors, including dietary fat, may affect the biological aging process, as reflected by the shortening of telomere length (TL), by affecting levels of oxidative stress and inflammatory responses. We examined the direct relations of total and types of dietary fats and fat-rich foods to peripheral leukocyte TL. In 4029 apparently healthy postmenopausal women who participated in the Women’s Health Initiative, intakes of total fat, individual fatty acids, and fat-rich foods were assessed by a questionnaire. TL was measured by quantitative polymerase chain reaction. Intake of short-to-medium-chain saturated fatty acids (SMSFAs; aliphatic tails of ≤12 carbons) was inversely associated with TL. Compared with participants in other quartiles of SMSFA intake, women who were in the highest quartile (median: 1.29% of energy) had shorter TLs [mean: 4.00 kb (95% CI: 3.89, 4.11 kb)], whereas women in the lowest quartile of intake (median: 0.29% of energy) had longer TLs [mean: 4.13 kb (95% CI: 4.03, 4.24 kb); P-trend = 0.046]. Except for lauric acid, all other individual SMSFAs were inversely associated with TL (P < 0.05). In isoenergetic substitution models, the substitution of 1% of energy from SMSFAs with any other energy source was associated with 119 bp longer TLs (95% CI: 21, 216 bp). Intakes of nonskim milk, butter, and whole-milk cheese (major sources of SMSFAs) were all inversely associated with TL. No significant associations were found with long-chain saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids. In conclusion, we found that higher intakes of SMSFAs and SMSFA-rich foods were associated with shorter peripheral leukocyte TL among postmenopausal women. These findings suggest the potential roles of SMSFAs in the rate of biological aging.",
"title": "Intake of Small-to-Medium-Chain Saturated Fatty Acids Is Associated with Peripheral Leukocyte Telomere Length in Postmenopausal Women"
},
{
"docid": "MED-2649",
"text": "Background Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan. Methods Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index. Results The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, P for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis. Conclusions The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women.",
"title": "Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study"
},
{
"docid": "MED-5096",
"text": "BACKGROUND/AIMS: The objective of the study was to collect data on dietary fat intake of omnivores, vegetarians, vegans and semi-omnivores as well as its impact on n-3 and n-6 fatty acids in long-term markers such as sphingolipids, phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE) as well as the calculated sphingo- and phospholipids (SPL) of erythrocytes. METHOD: The present observational study included 98 Austrian adult volunteers of both genders, of which 23 were omnivores, 25 vegetarians, 37 vegans, and 13 semi-omnivores. Information on anthropometry using measured body weight and height was obtained. The amount and composition of ingested fat were calculated from 24-hour recalls and the fatty acid pattern in the phospholipids was assessed using gas chromatography. RESULTS: The unbalanced n-6/n-3 ratio and the limited dietary sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in vegans and vegetarians led to reductions in C20:5n-3, C22:5n-3, C22:6n-3 and total n-3 fatty acids in SPL, PC, PS and PE compared with omnivores and semi-omnivores. The total content of polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids remained unchanged. CONCLUSION: The vegetarian diet, with an average n-6/n-3 ratio of 10/1, promotes biochemical n-3 tissue decline. To ensure physical, mental and neurological health vegetarians have to reduce the n-6/n-3 ratio with an additional intake of direct sources of EPA and DHA, regardless of age and gender. (c) 2008 S. Karger AG, Basel.",
"title": "Very low n-3 long-chain polyunsaturated fatty acid status in Austrian vegetarians and vegans."
},
{
"docid": "MED-4292",
"text": "There is currently no single dietary or lifestyle intervention that is effective in long-term weight loss. Traditional weight loss diets tend to be low in total fat and therefore often restrict nut consumption. However, nuts are an important source of many vitamins, minerals, monounsaturated and polyunsaturated fatty acids. This paper reviewed all the available evidence from the literature in relation to nut consumption and body weight. The findings show that the role of nut consumption in body weight management is varied. Nuts, when included as part of an energy-controlled diet, were found in some instances to assist with weight loss. However, when nuts were added to an existing diet without controlling for energy intake, body weight increased, although to a lesser extent than theoretically predicted. There is limited evidence on the effect nut consumption has on type 2 diabetes, although available evidence indicates that nuts as part of a healthy diet do not cause weight gain and can have a positive influence on the fatty acid profile of a person with diabetes. This review shows there is a lack of evidence to support the restriction of nut consumption in weight management, indicating that further research is needed to assess the role of nuts in weight management.",
"title": "A review of the evidence: nuts and body weight."
},
{
"docid": "MED-4551",
"text": "Interest has increased in the possibility that maternal dietary intake during pregnancy might influence the development of allergic disorders in children. The present prospective study examined the association of maternal intake of selected foods high in fatty acids and specific types of fatty acids during pregnancy with the risk of suspected atopic eczema among Japanese infants aged 3-4 months. Subjects were 771 mother-child pairs. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered diet history questionnaire. The term 'suspected atopic eczema' was used to define an outcome based on results of our questionnaire completed by mothers 3-4 months postpartum. The risk of suspected atopic eczema was 8.4% (n = 65). Higher maternal intake of meat during pregnancy was significantly associated with an increased risk of suspected atopic eczema in the offspring: the multivariate odds ratio (OR) for the highest vs. lowest quartile was 2.59 [95% confidence interval (CI): 1.15-6.17, p for trend = 0.01]. The positive association was strengthened when the definition of the outcome was confined to a definite physician's diagnosis of atopic eczema (n = 35): the multivariate OR between extreme quartiles was 3.53 (95% CI: 1.19-12.23, p for trend = 0.02). No material exposure-response relationships were observed between maternal intake of eggs, dairy products, fish, total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid consumption and the risk of suspected atopic eczema. Higher maternal meat intake may increase the risk of infantile atopic eczema, whereas we found no evidence that maternal intake of fish and n-3 polyunsaturated fatty acids are preventive against infantile atopic eczema. (c) 2009 John Wiley & Sons A/S",
"title": "Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3-4 months: the Osaka Maternal and Child He..."
},
{
"docid": "MED-5262",
"text": "CONTEXT: The metabolic syndrome has been identified as a target for dietary therapies to reduce risk of cardiovascular disease; however, the role of diet in the etiology of the metabolic syndrome is poorly understood. OBJECTIVE: To assess the effect of a Mediterranean-style diet on endothelial function and vascular inflammatory markers in patients with the metabolic syndrome. DESIGN, SETTING, AND PATIENTS: Randomized, single-blind trial conducted from June 2001 to January 2004 at a university hospital in Italy among 180 patients (99 men and 81 women) with the metabolic syndrome, as defined by the Adult Treatment Panel III. INTERVENTIONS: Patients in the intervention group (n = 90) were instructed to follow a Mediterranean-style diet and received detailed advice about how to increase daily consumption of whole grains, fruits, vegetables, nuts, and olive oil; patients in the control group (n = 90) followed a prudent diet (carbohydrates, 50%-60%; proteins, 15%-20%; total fat, <30%). MAIN OUTCOME MEASURES: Nutrient intake; endothelial function score as a measure of blood pressure and platelet aggregation response to l-arginine; lipid and glucose parameters; insulin sensitivity; and circulating levels of high-sensitivity C-reactive protein (hs-CRP) and interleukins 6 (IL-6), 7 (IL-7), and 18 (IL-18). RESULTS: After 2 years, patients following the Mediterranean-style diet consumed more foods rich in monounsaturated fat, polyunsaturated fat, and fiber and had a lower ratio of omega-6 to omega-3 fatty acids. Total fruit, vegetable, and nuts intake (274 g/d), whole grain intake (103 g/d), and olive oil consumption (8 g/d) were also significantly higher in the intervention group (P<.001). The level of physical activity increased in both groups by approximately 60%, without difference between groups (P =.22). Mean (SD) body weight decreased more in patients in the intervention group (-4.0 [1.1] kg) than in those in the control group (-1.2 [0.6] kg) (P<.001). Compared with patients consuming the control diet, patients consuming the intervention diet had significantly reduced serum concentrations of hs-CRP (P =.01), IL-6 (P =.04), IL-7 (P = 0.4), and IL-18 (P = 0.3), as well as decreased insulin resistance (P<.001). Endothelial function score improved in the intervention group (mean [SD] change, +1.9 [0.6]; P<.001) but remained stable in the control group (+0.2 [0.2]; P =.33). At 2 years of follow-up, 40 patients in the intervention group still had features of the metabolic syndrome, compared with 78 patients in the control group (P<.001). CONCLUSION: A Mediterranean-style diet might be effective in reducing the prevalence of the metabolic syndrome and its associated cardiovascular risk.",
"title": "Effect of a mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial."
},
{
"docid": "MED-1061",
"text": "BACKGROUND: To determine whether there is an association between diet and plasma insulin concentration that is independent of obesity, we studied the relation of dietary composition and caloric intake to obesity and plasma insulin concentrations in 215 nondiabetic men aged 32-74 years with angiographically proven coronary artery disease. METHODS AND RESULTS: After adjusting for age, the intake of saturated fatty acids and cholesterol were positively correlated (p less than 0.05) with body mass index (r = 0.18, r = 0.16), waist-to-hip circumference ratio (r = 0.21, r = 0.22), and fasting insulin (r = 0.26, r = 0.23). Carbohydrate intake was negatively correlated with body mass index (r = -0.21), waist-to-hip ratio (r = -0.21), and fasting insulin (r = -0.16). Intake of monounsaturated fatty acids did not correlate significantly with body mass index or waist-to-hip circumference ratio but did correlate positively with fasting insulin (r = 0.24). Intake of dietary calories was negatively correlated with body mass index (r = -0.15). In multivariate analysis, intake of saturated fatty acids was significantly related to elevated fasting insulin concentration independently of body mass index. CONCLUSIONS: These cross-sectional findings in nondiabetic men with coronary artery disease suggest that increased consumption of saturated fatty acids is associated independently with higher fasting insulin concentrations.",
"title": "Saturated fat intake and insulin resistance in men with coronary artery disease. The Stanford Coronary Risk Intervention Project Investigators and ..."
},
{
"docid": "MED-4627",
"text": "The emerging role of chronic inflammation in the major degenerative diseases of modern society has stimulated research into the influence of nutrition and dietary patterns on inflammatory indices. Most human studies have correlated analyses of habitual dietary intake as determined by a food frequency questionnaire or 24-hour recall with systemic markers of inflammation like high-sensitivity C-reactive protein (HS-CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). An occasional study also includes nutrition analysis of blood components. There have been several controlled interventions which evaluated the effect of a change in dietary pattern or of single foods on inflammatory markers in defined populations. Most studies reveal a modest effect of dietary composition on some inflammatory markers in free-living adults, although different markers do not vary in unison. Significant dietary influences have been established for glycemic index (GI) and load (GL), fiber, fatty acid composition, magnesium, carotenoids, and flavonoids. A traditional Mediterranean dietary pattern, which typically has a high ratio of monounsaturated (MUFA) to saturated (SFA) fats and ω-3 to ω-6 polyunsaturated fatty acid (PUFAs) and supplies an abundance of fruits, vegetables, legumes, and grains, has shown anti-inflammatory effects when compared with typical North American and Northern European dietary patterns in most observational and interventional studies and may become the diet of choice for diminishing chronic inflammation in clinical practice.",
"title": "Diet and inflammation."
},
{
"docid": "MED-1067",
"text": "BACKGROUND AND AIM: Studies have shown monounsaturated oleic acid to be less toxic than palmitic acid and to prevent/attenuate palmitic acid hepatocites toxicity in steatosis models in vitro. However, to what degree these effects are mediated by steatosis extent is unknown. METHODS: We evaluated whether steatosis per se is associated with hepatocytes apoptosis and determined the role of oleic and palmitic acid, the most abundant fatty acids in western diets, on triglyceride accumulation and apoptosis in an in vitro model of steatosis induced in three hepatocytic cell lines (HepG2, HuH7, WRL68). The impact of incubation for 24 h with oleic (0.66 and 1.32 mM) and palmitic acid (0.33 and 0.66 mM), alone or combined (molar ratio 2 : 1) on steatosis, apoptosis, and insulin signalling, was evaluated. RESULTS: Concurrent with PPARgamma and SREBP-1 gene activation, steatosis extent was larger when cells were treated with oleic than with palmitic acid; the latter fatty acid was associated with increased PPARalpha expression. Cell apoptosis was inversely proportional to steatosis deposition. Moreover, palmitic, but not oleic acid, impaired insulin signalling. Despite the higher amount of fat resulting from incubation of the two fatty acids combined, the apoptosis rate and impaired insulin signalling were lower than in cells treated with palmitic acid alone, indicating a protective effect of oleic acid. CONCLUSIONS: Oleic acid is more steatogenic but less apoptotic than palmitic acid in hepatocityc cell cultures. These data may provide a biological basis for clinical findings on dietary patterns and pathogenetic models of nonalcoholic fatty liver disease.",
"title": "Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes."
},
{
"docid": "MED-2526",
"text": "Investigators collected and analyzed mortality data for >50 diseases, including 7 different cancers, from 65 counties and 130 villages in rural mainland China. Blood, urine, food samples, and detailed dietary data were collected from 50 adults in each village and analyzed for a variety of nutritional, viral, hormonal, and toxic chemical factors. In rural China, fat intake was less than half that in the United States, and fiber intake was 3 times higher. Animal protein intake was very low, only about 10% of the US intake. Mean serum total cholesterol was 127 mg/dL in rural China versus 203 mg/dL for adults aged 20-74 years in the United States. Coronary artery disease mortality was 16.7-fold greater for US men and 5.6-fold greater for US women than for their Chinese counterparts. The combined coronary artery disease mortality rates for both genders in rural China were inversely associated with the frequency of intake of green vegetables and plasma erythrocyte monounsaturated fatty acids, but positively associated with a combined index of salt intake plus urinary sodium and plasma apolipoprotein B. These apolipoproteins, in turn, are positively associated with animal protein intake and the frequency of meat intake and inversely associated with plant protein, legume, and light-colored vegetable intake. Rates of other diseases were also correlated with dietary factors. There was no evidence of a threshold beyond which further benefits did not accrue with increasing proportions of plant-based foods in the diet.",
"title": "Diet, lifestyle, and the etiology of coronary artery disease: the Cornell China study."
},
{
"docid": "MED-4615",
"text": "Investigators collected and analyzed mortality data for >50 diseases, including 7 different cancers, from 65 counties and 130 villages in rural mainland China. Blood, urine, food samples, and detailed dietary data were collected from 50 adults in each village and analyzed for a variety of nutritional, viral, hormonal, and toxic chemical factors. In rural China, fat intake was less than half that in the United States, and fiber intake was 3 times higher. Animal protein intake was very low, only about 10% of the US intake. Mean serum total cholesterol was 127 mg/dL in rural China versus 203 mg/dL for adults aged 20-74 years in the United States. Coronary artery disease mortality was 16.7-fold greater for US men and 5.6-fold greater for US women than for their Chinese counterparts. The combined coronary artery disease mortality rates for both genders in rural China were inversely associated with the frequency of intake of green vegetables and plasma erythrocyte monounsaturated fatty acids, but positively associated with a combined index of salt intake plus urinary sodium and plasma apolipoprotein B. These apolipoproteins, in turn, are positively associated with animal protein intake and the frequency of meat intake and inversely associated with plant protein, legume, and light-colored vegetable intake. Rates of other diseases were also correlated with dietary factors. There was no evidence of a threshold beyond which further benefits did not accrue with increasing proportions of plant-based foods in the diet.",
"title": "Diet, lifestyle, and the etiology of coronary artery disease: the Cornell China study."
}
] |
PLAIN-2096
|
sleep
|
[
{
"docid": "MED-2971",
"text": "Diabetes mellitus is associated with increased ROS generation, oxidative injury and obesity. To elucidate the relationship between nutrition and ROS generation, we have investigated the effect of glucose challenge on ROS generation by leucocytes, p47phox protein, a key protein in the enzyme NADPH oxidase and alpha-tocopherol levels. Blood samples were drawn from 14 normal subjects prior to, at 1, 2 and 3 h following ingestion of 75 g glucose. ROS generation by polymorphonuclear leucocytes (PMNL) and mononuclear cells (MNC) increased to a peak of 244 +/- 42% and 233 +/- 34% of the basal respectively at 2h. The levels of p47phox in MNC homogenates increased significantly at 2 h and 3 h after glucose intake. alpha-Tocopherol levels decreased significantly at 1 h, 2 h and 3 h. We conclude that glucose intake stimulates ROS generation and p417phox of NADPH oxidase; increases oxidative load and causes a fall in alpha-tocopherol concentration.",
"title": "Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes."
},
{
"docid": "MED-4079",
"text": "BACKGROUND: An effective treatment for fibromyalgia (FM) has yet to become available. OBJECTIVE: To assess the efficacy ofa lifestyle program consisting of a modified elimination diet and a supplemental medical food on clinical symptoms of FM assessed by the Fibromyalgia Impact Questionnaire (FIQ), FibroQuest Symptoms Survey (FibroQuest), Medical Symptoms Questionnaire (MSQ), metallothionein mRNA expression, and urinary toxic element excretion. METHODS: Eight women (aged 48-74 years) were enrolled in an 8-week pilot trial employing a sequential design. During the initial 4-week Program A (control), participants consumed a modified US Department of Agriculture food pyramid diet and a rice protein powder supplement that provided basic macronutrient support. During the second 4-week Program B (intervention), participants consumed a modified elimination diet and a phytonutrient-rich medical food. RESULTS: Compared to baseline, both programs showed trends toward lower mean FIQ total score, MSQ total score, and FibroQuest total score, FIQ stiffness score, and FibroQuest headaches score. Compared to Program A, Program B resulted in a significant decrease (P< .05) in the FIQpain score and stiffness score. Participants also had better pain tolerance at five tender points during Program B than during Program A. Higher metallothionein mRNA expression was observed during Program B. An increase in creatinine-adjusted mercury excretion and suggestive increase in creatinine-adjusted arsenic excretion were noted when Program B was compared to baseline. Urinary mercury/arsenic concentrations were inversely associated with FIQand FibroQuest scores. CONCLUSIONS: Program B was shown to be a safe and efficacious botanically derived medical food treatment program for the amelioration of FM symptoms.",
"title": "A program consisting of a phytonutrient-rich medical food and an elimination diet ameliorated fibromyalgia symptoms and promoted toxic-element deto..."
},
{
"docid": "MED-2968",
"text": "There is increasing evidence implicating a dietary source of plasma lipid peroxides that become elevated in the postprandial state. This phenomenon may be a contributing factor to the correlation found between postprandial hyperlipidemia and increased risk of cardiovascular disease. Using a newly developed method for measuring lipid hydroperoxides directly in plasma, a pilot study was performed which revealed that lipid hydroperoxides are indeed elevated following a fatty meal. Lipid hydroperoxides increased within 2-4 h after the meal and returned to basal levels, corresponding to the usual postprandial hyperlipidemia. A marked suppression of postprandial hydroperoxides was found when a meal was consumed with wine, suggesting that these hydroperoxides can be formed and then absorbed during the digestive process.",
"title": "Postprandial plasma lipid hydroperoxides: a possible link between diet and atherosclerosis."
},
{
"docid": "MED-3504",
"text": "OBJECTIVES: To assess the effectiveness of surgical interruption of pelvic nerve pathways in primary and secondary dysmenorrhea. Data sources. The Cochrane Menstrual Disorders and Subfertility Group Trials Register (9 June 2004), CENTRAL (The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to Nov. 2003), EMBASE (1980 to Nov. 2003), CINAHL (1982 to Oct. 2003), MetaRegister of Controlled Trials, the citation lists of review articles and included trials, and contact with the corresponding author of each included trial. REVIEW METHODS: The inclusion criteria were randomized controlled trials of uterosacral nerve ablation or presacral neurectomy (both open and laparoscopic procedures) for the treatment of dysmenorrhea. The main outcome measures were pain relief and adverse effects. Two reviewers extracted data on characteristics of the study quality and the population, intervention, and outcome independently. RESULTS: Nine randomized controlled trials were included in the systematic review. There were two trials with open presacral neurectomy; all other trials used laparoscopic techniques. For the treatment of primary dysmenorrhea, laparoscopic uterosacral nerve ablation at 12 months was better when compared to a control or no treatment (OR 6.12; 95% CI 1.78-21.03). The comparison of laparoscopic uterosacral nerve ablation with presacral neurectomy for primary dysmenorrhea showed that at 12 months follow-up, presacral neurectomy was more effective (OR 0.10; 95% CI 0.03-0.32). In secondary dysmenorrhea, along with laparoscopic surgical treatment of endometriosis, the addition of laparoscopic uterosacral nerve ablation did not improve the pain relief (OR 0.77; 95% CI 0.43-1.39), while presacral neurectomy did (OR 3.14; 95% CI 1.59-6.21). Adverse events were more common for presacral neurectomy than procedures without presacral neurectomy (OR 14.6; 95% CI 5-42.5). CONCLUSION: The evidence for nerve interruption in the management of dysmenorrhea is limited. Methodologically sound and sufficiently powered randomized controlled trials are needed.",
"title": "Surgical interruption of pelvic nerve pathways in dysmenorrhea: a systematic review of effectiveness."
},
{
"docid": "MED-4084",
"text": "Experiences with food intake, diet manipulations and fast were registered in rheumatic patients. The study was a questionnaire-based survey in which 742 patients participated. It comprised 290 patients with rheumatoid arthritis, 51 patients with juvenile rheumatoid arthritis, 87 patients with ankylosing spondylitis, 51 patients with psoriatic arthropathy, 65 patients with primary fibromyalgia and 34 patients with osteoarthritis. One third of the patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthropathy reported aggravation of disease symptoms after intake of certain foods while 43% of the patients with juvenile rheumatoid arthritis and 42% of the patients with primary fibromyalgia stated the same. Twenty-six percent of the patients with juvenile rheumatoid arthritis and 23% of the patients with rheumatoid arthritis, ankylosing spondylitis and primary fibromyalgia had previously tried certain diets in the attempt to alleviate disease symptoms, whereas 13% of the patients with psoriatic arthropathy and 10% with osteoarthritis had tried diet therapy. Less pain and stiffness were reported by 46% of the patients and 36% reported reduced joint swelling. Similar beneficial effects of diet were also reported in other rheumatic disease groups. Fifteen percent of the patients with rheumatoid arthritis and ankylosing spondylitis had been through a fasting period. Less pain and stiffness were reported by 2/3 of the patients in both groups and half of the patients in both groups reported a reduced number of swollen joints.",
"title": "Diet and disease symptoms in rheumatic diseases--results of a questionnaire based survey."
},
{
"docid": "MED-4523",
"text": "Both lipophilic and hydrophilic antioxidant capacities were determined using the oxygen radical absorbance capacity (ORAC(FL)) assay with fluorescein as the fluorescent probe and 2,2'-azobis(2-amidinopropane) dihydrochloride as a peroxyl radical generator on over 100 different kinds of foods, including fruits, vegetables, nuts, dried fruits, spices, cereals, infant, and other foods. Most of the foods were collected from four different regions and during two different seasons in U.S. markets. Total phenolics of each sample were also measured using the Folin-Ciocalteu reagent. Hydrophilic ORAC(FL) values (H-ORAC(FL)) ranged from 0.87 to 2641 micromol of Trolox equivalents (TE)/g among all of the foods, whereas lipophilic ORAC(FL) values (L-ORAC(FL)) ranged from 0.07 to 1611 micromol of TE/g. Generally, L-ORAC(FL) values were <10% of the H-ORAC(FL) values except for a very few samples. Total antioxidant capacity was calculated by combining L-ORAC(FL) and H-ORAC(FL). Differences of ORAC(FL) values in fruits and vegetables from different seasons and regions were relatively large for some foods but could not be analyzed in detail because of the sampling scheme. Two different processing methods, cooking and peeling, were used on selected foods to evaluate the impact of processing on ORAC(FL). The data demonstrated that processing can have significant effects on ORAC(FL). Considering all of the foods analyzed, the relationship between TP and H-ORAC(FL) showed a very weak correlation. Total hydrophilic and lipophilic antioxidant capacity intakes were calculated to be 5558 and 166 micromol of TE/day, respectively, on the basis of data from the USDA Continuing Survey of Food Intakes by Individuals (1994-1996).",
"title": "Lipophilic and hydrophilic antioxidant capacities of common foods in the United States."
},
{
"docid": "MED-2970",
"text": "There is increasing evidence that the postprandial state is an important contributing factor to chronic disease. The role of fruit phenolic compounds to protect health and lower disease risk through their actions in mitigating fed-state metabolic and oxidative stressors is of interest and the topic of the present paper. Two main questions are posed: first, what is the role of plant foods, specifically fruits rich in complex and simple phenolic compounds in postprandial metabolic management; and second, does the evidence support consuming these fruits with meals as a practical strategy to preserve health and lower risk for disease? This review provides an overview of the postprandial literature, specifically on the effect of fruits and their inherent phenolic compounds in human subjects on postprandial lipaemia, glycaemia/insulinaemia and associated events, such as oxidative stress and inflammation. Among the identified well-controlled human trials using a postprandial paradigm, >50 % of the trials used wine or wine components and the remaining used various berries. Notwithstanding the need for more research, the collected data suggest that consuming phenolic-rich fruits increases the antioxidant capacity of the blood, and when they are consumed with high fat and carbohydrate 'pro-oxidant and pro-inflammatory' meals, they may counterbalance their negative effects. Given the content and availability of fat and carbohydrate in the Western diet, regular consumption of phenolic-rich foods, particularly in conjunction with meals, appears to be a prudent strategy to maintain oxidative balance and health.",
"title": "Postprandial metabolic events and fruit-derived phenolics: a review of the science."
},
{
"docid": "MED-3535",
"text": "Cherries, and in particular sweet cherries, are a nutritionally dense food rich in anthocyanins, quercetin, hydroxycinnamates, potassium, fiber, vitamin C, carotenoids, and melatonin. UV concentration, degree of ripeness, postharvest storage conditions, and processing, each can significantly alter the amounts of nutrients and bioactive components. These constituent nutrients and bioactive food components support the potential preventive health benefits of cherry intake in relation to cancer, cardiovascular disease, diabetes, inflammatory diseases, and Alzheimer's disease. Mechanistically, cherries exhibit relatively high antioxidant activity, low glycemic response, COX 1 and 2 enzyme inhibition, and other anti-carcinogenic effects in vitro and in animal experiments. Well-designed cherry feeding studies are needed to further substantiate any health benefits in humans.",
"title": "Cherries and health: a review."
},
{
"docid": "MED-4695",
"text": "Night is no longer dark in the modern world, and the Milky Way has disappeared. Electric light has benefits but there are also a few detriments. These are (1) loss of the night sky, (2) wasted energy, (3) harm to animal and plant life, (4) and perhaps increases in some severe human maladies such as cancers of breast and prostate. The science on phototransduction for the circadian system and on clock gene function is evolving rapidly, and it provides a rationale for the idea that circadian disruption from light at night could cause disease. Direct evidence from humans and rodent models has also accumulated to the point where the idea is no longer fanciful. Although it may seem logical now, the journey on the path from electric light to breast cancer has been a tortuous one, at least for me.",
"title": "Electric light causes cancer? Surely you're joking, Mr. Stevens."
},
{
"docid": "MED-3525",
"text": "Although the hormone melatonin is a key factor for the proper functioning of the circadian timing system (CTS) and exogenous melatonin has been shown to be beneficial in cases of CTS disturbances, a deficit of melatonin has yet to be defined as a disorder. The aim of our study was to collect a normative data set on 24-h melatonin excretion in healthy human adults living in a natural environment. Urine samples were collected from 75 healthy subjects (45 women/30 men; mean age 47.2, SD 19.5, range 20-84) after five consecutive periods: 2300-0700, 0700-1100, 1100-1800, 1800-2300 and 2300-0700 h. 6-Sulfatoxymelatonin (aMT6s) concentrations were analyzed in duplicate by IBL (Hamburg) using a highly sensitive, competitive ELISA kit. Twenty-four hour-aMT6s total amount (rho=-0.68, p<0.001), aMT6s nighttime excretion (rho=-0.69, p<0.001), aMT6s morning excretion (rho=-0.66, p<0.001) and evening excretion (r=-0.26, p=0.023) were negatively associated with age, whereas daytime excretion (r=-0.17, p=0.15) was not. The intra-subject night-day ratio varied up to 10.5 (mean 6.0) in young subjects (aged 20-35) and up to 5.4 (mean 2.8) in older individuals (age>65). The total amount of 24 h-aMT6s (range 7.5-58 microg) as well as the amount of aMT6s excreted during the nighttime period (range 327-6.074 ng/h) varied as much as 20-fold between individuals. Our data show an age-related decline in melatonin excretion in healthy subjects living in a natural environment. The high inter-individual variability of excretion rates may explain why a normative data set is of no use in replacement strategies.",
"title": "Normative data on the daily profile of urinary 6-sulfatoxymelatonin in healthy subjects between the ages of 20 and 84."
},
{
"docid": "MED-3380",
"text": "Attention deficit hyperactivity disorder (ADHD) is one of the most common behavioral disorders in children. Symptoms of ADHD include hyperactivity, low frustration tolerance, impulsivity, and inattention. While the biological pathways leading to ADHD are not clearly delineated, a number of genetic and environmental risk factors for the disorder are recognized. In the early 1970s, research conducted by Dr. Benjamin Feingold found that when hyperactive children were given a diet free of artificial food additives and dyes, symptoms of hyperactivity were reduced. While some clinical studies supported these findings, more rigorous empirical studies conducted over the next 20 years were less positive. As a result, research on the role of food additives in contributing to ADHD waned. In recent years, however, interest in this area has revived. In response to more recent research and public petitions, in December 2009 the British government requested that food manufacturers remove most artificial food dyes from their products. While these strictures could have positive effects on behavior, the removal of food dyes is not a panacea for ADHD, which is a multifaceted disorder with both biological and environmental underpinnings. © 2011 International Life Sciences Institute.",
"title": "Artificial food dyes and attention deficit hyperactivity disorder."
},
{
"docid": "MED-4081",
"text": "This article reviews the existing literature on fibromyalgia (FM) and diet, discusses the possible role of diet on central sensitization in FM, proposes a novel hypothesis of possible food-related contributors to central sensitization, and makes recommendations for future dietary research directions.",
"title": "Potential dietary links to central sensitization in fibromyalgia: past reports and future directions."
},
{
"docid": "MED-4850",
"text": "Plants are rich natural sources of antioxidants in addition to other nutrients. Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food (LF) have been carried out. We have clarified the efficacy of LF in rheumatoid diseases as an example of a health problem where inflammation is one of the main concerns. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts, i.e. rich sources of carotenoids, vitamins C and E. The subjects eating LF showed highly increased levels of beta and alfa carotenes, lycopen and lutein in their sera. Also the increases of vitamin C and vitamin E (adjusted to cholesterol) were statistically significant. As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin, myricetin and kaempherol was much higher than in the omnivorous controls. The LF diet is rich in fibre, substrate of lignan production, and the urinary excretion of polyphenols like enterodiol and enterolactone as well as secoisolaricirecinol were much increased in subjects eating LF. The shift of fibromyalgic subjects to LF resulted in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health. The rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding. The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms. In conclusion the rheumatoid patients subjectively benefited from the vegan diet rich in antioxidants, lactobacilli and fibre, and this was also seen in objective measures.",
"title": "Antioxidants in vegan diet and rheumatic disorders."
},
{
"docid": "MED-2966",
"text": "OBJECTIVE: Determine 1) if consumption of a meal of different fruits or berries increases plasma hydrophilic (H-) or lipophilic (L-) antioxidant capacity (AOC) measured as Oxygen Radical Absorbance Capacity (ORAC(FL)); 2) if including macronutrients in the meal alters postprandial changes in AOC; and 3) if preliminary recommendations can be developed for antioxidant intake. METHODS: Changes in plasma AOC following consumption of a single meal of berries/fruits (blueberry, dried plum, dried plum juice, grape, cherry, kiwifruit and strawberry) were studied in 5 clinical trials with 6-10 subjects per experiment. In two studies with blueberry or grape, additional macronutrients (carbohydrate, fat, protein) were included in the control and treatment meals. Blood samples collected before and after the meal were analyzed for AOC. RESULTS: Consumption of dried plums or dried plum juice did not alter either the H- or L-AOC area under the curve (AUC). Consumption of blueberry in 2 studies and of mixed grape powder [12.5 (Study #1), 39.9 (Study #4) and 8.6 (Study #5) mmole Trolox Equivalents (TE) AOC, respectively] increased hydrophilic AOC AUC. L-AOC increased following a meal of blueberry containing 12.5 mmole TE AOC (Study #1). Consumption of 280 g of cherries (4.5 mmol TE AOC) increased plasma L-AOC but not H-AOC. The AOC in the control groups in which additional macronutrients (Studies #4 and #5) were added decreased from the postprandial baseline AOC measurement. CONCLUSION: We have demonstrated that consumption of certain berries and fruits such as blueberries, mixed grape and kiwifruit, was associated with increased plasma AOC in the postprandial state and consumption of an energy source of macronutrients containing no antioxidants was associated with a decline in plasma AOC. However, without further long term clinical studies, one cannot necessarily translate increased plasma AOC into a potential decreased risk of chronic degenerative disease. Preliminary estimates of antioxidant needs based upon energy intake were developed. Consumption of high antioxidant foods with each meal is recommended in order to prevent periods of postprandial oxidative stress.",
"title": "Plasma antioxidant capacity changes following a meal as a measure of the ability of a food to alter in vivo antioxidant status."
},
{
"docid": "MED-3520",
"text": "Melatonin has been attributed a role in a number of physiological processes. Changes in distal skin temperature and blood pressure after intake of melatonin suggest that melatonin induces peripheral vasodilation. The effect on the cerebral blood flow is still unknown. We examined the effect of a single pulse of melatonin on cerebral and peripheral blood flow, using the latter as a positive control. Ten male healthy volunteers (mean age, 22 +/- 3.2 yr) participated in a double-blind, randomized, placebo-controlled, cross-over study. On one occasion 10 microg melatonin were infused i.v., and on the other occasion saline was infused as the matching placebo. Cerebral blood flow was measured using phase contrast magnetic resonance imaging. Peripheral blood flow was determined from changes in the distal to proximal skin temperature gradient and finger pulse volume. Serum melatonin concentration increased from 12 +/- 5 pg/ml at baseline to 487 +/- 377 pg/ml at 5 min and 156 +/- 68 pg/ml at 10 min after melatonin administration. There was no significantly different time course for cerebral blood flow and cerebrovascular resistance. Compared with placebo, melatonin significantly increased peripheral blood flow, as measured by distal to proximal skin temperature gradient and finger pulse volume. These data demonstrate that melatonin does not have an acute regulatory effect on cerebral blood flow in humans.",
"title": "No influence of melatonin on cerebral blood flow in humans."
},
{
"docid": "MED-3524",
"text": "Sleep, much like eating, is an essential part of life. The mechanisms of sleep are only partially clear and are the subject of intense research. There is increasing evidence showing that sleep has an influence on dietary choices. Both cross-sectional and epidemiologic studies have demonstrated that those who sleep less are more likely to consume energy-rich foods (such as fats or refined carbohydrates), to consume fewer portions of vegetables, and to have more irregular meal patterns. In this narrative review, we pose the opposite question: can ingested food affect sleep? The purpose of this review is to discuss the evidence linking diet and sleep and to determine whether what we eat and what kind of nutrients we obtain from the food consumed before bedtime matter. In addition, scientific evidence behind traditional sleep-promoting foods such as milk and some herbal products is briefly described. These are reviewed using data from clinical trials, mostly in healthy subjects. In addition, we discuss the possible mechanisms behind these observations. Lastly, we summarize our findings that emerging evidence confirms a link between diet and sleep. Overall, foods impacting the availability of tryptophan, as well as the synthesis of serotonin and melatonin, may be the most helpful in promoting sleep. Although there are clear physiological connections behind these effects, the clinical relevance needs to be studied further. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Diet promotes sleep duration and quality."
},
{
"docid": "MED-3528",
"text": "The antioxidant melatonin was recently identified in a variety of edible plants and seeds in high concentrations. In plants, as in animals, melatonin is believed to function as a free radical scavenger and possibly in photoperiodism. In this study, melatonin was detected and quantified in fresh-frozen Balaton and Montmorency tart cherries (Prunus cerasus) using high-performance liquid chromatography. Both cherry species contain high levels of melatonin compared to the melatonin concentrations in the blood of mammals. Montmorency cherries (13.46 +/- 1.10 ng/g) contain approximately 6 times more melatonin than do Balaton cherries (2.06 +/- 0.17 ng/g). Neither the orchard of origin nor the time of harvest influenced the amount of melatonin in fresh cherries. The implication of the current findings is that consuming cherries could be an important source of dietary melatonin inasmuch as melatonin is readily absorbed when taken orally. Also, previously published data and the results presented here show that melatonin is not only endogenously produced but also present in the diet.",
"title": "Detection and quantification of the antioxidant melatonin in Montmorency and Balaton tart cherries (Prunus cerasus)."
},
{
"docid": "MED-4704",
"text": "Introduction Lipoid pneumonia is a rare form of pneumonia caused by inhalation or aspiration of fat containing substances like, petroleum jelly, mineral oils, few laxatives etc. It usually presents as insidious onset chronic respiratory illness simulating interstitial lung diseases. Rarely, it may present as an acute respiratory illness, specially, when exposure to fatty substance is acute and/or massive. Radiologically, it may mimic carcinoma, acute or chronic pneumonia, ARDS, or a localized granuloma. Diagnosis of LP requires demonstration of lipid laden macrophages in sputum, bronchoalveolar lavage fluid or fine needle aspiration cytology/biopsy from lung lesion. Treatment of this illness is poorly defined and constitutes supportive therapy and corticosteroids. Case presentation A 20-year old Indian farmer was referred to us with a diagnosis of non resolving community acquired pneumonia. Respiratory examination revealed signs of consolidation. Chest radiograph revealed findings suggestive of bilateral consolidation. Sputum and blood culture were sterile. He was treated with prolonged course of various antibiotics without any significant response. For evaluation of non resolving pneumonia fibreoptic bronchoscopy was done. Bronchoalveolar lavage fluid and biopsy from lung lesion showed lipid laden macrophages. Hence diagnosis of lipoid pneumonia was made. Patient was treated with course of corticosteroids with good response. Literature on this rare entity is discussed. Conclusion Lipoid pneumonia is a rare form of pneumonia which rarely present acutely resembling community acquired pneumonia and requires high degree of suspicion for diagnosis. Its treatment is difficult and poorly defined. However, prolonged corticosteroids may be effective.",
"title": "Lipoid pneumonia presenting as non resolving community acquired pneumonia: a case report"
},
{
"docid": "MED-5047",
"text": "Our objective was to examine whether habitual green tea consumption is associated with blood glucose levels and other biomarkers of glucose metabolism. We conducted a cross-sectional study of 35 male volunteers, 23–63 years old and residing in Shizuoka Prefecture in Japan. Biochemical data were measured and we conducted a questionnaire survey on health, lifestyle, and nutrition, as well as frequency of consumption and concentrations (1%, 2%, and 3%) of green tea. Men who consumed a 3% concentration of green tea showed lower mean values of fasting blood glucose and fructosamine than those who consumed a 1% concentration. Fasting blood glucose levels were found to be significantly associated with green tea concentration (β = −0.14, p = 0.03). However, green tea consumption frequency showed no significant differences in mean levels of blood glucose, fructosamine and hemoglobin A1c. In conclusion, our findings suggest that the consumption of green tea at a high concentration has the potential to reduce blood glucose levels.",
"title": "The Association between Concentrations of Green Tea and Blood Glucose Levels"
},
{
"docid": "MED-3794",
"text": "OBJECTIVE: To test the hypothesis that a low-fat, vegetarian diet reduces dysmenorrhea and premenstrual symptoms by its effect on serum sex-hormone binding globulin concentration and estrogen activity. METHODS: In a crossover design, 33 women followed a low-fat, vegetarian diet for two menstrual cycles. For two additional cycles, they followed their customary diet while taking a supplement placebo pill. Dietary intake, serum sex-hormone binding globulin concentration, body weight, pain duration and intensity, and premenstrual symptoms were assessed during each study phase. RESULTS: Mean (+/- standard deviation [SD]) serum sex-hormone binding globulin concentration was higher during the diet phase (46.7 +/- 23.6 nmol/L) than during the supplement phase (39.3 +/- 19.8 nmol/L, P < .001). Mean (+/- SD) body weight was lower during the diet (66.1 +/- 11.3 kg) compared with the supplement phase (67.9 +/- 12.1 kg, P < .001). Mean dysmenorrhea duration fell significantly from baseline (3.9 +/- 1.7 days) to diet phase (2.7 +/- 1.9 days) compared with change from baseline to supplement phase (3.6 +/- 1.7 days, P < .01). Pain intensity fell significantly during the diet phase, compared with baseline, for the worst, second-worst, and third-worst days, and mean durations of premenstrual concentration, behavioral change, and water retention symptoms were reduced significantly, compared with the supplement phase. CONCLUSION: A low-fat vegetarian diet was associated with increased serum sex-hormone binding globulin concentration and reductions in body weight, dysmenorrhea duration and intensity, and premenstrual symptom duration. The symptom effects might be mediated by dietary influences on estrogen activity.",
"title": "Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms."
},
{
"docid": "MED-3526",
"text": "Tryptophan, serotonin, and melatonin, present in Jerte Valley cherries, participate in sleep regulation and exhibit antioxidant properties. The effect of the intake of seven different Jerte Valley cherry cultivars on the sleep-wake cycle, 6-sulfatoxymelatonin levels, and urinary total antioxidant capacity in middle-aged and elderly participants was evaluated. Volunteers were subjected to actigraphic monitoring to record and display the temporal patterns of their nocturnal activity and rest. 6-sulfatoxymelatonin and total antioxidant capacity were quantified by enzyme-linked immunosorbent assay and colorimetric assay kits, respectively. The intake of each of the cherry cultivars produced beneficial effects on actual sleep time, total nocturnal activity, assumed sleep, and immobility. Also, there were significant increases in 6-sulfatoxymelatonin levels and total antioxidant capacity in urine after the intake of each cultivar. These findings suggested that the intake of Jerte Valley cherries exerted positive effect on sleep and may be seen as a potential nutraceutical tool to counteract oxidation.",
"title": "Jerte Valley cherry-enriched diets improve nocturnal rest and increase 6-sulfatoxymelatonin and total antioxidant capacity in the urine of middle-a..."
},
{
"docid": "MED-3537",
"text": "Study Objectives: To examine the association between sleep-related factors and memory impairment. Design: Cross-sectional study Setting: Community-based study in Guangzhou, China. Participants: 28,670 older Chinese (20,776 women and 7,894 men) aged 50 to 85 years. Measurements and Results: Demographic and socioeconomic data, sleep-related factors, and cognitive function were collected by face-to-face interview. Potential confounders, such as employment and occupational status, smoking, alcohol and tea use, physical activity, self-rated health, anthropometry, blood pressure, and fasting plasma glucose and lipids were measured. After adjusting for multiple potential confounders, an inverted U-shaped association between sleep duration and delayed word recall test (DWRT) score, a validated measure of memory impairment, was found, with 7 to 8 h of habitual sleep duration showing the highest score (P-values for trend from 3 to 7 h and from 7 to ≥ 10 h were all ≤ 0.001). Compared to sleep duration of 7 h, the adjusted odds ratio for memory impairment from the sleep duration of 3 to 4 or ≥ 10 h was 1.29 (95% confidence interval 1.07-1.56) and 1.52 (1.25-1.86), respectively. Subjects with daily napping, morning tiredness, or insomnia had significantly lower DWRT scores than those without (P ranged from < 0.001 to 0.01). Conclusions: Short or long sleep duration was an important sleep-related factor independently associated with memory impairment and may be a useful marker for increased risk of cognitive impairment in older people. Citation: Xu L; Jiang CQ; Lam TH; Liu B; Jin YL; Zhu T; Zhang WS; Cheng KK; Thomas GN. Short or long sleep duration is associated with memory impairment in older Chinese: the Guangzhou Biobank Cohort Study. SLEEP 2011;34(5):575-580.",
"title": "Short or Long Sleep Duration Is Associated with Memory Impairment in Older Chinese: the Guangzhou Biobank Cohort Study"
},
{
"docid": "MED-4088",
"text": "The influence of a 3-week vegetarian diet and fasting on serum concentration of peroxides, lipids, apolipoproteins, and plasma fibrinogen was studied in ten middle-aged fibromyalgia/fibrositis patients (eight women, two men). Mean serum peroxide concentration (estimated as thiobarbituric acid reacting substances) was reduced from 3.60 +/- 0.14 to 2.82 +/- 0.15 umol/l (p = 0.01) and plasma fibrinogen from 3.33 +/- 0.25 to 2.74 +/- 0.15 g/l (p = 0.02). Serum total cholesterol fell from 6.61 +/- 0.50 to 4.83 +/- 0.35 mmol/l (p < 0.0001), apolipoprotein B from 1.77 +/- 0.14 to 1.31 +/- 0.11 g/l (p < 0.0001), and apolipoprotein A from 1.41 +/- 0.09 to 1.23 +/- 0.05 g/l (p = 0.03). High density lipoprotein cholesterol concentration also decreased somewhat (from 1.26 +/- 0.09 to 1.07 +/- 0.04 mmol/l, p = 0.03) An atherogenic index, reflecting the balance between low and high density lipoproteins, was reduced by 31% (from 5.74 +/- 0.79 to 3.97 +/- 0.60, p = 0.02). The results suggest that vegetarian diet/fasting may have a beneficial influence on the concentration of serum peroxides and plasma fibrinogen concentration, and on the serum level of several lipoprotein-related coronary risk factors.",
"title": "Reduced plasma fibrinogen, serum peroxides, lipids, and apolipoproteins after a 3-week vegetarian diet."
},
{
"docid": "MED-3146",
"text": "Seeds of the opium poppy plant are legally sold and widely consumed as food. Due to contamination during harvesting, the seeds can contain morphine and other opiate alkaloids. The objective of this study is to review the toxicology of poppy seed foods regarding influence on opiate drug tests. Computer-assisted literature review resulted in 95 identified references. Normal poppy seed consumption is generally regarded as safe. During food processing, the morphine content is considerably reduced (up to 90%). The possibility of false-positive opiate drug tests after poppy food ingestion exists. There are no unambiguous markers available to differentiate poppy food ingestion from heroin or pharmaceutical morphine use. This is also a problem in heroin-assisted maintenance programs. A basic requirement in such substitution programs is the patients' abstinence from any other drugs, including additional illicit heroin. Also a lack of forensic ingestion trials was detected that consider all factors influencing the morphine content in biologic matrices after consumption. Most studies did not control for the losses during food processing, so that the initial morphine dosage was overestimated. The large reduction of the morphine content during past years raises questions about the validity of the \"poppy seed defence.\" However, a threshold of food use that would not lead to positive drug tests with certainty is currently unavailable. Research is needed to prove if the morphine contents in today's foods still pose the possibility of influencing drug tests. Future trials should consider processing-related morphine losses.",
"title": "Poppy seed foods and opiate drug testing--where are we today?"
},
{
"docid": "MED-3145",
"text": "Urine morphine levels after the consumption of poppy seeds were measured in two separate trials. Maximum levels of approximately 18 micrograms/ml were found using RIA, EMIT-ST and GC methodologies. Positive immunoassay results were seen up to 60 h post-ingestion. Several different lots of seeds from various sources were assayed for morphine and found to range from 4-200 mg/kg. Differentiation of poppy seed eaters from opiate users was not possible via the identification of minor alkaloid constituents of poppy seeds. It is, however, possible to analyse opiate urines with respect to 6-O-acetylmorphine. Below the level of approximately 5 micrograms/ml total opiates, GC/MS is the method of choice for this analysis.",
"title": "Morphine levels in urine subsequent to poppy seed consumption."
},
{
"docid": "MED-557",
"text": "Dysmenorrhea is the leading cause of recurrent short-term school absence in adolescent girls and a common problem in women of reproductive age. Risk factors for dysmenorrhea include nulliparity, heavy menstrual flow, smoking, and depression. Empiric therapy can be initiated based on a typical history of painful menses and a negative physical examination. Nonsteroidal anti-inflammatory drugs are the initial therapy of choice in patients with presumptive primary dysmenorrhea. Oral contraceptives and depo-medroxyprogesterone acetate also may be considered. If pain relief is insufficient, prolonged-cycle oral contraceptives or intravaginal use of oral contraceptive pills can be considered. In women who do not desire hormonal contraception, there is some evidence of benefit with the use of topical heat; the Japanese herbal remedy toki-shakuyaku-san; thiamine, vitamin E, and fish oil supplements; a low-fat vegetarian diet; and acupressure. If dysmenorrhea remains uncontrolled with any of these approaches, pelvic ultrasonography should be performed and referral for laparoscopy should be considered to rule out secondary causes of dysmenorrhea. In patients with severe refractory primary dysmenorrhea, additional safe alternatives for women who want to conceive include transcutaneous electric nerve stimulation, acupuncture, nifedipine, and terbutaline. Otherwise, the use of danazol or leuprolide may be considered and, rarely, hysterectomy. The effectiveness of surgical interruption of the pelvic nerve pathways has not been established.",
"title": "Dysmenorrhea."
},
{
"docid": "MED-3378",
"text": "BACKGROUND AND OBJECTIVE: In 1981, a Petrol-Lead Phase-Out Program (PLPOP) was launched in Taiwan for the abatement of environmental lead emissions. The present study was intended to examine whether the high Petrol-Lead Emission Areas (PLEA) would result in an increase in the incidence rate of brain cancer based on a national data bank. METHODS: The national brain cancer incidence data was obtained from the Taiwan National Cancer Registry. Age standardized incidence rates were calculated based on the 2000 WHO world standard population, and gasoline consumption data was obtained from the Bureau of Energy. The differences in the trend tests for age-standardized incidence rates of brain cancer between high, median, low, and small PLEA were analyzed. RESULTS: A significant increase was found from small to high PLEA in age-standardized incidence rates of brain cancer. By taking six possible confounders into account, the age-standardized incidence rates for brain cancer were highly correlated with the median and high PLEA by reference to the small PLEA. CONCLUSION: After being adjusted for a number of relevant confounders, it could be concluded that high PLEA might result in an increase in the incidence rate of brain cancer resulting from high lead exposures. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Brain cancer associated with environmental lead exposure: evidence from implementation of a National Petrol-Lead Phase-Out Program (PLPOP) in Taiwa..."
},
{
"docid": "MED-3521",
"text": "The identification of phenolics from various cultivars of fresh sweet and sour cherries and their protective effects on neuronal cells were comparatively evaluated in this study. Phenolics in cherries of four sweet and four sour cultivars were extracted and analyzed for total phenolics, total anthocyanins, and their antineurodegenerative activities. Total phenolics in sweet and sour cherries per 100 g ranged from 92.1 to 146.8 and from 146.1 to 312.4 mg gallic acid equivalents, respectively. Total anthocyanins of sweet and sour cherries ranged from 30.2 to 76.6 and from 49.1 to 109.2 mg cyanidin 3-glucoside equivalents, respectively. High-performance liquid chromatography (HPLC) analysis revealed that anthocyanins such as cyanidin and peonidin derivatives were prevalent phenolics. Hydroxycinnamic acids consisted of neochlorogenic acid, chlorogenic acid, and p-coumaric acid derivatives. Glycosides of quercetin, kaempferol, and isorhamnetin were also found. Generally, sour cherries had higher concentrations of total phenolics than sweet cherries, due to a higher concentration of anthocyanins and hydroxycinnamic acids. A positive linear correlation (r2 = 0.985) was revealed between the total anthocyanins measured by summation of individual peaks from HPLC analysis and the total anthocyanins measured by the pH differential method, indicating that there was in a close agreement with two quantifying methods for measuring anthocyanin contents. Cherry phenolics protected neuronal cells (PC 12) from cell-damaging oxidative stress in a dose-dependent manner mainly due to anthocyanins. Overall results showed that cherries are rich in phenolics, especially in anthocyanins, with a strong antineurodegenerative activity and that they can serve as a good source of biofunctional phytochemicals in our diet.",
"title": "Sweet and sour cherry phenolics and their protective effects on neuronal cells."
},
{
"docid": "MED-4694",
"text": "OBJECTIVE: Observational data, though sparse and based on small studies with limited ability to control for known breast cancer risk factors, support a lower risk of breast cancer in blind women compared to sighted women. Mechanisms influenced by ocular light perception, such as melatonin or circadian synchronization, are thought to account for this lower risk. METHODS: To evaluate whether blind women with no perception of light (NPL) have a lower prevalence of breast cancer compared to blind women with light perception (LP), we surveyed a cohort of 1,392 blind women living in North America (66 breast cancer cases). RESULTS: In multivariate-logistic regression models controlling for breast cancer risk factors, women with NPL had a significantly lower prevalence of breast cancer than women with LP (odds ratio, 0.43; 95% confidence interval, 0.21-0.85). We observed little difference in these associations when restricting to postmenopausal women, non-shift workers or when excluding women diagnosed with breast cancer within 2 or 4 years of onset of blindness. Blind women with NPL appear to have a lower risk of breast cancer, compared to blind women with LP. More research is needed to elucidate the impact of LP on circadian coordination and melatonin production in the blind and how these factors may relate to breast cancer risk.",
"title": "Total visual blindness is protective against breast cancer."
},
{
"docid": "MED-3536",
"text": "Epidemiologists have published more than 50 studies of insomnia based on data collected in various representative community-dwelling samples or populations. These surveys provide estimates of the prevalence of insomnia according to four definitions: insomnia symptoms, insomnia symptoms with daytime consequences, sleep dissatisfaction and insomnia diagnoses. The first definition, based on insomnia criteria as defined by the DSM-IV, recognizes that about one-third of a general population presents at least one of them. The second definition shows that, when daytime consequences of insomnia are taken into account, the prevalence is between 9% and 15%. The third definition represents 8-18% of the general population. The last definition, more precise and corresponding to a decision-making diagnosis, sets the prevalence at 6% of insomnia diagnoses according to the DSM-IV classification. These four definitions of insomnia have higher prevalence rates in women than in men. The prevalence of insomnia symptoms generally increases with age, while the rates of sleep dissatisfaction and diagnoses have little variation with age. Numerous factors can initiate or maintain insomnia. Mental disorders and organic diseases are the factors that have been the most frequently studied. The association between insomnia and major depressive episodes has been constantly reported: individuals with insomnia are more likely to have a major depressive illness. Longitudinal studies have shown that the persistence of insomnia is associated with the appearance of a new depressive episode. Future epidemiological studies should focus on the natural evolution of insomnia. Epidemiological genetic links of insomnia are yet to be studied.",
"title": "Epidemiology of insomnia: what we know and what we still need to learn."
},
{
"docid": "MED-3534",
"text": "Background Numerous antioxidant and anti‐inflammatory agents have been identified in tart cherries. Objective To test the efficacy of a tart cherry juice blend in preventing the symptoms of exercise induced muscle damage. Methods This was a randomised, placebo controlled, crossover design. Fourteen male college students drank 12 fl oz of a cherry juice blend or a placebo twice a day for eight consecutive days. A bout of eccentric elbow flexion contractions (2 × 20 maximum contractions) was performed on the fourth day of supplementation. Isometric elbow flexion strength, pain, muscle tenderness, and relaxed elbow angle were recorded before and for four days after the eccentric exercise. The protocol was repeated two weeks later with subjects who took the placebo initially, now taking the cherry juice (and vice versa). The opposite arm performed the eccentric exercise for the second bout to avoid the repeated bout protective effect. Results Strength loss and pain were significantly less in the cherry juice trial versus placebo (time by treatment: strength p<0.0001, pain p = 0.017). Relaxed elbow angle (time by treatment p = 0.85) and muscle tenderness (time by treatment p = 0.81) were not different between trials. Conclusions These data show efficacy for this cherry juice in decreasing some of the symptoms of exercise induced muscle damage. Most notably, strength loss averaged over the four days after eccentric exercise was 22% with the placebo but only 4% with the cherry juice.",
"title": "Efficacy of a tart cherry juice blend in preventing the symptoms of muscle damage"
},
{
"docid": "MED-3530",
"text": "An analytical method was developed for the simultaneous quantification of serotonin, melatonin, trans- and cis-piceid, and trans- and cis-resveratrol using reversed-phase high performance liquid chromatography coupled to mass spectrometry (HPLC-MS) with electrospray ionization (ESI) in both positive and negative ionization modes. HPLC optimal analytical separation was achieved using a mixture of acetonitrile and water with 0.1% formic acid as the mobile phase in linear gradient elution. The mass spectrometry parameters were optimized for reliable quantification and the enhanced selectivity and sensitivity selected reaction monitoring mode (SRM) was applied. For extraction, the direct analysis of initial methanol extracts was compared with further ethyl acetate extraction. In order to demonstrate the applicability of this analytical method, serotonin, melatonin, trans- and cis-piceid, and trans- and cis-resveratrol from 24 kinds of commonly consumed fruits were quantified. The highest serotonin content was found in plantain, while orange bell peppers had the highest melatonin content. Grape samples possessed higher trans- and cis-piceid, and trans- and cis-resveratrol contents than the other fruits. The results indicate that the combination of HPLC-MS detection and simple sample preparation allows the rapid and accurate quantification of serotonin, melatonin, trans- and cis-piceid, and trans- and cis-resveratrol in fruits. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Simultaneous analysis of serotonin, melatonin, piceid and resveratrol in fruits using liquid chromatography tandem mass spectrometry."
},
{
"docid": "MED-4548",
"text": "Background The risk of indoor exposure to volatile organic compounds (VOCs) on allergic airway diseases in children remains unknown. Objective We examined the residential concentrations of VOCs, emitted from building materials, paints, furniture, and other lifestyle practices and the risks of multiple allergic diseases as well as the IgE-sensitization in pre-school age children in Sweden. Methods In a case-control investigation (198 case children with asthma and allergy and 202 healthy controls), air samples were collected in the room where the child slept. The air samples were analyzed for the levels of eight classes of VOCs. Results A natural-log unit of summed propylene glycol and glycol ethers (PGEs) in bedroom air (equal to interquartile range, or 3.43 – 15.65 µg/m3) was associated with 1.5-fold greater likelihood of being a case (95% CI, 1.1 – 2.1), 1.5-fold greater likelihood of asthma (95% CI, 1.0 – 2.3), 2.8-fold greater likelihood of rhinitis (95% CI, 1.6 – 4.7), and 1.6-fold greater likelihood of eczema (95% CI, 1.1 – 2.3), accounting for gender, secondhand smoke, allergies in both parents, wet cleaning with chemical agents, construction period of the building, limonene, cat and dog allergens, butyl benzyl phthalate (BBzP), and di(2-ethylhexyl)phthalate (DEHP). When the analysis was restricted to the cases, the same unit concentration was associated with 1.8-fold greater likelihood of IgE-sensitization (95% CI, 1.1 – 2.8) compared to the non-IgE sensitized cases. No similar associations were found for the other classes of VOCs. Conclusion We propose a novel hypothesis that PGEs in indoor air exacerbate and/or induce the multiple allergic symptoms, asthma, rhinitis and eczema, as well as IgE sensitization respectively.",
"title": "Common Household Chemicals and the Allergy Risks in Pre-School Age Children"
},
{
"docid": "MED-2969",
"text": "OBJECTIVE: We have previously shown that 300 kcal from glucose intake induces a significant increase in reactive oxygen species (ROS) generation and nuclear factor-kappaB (NF-kappaB) binding in the circulating mononuclear cells in healthy normal subjects. We hypothesized that the intake of 300 calories as orange juice or fructose, the other major carbohydrate in orange juice, would induce a significantly smaller response than that of glucose. RESEARCH DESIGN AND METHODS: Four groups (eight subjects each) of normal-weight subjects were given a 300-cal drink of glucose (75 g), fructose (75 g), or orange juice or water sweetened with saccharin (control group) to drink, and then blood samples were collected. RESULTS: There was a significant increase in ROS generation by mononuclear cells (by 130 +/- 18%, P < 0.001), polymorph nuclear cells (by 95 +/- 22%, P < 0.01), and in NF-kappaB binding in mononuclear cells by 82 +/- 16% (P < 0.01) over the baseline after 2 h of glucose intake. These changes were absent following fructose, orange juice, or water intake. There was significantly lower ROS generation and NF-kappaB binding following orange juice, fructose, and water compared with glucose (P < 0.001 for all). Furthermore, incubation of mononuclear cells in vitro with 50 mmol/l of the flavonoids hesperetin or naringenin reduced ROS generation by 52 +/- 7% and 77 +/- 8% (P < 0.01), respectively, while fructose or ascorbic acid did not cause any change. CONCLUSIONS: Caloric intake in the form of orange juice or fructose does not induce either oxidative or inflammatory stress, possibly due to its flavonoids content and might, therefore, represent a potentially safe energy source.",
"title": "Orange juice or fructose intake does not induce oxidative and inflammatory response."
},
{
"docid": "MED-4085",
"text": "The effect of a strict, low-salt, uncooked vegan diet rich in lactobacteria on symptoms in 18 fibromyalgia patients during and after a 3-month intervention period in an open, non-randomized controlled study was evaluated. As control 15 patients continued their omnivorous diet. The groups did not differ significantly from each other in the beginning of the study in any other parameters except in pain and urine sodium. The results revealed significant improvements in Visual analogue scale of pain (VAS) (p=0.005), joint stiffness (p=0.001), quality of sleep (p=0.0001), Health assessment questionnaire (HAQ) (p=0.031), General health questionnaire (GHQ) (p=0.021), and a rheumatologist's own questionnaire (p=0.038). The majority of patients were overweight to some extent at the beginning of the study and shifting to a vegan food caused a significant reduction in body mass index (BMI) (p=0.0001). Total serum cholesterol showed a statistically significant lowering (p=0.003). Urine sodium dropped to 1/3 of the beginning values (p=0.0001) indicating good diet compliance. It can be concluded that vegan diet had beneficial effects on fibromyalgia symptoms at least in the short run.",
"title": "Vegan diet alleviates fibromyalgia symptoms."
},
{
"docid": "MED-2967",
"text": "The hypothesis that plasma chylomicrons in persons who ingest a cholesterol-rich diet are atherogenic is evaluated. Evidence is presented that in humans, and experimental animals, chylomicron remnants as well as low-density lipoproteins are taken up by arterial cells. In persons who do not have familial hyperlipoproteinemia, atherogenesis may occur during the postprandial period. Research directions that may contribute to the evaluation of chylomicron remnants as a risk factor for atherogenesis are discussed. Lipoprotein studies after administration of a test meal containing fat and cholesterol are urgently needed.",
"title": "Atherogenesis: a postprandial phenomenon."
},
{
"docid": "MED-4080",
"text": "Background Alterations in the intestinal bacterial flora are believed to be contributing factors to many chronic inflammatory and degenerative diseases including rheumatic diseases. While microbiological fecal culture analysis is now increasingly used, little is known about the relationship of changes in intestinal flora, dietary patterns and clinical outcome in specific diseases. To clarify the role of microbiological culture analysis we aimed to evaluate whether in patients with rheumatoid arthritis (RA) or fibromyalgia (FM) a Mediterranean diet or an 8-day fasting period are associated with changes in fecal flora and whether changes in fecal flora are associated with clinical outcome. Methods During a two-months-period 51 consecutive patients from an Integrative Medicine hospital department with an established diagnosis of RA (n = 16) or FM (n = 35) were included in the study. According to predefined clinical criteria and the subjects' choice the patients received a mostly vegetarian Mediterranean diet (n = 21; mean age 50.9 +/-13.3 y) or participated in an intermittent modified 8-day fasting therapy (n = 30; mean age 53.7 +/- 9.4 y). Quantitative aerob and anaerob bacterial flora, stool pH and concentrations of secretory immunoglobulin A (sIgA) were analysed from stool samples at the beginning, at the end of the 2-week hospital stay and at a 3-months follow-up. Clinical outcome was assessed with the DAS 28 for RA patients and with a disease severity rating scale in FM patients. Results We found no significant changes in the fecal bacterial counts following the two dietary interventions within and between groups, nor were significant differences found in the analysis of sIgA and stool ph. Clinical improvement at the end of the hospital stay tended to be greater in fasting vs. non-fasting patients with RA (p = 0.09). Clinical outcome was not related to alterations in the intestinal flora. Conclusion Neither Mediterranean diet nor fasting treatments affect the microbiologically assessed intestinal flora and sIgA levels in patients with RA and FM. The impact of dietary interventions on the human intestinal flora and the role of the fecal flora in rheumatic diseases have to be clarified with newer molecular analysis techniques. The potential benefit of fasting treatment in RA and FM should be further tested in randomised trials.",
"title": "Mediterranean diet or extended fasting's influence on changing the intestinal microflora, immunoglobulin A secretion and clinical outcome in patients with rheumatoid arthritis and fibromyalgia: an observational study"
},
{
"docid": "MED-4693",
"text": "Background Breast cancer incidence is increasing globally for largely unknown reasons. The possibility that a portion of the breast cancer burden might be explained by the introduction and increasing use of electricity to light the night was suggested >20 years ago. Methods The theory is based on nocturnal light-induced disruption of circadian rhythms, notably reduction of melatonin synthesis. It has formed the basis for a series of predictions including that non-day shift work would increase risk, blind women would be at lower risk, long sleep duration would lower risk and community nighttime light level would co-distribute with breast cancer incidence on the population level. Results Accumulation of epidemiological evidence has accelerated in recent years, reflected in an International Agency for Research on Cancer (IARC) classification of shift work as a probable human carcinogen (2A). There is also a strong rodent model in support of the light-at-night (LAN) idea. Conclusion If a consensus eventually emerges that LAN does increase risk, then the mechanisms for the effect are important to elucidate for intervention and mitigation. The basic understanding of phototransduction for the circadian system, and of the molecular genetics of circadian rhythm generation are both advancing rapidly, and will provide for the development of lighting technologies at home and at work that minimize circadian disruption, while maintaining visual efficiency and aesthetics. In the interim, there are strategies now available to reduce the potential for circadian disruption, which include extending the daily dark period, appreciate nocturnal awakening in the dark, using dim red light for nighttime necessities, and unless recommended by a physician, not taking melatonin tablets.",
"title": "Light-at-night, circadian disruption and breast cancer: assessment of existing evidence"
},
{
"docid": "MED-4691",
"text": "Background: Age and certain lifestyle factors, including a higher body mass index and exposure to light at night, are related to lower circulating concentrations of melatonin—a hormone with probable cancer-protective properties. Although melatonin is a direct derivative of the essential amino acid tryptophan, little is known about the relation of diet with melatonin concentrations. Objective: The objective was to examine cross-sectional associations of various nutrients and dietary factors as well as food groups with creatinine-adjusted first morning urinary melatonin (6-sulfatoxymelatonin; aMT6s) concentrations. Design: Participants were 998 healthy women from 2 independent cohorts: the Nurses' Health Study (NHS; n = 585) and NHS II (n = 413). We computed least-squares mean hormone concentrations across categories of dietary variables, with adjustment for total energy intake, age, and other nondietary factors known to be associated with aMT6s concentrations. Results: In multivariate analyses, we found no significant associations between the intake of various nutrients, including tryptophan and urinary melatonin concentrations. A higher intake of meat, particularly red meat, was associated with lower concentrations of aMT6s (adjusted mean concentrations of aMT6s across increasing quartiles of red meat intake were 17.9, 17.0, 18.1, and 15.3 ng/mg creatinine; P for trend = 0.02). In contrast, neither poultry intake (including turkey) nor fish intake was associated with aMT6s concentrations. Conclusion: Although no specific nutrients were associated with altered concentrations of melatonin, our findings raise the possibility that several specific foods, including red meat, could affect cancer risk through the lowering of melatonin concentrations.",
"title": "Dietary correlates of urinary 6-sulfatoxymelatonin concentrations in the Nurses' Health Study cohorts"
},
{
"docid": "MED-3533",
"text": "This study ascertained whether a proprietary tart cherry juice blend (CherryPharm, Inc., Geneva, NY, USA) associated with anecdotal reports of sleep enhancement improves subjective reports of insomnia compared to a placebo beverage. The pilot study used a randomized, double-blind, crossover design where each participant received both treatment and placebo for 2 weeks with an intervening 2-week washout period. Sleep continuity (sleep onset, wake after sleep onset, total sleep time, and sleep efficiency) was assessed by 2-week mean values from daily sleep diaries and disease severity by the Insomnia Severity Index in a cohort of 15 older adults with chronic insomnia who were otherwise healthy. The tart cherry juice beverage was associated with statistically significant pre- to post-treatment improvements on all sleep variables. When compared to placebo, the study beverage produced significant reductions in insomnia severity (minutes awake after sleep onset); no such improvements were observed for sleep latency, total sleep time, or sleep efficiency compared to placebo. Effect sizes were moderate and in some cases negligible. The results of this pilot study suggest that CherryPharm, a tart cherry juice blend, has modest beneficial effects on sleep in older adults with insomnia with effect sizes equal to or exceeding those observed in studies of valerian and in some, but not all, studies of melatonin, the two most studied natural products for insomnia. These effects, however, were considerably less than those for evidence-based treatments of insomnia: hypnotic agents and cognitive-behavioral therapies for insomnia.",
"title": "Effects of a Tart Cherry Juice Beverage on the Sleep of Older Adults with Insomnia: A Pilot Study"
},
{
"docid": "MED-5062",
"text": "BACKGROUND: We undertook a randomised, double-blinded, placebo-controlled, crossover trial to test whether intake of artificial food colour and additives (AFCA) affected childhood behaviour. METHODS: 153 3-year-old and 144 8/9-year-old children were included in the study. The challenge drink contained sodium benzoate and one of two AFCA mixes (A or B) or a placebo mix. The main outcome measure was a global hyperactivity aggregate (GHA), based on aggregated z-scores of observed behaviours and ratings by teachers and parents, plus, for 8/9-year-old children, a computerised test of attention. This clinical trial is registered with Current Controlled Trials (registration number ISRCTN74481308). Analysis was per protocol. FINDINGS: 16 3-year-old children and 14 8/9-year-old children did not complete the study, for reasons unrelated to childhood behaviour. Mix A had a significantly adverse effect compared with placebo in GHA for all 3-year-old children (effect size 0.20 [95% CI 0.01-0.39], p=0.044) but not mix B versus placebo. This result persisted when analysis was restricted to 3-year-old children who consumed more than 85% of juice and had no missing data (0.32 [0.05-0.60], p=0.02). 8/9-year-old children showed a significantly adverse effect when given mix A (0.12 [0.02-0.23], p=0.023) or mix B (0.17 [0.07-0.28], p=0.001) when analysis was restricted to those children consuming at least 85% of drinks with no missing data. INTERPRETATION: Artificial colours or a sodium benzoate preservative (or both) in the diet result in increased hyperactivity in 3-year-old and 8/9-year-old children in the general population.",
"title": "Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled..."
},
{
"docid": "MED-4981",
"text": "Variation in the level of the carotenoid antioxidant substances beta-carotene and lycopene in the human skin of ten healthy volunteers was measured with resonance Raman spectroscopy in an in vivo experiment over the course of 12 months. Information on the lifestyle of the volunteers concerning dietary supplementation and stress factors was obtained daily by the completion of questionnaires. The results showed individual variations in the levels of carotenoid antioxidant substances in the skin of the volunteers, which strongly correlated to specific lifestyles, such as the intake of dietary supplementations rich in carotenoids, and the influence of stress factors. A carotenoid-rich nutrition, based on large amounts of fruit and vegetables, increased the measured carotenoid levels of skin, while stress factors such as fatigue, illness, smoking, and alcohol consumption gave rise to a decrease in carotenoid levels of the skin. These decreases occurred relatively quickly over the course of one day, while the subsequent increases lasted for up to 3 days. During the summer and autumn months, an increase in the level of carotenoids in the skin was measured for all volunteers. The average \"seasonal increase\" of the carotenoid content in the skin was determined to be 1.26-fold.",
"title": "One-year study on the variation of carotenoid antioxidant substances in living human skin: influence of dietary supplementation and stress factors."
},
{
"docid": "MED-3503",
"text": "BACKGROUND: Dysmenorrhoea is a common gynaecological complaint consisting of painful cramps accompanying menstruation, which in the absence of any underlying abnormality is known as primary dysmenorrhoea. Research has shown that women with dysmenorrhoea have high levels of prostaglandins, hormones known to cause cramping abdominal pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs which act by blocking prostaglandin production. OBJECTIVES: The purpose of this review is to compare all nonsteroidal anti-inflammatory drugs used in the treatment of primary dysmenorrhoea with placebo, with paracetamol and with each other to evaluate their effectiveness and safety. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (11 April 2003), Cochrane Central Register of Controlled Trials (1st quarter 2003), MEDLINE (1966-April 2003), and EMBASE (1980 - Week 15 2003). Attempts were also made to identify trials from the National Research Register and the Clinical Trials Register. Citation lists of relevant publications, review articles, abstracts of major scientific meetings and included studies were also searched. SELECTION CRITERIA: All randomised controlled comparisons of NSAID therapies versus placebo, versus other NSAIDs or versus paracetamol when used to treat primary dysmenorrhoea. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for quality and extracted data, calculating odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Crossover trial data were presented in additional tables and other data were summarised descriptively. MAIN RESULTS: In women with dysmenorrhoea, NSAIDs were found significantly more effective for pain relief than placebo (OR 7.91, 95% CI 5.65 to 11.09), though overall adverse effects were also significantly more common (OR 1.52 95% CI 1.09 to 2.12). When NSAIDs were compared with each other or with paracetamol, there was little evidence of the superiority of any individual NSAID with regard to either efficacy or safety. However the available evidence had little power to detect such differences, as most individual comparisons were based on very few small trials, most of which were unsuitable for meta-analysis. REVIEWER'S CONCLUSIONS: NSAIDs are an effective treatment for dysmenorrhoea, though women using them need to be aware of the significant risk of adverse effects. There is insufficient evidence to determine which (if any) individual NSAID is the most safe and effective for the treatment of dysmenorrhoea.",
"title": "Nonsteroidal anti-inflammatory drugs for primary dysmenorrhoea."
},
{
"docid": "MED-3379",
"text": "We evaluate air Pb emissions and latent aggravated assault behavior at the scale of the city. We accomplish this by regressing annual Federal Bureau of Investigation aggravated assault rate records against the rise and fall of annual vehicle Pb emissions in Chicago (Illinois), Indianapolis (Indiana), Minneapolis (Minnesota), San Diego (California), Atlanta (Georgia), and New Orleans (Louisiana). Other things held equal, a 1% increase in tonnages of air Pb released 22 years prior raises the present period aggravated assault rate by 0.46% (95% CI, 0.28 to 0.64). Overall our model explains 90% of the variation in aggravated assault across the cities examined. In the case of New Orleans, 85% of temporal variation in the aggravated assault rate is explained by the annual rise and fall of air Pb (total=10,179 metric tons) released on the population of New Orleans 22 years earlier. For every metric ton of Pb released 22 years prior, a latent increase of 1.59 (95% CI, 1.36 to 1.83, p<0.001) aggravated assaults per 100,000 were reported. Vehicles consuming fuel containing Pb additives contributed much larger quantities of Pb dust than generally recognized. Our findings along with others predict that prevention of children's lead exposure from lead dust now will realize numerous societal benefits two decades into the future, including lower rates of aggravated assault. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "The urban rise and fall of air lead (Pb) and the latent surge and retreat of societal violence."
},
{
"docid": "MED-5031",
"text": "Background Sleep quality is thought to be an important predictor of immunity and in turn susceptibility to the common cold. This article examines whether sleep duration and efficiency in the weeks preceding viral exposure are associated with cold susceptibility. Methods Participants were 153 healthy men and women volunteers, ages 21–55. For 14 consecutive days, they reported their sleep duration and sleep efficiency (percent of time in bed actually asleep) for the previous night, and whether they felt rested. Average scores for each sleep variable were calculated over the 14-day baseline. Subsequently, participants were administered nasal drops containing a rhinovirus, quarantined and monitored on the day before and for five days following exposure for development of a clinical cold (infection in the presence of objective signs of illness). Results There was a graded association with average sleep duration, with those with <7 hours sleep 2.94 times (CI[95%]=1.18–7.30) more likely to develop a cold than those with ≥ 8 hours. The association with sleep efficiency was also graded with those with < 92% efficiency 5.50 times (CI[95%]=2.08–14.48) more likely to develop a cold than those with efficiencies ≥98%. These relations could not be explained by differences in pre-challenge virus-specific antibody, demographics, season of the year, body mass, socioeconomic status, psychological variables or health practices. Percent of days feeling rested was not associated with colds. Conclusions Poorer sleep efficiency and shorter sleep duration in the weeks preceding an exposure to a rhinovirus were associated with lower resistance to illness.",
"title": "Sleep Habits and Susceptibility to the Common Cold"
},
{
"docid": "MED-5048",
"text": "Despite the continuing reports supporting the hepatoprotective effects of green tea against ethanol intoxication, there remain controversies regarding the active compound(s) and molecular mechanism. These issues were addressed in the present study using cultured HepG2 cells exposed to a lethal dose of ethanol. Gamma-glutamyl transferase (GGT) was chosen as a marker of ethanol toxicity because it is widely used in clinics. When the cells were treated with ethanol at various concentrations, there was a dose-dependent increase of GGT activity in the culture media and loss of cell viability. Pretreatment of the cells with green tea extract attenuated the changes significantly. Among the green tea constituents, (-)-epigallocatechin gallate (EGCG) attenuated the ethanol cytotoxicity effectively, whereas L-theanine and caffeine had no effects. The ethanol cytotoxicity was also attenuated by alcohol dehydrogenase inhibitor 4-methyl pyrazol and GGT inhibitor acivicin as well as by thiol modulators such as S-adenosyl-L-methionine, N-acetyl-L-cysteine and glutathione. EGCG failed to prevent the intracellular glutathione loss caused by ethanol, but it appeared to be a strong GGT inhibitor. Therefore the cytoprotective effects of green tea could be attributed to the inhibition of GGT activity by EGCG. This study suggests that GGT inhibitors including EGCG may provide a novel strategy for attenuating ethanol-induced liver damage.",
"title": "Effect of green tea and (-)-epigallocatechin gallate on ethanol-induced toxicity in HepG2 cells."
},
{
"docid": "MED-3531",
"text": "The anthocyanins (1-3) and cyanidin isolated from tart cherries exhibited in vitro antioxidant and antiinflammatory activities comparable to commercial products. The inhibition of lipid peroxidation of anthocyanins 1-3 and their aglycon, cyanidin, were 39, 70, 75, and 57%, respectively, at 2-mM concentrations. The antioxidant activities of 1-3 and cyanidin were comparable to the antioxidant activities of tert-butylhydroquinone and butylated hydroxytoluene and superior to vitamin E at 2-mM concentrations. In the antiinflammatory assay, cyanidin gave IC50 values of 90 and 60 mM, respectively, for prostaglandin H endoperoxide synthase-1 and prostaglandin H endoperoxide synthase-2 enzymes.",
"title": "Antioxidant and antiinflammatory activities of anthocyanins and their aglycon, cyanidin, from tart cherries."
},
{
"docid": "MED-4692",
"text": "Recent studies of shift-working women have reported that excessive exposure to light at night (LAN) may be a risk factor for breast cancer. However, no studies have yet attempted to examine the co-distribution of LAN and breast cancer incidence on a population level with the goal to assess the coherence of these earlier findings with population trends. Coherence is one of Hill's \"criteria\" (actually, viewpoints) for an inference of causality. Nighttime satellite images were used to estimate LAN levels in 147 communities in Israel. Multiple regression analysis was performed to investigate the association between LAN and breast cancer incidence rates and, as a test of the specificity of our method, lung cancer incidence rates in women across localities under the prediction of a link with breast cancer but not lung cancer. After adjusting for several variables available on a population level, such as ethnic makeup, birth rate, population density, and local income level, a strong positive association between LAN intensity and breast cancer rate was revealed (p<0.05), and this association strengthened (p<0.01) when only statistically significant factors were filtered out by stepwise regression analysis. Concurrently, no association was found between LAN intensity and lung cancer rate. These results provide coherence of the previously reported case-control and cohort studies with the co-distribution of LAN and breast cancer on a population basis. The analysis yielded an estimated 73% higher breast cancer incidence in the highest LAN exposed communities compared to the lowest LAN exposed communities.",
"title": "Light at night co-distributes with incident breast but not lung cancer in the female population of Israel."
},
{
"docid": "MED-5030",
"text": "Study Objectives: To examine sex-specific associations between sleep duration and mortality from cardiovascular disease and other causes. Design: Cohort study. Setting: Community-based study. Participants: A total of 98,634 subjects (41,489 men and 57,145 women) aged 40 to 79 years from 1988 to 1990 and were followed until 2003. Interventions: N/A. Measurements and Results: During a median follow-up of 14.3 years, there were 1964 deaths (men and women: 1038 and 926) from stroke, 881 (508 and 373) from coronary heart disease, 4287 (2297 and 1990) from cardiovascular disease, 5465 (3432 and 2033) from cancer, and 14,540 (8548 and 5992) from all causes. Compared with a sleep duration of 7 hours, sleep duration of 4 hours or less was associated with increased mortality from coronary heart disease for women and noncardiovascular disease/noncancer and all causes in both sexes. The respective multivariable hazard ratios were 2.32 (1.19–4.50) for coronary heart disease in women, 1.49 (1.02–2.18) and 1.47 (1.01–2.15) for noncardiovascular disease/noncancer, and 1.29 (1.02–1.64) and 1.28 (1.03–1.60) for all causes in men and women, respectively. Long sleep duration of 10 hours or longer was associated with 1.5- to 2-fold increased mortality from total and ischemic stroke, total cardiovascular disease, noncardiovascular disease/noncancer, and all causes for men and women, compared with 7 hours of sleep in both sexes. There was no association between sleep duration and cancer mortality in either sex. Conclusions: Both short and long sleep duration were associated with increased mortality from cardiovascular disease, noncardiovascular disease/noncancer, and all causes for both sexes, yielding a U-shaped relationship with total mortality with a nadir at 7 hours of sleep. Citation: Ikehara S; Iso H; Date C; Kikuchi S; Watanabe Y; Wada Y; Inaba Y; Tamakoshi A. Association of sleep duration with mortality from cardiovascular disease and other causes for Japanese men and women: the JACC study. SLEEP 2009;32(3):259–301.",
"title": "Association of Sleep Duration with Mortality from Cardiovascular Disease and Other Causes for Japanese Men and Women: the JACC Study"
},
{
"docid": "MED-3523",
"text": "Melatonin, which is contained in certain vegetables, may have an influence on circulatory melatonin concentrations. This study examined the effects of the consumption of vegetables on 6-sulfatoxymelatonin concentrations in morning urine. Ninety-four healthy women aged 24-55 were recruited through a city public health center in Japan. The women randomly allocated to the intervention group were requested to consume high amounts of six selected vegetables, with a target of 350 g/day for 65 days, while those in the control group were asked to avoid the same six vegetables during the same period. First-void morning urine was collected before and at the end of the intervention period, and creatinine-adjusted 6-sulfatoxymelatonin concentrations were measured. At the end of the intervention period, daily mean intake of melatonin from the six vegetables was 1288.0 ng in the intervention group and 5.3 ng in the control group. In the intervention group, the mean concentration of 6-sulfatoxymelatonin changed from 48.1 [95% confidence interval (CI): 40.4-57.2] ng/mg creatinine to 49.6 (95% CI: 42.8-57.3) ng/mg creatinine across the intervention period. In the control group, the mean concentration of 6-sulfatoxymelatonin changed from 55.5 (95% CI: 48.7-63.2) ng/mg creatinine to 50.8 (95% CI: 44.0-58.7) ng/mg creatinine across the intervention period. A comparison of the two groups with regard to the changes in the 6-sulfatoxymelatonin concentrations across the intervention period showed a significant difference (P = 0.03). The results indicate that increased consumption of vegetables raises circulatory melatonin concentrations.",
"title": "Consumption of vegetables alters morning urinary 6-sulfatoxymelatonin concentration."
},
{
"docid": "MED-3527",
"text": "BACKGROUND: : Jet-lag commonly affects air travellers who cross several time zones. It results from the body's internal rhythms being out of step with the day-night cycle at the destination. Melatonin is a pineal hormone that plays a central part in regulating bodily rhythms and has been used as a drug to re-align them with the outside world. OBJECTIVES: : To assess the effectiveness of oral melatonin taken in different dosage regimens for alleviating jet-lag after air travel across several time zones. SEARCH STRATEGY: : We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, PsychLit and Science Citation Index electronically, and the journals 'Aviation, Space and Environmental Medicine' and 'Sleep' by hand. We searched citation lists of relevant studies for other relevant trials. We asked principal authors of relevant studies to tell us about unpublished trials. Reports of adverse events linked to melatonin use outside randomised trials were searched for systematically in 'Side Effects of Drugs' (SED) and SED Annuals, 'Reactions Weekly', MEDLINE, and the adverse drug reactions databases of the WHO Uppsala Monitoring Centre (UMC) and the US Food & Drug Administration. SELECTION CRITERIA: : Randomised trials in airline passengers, airline staff or military personnel given oral melatonin, compared with placebo or other medication. Outcome measures should consist of subjective rating of jet-lag or related components, such as subjective wellbeing, daytime tiredness, onset and quality of sleep, psychological functioning, duration of return to normal, or indicators of circadian rhythms. DATA COLLECTION AND ANALYSIS: : Ten trials met the inclusion criteria. All compared melatonin with placebo; one in addition compared it with a hypnotic, zolpidem. Nine of the trials were of adequate quality to contribute to the assessment, one had a design fault and could not be used in the assessment. Reports of adverse events outside trials were found through MEDLINE, 'Reactions Weekly', and in the WHO UMC database. MAIN RESULTS: : Nine of the ten trials found that melatonin, taken close to the target bedtime at the destination (10pm to midnight), decreased jet-lag from flights crossing five or more time zones. Daily doses of melatonin between 0.5 and 5mg are similarly effective, except that people fall asleep faster and sleep better after 5mg than 0.5mg. Doses above 5mg appear to be no more effective. The relative ineffectiveness of 2mg slow-release melatonin suggests that a short-lived higher peak concentration of melatonin works better. Based on the review, the number needed to treat (NNT) is 2. The benefit is likely to be greater the more time zones are crossed, and less for westward flights. The timing of the melatonin dose is important: if it is taken at the wrong time, early in the day, it is liable to cause sleepiness and delay adaptation to local time. The incidence of other side effects is low. Case reports suggest that people with epilepsy, and patients taking warfarin may come to harm from melatonin. REVIEWER'S CONCLUSIONS: : Melatonin is remarkably effective in preventing or reducing jet-lag, and occasional short-term use appears to be safe. It should be recommended to adult travellers flying across five or more time zones, particularly in an easterly direction, and especially if they have experienced jet-lag on previous journeys. Travellers crossing 2-4 time zones can also use it if need be. The pharmacology and toxicology of melatonin needs systematic study, and routine pharmaceutical quality control of melatonin products must be established. The effects of melatonin in people with epilepsy, and a possible interaction with warfarin, need investigation.",
"title": "Melatonin for the prevention and treatment of jet lag."
},
{
"docid": "MED-2972",
"text": "BACKGROUND: Elevated levels of lipids, such as total cholesterol (TC), low-density lipoprotein cholesterol (LDL), and triglycerides (TG), are widely recognized as risk factors for cardiovascular disease (CVD). Oxidized LDL (OxLDL) is an emerging risk factor considered relevant in oxidative stress and endothelial dysfunction, which is implicated in the progression of CVD. Consumption of a diet rich in polyphenols may be cardioprotective through its impact on oxidative stress and protecting LDL from oxidation. OBJECTIVES: This study was designed to test the ability of strawberry phenolic compounds to mitigate the postprandial effects of a high-fat meal on OxLDL as well as investigate the effects of phenolic compounds on lipid metabolism. METHODS: Twenty-four hyperlipidemic men and women (14 women, 10 men; mean age 50.9 +/- SD 15 years) were recruited to participate in this randomized, single-blind, placebo-controlled, 12-wk crossover trial. After a 10-day run-in period, subjects consumed either an active strawberry beverage (Str; containing 10 g freeze-dried fruit) or a placebo (Pbo) beverage matched in energy and macronutrient composition for 6 weeks. Twice before randomization and once at the 6-week crossover point, subjects received either Str or Pbo with a high-fat challenge meal (HFM). TC, LDL, high-density lipoprotein cholesterol, TG, and OxLDL were measured at defined intervals for 6 h before and after HFM challenge. Fasting concentrations of blood variables at 0, 6, and 12 weeks were compared to assess chronic intake of Str or Pbo. RESULTS: After the HFM during the run-in period, TG and OxLDL were lower after Str than Pbo (p = 0.005, p = 0.01, and p = 0.0008, respectively). HFM responses after 6 weeks of Str versus Pbo resulted in decreased lipid levels and a sex by treatment interaction for OxLDL (p = < 0.0001, and p = 0.0002). CONCLUSION: The present results support a role for strawberry in mitigating fed-state oxidative stressors that may contribute to atherogenesis.",
"title": "Strawberry modulates LDL oxidation and postprandial lipemia in response to high-fat meal in overweight hyperlipidemic men and women."
},
{
"docid": "MED-3522",
"text": "Melatonin has been detected in bacteria, eukaryotic unicells, macroalgae, plants, fungi and various taxa of invertebrates. Although precise determinations are missing in many of these organisms and the roles of melatonin are still unknown, investigations in some species allow more detailed conclusions. Non-vertebrate melatonin is not necessarily circadian, and if so, not always peaking at night, although nocturnal maxima are frequently found. In the cases under study, the major biosynthetic pathway is identical with that of vertebrates. Mimicking of photoperiodic responses and concentration changes upon temperature decreases have been studied in more detail only in dinoflagellates. In plants, an involvement in photoperiodism seems conceivable but requires further support. No stimulation of flowering has been demonstrated to date. A participation in antioxidative protection might be possible in many aerobic non-vertebrates, although evidence for a contribution at physiological levels is mostly missing. Protection from stress by oxidotoxins or/and extensions of lifespan have been shown in very different organisms, such as the dinoflagellate Lingulodinium, the ciliate Paramecium, the rotifer Philodina and Drosophila. Melatonin can be taken up from the food, findings with possible implications in ecophysiology as well as for human nutrition and, with regard to high levels in medicinal plants, also in pharmacology.",
"title": "Non-vertebrate melatonin."
},
{
"docid": "MED-4087",
"text": "Many people suffer from fibromyalgia (FM) without an effective treatment. They do not have a good quality of life and cannot maintain normal daily activity. Among the different hypotheses for its ethiopathophysiology, oxidative stress is one of the possibilities. Non-scientific information addressed to patients regarding the benefits of nutrition is widely available, and they are used to trying non-evidenced strategies. The aim of this paper is to find out what we know right now from scientific studies regarding fibromyalgia disease and nutritional status, diets and food supplements. A systematic search has been performed on Medline with a wide range of terms about these nutritional issues. The search has been made during 2009, for articles published between 1998 and 2008. TARGET POPULATION: people suffering from FM. Vegetarian diets could have some beneficial effects probably due to the increase in antioxidant intake. There is a high prevalence of obesity and overweight in patients, and weight control seems to be an effective tool to improve the symptoms. Some nutritional deficiencies have been described, it is not clear whether they are directly related to this disease or not. About the usefulness of some food supplements we found very little data, and it seems that more studies are needed to prove which ones could be of help. Dietary advice is necessary to these patients to improve their diets and maintain normal weight. It would be interesting to investigate more in the field of nutrition and FM to reveal any possible relationships.",
"title": "Fibromyalgia and nutrition, what do we know?"
},
{
"docid": "MED-3519",
"text": "BACKGROUND: Tart Montmorency cherries have been reported to contain high levels of phytochemicals including melatonin, a molecule critical in regulating the sleep-wake cycle in humans. PURPOSE: The aim of our investigation was to ascertain whether ingestion of a tart cherry juice concentrate would increase the urinary melatonin levels in healthy adults and improve sleep quality. METHODS: In a randomised, double-blind, placebo-controlled, crossover design, 20 volunteers consumed either a placebo or tart cherry juice concentrate for 7 days. Measures of sleep quality recorded by actigraphy and subjective sleep questionnaires were completed. Sequential urine samples over 48 h were collected and urinary 6-sulfatoxymelatonin (major metabolite of melatonin) determined; cosinor analysis was used to determine melatonin circadian rhythm (mesor, acrophase and amplitude). In addition, total urinary melatonin content was determined over the sampled period. Trial differences were determined using a repeated measures ANOVA. RESULTS: Total melatonin content was significantly elevated (P < 0.05) in the cherry juice group, whilst no differences were shown between baseline and placebo trials. There were significant increases in time in bed, total sleep time and sleep efficiency total (P < 0.05) with cherry juice supplementation. Although there was no difference in timing of the melatonin circardian rhythm, there was a trend to a higher mesor and amplitude. CONCLUSIONS: These data suggest that consumption of a tart cherry juice concentrate provides an increase in exogenous melatonin that is beneficial in improving sleep duration and quality in healthy men and women and might be of benefit in managing disturbed sleep.",
"title": "Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality."
},
{
"docid": "MED-3382",
"text": "Artificial food colors (AFCs) have not been established as the main cause of attention-deficit hyperactivity disorder (ADHD), but accumulated evidence suggests that a subgroup shows significant symptom improvement when consuming an AFC-free diet and reacts with ADHD-type symptoms on challenge with AFCs. Of children with suspected sensitivities, 65% to 89% reacted when challenged with at least 100 mg of AFC. Oligoantigenic diet studies suggested that some children in addition to being sensitive to AFCs are also sensitive to common nonsalicylate foods (milk, chocolate, soy, eggs, wheat, corn, legumes) as well as salicylate-containing grapes, tomatoes, and orange. Some studies found \"cosensitivity\" to be more the rule than the exception. Recently, 2 large studies demonstrated behavioral sensitivity to AFCs and benzoate in children both with and without ADHD. A trial elimination diet is appropriate for children who have not responded satisfactorily to conventional treatment or whose parents wish to pursue a dietary investigation.",
"title": "Dietary sensitivities and ADHD symptoms: thirty-five years of research."
},
{
"docid": "MED-5049",
"text": "OBJECTIVE: To evaluate the hypolipemic and antioxidant effects of soy and green tea alone and/or in association in dyslipidemic subjects. METHODS: One hundred dyslipidemic individuals were allocated into four groups. The soy group ingested 50 g of soy (kinako) daily, and the green tea group ingested 3 g of green tea in 500 mL of water per day. A third group ingested 50 g of soy and 3 g of green tea daily, and the control group had a hypocholesterolemic diet. Evaluations were performed at baseline and after 45 and 90 d. Plasma levels of total cholesterol, high-density lipoprotein, and triacylglycerols were evaluated by automated methods. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. LDL was isolated by ultracentrifugation. Total plasma antioxidant capacity and plasma levels of total lipid hydroperoxides and those linked to LDL were evaluated by chemiluminescence. The results were expressed as median values and their 25th to 75th percentiles, with a 5% level of significance. RESULTS: No significant difference occurred in LDL, high-density lipoprotein cholesterol, and triacylglycerol levels across groups. However, a statistically significant difference in total cholesterol occurred within the soy/green tea group 45 and 90 d after intervention. No statistically significant difference occurred in plasma levels of lipid hydroperoxides or those linked to LDL in any of the groups studied. All the groups that used soy and/or green tea presented increased total plasma antioxidant potential. CONCLUSION: Soy and green tea, alone or in combination, increased the total antioxidant potential of hypercholesterolemic patients, whereas only the combination decreased total cholesterol levels.",
"title": "Association between soy and green tea (Camellia sinensis) diminishes hypercholesterolemia and increases total plasma antioxidant potential in dysli..."
},
{
"docid": "MED-4690",
"text": "Physiological and pharmacological blood concentrations of melatonin inhibit tumorigenesis in a variety of in vivo and in vitro experimental models of neoplasia. Evidence indicates that melatonin's anticancer effects are exerted via inhibition of cell proliferation and a stimulation of differentiation and apoptosis. A new mechanism by which physiological and pharmacological blood levels of melatonin inhibit cancer growth in vivois via a melatonin-induced suppression of tumor linoleic acid (LA) uptake and its metabolism to the important mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Melatonin suppresses cAMP formation and inhibits tumor uptake of LA and its metabolism to 13-HODE via a melatonin receptor-mediated mechanism in both tissue-isolated rat hepatoma 7288 CTC and human breast cancer xenografts. It has been postulated that in industrialized societies, light at night, by suppressing melatonin production, poses a new risk for the development of breast cancer and, perhaps, other cancers as well. In support of this hypothesis, light during darkness suppresses nocturnal melatonin production and stimulates the LA metabolism and growth of rat hepatoma and human breast cancer xenografts. Nocturnal dietary supplementation with melatonin, at levels contained in a melatonin-rich diet, inhibits rat hepatoma growth via the mechanisms described above. The nocturnal melatonin signal organizes tumor metabolism and growth within circadian time structure that can be further reinforced by appropriately timed melatonin supplementation. Dietary melatonin supplementation working in concert with the endogenous melatonin signal has the potential to be a new preventive/therapeutic strategy to optimize the host/cancer balance in favor of host survival and quality of life.",
"title": "Putting cancer to sleep at night: the neuroendocrine/circadian melatonin signal."
},
{
"docid": "MED-3144",
"text": "The opiate alkaloids present in poppy seed intended for use in food recently have raised major concerns. An efficient method for routine analysis of morphine and codeine using liquid chromatography in combination with tandem mass spectrometry on a triple quadrupole instrument (LC/MS/MS) was therefore developed. The optimal sample preparation was found to be cold extraction of 10 g of unground poppy seed with 30 mL of methanol containing 0.1% acetic acid for 60 min shaken at 250 rpm. The fate of morphine during food processing was also studied. All experiments led to a significant reduction of morphine and codeine. For poppy cake only 16-50% of the morphine was recovered, and in poppy buns at the highest temperature (220 degrees C) only 3% of the original morphine content was found. Ground poppy seed showed significantly lower recoveries than untreated seed. Morphine elimination during food processing has to be taken into account in the current discussion about its maximum limits in poppy seed.",
"title": "Optimized LC/MS/MS analysis of morphine and codeine in poppy seed and evaluation of their fate during food processing as a basis for risk analysis."
},
{
"docid": "MED-3538",
"text": "OBJECTIVES: To inform the debate over whether human sleep can be chronically reduced without consequences, we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation. DESIGN: The chronic sleep restriction experiment involved randomization to one of three sleep doses (4 h, 6 h, or 8 h time in bed per night), which were maintained for 14 consecutive days. The total sleep deprivation experiment involved 3 nights without sleep (0 h time in bed). Each study also involved 3 baseline (pre-deprivation) days and 3 recovery days. SETTING: Both experiments were conducted under standardized laboratory conditions with continuous behavioral, physiological and medical monitoring. PARTICIPANTS: A total of n = 48 healthy adults (ages 21-38) participated in the experiments. INTERVENTIONS: Noctumal sleep periods were restricted to 8 h, 6 h or 4 h per day for 14 days, or to 0 h for 3 days. All other sleep was prohibited. RESULTS: Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks. Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days, and did not significantly differentiate the 6 h and 4 h conditions. Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis--displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights. Comparison of chronic sleep restriction to total sleep deprivation showed that the latter resulted in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost. A statistical model revealed that, regardless of the mode of sleep deprivation, lapses in behavioral alertness were near-linearly related to the cumulative duration of wakefulness in excess of 15.84 h (s.e. 0.73 h). CONCLUSIONS: Since chronic restriction of sleep to 6 h or less per night produced cognitive performance deficits equivalent to up to 2 nights of total sleep deprivation, it appears that even relatively moderate sleep restriction can seriously impair waking neurobehavioral functions in healthy adults. Sleepiness ratings suggest that subjects were largely unaware of these increasing cognitive deficits, which may explain why the impact of chronic sleep restriction on waking cognitive functions is often assumed to be benign. Physiological sleep responses to chronic restriction did not mirror waking neurobehavioral responses, but cumulative wakefulness in excess of a 15.84 h predicted performance lapses across all four experimental conditions. This suggests that sleep debt is perhaps best understood as resulting in additional wakefulness that has a neurobiological \"cost\" which accumulates over time.",
"title": "The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restricti..."
},
{
"docid": "MED-3381",
"text": "Background: The proposition that synthetic food colors can induce adverse behavioral effects in children was first enunciated in 1975 by Feingold [Why Your Child Is Hyperactive. New York:Random House (1975)], who asserted that elevated sensitivity to food additives underlies the signs of hyperactivity observed in some children. Although the evidence suggested that some unknown proportion of children did respond to synthetic food colors, the U.S. Food and Drug Administration (FDA) interpreted the evidence as inconclusive. A study published in 2007 [McCann et al. Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial. Lancet 370:1560–1567 (2007)] drew renewed attention to the hypothesis because of the study’s size and scope. It led the FDA to review the evidence, hold a public hearing, and seek the advice of its Food Advisory Committee. In preparation for the hearing, the FDA reviewed the available evidence and concluded that it did not warrant further agency action. Objectives: In this commentary I examine the basis of the FDA’s position, the elements of the review that led to its decision and that of the Food Advisory Committee, and the reasons that this is an environmental health issue. Discussion: The FDA review confined itself, in essence, to the clinical diagnosis of hyperactivity, as did the charge to the committee, rather than asking the broader environmental question of behavioral effects in the general population; it failed to recognize the significance of vulnerable subpopulations; and it misinterpreted the meaning of effect size as a criterion of risk. The FDA’s response would have benefited from adopting the viewpoints and perspectives common to environmental health research. At the same time, the food color debate offers a lesson to environmental health researchers; namely, too narrow a focus on a single outcome or criterion can be misleading.",
"title": "Synthetic Food Colors and Neurobehavioral Hazards: The View from Environmental Health Research"
},
{
"docid": "MED-3539",
"text": "Numerous studies have revealed that kiwifruit contains many medicinally useful compounds, among which antioxidants and serotonin may be beneficial in the treatment of the sleep disorders. The aim of this study was to evaluate the effects of kiwifruit on sleep patterns, including sleep onset, duration, and quality. In this study, we applied a free-living, self-controlled diet design. Twenty-four subjects (2 males, 22 females) 20 to 55 years of age consumed 2 kiwifruits 1 hour before bedtime nightly for 4 weeks. The Chinese version of the Pittsburgh Sleep Quality Index (CPSQI), a 3-day sleep diary, and the Actigraph sleep/activity logger watch were used to assess the subjective and objective parameters of sleep quality, including time to bed, time of sleep onset, waking time after sleep onset, time of getting up, total sleep time, and self-reported sleep quality and sleep onset latency, waking time after sleep onset, total sleep time, and sleep efficiency before and after the intervention. After 4 weeks of kiwifruit consumption, the subjective CPSQI score, waking time after sleep onset, and sleep onset latency were significantly decreased (42.4%, 28.9%, and 35.4%, respectively). Total sleep time and sleep efficiency were significantly increased (13.4% and 5.41%, respectively). Kiwifruit consumption may improve sleep onset, duration, and efficiency in adults with self-reported sleep disturbances. Further investigation of the sleep-promoting properties of kiwifruit may be warranted.",
"title": "Effect of kiwifruit consumption on sleep quality in adults with sleep problems."
},
{
"docid": "MED-3532",
"text": "Melatonin is a neurohormone produced by the pineal gland of animals. Serotonin is a monoamine neurotransmitter and one of the precursors of melatonin biosynthesis. These two indoleamines have recently been reported to have widespread occurrence in many edible plants. Consuming foodstuffs containing melatonin and serotonin could raise their physiologic concentrations in blood and enhance human health. Literature concerning analytical methods suitable for determination of melatonin and serotonin in edible plants is limited, although several liquid chromatographic (LC) techniques have been used for their quantification. Liquid chromatography-mass spectrometry (LC-MS) methods combine selectivity, sensitivity, and high precision, and enable the simultaneous determination of melatonin and serotonin. This work reviews LC and LC-MS techniques used to determine melatonin and serotonin, and the available data on melatonin and serotonin levels in edible plants. © 2011 Crown Copyright",
"title": "Application of LC and LC-MS to the analysis of melatonin and serotonin in edible plants."
},
{
"docid": "MED-3518",
"text": "Compared with other industrialized countries, the lower incidence of chronic-degenerative disorders in Mediterranean populations has been emphasized in recent decades. The health-promoting effects arising from Mediterranean dietary habits have been attributed to the large intake of plant foodstuffs rich in bioactive phytochemicals, such as melatonin. Recently, it has been suggested that melatonin present in edible plants may improve human health, by virtue of its biological activities and its good bioavailability. Plant melatonin, besides contributing to optimize the physiological functions regulated, in humans, by endogenous melatonin, may be involved in nutritional therapy to reduce the risk of cancer, cardiovascular and neurodegenerative diseases in western populations. In this view, the presence of melatonin in some Mediterranean foods and beverages adds a new element to the hypothesis of health benefits associated to Mediterranean dietary patterns, although the available data are still preliminary and incomplete.",
"title": "Melatonin in traditional Mediterranean diets."
},
{
"docid": "MED-5050",
"text": "Tea is the most widely consumed beverage in the world after water. Tea is known to be a rich source of flavonoid antioxidants. However tea also contains a unique amino acid, L-theanine that may modulate aspects of brain function in humans. Evidence from human electroencephalograph (EEG) studies show that it has a direct effect on the brain (Juneja et al. Trends in Food Science & Tech 1999;10;199-204). L-theanine significantly increases activity in the alpha frequency band which indicates that it relaxes the mind without inducing drowsiness. However, this effect has only been established at higher doses than that typically found in a cup of black tea (approximately 20mg). The aim of the current research was to establish this effect at more realistic dietary levels. EEG was measured in healthy, young participants at baseline and 45, 60, 75, 90 and 105 minutes after ingestion of 50mg L-theanine (n=16) or placebo (n=19). Participants were resting with their eyes closed during EEG recording. There was a greater increase in alpha activity across time in the L-theanine condition (relative to placebo (p+0.05). A second study replicated this effect in participants engaged in passive activity. These data indicate that L-theanine, at realistic dietary levels, has a significant effect on the general state of mental alertness or arousal. Furthermore, alpha activity is known to play an important role in critical aspects of attention, and further research is therefore focussed on understanding the effect of L-theanine on attentional processes.",
"title": "L-theanine, a natural constituent in tea, and its effect on mental state."
}
] |
[
{
"docid": "MED-4152",
"text": "PURPOSE OF REVIEW: To discuss the benefits of having a good night's sleep for body weight stability. RECENT FINDINGS: Experimental studies have shown that short-term partial sleep restriction decreases glucose tolerance, increases sympathetic tone, elevates cortisol concentrations, decreases the satiety hormone leptin, increases the appetite-stimulating hormone ghrelin, and increases hunger and appetite. Short sleep duration might increase the risk of becoming obese, because it does not allow the recovery of a hormonal profile facilitating appetite control. Lack of sleep could also lead to weight gain and obesity by increasing the time available for eating and by making the maintenance of a healthy lifestyle more difficult. Furthermore, the increased fatigue and tiredness associated with sleeping too little could lessen one's resolve to follow exercise regimens. SUMMARY: Short sleep duration appears to be a novel and independent risk factor for obesity. With the growing prevalence of chronic sleep restriction, any causal association between reduced sleep and obesity would have substantial importance from a public health standpoint. Future research is needed to determine whether sleep extension in sleep-deprived obese individuals will influence appetite control and/or reduce the amount of body fat.",
"title": "Do all sedentary activities lead to weight gain: sleep does not."
},
{
"docid": "MED-5347",
"text": "BACKGROUND: There has been increasing interest in the impact of resident-physician and nurse work hours on patient safety. The evidence demonstrates that work schedules have a profound effect on providers' sleep and performance, as well as on their safety and that of their patients. Nurses working shifts greater than 12.5 hours are at significantly increased risk of experiencing decreased vigilance on the job, suffering an occupational injury, or making a medical error. Physicians-in-training working traditional > 24-hour on-call shifts are at greatly increased risk of experiencing an occupational sharps injury or a motor vehicle crash on the drive home from work and of making a serious or even fatal medical error. As compared to when working 16-hours shifts, on-call residents have twice as many attentional failures when working overnight and commit 36% more serious medical errors. They also report making 300% more fatigue-related medical errors that lead to a patient's death. CONCLUSION: The weight of evidence strongly suggests that extended-duration work shifts significantly increase fatigue and impair performance and safety. From the standpoint of both providers and patients, the hours routinely worked by health care providers in the United States are unsafe. To reduce the unacceptably high rate of preventable fatigue-related medical error and injuries among health care workers, the United States must establish and enforce safe work-hour limits.",
"title": "Effects of health care provider work hours and sleep deprivation on safety and performance."
},
{
"docid": "MED-3927",
"text": "Objective: Epidemiologic studies consistently link caffeine, a nonselective adenosine antagonist, to lower risk of Parkinson disease (PD). However, the symptomatic effects of caffeine in PD have not been adequately evaluated. Methods: We conducted a 6-week randomized controlled trial of caffeine in PD to assess effects upon daytime somnolence, motor severity, and other nonmotor features. Patients with PD with daytime somnolence (Epworth >10) were given caffeine 100 mg twice daily ×3 weeks, then 200 mg twice daily ×3 weeks, or matching placebo. The primary outcome was the Epworth Sleepiness Scale score. Secondary outcomes included motor severity, sleep markers, fatigue, depression, and quality of life. Effects of caffeine were analyzed with Bayesian hierarchical models, adjusting for study site, baseline scores, age, and sex. Results: Of 61 patients, 31 were randomized to placebo and 30 to caffeine. On the primary intention-to-treat analysis, caffeine resulted in a nonsignificant reduction in Epworth Sleepiness Scale score (−1.71 points; 95% confidence interval [CI] −3.57, 0.13). However, somnolence improved on the Clinical Global Impression of Change (+0.64; 0.16, 1.13, intention-to-treat), with significant reduction in Epworth Sleepiness Scale score on per-protocol analysis (−1.97; −3.87, −0.05). Caffeine reduced the total Unified Parkinson's Disease Rating Scale score (−4.69 points; −7.7, −1.6) and the objective motor component (−3.15 points; −5.50, −0.83). Other than modest improvement in global health measures, there were no changes in quality of life, depression, or sleep quality. Adverse events were comparable in caffeine and placebo groups. Conclusions: Caffeine provided only equivocal borderline improvement in excessive somnolence in PD, but improved objective motor measures. These potential motor benefits suggest that a larger long-term trial of caffeine is warranted. Classification of evidence: This study provides Class I evidence that caffeine, up to 200 mg BID for 6 weeks, had no significant benefit on excessive daytime sleepiness in patients with PD.",
"title": "Caffeine for treatment of Parkinson disease"
},
{
"docid": "MED-1042",
"text": "The human colon is still a relatively unknown viscus, especially concerning its motor activity. However, in recent years, techniques have been perfected that allow a better understanding of colonic motility, especially through prolonged recording periods. In this way, it has been demonstrated that the viscus contracts according to a circadian trend, is responsive to physiological stimuli (meals, sleep), and features high amplitude, propulsive contractions that are part of the complex dynamic of the defecatory process. These physiological properties and their alterations in patients with chronic idiopathic constipation are reviewed in this article.",
"title": "Colonic motility in man: features in normal subjects and in patients with chronic idiopathic constipation."
},
{
"docid": "MED-1032",
"text": "To our knowledge, there is no previous clinical description in the literature of patients with defecation syncope. We evaluated 20 patients with this disorder who were a subgroup of a larger, prospective study of syncope, 13 women and seven men, with a mean age of 59 years. Eleven patients had had one episode and nine had experienced multiple episodes. Fourteen patients were recumbent before the urge to defecate, nine of these asleep. The diagnostic evaluation disclosed that two patients had gastrointestinal tract problems, three had cardiac diseases, and one had transient ischemic attacks. Three additional patients had marked orthostatic hypotension. No identifiable cause for defecation syncope was found in 11 patients, but new medical problems were noted in four of those patients. In follow-up at two years, syncope had recurred in ten patients, but the majority of recurrences were unassociated with defecation. Seven patients died during the follow-up period of underlying chronic diseases. We conclude that defecation syncope is not a single distinct clinical entity. Multiple pathologic abnormalities in association with physiologic changes during sleep and defecation may contribute to syncope. Patients with defecation syncope should undergo a careful evaluation for diagnosis of underlying illness causing syncope.",
"title": "Defecation syncope. A symptom with multiple etiologies."
},
{
"docid": "MED-2442",
"text": "A few patients remain severely affected by atopic dermatitis into adult life despite treatment with systemic steroids, azathioprine, and photochemotherapy. 33 patients took part in a double-blind, placebo-controlled, crossover study to assess the efficacy and safety of cyclosporin (5 mg/kg per day) in adults with severe refractory atopic dermatitis. Treatments were given for eight weeks each with one group (n = 16) receiving placebo followed by cyclosporin and another (n = 17) receiving cyclosporin and then placebo. Disease activity, extent of disease, sleep and itch, topical steroid use, and adverse events were assessed every two weeks. Both extent and activity of dermatitis were significantly improved (p less than 0.001) as were subjective measures of disease. 20 patients receiving cyclosporin reported adverse events compared with 8 taking placebo, although no patient required withdrawal from the study. Cyclosporin therapy led to an increase in the mean serum urea, creatinine, and bilirubin concentrations, although only the rise in bilirubin was significant (p = 0.001). Our results confirm that cyclosporin is a safe and effective short-term treatment for severe, refractory atopic dermatitis.",
"title": "Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis."
},
{
"docid": "MED-1300",
"text": "Purpose The effect of brewers’ yeast (1,3)-(1,6)-beta-d-glucan consumption on the number of common cold episodes in healthy subject was investigated. Methods In a placebo-controlled, double-blind, randomized, multicentric clinical trial, 162 healthy participants with recurring infections received 900 mg of either placebo (n = 81) or an insoluble yeast (1,3)-(1,6)-beta-d-glucan preparation (n = 81) per day over a course of 16 weeks. Subjects were instructed to document each occurring common cold episode in a diary and to rate ten predefined infection symptoms during an infections period, resulting in a symptom score. The subjects were examined by the investigator during the episode visit on the 5th day of each cold episode. Results In the per protocol population, supplementation with insoluble yeast (1,3)-(1,6)-beta-glucan reduced the number of symptomatic common cold infections by 25 % as compared to placebo (p = 0.041). The mean symptom score was 15 % lower in the beta-glucan as opposed to the placebo group (p = 0.125). Beta-glucan significantly reduced sleep difficulties caused by cold episode as compared to placebo (p = 0.028). Efficacy of yeast beta-glucan was rated better than the placebo both by physicians (p = 0.004) participants (p = 0.012). Conclusion The present study demonstrated that yeast beta-glucan preparation increased the body’s potential to defend against invading pathogens.",
"title": "Yeast (1,3)-(1,6)-beta-glucan helps to maintain the body’s defence against pathogens: a double-blind, randomized, placebo-controlled, multicentric study in healthy subjects"
},
{
"docid": "MED-2793",
"text": "Piperine, a major active component of black and long peppers, has been reported to enhance drug bioavailability. The present studies were aimed at understanding the interaction of piperine with enzymatic drug biotransforming reactions in hepatic tissue in vitro and in vivo. Piperine inhibited arylhydrocarbon hydroxylation, ethylmorphine-N-demethylation, 7-ethoxycoumarin-O-deethylation and 3-hydroxy-benzo(a)pyrene glucuronidation in rat postmitochondrial supernatant in vitro in a dose-dependent manner. Piperine inhibition of these reactions in postmitochondrial supernatant from 3-methylcholanthrene- and phenobarbital-treated rats was similar to the controls. Inhibition by piperine of arylhydrocarbon hydroxylase (AHH) from 3-methylcholanthrene-treated rats was comparable to that observed with 7,8-benzoflavone. Piperine caused noncompetitive inhibition of hepatic microsomal AHH from the untreated and 3-methylcholanthrene-treated rats with a Ki of 30 microM which was close to the apparent Km of AHH observed in the controls. Similarly, the kinetics of inhibition of ethylmorphine-N-demethylase from control rat liver microsomes exhibited noncompetitive inhibition with an apparent Km of 0.8 mM and Ki of 35 microM. These studies demonstrated that piperine is a nonspecific inhibitor of drug metabolism which shows little discrimination between different cytochrome P-450 forms. Oral administration of piperine in rats strongly inhibited the hepatic AHH and UDP-glucuronyltransferase activities. The maximal inhibition of AHH observed within 1 hr restored to normal value in 6 hr. Pretreatment with piperine prolonged hexobarbital sleeping time and zoxazolamine paralysis time in mice at half the dose of SKF-525A. These results demonstrate that piperine is a potent inhibitor of drug metabolism.",
"title": "Biochemical basis of enhanced drug bioavailability by piperine: evidence that piperine is a potent inhibitor of drug metabolism."
},
{
"docid": "MED-2925",
"text": "Lycium barbarum has been traditionally used in combination with several herbs for medicinal properties, but systematic modern clinical evaluation as a single herb has not been reported. To examine the systematic effects of L. barbarum on immune function, general well-being, and safety, we tested the effects of a standardized L. barbarum fruit juice (GoChi, FreeLife International, Phoenix, AZ, USA) at 120 mL/day, equivalent to at least 150 g of fresh fruit, the amount traditionally used, or placebo for 30 days in a randomized, double-blind, placebo-controlled clinical study in 60 older healthy adults (55-72 years old). The GoChi group showed a statistically significant increase in the number of lymphocytes and levels of interleukin-2 and immunoglobulin G compared to pre-intervention and the placebo group, whereas the number of CD4, CD8, and natural killer cells or levels of interleukin-4 and immunoglobulin A were not significantly altered. The placebo group showed no significant changes in any immune measures. Whereas the GoChi group showed a significant increase in general feelings of well-being, such as fatigue and sleep, and showed a tendency for increased short-term memory and focus between pre- and post-intervention, the placebo group showed no significant positive changes in these measures. No adverse reactions, abnormal symptoms, or changes in body weight, blood pressure, pulse, visual acuity, urine, stool, or blood biochemistry were seen in either group. In conclusion, daily consumption of GoChi significantly increased several immunological responses and subjective feelings of general well-being without any adverse reactions.",
"title": "Immunomodulatory effects of a standardized Lycium barbarum fruit juice in Chinese older healthy human subjects."
},
{
"docid": "MED-826",
"text": "Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS. © 2014 European Society of Endocrinology.",
"title": "The polycystic ovary syndrome: a position statement from the European Society of Endocrinology."
},
{
"docid": "MED-4988",
"text": "OBJECTIVE We assessed the prevalence of type 2 diabetes in people following different types of vegetarian diets compared with that in nonvegetarians. RESEARCH DESIGN AND METHODS The study population comprised 22,434 men and 38,469 women who participated in the Adventist Health Study-2 conducted in 2002–2006. We collected self-reported demographic, anthropometric, medical history, and lifestyle data from Seventh-Day Adventist church members across North America. The type of vegetarian diet was categorized based on a food-frequency questionnaire. We calculated odds ratios (ORs) and 95% CIs using multivariate-adjusted logistic regression. RESULTS Mean BMI was lowest in vegans (23.6 kg/m2) and incrementally higher in lacto-ovo vegetarians (25.7 kg/m2), pesco-vegetarians (26.3 kg/m2), semi-vegetarians (27.3 kg/m2), and nonvegetarians (28.8 kg/m2). Prevalence of type 2 diabetes increased from 2.9% in vegans to 7.6% in nonvegetarians; the prevalence was intermediate in participants consuming lacto-ovo (3.2%), pesco (4.8%), or semi-vegetarian (6.1%) diets. After adjustment for age, sex, ethnicity, education, income, physical activity, television watching, sleep habits, alcohol use, and BMI, vegans (OR 0.51 [95% CI 0.40–0.66]), lacto-ovo vegetarians (0.54 [0.49–0.60]), pesco-vegetarians (0.70 [0.61–0.80]), and semi-vegetarians (0.76 [0.65–0.90]) had a lower risk of type 2 diabetes than nonvegetarians. CONCLUSIONS The 5-unit BMI difference between vegans and nonvegetarians indicates a substantial potential of vegetarianism to protect against obesity. Increased conformity to vegetarian diets protected against risk of type 2 diabetes after lifestyle characteristics and BMI were taken into account. Pesco- and semi-vegetarian diets afforded intermediate protection.",
"title": "Type of Vegetarian Diet, Body Weight, and Prevalence of Type 2 Diabetes"
},
{
"docid": "MED-4990",
"text": "OBJECTIVE We assessed the prevalence of type 2 diabetes in people following different types of vegetarian diets compared with that in nonvegetarians. RESEARCH DESIGN AND METHODS The study population comprised 22,434 men and 38,469 women who participated in the Adventist Health Study-2 conducted in 2002–2006. We collected self-reported demographic, anthropometric, medical history, and lifestyle data from Seventh-Day Adventist church members across North America. The type of vegetarian diet was categorized based on a food-frequency questionnaire. We calculated odds ratios (ORs) and 95% CIs using multivariate-adjusted logistic regression. RESULTS Mean BMI was lowest in vegans (23.6 kg/m2) and incrementally higher in lacto-ovo vegetarians (25.7 kg/m2), pesco-vegetarians (26.3 kg/m2), semi-vegetarians (27.3 kg/m2), and nonvegetarians (28.8 kg/m2). Prevalence of type 2 diabetes increased from 2.9% in vegans to 7.6% in nonvegetarians; the prevalence was intermediate in participants consuming lacto-ovo (3.2%), pesco (4.8%), or semi-vegetarian (6.1%) diets. After adjustment for age, sex, ethnicity, education, income, physical activity, television watching, sleep habits, alcohol use, and BMI, vegans (OR 0.51 [95% CI 0.40–0.66]), lacto-ovo vegetarians (0.54 [0.49–0.60]), pesco-vegetarians (0.70 [0.61–0.80]), and semi-vegetarians (0.76 [0.65–0.90]) had a lower risk of type 2 diabetes than nonvegetarians. CONCLUSIONS The 5-unit BMI difference between vegans and nonvegetarians indicates a substantial potential of vegetarianism to protect against obesity. Increased conformity to vegetarian diets protected against risk of type 2 diabetes after lifestyle characteristics and BMI were taken into account. Pesco- and semi-vegetarian diets afforded intermediate protection.",
"title": "Type of Vegetarian Diet, Body Weight, and Prevalence of Type 2 Diabetes"
},
{
"docid": "MED-5328",
"text": "Aim To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. Methods and Results Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses. Conclusion Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.",
"title": "Vegetarian diets and incidence of diabetes in the Adventist Health Study-2"
},
{
"docid": "MED-3670",
"text": "Generalized and persistent anxiety, accompanied by nervousness and other symptoms (Generalised Anxiety Disorder, GAD) is frequent in the general population and leads to benzodiazepine usage. Unfortunately, these substances induce sedation and have a high potential for drug abuse, and there is thus a need for alternatives. As the anxiolytic properties of lavender have already been demonstrated in pharmacological studies and small-scale clinical trials, it was postulated that lavender has a positive effect in GAD. A controlled clinical study was then performed to evaluate the efficacy of silexan, a new oral lavender oil capsule preparation, versus a benzodiazepine. In this study, the efficacy of a 6-week-intake of silexan compared to lorazepam was investigated in adults with GAD. The primary target variable was the change in the Hamilton Anxiety Rating Scale (HAM-A-total score) as an objective measurement of the severity of anxiety between baseline and week 6. The results suggest that silexan effectively ameliorates generalized anxiety comparable to a common benzodiazepine (lorazepam). The mean of the HAM-A-total score decreased clearly and to a similar extent in both groups (by 11.3+/-6.7 points (45%) in the silexan group and by 11.6+/-6.6 points (46%) in the lorazepam group, from 25+/-4 points at baseline in both groups). During the active treatment period, the two HAM-A subscores \"somatic anxiety\" (HAM-A subscore I) and \"psychic anxiety\" (HAM-A subscore II) also decreased clearly and to a similar extent in both groups. The changes in other subscores measured during the study, such as the SAS (Self-rating Anxiety Scale), PSWQ-PW (Penn State Worry Questionnaire), SF 36 Health survey Questionnaire and Clinical Global Impressions of severity of disorder (CGI item 1, CGI item 2, CGI item 3), and the results of the sleep diary demonstrated comparable positive effects of the two compounds. In conclusion, our results demonstrate that silexan is as effective as lorazepam in adults with GAD. The safety of silexan was also demonstrated. Since lavender oil showed no sedative effects in our study and has no potential for drug abuse, silexan appears to be an effective and well tolerated alternative to benzodiazepines for amelioration of generalised anxiety. Copyright 2009 Elsevier GmbH. All rights reserved.",
"title": "A multi-center, double-blind, randomised study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder."
},
{
"docid": "MED-5310",
"text": "Background Addition of capsaicin (CAPS) to the diet has been shown to increase energy expenditure; therefore capsaicin is an interesting target for anti-obesity therapy. Aim We investigated the 24 h effects of CAPS on energy expenditure, substrate oxidation and blood pressure during 25% negative energy balance. Methods Subjects underwent four 36 h sessions in a respiration chamber for measurements of energy expenditure, substrate oxidation and blood pressure. They received 100% or 75% of their daily energy requirements in the conditions ‘100%CAPS’, ‘100%Control’, ‘75%CAPS’ and ‘75%Control’. CAPS was given at a dose of 2.56 mg (1.03 g of red chili pepper, 39,050 Scoville heat units (SHU)) with every meal. Results An induced negative energy balance of 25% was effectively a 20.5% negative energy balance due to adapting mechanisms. Diet-induced thermogenesis (DIT) and resting energy expenditure (REE) at 75%CAPS did not differ from DIT and REE at 100%Control, while at 75%Control these tended to be or were lower than at 100%Control (p = 0.05 and p = 0.02 respectively). Sleeping metabolic rate (SMR) at 75%CAPS did not differ from SMR at 100%CAPS, while SMR at 75%Control was lower than at 100%CAPS (p = 0.04). Fat oxidation at 75%CAPS was higher than at 100%Control (p = 0.03), while with 75%Control it did not differ from 100%Control. Respiratory quotient (RQ) was more decreased at 75%CAPS (p = 0.04) than at 75%Control (p = 0.05) when compared with 100%Control. Blood pressure did not differ between the four conditions. Conclusion In an effectively 20.5% negative energy balance, consumption of 2.56 mg capsaicin per meal supports negative energy balance by counteracting the unfavorable negative energy balance effect of decrease in components of energy expenditure. Moreover, consumption of 2.56 mg capsaicin per meal promotes fat oxidation in negative energy balance and does not increase blood pressure significantly. Trial Registration Nederlands Trial Register; registration number NTR2944",
"title": "Acute Effects of Capsaicin on Energy Expenditure and Fat Oxidation in Negative Energy Balance"
},
{
"docid": "MED-885",
"text": "Oxalate bioavailability from sugar beet fibre (40 g), spinach (25 g) and a solution of sodium oxalate (182 mg) was tested in nine women using a triplicated 3 x 3 Latin square arrangement. Each test substance provided 120 mg oxalic acid. Throughout the study the volunteers consumed a control diet and the test substances were administered at breakfast on specified days. After an initial 2-day control period, oxalate was administered in three test periods that consisted of one test day followed by one control day. Urine collected during 24-hr periods was analysed daily for oxalate. Oxalate excretion did not differ among the five control days and was not increased significantly following the ingestion of sugar beet fibre by the volunteers. Oxalate excretion was greater (P less than 0.0001) for the mean of the spinach and sodium oxalate solution diets than for the mean of the sugar beet fibre and control diets. Oxalate bioavailability from sugar beet fibre was 0.7% compared with bioavailabilities of 4.5 and 6.2% for spinach and oxalate solutions, respectively. The low bioavailability of oxalate from sugar beet fibre may be attributable to its high ratio of minerals (calcium and magnesium) to oxalate, its complex fibre matrix or the loss of the soluble oxalate during processing of sugar beets.",
"title": "Bioavailability of oxalic acid from spinach, sugar beet fibre and a solution of sodium oxalate consumed by female volunteers."
},
{
"docid": "MED-5313",
"text": "The supraclavicular region is a common site for lymph node metastases. A commonly reported type of nonmalignant (18)F-FDG uptake on PET imaging in the supraclavicular region is \"muscle uptake\" purportedly due to muscle contraction in tense patients during the (18)F-FDG uptake phase. PET/CT offers the unique opportunity to correlate PET findings with CT anatomy in the supraclavicular region. METHODS: Images from the first 359 consecutive clinical whole-body studies (in 347 patients) using (18)F-FDG and a PET/CT scanner (with CT attenuation correction and ordered-subsets expectation maximization [OSEM] reconstruction) were retrospectively reviewed. The supraclavicular region was evaluated for the presence of abnormal uptake on PET images, and the corresponding CT findings were assessed. Three distinct patterns of abnormal (18)F-FDG uptake were noted: pattern A (uptake localizing to supraclavicular area fat [USA-fat], i.e., without corresponding lymph node or muscle uptake on CT), pattern B (uptake localizing to muscle on CT), and pattern C (uptake localizing to lymph nodes or soft-tissue masses on CT). RESULTS: Forty-nine patients (14.1%) (32 female, 17 male; mean age, 51.4 +/- 15.6 y; age range, 12-77 y) showed abnormal (18)F-FDG uptake in the supraclavicular region. Twenty patients (5.8%) had muscle uptake (group B); 15 (4.3%) had definite abnormal lymph nodes (group C). However, 14 patients (4.0%) had USA-fat (group A) and foci of very low Hounsfield units on CT. These foci were also present on (68)Ge attenuation-corrected images (when obtained) and non-attenuation-corrected images. Uptake in USA-fat was typically bilateral and symmetric, intense, more often multifocal than linear, and located in fat on PET/CT. Age was not significantly different for group C versus the 2 other groups. Intensity; mean standardized uptake value, lean (SUV(L MEAN)); or maximum standardized uptake value, lean (SUV(L MAX)), did not allow differentiation between patterns A and C (P > 0.05). Standardized uptake values (SUV(L MAX), 3.1; SUV(L MEAN), 2.1) were significantly lower in group B than in the 2 other groups (P < 0.005). CONCLUSION: So-called muscle uptake in the supraclavicular region may be caused in a significant proportion of cases by an unrelated process we call the USA-fat finding, with (18)F-FDG uptake in tissues of low-Hounsfield (fat) density. This finding most likely reflects an underlying nonpathologic process that we hypothesize to be in foci of brown fat. This intense supraclavicular uptake should be recognized and should not be misinterpreted as a malignant metastatic process or as muscle uptake.",
"title": "Uptake in supraclavicular area fat (\"USA-Fat\"): description on 18F-FDG PET/CT."
},
{
"docid": "MED-3937",
"text": "BACKGROUND: The goal of the present study was to analyze the epidemiology and specific risk factors of traumatic brain injury (TBI) in the Asterix illustrated comic books. Among the illustrated literature, TBI is a predominating injury pattern. METHODS: A retrospective analysis of TBI in all 34 Asterix comic books was performed by examining the initial neurological status and signs of TBI. Clinical data were correlated to information regarding the trauma mechanism, the sociocultural background of victims and offenders, and the circumstances of the traumata, to identify specific risk factors. RESULTS: Seven hundred and four TBIs were identified. The majority of persons involved were adult and male. The major cause of trauma was assault (98.8%). Traumata were classified to be severe in over 50% (GCS 3-8). Different neurological deficits and signs of basal skull fractures were identified. Although over half of head-injury victims had a severe initial impairment of consciousness, no case of death or permanent neurological deficit was found. The largest group of head-injured characters was constituted by Romans (63.9%), while Gauls caused nearly 90% of the TBIs. A helmet had been worn by 70.5% of victims but had been lost in the vast majority of cases (87.7%). In 83% of cases, TBIs were caused under the influence of a doping agent called \"the magic potion\". CONCLUSIONS: Although over half of patients had an initially severe impairment of consciousness after TBI, no permanent deficit could be found. Roman nationality, hypoglossal paresis, lost helmet, and ingestion of the magic potion were significantly correlated with severe initial impairment of consciousness (p ≤ 0.05).",
"title": "Traumatic brain injuries in illustrated literature: experience from a series of over 700 head injuries in the Asterix comic books."
},
{
"docid": "MED-4424",
"text": "OBJECTIVES: Atherosclerosis can obstruct branching arteries of the abdominal aorta, including four paired lumbar arteries and the middle sacral artery that feed the lumbar spine. The diminished blood flow could result in various back problems. The aim of this systematic literature review was to assess associations between atherosclerosis and disc degeneration (DD) or low-back pain (LBP). DATA SOURCES: A systematic search of the Medline/PubMed database for all original articles on atherosclerosis and DD/LBP published until October 2008. The search was performed with the medical subject headings atherosclerosis, cardiovascular risk factor, or vascular disease and keywords \"disc degeneration\", \"disc herniation\", and \"back pain\" on the basis of MeSH tree and as a text search. In addition reference lists were studied and searched manually. Observational studies investigating the association of atherosclerosis or its risk factors and lumbar DD/LBP were selected. REVIEW METHODS: The following data were extracted: study characteristics, duration of follow-up, year of publication, findings of atherosclerosis/cardiovascular risk factors and DD/LBP. Disc herniation was regarded as a form of disc degeneration and cardiovascular risk factors were regarded as surrogate for atherosclerosis in epidemiological studies. RESULTS: One hundred and seventy-nine papers were identified. After exclusion of case reports, letters, editorials, papers not related to the lumbar spine, and animal studies, 25 papers were included. Post-mortem studies showed an association between atheromatous lesions in the aorta and DD, as well as between occluded lumbar arteries and life-time LBP. In clinical studies, aortic calcification was associated with LBP, and stenosis of lumbar arteries was associated with both DD and LBP. In epidemiological studies, smoking and high serum cholesterol levels were found to have the most consistent associations with DD and LBP. CONCLUSION: Aortic atherosclerosis and stenosis of the feeding arteries of the lumbar spine were associated with DD and LBP. Cardiovascular risk factors had weaker associations, being clearly apparent only in cohorts on elderly people or in large study samples. More prospective clinical studies are needed to further clarify the association of atherosclerosis and low-back disorders.",
"title": "Atherosclerosis and disc degeneration/low-back pain--a systematic review."
},
{
"docid": "MED-4724",
"text": "We report on the case of an infant who was hospitalized because of failure to thrive, megaloblastic anemia, and delayed psychomotor development. He was 10 months old and had been exclusively breast-fed by his vegan mother. Investigations showed vitamin B(12) deficiency with hematocytopenia and pervasive developmental disorders as well as vitamin K and vitamin D deficiencies. The infant's mother presented the same deficiencies. Introduction of vitamin supplementation normalized the biological disorders, and the infant showed weight gain and neurological improvement. This case highlights that a vegan diet during pregnancy followed by exclusive breast-feeding can induce nutritional deficiencies in the newborn, with clinical consequences. Detecting mother and child vitamin deficiencies and preventing them is essential.",
"title": "[Consequences of exclusive breast-feeding in vegan mother newborn--case report]."
},
{
"docid": "MED-4740",
"text": "The US Environmental Protection Agency's 2004 Dioxin Reassessment included a characterization of background exposures to dioxin-like compounds, including an estimate of an average background intake dose and an average background body burden. These quantities were derived from data generated in the mid-1990s. Studies conducted in the 2000s were gathered in an attempt to update the estimates generated by the Reassessment. While these studies suggest declines in the average background dose and body burden, a precise quantification of this decline, much less a conclusion that a decline has indeed occurred, cannot be made because of the inconsistency of study design and data sources, and the treatment of non-detects in the generation of congener average concentrations. The average background intake of the Reassessment was 61.0 pg TEQ/day, and using more current data, the average background intake was 40.6 pg TEQ/day. The average body burden from the surveys in the mid-1990s was 22.9 pg TEQ/g lipid weight (pg/g lwt). More recent blood concentration data, from NHANES 2001/2, suggest an adult average at 21.7 pg/g TEQ lwt. These TEQ values include the 17 dioxin and furan congeners and 3 coplanar PCBs, and were generated substituting ND=(1/2)DL or ND=DL/sq rt (2). Results are provided for ND=0 and analyses conducted to evaluate the impacts of this substitution. A more detailed examination of beef and pork data from similarly designed national statistical surveys show that declines in pork are statistically significant while the beef concentrations appeared to have remained constant between the time periods.",
"title": "Evaluation of background exposures of Americans to dioxin-like compounds in the 1990s and the 2000s."
},
{
"docid": "MED-2792",
"text": "Two populations of immigrants to London and to the West Indies from the Indian subcontinent have higher than expected morbidity and mortality from atherosclerosis but do not show the commonly accepted major risk factors. This study investigated the hypothesis that ghee, a clarified butter product prized in Indian cooking, contains cholesterol oxides and could therefore be an important source of dietary exposure to cholesterol oxides and an explanation for the high atherosclerosis risk. Substantial amounts of cholesterol oxides were found in ghee (12.3% of sterols), but not in fresh butter, by thin-layer and high-performance-liquid chromatography. Dietary exposure to cholesterol oxides from ghee may offer a logical explanation for the high frequency of atherosclerotic complications in these Indian populations.",
"title": "Cholesterol oxides in Indian ghee: possible cause of unexplained high risk of atherosclerosis in Indian immigrant populations."
},
{
"docid": "MED-4758",
"text": "AIM: To examine the relation between meat intake and diabetes occurrence in adults. METHODS: In a prospective cohort study we examined the relation between diet and incident diabetes recorded among 8,401 cohort members (ages 45-88 years) of the Adventist Mortality Study and Adventist Health Study (California, USA) who were non-diabetic at baseline. During the 17-year follow-up, we identified 543 incident diabetes cases. RESULTS: (1) Subjects who were weekly consumers of all meats were 29% (OR = 1.29; 95% CI 1.08, 1.55) more likely (relative to zero meat intake) to develop diabetes. (2) Subjects who consumed any processed meats (salted fish and frankfurters) were 38% (OR = 1.38; 95% CI 1.05-1.82) more likely to develop diabetes. (3) Long-term adherence (over a 17-year interval) to a diet that included at least weekly meat intake was associated with a 74% increase (OR = 1.74; 95% CI 1.36-2.22) in odds of diabetes relative to long-term adherence to a vegetarian diet (zero meat intake). Further analyses indicated that some of this risk may be attributable to obesity and/or weight gain--both of which were strong risk factors in this cohort. It is noteworthy that even after control for weight and weight change, weekly meat intake remained an important risk factor (OR = 1.38; 95% CI 1.06-1.68) for diabetes [corrected]. CONCLUSIONS: Our findings raise the possibility that meat intake, particularly processed meats, is a dietary risk factor for diabetes. 2008 S. Karger AG, Basel.",
"title": "Meats, processed meats, obesity, weight gain and occurrence of diabetes among adults: findings from Adventist Health Studies."
},
{
"docid": "MED-1552",
"text": "OBJECTIVE: To determine the quantitative importance of dietary fatty acids and dietary cholesterol to blood concentrations of total, low density lipoprotein, and high density lipoprotein cholesterol. DESIGN: Meta-analysis of metabolic ward studies of solid food diets in healthy volunteers. SUBJECTS: 395 dietary experiments (median duration 1 month) among 129 groups of individuals. RESULTS: Isocaloric replacement of saturated fats by complex carbohydrates for 10% of dietary calories resulted in blood total cholesterol falling by 0.52 (SE 0.03) mmol/l and low density lipoprotein cholesterol falling by 0.36 (0.05) mmol/l. Isocaloric replacement of complex carbohydrates by polyunsaturated fats for 5% of dietary calories resulted in total cholesterol falling by a further 0.13 (0.02) mmol/l and low density lipoprotein cholesterol falling by 0.11 (0.02) mmol/l. Similar replacement of carbohydrates by monounsaturated fats produced no significant effect on total or low density lipoprotein cholesterol. Avoiding 200 mg/day dietary cholesterol further decreased blood total cholesterol by 0.13 (0.02) mmol/l and low density lipoprotein cholesterol by 0.10 (0.02) mmol/l. CONCLUSIONS: In typical British diets replacing 60% of saturated fats by other fats and avoiding 60% of dietary cholesterol would reduce blood total cholesterol by about 0.8 mmol/l (that is, by 10-15%), with four fifths of this reduction being in low density lipoprotein cholesterol.",
"title": "Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies."
},
{
"docid": "MED-5092",
"text": "BACKGROUND: While there is a large body of data on the effects of long-chain polyunsaturated fatty acid supplementation of infant formula on visual and cognitive maturation during infancy, longterm visual and cognitive outcome data from randomized trials are scarce. AIM: To evaluate docosahexaenoic acid (DHA) and arachidonic acid (ARA)-supplementation of infant formula on visual and cognitive outcomes at 4 years of age. METHODS: Fifty-two of 79 healthy term infants who were enrolled in a single-center, double-blind, randomized clinical trial of DHA and ARA supplementation of infant formula were available for follow-up at 4 years of age. In addition, 32 breast-fed infants served as a \"gold standard\". Outcome measures were visual acuity and the Wechsler Preschool and Primary Scale of Intelligence--Revised. RESULTS: At 4 years, the control formula group had poorer visual acuity than the breast-fed group; the DHA- and DHA+ARA-supplemented groups did not differ significantly from the breast-fed group. The control formula and DHA-supplemented groups had Verbal IQ scores poorer than the breast-fed group. CONCLUSION: DHA and ARA-supplementation of infant formula supports visual acuity and IQ maturation similar to that of breast-fed infants.",
"title": "Visual acuity and cognitive outcomes at 4 years of age in a double-blind, randomized trial of long-chain polyunsaturated fatty acid-supplemented in..."
},
{
"docid": "MED-2298",
"text": "Exercise is a fundamental component of good health. The American College of Sports Medicine and \"Exercise is Medicine\" recommend treating exercise as a vital sign, and assessing and prescribing physical activity at every medical visit. Meeting the recommended goals of physical activity results in a significant reduction in all-cause mortality. Physicians can improve health by prescribing exercise. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "A guide to exercise prescription."
},
{
"docid": "MED-3105",
"text": "The gastrointestinal tract is the central organ for uptake of fluids and nutrients, and at the same time it forms the main protective barrier between the sterile environment of the body and the outside world. In mammals, the intestine has further evolved to harbor a vast load of commensal bacteria that have important functions for the host. Discrimination by the host defense system of nonself from self can prevent invasion of pathogens, but equivalent responses to dietary or colonizing bacteria can lead to devastating consequences for the organism. This dilemma imposed by the gut environment has probably contributed significantly to the evolutionary drive that has led to sophisticated mechanisms and diversification of the immune system to allow for protection while maintaining the integrity of the mucosal barrier. The immense expansion and specialization of the immune system is particularly mirrored in the phylogeny, ontogeny, organization, and regulation of the adaptive intraepithelial lymphocytes, or IEL, which are key players in the unique intestinal defense mechanisms that have evolved in mammals.",
"title": "Starting at the beginning: new perspectives on the biology of mucosal T cells."
},
{
"docid": "MED-1757",
"text": "During 1 year, samples were taken on 4 days, one sample in each season, from pigs, the floor, and the air inside pig barns and from the ambient air and soil at different distances outside six commercial livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA)-positive pig barns in the north and east of Germany. LA-MRSA was isolated from animals, floor, and air samples in the barn, showing a range of airborne LA-MRSA between 6 and 3,619 CFU/m3 (median, 151 CFU/m3). Downwind of the barns, LA-MRSA was detected in low concentrations (11 to 14 CFU/m3) at distances of 50 and 150 m; all upwind air samples were negative. In contrast, LA-MRSA was found on soil surfaces at distances of 50, 150, and 300 m downwind from all barns, but no statistical differences could be observed between the proportions of positive soil surface samples at the three different distances. Upwind of the barns, positive soil surface samples were found only sporadically. Significantly more positive LA-MRSA samples were found in summer than in the other seasons both in air and soil samples upwind and downwind of the pig barns. spa typing was used to confirm the identity of LA-MRSA types found inside and outside the barns. The results show that there is regular airborne LA-MRSA transmission and deposition, which are strongly influenced by wind direction and season, of up to at least 300 m around positive pig barns. The described boot sampling method seems suitable to characterize the contamination of the vicinity of LA-MRSA-positive pig barns by the airborne route.",
"title": "Longitudinal Study of the Contamination of Air and of Soil Surfaces in the Vicinity of Pig Barns by Livestock-Associated Methicillin-Resistant Staphylococcus aureus"
},
{
"docid": "MED-4383",
"text": "OBJECTIVE: We investigated the relation between plasma carotenoids, retinol and tocopherol levels and ovarian cancer risk in Korean women. DESIGN: Hospital-based case-control study. SETTING: Six tertiary medical institutes in Korea. POPULATION: Forty-five epithelial ovarian cancers and 135 age-matched controls. METHODS: Preoperative plasma concentrations of beta-carotene, lycopene, zeaxanthin plus lutein, retinol, alpha-tocopherol, and gamma-tocopherol were measured by reverse-phase, gradient high-pressure liquid chromatography. MAIN OUTCOME MEASURES: Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated by tertiles to evaluate the effect of micronutrients on endometrial cancer risk after adjustment for body mass (BMI) index, menopause, parity, oral contraceptive use, smoking status, and alcohol consumption status. RESULTS: Women in the highest tertile for beta-carotene had 0.12-times the risk of ovarian cancer of in the lowest tertile (OR 0.12; 95%CI 0.04-0.36). Women with the highest tertiles of lycopene (OR 0.09; 95%CI 0.03-0.32), zeaxanthin/lutein (OR 0.21; 95%CI 0.09-0.52), retinol (OR 0.45; 95%CI 0.21-0.98), alpha-tocopherol (OR 0.23; 95%CI 0.10-0.53) and gamma-tocopherol (OR 0.28; 95%CI 0.11-0.70) had lower risk of ovarian cancer than women in the lowest tertiles. Results were consistent across strata of socio-epidemiologic factors. CONCLUSIONS: Micronutrients, specifically ss-carotene, lycopene, zeaxanthin, lutein, retinol, alpha-tocopherol, and gamma-tocopherol, may play a role in reducing the risk of ovarian cancer.",
"title": "Plasma carotenoids, retinol and tocopherol levels and the risk of ovarian cancer."
},
{
"docid": "MED-4178",
"text": "A method has been developed to identify pesticide residues and foodstuffs for inclusion in national monitoring programs with different priority levels. It combines two chronic dietary intake indicators: ATMDI based on maximum residue levels and agricultural uses, and EDI on food contamination data. The mean and 95th percentile of exposure were calculated for 490 substances using individual and national consumption data. The results show that mean ATMDI exceeds the acceptable daily intake (ADI) for 10% of the pesticides, and the mean upper-bound EDI is above the ADI for 1.8% of substances. A seven-level risk scale is presented for substances already analyzed in food in France and substances not currently sought. Of 336 substances analyzed, 70 pesticides of concern (levels 2-5) should be particularly monitored, 22 of which are priority pesticides (levels 4 and 5). Of 154 substances not sought, 36 pesticides of concern (levels 2-4) should be included in monitoring programs, including 8 priority pesticides (level 4). In order to refine exposure assessment, analytical improvements and developments are needed to lower the analytical limits for priority pesticide/commodity combinations. Developed nationally, this method could be applied at different geographic scales. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Chronic dietary risk characterization for pesticide residues: a ranking and scoring method integrating agricultural uses and food contamination data."
}
] |
935
|
Peroxynitrite is required for induction of T cell tolerance.
|
[
{
"docid": "5483793",
"text": "Antigen-specific CD8+ T-cell tolerance, induced by myeloid-derived suppressor cells (MDSCs), is one of the main mechanisms of tumor escape. Using in vivo models, we show here that MDSCs directly disrupt the binding of specific peptide–major histocompatibility complex (pMHC) dimers to CD8-expressing T cells through nitration of tyrosines in a T-cell receptor (TCR)-CD8 complex. This process makes CD8-expressing T cells unable to bind pMHC and to respond to the specific peptide, although they retain their ability to respond to nonspecific stimulation. Nitration of TCR-CD8 is induced by MDSCs through hyperproduction of reactive oxygen species and peroxynitrite during direct cell-cell contact. Molecular modeling suggests specific sites of nitration that might affect the conformational flexibility of TCR-CD8 and its interaction with pMHC. These data identify a previously unknown mechanism of T-cell tolerance in cancer that is also pertinent to many pathological conditions associated with accumulation of MDSCs.",
"title": "Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer"
}
] |
[
{
"docid": "42693833",
"text": "Foxp3(+) T cells play a critical role for the maintenance of immune tolerance. Here we show that in mice, Foxp3(+) T cells contributed to diversification of gut microbiota, particularly of species belonging to Firmicutes. The control of indigenous bacteria by Foxp3(+) T cells involved regulatory functions both outside and inside germinal centers (GCs), consisting of suppression of inflammation and regulation of immunoglobulin A (IgA) selection in Peyer's patches, respectively. Diversified and selected IgAs contributed to maintenance of diversified and balanced microbiota, which in turn facilitated the expansion of Foxp3(+) T cells, induction of GCs, and IgA responses in the gut through a symbiotic regulatory loop. Thus, the adaptive immune system, through cellular and molecular components that are required for immune tolerance and through the diversification as well as selection of antibody repertoire, mediates host-microbial symbiosis by controlling the richness and balance of bacterial communities required for homeostasis.",
"title": "Foxp3(+) T cells regulate immunoglobulin a selection and facilitate diversification of bacterial species responsible for immune homeostasis."
},
{
"docid": "18237384",
"text": "Induction of tumor-specific immunity requires that dendritic cells (DCs) efficiently capture and present tumor antigens to result in the expansion and activation of tumor-specific cytotoxic T cells. The transition from antigen capture to T cell stimulation requires a maturation signal; in its absence tolerance, rather than immunity may develop. While immune complexes (ICs) are able to enhance antigen capture, they can be poor at inducing DC maturation, naive T cell activation and protective immunity. We now demonstrate that interfering with the inhibitory signal delivered by FcγRIIB on DCs converts ICs to potent maturation agents and results in T cell activation. Applying this approach to immunization with DCs pulsed ex-vivo with ICs, we have generated antigen-specific CD8+ T cells in vivo and achieved efficient protective immunity in a murine melanoma model. These data imply that ICs may normally function to maintain tolerance through the binding to inhibitory FcγRs on DCs, but they can be converted to potent immunogenic stimuli by selective engagement of activating FcγRs. This mechanism suggests a novel approach to the development of tumor vaccines.",
"title": "Inducing Tumor Immunity through the Selective Engagement of Activating Fcγ Receptors on Dendritic Cells"
},
{
"docid": "994800",
"text": "T cell receptor (TCR) ligation is required for the extrathymic differentiation of forkhead box p3(+) (Foxp3(+)) regulatory T cells. Several lines of evidence indicate that weak TCR stimulation favors induction of Foxp3 in the periphery; however, it remains to be determined how TCR ligand potency influences this process. We characterized the density and affinity of TCR ligand favorable for Foxp3 induction and found that a low dose of a strong agonist resulted in maximal induction of Foxp3 in vivo. Initial Foxp3 induction by weak agonist peptide could be enhanced by disruption of TCR-peptide major histocompatibility complex (pMHC) interactions or alteration of peptide dose. However, time course experiments revealed that Foxp3-positive cells induced by weak agonist stimulation are deleted, along with their Foxp3-negative counterparts, whereas Foxp3-positive cells induced by low doses of the strong agonist persist. Our results suggest that, together, pMHC ligand potency, density, and duration of TCR interactions define a cumulative quantity of TCR stimulation that determines initial peripheral Foxp3 induction. However, in the persistence of induced Foxp3(+) T cells, TCR ligand potency and density are noninterchangeable factors that influence the route to peripheral tolerance.",
"title": "TCR ligand density and affinity determine peripheral induction of Foxp3 in vivo"
},
{
"docid": "24069089",
"text": "Modified anti-CD3 mAbs are emerging as a possible means of inducing immunologic tolerance in settings including transplantation and autoimmunity such as in type 1 diabetes. In a trial of a modified anti-CD3 mAb [hOKT3gamma1(Ala-Ala)] in patients with type 1 diabetes, we identified clinical responders by an increase in the number of peripheral blood CD8+ cells following treatment with the mAb. Here we show that the anti-CD3 mAb caused activation of CD8+ T cells that was similar in vitro and in vivo and induced regulatory CD8+CD25+ T cells. These cells inhibited the responses of CD4+ cells to the mAb itself and to antigen. The regulatory CD8+CD25+ cells were CTLA4 and Foxp3 and required contact for inhibition. Foxp3 was also induced on CD8+ T cells in patients during mAb treatment, which suggests a potential mechanism of the anti-CD3 mAb immune modulatory effects involving induction of a subset of regulatory CD8+ T cells.",
"title": "TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs."
},
{
"docid": "10190778",
"text": "As the immune system develops, T cells are selected or regulated to become tolerant of self antigens and reactive against foreign antigens. In mice, the induction of such tolerance is thought to be attributable to the deletion of self-reactive cells. Here, we show that the human fetal immune system takes advantage of an additional mechanism: the generation of regulatory T cells (Tregs) that suppress fetal immune responses. We find that substantial numbers of maternal cells cross the placenta to reside in fetal lymph nodes, inducing the development of CD4+CD25highFoxP3+ Tregs that suppress fetal antimaternal immunity and persist at least until early adulthood. These findings reveal a form of antigen-specific tolerance in humans, induced in utero and probably active in regulating immune responses after birth.",
"title": "Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero."
},
{
"docid": "301838",
"text": "The thymic medulla provides a specialized microenvironment for the negative selection of T cells, with the presence of autoimmune regulator (Aire)-expressing medullary thymic epithelial cells (mTECs) during the embryonic-neonatal period being both necessary and sufficient to establish long-lasting tolerance. Here we showed that emergence of the first cohorts of Aire(+) mTECs at this key developmental stage, prior to αβ T cell repertoire selection, was jointly directed by Rankl(+) lymphoid tissue inducer cells and invariant Vγ5(+) dendritic epidermal T cell (DETC) progenitors that are the first thymocytes to express the products of gene rearrangement. In turn, generation of Aire(+) mTECs then fostered Skint-1-dependent, but Aire-independent, DETC progenitor maturation and the emergence of an invariant DETC repertoire. Hence, our data attributed a functional importance to the temporal development of Vγ5(+) γδ T cells during thymus medulla formation for αβ T cell tolerance induction and demonstrated a Rank-mediated reciprocal link between DETC and Aire(+) mTEC maturation.",
"title": "Rank Signaling Links the Development of Invariant γδ T Cell Progenitors and Aire+ Medullary Epithelium"
},
{
"docid": "20155713",
"text": "Expression of peripheral antigens in the thymus has been implicated in T cell tolerance and autoimmunity. Here we identified medullary thymic epithelial cells as being a unique cell type that expresses a diverse range of tissue-specific antigens. We found that this promiscuous gene expression was a cell-autonomous property of medullary epithelial cells and was maintained during the entire period of thymic T cell output. It may facilitate tolerance induction to self-antigens that would otherwise be temporally or spatially secluded from the immune system. However, the array of promiscuously expressed self-antigens appeared random rather than selected and was not confined to secluded self-antigens.",
"title": "Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self"
},
{
"docid": "6123924",
"text": "Immune tolerance and activation depend on precise control over the number and function of immunosuppressive Foxp3(+) regulatory T (T reg) cells, and the importance of IL-2 in maintaining tolerance and preventing autoimmunity is clear. However, the homeostatic requirement for IL-2 among specific populations of peripheral T reg cells remains poorly understood. We show that IL-2 selectively maintains a population of quiescent CD44(lo)CD62L(hi) T reg cells that gain access to paracrine IL-2 produced in the T cell zones of secondary lymphoid tissues due to their expression of the chemokine receptor CCR7. In contrast, CD44(hi)CD62L(lo)CCR7(lo) T reg cells that populate nonlymphoid tissues do not access IL-2-prevalent regions in vivo and are insensitive to IL-2 blockade; instead, their maintenance depends on continued signaling through the co-stimulatory receptor ICOS (inducible co-stimulator). Thus, we define a fundamental homeostatic subdivision in T reg cell populations based on their localization and provide an integrated framework for understanding how T reg cell abundance and function are controlled by unique signals in different tissue environments.",
"title": "CCR7 provides localized access to IL-2 and defines homeostatically distinct regulatory T cell subsets"
},
{
"docid": "39550665",
"text": "BACKGROUND & AIMS Chronic infection with the bacterial pathogen Helicobacter pylori causes gastric disorders, ranging from chronic gastritis to gastric adenocarcinoma. Only a subset of infected persons will develop overt disease; most remains asymptomatic despite lifelong colonization. This study aims to elucidate the differential susceptibility to H pylori that is found both across and within populations. METHODS We have established a C57BL/6 mouse model of H pylori infection with a strain that is capable of delivering the virulence factor cytotoxin-associated gene A (CagA) into host cells through the activity of a Cag-pathogenicity island-encoded type IV secretion system. RESULTS Mice infected at 5-6 weeks of age with CagA(+)H pylori rapidly develop gastritis, gastric atrophy, epithelial hyperplasia, and metaplasia in a type IV secretion system-dependent manner. In contrast, mice infected during the neonatal period with the same strain are protected from preneoplastic lesions. Their protection results from the development of H pylori-specific peripheral immunologic tolerance, which requires transforming growth factor-β signaling and is mediated by long-lived, inducible regulatory T cells, and which controls the local CD4(+) T-cell responses that trigger premalignant transformation. Tolerance to H pylori develops in the neonatal period because of a biased ratio of T-regulatory to T-effector cells and is favored by prolonged low-dose exposure to antigen. CONCLUSIONS Using a novel CagA(+)H pylori infection model, we report here that the development of tolerance to H pylori protects from gastric cancer precursor lesions. The age at initial infection may thus account for the differential susceptibility of infected persons to H pylori-associated disease manifestations.",
"title": "Tolerance rather than immunity protects from Helicobacter pylori-induced gastric preneoplasia."
},
{
"docid": "23100962",
"text": "Besides synthesizing nitric oxide (NO), purified neuronal NO synthase (nNOS) can produce superoxide (.O2-) at lower L-Arg concentrations. By using electron paramagnetic resonance spin-trapping techniques, we monitored NO and .O2- formation in nNOS-transfected human kidney 293 cells. In control transfected cells, the Ca2+ ionophore A23187 triggered NO generation but no .O2- was seen. With cells in L-Arg-free medium, we observed .O2- formation that increased as the cytosolic L-Arg levels decreased, while NO generation declined. .O2- formation was virtually abolished by the specific NOS blocker, N-nitro-L-arginine methyl ester (L-NAME). Nitrotyrosine, a specific nitration product of peroxynitrite, accumulated in L-Arg-depleted cells but not in control cells. Activation by A23187 was cytotoxic to L-Arg-depleted, but not to control cells, with marked lactate dehydrogenase release. The cytotoxicity was largely prevented by either superoxide dismutase or L-NAME. Thus, with reduced L-Arg availability NOS elicits cytotoxicity by generating .O2- and NO that interact to form the potent oxidant peroxynitrite. Regulating arginine levels may provide a therapeutic approach to disorders involving .O2-/NO-mediated cellular injury.",
"title": "Nitric oxide synthase generates superoxide and nitric oxide in arginine-depleted cells leading to peroxynitrite-mediated cellular injury."
},
{
"docid": "7343711",
"text": "Successful cancer treatment requires understanding host immune response against tumor cells. PD-1 belongs to the CD28 superfamily of receptors that work as “checkpoints” of immune activation. PD-1 maintains immune self-tolerance to prevent autoimmunity and controls T-cell reaction during infection to prevent excessive tissue damage. Tumor cells that arise from normal tissue acquire mutations that can be targeted by lymphocytes. Accumulating lines of evidence suggest that tumor cells evade host immune attack by expressing physiological PD-1 ligands and stimulating PD-1 on the lymphocytes. Based on this idea, researchers have successfully demonstrated that systemic administration of monoclonal antibodies that inhibit the binding of PD-1 to the ligands reactivated T cells and augmented the anti-cancer immune response. In this review, I summarize the basics of T-cell biology and its regulation by PD-1 and discuss the current understanding and questions about this multifaceted molecule.",
"title": "Basics of PD-1 in self-tolerance, infection, and cancer immunity"
},
{
"docid": "5003144",
"text": "Maintenance of immunological self-tolerance requires lymphocytes carrying self-reactive antigen receptors to be selectively prevented from mounting destructive or inflammatory effector responses. Classically, self-tolerance is viewed in terms of the removal, editing, or silencing of B and T cells that have formed self-reactive antigen receptors during their early development. However, B cells activated by foreign antigen can enter germinal centers (GCs), where they further modify their antigen receptor by somatic hypermutation (SHM) of their immunoglobulin genes. The inevitable emergence of activated, self-reactive GC B cells presents a unique challenge to the maintenance of self-tolerance that must be rapidly countered to avoid autoantibody production. Here we discuss current knowledge of the mechanisms that enforce B cell self-tolerance, with particular focus on the control of self-reactive GC B cells. We also consider how self-reactive GC B cells can escape self-tolerance to initiate autoantibody production or instead be redeemed via SHM and used in productive antibody responses.",
"title": "Self-Reactive B Cells in the Germinal Center Reaction."
},
{
"docid": "36642096",
"text": "BACKGROUND Type 1 diabetes mellitus is a chronic autoimmune disease caused by the pathogenic action of T lymphocytes on insulin-producing beta cells. Previous clinical studies have shown that continuous immune suppression temporarily slows the loss of insulin production. Preclinical studies suggested that a monoclonal antibody against CD3 could reverse hyperglycemia at presentation and induce tolerance to recurrent disease. METHODS We studied the effects of a nonactivating humanized monoclonal antibody against CD3--hOKT3gamma1(Ala-Ala)--on the loss of insulin production in patients with type 1 diabetes mellitus. Within 6 weeks after diagnosis, 24 patients were randomly assigned to receive either a single 14-day course of treatment with the monoclonal antibody or no antibody and were studied during the first year of disease. RESULTS Treatment with the monoclonal antibody maintained or improved insulin production after one year in 9 of the 12 patients in the treatment group, whereas only 2 of the 12 controls had a sustained response (P=0.01). The treatment effect on insulin responses lasted for at least 12 months after diagnosis. Glycosylated hemoglobin levels and insulin doses were also reduced in the monoclonal-antibody group. No severe side effects occurred, and the most common side effects were fever, rash, and anemia. Clinical responses were associated with a change in the ratio of CD4+ T cells to CD8+ T cells 30 and 90 days after treatment. CONCLUSIONS Treatment with hOKT3gamma1(Ala-Ala) mitigates the deterioration in insulin production and improves metabolic control during the first year of type 1 diabetes mellitus in the majority of patients. The mechanism of action of the anti-CD3 monoclonal antibody may involve direct effects on pathogenic T cells, the induction of populations of regulatory cells, or both.",
"title": "Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus."
},
{
"docid": "33499189",
"text": "T cell receptor (TCR-CD3) triggering involves both receptor clustering and conformational changes at the cytoplasmic tails of the CD3 subunits. The mechanism by which TCRalphabeta ligand binding confers conformational changes to CD3 is unknown. By using well-defined ligands, we showed that induction of the conformational change requires both multivalent engagement and the mobility restriction of the TCR-CD3 imposed by the plasma membrane. The conformational change is elicited by cooperative rearrangements of two TCR-CD3 complexes and does not require accompanying changes in the structure of the TCRalphabeta ectodomains. This conformational change at CD3 reverts upon ligand dissociation and is required for T cell activation. Thus, our permissive geometry model provides a molecular mechanism that rationalizes how the information of ligand binding to TCRalphabeta is transmitted to the CD3 subunits and to the intracellular signaling machinery.",
"title": "Full activation of the T cell receptor requires both clustering and conformational changes at CD3."
},
{
"docid": "2734421",
"text": "Medullary thymic epithelial cells (mTECs) establish T cell self-tolerance through the expression of autoimmune regulator (Aire) and peripheral tissue-specific self-antigens. However, signals underlying mTEC development remain largely unclear. Here, we demonstrate crucial regulation of mTEC development by receptor activator of NF-kappaB (RANK) and CD40 signals. Whereas only RANK signaling was essential for mTEC development during embryogenesis, in postnatal mice, cooperation between CD40 and RANK signals was required for mTEC development to successfully establish the medullary microenvironment. Ligation of RANK or CD40 on fetal thymic stroma in vitro induced mTEC development in a tumor necrosis factor-associated factor 6 (TRAF6)-, NF-kappaB inducing kinase (NIK)-, and IkappaB kinase beta (IKKbeta)-dependent manner. These results show that developmental-stage-dependent cooperation between RANK and CD40 promotes mTEC development, thereby establishing self-tolerance.",
"title": "The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance."
},
{
"docid": "10162553",
"text": "Immunosuppressive drugs and cytotoxic chemotherapy agents are designed to kill or suppress autoreactive, alloaggressive, or hyperinflammatory T cells, or disseminated malignancies. However, they also cause severe immunological side effects ranging from interrupted thymopoiesis and general immunodeficiency to, paradoxically, autoimmunity. Consistent with the cross-talk between thymocytes and stromal cells, we now show that these common therapeutic agents have major effects on murine thymic epithelial cells (TEC), crucially required to rebuild immunity posttreatment. We show that the immunosuppressant cyclosporine A, which has been linked to a thymus-dependent autoimmune syndrome in some patients, causes extensive loss of autoimmune regulator (Aire(+)) tolerance-inducing MHC class II(high) medullary TEC (mTEC(high)). Post-cyclosporine A, Aire expression was restored within 7 days. Full recovery of the mTEC(high) subset occurred within 10 days and was linked to a decrease in a relatively resistant MHC class II(low) mTEC subset (mTEC(low)), consistent with a previously described precursor-product relationship. Cyclophosphamide and dexamethasone caused more extensive ablation of thymocytes and stromal cells but again severely depleted tolerance-inducing mTEC(high). Together, these data show that Aire(+) mTECs are highly sensitive to damage and that mTEC regeneration follows a conserved pattern regardless of the treatment regimen used.",
"title": "Ablation and regeneration of tolerance-inducing medullary thymic epithelial cells after cyclosporine, cyclophosphamide, and dexamethasone treatment."
},
{
"docid": "21185923",
"text": "CD25+CD4+ regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance. We show here that glucocorticoid-induced tumor necrosis factor receptor family–related gene (GITR, also known as TNFRSF18)—a member of the tumor necrosis factor–nerve growth factor (TNF-NGF) receptor gene superfamily—is predominantly expressed on CD25+CD4+ T cells and on CD25+CD4+CD8− thymocytes in normal naïve mice. We found that stimulation of GITR abrogated CD25+CD4+ T cell–mediated suppression. In addition, removal of GITR-expressing T cells or administration of a monoclonal antibody to GITR produced organ-specific autoimmune disease in otherwise normal mice. Thus, GITR plays a key role in dominant immunological self-tolerance maintained by CD25+CD4+ regulatory T cells and could be a suitable molecular target for preventing or treating autoimmune disease.",
"title": "Stimulation of CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance"
},
{
"docid": "14644164",
"text": "TLR sense microbial infections, and control activation of immune responses. Dendritic cells, macrophages, and B lymphocytes express TLR and the TLR-signaling adaptor protein MyD88. The impact of TLR-activated B cells on T cell-mediated inflammation is unknown. In this study, we have used mice carrying B cell-restricted deficiencies in MyD88 or in distinct TLR to examine the impact of TLR-activated B cells on a T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis (EAE). We demonstrate that TLR-signaling in B cells suppresses inflammatory T cell responses (both Th1 and Th17), and stimulates recovery from EAE. Only certain TLR are required on B cells for resolution of EAE, and these are dispensable for disease initiation, indicating that a category of TLR agonists preferentially triggers a suppressive function in B cells and thereby limits autoimmune disease. The TLR agonists controlling the regulatory function of B cells are provided by components of Mycobacterium tuberculosis present in the adjuvant. Thus, MyD88 signaling in B cells antagonizes MyD88 signaling in other cells, which drives differentiation of Th17 cells and is required for induction of EAE. Altogether, our data indicate that B cells link recognition of microbial products via TLR to suppression of a T cell-mediated autoimmune disease.",
"title": "TLR-activated B cells suppress T cell-mediated autoimmunity."
},
{
"docid": "9507605",
"text": "The transition of cell–matrix adhesions from the initial punctate focal complexes into the mature elongated form, known as focal contacts, requires GTPase Rho activity. In particular, activation of myosin II–driven contractility by a Rho target known as Rho-associated kinase (ROCK) was shown to be essential for focal contact formation. To dissect the mechanism of Rho-dependent induction of focal contacts and to elucidate the role of cell contractility, we applied mechanical force to vinculin-containing dot-like adhesions at the cell edge using a micropipette. Local centripetal pulling led to local assembly and elongation of these structures and to their development into streak-like focal contacts, as revealed by the dynamics of green fluorescent protein–tagged vinculin or paxillin and interference reflection microscopy. Inhibition of Rho activity by C3 transferase suppressed this force-induced focal contact formation. However, constitutively active mutants of another Rho target, the formin homology protein mDia1 (Watanabe, N., T. Kato, A. Fujita, T. Ishizaki, and S. Narumiya. 1999. Nat. Cell Biol. 1:136–143), were sufficient to restore force-induced focal contact formation in C3 transferase-treated cells. Force-induced formation of the focal contacts still occurred in cells subjected to myosin II and ROCK inhibition. Thus, as long as mDia1 is active, external tension force bypasses the requirement for ROCK-mediated myosin II contractility in the induction of focal contacts. Our experiments show that integrin-containing focal complexes behave as individual mechanosensors exhibiting directional assembly in response to local force.",
"title": "Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCKindependent mechanism"
},
{
"docid": "23122306",
"text": "In an experiment to clarify the involvement of oxygen radicals in lung carcinogenesis induced by diesel exhaust particles (DEP), we found that there is a strong relation between lung tumor response and formation of 8-hydroxydeoxyguanosine (8-OHdG) in lung DNA of mice administered DEP by repeated intratracheal instillation. Repeated intratracheal instillation of DEP also induced the activity of cytochrome P-450 reductase in the lungs as a representative enzyme of superoxide generation, and two types of nitric oxide (NO) synthase, cNOS and iNOS, in the lungs. On the other hand, activities of CuZn-superoxide dismutase (SOD) and Mn-SOD antioxidant enzymes were depressed by the instillation of DEP. These results suggest that generation of superoxide, hydroxyI radical, and nitric oxide are increased in epithelial cells in airways, and that the increased superoxide and nitric oxide react very easily to produce peroxynitrite (ONOO(-)). The peroxynitrite also produce hydroxyI radical. The hydroxyl radical may play an important role in carcinogenesis by DEP.",
"title": "Lung Carcinogenesis by Diesel Exhaust Particles and the Carcinogenic Mechanism Via Active Oxygens."
},
{
"docid": "18429416",
"text": "Food allergy is a major public health concern in westernized countries, estimated to affect 5 % of children and 3–4 % of adults. Allergen-specific immunotherapy for food allergy is currently being actively evaluated, but is still experimental. The optimal protocol, in terms of the route of administration of the food, target maintenance dose, and duration of maintenance therapy, and the optimal patient for these procedures are still being worked out. The mechanisms underlying successful food desensitization are also unclear, in part, because there is no standard immunotherapy protocol. The mechanisms involved, however, may include mast cell and basophil suppression, development of food-specific IgG4 antibodies, reduction in the food-specific IgE/IgG4 ratio, up-regulation and expansion of natural or inducible regulatory T cells, a skewing from a Th2 to a Th1 profile, and the development of anergy and/or deletion in antigen-specific cells. Additional studies are required to elucidate and understand these mechanisms by which desensitization and tolerance are achieved, which may reveal valuable biomarkers for evaluating and following food allergic patients on immunotherapy.",
"title": "Immunological mechanisms for desensitization and tolerance in food allergy"
},
{
"docid": "24177706",
"text": "Animal host defense against infection requires the expression of defense genes at the right place and the right time. Understanding such tight control of host defense requires the elucidation of the transcription factors involved. By using an unbiased approach in the model Caenorhabditis elegans, we discovered that HLH-30 (known as TFEB in mammals) is a key transcription factor for host defense. HLH-30 was activated shortly after Staphylococcus aureus infection, and drove the expression of close to 80% of the host response, including antimicrobial and autophagy genes that were essential for host tolerance of infection. TFEB was also rapidly activated in murine macrophages upon S. aureus infection and was required for proper transcriptional induction of several proinflammatory cytokines and chemokines. Thus, our data suggest that TFEB is a previously unappreciated, evolutionarily ancient transcription factor in the host response to infection.",
"title": "Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes."
},
{
"docid": "25726838",
"text": "The role of immune responses in tumor development is a central issue for tumor biology and immunology. IL-17 is an important cytokine for inflammatory and autoimmune diseases. Although IL-17-producing cells are detected in cancer patients and tumor-bearing mice, the role of IL-17 in tumor development is controversial, and mechanisms remain to be fully elucidated. In the current study, we found that the development of tumors was inhibited in IL-17R-deficient mice. A defect in IFN-gammaR increased tumor growth, whereas tumor growth was inhibited in mice that were deficient in both IL-17R and IFN-gammaR compared with wild-type animals. Further experiments showed that neutralization of IL-17 by Abs inhibited tumor growth in wild-type mice, whereas systemic administration of IL-17 promoted tumor growth. The IL-17R deficiency increased CD8 T cell infiltration, whereas it reduced the infiltration of myeloid-derived suppressor cells (MDSCs) in tumors. In contrast, administration of IL-17 inhibited CD8 T cell infiltration and increased MDSCs in tumors. Further analysis indicated that IL-17 was required for the development and tumor-promoting activity of MDSCs in tumor-bearing mice. These data demonstrate that IL-17-mediated responses promote tumor development through the induction of tumor-promoting microenvironments at tumor sites. IL-17-mediated regulation of MDSCs is a primary mechanism for its tumor-promoting effects. The study provides novel insights into the role of IL-17 in tumor development and has major implications for targeting IL-17 in treatment of tumors.",
"title": "IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells."
},
{
"docid": "4561402",
"text": "Autoimmune polyendocrinopathy syndrome type 1 is a recessive Mendelian disorder resulting from mutations in a novel gene, AIRE, and is characterized by a spectrum of organ-specific autoimmune diseases. It is not known what tolerance mechanisms are defective as a result of AIRE mutation. By tracing the fate of autoreactive CD4+ T cells with high affinity for a pancreatic antigen in transgenic mice with an Aire mutation, we show here that Aire deficiency causes almost complete failure to delete the organ-specific cells in the thymus. These results indicate that autoimmune polyendocrinopathy syndrome 1 is caused by failure of a specialized mechanism for deleting forbidden T cell clones, establishing a central role for this tolerance mechanism.",
"title": "Aire regulates negative selection of organ-specific T cells"
},
{
"docid": "32906513",
"text": "Recent elucidation of the role of central tolerance in preventing organ-specific autoimmunity has changed our concepts of self/nonself discrimination. This paradigmatic shift is largely attributable to the discovery of promiscuous expression of tissue-restricted self-antigens (TRAs) by medullary thymic epithelial cells (mTECs). TRA expression in mTECs mirrors virtually all tissues of the body, irrespective of developmental or spatio-temporal expression patterns. This review summarizes current knowledge on the cellular and molecular regulation of TRA expression in mTECs, outlines relevant mechanisms of antigen presentation and modes of tolerance induction, and discusses implications for the pathogenesis of autoimmune diseases and other biological processes such as fertility, pregnancy, puberty, and tumor defense.",
"title": "A central role for central tolerance."
},
{
"docid": "18488986",
"text": "The expression of melanoma-associated antigens (MAA) being limited to normal melanocytes and melanomas, MAAs are ideal targets for immunotherapy and melanoma vaccines. As MAAs are derived from self, immune responses to these may be limited by thymic tolerance. The extent to which self-tolerance prevents efficient immune responses to MAAs remains unknown. The autoimmune regulator (AIRE) controls the expression of tissue-specific self-antigens in thymic epithelial cells (TECs). The level of antigens expressed in the TECs determines the fate of auto-reactive thymocytes. Deficiency in AIRE leads in both humans (APECED patients) and mice to enlarged autoreactive immune repertoires. Here we show increased IgG levels to melanoma cells in APECED patients correlating with autoimmune skin features. Similarly, the enlarged T cell repertoire in AIRE(-/-) mice enables them to mount anti-MAA and anti-melanoma responses as shown by increased anti-melanoma antibodies, and enhanced CD4(+) and MAA-specific CD8(+) T cell responses after melanoma challenge. We show that thymic expression of gp100 is under the control of AIRE, leading to increased gp100-specific CD8(+) T cell frequencies in AIRE(-/-) mice. TRP-2 (tyrosinase-related protein), on the other hand, is absent from TECs and consequently TRP-2 specific CD8(+) T cells were found in both AIRE(-/-) and AIRE(+/+) mice. This study emphasizes the importance of investigating thymic expression of self-antigens prior to their inclusion in vaccination and immunotherapy strategies.",
"title": "The Immune Response to Melanoma Is Limited by Thymic Selection of Self-Antigens"
},
{
"docid": "32454714",
"text": "Mucosal tolerance has been considered a potentially important pathway for the treatment of autoimmune disease, including human multiple sclerosis and experimental conditions such as experimental autoimmune encephalomyelitis (EAE). There is limited information on the capacity of commensal gut bacteria to induce and maintain peripheral immune tolerance. Inbred SJL and C57BL/6 mice were treated orally with a broad spectrum of antibiotics to reduce gut microflora. Reduction of gut commensal bacteria impaired the development of EAE. Intraperitoneal antibiotic-treated mice showed no significant decline in the gut microflora and developed EAE similar to untreated mice, suggesting that reduction in disease activity was related to alterations in the gut bacterial population. Protection was associated with a reduction of proinflammatory cytokines and increases in IL-10 and IL-13. Adoptive transfer of low numbers of IL-10-producing CD25(+)CD4(+) T cells (>75% FoxP3(+)) purified from cervical lymph nodes of commensal bacteria reduced mice and in vivo neutralization of CD25(+) cells suggested the role of regulatory T cells maintaining peripheral immune homeostasis. Our data demonstrate that antibiotic modification of gut commensal bacteria can modulate peripheral immune tolerance that can protect against EAE. This approach may offer a new therapeutic paradigm in the treatment of multiple sclerosis and perhaps other autoimmune conditions.",
"title": "Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis."
},
{
"docid": "1855679",
"text": "It was recently demonstrated that interleukin (IL)-23–driven IL-17–producing (ThIL-17) T cells mediate inflammatory pathology in certain autoimmune diseases. We show that the induction of antigen-specific ThIL-17 cells, but not T helper (Th)1 or Th2 cells, by immunization with antigens and adjuvants is abrogated in IL-1 receptor type I–deficient (IL-1RI−/−) mice. Furthermore, the incidence of experimental autoimmune encephalomyelitis (EAE) was significantly lower in IL-1RI−/− compared with wild-type mice, and this correlated with a failure to induce autoantigen-specific ThIL-17 cells, whereas induction of Th1 and Th2 responses was not substantially different. However, EAE was induced in IL-1RI−/− mice by adoptive transfer of autoantigen-specific cells from wild-type mice with EAE. IL-23 alone did not induce IL-17 production by T cells from IL-1RI−/− mice, and IL-23–induced IL-17 production was substantially enhanced by IL-1α or IL-1β, even in the absence of T cell receptor stimulation. We demonstrate essential roles for phosphatidylinositol 3-kinase, nuclear factor κB, and novel protein kinase C isoforms in IL-1– and IL-23–mediated IL-17 production. Tumor necrosis factor α also synergized with IL-23 to enhance IL-17 production, and this was IL-1 dependent. Our findings demonstrate that IL-1 functions upstream of IL-17 to promote pathogenic ThIL-17 cells in EAE.",
"title": "A crucial role for interleukin (IL)-1 in the induction of IL-17–producing T cells that mediate autoimmune encephalomyelitis"
},
{
"docid": "7399084",
"text": "T cell homeostasis is crucial for a functional immune system, as the accumulation of T cells resulting from lack of regulatory T cells or an inability to shut down immune responses can lead to inflammation and autoimmune pathology. Here we show that Blimp-1, a transcriptional repressor that is a 'master regulator' of terminal B cell differentiation, was expressed in a subset of antigen-experienced CD4+ and CD8+ T cells. Mice reconstituted with fetal liver stem cells expressing a mutant Blimp-1 lacking the DNA-binding domain developed a lethal multiorgan inflammatory disease caused by an accumulation of effector and memory T cells. These data identify Blimp-1 as an essential regulator of T cell homeostasis and suggest that Blimp-1 regulates both B cell and T cell differentiation.",
"title": "Transcriptional repressor Blimp-1 is essential for T cell homeostasis and self-tolerance"
},
{
"docid": "24612804",
"text": "IL-17 is a novel, CD4+ T cell-restricted cytokine. In vivo, it stimulates hematopoiesis and causes neutrophilia consisting of mature granulocytes. In this study, we show that IL-17-mediated granulopoiesis requires G-CSF release and the presence or induction of the transmembrane form of stem cell factor (SCF) for optimal granulopoiesis. However, IL-17 also protects mice from G-CSF neutralization-induced neutropenia. G-CSF neutralization completely reversed IL-17-induced BM progenitor expansion, whereas splenic CFU-GM/CFU-granulocyte-erythrocyte-megakaryocyte-monocyte was only reduced by 50% in both Sl/Sld and littermate control mice. Thus, there remained a significant SCF/G-CSF-independent effect of IL-17 on splenic granulopoiesis, resulting in a preservation of mature circulating granulocytes. IL-17 is a cytokine that potentially interconnects lymphocytic and myeloid host defense and may have potential for therapeutic development.",
"title": "Requirement of endogenous stem cell factor and granulocyte-colony-stimulating factor for IL-17-mediated granulopoiesis."
}
] |
103259
|
Kong: Skull Island stars an American actor.
|
[
{
"docid": "Kong:_Skull_Island",
"text": "Kong : Skull Island is a 2017 American action-adventure monster film directed by Jordan Vogt-Roberts and written by Dan Gilroy , Max Borenstein and Derek Connolly , from a story by John Gatins . The film is a reboot of the King Kong franchise and serves as the second film in Legendary 's MonsterVerse . It stars an ensemble cast consisting of Tom Hiddleston , Samuel L. Jackson , John Goodman , Brie Larson , Jing Tian , Toby Kebbell , John Ortiz , Corey Hawkins , Jason Mitchell , Shea Whigham , Thomas Mann , Terry Notary and John C. Reilly . The film follows a team of scientists and Vietnam War soldiers who travel to an uncharted island in the Pacific and encounter terrifying creatures and the mighty Kong . Principal photography took place from October 2015 to March 2016 in Hawaii and various locations around Vietnam . Kong : Skull Island premiered on February 28 , 2017 , in London and was released in the United States on March 10 , 2017 , in 2D , 3D , IMAX 3D and in Dolby Cinemas . The film was a critical and commercial success , grossing $ 565 million worldwide against its $ 185 million budget and making it the fifth highest-grossing film of 2017 .",
"title": ""
},
{
"docid": "Samuel_L._Jackson",
"text": "Samuel Leroy Jackson ( born December 21 , 1948 ) is an American actor and film producer . He achieved prominence and critical acclaim in the early 1990s with films such as Jungle Fever ( 1991 ) , Patriot Games ( 1992 ) , Amos & Andrew ( 1993 ) , True Romance ( 1993 ) , Jurassic Park ( 1993 ) and his collaborations with director Quentin Tarantino including Pulp Fiction ( 1994 ) , Jackie Brown ( 1997 ) , Django Unchained ( 2012 ) , and The Hateful Eight ( 2015 ) . He is a highly prolific actor , having appeared in over 100 films , including Die Hard with a Vengeance ( 1995 ) , Unbreakable ( 2000 ) , Shaft ( 2000 ) , The 51st State ( 2001 ) , Black Snake Moan ( 2006 ) , Snakes on a Plane ( 2006 ) , and the Star Wars prequel trilogy ( 1999 -- 2005 ) , as well as the Marvel Cinematic Universe . With Jackson 's permission , his likeness was used for the Ultimate version of the Marvel Comics character Nick Fury . He later cameoed as the character in a post-credits scene from Iron Man ( 2008 ) , and went on to sign a nine-film commitment to reprise this role in future films , including major roles in Iron Man 2 ( 2010 ) , Marvel 's The Avengers ( 2012 ) , Captain America : The Winter Soldier ( 2014 ) and Avengers : Age of Ultron ( 2015 ) and minor roles in Thor ( 2011 ) and Captain America : The First Avenger ( 2011 ) . He has also portrayed the character in the second and final episodes of the first season of the TV show Marvel 's Agents of S.H.I.E.L.D. . He has provided his voice to several animated films , television series and video games , including the roles of Lucius Best / Frozone in Pixar Animation Studios ' film The Incredibles ( 2004 ) , Mace Windu in Star Wars : The Clone Wars ( 2008 ) , Afro Samurai in the anime television series Afro Samurai ( 2007 ) , and Frank Tenpenny in the video game Grand Theft Auto : San Andreas ( 2004 ) . Jackson has achieved critical and commercial acclaim , surpassing Frank Welker as the actor with the highest-grossing film total of all time in October 2011 , and he has received numerous accolades and awards . He is married to LaTanya Richardson , with whom he has a daughter , Zoe . Samuel L. Jackson is ranked as the highest all-time box office star with over $ 4.9053 billion total box office gross , an average of $ 69.1 million per film .",
"title": ""
}
] |
[
{
"docid": "Skull_Island",
"text": "Skull Island is the name most often used to describe a fictional island that first appeared in the 1933 film King Kong and later appearing in its sequels , the two remakes , and any other King Kong-based media . It is the home of the eponymous King Kong and several other species of creatures , mostly prehistoric and in some cases species that should have been extinct long before the rise of mammalian creatures , along with a primitive society of humans . In the 1962 film King Kong vs. Godzilla and the 1967 film King Kong Escapes , the comparable islands are called `` Farou Island '' and `` Mondo Island '' , respectively . Kong plays a similar role in these islands as the godlike being of the land , a role he plays in all versions of the King Kong story . Skull Island 's origins are unknown , but Kong appears to be the only giant gorilla known to exist on the island . However , the 2005 remake shows other skeletons of Kong-sized gorillas , indicating that there was once a group of such creatures of an unknown number living on the island . Additionally , 2017 's Kong : Skull Island showed the skeletons of Kong 's parents .",
"title": ""
},
{
"docid": "Victor_Wong_(actor_born_1906)",
"text": "Victor Wong ( September 24 , 1906 in Los Angeles , California -- April 7 , 1972 in Los Angeles , California ) was an American actor . While Wong appeared in numerous films through the 1930s and 1940s , they were largely small uncredited parts . His biggest role was as Charlie the Cook in the movie King Kong ( 1933 ) and Son of Kong ( 1933 ) . Wong 's most memorable scene came in King Kong when he finds evidence that natives from Skull Island have been aboard the ship Venture , resulting in the kidnapping of heroine Ann Darrow . As Charlie the Cook , Wong yells , `` All hands on deck ! Everybody on deck ! '' This causes panic aboard ship which begins the quest for Ann 's whereabouts and the discovery of King Kong . The Charlie character in the sequel Son of Kong was more prominent to the story and included significantly more screen time for Wong .",
"title": ""
},
{
"docid": "Skull_Island_(disambiguation)",
"text": "Skull Island is a fictional island in the King Kong franchise . Skull Island may also refer to :",
"title": ""
},
{
"docid": "John_Gatins",
"text": "John Gatins ( born April 16 , 1968 ) is an American screenwriter , director , and actor . For writing the action-drama film Flight ( 2012 ) , he was nominated for the Academy Award for Best Original Screenplay . Gatins made his directorial feature debut by filming his screenplay for Dreamer ( 2005 ) , and also wrote or co-wrote Coach Carter ( 2005 ) , Real Steel ( 2011 ) , and Kong : Skull Island ( 2017 ) . As an actor , he has collaborated three times with Eddie Murphy , on Norbit ( 2007 ) , Meet Dave ( 2008 ) and A Thousand Words ( 2012 ) .",
"title": ""
},
{
"docid": "Skull_Island:_Reign_of_Kong",
"text": "Skull Island : Reign of Kong is a ride at Islands of Adventure theme park at Universal Orlando in Florida . It began soft openings on June 9 , 2016 , and officially opened on July 13 , 2016 .",
"title": ""
},
{
"docid": "King_Kong_(1933_film)",
"text": "King Kong is a 1933 American pre-Code monster adventure film directed and produced by Merian C. Cooper and Ernest B. Schoedsack . The screenplay by James Ashmore Creelman and Ruth Rose was from an idea conceived by Cooper and Edgar Wallace . It stars Fay Wray , Bruce Cabot and Robert Armstrong , and opened in New York City on March 2 , 1933 , to rave reviews . It has been ranked by Rotten Tomatoes as the greatest horror film of all time and the twentieth greatest film of all time . The film tells of a gigantic , prehistoric , island-dwelling ape called Kong who dies in an attempt to possess a beautiful young woman . King Kong is especially noted for its stop-motion animation by Willis O'Brien and a groundbreaking musical score by Max Steiner . In 1991 , it was deemed `` culturally , historically and aesthetically significant '' by the Library of Congress and selected for preservation in the National Film Registry . It has been remade twice , in 1976 and 2005 , while a reboot , Kong : Skull Island , was released in 2017 .",
"title": ""
},
{
"docid": "Carl_Denham",
"text": "Carl Denham is a fictional character in the films King Kong and Son of Kong ( both released in 1933 ) , as well as in the 2005 remake of King Kong , and a 2004 illustrated-novel titled Kong : King of Skull Island . The role was played by Robert Armstrong in the 1933 films and by Jack Black in the 2005 remake . Denham 's function in the story is to initiate the action by bringing the characters to Skull Island , where they encounter the giant beast Kong . Denham then brings Kong to New York City to put him on display as entertainment , but he escapes and rampages through the city .",
"title": ""
},
{
"docid": "Toby_Kebbell",
"text": "Tobias Alistair Patrick `` Toby '' Kebbell ( born 9 July 1982 ) is an English stage and film actor . He is known for his roles in films such as Dead Man 's Shoes ( 2004 ) , RocknRolla ( 2008 ) , Prince of Persia : The Sands of Time ( 2010 ) , War Horse ( 2011 ) , Wrath of the Titans ( 2012 ) , Dawn of the Planet of the Apes ( 2014 ) , Fantastic Four ( 2015 ) , Warcraft ( 2016 ) , A Monster Calls ( 2016 ) , and Gold ( 2016 ) . He is also known for his work in the Black Mirror episode , `` The Entire History of You '' . He most recently starred in the second film of the MonsterVerse film series , Kong : Skull Island , which was released in March , 2017 .",
"title": ""
},
{
"docid": "Kong:_The_8th_Wonder_of_the_World",
"text": "Kong : The 8th Wonder of the World is an action/adventure video game developed by Ubisoft for the Nintendo Game Boy Advance . In Europe , it is known as King Kong : The Official Game of the Movie . Due to the limited technology the Game Boy Advance has , King Kong : The 8th Wonder of the World is very different from the home console versions of the game . In this game , players switch between various roles - one being the movie exhibition visiting Skull Island to do filming which comprises actress Ann Darrow , director Carl Denham and scriptwriter Jack Driscoll , and the 25 ft gorilla and king of Skull Island , King Kong . While the overhead human section focuses on puzzle-solving and adventuring elements , Kong sections are combat-oriented side-scrollers .",
"title": ""
},
{
"docid": "Jack_Driscoll",
"text": "Jack Driscoll is a fictional character in the King Kong franchise . In the original 1933 film he was the first mate of the ship The Venture , while in its 2005 remake he was a playwright ( the less faithful 1976 remake had an analogous character named Jack Prescott , played by Jeff Bridges ) . He was played by Bruce Cabot in the original and by Adrien Brody in the remake . In both versions he is one of the main heroes of the story , a man who is on a ship heading for the mysterious Skull Island where Carl Denham intends to make a film . On the way , Driscoll falls in love with the actress , Ann Darrow , and when she is kidnapped by a giant ape on the island , Kong , Driscoll rescues her after helping to lead a search . Beyond these facts , even his characterization is quite different in the two films . Driscoll is a supporting character in Kong : King of Skull Island , an `` authorized '' illustrated-novel that continues the Kong story in 1957 . Driscoll is also a playable character in the video game Peter Jackson 's King Kong : The Official Game of the Movie , along with Kong himself .",
"title": ""
},
{
"docid": "List_of_King_Kong_amusement_park_attractions",
"text": "There are multiple amusement park attractions themed to King Kong . King Kong : 360 3-D currently at Universal Studios Hollywood King Kong Encounter previously at Universal Studios Hollywood Kongfrontation previously at Universal Studios Florida KONG currently at Morey 's Piers Skull Island : Reign of Kong currently at Islands of Adventure Category : Universal Parks & Resorts attractions by name King Kong",
"title": ""
},
{
"docid": "Derek_Connolly",
"text": "Derek Connolly ( born c. 1976 ) is an American screenwriter and film producer , mostly known for his collaborations with director Colin Trevorrow on the films Safety Not Guaranteed , Jurassic World , and the upcoming Star Wars IX . Connolly was also reported to be working on a remake of the film Flight of the Navigator as well as writing an upcoming Pixar film with Teddy Newton . Connolly was listed on Variety 's Ten Screenwriters to Watch in 2012 . Connolly rewrote Kong : Skull Island ( 2017 ) , for Warner Bros. and Legendary Pictures . Connolly attended Palmetto High School in Miami and NYU Film School .",
"title": ""
},
{
"docid": "MonsterVerse",
"text": "The MonsterVerse is an American media franchise and shared fictional universe that is centered on a series of monster films featuring Godzilla and King Kong , distributed by Warner Bros. and produced by Legendary Entertainment in partnership with Toho ( for the Godzilla films ) . The first installment was Godzilla ( 2014 ) , a reboot of the Godzilla franchise , which was followed by Kong : Skull Island ( 2017 ) , a reboot of the King Kong franchise . The next film to be released will be Godzilla : King of the Monsters ( 2019 ) , followed by Godzilla vs. Kong ( 2020 ) . The series has grossed over $ 1 billion worldwide so far .",
"title": ""
},
{
"docid": "King_Kong_(disambiguation)",
"text": "King Kong is a fictional giant ape from Skull Island who has appeared in several works since 1933 . King Kong may also refer to :",
"title": ""
},
{
"docid": "Kong",
"text": "Kong may refer to : King Kong , a fictional giant ape appearing in several films and other works Kōng , a concept in Chinese Zen Buddhism Kong Company , a dog toy producer KONG ( TV ) , a television station in Washington , United States Kong ( Six Flags Discovery Kingdom ) , a roller coaster KONG ( ride ) , a ride at Morey 's Piers in Wildwood , New Jersey Donkey Kong , a series of video games that feature various ape characters that use the Kong name Donkey Kong ( character ) , a fictional character from the series of the same name Diddy Kong Donkey Kong 's partner The Mighty Kong , an animated adaptation of the King Kong story Kong : The Animated Series , an unofficial animated series based on the King Kong character Kong : Skull Island , 2017 American film Mammoth Kong , a gigantic ape monster from the Moonlight Mask Marine Kong , a Japanese TV show about a huge robotic monster Blues Kong , a blue colored bulldog/ape hybrid from Android Kikaider Kong Island , a 1968 film Kong ( band ) , a Dutch progressive metal band Kong the Untamed , a 1975 comicbook series Giant Robots Kongs , various characters from the Dai Sentai Goggle-V series Jake Kong , one of the three main characters from the original The Ghost Busters `` Kong '' , a song by Tenacious D , released as a B-side on the `` POD '' single",
"title": ""
},
{
"docid": "Brie_Larson",
"text": "Brianne Sidonie Desaulniers ( born October 1 , 1989 ) , known professionally as Brie Larson , is an American actress , director , and singer . Born in Sacramento , California , Larson was home-schooled before she studied acting at the American Conservatory Theater . She began her acting career in television , appearing as a regular on the 2001 sitcom Raising Dad , for which she was nominated for a Young Artist Award . As a teenager , Larson had brief roles in the 2004 films 13 Going on 30 and Sleepover . Her performance in the comedy film Hoot ( 2006 ) was praised , and she subsequently played supporting roles in the films Greenberg ( 2010 ) , Scott Pilgrim vs. the World ( 2010 ) , 21 Jump Street ( 2012 ) , and Don Jon ( 2013 ) . From 2009 to 2011 , Larson featured as a rebellious teenager in the television series United States of Tara . Larson 's breakthrough role came with the independent drama Short Term 12 ( 2013 ) , for which she received critical acclaim . Further success came in 2015 when she starred in Room , an acclaimed drama based on Emma Donoghue 's novel of the same name . She won several awards for her portrayal of a troubled mother kidnap victim in the film , including the Academy Award , BAFTA Award , Critic 's Choice Award , Golden Globe Award , Screen Actors Guild Award and Canadian Screen Award for Best Actress . In 2017 , she starred as a war photographer in the adventure film Kong : Skull Island , her highest-grossing release . In 2016 , Larson was cast as Carol Danvers / Captain Marvel in the Marvel Cinematic Universe .",
"title": ""
},
{
"docid": "Miyavi",
"text": ", better known by his stage name , is a Japanese singer-songwriter , guitarist , record producer , and actor . He is known for his finger-slapping style of playing a guitar . He has been active since 1999 , first as guitarist for the now defunct visual kei rock band Dué le Quartz and then as a solo artist starting in 2002 . In 2007 , he became a member of the rock supergroup S.K.I.N. , and in 2009 founded his own company , J-Glam . He toured worldwide several times , with over 250 shows in 30 countries as of 2015 . As of 2016 , he released ten solo albums and 27 singles . He married Japanese-American singer Melody . The couple have two daughters and the family lives in Los Angeles . In 2014 , Miyavi appeared in the motion picture , Unbroken , directed by Angelina Jolie , and went on to undertake smaller roles in American productions like Kong : Skull Island and Stray . Since 2013 , Miyavi is a volunteer at UNHCR , visiting refugee camps around the world .",
"title": ""
},
{
"docid": "Douglas_Tait_(actor)",
"text": "Douglas Tait ( born December 17 , 1978 ) is an American actor , stuntman , and independent filmmaker . Tait has played `` monster '' and creature characters in several films , including Star Trek , Zathura : A Space Adventure , Thor , Indiana Jones and the Kingdom of the Crystal Skull , and Land of the Lost .",
"title": ""
},
{
"docid": "King_Kong:_360_3-D",
"text": "King Kong : 360 3-D is an attraction which is included in the Studio Tour at Universal Studios Hollywood . The attraction takes guests to a recreated version of Skull Island from Peter Jackson 's 2005 award-winning blockbuster remake King Kong . It employs 3-D HD imagery on two 200 ft wide screens , tram motion , wind , water , and scent resulting in an immersive two and a half minute film . The attraction replaced King Kong Encounter which burned down in 2008 . King Kong : 360 3-D made its debut on the Studio Tour on July 1 , 2010 .",
"title": ""
},
{
"docid": "King_Kong_(2005_film)",
"text": "King Kong is a 2005 epic monster adventure film co-written , produced , and directed by Peter Jackson . A remake of the 1933 film of the same name , the film stars Naomi Watts , Jack Black , Adrien Brody , and , through motion capture , Andy Serkis as the title character . Set in 1933 , King Kong tells the story of an ambitious filmmaker who coerces his cast and hired ship crew to travel to the mysterious Skull Island . There they encounter Kong , a legendary giant gorilla , whom they capture and take to New York City . Filming for King Kong took place in New Zealand from September 2004 to March 2005 . The project 's budget climbed from an initial $ 150 million to a then-record-breaking $ 207 million . It was released on December 14 , 2005 in Germany and on December 16 in the United States , and made an opening of $ 50.1 million . While it performed lower than expected , King Kong made domestic and worldwide grosses that eventually added up to $ 550 million , becoming the fourth-highest-grossing film in Universal Pictures history . It also generated $ 100 million in DVD sales upon its home video release . The film garnered positive reviews from critics and appeared on several top ten lists for 2005 . It was praised for its special effects , performances , sense of spectacle and comparison to the 1933 original . It won three Academy Awards for Best Sound Editing , Best Sound Mixing and Best Visual Effects .",
"title": ""
},
{
"docid": "Drew_Crevello",
"text": "Drew Crevello is an American film studio executive known for his work with Warner Bros. studios . He has produced such films as The Grudge 2 and the upcoming 2018 reboot of Tomb Raider . As a senior vice president of film production at Warner Bros. he worked on such films as Ben Affleck 's Live by Night , X-Men : First Class , Kong : Skull Island and Knight and Day . Crevello 's long-term girlfriend is screenwriter Katie Dippold .",
"title": ""
},
{
"docid": "Adrien_Brody",
"text": "Adrien Brody ( born April 14 , 1973 ) is an American actor . He received widespread recognition and acclaim after starring in Roman Polanski 's The Pianist ( 2002 ) , for which he won the Academy Award for Best Actor at age 29 , making him the youngest actor to win in that category . Brody is also the only male American actor to receive the French César Award . Other successful films that Brody has starred in are Bread and Roses , the 2005 version of King Kong , The Village , Predators , New York Stories , and The Thin Red Line . He is a frequent collaborator of Wes Anderson 's and has starred in two of Anderson 's films . Both of these films , The Grand Budapest Hotel and The Darjeeling Limited , were major successes .",
"title": ""
},
{
"docid": "Jacques_Haitkin",
"text": "Jacques Adam Haitkin , ( born August 29 , 1950 , in Brooklyn , New York ) is an American cinematographer . He is well known as the cinematographer for A Nightmare on Elm Street Series 1 and 2 . He studied at the film school of New York University , and American Film Institute , and graduated in 1975 . He is well-known mainly as a horror film cinematographer , especially Wes Craven and Jack Sholder films . He also worked as additional or second unit director of photography on The Expendables , X-Men : First Class , X-Men : The Last Stand , Furious 7 , Teenage Mutant Ninja Turtles : Out of the Shadows , Captain America : Civil War , Kong : Skull Island and The Fate of the Furious .",
"title": ""
},
{
"docid": "The_Skull",
"text": "The Skull is a 1965 British horror film directed by Freddie Francis for Amicus Productions . It starred the frequently paired horror actors Peter Cushing and Christopher Lee , alongside Patrick Wymark , Jill Bennett , Nigel Green , Patrick Magee and Peter Woodthorpe . It was one of a number of British horror films of the sixties to be scored by avant-garde composer Elisabeth Lutyens , including several others for Amicus . The script was written by Milton Subotsky , from a short story by Robert Bloch , `` The Skull of the Marquis de Sade '' .",
"title": ""
},
{
"docid": "Skull_Island_(Washington)",
"text": "Skull Island is a 2.5 acre uninhabited island at the center of Skull Island State Park in the U.S. state of Washington , in Massacre Bay , off the coast of Orcas Island , the largest of the San Juan Archipelago . It was named for holding skulls and bones of a band of Lummi who were killed by raiding Haida in 1858 . Another Skull Island in the same archipelago is located at in Mud Bay , part of Lopez Sound , between the Sperry Peninsula of Lopez Island and Fortress Island .",
"title": ""
},
{
"docid": "Trouble_Maker_(film)",
"text": "Trouble Maker is a 1995 joint Taiwan and Hong Kong romance comedy film directed by Taiwanese director Kevin Chu and produced by Hong Kong director Wong Jing . Starring Taiwanese actor singer Takeshi Kaneshiro , Hong Kong actor Ng Man-tat , Hong Kong actress Athena Chu and Taiwanese child actor Steven Hao Shao Wen . The Hong Kong Chinese title 蠟筆小小生 translates as `` Crayon Siao Siao San '' which is derived from the popular Japanese manga `` Crayon Shin-chan '' about a mischievous little boy . The movie was first released in Taiwan under the title `` Fart King 臭屁王 '' . The movie was renamed and dubbed in Cantonese for all the Taiwanese actors to cater to the Hong Kong audiences . Hong Kong actors Ng Man-tat , Athena Chu and Gabriel Wong Yat-San ( known by his nickname `` Small Turtle '' ) filmed their lines in Cantonese which was dubbed over by an actor for the Mandarin version . The movie was released in Taiwan on 25 March 1995 and then a week later on 1 April 1995 in Hong Kong .",
"title": ""
},
{
"docid": "The_Cannonball_Run",
"text": "The Cannonball Run is a 1981 American-Hong Kong comedy film starring Burt Reynolds , Jackie Chan , Roger Moore , Dom DeLuise , Farrah Fawcett , and an all-star supporting cast . Filmed in Panavision , it was directed by Hal Needham , produced by Hong Kong 's Golden Harvest films , and distributed by 20th Century Fox . One of 1981 's most successful films at the box office , it was followed by Cannonball Run II ( 1984 ) , and Speed Zone ( 1989 ) . This and the 1984 sequel were the final film appearances of actor Dean Martin .",
"title": ""
},
{
"docid": "Shelly_Bay",
"text": "Shelly Bay is a bay on the Miramar Peninsula of Wellington , New Zealand . The New Zealand Defence Force owned the land on Shelly Bay for 124 years until 2009 . Shelly Bay was where most of the scenes depicting `` Skull Island '' in the 2005 film King Kong were filmed .",
"title": ""
},
{
"docid": "Island_of_Fire",
"text": "Island of Fire is a 1990 Hong Kong action film directed by Kevin Chu , and starring Jackie Chan , Andy Lau , Sammo Hung , Tony Leung Ka-fai and Barry Wong . The film was shot in Taiwan and the Philippines in 42 days from 5 April until 17 May 1989 . The film 's theme song , The Last Gunshot by Cui Jian , was written as a response to the 4 June 1989 Tiananmen massacre in Beijing , China . After appearing with Chan in Killer Meteors in 1976 , the film 's producer and co-star , Jimmy Wang Yu , came to Chan 's aid when the then young actor sought his help in settling a dispute with veteran director , Lo Wei . Chan repaid the favour by playing roles in Wang 's films , which included this film as well as the 1982 film Fantasy Mission Force . As with both of those earlier films , recent DVD and VHS releases market Island of Fire & Jackie Chan Is the Prisoner as a Jackie Chan film , displaying an image of Chan on the cover as though the lead actor . In fact , Chan only appears in a supporting role , with Tony Leung Ka-fai as the central character .",
"title": ""
},
{
"docid": "The_Skulls_(film)",
"text": "The Skulls is a 2000 American psychological thriller film starring Joshua Jackson , Paul Walker and Leslie Bibb , directed by Rob Cohen . Its plot is based upon some of the conspiracy theories surrounding Yale University 's Skull and Bones student society . The film was critically panned , but successful enough to spawn two direct-to-video sequels , The Skulls II ( 2002 ) and The Skulls III ( 2004 ) .",
"title": ""
}
] |
531
|
Human embryonic stem cells have the capacity to give rise to differentiated progeny representative of all three embryonic germ layers.
|
[
{
"docid": "36651210",
"text": "Embryonic stem cells have the ability to remain undifferentiated and proliferate indefinitely in vitro while maintaining the potential to differentiate into derivatives of all three embryonic germ layers. These cells have, therefore, potential for in vitro differentiation studies, gene function, and so on. The aim of this study was to produce a human embryonic stem cell line. An inner cell mass of a human blastocyst was separated and cultured on mouse embryonic fibroblasts in embryonic stem cell medium with related additives. The established line was evaluated by morphology; passaging; freezing and thawing; alkaline phosphatase; Oct-4 expression; anti-surface markers including Tra-1-60 and Tra-1-81; and karyotype and spontaneous differentiation. Differentiated cardiomyocytes and neurons were evaluated by transmission electron microscopy and immunocytochemistry. Here, we report the derivation of a new embryonic stem cell line (Royan H1) from a human blastocyst that remains undifferentiated in morphology during continuous passaging for more than 30 passages, maintains a normal XX karyotype, is viable after freezing and thawing, and expresses alkaline phosphatase, Oct-4, Tra-1-60, and Tra-1-81. These cells remain undifferentiated when grown on mouse embryonic fibroblast feeder layers in the presence or absence of recombinant human leukemia inhibitory factor. Royan H1 cells can differentiate in vitro in the absence of feeder cells and can produce embryoid bodies that can further differentiate into beating cardiomyocytes as well as neurons. These results define Royan H1 cells as a new human embryonic stem cell line.",
"title": "Establishment and in vitro differentiation of a new embryonic stem cell line from human blastocyst."
},
{
"docid": "25413327",
"text": "Embryonic stem (ES) cell lines derived from human blastocysts have the developmental potential to form derivatives of all three embryonic germ layers even after prolonged culture. Here we describe the clonal derivation of two human ES cell lines, H9.1 and H9.2. At the time of the clonal derivation of the H9.1 and H9.2 ES cell lines, the parental ES cell line, H9, had already been continuously cultured for 6 months. After an additional 8 months of culture, H9.1 and H9.2 ES cell lines continued to: (1) actively proliferate, (2) express high levels of telomerase, and (3) retain normal karyotypes. Telomere lengths, while somewhat variable, were maintained between 8 and 12 kb in high-passage H9.1 and H9.2 cells. High-passage H9.1 and H9.2 cells both formed teratomas in SCID-beige mice that included differentiated derivatives of all three embryonic germ layers. These results demonstrate the pluripotency of single human ES cells, the maintenance of pluripotency during an extended period of culture, and the long-term self-renewing properties of cultured human ES cells. The remarkable developmental potential, proliferative capacity, and karyotypic stability of human ES cells distinguish them from adult cells.",
"title": "Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture."
},
{
"docid": "10546779",
"text": "Somatic cell nuclear transfer (SCNT) technology has recently been used to generate animals with a common genetic composition. In this study, we report the derivation of a pluripotent embryonic stem (ES) cell line (SCNT-hES-1) from a cloned human blastocyst. The SCNT-hES-1 cells displayed typical ES cell morphology and cell surface markers and were capable of differentiating into embryoid bodies in vitro and of forming teratomas in vivo containing cell derivatives from all three embryonic germ layers in severe combined immunodeficient mice. After continuous proliferation for more than 70 passages, SCNT-hES-1 cells maintained normal karyotypes and were genetically identical to the somatic nuclear donor cells. Although we cannot completely exclude the possibility that the cells had a parthenogenetic origin, imprinting analyses support a SCNT origin of the derived human ES cells.",
"title": "Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst."
}
] |
[
{
"docid": "3360421",
"text": "We describe the derivation of pluripotent embryonic stem (ES) cells from human blastocysts. Two diploid ES cell lines have been cultivated in vitro for extended periods while maintaining expression of markers characteristic of pluripotent primate cells. Human ES cells express the transcription factor Oct-4, essential for development of pluripotential cells in the mouse. When grafted into SCID mice, both lines give rise to teratomas containing derivatives of all three embryonic germ layers. Both cell lines differentiate in vitro into extraembryonic and somatic cell lineages. Neural progenitor cells may be isolated from differentiating ES cell cultures and induced to form mature neurons. Embryonic stem cells provide a model to study early human embryology, an investigational tool for discovery of novel growth factors and medicines, and a potential source of cells for use in transplantation therapy.",
"title": "Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro"
},
{
"docid": "4325137",
"text": "Murine embryonic stem (ES) cells are pluripotent cell lines established directly from the early embryo1,2 which can contribute differentiated progeny to all adult tissues, including the germ-cell lineage3, after re-incorporation into the normal embryo. They provide both a cellular vector for the generation of transgenic animals4 and a useful system for the identification of polypeptide factors controlling differentiation processes in early development5. In particular, medium conditioned by Buffalo rat liver cells contains a polypeptide factor, ES cell differentiation inhibitory activity (DIA), which specifically suppresses the spontaneous differentiation of ES cells in vitro, thereby permitting their growth as homogeneous stem cell populations in the absence of heterologous feeder cells6. ES cell pluripotentiality, including the ability to give rise to functional gametes, is preserved after prolonged culture in Buffalo rat liver media as a source of DIA7. Here, we report that purified DIA is related in structure and function to the recently identified haemopoetic regulatory factors human interleukin for DA cells8,9 and leukaemia inhibitory factor10. DIA and human interleukin DA/leukaemia inhibitory factor have thus been identified as related multifunctional regulatory factors with distinct biological activities in both early embryonic and haemopoetic stem cell systems.",
"title": "Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides"
},
{
"docid": "26374799",
"text": "Human embryonic stem cells (hESCs) self-renew indefinitely and give rise to derivatives of all three primary germ layers, yet little is known about the signaling cascades that govern their pluripotent character. Because it plays a prominent role in the early cell fate decisions of embryonic development, we have examined the role of TGFbeta superfamily signaling in hESCs. We found that, in undifferentiated cells, the TGFbeta/activin/nodal branch is activated (through the signal transducer SMAD2/3) while the BMP/GDF branch (SMAD1/5) is only active in isolated mitotic cells. Upon early differentiation, SMAD2/3 signaling is decreased while SMAD1/5 signaling is activated. We next tested the functional role of TGFbeta/activin/nodal signaling in hESCs and found that it is required for the maintenance of markers of the undifferentiated state. We extend these findings to show that SMAD2/3 activation is required downstream of WNT signaling, which we have previously shown to be sufficient to maintain the undifferentiated state of hESCs. Strikingly, we show that in ex vivo mouse blastocyst cultures, SMAD2/3 signaling is also required to maintain the inner cell mass (from which stem cells are derived). These data reveal a crucial role for TGFbeta signaling in the earliest stages of cell fate determination and demonstrate an interconnection between TGFbeta and WNT signaling in these contexts.",
"title": "TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells."
},
{
"docid": "36398420",
"text": "The purpose of this study was to determine the lineage progression of human and murine very small embryonic-like (HuVSEL or MuVSEL) cells in vitro and in vivo. In vitro, HuVSEL and MuVSEL cells differentiated into cells of all three embryonic germ layers. HuVSEL cells produced robust mineralized tissue of human origin compared with controls in calvarial defects. Immunohistochemistry demonstrated that the HuVSEL cells gave rise to neurons, adipocytes, chondrocytes, and osteoblasts within the calvarial defects. MuVSEL cells were also able to differentiate into similar lineages. First round serial transplants of MuVSEL cells into irradiated osseous sites demonstrated that ∼60% of the cells maintained their VSEL cell phenotype while other cells differentiated into multiple tissues at 3 months. Secondary transplants did not identify donor VSEL cells, suggesting limited self renewal but did demonstrate VSEL cell derivatives in situ for up to 1 year. At no point were teratomas identified. These studies show that VSEL cells produce multiple cellular structures in vivo and in vitro and lay the foundation for future cell-based regenerative therapies for osseous, neural, and connective tissue disorders.",
"title": "Human and murine very small embryonic-like cells represent multipotent tissue progenitors, in vitro and in vivo."
},
{
"docid": "4427392",
"text": "The functional heart is comprised of distinct mesoderm-derived lineages including cardiomyocytes, endothelial cells and vascular smooth muscle cells. Studies in the mouse embryo and the mouse embryonic stem cell differentiation model have provided evidence indicating that these three lineages develop from a common Flk-1+ (kinase insert domain protein receptor, also known as Kdr) cardiovascular progenitor that represents one of the earliest stages in mesoderm specification to the cardiovascular lineages. To determine whether a comparable progenitor is present during human cardiogenesis, we analysed the development of the cardiovascular lineages in human embryonic stem cell differentiation cultures. Here we show that after induction with combinations of activin A, bone morphogenetic protein 4 (BMP4), basic fibroblast growth factor (bFGF, also known as FGF2), vascular endothelial growth factor (VEGF, also known as VEGFA) and dickkopf homolog 1 (DKK1) in serum-free media, human embryonic-stem-cell-derived embryoid bodies generate a KDRlow/C-KIT(CD117)neg population that displays cardiac, endothelial and vascular smooth muscle potential in vitro and, after transplantation, in vivo. When plated in monolayer cultures, these KDRlow/C-KITneg cells differentiate to generate populations consisting of greater than 50% contracting cardiomyocytes. Populations derived from the KDRlow/C-KITneg fraction give rise to colonies that contain all three lineages when plated in methylcellulose cultures. Results from limiting dilution studies and cell-mixing experiments support the interpretation that these colonies are clones, indicating that they develop from a cardiovascular colony-forming cell. Together, these findings identify a human cardiovascular progenitor that defines one of the earliest stages of human cardiac development.",
"title": "Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population"
},
{
"docid": "11335860",
"text": "Pluripotent human embryonic stem (hES) cells can differentiate into various cell types derived from the three embryonic germ layers and extraembryonic tissues such as trophoblasts. The mechanisms governing lineage choices of hES cells are largely unknown. Here, we report that we established two independent hES cell clones lacking a group of cell surface molecules, glycosyl-phosphatidyl-inositol-anchored proteins (GPI-APs). The GPI-AP deficiency in these two hES clones is due to the deficiency in the gene expression of PIG-A (phosphatidyl-inositol-glycan class A), which is required for the first step of GPI synthesis. GPI-AP-deficient hES cells were capable of forming embryoid bodies and initiating cell differentiation into the three embryonic germ layers. However, GPI-AP-deficient hES cells failed to form trophoblasts after differentiation induction by embryoid body formation or by adding exogenous BMP4. The defect in trophoblast formation was due to the lack of GPI-anchored BMP coreceptors, resulting in the impairment of full BMP4 signaling activation in the GPI-AP-deficient hES cells. These data reveal that GPI-AP-enhanced full activation of BMP signaling is required for human trophoblast formation.",
"title": "Trophoblast differentiation defect in human embryonic stem cells lacking PIG-A and GPI-anchored cell-surface proteins."
},
{
"docid": "19770974",
"text": "Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages. After undifferentiated proliferation in vitro for 4 to 5 months, these cells still maintained the developmental potential to form trophoblast and derivatives of all three embryonic germ layers, including gut epithelium (endoderm); cartilage, bone, smooth muscle, and striated muscle (mesoderm); and neural epithelium, embryonic ganglia, and stratified squamous epithelium (ectoderm). These cell lines should be useful in human developmental biology, drug discovery, and transplantation medicine.",
"title": "Prev | Table of Contents Reports Embryonic Stem Cell Lines Derived from Human"
},
{
"docid": "86129154",
"text": "Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells. These induced pluripotent human stem cells have normal karyotypes, express telomerase activity, express cell surface markers and genes that characterize human ES cells, and maintain the developmental potential to differentiate into advanced derivatives of all three primary germ layers. Such induced pluripotent human cell lines should be useful in the production of new disease models and in drug development, as well as for applications in transplantation medicine, once technical limitations (for example, mutation through viral integration) are eliminated.",
"title": "Induced pluripotent stem cell lines derived from human somatic cells."
},
{
"docid": "27588420",
"text": "Human induced pluripotent stem cells (HiPSCs) appear to be highly similar to human embryonic stem cells (HESCs). Using two genetic lineage-tracing systems, we demonstrate the generation of iPSC lines from human pancreatic islet beta cells. These reprogrammed cells acquired markers of pluripotent cells and differentiated into the three embryonic germ layers. However, the beta cell-derived iPSCs (BiPSCs) maintained open chromatin structure at key beta-cell genes, together with a unique DNA methylation signature that distinguishes them from other PSCs. BiPSCs also demonstrated an increased ability to differentiate into insulin-producing cells both in vitro and in vivo, compared with ESCs and isogenic non-beta iPSCs. Our results suggest that the epigenetic memory may predispose BiPSCs to differentiate more readily into insulin producing cells. These findings demonstrate that HiPSC phenotype may be influenced by their cells of origin, and suggest that their skewed differentiation potential may be advantageous for cell replacement therapy.",
"title": "Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells."
},
{
"docid": "4423327",
"text": "Nanog is a divergent homeodomain protein found in mammalian pluripotent cells and developing germ cells. Deletion of Nanog causes early embryonic lethality, whereas constitutive expression enables autonomous self-renewal of embryonic stem cells. Nanog is accordingly considered a core element of the pluripotent transcriptional network. However, here we report that Nanog fluctuates in mouse embryonic stem cells. Transient downregulation of Nanog appears to predispose cells towards differentiation but does not mark commitment. By genetic deletion we show that, although they are prone to differentiate, embryonic stem cells can self-renew indefinitely in the permanent absence of Nanog. Expanded Nanog null cells colonize embryonic germ layers and exhibit multilineage differentiation both in fetal and adult chimaeras. Although they are also recruited to the germ line, primordial germ cells lacking Nanog fail to mature on reaching the genital ridge. This defect is rescued by repair of the mutant allele. Thus Nanog is dispensible for expression of somatic pluripotency but is specifically required for formation of germ cells. Nanog therefore acts primarily in construction of inner cell mass and germ cell states rather than in the housekeeping machinery of pluripotency. We surmise that Nanog stabilizes embryonic stem cells in culture by resisting or reversing alternative gene expression states.",
"title": "Nanog safeguards pluripotency and mediates germline development"
},
{
"docid": "22428640",
"text": "Embryonic stem cells have an unlimited potential for self-renewal yet are pluripotent, capable of differentiating into three different germ layers and ultimately into multiple cell lineages. Key pluripotency specific factors maintain an undifferentiated ES cell phenotype while lineage specific factors work in opposition to promote cell specialization. In addition to these important transcriptional regulators, epigenetic modifiers play a defining role in regulating the balance between pluripotency and differentiation by promoting changes in chromatin structure.",
"title": "Chromatin remodeling in embryonic stem cells: regulating the balance between pluripotency and differentiation."
},
{
"docid": "4452318",
"text": "Pluripotency is defined by the ability of a cell to differentiate to the derivatives of all the three embryonic germ layers: ectoderm, mesoderm and endoderm. Pluripotent cells can be captured via the archetypal derivation of embryonic stem cells or via somatic cell reprogramming. Somatic cells are induced to acquire a pluripotent stem cell (iPSC) state through the forced expression of key transcription factors, and in the mouse these cells can fulfil the strictest of all developmental assays for pluripotent cells by generating completely iPSC-derived embryos and mice. However, it is not known whether there are additional classes of pluripotent cells, or what the spectrum of reprogrammed phenotypes encompasses. Here we explore alternative outcomes of somatic reprogramming by fully characterizing reprogrammed cells independent of preconceived definitions of iPSC states. We demonstrate that by maintaining elevated reprogramming factor expression levels, mouse embryonic fibroblasts go through unique epigenetic modifications to arrive at a stable, Nanog-positive, alternative pluripotent state. In doing so, we prove that the pluripotent spectrum can encompass multiple, unique cell states.",
"title": "Divergent reprogramming routes lead to alternative stem-cell states"
},
{
"docid": "35443524",
"text": "Cancer stem cells (CSCs) are a subpopulation of tumor cells that selectively possess tumor initiation and self-renewal capacity and the ability to give rise to bulk populations of nontumorigenic cancer cell progeny through differentiation. As we discuss here, they have been prospectively identified in several human malignancies, and their relative abundance in clinical cancer specimens has been correlated with malignant disease progression in human patients. Furthermore, recent findings suggest that clinical cancer progression driven by CSCs may contribute to the failure of existing therapies to consistently eradicate malignant tumors. Therefore, CSC-directed therapeutic approaches might represent translationally relevant strategies to improve clinical cancer therapy, in particular for those malignancies that are currently refractory to conventional anticancer agents directed predominantly at tumor bulk populations.",
"title": "The therapeutic promise of the cancer stem cell concept."
},
{
"docid": "14296612",
"text": "BACKGROUND Pluripotent embryonic stem (ES) cells, which have the capacity to give rise to all tissue types in the body, show great promise as a versatile source of cells for regenerative therapy. However, the basic mechanisms of lineage specification of pluripotent stem cells are largely unknown, and generating sufficient quantities of desired cell types remains a formidable challenge. Small molecules, particularly those that modulate key developmental pathways like the bone morphogenetic protein (BMP) signaling cascade, hold promise as tools to study in vitro lineage specification and to direct differentiation of stem cells toward particular cell types. METHODOLOGY/ PRINCIPAL FINDINGS We describe the use of dorsomorphin, a selective small molecule inhibitor of BMP signaling, to induce myocardial differentiation in mouse ES cells. Cardiac induction is very robust, increasing the yield of spontaneously beating cardiomyocytes by at least 20 fold. Dorsomorphin, unlike the endogenous BMP antagonist Noggin, robustly induces cardiomyogenesis when treatment is limited to the initial 24-hours of ES cell differentiation. Quantitative-PCR analyses of differentiating ES cells indicate that pharmacological inhibition of BMP signaling during the early critical stage promotes the development of the cardiomyocyte lineage, but reduces the differentiation of endothelial, smooth muscle, and hematopoietic cells. CONCLUSIONS/ SIGNIFICANCE Administration of a selective small molecule BMP inhibitor during the initial stages of ES cell differentiation substantially promotes the differentiation of primitive pluripotent cells toward the cardiomyocytic lineage, apparently at the expense of other mesodermal lineages. Small molecule modulators of developmental pathways like dorsomorphin could become versatile pharmacological tools for stem cell research and regenerative medicine.",
"title": "Dorsomorphin, a Selective Small Molecule Inhibitor of BMP Signaling, Promotes Cardiomyogenesis in Embryonic Stem Cells"
},
{
"docid": "10273147",
"text": "Human induced pluripotent stem cells (iPSCs) present exciting opportunities for studying development and for in vitro disease modeling. However, reported variability in the behavior of iPSCs has called their utility into question. We established a test set of 16 iPSC lines from seven individuals of varying age, sex and health status, and extensively characterized the lines with respect to pluripotency and the ability to terminally differentiate. Under standardized procedures in two independent laboratories, 13 of the iPSC lines gave rise to functional motor neurons with a range of efficiencies similar to that of human embryonic stem cells (ESCs). Although three iPSC lines were resistant to neural differentiation, early neuralization rescued their performance. Therefore, all 16 iPSC lines passed a stringent test of differentiation capacity despite variations in karyotype and in the expression of early pluripotency markers and transgenes. This iPSC and ESC test set is a robust resource for those interested in the basic biology of stem cells and their applications.",
"title": "A functionally characterized test set of human induced pluripotent stem cells"
},
{
"docid": "40087494",
"text": "Imprinting is an epigenetic modification leading to monoallelic expression of some genes, and disrupted imprinting is believed to be a barrier to human stem cell transplantation, based on studies that suggest that epigenetic marks are unstable in mouse embryonic germ (EG) and embryonic stem (ES) cells. However, stem cell imprinting has not previously been examined directly in humans. We found that three imprinted genes, TSSC5, H19, and SNRPN, show monoallelic expression in in vitro differentiated human EG-derived cells, and a fourth gene, IGF2, shows partially relaxed imprinting at a ratio from 4:1 to 5:1, comparable to that found in normal somatic cells. In addition, we found normal methylation of an imprinting control region (ICR) that regulates H19 and IGF2 imprinting, suggesting that imprinting may not be a significant epigenetic barrier to human EG cell transplantation. Finally, we were able to construct an in vitro mouse model of genomic imprinting, by generating EG cells from 8.5-day embryos of an interspecific cross, in which undifferentiated cells show biallelic expression and acquire preferential parental allele expression after differentiation. This model should allow experimental manipulation of epigenetic modifications of cultured EG cells that may not be possible in human stem cell studies.",
"title": "Monoallelic expression and methylation of imprinted genes in human and mouse embryonic germ cell lineages."
},
{
"docid": "26612216",
"text": "ATP-dependent chromatin remodeling complexes are a notable group of epigenetic modifiers that use the energy of ATP hydrolysis to change the structure of chromatin, thereby altering its accessibility to nuclear factors. BAF250a (ARID1a) is a unique and defining subunit of the BAF chromatin remodeling complex with the potential to facilitate chromosome alterations critical during development. Our studies show that ablation of BAF250a in early mouse embryos results in developmental arrest (about embryonic day 6.5) and absence of the mesodermal layer, indicating its critical role in early germ-layer formation. Moreover, BAF250a deficiency compromises ES cell pluripotency, severely inhibits self-renewal, and promotes differentiation into primitive endoderm-like cells under normal feeder-free culture conditions. Interestingly, this phenotype can be partially rescued by the presence of embryonic fibroblast cells. DNA microarray, immunostaining, and RNA analyses revealed that BAF250a-mediated chromatin remodeling contributes to the proper expression of numerous genes involved in ES cell self-renewal, including Sox2, Utf1, and Oct4. Furthermore, the pluripotency defects in BAF250a mutant ES cells appear to be cell lineage-specific. For example, embryoid body-based analyses demonstrated that BAF250a-ablated stem cells are defective in differentiating into fully functional mesoderm-derived cardiomyocytes and adipocytes but are capable of differentiating into ectoderm-derived neurons. Our results suggest that BAF250a is a key component of the gene regulatory machinery in ES cells controlling self-renewal, differentiation, and cell lineage decisions.",
"title": "ES cell pluripotency and germ-layer formation require the SWI/SNF chromatin remodeling component BAF250a."
},
{
"docid": "7492420",
"text": "Human embryonic stem cells (hESCs) and induced pluripotent stem cells proliferate rapidly and divide symmetrically producing equivalent progeny cells. In contrast, lineage committed cells acquire an extended symmetrical cell cycle. Self-renewal of tissue-specific stem cells is sustained by asymmetric cell division where one progeny cell remains a progenitor while the partner progeny cell exits the cell cycle and differentiates. There are three principal contexts for considering the operation and regulation of the pluripotent cell cycle: temporal, regulatory, and structural. The primary temporal context that the pluripotent self-renewal cell cycle of hESCs is a short G1 period without reducing periods of time allocated to S phase, G2, and mitosis. The rules that govern proliferation in hESCs remain to be comprehensively established. However, several lines of evidence suggest a key role for the naïve transcriptome of hESCs, which is competent to stringently regulate the embryonic stem cell (ESC) cell cycle. This supports the requirements of pluripotent cells to self-propagate while suppressing expression of genes that confer lineage commitment and/or tissue specificity. However, for the first time, we consider unique dimensions to the architectural organization and assembly of regulatory machinery for gene expression in nuclear microenviornments that define parameters of pluripotency. From both fundamental biological and clinical perspectives, understanding control of the abbreviated ESC cycle can provide options to coordinate control of proliferation versus differentiation. Wound healing, tissue engineering, and cell-based therapy to mitigate developmental aberrations illustrate applications that benefit from knowledge of the biology of the pluripotent cell cycle.",
"title": "The abbreviated pluripotent cell cycle."
},
{
"docid": "28071965",
"text": "The earliest aspects of human embryogenesis remain mysterious. To model patterning events in the human embryo, we used colonies of human embryonic stem cells (hESCs) grown on micropatterned substrate and differentiated with BMP4. These gastruloids recapitulate the embryonic arrangement of the mammalian germ layers and provide an assay to assess the structural and signaling mechanisms patterning the human gastrula. Structurally, high-density hESCs localize their receptors to transforming growth factor β at their lateral side in the center of the colony while maintaining apical localization of receptors at the edge. This relocalization insulates cells at the center from apically applied ligands while maintaining response to basally presented ones. In addition, BMP4 directly induces the expression of its own inhibitor, NOGGIN, generating a reaction-diffusion mechanism that underlies patterning. We develop a quantitative model that integrates edge sensing and inhibitors to predict human fate positioning in gastruloids and, potentially, the human embryo.",
"title": "A Balance between Secreted Inhibitors and Edge Sensing Controls Gastruloid Self-Organization."
},
{
"docid": "16375102",
"text": "The simple yet powerful technique of induced pluripotency may eventually supply a wide range of differentiated cells for cell therapy and drug development. However, making the appropriate cells via induced pluripotent stem cells (iPSCs) requires reprogramming of somatic cells and subsequent redifferentiation. Given how arduous and lengthy this process can be, we sought to determine whether it might be possible to convert somatic cells into lineage-specific stem/progenitor cells of another germ layer in one step, bypassing the intermediate pluripotent stage. Here we show that transient induction of the four reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) can efficiently transdifferentiate fibroblasts into functional neural stem/progenitor cells (NPCs) with appropriate signaling inputs. Compared with induced neurons (or iN cells, which are directly converted from fibroblasts), transdifferentiated NPCs have the distinct advantage of being expandable in vitro and retaining the ability to give rise to multiple neuronal subtypes and glial cells. Our results provide a unique paradigm for iPSC-factor-based reprogramming by demonstrating that it can be readily modified to serve as a general platform for transdifferentiation.",
"title": "Direct reprogramming of mouse fibroblasts to neural progenitors."
},
{
"docid": "13244602",
"text": "CD133+ populations of human glioblastoma multiforme (GBM) cells are reportedly enriched for tumor stem cells (TSCs) or tumor-initiating cells (TICs). Approximately 40% of freshly isolated GBM specimens, however, do not contain CD133+ tumor cells, raising the possibility that CD133 may not be a universal enrichment marker for GBM TSCs/TICs. Here we demonstrate that stage-specific embryonic antigen 1(SSEA-1/LeX)+ GBM cells fulfill the functional criteria for TSC/TIC, since (1) SSEA-1+ cells are highly tumorigenic in vivo, unlike SSEA-1- cells; (2) SSEA-1+ cells can give rise to both SSEA-1+ and SSEA-1- cells, thereby establishing a cellular hierarchy; and (3) SSEA-1+ cells have self-renewal and multilineage differentiation potentials. A distinct subpopulation of SSEA-1+ cells was present in all but one of the primary GBMs examined (n = 24), and most CD133+ tumor cells were also SSEA-1+, suggesting that SSEA-1 may be a general TSC/TIC enrichment marker in human GBMs.",
"title": "SSEA-1 is an enrichment marker for tumor-initiating cells in human glioblastoma."
},
{
"docid": "4380451",
"text": "Pluripotency pertains to the cells of early embryos that can generate all of the tissues in the organism. Embryonic stem cells are embryo-derived cell lines that retain pluripotency and represent invaluable tools for research into the mechanisms of tissue formation. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors (Oct4, Sox2, Klf4 and Myc) to yield induced pluripotent stem (iPS) cells. Using these same factors, we have derived iPS cells from fetal, neonatal and adult human primary cells, including dermal fibroblasts isolated from a skin biopsy of a healthy research subject. Human iPS cells resemble embryonic stem cells in morphology and gene expression and in the capacity to form teratomas in immune-deficient mice. These data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture.",
"title": "Reprogramming of human somatic cells to pluripotency with defined factors"
},
{
"docid": "21272977",
"text": "This review summarizes our current understanding of exocrine pancreas development, including the formation of acinar, ductal and centroacinar cells. We discuss the transcription factors associated with various stages of exocrine differentiation, from multipotent progenitor cells to fully differentiated acinar and ductal cells. Within the branching epithelial tree of the embryonic pancreas, this involves the progressive restriction of multipotent pancreatic progenitor cells to either a central \"trunk\" domain giving rise to the islet and ductal lineages, or a peripheral \"tip\" domain giving rise to acinar cells. This review also discusses the soluble morphogens and other signaling pathways that influence these events. Finally, we examine centroacinar cells as an enigmatic pancreatic cell type whose lineage remains uncertain, and whose possible progenitor capacities continue to be explored.",
"title": "Exocrine ontogenies: on the development of pancreatic acinar, ductal and centroacinar cells."
},
{
"docid": "4457834",
"text": "The transfer of somatic cell nuclei into oocytes can give rise to pluripotent stem cells that are consistently equivalent to embryonic stem cells, holding promise for autologous cell replacement therapy. Although methods to induce pluripotent stem cells from somatic cells by transcription factors are widely used in basic research, numerous differences between induced pluripotent stem cells and embryonic stem cells have been reported, potentially affecting their clinical use. Because of the therapeutic potential of diploid embryonic stem-cell lines derived from adult cells of diseased human subjects, we have systematically investigated the parameters affecting efficiency of blastocyst development and stem-cell derivation. Here we show that improvements to the oocyte activation protocol, including the use of both kinase and translation inhibitors, and cell culture in the presence of histone deacetylase inhibitors, promote development to the blastocyst stage. Developmental efficiency varied between oocyte donors, and was inversely related to the number of days of hormonal stimulation required for oocyte maturation, whereas the daily dose of gonadotropin or the total number of metaphase II oocytes retrieved did not affect developmental outcome. Because the use of concentrated Sendai virus for cell fusion induced an increase in intracellular calcium concentration, causing premature oocyte activation, we used diluted Sendai virus in calcium-free medium. Using this modified nuclear transfer protocol, we derived diploid pluripotent stem-cell lines from somatic cells of a newborn and, for the first time, an adult, a female with type 1 diabetes.",
"title": "Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells"
},
{
"docid": "27279525",
"text": "The present study was undertaken to detect, characterize, and study differentiation potential of stem cells in adult rabbit, sheep, monkey, and menopausal human ovarian surface epithelium (OSE). Two distinct populations of putative stem cells (PSCs) of variable size were detected in scraped OSE, one being smaller and other similar in size to the surrounding red blood cells in the scraped OSE. The smaller 1-3 μm very small embryonic-like PSCs were pluripotent in nature with nuclear Oct-4 and cell surface SSEA-4, whereas the bigger 4-7 μm cells with cytoplasmic localization of Oct-4 and minimal expression of SSEA-4 were possibly the tissue committed progenitor stem cells. Pluripotent gene transcripts of Oct-4, Oct-4A, Nanog, Sox-2, TERT, and Stat-3 in human and sheep OSE were detected by reverse transcriptase-polymerase chain reaction. The PSCs underwent spontaneous differentiation into oocyte-like structures, parthenote-like structures, embryoid body-like structures, cells with neuronal-like phenotype, and embryonic stem cell-like colonies, whereas the epithelial cells transformed into mesenchymal phenotype by epithelial-mesenchymal transition in 3 weeks of OSE culture. Germ cell markers like c-Kit, DAZL, GDF-9, VASA, and ZP4 were immuno-localized in oocyte-like structures. In conclusion, as opposed to the existing view of OSE being a bipotent source of oocytes and granulosa cells, mammalian ovaries harbor distinct very small embryonic-like PSCs and tissue committed progenitor stem cells population that have the potential to develop into oocyte-like structures in vitro, whereas mesenchymal fibroblasts appear to form supporting granulosa-like somatic cells. Research at the single-cell level, including complete gene expression profiling, is required to further confirm whether postnatal oogenesis is a conserved phenomenon in adult mammals.",
"title": "Detection, characterization, and spontaneous differentiation in vitro of very small embryonic-like putative stem cells in adult mammalian ovary."
},
{
"docid": "19204979",
"text": "Cells derived from blood vessels of human skeletal muscle can regenerate skeletal muscle, similarly to embryonic mesoangioblasts. However, adult cells do not express endothelial markers, but instead express markers of pericytes, such as NG2 proteoglycan and alkaline phosphatase (ALP), and can be prospectively isolated from freshly dissociated ALP+ cells. Unlike canonical myogenic precursors (satellite cells), pericyte-derived cells express myogenic markers only in differentiated myotubes, which they form spontaneously with high efficiency. When transplanted into severe combined immune deficient–X-linked, mouse muscular dystrophy (scid–mdx) mice, pericyte-derived cells colonize host muscle and generate numerous fibres expressing human dystrophin. Similar cells isolated from Duchenne patients, and engineered to express human mini-dystrophin, also give rise to many dystrophin-positive fibres in vivo. These data show that myogenic precursors, distinct from satellite cells, are associated with microvascular walls in the human skeletal muscle, may represent a correlate of embryonic 'mesoangioblasts' present after birth and may be a promising candidate for future cell-therapy protocols in patients.",
"title": "Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells"
},
{
"docid": "35811036",
"text": "Embryonic-like stem cell (ELSC), expressing part of surface markers of human embryonic stem cells, may be a better candidate for cell therapy of degenerative muscular disease than mesenchymal stem cell (MSC). We isolated ELSC and MSC from bone marrow, respectively, and compared their differences in the characteristics and the capacity of myogenic differentiation. Results showed that ELSC could be isolated successfully from 3 adult bone marrow samples by using serum-free medium with 10ng/ml basic fibroblast growth factor (bFGF). At the same cell density, MSC could also be isolated from the same samples by using DMEM/F12 medium containing 10% new cattle serum. However, ELSC appeared as small, morphologically slenderer, upregulated expression of SSEA-4 and ultramicroscopically more immature than MSC derived from the same samples. Immunofluorescent staining and RT-PCR analysis showed ELSC weakly expressed Oct-4, Nanog-3 and Sox-2. Moreover, ELSC and MSC could be induced into long, multinucleated fibers expressing myogenin and myosin heavy chain (MHC) in myogenic differentiation medium, but by day 10, proportion of multinucleated fibers positive for MHC was respectively 25.0%+/-6.9% and 13.8%+/-7.6% in ELSC and MSC culture. These data suggest that bone marrow derived ELSC represent an ideal candidate for cell therapy of degenerative muscular disease.",
"title": "Embryonic-like stem cell derived from adult bone marrow: immature morphology, cell surface markers, ultramicrostructure and differentiation into multinucleated fibers in vitro."
},
{
"docid": "17685207",
"text": "The fate of cells in the epiblast at prestreak and early primitive streak stages has been studied by injecting horseradish peroxidase (HRP) into single cells in situ of 6.7-day mouse embryos and identifying the labelled descendants at midstreak to neural plate stages after one day of culture. Ectoderm was composed of descendants of epiblast progenitors that had been located in the embryonic axis anterior to the primitive streak. Embryonic mesoderm was derived from all areas of the epiblast except the distal tip and the adjacent region anterior to it: the most anterior mesoderm cells originated posteriorly, traversing the primitive streak early; labelled cells in the posterior part of the streak at the neural plate stage were derived from extreme anterior axial and paraxial epiblast progenitors; head process cells were derived from epiblast at or near the anterior end of the primitive streak. Endoderm descendants were most frequently derived from a region that included, but extended beyond, the region producing the head process: descendants of epiblast were present in endoderm by the midstreak stage, as well as at later stages. Yolk sac and amnion mesoderm developed from posterolateral and posterior epiblast. The resulting fate map is essentially the same as those of the chick and urodele and indicates that, despite geometrical differences, topological fate relationships are conserved among these vertebrates. Clonal descendants were not necessarily confined to a single germ layer or to extraembryonic mesoderm, indicating that these lineages are not separated at the beginning of gastrulation. The embryonic axis lengthened up to the neural plate stage by (1) elongation of the primitive streak through progressive incorporation of the expanding lateral and initially more anterior regions of epiblast and, (2) expansion of the region of epiblast immediately cranial to the anterior end of the primitive streak. The population doubling time of labelled cells was 7.5 h; a calculated 43% were in, or had completed, a 4th cell cycle, and no statistically significant regional differences in the number of descendants were found. This clonal analysis also showed that (1) growth in the epiblast was noncoherent and in most regions anisotropic and directed towards the primitive streak and (2) the midline did not act as a barrier to clonal spread, either in the epiblast in the anterior half of the axis or in the primitive streak. These results taken together with the fate map indicate that, while individual cells in the epiblast sheet behave independently with respect to their neighbours, morphogenetic movement during germ layer formation is coordinated in the population as a whole.",
"title": "Clonal analysis of epiblast fate during germ layer formation in the mouse embryo."
},
{
"docid": "16999023",
"text": "To characterize the properties of adult neural stem cells (NSCs), we generated and analyzed Sox2-GFP transgenic mice. Sox2-GFP cells in the subgranular zone (SGZ) express markers specific for progenitors, but they represent two morphologically distinct populations that differ in proliferation levels. Lentivirus- and retrovirus-mediated fate-tracing studies showed that Sox2+ cells in the SGZ have potential to give rise to neurons and astrocytes, revealing their multipotency at the population as well as at a single-cell level. A subpopulation of Sox2+ cells gives rise to cells that retain Sox2, highlighting Sox2+ cells as a primary source for adult NSCs. In response to mitotic signals, increased proliferation of Sox2+ cells is coupled with the generation of Sox2+ NSCs as well as neuronal precursors. An asymmetric contribution of Sox2+ NSCs may play an important role in maintaining the constant size of the NSC pool and producing newly born neurons during adult neurogenesis.",
"title": "Cell Stem Cell Article In Vivo Fate Analysis Reveals the Multipotent and Self-Renewal Capacities of Sox2 + Neural Stem Cells in the Adult Hippocampus"
},
{
"docid": "10937190",
"text": "The morphogenesis of the C. elegans embryo is largely controlled by the development of the epidermis, also known as the hypodermis, a single epithelial layer that surrounds the animal. Morphogenesis of the epidermis involves cell-cell interactions with internal tissues, such as the developing nervous system and musculature. Genetic analysis of mutants with aberrant epidermal morphology has defined multiple steps in epidermal morphogenesis. In the wild type, epidermal cells are generated on the dorsal side of the embryo among the progeny of four early embryonic blastomeres. Specification of epidermal fate is regulated by a hierarchy of transcription factors. After specification, dorsal epidermal cells rearrange, a process known as dorsal intercalation. Most epidermal cells fuse to generate multinucleate syncytia. The dorsally located epidermal sheet undergoes epiboly to enclose the rest of the embryo in a process known as ventral enclosure; this movement requires both an intact epidermal layer and substrate neuroblasts. At least three distinct types of cellular behavior underlie the enclosure of different regions of the epidermis. Following enclosure, the epidermis elongates, a process driven by coordinated cell shape changes. Epidermal actin microfilaments, microtubules, and intermediate filaments all play roles in elongation, as do body wall muscles. The final shape of the epidermis is maintained by the collagenous exoskeleton, secreted by the apical surface of the epidermis.",
"title": "Table of Contents"
}
] |
989
|
Pure neural progenitor cell (NPC) populations can only be obtained from cell cultures that undergo passaging, filtration, or other isolation and cell sorting methods.
|
[
{
"docid": "9988425",
"text": "Pluripotent mouse embryonic stem (ES) cells multiply in simple monoculture by symmetrical divisions. In vivo, however, stem cells are generally thought to depend on specialised cellular microenvironments and to undergo predominantly asymmetric divisions. Ex vivo expansion of pure populations of tissue stem cells has proven elusive. Neural progenitor cells are propagated in combination with differentiating progeny in floating clusters called neurospheres. The proportion of stem cells in neurospheres is low, however, and they cannot be directly observed or interrogated. Here we demonstrate that the complex neurosphere environment is dispensable for stem cell maintenance, and that the combination of fibroblast growth factor 2 (FGF-2) and epidermal growth factor (EGF) is sufficient for derivation and continuous expansion by symmetrical division of pure cultures of neural stem (NS) cells. NS cells were derived first from mouse ES cells. Neural lineage induction was followed by growth factor addition in basal culture media. In the presence of only EGF and FGF-2, resulting NS cells proliferate continuously, are diploid, and clonogenic. After prolonged expansion, they remain able to differentiate efficiently into neurons and astrocytes in vitro and upon transplantation into the adult brain. Colonies generated from single NS cells all produce neurons upon growth factor withdrawal. NS cells uniformly express morphological, cell biological, and molecular features of radial glia, developmental precursors of neurons and glia. Consistent with this profile, adherent NS cell lines can readily be established from foetal mouse brain. Similar NS cells can be generated from human ES cells and human foetal brain. The extrinsic factors EGF plus FGF-2 are sufficient to sustain pure symmetrical self-renewing divisions of NS cells. The resultant cultures constitute the first known example of tissue-specific stem cells that can be propagated without accompanying differentiation. These homogenous cultures will enable delineation of molecular mechanisms that define a tissue-specific stem cell and allow direct comparison with pluripotent ES cells.",
"title": "Niche-Independent Symmetrical Self-Renewal of a Mammalian Tissue Stem Cell"
}
] |
[
{
"docid": "19756935",
"text": "Isolated pure human beta cells would be helpful for a number of research purposes. However, lack of beta cell-specific surface antigens has been a major problem. We aimed to develop a simple method for human beta cell isolation based on the initial elimination of ductal cells by their expression of carbohydrate antigen 19-9 (CA19-9), followed by positive selection of beta cells by their expression of polysialic acid–neural cell adhesion molecule (PSA-NCAM). Cell type-specific expression of CA19-9, NCAM and PSA-NCAM was studied in sections of adult human pancreas and in cultured primary endocrine and exocrine cells. Dispersed human islet cells were purified in two steps, after 4 days of suspension culture, by binding to magnetic microbeads coupled to antibodies against CA19-9 and PSA-NCAM. NCAM expression was detected in ducts and islets in the human pancreas. In contrast, PSA-NCAM immunoreactivity was detected only in islets. PSA-NCAM staining in dispersed cells revealed that the marker is expressed in all endocrine cell types, but not in duct cells. Purification of dispersed islet cells using PSA-NCAM microbeads alone did not completely eliminate contaminating duct cells. However, elimination of the duct cells by CA19-9 microbeads followed by positive sorting of the PSA-NCAM-positive cells in five consecutive islet preparations resulted in 90 to 98% pure endocrine cells, of which 89 to 97% were beta cells. We describe a simple and reproducible method for purification of viable human pancreatic beta cells devoid of exocrine acini and ducts.",
"title": "A simple two-step protocol for the purification of human pancreatic beta cells"
},
{
"docid": "12742164",
"text": "Stem cells, which are clonogenic cells with self-renewal and multilineage differentiation properties, have the potential to replace or repair damaged tissue. We have directly isolated clonogenic human central nervous system stem cells (hCNS-SC) from fresh human fetal brain tissue, using antibodies to cell surface markers and fluorescence-activated cell sorting. These hCNS-SC are phenotypically 5F3 (CD133)(+), 5E12(+), CD34(-), CD45(-), and CD24(-/lo). Single CD133(+) CD34(-) CD45(-) sorted cells initiated neurosphere cultures, and the progeny of clonogenic cells could differentiate into both neurons and glial cells. Single cells from neurosphere cultures initiated from CD133(+) CD34(-) CD45(-) cells were again replated as single cells and were able to reestablish neurosphere cultures, demonstrating the self-renewal potential of this highly enriched population. Upon transplantation into brains of immunodeficient neonatal mice, the sorted/expanded hCNS-SC showed potent engraftment, proliferation, migration, and neural differentiation.",
"title": "Direct isolation of human central nervous system stem cells."
},
{
"docid": "9675944",
"text": "Somatic cells can be induced into pluripotent stem cells (iPSCs) with a combination of four transcription factors, Oct4/Sox2/Klf4/c-Myc or Oct4/Sox2/Nanog/LIN28. This provides an enabling platform to obtain patient-specific cells for various therapeutic and research applications. However, several problems remain for this approach to be therapeutically relevant due to drawbacks associated with efficiency and viral genome integration. Recently, it was shown that neural progenitor cells (NPCs) transduced with Oct4/Klf4 can be reprogrammed into iPSCs. However, NPCs express Sox2 endogenously, possibly facilitating reprogramming in the absence of exogenous Sox2. In this study, we identified a small-molecule combination, BIX-01294 and BayK8644, that enables reprogramming of Oct4/Klf4-transduced mouse embryonic fibroblasts, which do not endogenously express the factors essential for reprogramming. This study demonstrates that small molecules identified through a phenotypic screen can compensate for viral transduction of critical factors, such as Sox2, and improve reprogramming efficiency.",
"title": "Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds."
},
{
"docid": "16375102",
"text": "The simple yet powerful technique of induced pluripotency may eventually supply a wide range of differentiated cells for cell therapy and drug development. However, making the appropriate cells via induced pluripotent stem cells (iPSCs) requires reprogramming of somatic cells and subsequent redifferentiation. Given how arduous and lengthy this process can be, we sought to determine whether it might be possible to convert somatic cells into lineage-specific stem/progenitor cells of another germ layer in one step, bypassing the intermediate pluripotent stage. Here we show that transient induction of the four reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) can efficiently transdifferentiate fibroblasts into functional neural stem/progenitor cells (NPCs) with appropriate signaling inputs. Compared with induced neurons (or iN cells, which are directly converted from fibroblasts), transdifferentiated NPCs have the distinct advantage of being expandable in vitro and retaining the ability to give rise to multiple neuronal subtypes and glial cells. Our results provide a unique paradigm for iPSC-factor-based reprogramming by demonstrating that it can be readily modified to serve as a general platform for transdifferentiation.",
"title": "Direct reprogramming of mouse fibroblasts to neural progenitors."
},
{
"docid": "18399038",
"text": "Glioma tumour-initiating cells (GTICs) can originate upon the transformation of neural progenitor cells (NPCs). Studies on GTICs have focused on primary tumours from which GTICs could be isolated and the use of human embryonic material. Recently, the somatic genomic landscape of human gliomas has been reported. RTK (receptor tyrosine kinase) and p53 signalling were found dysregulated in ∼90% and 86% of all primary tumours analysed, respectively. Here we report on the use of human-induced pluripotent stem cells (hiPSCs) for modelling gliomagenesis. Dysregulation of RTK and p53 signalling in hiPSC-derived NPCs (iNPCs) recapitulates GTIC properties in vitro. In vivo transplantation of transformed iNPCs leads to highly aggressive tumours containing undifferentiated stem cells and their differentiated derivatives. Metabolic modulation compromises GTIC viability. Last, screening of 101 anti-cancer compounds identifies three molecules specifically targeting transformed iNPCs and primary GTICs. Together, our results highlight the potential of hiPSCs for studying human tumourigenesis.",
"title": "Establishment of human iPSC-based models for the study and targeting of glioma initiating cells"
},
{
"docid": "31439189",
"text": "BACKGROUND Recent studies indicate the presence of a small, stem-like cell population in several human cancers that is crucial for the tumour (re)population. OBJECTIVE Six established prostate cancer (PCa) cell lines-DU145, DuCaP, LAPC-4, 22Rv1, LNCaP, and PC-3-were examined for their stem cell properties in vitro. DESIGN, SETTINGS, AND PARTICIPANTS The colony-forming efficiency and self-renewal ability of morphologically distinguishable holoclones and paraclones were tested with low-density plating and serial passaging. Expression of the putative stem cell marker CD133 and breast cancer resistance protein (BCRP) was examined with flow cytometry, and immunohistochemical stainings were made for CD133, alpha2-integrin, nestin, BCRP, cytokeratin 5 (CK5), and cytokeratin 18 (CK18). RESULTS AND LIMITATIONS Five out of six cell lines formed clear holo-, mero-, and paraclones. Unlike paraclones, we can maintain DU145 holoclones in culture for several passages, which is indicative of self-renewal ability. Using fluorescence-activated cell sorting (FACS) analysis only in DU145 cells, a small fraction (0.01%) of CD133(+) cells was detected. CD133(+) cells; however, like DU145 BCRP(+) (0.15%) cells, they were not more clonogenic, and they did not show more holoclone formation than the marker-negative cells or unselected cells. Immunohistochemistry revealed alpha2-integrin and BCRP as potential stem cell markers and CK5 with the combination of CK18 to distinguish transient amplifying cells. CONCLUSIONS These results indicate the possible presence of stem-like cells in several established PCa cell lines. CD133 selection does not enrich for stem-like cells in PCa cell lines.",
"title": "Stem cell characteristics in prostate cancer cell lines."
},
{
"docid": "33390472",
"text": "We have developed a novel panel of cell-surface markers for the isolation and study of all major cell types of the human pancreas. Hybridomas were selected after subtractive immunization of Balb/C mice with intact or dissociated human islets and assessed for cell-type specificity and cell-surface reactivity by immunohistochemistry and flow cytometry. Antibodies were identified by specific binding of surface antigens on islet (panendocrine or alpha-specific) and nonislet pancreatic cell subsets (exocrine and duct). These antibodies were used individually or in combination to isolate populations of alpha, beta, exocrine, or duct cells from primary human pancreas by FACS and to characterize the detailed cell composition of human islet preparations. They were also employed to show that human islet expansion cultures originated from nonendocrine cells and that insulin expression levels could be increased to up to 1% of normal islet cells by subpopulation sorting and overexpression of the transcription factors Pdx-1 and ngn3, an improvement over previous results with this culture system. These methods permit the analysis and isolation of functionally distinct pancreatic cell populations with potential for cell therapy.",
"title": "Isolation of major pancreatic cell types and long-term culture-initiating cells using novel human surface markers."
},
{
"docid": "39532074",
"text": "INTRODUCTION The hostile environment after spinal cord injury (SCI) can compromise effects of regenerative therapies. We hypothesized that optimizing the post-traumatic environment with QL6 self-assembling peptides (SAPs) before neural precursor cell (NPC) transplantation would improve cell survival, differentiation and functional recovery. METHODS A total of 90 Wistar rats received a clip-compression SCI at C7. Within each of two study arms, animals were randomized into 5 groups (NPC, SAP, NPC+SAP, vehicle, and sham). SAPs and NPCs were injected into the spinal cord 1day and 14days post-injury, respectively. Animals received growth factors over 7days and were immunosuppressed. Rats were sacrificed at 4weeks and sections of the cervical spinal cord prepared for immunohistochemistry (first study arm). Neurological function was assessed weekly for 8weeks using a battery of behavioral tests. Nine weeks post-SCI, the corticospinal tract was assessed using fiber-tracking (second arm). RESULTS SAP-treated animals had significantly more surviving NPCs which showed increased differentiation to neurons and oligodendrocytes compared to controls. SAPs alone or in combination with NPCs resulted in smaller intramedullary cysts and larger volume of preserved tissue compared to other groups. The combined treatment group showed reduced astrogliosis and chondroitin sulfate proteoglycan deposition. Synaptic connectivity was increased in the NPC and combined treatment groups. Corticospinal tract preservation and behavioral outcomes improved with combinatorial treatment. CONCLUSION Injecting SAPs after SCI enhances subsequent NPC survival, integration and differentiation and improves functional recovery. STATEMENT OF SIGNIFICANCE The hostile environment after spinal cord injury (SCI) can compromise effects of regenerative therapies. We hypothesized that improving this environment with self-assembling peptides (SAPs) before neural precursor cell (NPC) transplantation would support their beneficial effects. SAPs assemble once injected, providing a supportive scaffold for repair and regeneration. We investigated this in a rat model of spinal cord injury. More NPCs survived in SAP-treated animals and these showed increased differentiation compared to controls. SAPS alone or in combination with NPCs resulted in smaller cysts and larger volume of preserved tissue with the combined treatment also reducing scarring and improving behavioral outcomes. Overall, injection of SAPs was shown to improve the efficacy of NPC treatment, a promising finding for those with SCIs.",
"title": "Self-assembling peptides optimize the post-traumatic milieu and synergistically enhance the effects of neural stem cell therapy after cervical spinal cord injury."
},
{
"docid": "6148876",
"text": "RATIONALE Islet1 (Isl1) has been proposed as a marker of cardiac progenitor cells derived from the second heart field and is utilized to identify and purify cardiac progenitors from murine and human specimens for ex vivo expansion. The use of Isl1 as a specific second heart field marker is dependent on its exclusion from other cardiac lineages such as neural crest. OBJECTIVE Determine whether Isl1 is expressed by cardiac neural crest. METHODS AND RESULTS We used an intersectional fate-mapping system using the RC::FrePe allele, which reports dual Flpe and Cre recombination. Combining Isl1(Cre/+), a SHF driver, and Wnt1::Flpe, a neural crest driver, with Rc::FrePe reveals that some Isl1 derivatives in the cardiac outflow tract derive from Wnt1-expressing neural crest progenitors. In contrast, no overlap was observed between Wnt1-derived neural crest and an alternative second heart field driver, Mef2c-AHF-Cre. CONCLUSIONS Isl1 is not restricted to second heart field progenitors in the developing heart but also labels cardiac neural crest. The intersection of Isl1 and Wnt1 lineages within the heart provides a caveat to using Isl1 as an exclusive second heart field cardiac progenitor marker and suggests that some Isl1-expressing progenitor cells derived from embryos, embryonic stem cultures, or induced pluripotent stem cultures may be of neural crest lineage.",
"title": "Islet1 derivatives in the heart are of both neural crest and second heart field origin."
},
{
"docid": "17049436",
"text": "During development of the vertebrate neuroepithelium, the nucleus in neural progenitor cells (NPCs) moves from the apex toward the base and returns to the apex (called interkinetic nuclear migration) at which point the cell divides. The fate of the resulting daughter cells is thought to depend on the sampling by the moving nucleus of a spatial concentration profile of the cytoplasmic Notch intracellular domain (NICD). However, the nucleus executes complex stochastic motions including random waiting and back and forth motions, which can expose the nucleus to randomly varying levels of cytoplasmic NICD. How nuclear position can determine daughter cell fate despite the stochastic nature of nuclear migration is not clear. Here we derived a mathematical model for reaction, diffusion, and nuclear accumulation of NICD in NPCs during interkinetic nuclear migration (INM). Using experimentally measured trajectory-dependent probabilities of nuclear turning, nuclear waiting times and average nuclear speeds in NPCs in the developing zebrafish retina, we performed stochastic simulations to compute the nuclear trajectory-dependent probabilities of NPC differentiation. Comparison with experimentally measured nuclear NICD concentrations and trajectory-dependent probabilities of differentiation allowed estimation of the NICD cytoplasmic gradient. Spatially polarized production of NICD, rapid NICD cytoplasmic consumption and the time-averaging effect of nuclear import/export kinetics are sufficient to explain the experimentally observed differentiation probabilities. Our computational studies lend quantitative support to the feasibility of the nuclear concentration-sensing mechanism for NPC fate determination in zebrafish retina.",
"title": "Concentration Sensing by the Moving Nucleus in Cell Fate Determination: A Computational Analysis"
},
{
"docid": "33986200",
"text": "Probing a wide range of cellular phenotypes in neurodevelopmental disorders using patient-derived neural progenitor cells (NPCs) can be facilitated by 3D assays, as 2D systems cannot entirely recapitulate the arrangement of cells in the brain. Here, we developed a previously unidentified 3D migration and differentiation assay in layered hydrogels to examine how these processes are affected in neurodevelopmental disorders, such as Rett syndrome. Our soft 3D system mimics the brain environment and accelerates maturation of neurons from human induced pluripotent stem cell (iPSC)-derived NPCs, yielding electrophysiologically active neurons within just 3 wk. Using this platform, we revealed a genotype-specific effect of methyl-CpG-binding protein-2 (MeCP2) dysfunction on iPSC-derived neuronal migration and maturation (reduced neurite outgrowth and fewer synapses) in 3D layered hydrogels. Thus, this 3D system expands the range of neural phenotypes that can be studied in vitro to include those influenced by physical and mechanical stimuli or requiring specific arrangements of multiple cell types.",
"title": "Layered hydrogels accelerate iPSC-derived neuronal maturation and reveal migration defects caused by MeCP2 dysfunction."
},
{
"docid": "23262027",
"text": "Eight isolates of Desulfovibrio spp. have been obtained over 5 years from abdominal or brain abscesses or blood. Seven isolates were part of a mixed flora [corrected]. One strain was isolated in pure culture from the blood of a patient with peritonitis of appendicular origin. According to the 16S rRNA gene sequences, this strain was close to Desulfovibrio fairfieldensis. The present report describes the fourth isolate of this recently described species to be isolated in pure culture or as a predominant part of the flora and to be associated with infectious processes. Thus, D. fairfieldensis may possess a higher pathogenic potential than other Desulfovibrio species.",
"title": "Bacteremia caused by a strain of Desulfovibrio related to the provisionally named Desulfovibrio fairfieldensis."
},
{
"docid": "25985964",
"text": "Very small embryonic-like stem cells (VSELs) are possibly lost during cord blood banking and bone marrow (BM) processing for autologus stem cell therapy mainly because of their small size. The present study was conducted on human umbilical cord blood (UCB, n=6) and discarded red blood cells (RBC) fraction obtained after separation of mononuclear cells from human BM (n=6), to test this hypothesis. The results show that VSELs, which are pluripotent stem cells with maximum regenerative potential, settle along with the RBCs during Ficoll-Hypaque density separation. These cells are very small in size (3-5 μm), have high nucleo-cytoplasmic ratio, and express nuclear Oct-4, cell surface protein SSEA-4, and other pluripotent markers such as Nanog, Sox-2, Rex-1, and Tert as indicated by immunolocalization and quantitative polymerase chain reaction (Q-PCR) studies. Interestingly, a distinct population of slightly larger, round hematopoietic stem cells (HSCs) with cytoplasmic Oct-4 were detected in the \"buffy\" coat, which usually gets banked or used during autologus stem cell therapy. Immunohistochemical studies on the umbilical cord tissue (UCT) sections (n=3) showed the presence of nuclear Oct-4-positive VSELs and many fibroblast-like mesenchymal stem cells (MSCs) with cytoplasmic Oct-4. These VSELs with nuclear Oct-4, detected in UCB, UCT, and discarded RBC fraction obtained after BM processing, may persist throughout life, maintain tissue homeostasis, and undergo asymmetric cell division to self-renew as well as produce larger progenitor stem cells, viz. HSCs or MSCs, which follow differentiation trajectories depending on the somatic niche. Hence, it can be concluded that the true stem cells in adult body tissues are the VSELs, whereas the HSCs and MSCs are actually progenitor stem cells that arise by asymmetric cell division of VSELs. The results of the present study may help explain low efficacy reported during adult autologous stem cell trials, wherein unknowingly progenitor stem cells are injected rather than the pluripotent stem cells with maximum regenerative potential.",
"title": "Very small embryonic-like stem cells with maximum regenerative potential get discarded during cord blood banking and bone marrow processing for autologous stem cell therapy."
},
{
"docid": "33955641",
"text": "Procedures are described for the isolation of lipoproteins from human serum by precipitation with polyanions and divalent cations. A mixture of low and very low density lipoproteins can be prepared without ultracentrifugation by precipitation with heparin and either MnCl(2) alone or MgCl(2) plus sucrose. In both cases the precipitation is reversible, selective, and complete. The highly concentrated isolated lipoproteins are free of other plasma proteins as judged by immunological and electrophoretic methods. The low density and very low density lipoproteins can then be separated from each other by ultracentrifugation. The advantage of the method is that large amounts of lipoproteins can be prepared with only a single preparative ultracentrifugation. Polyanions other than heparin may also be used; when the precipitation of the low and very low density lipoproteins is achieved with dextran sulfate and MnCl(2), or sodium phosphotungstate and MgCl(2), the high density lipoproteins can subsequently be precipitated by increasing the concentrations of the reagents. These lipoproteins, containing small amounts of protein contaminants, are further purified by ultracentrifugation at d 1.22. With a single preparative ultracentrifugation, immunologically pure high density lipoproteins can be isolated from large volumes of serum.",
"title": "Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions."
},
{
"docid": "25419778",
"text": "Cellular senescence is a fundamental mechanism by which cells remain metabolically active yet cease dividing and undergo distinct phenotypic alterations, including upregulation of p16Ink4a , profound secretome changes, telomere shortening, and decondensation of pericentromeric satellite DNA. Because senescent cells accumulate in multiple tissues with aging, these cells and the dysfunctional factors they secrete, termed the senescence-associated secretory phenotype (SASP), are increasingly recognized as promising therapeutic targets to prevent age-related degenerative pathologies, including osteoporosis. However, the cell type(s) within the bone microenvironment that undergoes senescence with aging in vivo has remained poorly understood, largely because previous studies have focused on senescence in cultured cells. Thus in young (age 6 months) and old (age 24 months) mice, we measured senescence and SASP markers in vivo in highly enriched cell populations, all rapidly isolated from bone/marrow without in vitro culture. In both females and males, p16Ink4a expression by real-time quantitative polymerase chain reaction (rt-qPCR) was significantly higher with aging in B cells, T cells, myeloid cells, osteoblast progenitors, osteoblasts, and osteocytes. Further, in vivo quantification of senescence-associated distension of satellites (SADS), ie, large-scale unraveling of pericentromeric satellite DNA, revealed significantly more senescent osteocytes in old compared with young bone cortices (11% versus 2%, p < 0.001). In addition, primary osteocytes from old mice had sixfold more (p < 0.001) telomere dysfunction-induced foci (TIFs) than osteocytes from young mice. Corresponding with the age-associated accumulation of senescent osteocytes was significantly higher expression of multiple SASP markers in osteocytes from old versus young mice, several of which also showed dramatic age-associated upregulation in myeloid cells. These data show that with aging, a subset of cells of various lineages within the bone microenvironment become senescent, although senescent myeloid cells and senescent osteocytes predominantly develop the SASP. Given the critical roles of osteocytes in orchestrating bone remodeling, our findings suggest that senescent osteocytes and their SASP may contribute to age-related bone loss. © 2016 American Society for Bone and Mineral Research.",
"title": "Identification of Senescent Cells in the Bone Microenvironment."
},
{
"docid": "3619372",
"text": "Stem cell-based approaches to cardiac regeneration are increasingly viable strategies for treating heart failure. Generating abundant and functional autologous cells for transplantation in such a setting, however, remains a significant challenge. Here, we isolated a cell population with extensive proliferation capacity and restricted cardiovascular differentiation potentials during cardiac transdifferentiation of mouse fibroblasts. These induced expandable cardiovascular progenitor cells (ieCPCs) proliferated extensively for more than 18 passages in chemically defined conditions, with 10(5) starting fibroblasts robustly producing 10(16) ieCPCs. ieCPCs expressed cardiac signature genes and readily differentiated into functional cardiomyocytes (CMs), endothelial cells (ECs), and smooth muscle cells (SMCs) in vitro, even after long-term expansion. When transplanted into mouse hearts following myocardial infarction, ieCPCs spontaneously differentiated into CMs, ECs, and SMCs and improved cardiac function for up to 12 weeks after transplantation. Thus, ieCPCs are a powerful system to study cardiovascular specification and provide strategies for regenerative medicine in the heart.",
"title": "Expandable Cardiovascular Progenitor Cells Reprogrammed from Fibroblasts."
},
{
"docid": "23901235",
"text": "Neurogenesis occurs in the hippocampus of the developing and adult brain due to the presence of multipotent stem cells and restricted precursor cells at different stages of differentiation. It has been proposed that they may be of potential benefit for use in cell transplantation approaches for neurodegenerative disorders and trauma. Prolonged release of interleukin-1β (IL-1β) from activated microglia has a deleterious effect on hippocampal neurons and is implicated in the impaired neurogenesis and cognitive dysfunction associated with aging, Alzheimer's disease and depression. This study assessed the effect of IL-1β on the proliferation and differentiation of embryonic rat hippocampal NPCs in vitro. We show that IL-1R1 is expressed on proliferating NPCs and that IL-1β treatment decreases cell proliferation and neurosphere growth. When NPCs were differentiated in the presence of IL-1β, a significant reduction in the percentages of newly-born neurons and post-mitotic neurons and a significant increase in the percentage of astrocytes was observed in these cultures. These effects were attenuated by IL-1 receptor antagonist. These data reveal that IL-1β exerts an anti-proliferative, anti-neurogenic and pro-gliogenic effect on embryonic hippocampal NPCs, which is mediated by IL-1R1. The present results emphasise the consequences of an inflammatory environment during NPC development, and indicate that strategies to inhibit IL-1β signalling may be necessary to facilitate effective cell transplantation approaches or in conditions where endogenous hippocampal neurogenesis is impaired.",
"title": "A role for interleukin-1β in determining the lineage fate of embryonic rat hippocampal neural precursor cells."
},
{
"docid": "3756384",
"text": "BACKGROUND & AIMS Hepatocytes in which the hepatitis B virus (HBV) is replicating exhibit loss of the chromatin modifying polycomb repressive complex 2 (PRC2), resulting in re-expression of specific, cellular PRC2-repressed genes. Epithelial cell adhesion molecule (EpCAM) is a PRC2-repressed gene, normally expressed in hepatic progenitors, but re-expressed in hepatic cancer stem cells (hCSCs). Herein, we investigated the functional significance of EpCAM re-expression in HBV-mediated hepatocarcinogenesis. METHODS Employing molecular approaches (transfections, fluorescence-activated cell sorting, immunoblotting, qRT-PCR), we investigated the role of EpCAM-regulated intramembrane proteolysis (RIP) in HBV replicating cells in vitro, and in liver tumors from HBV X/c-myc mice and chronically HBV infected patients. RESULTS EpCAM undergoes RIP in HBV replicating cells, activating canonical Wnt signaling. Transfection of Wnt-responsive plasmid expressing green fluorescent protein (GFP) identified a GFP + population of HBV replicating cells. These GFP+/Wnt+ cells exhibited cisplatin- and sorafenib-resistant growth resembling hCSCs, and increased expression of pluripotency genes NANOG, OCT4, SOX2, and hCSC markers BAMBI, CD44 and CD133. These genes are referred as EpCAM RIP and Wnt-induced hCSC-like gene signature. Interestingly, this gene signature is also overexpressed in liver tumors of X/c-myc bitransgenic mice. Clinically, a group of HBV-associated hepatocellular carcinomas was identified, exhibiting elevated expression of the hCSC-like gene signature and associated with reduced overall survival post-surgical resection. CONCLUSIONS The hCSC-like gene signature offers promise as prognostic tool for classifying subtypes of HBV-induced HCCs. Since EpCAM RIP and Wnt signaling drive expression of this hCSC-like signature, inhibition of these pathways can be explored as therapeutic strategy for this subtype of HBV-associated HCCs. LAY SUMMARY In this study, we provide evidence for a molecular mechanism by which chronic infection by the hepatitis B virus results in the development of poor prognosis liver cancer. Based on this mechanism our results suggest possible therapeutic interventions.",
"title": "EpCAM-regulated intramembrane proteolysis induces a cancer stem cell-like gene signature in hepatitis B virus-infected hepatocytes."
},
{
"docid": "427082",
"text": "The neural crest (NC) is an embryonic stem/progenitor cell population that generates a diverse array of cell lineages, including peripheral neurons, myelinating Schwann cells, and melanocytes, among others. However, there is a long-standing controversy as to whether this broad developmental perspective reflects in vivo multipotency of individual NC cells or whether the NC is comprised of a heterogeneous mixture of lineage-restricted progenitors. Here, we resolve this controversy by performing in vivo fate mapping of single trunk NC cells both at premigratory and migratory stages using the R26R-Confetti mouse model. By combining quantitative clonal analyses with definitive markers of differentiation, we demonstrate that the vast majority of individual NC cells are multipotent, with only few clones contributing to single derivatives. Intriguingly, multipotency is maintained in migratory NC cells. Thus, our findings provide definitive evidence for the in vivo multipotency of both premigratory and migrating NC cells in the mouse.",
"title": "Premigratory and migratory neural crest cells are multipotent in vivo."
},
{
"docid": "4412772",
"text": "Unicellular organisms such as yeasts require a single cyclin-dependent kinase, Cdk1, to drive cell division. In contrast, mammalian cells are thought to require the sequential activation of at least four different cyclin-dependent kinases, Cdk2, Cdk3, Cdk4 and Cdk6, to drive cells through interphase, as well as Cdk1 to proceed through mitosis. This model has been challenged by recent genetic evidence that mice survive in the absence of individual interphase Cdks. Moreover, most mouse cell types proliferate in the absence of two or even three interphase Cdks. Similar results have been obtained on ablation of some of the activating subunits of Cdks, such as the D-type and E-type cyclins. Here we show that mouse embryos lacking all interphase Cdks (Cdk2, Cdk3, Cdk4 and Cdk6) undergo organogenesis and develop to midgestation. In these embryos, Cdk1 binds to all cyclins, resulting in the phosphorylation of the retinoblastoma protein pRb and the expression of genes that are regulated by E2F transcription factors. Mouse embryonic fibroblasts derived from these embryos proliferate in vitro, albeit with an extended cell cycle due to inefficient inactivation of Rb proteins. However, they become immortal on continuous passage. We also report that embryos fail to develop to the morula and blastocyst stages in the absence of Cdk1. These results indicate that Cdk1 is the only essential cell cycle Cdk. Moreover, they show that in the absence of interphase Cdks, Cdk1 can execute all the events that are required to drive cell division.",
"title": "Cdk1 is sufficient to drive the mammalian cell cycle"
},
{
"docid": "14192687",
"text": "The long-term goal of nuclear transfer or alternative reprogramming approaches is to create patient-specific donor cells for transplantation therapy, avoiding immunorejection, a major complication in current transplantation medicine. It was recently shown that the four transcription factors Oct4, Sox2, Klf4, and c-Myc induce pluripotency in mouse fibroblasts. However, the therapeutic potential of induced pluripotent stem (iPS) cells for neural cell replacement strategies remained unexplored. Here, we show that iPS cells can be efficiently differentiated into neural precursor cells, giving rise to neuronal and glial cell types in culture. Upon transplantation into the fetal mouse brain, the cells migrate into various brain regions and differentiate into glia and neurons, including glutamatergic, GABAergic, and catecholaminergic subtypes. Electrophysiological recordings and morphological analysis demonstrated that the grafted neurons had mature neuronal activity and were functionally integrated in the host brain. Furthermore, iPS cells were induced to differentiate into dopamine neurons of midbrain character and were able to improve behavior in a rat model of Parkinson's disease upon transplantation into the adult brain. We minimized the risk of tumor formation from the grafted cells by separating contaminating pluripotent cells and committed neural cells using fluorescence-activated cell sorting. Our results demonstrate the therapeutic potential of directly reprogrammed fibroblasts for neuronal cell replacement in the animal model.",
"title": "Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease."
},
{
"docid": "503050",
"text": "We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations.",
"title": "Genome-wide maps of chromatin state in pluripotent and lineage-committed cells"
},
{
"docid": "35321950",
"text": "During a certain period of the course of infection in white mice inoculated intraperitoneally with the pure culture of a proteolysing strain of Candida albicans, Staphylococcus aureus and C. albicans both, were isolated simultaneously from the peritoneal abscesses, especially those adhering to the stomach, duodenum, pancreas and the upper part of small intestine. This concommitant occurrence of the two pathogens was further corroborated by histopathological examination which revealed large number of staphylococci present in the close neighbourhood of Candida cells, usually in the center of the granulomata caused by the fungus. In view of the facts that the proteolytic end-products of C. albicans can offer a good substratum for the growth of S. aureus and the latter may be isolated from the intestinal tract of apparently healthy mice, possibly as a constituent of the transient microflora, the co-existence of these two important aetiologic agents of endogenous infections as encountered during this study appears to be of great clinical interest. Furthermore, these observations also demonstrate the importance of controlling the bacterial flora of mice for pure mycological studies.",
"title": "Staphylococcus aureus and Candida albicans infection (animal experiments)."
},
{
"docid": "23509593",
"text": "BACKGROUND Prostate development and maintenance in the adult results from an interaction of stromal and glandular components. Androgens can drive this process by direct action on the stroma. We investigated whether there was a direct link between androgens and another key regulator of stromal cells, intracellular Ca2+ ([Ca2+ ]i ). METHODS Prostate stromal cells were freshly obtained and cultures derived from patients with benign prostatic hyperplasia. Gene expression in dihydrotestosterone treated and untreated cells was compared using Affymetrix gene expression arrays and Ca2+ regulated features were identified by Gene Ontology (GO). Changes in [Ca2+]i were determined in Fluo-4 loaded cells. Androgen regulation was confirmed by chromatin immunoprecipitaion. RESULTS Stromal cell cultures were sorted for expression of integrin α1 β1 , which enriched for cells expressing the androgen receptor (AR). We identified key functional categories, within the androgen-induced gene expression signature, focusing on genes involved in calcium signaling. From this analysis, stromal interaction molecule-1 (STIM1) was identified as a significantly differentially expressed gene with four relevant associated GO terms. DNA sequence analysis showed that the promoter region of STIM1 contained putative androgen response element sequences in which AR binding ability of STIM1 was confirmed. Androgens directly regulated STIM1 expression and STIM1 effects on store-operated calcium entry were inhibited by STIM1 knock-down. Reduced STIM1 expression in prostate stromal cells led to a reduction in basal Ca2+ levels, the amount of Ca2+ released by thapsigargin and a reduction in store filling following TG-induced store depletion. CONCLUSIONS These results indicate that androgens modulate [Ca2+]i through the direct regulation of the STIM1 gene by AR binding to the STIM1 promoter.",
"title": "The calcium sensor STIM1 is regulated by androgens in prostate stromal cells."
},
{
"docid": "17685207",
"text": "The fate of cells in the epiblast at prestreak and early primitive streak stages has been studied by injecting horseradish peroxidase (HRP) into single cells in situ of 6.7-day mouse embryos and identifying the labelled descendants at midstreak to neural plate stages after one day of culture. Ectoderm was composed of descendants of epiblast progenitors that had been located in the embryonic axis anterior to the primitive streak. Embryonic mesoderm was derived from all areas of the epiblast except the distal tip and the adjacent region anterior to it: the most anterior mesoderm cells originated posteriorly, traversing the primitive streak early; labelled cells in the posterior part of the streak at the neural plate stage were derived from extreme anterior axial and paraxial epiblast progenitors; head process cells were derived from epiblast at or near the anterior end of the primitive streak. Endoderm descendants were most frequently derived from a region that included, but extended beyond, the region producing the head process: descendants of epiblast were present in endoderm by the midstreak stage, as well as at later stages. Yolk sac and amnion mesoderm developed from posterolateral and posterior epiblast. The resulting fate map is essentially the same as those of the chick and urodele and indicates that, despite geometrical differences, topological fate relationships are conserved among these vertebrates. Clonal descendants were not necessarily confined to a single germ layer or to extraembryonic mesoderm, indicating that these lineages are not separated at the beginning of gastrulation. The embryonic axis lengthened up to the neural plate stage by (1) elongation of the primitive streak through progressive incorporation of the expanding lateral and initially more anterior regions of epiblast and, (2) expansion of the region of epiblast immediately cranial to the anterior end of the primitive streak. The population doubling time of labelled cells was 7.5 h; a calculated 43% were in, or had completed, a 4th cell cycle, and no statistically significant regional differences in the number of descendants were found. This clonal analysis also showed that (1) growth in the epiblast was noncoherent and in most regions anisotropic and directed towards the primitive streak and (2) the midline did not act as a barrier to clonal spread, either in the epiblast in the anterior half of the axis or in the primitive streak. These results taken together with the fate map indicate that, while individual cells in the epiblast sheet behave independently with respect to their neighbours, morphogenetic movement during germ layer formation is coordinated in the population as a whole.",
"title": "Clonal analysis of epiblast fate during germ layer formation in the mouse embryo."
},
{
"docid": "27647593",
"text": "Cancer cells do not exist as pure homogeneous populations in vivo. Instead they are embedded in \"cancer cell nests\" that are surrounded by stromal cells, especially cancer associated fibroblasts. Thus, it is not unreasonable to suspect that stromal fibroblasts could influence the metabolism of adjacent cancer cells, and visa versa. In accordance with this idea, we have recently proposed that the Warburg effect in cancer cells may be due to culturing cancer cells by themselves, out of their normal stromal context or tumor microenvironment. In fact, when cancer cells are co-cultured with fibroblasts, then cancer cells increase their mitochondrial mass, while fibroblasts lose their mitochondria. An in depth analysis of this phenomenon reveals that aggressive cancer cells are \"parasites\" that use oxidative stress as a \"weapon\" to extract nutrients from surrounding stromal cells. Oxidative stress in fibroblasts induces the autophagic destruction of mitochondria, by mitophagy. Then, stromal cells are forced to undergo aerobic glycolysis, and produce energy-rich nutrients (such as lactate and ketones) to \"feed\" cancer cells. This mechanism would allow cancer cells to seed anywhere, without blood vessels as a food source, as they could simply induce oxidative stress wherever they go, explaining how cancer cells survive during metastasis. We suggest that stromal catabolism, via autophagy and mitophagy, fuels the anabolic growth of tumor cells, promoting tumor progression and metastasis. We have previously termed this new paradigm \"The Autophagic Tumor Stroma Model of Cancer Metabolism\", or the \"Reverse Warburg Effect\". We also discuss how glutamine addiction (glutaminolysis) in cancer cells fits well with this new model, by promoting oxidative mitochondrial metabolism in aggressive cancer cells.",
"title": "Stromal-epithelial metabolic coupling in cancer: integrating autophagy and metabolism in the tumor microenvironment."
},
{
"docid": "3360421",
"text": "We describe the derivation of pluripotent embryonic stem (ES) cells from human blastocysts. Two diploid ES cell lines have been cultivated in vitro for extended periods while maintaining expression of markers characteristic of pluripotent primate cells. Human ES cells express the transcription factor Oct-4, essential for development of pluripotential cells in the mouse. When grafted into SCID mice, both lines give rise to teratomas containing derivatives of all three embryonic germ layers. Both cell lines differentiate in vitro into extraembryonic and somatic cell lineages. Neural progenitor cells may be isolated from differentiating ES cell cultures and induced to form mature neurons. Embryonic stem cells provide a model to study early human embryology, an investigational tool for discovery of novel growth factors and medicines, and a potential source of cells for use in transplantation therapy.",
"title": "Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro"
},
{
"docid": "32797183",
"text": "Lineage analysis studies in the avian embryo have identified two types of smooth muscle cells (SMCs) in the tunica media of large elastic arteries; one that originates within the cardiac neural crest and is ectoderm in origin (Ect) and another that arises from local mesenchyme of mesodermal origin (Mes). To determine if differences in primary embryonic lineage can give rise to SMCs with stable differences in growth and differentiation properties, we isolated Ect and Mes SMCs from the Day 14 chick embryo aorta. We report that despite different primary embryonic origins, Ect and Mes SMCs express nearly identical levels of seven SMC differentiation markers in vitro, consistent with their common smooth muscle developmental fates in vivo. By contrast, Ect SMCs displayed a greater capacity for growth in serum-free medium than Mes SMCs, but only under conditions permitting short-range cell-cell interactions. Most of the peptide growth factors tested that might account for serum-independent growth (PDGF-AA, PDGF-BB, basic FGF, EGF, or activin) stimulated DNA synthesis to similar extents in Ect and Mes SMCs. However, we found dramatic, lineage-dependent differences in SMC responses to transforming growth factor-beta (TGF-beta). Exposure to TGF-beta 1 (0.4 to 400 pmole/liter) consistently increased DNA synthesis in Ect SMCs, whereas in paired cultures of Mes SMCs, TGF-beta 1 was growth inhibitory. In SMC cultures transfected with p3TP-lux, a luciferase reporter controlled by the TGF-beta 1-response elements of the human PAI-1 promoter, TGF-beta 1 (120 pM) produced 12 +/- 2-fold increases in luciferase activity in Ect SMCs and only 3 +/- 1.5-fold increases in Mes SMCs. Analysis of TGF-beta receptor phenotypes by Northern blot, radioligand binding, and crosslinking assays showed that Ect and Mes SMCs expressed similar levels of types I, II, and III TGF-beta receptors. However, using a polyclonal antibody specific for the chick type II TGF-beta receptor subunit, we demonstrate that Mes SMCs produce a fully glycosylated form of this protein while Ect SMCs elaborate only an unglycosylated type II TGF-beta receptor. These results show that Ect and Mes SMCs exhibit lineage-dependent differences in growth and receptor-mediated transcriptional responses to at least one important class of SMC morphogens and growth modifiers, e.g., the TGF-betas. Our findings suggest that different SMC populations within a common vessel wall may respond in lineage-dependent ways to signals that direct formation of the tunica media in the embryo and to factors involved in the progression of vascular disease later in life.",
"title": "Smooth muscle lineage diversity in the chick embryo. Two types of aortic smooth muscle cell differ in growth and receptor-mediated transcriptional responses to transforming growth factor-beta."
},
{
"docid": "1866911",
"text": "Basal-like breast cancers arising in women carrying mutations in the BRCA1 gene, encoding the tumor suppressor protein BRCA1, are thought to develop from the mammary stem cell. To explore early cellular changes that occur in BRCA1 mutation carriers, we have prospectively isolated distinct epithelial subpopulations from normal mammary tissue and preneoplastic specimens from individuals heterozygous for a BRCA1 mutation. We describe three epithelial subsets including basal stem/progenitor, luminal progenitor and mature luminal cells. Unexpectedly, we found that breast tissue from BRCA1 mutation carriers harbors an expanded luminal progenitor population that shows factor-independent growth in vitro. Moreover, gene expression profiling revealed that breast tissue heterozygous for a BRCA1 mutation and basal breast tumors were more similar to normal luminal progenitor cells than any other subset, including the stem cell–enriched population. The c-KIT tyrosine kinase receptor (encoded by KIT) emerged as a key marker of luminal progenitor cells and was more highly expressed in BRCA1-associated preneoplastic tissue and tumors. Our findings suggest that an aberrant luminal progenitor population is a target for transformation in BRCA1-associated basal tumors .",
"title": "Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers"
},
{
"docid": "15462523",
"text": "Natural killer (NK) cells are potent cytotoxic effector cells for cancer therapy and potentially for severe viral infections. However, there are technical challenges to obtain sufficient numbers of functionally active NK cells from a patient's blood since they represent only 10% of the lymphocytes and are often dysfunctional. The alternative is to obtain cells from a healthy donor, which requires depletion of the allogeneic T cells to prevent graft-versus-host reactions. Cytotoxic cell lines have been established from patients with clonal NK-cell lymphoma. Those cells can be expanded in culture in the presence of IL-2. Except for the NK-92 cell line, though, none of the other six known NK cell lines has consistently and reproducibly shown high antitumor cytotoxicity. Only NK-92 cells can easily be genetically manipulated to recognize specific tumor antigens or to augment monoclonal antibody activity through antibody-dependent cellular cytotoxicity. NK-92 is also the only cell line product that has been infused into patients with advanced cancer with clinical benefit and minimal side effects.",
"title": "Natural Killer Cells for Immunotherapy – Advantages of the NK-92 Cell Line over Blood NK Cells"
}
] |
57624
|
Cheyenne Jackson is an entertainer.
|
[
{
"docid": "Cheyenne_Jackson",
"text": "Cheyenne David Jackson ( born July 12 , 1975 ) is an American actor and singer-songwriter . His credits include leading roles in Broadway musicals and other stage roles , as well as film and television roles , concert singing , and music recordings . After beginning his acting career in regional theatre in Seattle , he moved to New York and was an understudy in Thoroughly Modern Millie ( 2002 ) and Aida ( 2003 ) . He next originated the role of Matthew in Altar Boyz ( 2004 ) . Jackson 's first leading role on Broadway was in All Shook Up ( 2005 ) , which earned him a Theatre World Award for `` Outstanding Broadway Debut . '' Since then , on the New York stage , he has starred in The Agony & the Agony ( 2006 ) , Xanadu ( 2007 ; Drama League , Drama Desk nominations ) , Damn Yankees ( 2008 ) , Finian 's Rainbow ( 2010 ; Drama Desk nomination ) , 8 ( 2011 ) , The Heart of the Matter ( 2012 ) and The Performers ( 2013 ) . He has also appeared in a number of films , including the 2006 Academy Award-nominated United 93 , in which his portrayal of Mark Bingham earned him the Boston Society of Film Critics 2006 award for Best Ensemble Cast . He also had a leading role in the 2014 independent romantic comedy ensemble , Mutual Friends , and guest roles in television series such as NBC 's 30 Rock and Fox 's Glee . Most recently , Jackson starred in the FX Horror-anthology , American Horror Story , in its fifth and sixth seasons . In concert , Jackson has sold out Carnegie Hall twice : The Power of Two in 2010 and Music of the Mad Men Era in 2011 . He also performs in cabaret . In addition to his Broadway cast albums , he has released three albums of popular music , including a joint album called The Power of Two with Michael Feinstein in 2008 . In 2012 , Jackson released two singles , `` Drive '' and `` Before You '' , from his 2013 album I 'm Blue , Skies . In 2016 , Jackson released his latest album , Renaissance , an album adapted and expanded from his solo concert Music of the Mad Men Era .",
"title": ""
}
] |
[
{
"docid": "Drive_(Cheyenne_Jackson_song)",
"text": "`` Drive '' is a song by American actor and singer Cheyenne Jackson from his album I 'm Blue , Skies . Although Cheyenne Jackson has released theatrical music releases , this is his first non-theatrical single release . `` Drive '' was produced by Thomas `` Tawgs '' Salter and written by Cheyenne and Stephen `` Stevie '' Aiello . A music video was released , also his first ever music video . About the meaning of the song , Cheyenne says : I wanted to write a song about keeping forward momentum in your life , and having the strength to leave a situation that you know in your heart is bad for you . It ended up being melancholy , but ultimately hopeful and optimistic , just like me . I felt like my head was exploding , because not only did I know that this was exactly what I was supposed to be doing , it kind of changed my perspective on everything . The songs started pouring out of me , and I 'm more proud of this work than any part I 've ever done . Drive was also remixed by Conair and appears as an additional 6:47 track on Jackson 's album I 'm Blue , Skies as `` Drive ( Conair mix ) '' .",
"title": ""
},
{
"docid": "Cheyenne_(given_name)",
"text": "Cheyenne is the given name of : Cheyenne Brando ( 1970-1995 ) , Tahitian model , daughter of Marlon Brando Cheyenne Campbell ( born 1986 ) , New Zealand-born rugby union player for Australia Chey Dunkley ( born 1992 ) , English footballer Cheyenne Haynes , American actress , dancer , singer , and model Cheyenne Jackson ( born 1975 ) , American actor and singer Cheyenne Kimball ( born 1990 ) , American singer/songwriter who has her own MTV reality program Cheyenne Marie Mize , American folk singer-songwriter Cheyenne Parker ( born 1992 ) , American WNBA basketball player Cheyenne Tozzi ( born 1988 ) , Australian model Cheyenne Woods ( born 1990 ) , American golfer Category : Unisex given names",
"title": ""
},
{
"docid": "Helen_Hunt_Falls",
"text": "Helen Hunt Falls is a waterfall located on Cheyenne Creek in the North Cheyenne Cañon Park of Colorado Springs , Colorado . The falls are named in honor of Helen Maria Hunt Jackson ( October 15 , 1830 -- August 12 , 1885 ) , a United States poet and writer who became an activist on behalf of improved treatment of Native Americans by the U.S. government . She died in San Francisco , California in 1885 and was later buried in Colorado Springs . The falls are located on North Cheyenne Creek immediately off of North Cheyenne Canyon Road in the North Cheyenne Canyon Park . There is parking for about 30 vehicles at the falls and it becomes crowded early during summer months when visits to the canyon are popular among locals and tourists . The Columbine Trail , which starts at the entrance of the Park by the Starsmore Visitor and Nature Center , terminates at Helen Hunt Falls . Visitors can hike a short distance of about 2/3 of a mile up a moderately steep trail above Helen Hunt Falls to reach Silver Cascade Falls .",
"title": ""
},
{
"docid": "Stargate:_Resistance",
"text": "Stargate : Resistance was an online third-person shooter owned and operated by Dark Comet Games , powered by the Unreal 3 engine , and based on the television series Stargate SG-1 . It was originally released in 2010 by Firesky and Cheyenne Mountain Entertainment , however Cheyenne Mountain Entertainment went into receivership in March 2010 and Firesky entered into an agreement with Dark Comet Games for the maintenance , operation and development of Stargate Resistance . The game used a `` buy to play '' business model , with a one-off purchase fee and no monthly subscription fee . The game servers were shut down on January 15 , 2011 . A fan powered central server solution has been put in place , making the game once again playable http://stargateresistance.us/",
"title": ""
},
{
"docid": "The_Power_of_Two",
"text": "The Power of Two is a 2009 studio album by American vocalists Michael Feinstein and Cheyenne Jackson arranged by John Oddo .",
"title": ""
},
{
"docid": "Centennial_Airlines",
"text": "Centennial Airlines was founded in Laramie , Wyoming and began operations on June 15 , 1981 with an initial route linking Denver to Laramie and Worland , Wyoming using a single Cessna 414 aircraft . The carrier flew until June 15 , 1987 when it was merged into Mesa Airlines . Centennial was first based in Laramie , Wyoming , moved its offices to Worland , then to Cheyenne for a brief time in 1982 , then back to Worland . Centennial served Denver , Colorado , Billings , Montana ; Logan and Salt Lake City , Utah ; Casper , Cheyenne , Cody , Jackson , Lander , Laramie , Rawlins , Riverton , Rock Springs and Worland , Wyoming . Routes operated include : Denver-Casper-Cody , Denver-Cheyenne-Rawlins , Denver-Rock Springs-Lander-Worland , Denver-Laramie-Riverton-Worland-Cody-Billings , Salt Lake City-Logan-Riverton-Worland-Cody The fleet included two Beechcraft 1900 's and one Beechcraft 99 at the time of its merger with Mesa Airlines .",
"title": ""
},
{
"docid": "OURsceneTV",
"text": "OURsceneTV is a lifestyle entertainment video site for the LGBT community , headquartered in New York City . Owned by OURscene Networks , LLC , it was founded in 2008 by Christine Alloro to `` bridge gaps for the LGBT community to the rest of the world , and also give those who are closeted a sense that they can come out . The site features original programming in short-form video format , and includes red carpet coverage , celebrity interviews , lifestyle segments , and a coverage of New York and Los Angeles gay-friendly businesses and nightlife . In October 2009 OURsceneTV was recognized by writer Cathy Brooks of The Huffington Post as a `` catalyst in the evolution of LGBT public expression . '' Brooks writes that OURsceneTV has a `` distinctly Entertainment Tonight/Access Hollywood feel , '' albeit from an LGBT perspective , balanced with more socially conscious features such as the site 's series , `` Stonewall : Profiles of Pride , '' tackling serious topics ranging from `` issues facing the trans ( gendered ) community , gay parents , immigration and adoption laws , and safeguarding your finances . '' OURsceneTV segments have been featured by The San Francisco Chronicle , The Village Voice , Towleroad.com , AfterEllen.com , and Queerty . Celebrity Interviews include Lady Gaga , Sean Penn , Mary Louise Parker , Cyndi Lauper , Marc Jacobs , Michael Bloomberg , Cheyenne Jackson , Chace Crawford , The Indigo Girls , Tyra Banks , Eve , Alan Cumming , Whoopi Goldberg , Wilson Cruz , Candis Cayne , and more .",
"title": ""
},
{
"docid": "List_of_hospitals_in_Wyoming",
"text": "List of hospitals in Wyoming ( U.S. state ) , sorted by hospital name . Carbon County Memorial Hospital - Rawlins Castle Rock Hospital District - Green River Cheyenne Regional Medical Center - Cheyenne Community Hospital - Torrington Crook County Medical Service - Sundance Evanston Regional Hospital - Evanston Hot Springs Memorial Hospital - Thermopolis Ivinson Memorial Hospital - Laramie Johnson County Health Care Center - Buffalo SageWest Healthcare - Lander - Lander Campbell County Memorial Hospital - Gillette Memorial Hospital of Converse County - Douglas Memorial Hospital of Sheridan County - Sheridan Mountain View Regional Hospital - Casper Niobrara Health and Life Center - Lusk Powell Valley Hospital - Powell SageWest Healthcare - Riverton - Riverton Sheridan Memorial Hospital - Sheridan South Big Horn County Hospital - Basin/Greybull St. John 's Medical Center - Jackson Star Valley Medical Center - Afton Summit Medical Center - Casper Sweetwater County Memorial Hospital - Rock Springs US Air Force Hospital - F. E. Warren Air Force Base VA Medical Center Cheyenne - Cheyenne Washakie Medical Center - Worland West Park Hospital - Cody Weston County Health Service - Newcastle Wyoming Medical Center - Casper Wyoming State Hospital - Evanston Wyoming Hospitals",
"title": ""
},
{
"docid": "Monte_Olsen",
"text": "Monte Olsen ( August 8 , 1956 -- April 8 , 2014 ) was an American politician and professional skier . Born in Cheyenne , Wyoming , Olsen went to Northwest College and University of Wyoming . He was a professor skier and a ski instructor at Jackson Hole Mountain Resort . Olsen served in the Wyoming House of Representatives from 2002 to 2008 as a Republican and had lived in Daniel , Wyoming . Olsen was found dead of a heart attack in a motel room in Jackson Hole , Wyoming .",
"title": ""
},
{
"docid": "Michael_Jackson_impersonator",
"text": "A Michael Jackson impersonator is someone who impersonates or copies the look and sound of American entertainer Michael Jackson . They work all over the world as entertainers , and such tribute acts remain in great demand due to the high popularity of Jackson .",
"title": ""
},
{
"docid": "The_Green_(film)",
"text": "The Green is a 2011 drama film directed by Steven Williford , written by Williford , Paul Marcarelli and Molly Pearson , and starring Jason Butler Harner , Cheyenne Jackson , Illeana Douglas and Julia Ormond .",
"title": ""
},
{
"docid": "Move_Like_Michael_Jackson",
"text": "Move Like Michael Jackson was a British talent show made by independent production company Fever Media and Gogglebox Entertainment and transmitted on BBC Three , which aimed to find people who can dance like the famous pop singer , Michael Jackson . The show began airing several months after the entertainer 's death in June 2009 . Presented by television personality Reggie Yates , the programme broadcast the auditions of hopefuls as they perform in front of the show 's judges : Mark Summers , contemporary R&B singer Jamelia , and Jackson 's elder brother and former Jackson 5 band member Jermaine .",
"title": ""
},
{
"docid": "Marlon_Jackson",
"text": "Marlon David Jackson ( born March 12 , 1957 ) is an American entertainer , singer , dancer . Jackson was a member of The Jackson 5 . Jackson is known as `` the Dancingest Jackson '' for his dancing performances on stage , as well as the `` Jokester '' for his sense of humor . Jackson is the seventh child of the Jackson family .",
"title": ""
},
{
"docid": "Joe_Jackson_(manager)",
"text": "Joseph Walter `` Joe '' Jackson ( born July 26 , 1928 ) is a talent manager and is the patriarch of the Jackson family of entertainers which includes the artists Janet Jackson and Michael Jackson .",
"title": ""
},
{
"docid": "Mike_Jackson_(Australian_entertainer)",
"text": "Mike Jackson OAM is an Australian children 's entertainer , recording artist , songwriter , radio show host , and author . He is perhaps best known for his version of Bananas In Pyjamas and appearances on ABC Television .",
"title": ""
},
{
"docid": "Brian_Jackson_(game_designer)",
"text": "Brian Jackson ( born 2 November 1972 ) is an American video game designer , having been in the video game industry since 1995 . He has helped produce games for Electronic Arts , Microsoft , Bethesda Softworks , and Nerjyzed Entertainment . Jackson has served as a designer for BCFx , The Elder Scrolls IV : Oblivion , IHRA Drag Racing -- Sportsman Edition , NFL Fever , NBA Inside Drive 2004 , NCAA March Madness , Madden NFL , and Viewpoint . Jackson received a Bachelor of Business Administration in Computer Based Information Systems from Howard University in 1992 , and is a member of Alpha Phi Alpha fraternity . Jackson , with Nerjyzed Entertainment CEO Jackie Beauchamp , was credited in the November 26 , 2007 issue of Jet Magazine for helping create the first Black College Football video game . Jackson was featured in a January 2001 , article in US Black Engineer : `` Their Work Is All Play , Turning Pastimes into Careers in the Video Games Industry . '' In September 1998 , in an article entitled : `` Who Got Game ? '' Source Magazine credited Jackson and designer Rob Jones with helping make John Madden Football appealing to the Hip Hop community .",
"title": ""
},
{
"docid": "Cheyenne",
"text": "The Cheyenne ( -LSB- ʃaɪˈæn -RSB- ) are one of the Indigenous peoples of the Great Plains and their language is of the Algonquian language family . The Cheyenne comprise two Native American tribes , the Só ` taeo'o or Só ` taétaneo'o ( more commonly spelled as Suhtai or Sutaio ) and the Tsétsêhéstâhese ( also spelled Tsitsistas ) . These tribes merged in the early 19th century . Today , the Cheyenne people are split into two federally recognized Nations : the Southern Cheyenne , who are enrolled in the Cheyenne and Arapaho Tribes in Oklahoma , and the Northern Cheyenne , who are enrolled in the Northern Cheyenne Tribe of the Northern Cheyenne Indian Reservation in Montana . At the time of their first contact with the Europeans , the Cheyenne were living in the area of what is now Minnesota . At times they have been allied with the Lakota and Arapaho , and at other points enemies of the Lakota . In the early 18th century they migrated west across the Mississippi River and into North and South Dakota , where they adopted the horse culture . Having settled the Black Hills of South Dakota and the Powder River Country of present-day Montana , they introduced the horse culture to Lakota bands about 1730 . Allied with the Arapaho , the Cheyenne pushed the Kiowa to the Southern Plains . In turn , they were pushed west by the more numerous Lakota . The Cheyenne Nation or Tsêhéstáno was at one time composed of ten bands that spread across the Great Plains from southern Colorado to the Black Hills in South Dakota . They fought their traditional enemies , the Crow and later ( 1856 -- 79 ) the United States Army forces . In the mid-19th century , the bands began to split , with some bands choosing to remain near the Black Hills , while others chose to remain near the Platte Rivers of central Colorado . The Northern Cheyenne , known in Cheyenne either as Notameohmésêhese , meaning `` Northern Eaters '' or simply as Ohmésêhese meaning `` Eaters '' , live in southeastern Montana on the Northern Cheyenne Indian Reservation . Tribal enrollment figures , as of late 2014 , indicate that there are approximately 10,840 members , of which about 4,939 reside on the reservation . Approximately 91 % of the population are Native Americans ( full or part race ) , with 72.8 % identifying themselves as Cheyenne . Slightly more than one quarter of the population five years or older spoke a language other than English . The Southern Cheyenne , known in Cheyenne as Heévâhetaneo'o meaning `` Roped People '' , together with the Southern Arapaho , form the Cheyenne and Arapaho Tribes , in western Oklahoma . Their combined population is 12,130 , . In 2003 , approximately 8,000 of these identified themselves as Cheyenne , although with continuing intermarriage it has become increasingly difficult to separate the tribes .",
"title": ""
},
{
"docid": "Cheyenne_County",
"text": "Cheyenne County is the name of several counties in the United States : Cheyenne County , Colorado Cheyenne County , Kansas Cheyenne County , Nebraska Cheyenne County , Jefferson Territory ru : Шайенн #Округа",
"title": ""
},
{
"docid": "Janet_Jackson_videography",
"text": "American entertainer Janet Jackson has released forty-nine music videos , in addition to eight video albums and two concert tour videos . Upon the debut of Control , she became a dominant figure in entertainment , establishing herself as one of the pioneers of the video era . Her videography is considered among the most influential in popular culture by critics , who have lauded their elaborate sets , intricate dance routines , fashion , and meticulous detail . Her story-telling videos display various concepts , ranging from large production pieces to socially conscious themes and controversial depictions of intimacy . Throughout her work , Jackson was a preeminent influence in establishing the art of performance and choreography within music video . Her videos have been described as the entertainment industry 's highest standard , which Rolling Stone observed to create templates for numerous artists . VH1 ranked her among the greatest women in music video , while MTV honored her with the Video Vanguard Award and inaugural Icon tribute for her impact within entertainment . Jackson 's music videos have collectively won numerous accolades , such as Grammy Awards for Best Long and Short Form videos , MTV Japan 's `` Inspiration Award '' , and Billboard Awards ' `` Music Video Award for Artistic Achievement '' . Her early videos , such as `` Nasty '' , `` The Pleasure Principle '' , and `` Alright '' , became iconic for their intense choreography and locale . `` Rhythm Nation '' has been thought to portray the most influential choreography and setting in a music video by multiple critics , achieving legendary status . `` Love Will Never Do ( Without You ) '' unveiled Jackson 's physical evolution to adulthood , while `` If '' showcased its famous dance routine , interracial lust , and futuristic technology . Other notable videos include the spiritual theme of `` Together Again '' and aquatic scenery in `` Every Time '' . Videos such as `` All for You '' and `` Feedback '' have also influenced a diverse array of artists . Jackson has multiple videos ranked among the most expensive of all-time , which include `` Does n't Really Matter '' and `` Scream '' , the most expensive in history .",
"title": ""
},
{
"docid": "Porcupine_(Cheyenne)",
"text": "Porcupine ( c. 1848 -- 1929 ) was a Cheyenne chief and medicine man . He is best known for bringing the Ghost Dance religion to the Cheyenne . Raised with the Sioux of a Cheyenne mother , he married a Cheyenne himself and became a warrior in the Cheyenne Dog Soldiers . Porcupine fought against the U.S. in Hancock 's War in 1867 in which the Cheyenne resisted moving to a reservation . Porcupine 's group was pursued by the 7th Cavalry from Kansas to Nebraska . In Nebraska he succeeded in derailing and wrecking a train , the first time this had been done by Indians . At the conclusion of the Great Sioux War of 1876 , the Cheyenne surrendered and were deported to Oklahoma . Porcupine took part in the Northern Cheyenne Exodus in which a part of the starving tribe fought their way back to their homeland in Montana . Porcupine was one of a group of Cheyennes who were subsequently arrested on charges of murdering settlers as the Cheyennes crossed Kansas . After spending most of 1879 in prison , the charges were dismissed without a full trial taking place . In 1889 , Porcupine undertook a long journey to visit Wovoka in Nevada . Wovoka was the prophet of the new Ghost Dance religion . Porcupine believed that Wovoka was the Messiah who would save the Indians and rid the continent of the white men . Porcupine returned to preach the new religion to the Cheyennes and began baptising converts into his church . The Ghost Dance spread throughout the plains tribes . Fear of it led to it being suppressed by the U.S. army . While the Cheyenne did not suffer tragedy on the scale of the Sioux at Wounded Knee , Porcupine could only perform the dance in secret from 1890 onwards . In 1900 he was imprisoned for attempting to revive the religion . Porcupine , like Wovoka , preached peace and took no part in the violence associated with the Ghost Dance elsewhere . He was a chief representing the Cheyenne in several treaty councils with the U.S. , including leading a delegation to Washington .",
"title": ""
},
{
"docid": "KGWN-TV",
"text": "KGWN-TV is a CBS-affiliated television station licensed to Cheyenne , Wyoming , United States . It broadcasts a high definition digital signal on UHF channel 30 ( or virtual channel 5.1 via PSIP ) from a transmitter in unincorporated Laramie County ( west of Cheyenne ) between I-80 / U.S. 30 and WYO 225 . Owned by Gray Television , KGWN has studios on East Lincolnway/East 14th Street/I -80 Business/U . S. 30 in Cheyenne . Syndicated programming on the station includes Who Wants to Be a Millionaire , Wheel of Fortune , Judge Judy , and Dr. Phil among others . It operates a digital fill-in translator , K19FX-D channel 19 , in Laramie from a transmitter in unincorporated Albany County near the Medicine Bow National Forest 's northwestern boundary . KSTF in Scottsbluff , Nebraska operates as a semi-satellite of KGWN . This station broadcasts a high definition digital signal on UHF channel 29 ( or virtual channel 10.1 via PSIP ) from a transmitter along N-71 at the Scotts Bluff and Sioux county line . It can also be seen locally in Nebraska on Charter channel 6 . The station is a full-time simulcast of KGWN except for preempting Dr. Phil and Wheel of Fortune on weeknights in favor of Recipe.tv , Justice for All with Judge Cristina Perez , and Entertainment Tonight . ( Dr. Phil and Wheel of Fortune are available to Scottsbluff viewers on sister station KNEP , a satellite of Rapid City , South Dakota-based KOTA-TV . ) KSTF also airs separate legal identifications and local commercial inserts during all programming . Although KSTF 's master control and most internal operations are based out of KGWN 's Cheyenne facility , it maintains an advertising sales office on North 10th Street/N -71 Business in Gering , Nebraska . There is no separate web address for KSTF , but Nebraska-specific headlines are provided through KGWN 's website .",
"title": ""
},
{
"docid": "Paul_Jackson_(game_producer)",
"text": "Paul Stafford Jackson , OBE ( born 1962 ) is a British video game producer and publisher . In 1993 , Jackson established the British office of Electronic Arts . At EA UK , he was involved in brand-building for the The Sims series of games . Whilst at EA , he was approached by Kuju Entertainment seeking interest in publishing Rail Simulator , a successor to Microsoft Train Simulator which Microsoft Games had declined to publish . On 1 August 2006 , Jackson took over from Roger Bennett as director-general of the Entertainment and Leisure Software Publishers Association ( ELSPA ) , the British video game industry trade group , having served on the ELSPA board for twelve years since 1992 , with three years as chairman . In 2008 , after leaving ELSPA , Jackson returned to the Rail Simulator franchise , arranging to buy the rights to the project , and becoming CEO of the resulting development company , RailSimulator.com Ltd. . The company released RailWorks , the successor to Rail Simulator , in 2009 . Since December 2013 , the company has been known as Dovetail Games . In 2010 , Jackson was made an Officer of the Order of the British Empire ( OBE ) in the New Year Honours for services to the video game industry .",
"title": ""
},
{
"docid": "Jackson_Records",
"text": "Jackson Records is a film and music publishing label based in India . The label and its sub-labels / imprints are owned and administered by Jackson Records Digital Entertainment LLP ( formerly known as Digisys Media Network until July 2014 ) . Jackson Records as a label started functioning from December , 2011 .",
"title": ""
},
{
"docid": "Cheyenne_Creek",
"text": "Cheyenne Creek is a stream in Colorado Springs , El Paso County , Colorado at 5920 ft in elevation . The stream is fed by the North Cheyenne Creek and South Cheyenne Creek and flows into Fountain Creek near Nevada Avenue , between Interstate 25 and the Pikes Peak Greenway trail . North Cheyenne Creek and South Cheyenne Creek flow through Teller and El Paso Counties . The source of South Cheyenne Creek is Mount Big Chief , near St. Peter 's Dome , and it flows to Seven Falls .",
"title": ""
},
{
"docid": "William_DuBois_(architect)",
"text": "William Dubois ( 1879-1953 ) was an American architect . He was a prolific architect in Wyoming and nearby states . William Robert Dubois designed more than 70 commercial buildings in Cheyenne , including almost all that were built in Cheyenne during 1900 to 1920 . He designed more than 100 houses , 27 schools , six churches , and four Carnegie libraries . He was born in Chicago , Illinois on November 15 , 1879 . He trained at the Chicago School of Architecture and worked for architectural firms in Chicago and in Albuquerque before coming to Cheyenne in 1901 . He arrived as the supervising architect for a Carnegie Library . He died May 31 , 1953 . A number of his works are listed on the U.S. National Register of Historic Places . Works include ( attribution ) : Carnegie Library ( 1901 ) , in Cheyenne Carnegie public libraries in Basin , in Green River , in Rock Springs , Wyoming , and in Eaton , Colorado Atlas Theatre ( built 1887 ) , 213 W. 16th St. Cheyenne , WY ( Dubois , William ) , NRHP-listed Charles L. Beatty House ( 1916 ) , 2320 Capitol Ave. Cheyenne , WY ( Dubois , William Robert ) , NRHP-listed Cheyenne High School , 2810 House Ave. Cheyenne , WY ( Dubois , William ) , NRHP-listed Churchill Public School , 510 W. 29th St. Cheyenne , WY ( Dubois , William ) , NRHP-listed City and County Building , 19th St. and Carey Ave. Cheyenne , WY ( Dubois , William ) , NRHP-listed Corlett School , 600 W. 22nd St. Cheyenne , WY ( Dubois , William ) , NRHP-listed Federal Office Building -- Cheyenne , 308 W. 21st St. Cheyenne , WY ( Dubois , William ) , NRHP-listed William Goodale House , 214 S. Fourteenth St. Laramie , WY ( Dubois , William ) , NRHP-listed Johnson Public School , 711 Warren Ave. Cheyenne , WY ( Dubois , William ) , NRHP-listed Lincoln School , 209 S. Cedar St. Laramie , WY ( Dubois , William R. ) , NRHP-listed Lulu McCormick Junior High School , 2001 Capitol Ave. Cheyenne , WY ( Dubois , William ) , NRHP-listed Morton Mansion , 425 Center St. Douglas , WY ( Dubois , William L. ) , NRHP-listed Rialto Theater , 102 E. Second St. Casper , WY ( Dubois & Goodrich ) , NRHP-listed Wyoming Fuel Company , 720 W. 18th St. Cheyenne , WY ( Dubois , William ) , NRHP-listed Wyoming State Insane Asylum , 831 WY 150 S Evanston , WY ( Dubois , William ) , NRHP-listed One or more works in Downtown Cheyenne Historic District , Roughly bounded by 15th and 16th Sts. , Central and Pioneer Aves . Cheyenne , WY ( Dubois , William ) , NRHP-listed One or more works in Downtown Cheyenne Historic District ( Boundary Increase I ) , Roughly bounded by 17th and 18th Sts. , Pioneer and Carey Aves. , also along Central Ave. and 17th St. Cheyenne , WY ( Dubois , William ) , NRHP-listed One or more works in Downtown Cheyenne Historic District ( Boundary Increase II ) , Roughly bounded by Nineteenth St. , Capital Ave. , Seventeenth St. , and Carey Ave. Cheyenne , WY ( Dubois , William ) , NRHP-listed One or more works in Moore Haven Heights Historic District , Between Bent Ave. on the W. , E. side of Central Ave. on the E. , W. 8th Ave. on the N. , W. Pershing Blvd on the S. Cheyenne , WY ( Dubois , William H. ) , NRHP-listed",
"title": ""
},
{
"docid": "Paul_Jackson_(producer)",
"text": "Kevin Paul Jackson ( born 2 October 1947 ) , credited as Paul Jackson ; sometimes as K. Paul Jackson , is a British television director , producer and executive . His father was former BBC Light Entertainment Producer , T. Leslie Jackson whose credits include 1950s classics This Is Your Life & What 's My Line . He was originally producer for the sci-fi sitcom Red Dwarf .",
"title": ""
},
{
"docid": "Northern_Cheyenne_Exodus",
"text": "The Northern Cheyenne Exodus , also known as Dull Knife 's Raid , the Cheyenne War , or the Cheyenne Campaign , was the attempt of the Northern Cheyenne to return to the north , after being placed on the Southern Cheyenne reservation in the Indian Territory , and the United States Army operations to stop them . The period lasted from 1878 to 1879 .",
"title": ""
},
{
"docid": "Jackson_Murphy",
"text": "Jackson Murphy , known as Lights Camera Jackson ( born July 1998 ) is a movie critic and entertainment columnist . He is the creator of the website Lights-Camera-Jackson . com , and has made appearances on television and radio . In 2010 , he became the youngest winner to date of a New York Emmy Award for `` On Camera Talent : Commentator/Editorialist '' .",
"title": ""
},
{
"docid": "Little_Shield",
"text": "Little Shield ( Cheyenne language : A-che-kan-koo-eni ) was a chieftain of the Northern Cheyenne from 1865-1879 . He is known for creating a collection of ledger drawings accounting the Indian wars along the North Platte river . Little Shield also fought in the Battle of Little Bighorn , leading the Dog Soldiers . Following the Battle of the Little Bighorn , the US Army increased attempts to capture the Cheyenne . In 1877 , after the Dull Knife Fight , when Crazy Horse surrendered at Fort Robinson , a few Cheyenne chiefs and their people surrendered as well . The Cheyenne chiefs who surrendered at the fort were Dull Knife , Little Wolf , Standing Elk , and Wild Hog , with nearly 1,000 Cheyenne . Later that year Two Moon surrendered at Fort Keogh with 300 Cheyenne . The Cheyenne wanted and expected to live on the reservation with the Sioux in accordance to an April 29 , 1868 treaty of Fort Laramie , which Dull Knife , Little Wolf and also Little Shield had signed . In the fall of 1878 somewhere beyond the North Platte River after crossing into Nebraska the Cheyenne held council and it was discovered that 34 of the original 297 were missing , most had been killed but a few had decided to take other paths to the north . This is where the Cheyenne split into two groups . Those that wished to stop running , including Little Shield , Wild Hog and Left Hand , planned to go with Dull Knife to the Red Cloud Agency . The Cheyenne that decided to keep heading to the Power River country followed Little Wolf . Little Shield lead the remaining Dog Soldiers who had stayed with Dull Knife . On October 23 , 1878 Dull Knife 's band of Cheyenne , in a blinding snowstorm , discovered that they were surrounded by the army ; the encounter was accidental , neither party having seen the other due to the snow . Dull Knife convinced his band not to attack the soldiers . The army offered some food and a few blankets to the Cheyenne and suggested a move to a better camp nearby at Fort Robinson in northwestern Nebraska . There the army confiscated the Cheyenne ponies but distributed more rations , including sugar and coffee . The next morning after a two-hour council , the Cheyenne agreed to turn over their weapons . However they turned over only the older ones , concealing many . After hearing that Red Cloud and Spotted Tail had been relocated to Pine Ridge , Dull Knife decided , due to the weather and his people 's condition , to go to Fort Robinson . The Cheyenne decided that night to take apart their best guns , women hid the barrels under their clothing and the smaller pieces were attached to cloths and moccasins as ornaments . Without telling the Cheyenne , it was determined by November 22 by Carl Schurz , the Secretary of the Interior that the Cheyenne would be returned to the south . That was also the course recommended by General Phillip Sheridan , commander of the Division of Missouri . When the Cheyenne refused to return to the reservation in the south , bars were put on windows and no rations were given , including wood for heat . On January 9 , 1879 Dull Knife still refused to go back south , however Wild Hog and Left Hand had agreed to talk but said their people would not go . Upon hearing this Wild Hog was held as a prisoner and shackled . That night the Cheyenne tried to make a daring escape using the dismantled guns they had hidden upon arriving at the fort . The Cheyenne were immediately followed and many were killed , Little Shield among them .",
"title": ""
},
{
"docid": "Cheyenne_metropolitan_area",
"text": "The Cheyenne Metropolitan Statistical Area is a United States Census Bureau defined Metropolitan Statistical Area ( MSA ) located in the Cheyenne region of the State of Wyoming . The Cheyenne Metropolitan Statistical Area is defined as Laramie County , Wyoming . Many consider the Cheyenne Metro Area to be the economic hub of eastern Wyoming . The Census Bureau estimates that the population was 86,353 in 2007 , ranking as the 340th most populous metropolitan area in the United States . The Cheyenne Metropolitan Statistical Area includes the City of Cheyenne , the Town of Albin , the Town of Burns , the Town of Pine Bluffs and the unincorporated areas of Laramie County .",
"title": ""
}
] |
5567
|
How much in cash equivalents should I keep in the bank? [duplicate]
|
[
{
"docid": "408307",
"text": "In personal finance circles this is called an Emergency Fund. There are many opinions about how big it needs to be but most seem to come in around 3-6 months worth of your average expenses. Any more than that and you're going to loose money to inflation, less and you will start having problems if you get laid off or have a medical issue.",
"title": ""
}
] |
[
{
"docid": "5188",
"text": "Basically you have 4 options: Use your cash to pay off the student loans. Put your cash in an interest-bearing savings account. Invest your cash, for example in the stock market. Spend your cash on fun stuff you want right now. The more you can avoid #4 the better it will be for you in the long term. But you're apparently wise enough that that wasn't included as an option in your question. To decide between 1, 2, and 3, the key questions are: What interest are you paying on the loan versus what return could you get on savings or investment? How much risk are you willing to take? How much cash do you need to keep on hand for unexpected expenses? What are the tax implications? Basically, if you are paying 2% interest on a loan, and you can get 3% interest on a savings account, then it makes sense to put the cash in a savings account rather than pay off the loan. You'll make more on the interest from the savings account than you'll pay on interest on the loan. If the best return you can get on a savings account is less than 2%, then you are better off to pay off the loan. However, you probably want to keep some cash reserve in case your car breaks down or you have a sudden large medical bill, etc. How much cash you keep depends on your lifestyle and how much risk you are comfortable with. I don't know what country you live in. At least here in the U.S., a savings account is extremely safe: even the bank goes bankrupt your money should be insured. You can probably get a much better return on your money by investing in the stock market, but then your returns are not guaranteed. You may even lose money. Personally I don't have a savings account. I put all my savings into fairly safe stocks, because savings accounts around here tend to pay about 1%, which is hardly worth even bothering. You also should consider tax implications. If you're a new grad maybe your income is low enough that your tax rates are low and this is a minor factor. But if you are in, say, a 25% marginal tax bracket, then the effective interest rate on the student loan would be more like 1.5%. That is, if you pay $20 in interest, the government will then take 25% of that off your taxes, so it's the equivalent of paying $15 in interest. Similarly a place to put your money that gives non-taxable interest -- like municipal bonds -- gives a better real rate of return than something with the same nominal rate but where the interest is taxable.",
"title": ""
},
{
"docid": "573874",
"text": "\"Probably a bad assumption, but I'm assuming your in the United States. Keep in mind, that the check number is printed in 2 places on the front of each check. First, in the upper right corner, and also along the bottom edge on of the check. Since the check number is scanned by the bank from the bottom edge of the check, covering or otherwise modifying the check number on the upper left corner will have no effect on the check number that is recorded when the check is processed. And, you can't modify or cover the numbers or place any marks in the area of the numbers along the bottom of the check as this will likely interfere with processing of checks. So, modifying the check numbers will not work. Your choices are basically to: The check numbers are not used in any way in clearing the check, the numbers are only for your convenience, so processing checks with duplicate numbers won't matter. The check numbers are recorded when processed at your bank so they can be shown on your printed and online statements. The only time the check number might be important is if you had to \"\"stop payment\"\" on a particular check, or otherwise inquire about a particular check. But this should not really be an issue because by the time you have used up the first batch of checks, and start using the checks with duplicate numbers, the first use of the early duplicate numbered checks will be sufficiently long ago that there should not be any chance of processing checks with duplicate numbers at the same time. You didn't mention how many checks you have with duplicate numbers, or how frequently you actually write checks so that may play a part in your decision. In my case, 100 checks will last me literally years, so it wouldn't be a problem for me.\"",
"title": ""
},
{
"docid": "583321",
"text": "\"You should dispute the transaction with the credit card. Describe the story and attach the cash payment receipt, and dispute it as a duplicate charge. There will be no impact on your score, but if you don't have the cash receipt or any other proof of the alternative payment - it's your word against the merchant, and he has proof that you actually used your card there. So worst case - you just paid twice. If you dispute the charge and it is accepted - the merchant will pay a penalty. If it is not accepted - you may pay the penalty (on top of the original charge, depending on your credit card issuer - some charge for \"\"frivolous\"\" charge backs). It will take several more years for either the European merchants to learn how to deal with the US half-baked chip cards, or the American banks to start issue proper chip-and-PIN card as everywhere else. Either way, until then - if the merchant doesn't know how to handle signatures with the American credit cards - just don't use them. Pay cash. Given the controversy in the comments - my intention was not to say \"\"no, don't talk to the merchant\"\". From the description of the situation it didn't strike me as the merchant would even bother to consider the situation. A less than honest merchant knows that you have no leverage, and since you're a tourist and will probably not be returning there anyway - what's the worst you can do to them? A bad yelp review? You can definitely get in touch with the merchant and ask for a refund, but I would not expect much to come out from that.\"",
"title": ""
},
{
"docid": "372223",
"text": "$1000 is not that much, and I think the best you can do with them is keeping them in a high-yield savings account (look at the online savings accounts that give 1% and more, not the regular bank savings accounts which are worthless). If you need money all of a sudden (for a school book, or rent, or bills, or some other emergency expense), you don't want to deal with selling stocks or funds (which may be at loss) or breaking into your CD's. It is usually considered a good practice to keep cash that would keep you afloat for 5-6 months in savings or some cash equivalent, as an emergency fund.",
"title": ""
},
{
"docid": "248697",
"text": "Maybe there's more to this story, because as written, your sister seems, well, a little irrational. Is it possible that the bank will try to cheat you and demand that you pay a loan again that you've already paid off? Or maybe not deliberately cheat you, but make a mistake and lose track of the fact that you paid? Sure, it's POSSIBLE. But if you're going to agonize about that, what about all the other possible ways that someone could cheat you? What if you go to a store, hand over your cash for the purchase, and then the clerk insists that you never gave him any cash? What if you buy a car and it turns out to be stolen? What if you buy insurance and when you have a claim the insurance company refuses to pay? What if someone you've never met or even heard of before suddenly claims that you are the father of her baby and demands child support? Etc etc. Realistically, banks are fanatical about record-keeping. Their business is pretty much all about record-keeping. Mistakes like this are very rare. And a big business like a bank is unlikely to blatantly cheat you. They can and do make millions of dollars legally. Why should they break the law and risk paying huge fines and going to prison for a few hundred dollars? They may give you a lousy deal, like charge you outrageous overdraft fees and pay piddling interest on your deposit, but they're not going to lie about how much you owe. They just don't. I suggest that you not live your life in fear of all the might-be's. Take reasonable steps to protect yourself and get on with it. Read contracts before you sign, even if the other person gets impatient while you sit there reading. ESPECIALLY if the other person insists that you sign without reading. When you pay off a loan, you should get a piece of paper from the bank saying the loan has been paid. Stuff this piece of paper in a filing cabinet and keep it for years and years. Get a copy of your credit report periodically and make sure that there are no errors on it, like incorrect loan balances. I check mine once every year or two. Some people advise checking it every couple of months. It all depends how nervous you are and how much time you want to spend on it. Then get on with your life. Has your sister had some bad experience with loans in the past? Or has she never borrowed money and she's just confused about how it works? That's why I wonder if there's more to the story, if there's some basis for her fears.",
"title": ""
},
{
"docid": "14989",
"text": "I know this is heresy but if you have funds for significantly more than 6 months of expenses (let's say 12 months), how risky would it be to put it all into stock index funds? Quite risky as if you do need to dip into it, how fast could you get the cash? Also, do you realize the tax implications when you do sell the shares should you have an emergency? In the worst-case scenario, let's say you have a financial emergency at the same time the stock market crashes and loses half its value. You could still liquidate the rest and have sufficient funds for 6 months. Am I underestimating the risks of this strategy? That's not worst case scenario though. Worst case scenario would be another 9/11 where the markets are closed for nearly a week and you need the money but can't get the funds converted to cash in the bank that you can use. This is in addition to the potential wait for a settlement in the case of using ETFs if you choose to go that way. In the case of money market funds, CDs and other near cash equivalents these can be accessed relatively easily which is part of the point. A staggered approach where some cash is kept in house, some in accounts that can easily accessed and some in other investments may make sense though the breakdown would differ depending on how much risk people are willing to take. If it truly is an emergency fund then the odds of needing it should be very slim, so why live with near zero return on that money? Something to consider is what is called an emergency here? For some people a sudden $1,000 bill to fix their car that just broke down is an emergency. For others, there could be emergency trips to visit family that may have gotten into accidents or gotten a diagnosis that they may pass away soon. Consider what do you want to call an emergency here as chances are you may not be considering all that people would think is an emergency. There is the question of what other sources of money do you have to cover should issues arise.",
"title": ""
},
{
"docid": "393838",
"text": "\"tl;dr It's a difference between cash and cash equivalents and net cash and cash equivalents. Download the 2016 annual report from http://www.diageo.com/en-us/investor/Pages/financialreports.aspx On page 99 is the Consolidated Statement of Cash Flows at the bottom is a section \"\"Net cash and cash equivalents consist of:\"\" Net cash and cash equivalents consist of: 2016-06-30 2015-06-30 Cash and cash equivalents 1,089 472 Bank overdrafts (280) (90) 809 382 The difference between net cash of 809 million and 382 million is 427 million, matching the \"\"Change in Cash and Cash Equivalents\"\" from Yahoo. I do not know that bank overdrafts mean in this situation, but appears to cause cash to show up on balance sheet without being reflected in the net cash portions of the cash flow statement. And the numbers seem like balances, not year of year changes like the rest of the statement of cash flows. 2015 net CCE 382 2016 cash flow + 427 ---- 2016 net CCE 809 Cash from overdrafts + 280 ---- 2015 balance sheet cash 1,089\"",
"title": ""
},
{
"docid": "494655",
"text": "\"Holding pure cash is a problem for 401K companies because they would then have follow banking rules because they would be holding your cash on their balance sheets. They don't want to be in that business. Instead, they should offer at least one option as a cash equivalent - a money market fund. This way the money is held by the fund, not by 401K administrator. Money Market funds invest in ultra-short term paper, such as overnight loans between banks and other debt instruments that mature in a matter of days. So it is all extremely liquid, as close to \"\"Money\"\" as you can get without actually being money. It is extremely rare for a money market fund to lose value, or \"\"break the buck.\"\" During the crisis of 2008, only one or two funds broke the buck, and it didn't last long. They had gotten greedy and their short term investments were a little more aggressive as they were trying to get extra returns. In short, your money is safe in a money market fund, and your 401K plan should offer one as the \"\"cash\"\" option, or at least it should offer a short-term bond fund. If you feel strongly that your money should be in actual cash, you can always stop contributing to the 401K and put the money in the bank. This is not a good idea though. Unless you're close to retirement, you'll be much better off investing in a well diversified portfolio, even through the ups and downs of the market.\"",
"title": ""
},
{
"docid": "225030",
"text": "\"It's a scam. The cashier's check will be forged. Craigslist has a warning about it here (item #3). What kind of payment do you think is not fakable? Or at least not likely to be used in scams? When on craigslist - deal only locally and in person. You can ask to see the person's ID if you're being paid by check When being paid by check, how can seeing his/her ID help? In case the check isn't cashable, I can find that person by keeping record of his/her ID? If you're paid by check, the payers details should be printed on the check. By checking the ID you can verify that the details match (name/address), so you can find the payer later. Of course the ID can be faked too, but there's so much you can do to protect yourself. You'll get better protection (including verified escrow service) by selling on eBay. Is being paid by cash the safest way currently, although cash can be faked too, but it is the least common thing that is faked currently? Do you recommend to first deposit the cash into a bank (so that let the bank verify if the cash is faked), before delivering the good? For Craigslist, use cash and meet locally. That rules out most scams as a seller. What payment methods do you think are relatively safe currently? Then getting checks must be the least favorite way of being paid. Do you think cash is better than money order or cashier order? You should only accept cash. If it is a large transaction, you can meet them at your bank, have them get cash, and you receive the cash from the bank. Back to the quoted scam, how will they later manipulate me? Are they interested in my stuffs on moving sale, or in my money? They will probably \"\"accidentally\"\" overpay you and ask for a refund of some portion of the overpayment. In that case you will be out the entire amount that you send back to them and possibly some fees from your bank for cashing a bad check.\"",
"title": ""
},
{
"docid": "367754",
"text": "I feel the need to separate my freelance accounts from my personal accounts. Yes, you should. Should I start another savings account or a current account? Do you need the money for daily spending? Do you need to re-invest in your business? Use a current account. If you don't need the money for business expenses, put it away in your savings account or even consider term deposits. Don't rule out a hybrid approach either (some in savings account, some in current account). What criteria should I keep in mind while choosing a bank? (I thought of SBI since it has a lot of branches and ATMs). If you are involved in online banking and that is sufficient for most of your needs, bank and ATM locations shouldn't matter all that much. If you are saving a good chunk of money, you want to at least have that keep up with inflation. Research bank term deposit interest rates. The tend to be higher than just having your money sit in a savings account. Again, it depends on how and when you expect to need the money. What do I keep in mind while paying myself? Paying yourself could have tax implications. This depends on how are set up to freelance. Are you a business entity or are you an individual? You should look in to the following in India: The other thing to consider is rewarding yourself for the good work done. Pay yourself a reasonable amount. If you decide to expand and hire people going forward, you will have a better sense of business expenses involved when paying salaries. Tips on managing money in the business account. This is a very generic question. I can only provide a generic response. Know how much you are earning and how much your are putting back in to the business. Be reasonable in how much you pay yourself and do the proper research and paperwork from a taxation point of view.",
"title": ""
},
{
"docid": "477357",
"text": "I have also tried Mvelopes in the past, and my experiences match yours. I currently use the desktop version of YNAB:You Need a Budget (YNAB 4), and I like it much better. Where we failed after a while with Mvelopes, we are succeeding with YNAB, and have been now for the last 3.5 years. I don't want this to sound like a commercial for YNAB (I will give important caveats about YNAB later), but here is why I believe we have done better now with YNAB than before with Mvelopes. I hope that these reasons will be useful to you when you are evaluating your next options. As you said, we also found Mvelopes' interface to be slow and glitchy. YNAB 4 is a desktop app (with synching capabilities) that we found to be much quicker and easier to work with than Mvelopes' Flash-based interface. (That was 4 years ago; hopefully Mvelopes has redone their interface since then.) We also struggled with Mvelopes' connection with our banks. With YNAB 4, there is no connection to the bank: everything has to be entered manually. I initially thought this might be worse, but for us it has been better. I can either enter transactions as they happen on the mobile app, or I can hold on to receipts and enter them every day or two in the evening, categorizing as I go. We always have an up-to-date picture of our finances, and we don't have to mess with trying to match up downloaded transactions that have been screwed up, duplicated, or are missing. We aren't really using YNAB much differently than we were using Mvelopes, but we have learned a few tricks that I think have contributed to our success. One of the things we do differently is that I don't obsess about the cash accounts too much. Cash accounts, for us, are the hardest to keep track of, because most of our cash transactions don't have a receipt: we are paying a friend or family member for something, or leaving a tip, or something like that which we forget about when it comes time to enter into the software. As a result, the cash account balances get off. I periodically enter a correcting transaction to get the balances right, and have a budget category specifically for this that we have to put money in for these unknown transactions. Fortunately for us, our cash spending is a small percent of our total spending (we usually pay with a credit card) so this bit of untracked spending isn't that big of a concern. With YNAB, the current month's budget is right in front of you as soon as you open up the app, which makes it easy to adjust your budget during the month, if necessary. With Mvelopes (at least how their app worked 4 years ago), the budget was somewhat hidden after you funded your budget categories, and it was a bit of a pain to move money around between categories. The ability to adjust your budget in the middle of the month is crucial; if you don't do that, you'll get frustrated the first time you find that you don't have enough money in a category for something you need. YNAB makes it very easy to move money around inside your budget. That having been said, you need to be aware that the current version of YNAB is not a desktop application but a web-based app. YNAB 4, the old desktop version which we have been using, is officially unsupported as of the end of 2016. However, I see that it is still available for sale, if you are interested in it, the YNAB4 help site is still up, and the mobile app you would need to work with it on your phone (called YNAB Classic) is still in the app store. As I said, the current YNAB is now a web app, complete with automatic downloading of transactions from your bank. I have no experience with it (other than playing around with it a little), and so I can't tell you how quick the interface is or how well the auto-downloading of transactions works. As an alternative, another web-based solution is EveryDollar, from Dave Ramsey's company. (I have never tried it.) The advantage of this one is that it is free if you choose not to link it to your banks; the automatic downloading of transactions is a paid feature. I wrote an answer a couple of years ago in which I describe two different approaches that budgeting software packages tend to take. I'm not familiar with Buxfer, so I don't know which approach it takes, but perhaps that answer will help you evaluate all of your software options. On the behavior side of things, besides the relaxing of the cash accounting I mentioned above, we also involve my wife a little less in the budgeting process than we used to. (This is by her choice!) I am the one who enters all the transactions into the software (she hands me all her receipts), I reconcile the accounts at the end of the month, and I set the budget for the next month. We have been doing this long enough now that she knows what the budget is, and we only need to discuss it if we want to do something different with the budget than we have been doing in the past. She has the YNAB app on her phone and can see where we are at with all of our budget categories.",
"title": ""
},
{
"docid": "53602",
"text": "There are a few options that I know of, but pretty much every one of them will cost more than you want to pay in fees, probably. You should be able to write a check/cheque to yourself. You might check with your US bank branch to see how much of a limit they'd have. You can also use a Canadian ATM card at a US ATM. The final option would be to use a Canadian credit card for all of your purchases in the US, and then pay the bill from the Canadian bank account. I don't recommend the last option because if you're not careful to pay off the bill every month, you're running up debt. Also, it's hard to pay some kinds of expenses by credit card, so you'd want a way to have cash available. Another option would be to use a service like Paypal or Hyperwallet to send yourself the money. Again, you'd be paying fees, but these might be cheaper than what the bank would charge. There may be other options, but these are the ones I'm aware of. Whatever you choose, look carefully at what the fees would be, and how long you'd have to wait to get the money. If you can plan ahead a bit, and take larger chunks of money at a time, that should help keep the fees down a bit. I believe there's also a point where you start having to report these transfers to the US government. The number $10,000 stick in my head, but they may have changed that recently.",
"title": ""
},
{
"docid": "351340",
"text": "In my opinion, every person, regardless of his or her situation, should be keeping track of their personal finances. In addition, I believe that everyone, regardless of their situation, should have some sort of budget/spending plan. For many people, it is tempting to ignore the details of their finances and not worry about it. After all, the bank knows how much money I have, right? I get a statement from them each month that shows what I have spent, and I can always go to the bank's website and find out how much money I have, right? Unfortunately, this type of thinking can lead to several different problems. Overspending. In olden days, it was difficult to spend more money than you had. Most purchases were made in cash, so if your wallet had cash in it, you could spend it, and when your wallet was empty, you were required to stop spending. In this age of credit and electronic transactions, this is no longer the case. It is extremely easy to spend money that you don't yet have, and find yourself in debt. Debt, of course, leads to interest charges and future burdens. Unpreparedness for the future. Without a plan, it is difficult to know if you have saved up enough for large future expenses. Will you have enough money to pay the water bill that only shows up once every three months or the property tax bill that only shows up once a year? Will you have enough money to pay to fix your car when it breaks? Will you have enough money to replace your car when it is time? How about helping out your kids with college tuition, or funding your retirement? Without a plan, all of these are very difficult to manage without proper accounting. Anxiety. Not having a clear picture of your finances can lead to anxiety. This can happen whether or not you are actually overspending, and whether or not you have enough saved up to cover future expenses, because you simply don't know if you have adequately covered your situation or not. Making a plan and doing the accounting necessary to ensure you are following your plan can take the worry out of your finances. Fear of spending. There was an interesting question from a user last year who was not at all in trouble with his finances, yet was always afraid to spend any money, because he didn't have a budget/spending plan in place. If you spend money on a vacation, are you putting your property tax bill in jeopardy? With a good budget in place, you can know for sure whether or not you will have enough money to pay your future expenses and can spend on something else today. This can all be done with or without the aid of software, but like many things, a computer makes the job easier. A good personal finance program will do two things: Keeps track of your spending and balances, apart from your bank. The bank can only show you things that have cleared the bank. If you set up future payments (outside of the bank), or you write a check that has not been cashed yet, or you spend money on a credit card and have not paid the bill yet, these will not be reflected in your bank balance online. However, if you manually enter these things into your own personal finance program, you can see how much money you actually have available to spend. Lets you plan for future spending. The spending plan, or budget, lets you assign a job to every dollar that you own. By doing this, you won't spend rent money at the bar, and you won't spend the car insurance money on a vacation. I've written before about the details on how some of these software packages work. To answer your question about double-entry accounting: Some software packages do use true double-entry accounting (GnuCash, Ledger) and some do not (YNAB, EveryDollar, Mvelopes). In my opinion, double-entry accounting is an unnecessary complication for personal finances. If you don't already know what double-entry accounting is, stick with one of the simpler solutions.",
"title": ""
},
{
"docid": "265551",
"text": "That's not what he's saying at all. Basically most of his argument (4 of 6 points) is the connection between bond prices and equity prices. It's not particularly interesting but it definitely doesn't always apply either. If bond yields fall, then so too should equity earnings yields if spreads remain relatively constant, i.e. higher equity prices. Additionally, if bond yields are low, then any future equity growth gets capitalized at a much higher value because discount rates are much lower. Again, not particularly insightful. The two interesting comments were about oil and cash as a % of assets at financial institutions. Both of these are likely linked to falling or low rates above, because banks can't invest profitably at low rates and hence hold cash and equivalents instead, and oil prices are more likely to fall in a low or falling inflation environment (implied by the low rates or Fed tightening). Really, I think hes's saying something more obvious but not necessarily trivial, which is if one asset class goes up, so too is another related one.",
"title": ""
},
{
"docid": "55422",
"text": "\"This is kind of halfway between the stuff I was talking about, and halfway to the stuff I don't want to get into. But it raises some very legitimate and relevant points that are kind of separate from the \"\"gold standard\"\" debate. The big question, taking the banks out of it, is a two-fold one, that goes something like this: - Is it possible to have a modern economy without credit-markets? and... - Is it possible to have functional credit-markets without some sort of fractional-reserve currency? For example, let's say Toyota decides to design a new car. Before they can sell a single unit, someone in Africa or somewhere has to dig up the minerals to make it, someone has to design it, tools have to be re-worked, all that kind of stuff. Building ONE CAR of a new design might cost [a billion dollars or more](http://en.wikipedia.org/wiki/Lexus_LS). Obviously it's not realistic for Toyota to expect the first customer to pay that much: they amortize the design and tooling costs over the expected production run or whatever. Moreover, we might say that only companies that have amassed a billion dollars in physical gold from previous sales should be *able* to do that kind of thing... But there is a relevant question of whether this makes any kind of sense. Should Toyota have to literally ship palettes or dufflebags of physical gold through middlemen and suppliers to the miner in Africa, down to the actual guy who digs up the aluminum or whatever, in order to make this transaction happen? How would that work, without some sort of intermediary \"\"promises\"\"? I'm imagining a scenario where Toyota sends an armored truck full of gold out to go find half-a-ton of aluminum. The drivers cannot rely on any promises or \"\"fractional reserve\"\", they must only trade the physical gold in their truck for actual aluminum or expenses along the way... This starts to defy sanity, in a modern economy. You have to rely on the promises of middle-men and suppliers and contractors and so on. And the instant you have promises, you have fractional reserves, because people are getting paid and money is changing hands that hasn't been minted yet. It's not just the impracticality of your local supermarket having to trade a bag full of gold for a shipment of lettuce, it's that contracts to purchase would be meaningless, because the driver would have had to give a smaller bag of gold to the supplier, who gave a smaller bag of gold to the grower, and so on... moreover, the supermarket would have to just wait to see what entrepreneurial driver shows up and what they have. The supermarket obviously cannot \"\"order\"\" a hundred heads of lettuce per week with a promise to pay, not unless we also give the supplier permission to order a hundred heads of lettuce a week from the grower, and the grower permission to order seed and hire workers sufficient to grow a hundred heads of lettuce a week, and the workers permission to set up car-payments to get to work, and the seed-supplier to so on and so on... That sequence of promises is ipso-facto a \"\"fractional reserve\"\" system, with or without a central bank. People are promising to deliver gold/cash/whatever that they don't currently have. Moreover, it is entirely possible in a gold-denominated currency for everyone to *keep* those promises, since the gold, like any currency, just keeps changing hands and cycling through the economy. Your example of \"\"gold certificates\"\" is exactly equivalent to privately-arranged contracts/promises to produce a certain amount of gold on completion. It's promises all the way down, unless we insist on instant cash-transactions, e.g., literally handing an employee a dollar's worth of gold every five minutes, or whatever. If the employee is counting on the good-faith of the employer to settle up at the end of the day or week, then we have a fractional-reserve system whether decreed or not. When you buy an iPhone or a laptop, someone had to dig up the stuff to make it, out of the ground. When you buy a cheeseburger, someone had to grow wheat and someone else had to raise and kill a cow. It's not a reasonable proposition that they should wait for you to show up with a bag of gold before doing those things, in this day and age. We trade in promises and IOUs. Sometimes that backfires, sometimes catastrophically. But it's remarkable how well it *does* work, most of the time, and how much better it works than the times and places where people had to trade physical goods for physical goods. This is not an argument against a gold-backed currency.\"",
"title": ""
},
{
"docid": "159235",
"text": "No cash is necessary for most people. In the modern day in the US there is no need to keep paper currency around for emergencies; any sort of emergency that knocked out all of the ability to use plastic (ATMs, credit cards, etc.) for an extended period of time AND knocked your bank out of service would be of the level that cash might not have any value either. Your $100 of cash for natural disasters is likely more than enough, and even that I wouldn't necessarily consider a vital thing in this day where even a major natural disaster probably isn't going to have too much impact on the financial sector outside of the immediate area (that you should be exiting quickly). Keep however much cash around that you need for day to day cash expenses, and that should be enough. The level of emergency that would suggest cash being needed would probably need more than you'd actually want to keep around, anyway - i.e., a complete collapse of the American or World financial system would imply you need months' worth of cash. That's just not feasible, nor is it practical financially. You should have your emergency fund making at least a bit of interest - 1% or so isn't hard to get right now, and in the near future that may increase substantially if interest rates go up. It also would make you a substantial theft target if it were known you had months' worth of cash around the house (i.e., thousands of dollars). Safes don't necessarily give you sufficient protection unless you've got a very good safe - commercial ones are only as safe as the ability to crack them and/or transport them is. Now, if you find yourself regularly out at 2am and run out of cash, and you live somewhere that ATMs don't exist, and you find yourself needing to pay cab drivers from time to time after a drunk bender... then I'd keep at least one cab's worth of cash at home.",
"title": ""
},
{
"docid": "160011",
"text": "\"While I certainly agree with the principle of paying down debt, there is some value in having a healthy cash cushion. If an emergency expense were to come up, and your credit has been cut-off or reduced to the point where you have no excess credit, then having real cash on hand is critical. I would perform the following thought-experiment: What if my available credit had been cut off? How much would I need in cash to survive for 1 month, 3 months, 5 months, etc.? Consider what time period you'd be comfortable with, and set that amount as your minimum desired cash on hand. While it may seem extreme to not have access to credit at all, during the credit crisis many banks and lenders \"\"tightened\"\" their lending: reducing credit limits, closing lines of credit, calling loans, raising rates, etc. Suze Orman recommends cash savings equivalent to 8 months living expenses. That doesn't mean 8 months salary, but 8 months of what it would take to live on. At one point, in the midst of the economic crisis, I thought that made sense. The Simple Dollar blog considers Suze's recommendation and the idea of emergency fund vs. debt repayment. Worth reading: Is Suze Right? Do Emergency Funds Now Trump Debt Repayment?.\"",
"title": ""
},
{
"docid": "350933",
"text": "A CD is guaranteed to pay its return on maturation. So if you need a certain amount of money at a specific time in the future, the CD is a more reliable way of getting it. The stock market might give you more money or less. More is obviously OK. Less is not if you're planning to pay basic expenses with it, e.g. food, rent, etc. Most retirement portfolios will have a mix of investments. Some securities (stocks and bonds), some guaranteed returns (CDs, treasuries), and some cash equivalents (money market, savings, and checking accounts). Cash equivalents are good for short term expenses and an emergency fund. Guaranteed returns are good for medium term expenses. Securities are good for the long term. Once retired, the general system is to maintain enough cash equivalents for the next few months of expenses and emergencies. Then schedule CDs for the next few years so that you have a predictable amount. Finally, keep the bulk of your wealth in securities. As you get older, your potential emergencies increase and your need for savings decreases, so the mix shifts more and more to the cash equivalents and guaranteed returns and away from securities. CDs have limited use prior to retirement (and the couple years right before retirement), mainly saving up for a large purchase like a house, car, or major appliance. Even there if you have the option of delaying the purchase, that might allow you to use securities instead. Perhaps some of your emergency fund in a short term CD that you keep rolling over. Note that the problem isn't so much that securities will fall. It's that they'll fall right when you need the money. So rather than sell 1% of your securities to meet your needs, you have to sell 2%. That's a dead weight loss of 1% that you have to deduct from your returns. That roughly matches the drop from the height of 2007 to the trough of 2009 of the S&P 500. And it was 2012 before it recovered. If in 2007, you had put the 1% of your portfolio in a two-year CD, you'd be ahead even at zero interest in 2009.",
"title": ""
},
{
"docid": "180673",
"text": "I don't think there's any law against having lots of bank accounts. But what are you really gaining? Every new account is a paperwork hassle. Every new account is another target for con men who might steal your information and write bad checks or make phony credit card purchases in your name. Yes, it's not unreasonable to have a credit card or two that you keep for emergencies. I'd advise anyone with running up debts while having no idea how you will pay them off. But to say that you might keep some credit available so that if you have a legitimate emergency -- like, say, your car breaks down and you don't have the cash to fix it and you can't get to work without it -- you have some a fallback. But do you really need ten credit cards for that sort of thing? And how much credit are they giving you on each card? I don't know how the banks work this, but I'd think if they're rational, they'd consider your total credit before giving you more. I have three credit cards that I use regularly -- two personal and one business. And I find that a real pain to keep track of, to make sure that I keep each one paid by the due date and to keep a handle on how much I owe and so forth. I can't imagine trying to deal with ten. I suppose you could just stuff all these cards in a drawer and only use them in case of emergency.",
"title": ""
},
{
"docid": "570318",
"text": "I'm not sure about your first two options. But given your situation, a variant of option three seems possible. That way you don't have to throw away your appraisal, although it's possible that you'll need to get some kind of addendum related to the repairs. You also don't have your liquid money tied up long term. You just need to float it for a month or two while the repairs are being done. The bank should be able to preapprove you for the loan. Note that you might be better off without the loan. You'll have to pay interest on the loan and there's extra red tape. I'd just prefer not to tie up so much money in this property. I don't understand this. With a loan, you are even more tied up. Anything you do, you have to work with the bank. Sure, you have $80k more cash available with the loan, but it doesn't sound like you need it. With the loan, the bank makes the profit. If you buy in cash, you lose your interest from the cash, but you save paying the interest on the loan. In general, the interest rate on the loan will be higher than the return on the cash equivalent. A fourth option would be to pay the $15k up front as earnest money. The seller does the repairs through your chosen contractor. You pay the remaining $12.5k for the downpayment and buy the house with the loan. This is a more complicated purchase contract though, so cash might be a better option. You can easily evaluate the difficulty of the second option. Call a different bank and ask. If you explain the situation, they'll let you know if they can use the existing appraisal or not. Also consider asking the appraiser if there are specific banks that will accept the appraisal. That might be quicker than randomly choosing banks. It may be that your current bank just isn't used to investment properties. Requiring the previous owner to do repairs prior to sale is very common in residential properties. It sounds like the loan officer is trying to use the rules for residential for your investment purchase. A different bank may be more inclined to work with you for your actual purchase.",
"title": ""
},
{
"docid": "22268",
"text": "\"They don't actually need to. They accept deposits for historical reasons and because they make money doing so, but there's nothing key to their business that requires them to do so. Here's a decent summary, but I'll explain in great detail below. By making loans, banks create money. This is what we mean when we say the monetary supply is endogenous. (At least if you believe Sir Mervyn King, who used to run England's central bank...) The only real checks on this are regulatory--capitalization requirements and reserve requirements, which impose a sort of tax on a bank's circulating loans. I'll get into that later. Let's start with Why should you believe that story--that loans create deposits? It seems like a bizarre assertion. But it actually matches how banks behave in practice. If you go borrow money from a bank, the loan officer will do many things. She'll want to look at your credit history. She'll want to look at your income and assets. She'll want to look at what kind of collateral or guarantees you're providing that the loan will be repaid. What she will not do is call down to the vaults and make sure that there's enough bills stacked up for them to lend out. Loans are judged based on a profitability function determined by the interest rate and the loan risk. If those add up to \"\"profitable\"\", the bank makes the loan. So the limiting factor on the loans a bank makes are the available creditworthy borrowers--not the bank's stock of cash. Further, the story makes sense because loans are how banks make money. If a bank that was short of money suddenly stopped making loans, it'd be screwed: no new loans = no way to make money to pay back depositors and also keep the lights on = no more bank. And the story is believable because of the way banks make so little effort to solicit commercial deposit business. Oh sure, they used to give you a free toaster if you opened an account; but now it's really quite challenging to find a no-fee checking account that doesn't impose a super-high deposit limit. And the interest paid on savings deposits is asymptotically approaching zero. If banks actually needed your deposits, they'd be making a lot more of effort to get them. I mean, they won't turn up their noses; your deposited allowance is a couple basis points cheaper to the bank than borrowing from the Fed; but banks seem to value small-potatoes depositors more as a source of fees and sales opportunities for services and consumer credit than as a source of cash. (It's a bit different if you get north of seven figures, but smaller depositors aren't really worth the hassle just for their cash.) This is where someone will mention the regulatory requirements of fractional reserve banking: banks are obliged by regulators to keep enough cash on hand to pay out a certain percentage of deposits. Note nothing about loans was said in that statement: this requirement does not serve as a check on the bank making bad loans, because the bank is ultimately liable to all its depositors for the full value of their deposits; it's more making sure they have enough liquidity to prevent bank runs, the self-fulfilling prophecy in which an undercapitalized bank could be forced into bankruptcy. As you noted in your question, banks can always borrow from the Fed at the Fed Discount Rate (or from other banks at the interbank overnight rate, which is a little lower) to meet this requirement. They do have to pledge collateral, but loans themselves are collateral, so this doesn't present much of a problem. In terms of paying off depositors if the bank should collapse (and minimizing the amount of FDIC insurance payout from the government), it's really capital requirements that are actually important. I.E. the bank has to have investors who don't have a right to be paid back and whose investment is on the hook if the bank goes belly-up. But that's just a safeguard for the depositors; it doesn't really have anything to do with loans other than that bad loans are the main reason a bank might go under. Banks, like any other private business, have assets (things of value) and liabilities (obligations to other people). But banking assets and liabilities are counterintuitive. The bank's assets are loans, because they are theoretically recoverable (the principal) and also generate a revenue stream (the interest payments). The money the bank holds in deposits is actually a liability, because it has to pay that money out to depositors on demand, and the deposited money will never (by itself) bring the bank any revenue at all. In fact, it's a drain, because the bank needs to pay interest to its depositors. (Well, they used to anyway.) So what happens when a bank makes a loan? From a balance sheet perspective, strangely enough, the answer is nothing at all. If I grant you a loan, the minute we shake hands and you sign the paperwork, a teller types on a keyboard and money appears in your account. Your account with my bank. My bank has simultaneously created an asset (the loan you now have to repay me) and an equal-sized liability (the funds I loaned you, which are now deposited in your account). I'll make money on the deal, because the interest you owe me is a much higher rate than the interest I pay on your deposits, or the rate I'd have to pay if I need to borrow cash to cover your withdrawal. (I might just have the cash on hand anyway from interest and origination fees and whatnot from previous loans.) From an accounting perspective, nothing has happened to my balance sheet, but suddenly you owe me closing costs and a stream of extraneous interest payments. (Nice work if you can get it...) Okay, so I've exhaustively demonstrated that I don't need to take deposits to make loans. But we live in a world where banks do! Here's a few reasons: You can probably think of more, but at the end of the day, a bank should be designed so that if every single (non-borrowing) depositor withdrew their deposits, the bank wouldn't collapse or cease to exist.\"",
"title": ""
},
{
"docid": "310112",
"text": "\"The first consideration for the banking part of your portfolio is safety. In the United States that is FDIC protection, or the equivalent for a Credit Union. The second consideration is does it have the level of service you need. For this I mean the location of branches, ATMs, or its online services meet your needs for speed, accuracy, and ability to access or move the money as you need. The rest are then balanced on the extras. For your situation those extras include the ability to make free trades. For other it might be a discount on their mortgage. For others it is free checking. In your current situation if the first two things are met, and you are using those extra benefits then don't change. For me the free trades wouldn't be a benefit, so any major degradation in the safety and service would cause me to leave. Keep in mind that free services exist to entice you to make a deposit: which they can then make money by lending it out; or they offer a free service to entice you to use a service they can charge you to use. All Free services come with a cost. I earned a completely paltry $3.33 YTD over the last 9 months on my savings at my bank presumably in exchange for these \"\"free\"\" trades. Without knowing how much you had deposited in your savings account there is no way to know how much you could have made at the bank across the street. But with the low rates of the last decade there is not big money to be made off the emergency savings of a typical american family.\"",
"title": ""
},
{
"docid": "392885",
"text": "\"20-year Treasury Bonds are not equivalent to cash, not even close. Even though the bonds are backed by the full faith and credit of the U.S. Government, they are long-term debt and therefore their principal value will fluctuate considerably as market interest rates change. When interest rates rise, the market value of 20-year bonds will drop, and drop more than shorter-term bonds would. Your principal is not protected in the short term. Principal is only guaranteed returned at the 20-year maturity of those bonds. But, oops, there is no maturity on the 20-year bond ETFs because every year the ETF rolls the 19-year positions into new 20-year positions! ;-) For an \"\"equivalent to cash\"\" piece of a portfolio, I'd want my principal to be intact over the short term, and continually reinvested at the higher short-term rates as rates are rising. Reinvesting at short-term rates can be an inflation-hedge. But, money locked in for 20-years is a sitting duck for inflation. Still, inflation aside, why do we want our \"\"equivalent to cash\"\" position to be relatively liquid and principal-protected? When it comes time to rebalance your portfolio after disastrous equity and/or bond returns, you've got in your cash component some excess weighting since it was unaffected by the disastrous performance. That excess cash is ready to be deployed to purchase equities and/or bonds at the lower current prices. Rebalancing from cash can add a bonus to your returns and smooth volatility. If you have no cash component and only equities and bonds, you have no money to deploy when both equities and bonds are depressed. You didn't keep any powder dry. And, BTW, I would personally keep a bit more than 3% of my powder dry. Consider a short-term cash deposit or good money-market fund for your \"\"equivalent to cash\"\" position.\"",
"title": ""
},
{
"docid": "194669",
"text": "\"While you want it to grow faster than inflation, there are things like I-bonds that can carry some inflation protection with them for an idea that may make sense for part of this. There are now some more details and I'd think this seems alright initially though I would suggest considering having some kind of on-going plan to handle periodically seeing how much more to invest here and what kind of taxes will this generate for you as taxable accounts can carry a mix of dividends, interest and capital gains that you may have to pay even though you didn't see the gain yourself. Keep in mind that if you do go with a big-name investment bank, this could well add more fees as well as other stuff. Lehman Brothers was a big name investment bank once upon a time and they went broke. While you may want to be hands-off, I'd still suggest having some kind of timeline for how often are your investments to be reviewed and things re-allocated. Each quarter, semi-annually, or annual? There isn't so much a right or wrong answer here as much as I'd point out that one should be aware of the trade-offs in each case. If you take annual and wonder each week how it is doing, then something a bit more frequent may make sense. On the other hand, some people may well \"\"set it and forget it\"\" which can work as long as there is something to know about where to go if something does go broke. As these are managed investments, the SIPC check I'd make may not hold though this would be the equivalent of FDIC for deposits when dealing with securities. The REIT can be useful for diversification, sure. You do realize that there may be some interesting taxes for you in the next few years given the nature of a REIT investment, right? The \"\"Return of Capital\"\" that a REIT may pass through as a REIT to maintain its tax status must distribute 90% of its net income each year that can be quite a off shoot of funds. Where would those proceeds be invested? This isn't mentioned in your post and thus I'm curious as if the REIT passes out a dividend yield of say 5% then this is $2,000/year that could go somewhere.\"",
"title": ""
},
{
"docid": "369445",
"text": "After talking to two CPAs it seems like managing it using an imprest system is the best idea. The base characteristic of an imprest system is that a fixed amount is reserved and later replenished as it runs low. This replenishment will come from another account source, e.g., petty cash will be replenished by cashing a cheque drawn on a bank account. Petty cash imprest system allows only the replenishment of the spend made. So, if you start the month with €100 in your petty cash float and spend €90 of that cash in the month, an amount of €90 will be then placed in your petty cash float to bring the balance of your petty cash float back to €100. The replenishment is credited to the primary cash account, usually a bank account (Dr - Petty Cash a/c, Cr - Bank a/c) and the debits will go to the respective expense accounts, based on the petty cash receipt dockets (Dr- Expense a/c, Cr - Petty Cash a/c). In a non imprest system where a fixed amount is issued every month, e.g., €100 every time cash is required, there is no incentive to ensure all money issued has been documented because when money is all spent a check for a fixed amount is issued. It is much more difficult to reconcile a non imprest system as you never know how much exactly should be in the float. In an imprest system the amount requested is documented, the documentation being the petty cash dockets and their associated receipts or invoices. So at all times you can check how much should be left in the petty cash float by deducting the amount spent from the opening petty cash float.",
"title": ""
},
{
"docid": "72168",
"text": "The prime rate is the interest rate banks use amongst themselves to lend money to each other only. It is used as the basis (sometimes) for what interest rate banks charge you. The prime rate is based loosely on the Fed rate. There is a committee that meets regularly to set this and other industry interest rates. http://en.wikipedia.org/wiki/Prime_rate I am not 100% positive the following is totally accurate The banks keep our deposits and pay us interest for doing so. They are paying us interest because they take yours, mine and everybody elses deposits as a large lump sum and invest that money. Sometimes as business loans, sometimes as mortgages and sometimes as credit card. The banks have a book of business that will be EXACTLY how much credit they have extended to everybody. But they do not keep that amount of cash in the vaults, only some smaller percentage of that large amount. When I use my credit card and they need to transfer money to amazon.com, if they don't happen to have enough cash that day, they will just borrow from another bank that does, and the interest rate they pay to do so is the prime rate. Since they are paying interest on the money they borrow to pay the debt I charged because they told me my credit was worth so much (...???...) they charge me a little bit more than that. Hence your credit card or mortgage's APR being based on the prime rate. I THINK that is what they do If I am wrong leave a comment and I will update, or the mods can.",
"title": ""
},
{
"docid": "405212",
"text": "\"In a comment you say, if the market crashes, doesn't \"\"regress to the mean\"\" mean that I should still expect 7% over the long run? That being the case, wouldn't I benefit from intentionally unbalancing my portfolio and going all in on equities? I can can still rebalance using new savings. No. Regress to the mean just tells you that the future rate is likely to average 7%. The past rate and the future rate are entirely unconnected. Consider a series: The running average is That running average is (slowly) regressing to the long term mean without ever a member of the series being above 7%. Real markets actually go farther than this though. Real value may be increasing by 7% per year, but prices may move differently. Then market prices may revert to the real value. This happened to the S&P 500 in 2000-2002. Then the market started climbing again in 2003. In your system, you would have bought into the falling markets of 2001 and 2002. And you would have missed the positive bond returns in those years. That's about a -25% annual shift in returns on that portion of your portfolio. Since that's a third of your portfolio, you'd have lost 8% more than with the balanced strategy each of those two years. Note that in that case, the market was in an over-valued bubble. The bubble spent three years popping and overshot the actual value. So 2003 was a good year for stocks. But the three year return was still -11%. In retrospect, investors should have gone all in on bonds before 2000 and switched back to stocks for 2003. But no one knew that in 2000. People in the know actually started backing off in 1998 rather than 2000 and missed out on the tail end of the bubble. The rebalancing strategy automatically helps with your regression to the mean. It sells expensive bonds and buys cheaper stocks on average. Occasionally it sells modest priced bonds and buys over-priced stocks. But rarely enough that it is a better strategy overall. Incidentally, I would consider a 33% share high for bonds. 30% is better. And that shouldn't increase as you age (less than 30% bonds may be practical when you are young enough). Once you get close to retirement (five to ten years), start converting some of your savings to cash equivalents. The cash equivalents are guaranteed not to lose value (but might not gain much). This gives you predictable returns for your immediate expenses. Once retired, try to keep about five years of expenses in cash equivalents. Then you don't have to worry about short term market fluctuations. Spend down your buffer until the market catches back up. It's true that bonds are less volatile than stocks, but they can still have bad years. A 70%/30% mix of stocks/bonds is safer than either alone and gives almost as good of a return as stocks alone. Adding more bonds actually increases your risk unless you carefully balance them with the right stocks. And if you're doing that, you don't need simplistic rules like a 70%/30% balance.\"",
"title": ""
},
{
"docid": "145238",
"text": "\"Judging from your comments, you seem to be confused about the way banking works. Banks can only lend out money that they actually have: whether from deposits or investors or loans taken from other banks/government entities. The rules on how this works varies from country to country, but the principle is always the same. There is no magic money. Let's imagine a closed system. There's only one town, and that town only has one bank. There are 100 people total in town, and each has $10,000. Everyone deposits all of their money in the bank. The bank now has $1,000,000 in total deposits. You take a loan for $100,000 and buy a house. The bank now has $900,000. You make your payments of $965 per month: $833 of interest and $132 toward principal. In this ideal world, the bank has no costs associated with doing business. After one month, the bank has $1,000,000 in deposits, $900,965 in cash on hand, $99,868 in loans, and $833 in profit (from interest). Now here's the confusing part. You bought a house from someone. That person also lives in town. He takes the $100,000 you gave him and... deposits it in the bank. The bank now has $1,100,000 in deposits, $1,000,965 in cash, $99,868 in loans, and $833 in profit. Assume 10 more people buy houses at $100,000 each, taking loans for that whole amount (for the same terms you did). Assume those sellers then deposit the money back in the bank. The bank now has $2,100,000 in deposits, $1,000,965 in cash, $1,099,868 in loans, and $833 in profit. The bank is taking in $10,615 per month ($965 x 11) in loan payments, making profit of $9,163 ($833 x 11) per month from interest. This process of loans and deposits and payments can go on forever without any outside influence. This is the primary way money is created. It's like printing money without the paper. Of course, we're not in a closed system. Banks are limited in endlessly creating money, primarily by two things: Reserve Requirements are set by government agencies. They might say banks can lend until their cash on hand (or liquid equivalent) is, at minimum, 35% of total deposits. So a bank with $1,000,000 in deposits would have to keep $350,000 in cash at any given time. Capital Requirements work largely the same way. It's more the bank saying, \"\"What happens if a bunch of people want their deposits back?\"\" They plan a reasonable amount of cash to have on hand for that scenario.\"",
"title": ""
},
{
"docid": "120691",
"text": "Credit cards are often more fool proof, against over-drawing. Consider Bill has solid cash flow, but most of their money is in his high interest savings account (earning interest) -- an account that doesn't have a card, but is accessible via online banking. Bill keeps enough in the debit (transactions) account for regular spending, much of which comes out automatically (E.g. rent, utilities), some of which he spends as needed eg shopping, lunch. On top of the day to day money Bill keeps an overhead amount, so if something happens he doesn't overdraw the account -- which would incur significant fees. Now oneday Bill sees that the giant flatscreen TV he has been saving for is on clearence sale -- half price!, and there is just one left. It costs more than he would normally spend in a week -- much more. But Bill knows that his pay should have just gone in, and his rent not yet come out. Plus the overhead he keep in the account . So there is money in his debit account. When he gets home he can open up online banking and transfer from his savings (After all the TV is what he was saving for) What Bill forgets is that there was a public holiday last week in the state where payroll is operated, and that his pay is going to go in a day late. So now he might have over drawn the account buying the TV, or maybe that was fine, but paying the rent over draws the account. Now he has a overdraft fee, probably on the order of $50. Most banks (at least where I am), will happily allow you to overdraw you account. Giving you a loan, at high interest and with an immediate overdraft fee. (They do this cos the fee is so high that they can tolerate the risk of the non-assessed loan.) Sometimes (if you ask) they don't let you do it with your own transcations (eg buying the TV), but they do let you do it on automated payements (eg the Rent). On the other hand banks will not let you over draw a credit card. They know exactly how much loan and risk they were going to take. If Bill had most of his transactions going on his credit card, then it would have just bounced at the cash register, and Bill would have remembered what was going on and then transferred the money. There are many ways you can accidentally overdraw your account. Particularly if it is a shared account.",
"title": ""
},
{
"docid": "302448",
"text": "$23,000 Student Loans at 4% This represents guaranteed loss. Paying this off quickly is a conservative move, while your other investments may easily surpass 4% return, they are not guaranteed. Should I just keep my money in my savings account since I want to keep my money available? Or are there other options I have that are not necessarily long term may provide better returns? This all depends on your plans, if you're just trying to keep cash in anticipation of the next big dip, you might strike gold, but you could just as easily miss out on significant market gains while waiting. People have a poor track record of predicting market down-turns. If you are concerned about how exposed to market risk you are in your current positions, then you may be more comfortable with a larger cash position. Savings/CDs are low-interest, but much lower risk. If you currently have no savings (you titled the section savings, but they all look like retirement/investment accounts), then I would recommend focusing on that first, getting a healthy emergency fund saved up, and budgeting for your car/house purchases. There's no way to know if you'd be better off investing everything or piling up cash in the short-term. You have to decide how much risk you are comfortable with and act accordingly.",
"title": ""
}
] |
120201
|
Freddie Mercury was the singer of Queen.
|
[
{
"docid": "Freddie_Mercury",
"text": "Farrokh `` Freddie '' Mercury ( née Bulsara ; 5 September 1946 -- 24 November 1991 ) was a British singer , songwriter and record producer , known as the lead vocalist and co-principal songwriter of the rock band Queen . He also became known for his flamboyant stage persona and four-octave vocal range . Mercury wrote and composed numerous hits for Queen ( including `` Bohemian Rhapsody '' , `` Killer Queen '' , `` Somebody to Love '' , `` Do n't Stop Me Now '' , `` Crazy Little Thing Called Love '' , and `` We Are the Champions '' ) ; occasionally served as a producer and guest musician ( piano or vocals ) for other artists ; and concurrently led a solo career while performing with Queen . Mercury was born of Parsi descent in the Sultanate of Zanzibar and grew up there and in India until his mid-teens , before moving with his family to Middlesex , England -- ultimately forming the band Queen in 1970 with Brian May and Roger Taylor . Mercury died in 1991 at age 45 due to complications from AIDS , having confirmed the day before his death that he had contracted the disease . In 1992 , Mercury was posthumously awarded the Brit Award for Outstanding Contribution to British Music , and had a tribute concert held at Wembley Stadium , London . As a member of Queen , he was inducted into the Rock and Roll Hall of Fame in 2001 , the Songwriters Hall of Fame in 2003 , the UK Music Hall of Fame in 2004 , and the band received a star on the Hollywood Walk of Fame in 2002 . In 2002 , he was placed at number 58 in the BBC 's poll of the 100 Greatest Britons . Consistently voted one of the greatest singers in the history of popular music , Mercury was voted best male singer of all time in a 2005 poll organised by Blender and MTV2 ; was elected in 2009 as the best rock singer of all time by Classic Rock readers ; was ranked at 18 on the 2008 Rolling Stone list of the 100 greatest singers ever ; -- and was described by Greg Prato of AllMusic as `` one of rock 's greatest all-time entertainers , '' with `` one of the greatest voices in all of music . ''",
"title": ""
}
] |
[
{
"docid": "The_Invisible_Man_(Queen_song)",
"text": "`` The Invisible Man '' is a song by the British rock band Queen , written by drummer Roger Taylor but credited to Queen . The song is sung mostly by Freddie Mercury , with vocal contributions from Taylor . Originally released on the album The Miracle , it was released as a single in 1989 . Taylor claims that he got the inspiration to create the song while reading a book ( possibly the book of the same name ) , and the bassline instantly came to his imagination . This song marks the only time in any of Queen 's songs that all four band members names are mentioned in the lyrics . The first being Freddie Mercury , followed by John Deacon . Brian May 's name is then said twice ( just before his guitar solo starts ) , and while saying `` Roger Taylor '' , the first `` r '' is rolled to emulate the drums at the end of the verse . Freddie Mercury 's name is said by drummer Roger Taylor , and the other ones by the lead singer Freddie Mercury .",
"title": ""
},
{
"docid": "Mercury_(name)",
"text": "Mercury is both a surname and a given name . Notable people with the name include : Surname : Daniela Mercury , Brazilian singer Eric Mercury , Canadian singer Freddie Mercury , singer of the rock group Queen Joey Mercury or Adam Birch , professional wrestler Given name : Mercury Hayes , former professional American football wide receiver born in 1973",
"title": ""
},
{
"docid": "Queen_+_Paul_Rodgers_Tour",
"text": "Queen + Paul Rodgers Tour was a world concert tour by Queen guitarist Brian May and drummer Roger Taylor , joined by singer Paul Rodgers under the moniker of Queen + Paul Rodgers . The tour was Queen 's first since The Magic Tour in 1986 , and the death of lead singer Freddie Mercury in November 1991 . The band 's drummer Roger Taylor commented ; `` We never thought we would tour again , Paul ( Rodgers ) came along by chance and we seemed to have a chemistry . Paul is just such a great singer . He 's not trying to be Freddie . '' Bassist John Deacon also did not take part due to his retirement in 1997 , however he gave the enterprise his blessing .",
"title": ""
},
{
"docid": "No-One_but_You_(Only_the_Good_Die_Young)",
"text": "`` No-One But You ( Only the Good Die Young ) '' is a song recorded by the remaining three members of the British rock band Queen in 1997 following the death of the lead singer Freddie Mercury in 1991 . Guitarist Brian May -- the writer of the song -- and drummer Roger Taylor share lead vocals . The song was released on the album Queen Rocks and it was also released as a double a-side single with `` Tie Your Mother Down '' . The impetus for the song came after the death of Diana , Princess of Wales in August 1997 , but is largely a eulogy to Freddie Mercury . It was dedicated to Mercury and all those that die too soon . It was originally written for a potential Brian May solo project , which eventually evolved into the album Another World . He sent the demo of the song to Roger Taylor , who according to Taylor himself , put it in a drawer and forgot about it . After eventually hearing it , Taylor suggested that it could be turned into a Queen song . Roger Taylor 's contribution was to change the tempo and make the lyrics less specific to Mercury . The song featured only the remaining three members of Queen , the final new recording to be released under the Queen name alone . This was also the last new recording to feature bass guitarist John Deacon , who subsequently retired from public life . This was the last original Queen release until the 2014 release Queen Forever .",
"title": ""
},
{
"docid": "Mercury:_The_Afterlife_and_Times_of_a_Rock_God",
"text": "Mercury : The Afterlife and Times of a Rock God is a monodrama written by Charles Messina about the life and death of Queen lead singer Freddie Mercury . It presents Mercury in the moments just after his death , during which he is confronted with self-examination as he `` seeks redemption before a God unimpressed by his celebrity . ''",
"title": ""
},
{
"docid": "Magic_Tour_(Queen)",
"text": "The Magic Tour was the biggest and final ever tour by the British rock band Queen with their lead singer Freddie Mercury and their bass guitarist John Deacon , which took place in 1986 . The band would not tour again until 19 years later , when the Queen + Paul Rodgers Tour began in 2005 , after the death of Freddie Mercury on 24 November 1991 , and the retirement of John Deacon in 1997 . The Magic Tour took in 26 dates around Europe 's stadiums , in support of their latest album A Kind of Magic . In 1987 , Mercury was diagnosed with AIDS and the band together made the decision to stop touring , making the concert at Knebworth on 9 August 1986 the last time ever the four members of Queen performed on stage together . Over a million people attended the Queen tour , making it one of the largest ever . Support acts included The Alarm , Big Country , Belouis Some , INXS , Level 42 , Marillion , Gary Moore , The Bangles and Status Quo . From this tour , Queen have since released Live at Wembley on CD , VHS & DVD , Live Magic on CD and Live in Budapest on VHS & Laserdisc ( later re-released and retitled as Hungarian Rhapsody : Queen Live in Budapest on DVD , Blu-ray and Deluxe editions ) .",
"title": ""
},
{
"docid": "Killer_Queen",
"text": "`` Killer Queen '' is a song by the British rock band Queen . It was their first big international hit , reaching number two in the UK and becoming their first US hit . Written by lead singer and pianist Freddie Mercury , the track was recorded for their third album Sheer Heart Attack . The song is about a high-class call girl . It has been characterised as `` Mercury 's piano-led paean to a Moët-quaffing courtesan '' . It has also been described by AllMusic as the true beginning of Queen 's `` radio sound '' and `` recalls the cabaret songs of yesteryear , but also shows how Queen was fast becoming a master of power pop '' . Rock historian Paul Fowles has written that `` Killer Queen '' , with its `` sleazy Parisian imagery '' , allowed `` free rein '' to Mercury 's `` unique brand of rock theater '' . The song won Mercury his first Ivor Novello Award .",
"title": ""
},
{
"docid": "Somebody_to_Love_(Queen_song)",
"text": "`` Somebody to Love '' is a song by the British rock band Queen , written by the lead singer/pianist Freddie Mercury . It debuted on the band 's 1976 album A Day at the Races and was also featured on their compilation album Greatest Hits . The song offers listeners something similar to that of Queen 's earlier hit `` Bohemian Rhapsody '' with its complex harmonies and guitar solos ; however instead of mimicking an English choir , the band turned to a gospel choir . It reached # 2 in the UK and # 13 on the Billboard Hot 100 in the US . This song made it clear to fans that `` Queen could swing as hard as it could rock , by channeling the spirit of gospel music . '' Written by Mercury at the piano , `` Somebody to Love '' is a soul-searching piece that questions God 's role in a life without love . Through voice layering techniques , Queen was able to create the soulful sound of a 100-voice choir , with that of only three voices : Mercury , Brian May and Roger Taylor . John Deacon did not sing backing vocals during the recorded album . Mercury 's fascination and admiration for Aretha Franklin was a major influence for the creation of this song . Queen played `` Somebody to Love '' live from 1977 -- 85 , and a live performance of the song is recorded on the album Queen Rock Montreal . In addition to these live performances , there has been collaboration on tributes to `` Somebody to Love '' after Mercury 's death in 1991 . The song was played live on 20 April 1992 , during The Freddie Mercury Tribute Concert , with George Michael on lead vocals . Since its release in 1976 , the song has appeared in a number of television shows , such as American Idol , The X Factor , Glee and Gossip Girl , as well as movies , including Happy Feet and Ella Enchanted . Additionally , it has been covered by many artists .",
"title": ""
},
{
"docid": "Freddie_Mercury_discography",
"text": "This is a discography of works by Freddie Mercury as a solo artist . For information about recordings made by Queen see Queen discography .",
"title": ""
},
{
"docid": "Freddie_Mercury:_The_Great_Pretender",
"text": "Freddie Mercury : The Great Pretender is an Emmy/Rose d'Or award winning 2012 feature-length documentary about Queen singer Freddie Mercury and his attempt to forge a solo career . The documentary premiered on BBC One in edited form as part of the Imagine series , and later the Director 's Cut was shown on BBC Four . It gained 3.5 million viewers when aired on BBC One in October 2012 and a further 1.2 million when shown on BBC Four . Reuniting the producer , editor and director of photography behind 2011 's widely acclaimed Queen : Days of Our Lives BBC documentary , The Great Pretender in similar vein presents a compelling insight into its subject matter , unearthing previously undiscovered or rarely seen footage . Produced and directed by Rhys Thomas , a lifelong Queen fan and expert ( to the extent that he famously broke the Mastermind all-time record points score with a specialist subject of Queen ) , Thomas has this time turned his attention to the Freddie Mercury archive , going back as early as 1976 in search of vintage gems which reveal more than ever before the inside story of Mercury 's life and career and the solo projects he worked on outside of Queen . The extensive archive footage is drawn from rare interviews with Mercury , concerts , video shoots and personal material , much of it being seen for the first time , along with newly filmed contributions from fellow Queen members Brian May and Roger Taylor , Queen manager Jim Beach , soprano Montserrat Caballé , composers David Arnold and Mike Moran , lyricist Tim Rice , comedian and lifelong fan Matt Lucas and many more . From it emerges a portrait of a man who was very different from his flamboyant onstage public persona . The Great Pretender includes for the first time ever Mercury and Rod Stewart singing their 1984 demo for `` Let Me Live '' , a snippet of the then unreleased Michael Jackson collaboration `` There Must Be More To Life Than This '' , and Mercury with The Royal Ballet in 1979 , never seen in full before . Thomas , whose extensive scouting for lost material turned up a copy of the band 's first TV appearance among the belongings of late comedian Dick Emery , brings to light Mercury 's earliest filmed interview from 1976 unearthed in Australia and another unseen interview from 1976 filmed by NBC in the USA . Thomas also found 10 cans of Mercury 's 39th Black and White birthday party in Mrs Henderson 's nightclub in Munich in 1985 . Originally filmed for the video for `` Living On My Own '' and promptly banned by Mercury 's record company because of its cross-dressing theme , there 's much to be enjoyed in watching Mercury and his friends go full out in their efforts to help him celebrate his last birthday before turning 40 . On top of this , The Great Pretender has a feast of outtakes from the video shoots for `` I Want to Break Free '' , `` One Vision '' , `` These Are the Days of Our Lives '' , `` I Want It All '' , `` A Kind of Magic '' , `` Princes of the Universe '' , `` Living on My Own '' , `` I Was Born to Love You '' , `` The Great Pretender '' , `` Made in Heaven '' , and `` Who Wants to Live Forever '' . Coinciding with the The Great Pretender came the release of the new Barcelona Special Edition album with Mercury and Caballé 's original album re-recorded with full 80 piece orchestra ( a feature on the making of this album is included on both formats ) and a new book , also entitled The Great Pretender , with matching artwork . The Great Pretender was released on DVD and Blu-ray through Eagle Rock Entertainment on 24 September 2012 . As bonus features that did not make up part of the version to be broadcast by the BBC , the programme included `` Freddie Mercury Goes Solo '' and an extended interview with Montserrat Caballé . In May 2013 the documentary won the Rose d'Or for Best Arts Documentary , and in November 2013 won the International Emmy for Best Arts Documentary .",
"title": ""
},
{
"docid": "A_Winter's_Tale_(Queen_song)",
"text": "`` A Winter 's Tale '' is a song by Queen , from the album Made in Heaven , released in 1995 after Freddie Mercury 's death in 1991 . It was written after the Innuendo sessions , inspired as Mercury was staring out the windows of his hospital , at Lake Geneva . The song has a psychedelic , dreamy feel , and describes what Mercury saw outside the windows . Freddie wrote , composed , and did the vocals and keyboards for it ( but the track is credited to Queen ) . In the documentary `` Queen - Champions of the World '' , it was stated that this was , if not the first , then an extremely rare style of recording for Freddie , as it was all performed in one take live in the studio . It was stated in the film that Freddie had always insisted upon music being completed prior to the vocal arrangement beginning , but acknowledged that he had little time left and there was not enough time to work on it differently . The song was released as the second single from the album . In the UK the single was also available in a special limited edition green paper CD case which resembled Christmas wrapping .",
"title": ""
},
{
"docid": "The_Freddie_Mercury_Tribute_Concert",
"text": "The Freddie Mercury Tribute Concert for AIDS Awareness was a concert held on Easter Monday , 20 April 1992 at Wembley Stadium in London , England for an audience of 72,000 . The concert was produced for television by Ray Burdis and broadcast live on television and radio to 76 countries around the world , with an audience of up to one billion . The concert was a tribute to the life of Queen lead vocalist , Freddie Mercury , with proceeds going to AIDS research . The show marked bassist John Deacon 's final full-length concert with Queen ( save a short live appearance with Brian May , Roger Taylor and Elton John in 1997 ) . The profits from the concert were used to launch The Mercury Phoenix Trust , an AIDS charity organisation .",
"title": ""
},
{
"docid": "There_Must_Be_More_To_Life_Than_This",
"text": "There Must Be More To Life Than This is a song recorded by Queen singer Freddie Mercury for his debut solo album Mr. Bad Guy . It was released as part of the album on 29 April 1985 by Columbia Records . It appears as the eighth track on the album . The song was originally recorded by Mercury 's band Queen for their 1982 album , Hot Space but eventually failed to make the final version of the album . The song was previously recorded as a duet between Mercury and Michael Jackson along with two other songs , State of Shock ( Which was released in 1984 by The Jacksons featuring Mick Jagger ) and Victory ( Which currently remains unreleased ) .",
"title": ""
},
{
"docid": "The_Story_of_Bohemian_Rhapsody",
"text": "The Story of Bohemian Rhapsody is a 2004 documentary about the song `` Bohemian Rhapsody '' , written by the lead singer of Queen , Freddie Mercury .",
"title": ""
},
{
"docid": "Love_Kills_(Freddie_Mercury_song)",
"text": "`` Love Kills '' is a song by Freddie Mercury , and his first song recorded as a solo artist . It was originally used in Giorgio Moroder 's 1984 restoration and edit of the 1927 silent film Metropolis , as part of the film 's new soundtrack . In 1985 , the film was nominated at the 5th Golden Raspberry Awards for Worst Musical Score , and the song itself was nominated for Worst Original Song . Nevertheless , the single reached number ten on the UK Singles Chart . `` Love Kills '' was also used for the closing credits of the 1993 film Loaded Weapon 1 . In 2009 , a cover version by English synthpop singer Little Boots was included on her extended plays Little Boots and Illuminations . In 2014 , Brian May and Roger Taylor reworked a previously unreleased ballad version of the song for inclusion on their new compilation Queen Forever , an album which focuses on Queen 's love songs and ballads .",
"title": ""
},
{
"docid": "Mr._Bad_Guy",
"text": "Mr. Bad Guy is the debut solo album from Queen singer , Freddie Mercury . Released in 1985 , during a period in which Queen were on hiatus from recordings , it contains eleven songs , all written by him . For the album , Mercury compiled influences ranging from disco to dance music . It was a contrast to typical Queen work , as they were rock-orientated . The album took nearly two years to record as Mercury had to gather enough material , while committing to band activities . Initially , the album was supposed to feature duets with Mercury and Michael Jackson . They recorded `` There Must Be More to Life Than This '' , but Mercury dropped out of any further collaboration after feeling uncomfortable working with Jackson 's pet llama in the studio . Recording was taxing on Mercury as he took part in everything from performing the tracks to sound engineering to obtain his desired effect . Mercury used synthesizers and orchestration in track development , adding to the diversity in each piece . The song `` Living on My Own '' was re-released in 1993 in a remixed form by No More Brothers , while `` I Was Born to Love You '' and `` Made in Heaven '' were later re-worked by the surviving three Queen members and included in the 1995 curtain-call Made in Heaven . The album was originally planned to be called Made in Heaven .",
"title": ""
},
{
"docid": "Too_Much_Love_Will_Kill_You",
"text": "`` Too Much Love Will Kill You '' is a song written by British guitarist Brian May of Queen , Frank Musker , and Elizabeth Lamers . The song reflected the breakdown of May 's first marriage and attraction to his future wife , Anita Dobson . It was first recorded by Queen around 1988 or before , and was intended to be on the band 's The Miracle album in 1989 , but did not make the cut due to legal disputes following the band 's decision that all songs on the album would be written by the group as oppose to individuals . After Freddie Mercury 's death in 1991 , May arranged a solo version , which he performed at the Freddie Mercury Tribute Concert in 1992 , and subsequently included on his solo album Back to the Light that same year . Released as a single , it reached No. 5 on the UK Singles Chart . Because it was first played publicly at The Freddie Mercury Tribute Concert , a common misconception is that it was written as a tribute to Freddie Mercury , although it had actually been written several years before he died .",
"title": ""
},
{
"docid": "Queen_at_the_Ballet",
"text": "Queen at the Ballet is a rock ballet in two acts created by Sean Bovim as a tribute to Freddie Mercury , that brings the music of Queen vividly back to life -- interpreting the stories behind classic songs such as `` Bohemian Rhapsody '' , `` Radio Ga Ga '' and `` Killer Queen '' . In February 2012 Cito , the lead singer of the band `` Wonderboom '' performed live vocals at Oude Libertas Wine Farm Amphitheatre Vocals in Stellenbosch , Western Cape , SA .",
"title": ""
},
{
"docid": "Lover_of_Life,_Singer_of_Songs",
"text": "Lover of Life , Singer of Songs ( with the subtitle The Very Best of Freddie Mercury Solo ) is a compilation album of Freddie Mercury 's solo songs . It was released ( except in the U.S. ) on 4 September 2006 , the day before Mercury 's 60th Birthday . It was released on 21 November 2006 in the U.S , three days before the 15th anniversary of Mercury 's death .",
"title": ""
},
{
"docid": "Barcelona_(Freddie_Mercury_and_Montserrat_Caballé_song)",
"text": "`` Barcelona '' is a single released by Queen vocalist Freddie Mercury and operatic soprano Montserrat Caballé . A part of their collaborative album Barcelona , it also appeared on Queen 's Greatest Hits III . The song reflects Mercury 's love of opera with his high notes and Caballé 's operatic vocals , backed by a full orchestra . Originally released in 1987 , it was one of the biggest hits of Mercury 's solo career , reaching number eight in the UK Singles Chart . After Mercury 's death in 1991 , it was featured at the 1992 Summer Olympics , after which the track climbed even higher , peaking at number 2 in the UK , the Netherlands and New Zealand . In 2004 , BBC Radio 2 listed Barcelona at # 41 in its Sold On Song Top 100 .",
"title": ""
},
{
"docid": "Mercury_Phoenix_Trust",
"text": "The Mercury Phoenix Trust is a charity organisation that fights HIV/AIDS worldwide . After the death of Freddie Mercury from AIDS-related causes in London in 1991 , the remaining members of Queen and Jim Beach , their manager , organised The Freddie Mercury Tribute Concert for AIDS Awareness , the proceeds of which were used to launch The Mercury Phoenix Trust . The organisation has been active ever since . The current Trustees are : Brian May , Roger Taylor , Jim Beach and Mary Austin ( Mercury 's closest friend and former girlfriend ) .",
"title": ""
},
{
"docid": "Innuendo_(song)",
"text": "`` Innuendo '' is a 1991 single by the British rock band Queen . Written by Freddie Mercury and Roger Taylor but credited to Queen , it is the opening track on the album of the same name , and was released as the first single from the album . The single went straight to Number 1 in the UK Singles Chart in January 1991 . At six and a half minutes , it is one of Queen 's epic songs and their longest ever released as a single , exceeding `` Bohemian Rhapsody '' by 35 seconds . The song has been described as `` reminiscent '' of `` Bohemian Rhapsody '' because it was `` harking back to their progressive rock roots '' . It features a flamenco guitar section performed by Yes guitarist Steve Howe and Brian May , an operatic interlude and sections of hard rock that recall early Queen , in addition to lyrics inspired in part by lead singer Freddie Mercury 's illness ; although media stories about his health were being strenuously denied , he was by now seriously ill with AIDS , which would claim his life in November 1991 , 10 months after the single was released . Accompanied by a music video featuring animated representations of the band on a cinema screen akin to Nineteen Eighty-Four , eerie plasticine figure stop-motion and harrowing imagery , it has been described as one of the band 's darkest and most moving works . AllMusic described the song as a `` superb epic '' , which deals with `` mankind 's inability to live harmoniously '' .",
"title": ""
},
{
"docid": "Body_Language_(Queen_song)",
"text": "`` Body Language '' ( printed as `` Body Language ↑ ⬱ '' ) is a 1982 dance/funk song by British rock band Queen . It was written by the band 's lead singer Freddie Mercury and was a hit in North America , where it received extensive radio play . However , the single only received a lukewarm response in the United Kingdom . The track was the second single released from their 1982 album Hot Space .",
"title": ""
},
{
"docid": "Logan_Place",
"text": "Logan Place is a small residential road in Kensington , west London . It lies off Earl 's Court Road . It is notable for being the home of Queen 's lead singer Freddie Mercury , who bought the Garden Lodge mansion during his time with the band .",
"title": ""
},
{
"docid": "Mother_Love_(Queen_song)",
"text": "`` Mother Love '' is a song by Queen , from the album Made in Heaven , released in 1995 after Freddie Mercury 's death in 1991 . It was written by Mercury and Brian May . The song features the last ever vocals sung by Mercury in May 1991 , 6 months before his death .",
"title": ""
},
{
"docid": "Staying_Power",
"text": "`` Staying Power '' is the first track on Queen 's 1982 album Hot Space . It was written by lead singer Freddie Mercury and is notable as being the only Queen song to have a horn section , which was arranged by Arif Mardin . The song is driven by a funk-styled bass riff ( played by Mercury ) beginning in D minor and modulating to E minor throughout the song . John Deacon does not play bass on this song -- instead playing rhythm guitar on a Fender Telecaster . Roger Taylor programmed a Linn LM-1 drum machine for the track . Brian May is on his Red Special . In a Stylus review of the album , critic Anthony Miccio described the song 's style as `` an electro-disco track with frenetic horns . '' The song was released as a single in Japan , the US and Poland where it reached # 21 .",
"title": ""
},
{
"docid": "Queen_Forever",
"text": "Queen Forever is a compilation album by the British rock band Queen . Released on 10 November 2014 , it features tracks the band had `` forgotten about '' with vocals from original lead singer Freddie Mercury . Original bass guitarist John Deacon is also on the tracks . Drummer Roger Taylor spoke about the album in December 2013 , stating that he and guitarist Brian May were `` getting together ... in the new year to finish what we 've got there and then we 're going to fashion some kind of album '' . May announced the title as a compilation album in a radio interview on BBC Radio Wales on 23 May 2014 at the Hay Festival . It is the first Queen album to feature unreleased material from Mercury ( who died from complications related to AIDS in November 1991 ) since the 1995 album Made in Heaven and Deacon ( who retired from the music business in 1997 ) since the 1997 compilation album Queen Rocks . The album was released by Hollywood Records on 10 November 2014 .",
"title": ""
},
{
"docid": "It's_a_Hard_Life",
"text": "`` It 's a Hard Life '' is a song by the British rock band Queen , written by lead singer Freddie Mercury . It was featured on their 1984 album The Works , and it was the third single from that album . It reached number 6 in the UK Singles Chart and was their third consecutive Top 10 single from the album . It also reached number 2 in Ireland and number 20 in the Netherlands . It also came 19th on a poll , The Nation 's Favourite Queen Song broadcast on ITV on Tuesday 11 November 2014 .",
"title": ""
},
{
"docid": "Crazy_Little_Thing_Called_Love",
"text": "`` Crazy Little Thing Called Love '' is a song by the British rock band Queen . Written by Freddie Mercury in 1979 , the track is featured on their 1980 album The Game , and also appears on the band 's compilation album , Greatest Hits in 1981 . The song peaked at number two in the UK Singles Chart in 1979 , and became the group 's first number-one single on the Billboard Hot 100 in the US in 1980 , remaining there for four consecutive weeks . It topped the Australian ARIA Charts for seven weeks . Having composed `` Crazy Little Thing Called Love '' on guitar , Mercury played rhythm guitar while performing the song live , which was the first time he played guitar in concert with Queen . Queen played the song live between 1979 and 1986 , and a live performance of the song is recorded in the albums Queen Rock Montreal , Queen on Fire - Live at the Bowl , Live at Wembley '86 and Hungarian Rhapsody : Queen Live in Budapest ' . Since its release , the song has been covered by a number of artists . The song was played live on 20 April 1992 during The Freddie Mercury Tribute Concert , performed by Robert Plant with Queen . The style of the song was described by author Karl Coryat as rockabilly in his 1999 book titled The Bass Player Book .",
"title": ""
},
{
"docid": "The_Show_Must_Go_On_(Queen_song)",
"text": "`` The Show Must Go On '' is a song by the British rock band Queen , featured as the twelfth and final track on their 1991 album Innuendo . It is credited to Queen , but written mainly by Brian May . The song chronicles the effort of Freddie Mercury continuing to perform despite approaching the end of his life ; he was dying from complications due to HIV/AIDS , although his illness had not yet been made public in spite of ongoing media speculation claiming that he was seriously ill . Mercury was so ill when the band recorded the song in 1990 , that May had concerns as to whether he was physically capable of singing it . Recalling Mercury 's performance , May states ; `` I said , ` Fred , I do n't know if this is going to be possible to sing . ' And he went , ` I 'll fucking do it , darling ' -- vodka down -- and went in and killed it , completely lacerated that vocal . '' It was released as a single in the United Kingdom on 14 October 1991 in promotion for the Greatest Hits II album , just six weeks before Mercury died . Following Mercury 's death on 24 November 1991 , the song re-entered the British charts and spent as many weeks in the top 75 ( five ) as it did upon its original release , initially reaching a peak of 16 . A live version with Elton John on vocals appeared on Queen 's Greatest Hits III album . The song was first played live on 20 April 1992 , during The Freddie Mercury Tribute Concert , performed by the three remaining members of Queen , with Elton John singing lead vocals and Black Sabbath guitarist Tony Iommi playing rhythm guitar . It has since been played live by Queen + Paul Rodgers with Rodgers citing one of the performances as the best of his career . Since its release , the song has appeared on television , film , and has been covered by a number of artists .",
"title": ""
}
] |
204
|
CDK6 shows impaired binding to loss-of-function variants of p18 INK4C.
|
[
{
"docid": "7898952",
"text": "We have developed a nonheuristic genome topography scan (GTS) algorithm to characterize the patterns of genomic alterations in human glioblastoma (GBM), identifying frequent p18(INK4C) and p16(INK4A) codeletion. Functional reconstitution of p18(INK4C) in GBM cells null for both p16(INK4A) and p18(INK4C) resulted in impaired cell-cycle progression and tumorigenic potential. Conversely, RNAi-mediated depletion of p18(INK4C) in p16(INK4A)-deficient primary astrocytes or established GBM cells enhanced tumorigenicity in vitro and in vivo. Furthermore, acute suppression of p16(INK4A) in primary astrocytes induced a concomitant increase in p18(INK4C). Together, these findings uncover a feedback regulatory circuit in the astrocytic lineage and demonstrate a bona fide tumor suppressor role for p18(INK4C) in human GBM wherein it functions cooperatively with other INK4 family members to constrain inappropriate proliferation.",
"title": "Feedback Circuit among INK4 Tumor Suppressors Constrains Human Glioblastoma Development"
}
] |
[
{
"docid": "470625",
"text": "Genomic alterations leading to aberrant activation of cyclin/cyclin-dependent kinase (cdk) complexes drive the pathogenesis of many common human tumor types. In the case of glioblastoma multiforme (GBM), these alterations are most commonly due to homozygous deletion of p16(INK4a) and less commonly due to genomic amplifications of individual genes encoding cyclins or cdks. Here, we describe deletion of the p18(INK4c) cdk inhibitor as a novel genetic alteration driving the pathogenesis of GBM. Deletions of p18(INK4c) often occurred in tumors also harboring homozygous deletions of p16(INK4a). Expression of p18(INK4c) was completely absent in 43% of GBM primary tumors studied by immunohistochemistry. Lentiviral reconstitution of p18(INK4c) expression at physiologic levels in p18(INK4c)-deficient but not p18(INK4c)-proficient GBM cells led to senescence-like G(1) cell cycle arrest. These studies identify p18(INK4c) as a GBM tumor suppressor gene, revealing an additional mechanism leading to aberrant activation of cyclin/cdk complexes in this terrible malignancy.",
"title": "Identification of p18 INK4c as a tumor suppressor gene in glioblastoma multiforme."
},
{
"docid": "7717468",
"text": "Microbial survival in a host is usually dependent on the ability of a pathogen to undergo changes that promote escape from host defense mechanisms. The human-pathogenic fungus Cryptococcus neoformans undergoes phenotypic switching in vivo that promotes persistence in tissue. By microarray and real-time PCR analyses, the allergen 1 gene (ALL1) was found to be downregulated in the hypervirulent mucoid switch variant, both during logarithmic growth and during intracellular growth in macrophages. The ALL1 gene encodes a small cytoplasmic protein that is involved in capsule formation. Growth of an all1Delta gene deletion mutant was normal. Similar to cells of the mucoid switch variant, all1Delta cells produced a larger polysaccharide capsule than cells of the smooth parent and the complemented strain produced, and the enlarged capsule inhibited macrophage phagocytosis. The mutant exhibited a modest defect in capsule induction compared to all of the other variants. In animal models the phenotype of the all1Delta mutant mimicked the hypervirulent phenotype of the mucoid switch variant, which is characterized by decreased host survival and elevated intracranial pressure. Decreased survival is likely the result of both an ineffective cell-mediated immune response and impaired phagocytosis by macrophages. Consequently, we concluded that, unlike loss of most virulence-associated genes, where loss of gene function results in attenuated virulence, loss of the ALL1 gene enhances virulence by altering the host-pathogen interaction and thereby impairing clearance. Our data identified the first cryptococcal gene associated with elevated intracranial pressure and support the hypothesis that an environmental opportunistic pathogen has modified its virulence in vivo by epigenetic downregulation of gene function.",
"title": "Loss of allergen 1 confers a hypervirulent phenotype that resembles mucoid switch variants of Cryptococcus neoformans."
},
{
"docid": "344240",
"text": "Actions of protein products resulting from alternative splicing of the Igf1 gene have received increasing attention in recent years. However, the significance and functional relevance of these observations remain poorly defined. To address functions of IGF-I splice variants, we examined the impact of loss of IGF-IEa and IGF-IEb on the proliferation and differentiation of cultured mouse myoblasts. RNA interference-mediated reductions in total IGF-I, IGF-IEa alone, or IGF-IEb alone had no effect on cell viability in growth medium. However, cells deficient in total IGF-I or IGF-IEa alone proliferated significantly slower than control cells or cells deficient in IGF-IEb in serum-free media. Simultaneous loss of both or specific loss of either splice variant significantly inhibited myosin heavy chain (MyHC) immunoreactivity by 70-80% (P < 0.01) under differentiation conditions (48 h in 2% horse serum) as determined by Western immunoblotting. This loss in protein was associated with reduced MyHC isoform mRNAs, because reductions in total IGF-I or IGF-IEa mRNA significantly reduced MyHC mRNAs by approximately 50-75% (P < 0.05). Loss of IGF-IEb also reduced MyHC isoform mRNA significantly, with the exception of Myh7, but to a lesser degree (∼20-40%, P < 0.05). Provision of mature IGF-I, but not synthetic E peptides, restored Myh3 expression to control levels in cells deficient in IGF-IEa or IGF-IEb. Collectively, these data suggest that IGF-I splice variants may regulate myoblast differentiation through the actions of mature IGF-I and not the E peptides.",
"title": "Loss of IGF-IEa or IGF-IEb impairs myogenic differentiation."
},
{
"docid": "3127341",
"text": "The glucagon-like peptide-1 receptor (GLP-1R) is a key physiological regulator of insulin secretion and a major therapeutic target for the treatment of type II diabetes. However, regulation of GLP-1R function is complex with multiple endogenous peptides that interact with the receptor, including full-length (1-37) and truncated (7-37) forms of GLP-1 that can exist in an amidated form (GLP-1(1-36)NH₂ and GLP-1(7-36)NH₂) and the related peptide oxyntomodulin. In addition, the GLP-1R possesses exogenous agonists, including exendin-4, and the allosteric modulator, compound 2 (6,7-dichloro-2-methylsulfonyl-3-tert-butylaminoquinoxaline). The complexity of this ligand-receptor system is further increased by the presence of several single nucleotide polymorphisms (SNPs) that are distributed across the receptor. We have investigated 10 GLP-1R SNPs, which were characterized in three physiologically relevant signaling pathways (cAMP accumulation, extracellular signal-regulated kinase 1/2 phosphorylation, and intracellular Ca²⁺ mobilization); ligand binding and cell surface receptor expression were also determined. We demonstrate both ligand- and pathway-specific effects for multiple SNPs, with the most dramatic effect observed for the Met¹⁴⁹ receptor variant. At the Met¹⁴⁹ variant, there was selective loss of peptide-induced responses across all pathways examined, but preservation of response to the small molecule compound 2. In contrast, at the Cys³³³ variant, peptide responses were preserved but there was attenuated response to compound 2. Strikingly, the loss of peptide function at the Met¹⁴⁹ receptor variant could be allosterically rescued by compound 2, providing proof-of-principle evidence that allosteric drugs could be used to treat patients with this loss of function variant.",
"title": "Polymorphism and ligand dependent changes in human glucagon-like peptide-1 receptor (GLP-1R) function: allosteric rescue of loss of function mutation."
},
{
"docid": "4407385",
"text": "Memory function often declines with age, and is believed to deteriorate initially because of changes in synaptic function rather than loss of neurons. Some individuals then go on to develop Alzheimer's disease with neurodegeneration. Here we use Tg2576 mice, which express a human amyloid-β precursor protein (APP) variant linked to Alzheimer's disease, to investigate the cause of memory decline in the absence of neurodegeneration or amyloid-β protein amyloidosis. Young Tg2576 mice (< 6 months old) have normal memory and lack neuropathology, middle-aged mice (6–14 months old) develop memory deficits without neuronal loss, and old mice (> 14 months old) form abundant neuritic plaques containing amyloid-β (refs 3–6). We found that memory deficits in middle-aged Tg2576 mice are caused by the extracellular accumulation of a 56-kDa soluble amyloid-β assembly, which we term Aβ*56 (Aβ star 56). Aβ*56 purified from the brains of impaired Tg2576 mice disrupts memory when administered to young rats. We propose that Aβ*56 impairs memory independently of plaques or neuronal loss, and may contribute to cognitive deficits associated with Alzheimer's disease.",
"title": "A specific amyloid-β protein assembly in the brain impairs memory"
},
{
"docid": "24311787",
"text": "Variant histone H2AZ-containing nucleosomes are involved in the regulation of gene expression. In Saccharomyces cerevisiae, chromatin deposition of histone H2AZ is mediated by the fourteen-subunit SWR1 complex, which catalyzes ATP-dependent exchange of nucleosomal histone H2A for H2AZ. Previous work defined the role of seven SWR1 subunits (Swr1 ATPase, Swc2, Swc3, Arp6, Swc5, Yaf9, and Swc6) in maintaining complex integrity and H2AZ histone replacement activity. Here we examined the function of three additional SWR1 subunits, bromodomain containing Bdf1, actin-related protein Arp4 and Swc7, by analyzing affinity-purified mutant SWR1 complexes. We observed that depletion of Arp4 (arp4-td) substantially impaired the association of Bdf1, Yaf9, and Swc4. In contrast, loss of either Bdf1 or Swc7 had minimal effects on overall complex integrity. Furthermore, the basic H2AZ histone replacement activity of SWR1 in vitro required Arp4, but not Bdf1 or Swc7. Thus, three out of fourteen SWR1 subunits, Bdf1, Swc7, and previously noted Swc3, appear to have roles auxiliary to the basic histone replacement activity. The N-terminal region of the Swr1 ATPase subunit is necessary and sufficient to direct association of Bdf1 and Swc7, as well as Arp4, Act1, Yaf9 and Swc4. This same region contains an additional H2AZ-H2B specific binding site, distinct from the previously identified Swc2 subunit. These findings suggest that one SWR1 enzyme might be capable of binding two H2AZ-H2B dimers, and provide further insight on the hierarchy and interdependency of molecular interactions within the SWR1 complex.",
"title": "N terminus of Swr1 binds to histone H2AZ and provides a platform for subunit assembly in the chromatin remodeling complex."
},
{
"docid": "4412772",
"text": "Unicellular organisms such as yeasts require a single cyclin-dependent kinase, Cdk1, to drive cell division. In contrast, mammalian cells are thought to require the sequential activation of at least four different cyclin-dependent kinases, Cdk2, Cdk3, Cdk4 and Cdk6, to drive cells through interphase, as well as Cdk1 to proceed through mitosis. This model has been challenged by recent genetic evidence that mice survive in the absence of individual interphase Cdks. Moreover, most mouse cell types proliferate in the absence of two or even three interphase Cdks. Similar results have been obtained on ablation of some of the activating subunits of Cdks, such as the D-type and E-type cyclins. Here we show that mouse embryos lacking all interphase Cdks (Cdk2, Cdk3, Cdk4 and Cdk6) undergo organogenesis and develop to midgestation. In these embryos, Cdk1 binds to all cyclins, resulting in the phosphorylation of the retinoblastoma protein pRb and the expression of genes that are regulated by E2F transcription factors. Mouse embryonic fibroblasts derived from these embryos proliferate in vitro, albeit with an extended cell cycle due to inefficient inactivation of Rb proteins. However, they become immortal on continuous passage. We also report that embryos fail to develop to the morula and blastocyst stages in the absence of Cdk1. These results indicate that Cdk1 is the only essential cell cycle Cdk. Moreover, they show that in the absence of interphase Cdks, Cdk1 can execute all the events that are required to drive cell division.",
"title": "Cdk1 is sufficient to drive the mammalian cell cycle"
},
{
"docid": "25479072",
"text": "Cytotoxic T cell (CTL) activation by antigen requires the specific detection of peptide–major histo-compatibility class I (pMHC) molecules on the target-cell surface by the T cell receptor (TCR). We examined the effect of mutations in the antigen-binding site of a Kb-restricted TCR on T cell activation, antigen binding and dissociation from antigen. These parameters were also examined for variants derived from a Kd-restricted peptide that was recognized by a CTL clone. Using these two independent systems, we show that T cell activation can be impaired by mutations that either decrease or increase the binding half-life of the TCR-pMHC interaction. Our data indicate that efficient T cell activation occurs within an optimal dwell-time range of TCR-pMHC interaction. This restricted dwell-time range is consistent with the exclusion of either extremely low or high affinity T cells from the expanded population during immune responses.",
"title": "Efficient T cell activation requires an optimal dwell-time of interaction between the TCR and the pMHC complex"
},
{
"docid": "16626264",
"text": "Histone variants help specialize chromatin regions; however, their impact on transcriptional regulation is largely unknown. Here, we determined the genome-wide localization and dynamics of Htz1, the yeast histone H2A variant. Htz1 localizes to hundreds of repressed/basal Pol II promoters and prefers TATA-less promoters. Specific Htz1 deposition requires the SWR1 complex, which largely colocalizes with Htz1. Htz1 occupancy correlates with particular histone modifications, and Htz1 deposition is partially reliant on Gcn5 (a histone acetyltransferase) and Bdf1, an SWR1 complex member that binds acetylated histones. Changes in growth conditions cause a striking redistribution of Htz1 from activated to repressed/basal promoters. Furthermore, Htz1 promotes full gene activation but does not generally impact repression. Importantly, Htz1 releases from purified chromatin in vitro under conditions where H2A and H3 remain associated. We suggest that Htz1-bearing nucleosomes are deposited at repressed/basal promoters but facilitate activation through their susceptibility to loss, thereby helping to expose promoter DNA.",
"title": "Genome-Wide Dynamics of Htz1, a Histone H2A Variant that Poises Repressed/Basal Promoters for Activation through Histone Loss"
},
{
"docid": "4993011",
"text": "ATRX (alpha thalassemia/mental retardation X-linked) complexes with DAXX to deposit histone variant H3.3 into repetitive heterochromatin. Recent genome sequencing studies in cancers have revealed mutations in ATRX and their association with ALT (alternative lengthening of telomeres) activation. Here we report depletion of ATRX in mouse ES cells leads to selective loss in ribosomal RNA gene (rDNA) copy number. Supporting this, ATRX-mutated human ALT-positive tumors also show a substantially lower rDNA copy than ALT-negative tumors. Further investigation shows that the rDNA copy loss and repeat instability are caused by a disruption in H3.3 deposition and thus a failure in heterochromatin formation at rDNA repeats in the absence of ATRX. We also find that ATRX-depleted cells are reduced in ribosomal RNA transcription output and show increased sensitivity to RNA polymerase I (Pol I) transcription inhibitor CX5461. In addition, human ALT-positive cancer cell lines are also more sensitive to CX5461 treatment. Our study provides insights into the contribution of ATRX loss of function to tumorigenesis through the loss of rDNA stability and suggests the therapeutic potential of targeting Pol I transcription in ALT cancers.",
"title": "Ribosomal DNA copy loss and repeat instability in ATRX-mutated cancers"
},
{
"docid": "17518195",
"text": "Histone variants within the H2A family show high divergences in their C-terminal regions. In this work, we have studied how these divergences and in particular, how a part of the H2A COOH-terminus, the docking domain, is implicated in both structural and functional properties of the nucleosome. Using biochemical methods in combination with Atomic Force Microscopy and Electron Cryo-Microscopy, we show that the H2A-docking domain is a key structural feature within the nucleosome. Deletion of this domain or replacement with the incomplete docking domain from the variant H2A.Bbd results in significant structural alterations in the nucleosome, including an increase in overall accessibility to nucleases, un-wrapping of ∼10 bp of DNA from each end of the nucleosome and associated changes in the entry/exit angle of DNA ends. These structural alterations are associated with a reduced ability of the chromatin remodeler RSC to both remodel and mobilize the nucleosomes. Linker histone H1 binding is also abrogated in nucleosomes containing the incomplete docking domain of H2A.Bbd. Our data illustrate the unique role of the H2A-docking domain in coordinating the structural-functional aspects of the nucleosome properties. Moreover, our data suggest that incorporation of a 'defective' docking domain may be a primary structural role of H2A.Bbd in chromatin.",
"title": "The docking domain of histone H2A is required for H1 binding and RSC-mediated nucleosome remodeling"
},
{
"docid": "4414547",
"text": "Improved sequencing technologies offer unprecedented opportunities for investigating the role of rare genetic variation in common disease. However, there are considerable challenges with respect to study design, data analysis and replication. Using pooled next-generation sequencing of 507 genes implicated in the repair of DNA in 1,150 samples, an analytical strategy focused on protein-truncating variants (PTVs) and a large-scale sequencing case–control replication experiment in 13,642 individuals, here we show that rare PTVs in the p53-inducible protein phosphatase PPM1D are associated with predisposition to breast cancer and ovarian cancer. PPM1D PTV mutations were present in 25 out of 7,781 cases versus 1 out of 5,861 controls (P = 1.12 × 10−5), including 18 mutations in 6,912 individuals with breast cancer (P = 2.42 × 10−4) and 12 mutations in 1,121 individuals with ovarian cancer (P = 3.10 × 10−9). Notably, all of the identified PPM1D PTVs were mosaic in lymphocyte DNA and clustered within a 370-base-pair region in the final exon of the gene, carboxy-terminal to the phosphatase catalytic domain. Functional studies demonstrate that the mutations result in enhanced suppression of p53 in response to ionizing radiation exposure, suggesting that the mutant alleles encode hyperactive PPM1D isoforms. Thus, although the mutations cause premature protein truncation, they do not result in the simple loss-of-function effect typically associated with this class of variant, but instead probably have a gain-of-function effect. Our results have implications for the detection and management of breast and ovarian cancer risk. More generally, these data provide new insights into the role of rare and of mosaic genetic variants in common conditions, and the use of sequencing in their identification.",
"title": "Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer"
},
{
"docid": "5273056",
"text": "Eukaryotes have numerous checkpoint pathways to protect genome fidelity during normal cell division and in response to DNA damage. Through a screen for G2/M checkpoint regulators in zebrafish, we identified ticrr (for TopBP1-interacting, checkpoint, and replication regulator), a previously uncharacterized gene that is required to prevent mitotic entry after treatment with ionizing radiation. Ticrr deficiency is embryonic-lethal in the absence of exogenous DNA damage because it is essential for normal cell cycle progression. Specifically, the loss of ticrr impairs DNA replication and disrupts the S/M checkpoint, leading to premature mitotic entry and mitotic catastrophe. We show that the human TICRR ortholog associates with TopBP1, a known checkpoint protein and a core component of the DNA replication preinitiation complex (pre-IC), and that the TICRR-TopBP1 interaction is stable without chromatin and requires BRCT motifs essential for TopBP1's replication and checkpoint functions. Most importantly, we find that ticrr deficiency disrupts chromatin binding of pre-IC, but not prereplication complex, components. Taken together, our data show that TICRR acts in association with TopBP1 and plays an essential role in pre-IC formation. It remains to be determined whether Ticrr represents the vertebrate ortholog of the yeast pre-IC component Sld3, or a hitherto unknown metazoan replication and checkpoint regulator.",
"title": "A vertebrate gene, ticrr, is an essential checkpoint and replication regulator."
},
{
"docid": "857189",
"text": "The protein cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential negative regulator of immune responses, and its loss causes fatal autoimmunity in mice. We studied a large family in which five individuals presented with a complex, autosomal dominant immune dysregulation syndrome characterized by hypogammaglobulinemia, recurrent infections and multiple autoimmune clinical features. We identified a heterozygous nonsense mutation in exon 1 of CTLA4. Screening of 71 unrelated patients with comparable clinical phenotypes identified five additional families (nine individuals) with previously undescribed splice site and missense mutations in CTLA4. Clinical penetrance was incomplete (eight adults of a total of 19 genetically proven CTLA4 mutation carriers were considered unaffected). However, CTLA-4 protein expression was decreased in regulatory T cells (Treg cells) in both patients and carriers with CTLA4 mutations. Whereas Treg cells were generally present at elevated numbers in these individuals, their suppressive function, CTLA-4 ligand binding and transendocytosis of CD80 were impaired. Mutations in CTLA4 were also associated with decreased circulating B cell numbers. Taken together, mutations in CTLA4 resulting in CTLA-4 haploinsufficiency or impaired ligand binding result in disrupted T and B cell homeostasis and a complex immune dysregulation syndrome.",
"title": "Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations"
},
{
"docid": "26625002",
"text": "The outer membrane channel TolC is a key component of multidrug efflux and type I secretion transporters in Escherichia coli. Mutational inactivation of TolC renders cells highly susceptible to antibiotics and leads to defects in secretion of protein toxins. Despite impairment of various transport functions, no growth defects were reported in cells lacking TolC. Unexpectedly, we found that the loss of TolC notably impairs cell division and growth in minimal glucose medium. The TolC-dependent phenotype was further exacerbated by the loss of ygiB and ygiC genes expressed in the same operon as tolC and their homologues yjfM and yjfC located elsewhere on the chromosome. Our results show that this growth deficiency is caused by depletion of the critical metabolite NAD(+) and high NADH/NAD(+) ratios. The increased amounts of PspA and decreased rates of NADH oxidation in Delta tolC membranes indicated stress on the membrane and dissipation of a proton motive force. We conclude that inactivation of TolC triggers metabolic shutdown in E. coli cells grown in minimal glucose medium. The Delta tolC phenotype is partially rescued by YgiBC and YjfMC, which have parallel functions independent from TolC.",
"title": "Metabolic shutdown in Escherichia coli cells lacking the outer membrane channel TolC."
},
{
"docid": "14717500",
"text": "Genome-wide association studies (GWAS) have now identified at least 2,000 common variants that appear associated with common diseases or related traits (http://www.genome.gov/gwastudies), hundreds of which have been convincingly replicated. It is generally thought that the associated markers reflect the effect of a nearby common (minor allele frequency >0.05) causal site, which is associated with the marker, leading to extensive resequencing efforts to find causal sites. We propose as an alternative explanation that variants much less common than the associated one may create \"synthetic associations\" by occurring, stochastically, more often in association with one of the alleles at the common site versus the other allele. Although synthetic associations are an obvious theoretical possibility, they have never been systematically explored as a possible explanation for GWAS findings. Here, we use simple computer simulations to show the conditions under which such synthetic associations will arise and how they may be recognized. We show that they are not only possible, but inevitable, and that under simple but reasonable genetic models, they are likely to account for or contribute to many of the recently identified signals reported in genome-wide association studies. We also illustrate the behavior of synthetic associations in real datasets by showing that rare causal mutations responsible for both hearing loss and sickle cell anemia create genome-wide significant synthetic associations, in the latter case extending over a 2.5-Mb interval encompassing scores of \"blocks\" of associated variants. In conclusion, uncommon or rare genetic variants can easily create synthetic associations that are credited to common variants, and this possibility requires careful consideration in the interpretation and follow up of GWAS signals.",
"title": "Rare Variants Create Synthetic Genome-Wide Associations"
},
{
"docid": "1127562",
"text": "Multicellular animals rapidly clear dying cells from their bodies. Many of the pathways that mediate this cell removal are conserved through evolution. Here, we identify srgp-1 as a negative regulator of cell clearance in both Caenorhabditis elegans and mammalian cells. Loss of srgp-1 function results in improved engulfment of apoptotic cells, whereas srgp-1 overexpression inhibits apoptotic cell corpse removal. We show that SRGP-1 functions in engulfing cells and functions as a GTPase activating protein (GAP) for CED-10 (Rac1). Interestingly, loss of srgp-1 function promotes not only the clearance of already dead cells, but also the removal of cells that have been brought to the verge of death through sublethal apoptotic, necrotic or cytotoxic insults. In contrast, impaired engulfment allows damaged cells to escape clearance, which results in increased long-term survival. We propose that C. elegans uses the engulfment machinery as part of a primitive, but evolutionarily conserved, survey mechanism that identifies and removes unfit cells within a tissue.",
"title": "Loss of the RhoGAP SRGP-1 promotes the clearance of dead and injured cells in Caenorhabditis elegans"
},
{
"docid": "21164071",
"text": "Integrins are membrane receptors which mediate cell-cell or cell-matrix adhesion. Integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) acts as a fibrinogen receptor of platelets and mediates platelet aggregation. Platelet activation is required for alpha IIb beta 3 to shift from noncompetent to competent for binding soluble fibrinogen. The steps involved in this transition are poorly understood. We have studied a variant of Glanzmann thrombasthenia, a congenital bleeding disorder characterized by absence of platelet aggregation and fibrinogen binding. The patient's platelets did not bind fibrinogen after platelet activation by ADP or thrombin, though his platelets contained alpha IIb beta 3. However, isolated alpha IIb beta 3 was able to bind to an Arg-Gly-Asp-Ser affinity column, and binding of soluble fibrinogen to the patient's platelets could be triggered by modulators of alpha IIb beta 3 conformation such as the Arg-Gly-Asp-Ser peptide and alpha-chymotrypsin. These data suggested that a functional Arg-Gly-Asp binding site was present within alpha IIb beta 3 and that the patient's defect was not secondary to a blockade of alpha IIb beta 3 in a noncompetent conformational state. This was evocative of a defect in the coupling between platelet activation and alpha IIb beta 3 up-regulation. We therefore sequenced the cytoplasmic domain of beta 3, following polymerase chain reaction (PCR) on platelet RNA, and found a T-->C mutation at nucleotide 2259, corresponding to a Ser-752-->Pro substitution. This mutation is likely to be responsible for the uncoupling of alpha IIb beta 3 from cellular activation because (i) it is not a polymorphism, (ii) it is the only mutation in the entire alpha IIb beta 3 sequence, and (iii) genetic analysis of the family showed that absence of the Pro-752 beta 3 allele was associated with the normal phenotype. Our data thus identify the C-terminal portion of the cytoplasmic domain of beta 3 as an intrinsic element in the coupling between alpha IIb beta 3 and platelet activation.",
"title": "Ser-752-->Pro mutation in the cytoplasmic domain of integrin beta 3 subunit and defective activation of platelet integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) in a variant of Glanzmann thrombasthenia."
},
{
"docid": "10698739",
"text": "Loss of Omi/HtrA2 function leads to nerve cell loss in mouse models and has been linked to neurodegeneration in Parkinson's and Huntington's disease. Omi/HtrA2 is a serine protease released as a pro-apoptotic factor from the mitochondrial intermembrane space into the cytosol. Under physiological conditions, Omi/HtrA2 is thought to be involved in protection against cellular stress, but the cytological and molecular mechanisms are not clear. Omi/HtrA2 deficiency caused an accumulation of reactive oxygen species and reduced mitochondrial membrane potential. In Omi/HtrA2 knockout mouse embryonic fibroblasts, as well as in Omi/HtrA2 silenced human HeLa cells and Drosophila S2R+ cells, we found elongated mitochondria by live cell imaging. Electron microscopy confirmed the mitochondrial morphology alterations and showed abnormal cristae structure. Examining the levels of proteins involved in mitochondrial fusion, we found a selective up-regulation of more soluble OPA1 protein. Complementation of knockout cells with wild-type Omi/HtrA2 but not with the protease mutant [S306A]Omi/HtrA2 reversed the mitochondrial elongation phenotype and OPA1 alterations. Finally, co-immunoprecipitation showed direct interaction of Omi/HtrA2 with endogenous OPA1. Thus, we show for the first time a direct effect of loss of Omi/HtrA2 on mitochondrial morphology and demonstrate a novel role of this mitochondrial serine protease in the modulation of OPA1. Our results underscore a critical role of impaired mitochondrial dynamics in neurodegenerative disorders.",
"title": "Modulation of mitochondrial function and morphology by interaction of Omi/HtrA2 with the mitochondrial fusion factor OPA1."
},
{
"docid": "13777706",
"text": "Polycomb repressor complexes (PRCs) are important chromatin modifiers fundamentally implicated in pluripotency and cancer. Polycomb silencing in embryonic stem cells (ESCs) can be accompanied by active chromatin and primed RNA polymerase II (RNAPII), but the relationship between PRCs and RNAPII remains unclear genome-wide. We mapped PRC repression markers and four RNAPII states in ESCs using ChIP-seq, and found that PRC targets exhibit a range of RNAPII variants. First, developmental PRC targets are bound by unproductive RNAPII (S5p(+)S7p(-)S2p(-)) genome-wide. Sequential ChIP, Ring1B depletion, and genome-wide correlations show that PRCs and RNAPII-S5p physically bind to the same chromatin and functionally synergize. Second, we identify a cohort of genes marked by PRC and elongating RNAPII (S5p(+)S7p(+)S2p(+)); they produce mRNA and protein, and their expression increases upon PRC1 knockdown. We show that this group of PRC targets switches between active and PRC-repressed states within the ESC population, and that many have roles in metabolism.",
"title": "Polycomb Associates Genome-wide with a Specific RNA Polymerase II Variant, and Regulates Metabolic Genes in ESCs"
},
{
"docid": "32743723",
"text": "We examined six patients with an abrupt change in behavior after infarction involving the inferior genu of the internal capsule. The acute syndrome featured fluctuating alertness, inattention, memory loss, apathy, abulia, and psychomotor retardation, suggesting frontal lobe dysfunction. Contralateral hemiparesis and dysarthria were generally mild, except when the infarct extended into the posterior limb. Neuropsychological testing in five patients with left-sided infarcts revealed severe verbal memory loss. Additional cognitive deficits consistent with dementia occurred in four patients. A right-sided infarct caused transient impairment in visuospatial memory. Functional brain imaging in three patients showed a focal reduction in hemispheric perfusion most prominent in the ipsilateral inferior and medial frontal cortex. We infer that the capsular genu infarct interrupted the inferior and anterior thalamic peduncles, resulting in functional deactivation of the ipsilateral frontal cortex. These observations suggest that one mechanism for cognitive deterioration from a lacunar infarct is thalamocortical disconnection of white-matter tracts, in some instances leading to \"strategic-infarct dementia. \"",
"title": "Confusion and memory loss from capsular genu infarction: a thalamocortical disconnection syndrome?"
},
{
"docid": "4455466",
"text": "Recognition of modified histones by ‘reader’ proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific ‘Ser 31’ residue in a composite pocket formed by the tandem bromo–PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.",
"title": "ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression"
},
{
"docid": "20418809",
"text": "A key determinant of geriatric frailty is sarcopenia, the age-associated loss of skeletal muscle mass and strength. Although the etiology of sarcopenia is unknown, the correlation during aging between the loss of activity of satellite cells, which are endogenous muscle stem cells, and impaired muscle regenerative capacity has led to the hypothesis that the loss of satellite cell activity is also a cause of sarcopenia. We tested this hypothesis in male sedentary mice by experimentally depleting satellite cells in young adult animals to a degree sufficient to impair regeneration throughout the rest of their lives. A detailed analysis of multiple muscles harvested at various time points during aging in different cohorts of these mice showed that the muscles were of normal size, despite low regenerative capacity, but did have increased fibrosis. These results suggest that lifelong reduction of satellite cells neither accelerated nor exacerbated sarcopenia and that satellite cells did not contribute to the maintenance of muscle size or fiber type composition during aging, but that their loss may contribute to age-related muscle fibrosis.",
"title": "Inducible depletion of satellite cells in adult, sedentary mice impairs muscle regenerative capacity without affecting sarcopenia"
},
{
"docid": "21487212",
"text": "Ex-FABP, an extracellular fatty acid binding lipocalin, is physiologically expressed by differentiating chicken chondrocytes and myoblasts. Its expression is enhanced after cell treatment with inflammatory stimuli and repressed by anti-inflammatory agents, behaving as an acute phase protein. Chicken liver fragments in culture show enhanced protein expression after bacterial endotoxin treatment. To investigate the biological role of Ex-FABP, we stably transfected proliferating chondrocytes with an expression vector carrying antisense oriented Ex-FABP cDNA. We observed a dramatic loss of cell viability and a strong inhibition of cell proliferation and differentiation. When chondrocytes were transfected with the antisense oriented Ex-FABP cDNA we observed that Ex-FABP down-modulation increased apoptotic cell number. Myoblasts transfected with the same expression vector showed extensive cell death and impaired myotube formation. We suggest that Ex-FABP acts as a constitutive survival protein and that its expression and activation are fundamental to protect chondrocytes from cell death.",
"title": "Inhibition of cell proliferation and induction of apoptosis by ExFABP gene targeting."
},
{
"docid": "23117928",
"text": "Infection of Sulfolobus islandicus REY15A with mixtures of different Sulfolobus viruses, including STSV2, did not induce spacer acquisition by the host CRISPR immune system. However, coinfection with the tailed fusiform viruses SMV1 and STSV2 generated hyperactive spacer acquisition in both CRISPR loci, exclusively from STSV2, with the resultant loss of STSV2 but not SMV1. SMV1 was shown to activate adaptation while itself being resistant to CRISPR-mediated adaptation and DNA interference. Exceptionally, a single clone S-1 isolated from an SMV1 + STSV2-infected culture, that carried STSV2-specific spacers and had lost STSV2 but not SMV1, acquired spacers from SMV1. This effect was also reproducible on reinfecting wild-type host cells with a variant SMV1 isolated from the S-1 culture. The SMV1 variant lacked a virion protein ORF114 that was shown to bind DNA. This study also provided evidence for: (i) limits on the maximum sizes of CRISPR loci; (ii) spacer uptake strongly retarding growth of infected cultures; (iii) protospacer selection being essentially random and non-directional, and (iv) the reversible uptake of spacers from STSV2 and SMV1. A hypothesis is presented to explain the interactive conflicts between SMV1 and the host CRISPR immune system.",
"title": "Inter-viral conflicts that exploit host CRISPR immune systems of Sulfolobus."
},
{
"docid": "7595742",
"text": "Frailty has long been considered synonymous with disability and comorbidity, to be highly prevalent in old age and to confer a high risk for falls, hospitalization and mortality. However, it is becoming recognized that frailty may be a distinct clinical syndrome with a biological basis. The frailty process appears to be a transitional state in the dynamic progression from robustness to functional decline. During this process, total physiological reserves decrease and become less likely to be sufficient for the maintenance and repair of the ageing body. Central to the clinical concept of frailty is that no single altered system alone defines it, but that multiple systems are involved. Clinical consensus regarding the phenotype which constitutes frailty, drawing upon the opinions of numerous authors, shows the characteristics to include wasting (loss of both muscle mass and strength and weight loss), loss of endurance, decreased balance and mobility, slowed performance, relative inactivity and, potentially, decreased cognitive function. Frailty is a distinct entity easily recognized by clinicians, with multiple manifestations and with no single symptom being sufficient or essential in its presentation. Manifestations include appearance (consistent or not with age), nutritional status (thin, weight loss), subjective health rating (health perception), performance (cognition, fatigue), sensory/physical impairments (vision, hearing, strength) and current care (medication, hospital). Although the early stages of the frailty process may be clinically silent, when depleted reserves reach an aggregate threshold leading to serious vulnerability, the syndrome may become detectable by looking at clinical, functional, behavioral and biological markers. Thus, a better understanding of these clinical changes and their underlying mechanisms, beginning in the pre-frail state, may confirm the impression held by many geriatricians that increasing frailty is distinguishable from ageing and in consequence is potentially reversible. We therefore provide an update of the physiopathology and clinical and biological characteristics of the frailty process and speculate on possible preventative approaches.",
"title": "Frailty Syndrome: A Transitional State in a Dynamic Process"
},
{
"docid": "10279084",
"text": "MAP kinase phosphatase-2 (MKP-2) is a member of the family of dual specificity phosphatases that functions to inactivate the ERK and JNK MAP kinase signalling pathways. Here, we identify a novel human MKP-2 variant (MKP-2-S) lacking the MAP kinase binding site but retaining the phosphatase catalytic domain. Endogenous MKP-2-S transcripts and proteins were found in PC3 prostate and MDA-MB-231 breast cancer cells and also human prostate biopsies. Cellular transfection of MKP-2-S gave rise to a nuclear protein of 33kDa which displayed phosphatase activity comparable to the formerly described long form of MKP-2 (MKP-2-L). Due to its lack of a kinase interacting motif (KIM), MKP-2-S did not bind to JNK or ERK; MKP-2-L bound ERK and to a lesser extent JNK. Protein turnover of adenoviral expressed MKP-2-S was accelerated relative to MKP-2-L, with a greater susceptibility to proteosomal-mediated degradation. MKP-2-S retained its ability to deactivate JNK in a similar manner as MKP-2-L and was an effective inhibitor of LPS-stimulated COX-2 induction. However, unlike MKP-2-L, MKP-2-S was unable to reverse serum-induced ERK activation or significantly inhibit endothelial cell proliferation. These findings reveal the occurrence of a novel splice variant of MKP-2 which is unable to bind ERK and may be significant in the dysregulation of MAP kinase activity in certain disease states, particularly in breast and prostate cancers.",
"title": "Differential regulation of MAP kinase activation by a novel splice variant of human MAP kinase phosphatase-2."
},
{
"docid": "23698769",
"text": "DNA polymerase μ (Pol μ) is the only template-dependent human DNA polymerase capable of repairing double-strand DNA breaks (DSBs) with unpaired 3′ ends in nonhomologous end joining (NHEJ). To probe this function, we structurally characterized Pol μ's catalytic cycle for single-nucleotide incorporation. These structures indicate that, unlike other template-dependent DNA polymerases, Pol μ shows no large-scale conformational changes in protein subdomains, amino acid side chains or DNA upon dNTP binding or catalysis. Instead, the only major conformational change is seen earlier in the catalytic cycle, when the flexible loop 1 region repositions upon DNA binding. Pol μ variants with changes in loop 1 have altered catalytic properties and are partially defective in NHEJ. The results indicate that specific loop 1 residues contribute to Pol μ's unique ability to catalyze template-dependent NHEJ of DSBs with unpaired 3′ ends.",
"title": "Sustained active site rigidity during synthesis by human DNA polymerase μ"
},
{
"docid": "29125354",
"text": "The mechanisms underlying the silencing of alternative fate potentials in very early B cell precursors remain unclear. Using gain- and loss-of-function approaches together with a synthetic Zinc-finger polypeptide (6ZFP) engineered to prevent transcription factor binding to a defined cis element, we show that the transcription factor EBF1 promotes B cell lineage commitment by directly repressing expression of the T-cell-lineage-requisite Gata3 gene. Ebf1-deficient lymphoid progenitors exhibited increased T cell lineage potential and elevated Gata3 transcript expression, whereas enforced EBF1 expression inhibited T cell differentiation and caused rapid loss of Gata3 mRNA. Notably, 6ZFP-mediated perturbation of EBF1 binding to a Gata3 regulatory region restored Gata3 expression, abrogated EBF1-driven suppression of T cell differentiation, and prevented B cell differentiation via a GATA3-dependent mechanism. Furthermore, EBF1 binding to Gata3 regulatory sites induced repressive histone modifications across this region. These data identify a transcriptional circuit critical for B cell lineage commitment.",
"title": "Transcriptional Repression of Gata3 Is Essential for Early B Cell Commitment"
},
{
"docid": "43220289",
"text": "Extreme obesity is associated with severe psychiatric and somatic comorbidity and impairment of psychosocial functioning. Bariatric surgery is the most effective treatment not only with regard to weight loss but also with obesity-associated illnesses. Health-related psychological and psychosocial variables have been increasingly considered as important outcome variables of bariatric surgery. However, the long-term impact of bariatric surgery on psychological and psychosocial functioning is largely unclear. The aim of this study was to evaluate the relationship between the course of weight and psychological variables including depression, anxiety, health-related quality of life (HRQOL), and self-esteem up to 4 years after obesity surgery. By standardized questionnaires prior to (T1) and 1 year (T2), 2 years (T3), and 4 years (T4) after surgery, 148 patients (47 males (31.8 %), 101 females (68.2 %), mean age 38.8 ± 10.2 years) were assessed. On average, participants lost 24.6 % of their initial weight 1 year after surgery, 25.1 % after 2 years, and 22.3 % after 4 years. Statistical analysis revealed significant improvements in depressive symptoms, physical dimension of quality of life, and self-esteem with peak improvements 1 year after surgery. These improvements were largely maintained. Significant correlations between weight loss and improvements in depression, physical aspects of HRQOL (T2, T3, and T4), and self-esteem (T3) were observed. Corresponding to the considerable weight loss after bariatric surgery, important aspects of mental health improved significantly during the 4-year follow-up period. However, parallel to weight regain, psychological improvements showed a slow but not significant decline over time.",
"title": "Psychological Outcome 4 Years after Restrictive Bariatric Surgery"
}
] |
3661
|
What would I miss out on by self insuring my car?
|
[
{
"docid": "157630",
"text": "You lose your agent services. When my wife wrecked our car 3 years ago our agent took care of everything. He got us a rental car, made the arrangements to get it fixed, checked in to see how we were doing, and even helped us set up a second opinion on my wifes wrist surgery. The accident was ruled the fault of the uninsured driver who decided to take off through the red light. But our insurance was the one that covered it all total expenses over 80k. We would have had to eat most of those with out full coverage. Most everything was set up (our rental car, estimates on repair, even her inital consutation with the surgeon) before the investigator had filed her report. Our agents first question was is everyone ok. His second was what can i do to help? He never asked us what happened and was always ahead of our needs in dealing with it. If these things are not important to you, you can probably save quite a bit of money self insuring. But if you are in an accident and unable to do them yourself, do you have someone to do it for you? Do you trust them to handle your business and are you willing to saddle them with the responsibility of dealing with it? To me insurance is less about me and more about my family. It was nice that my agent did all of that for me. I would have been willing to do it myself though. But I am glad to know he is there for my wife if something happens to me.",
"title": ""
},
{
"docid": "446714",
"text": "\"If you can afford to replace your car, it is more cost effective, on average and over time, not to carry comprehensive and collision insurance. The insurance companies do make a profit, after all. However, you may be able to worry less (\"\"What if someone steals my car if I park here?\"\") with the insurance, and you have the knowledge the you won't have to spend your own money on a new car if something happens to this one, which may help with financial planning.\"",
"title": ""
},
{
"docid": "434749",
"text": "You're trading a fixed liability for an unknown liability. When I graduated from college, I bought a nice used car. Two days later, a deer came out of nowhere, and I hit it going 70 mph on a highway. The damage? $4,500. If I didn't have comprehensive insurance, that would have been a real hit to me financially. For me, I'd rather just pay the modest cost for the comprehensive.",
"title": ""
},
{
"docid": "495977",
"text": "\"As others have pointed out, it's all about a fixed, small cost versus the potential of a large cost. If you have insurance, you know you will pay a fixed amount per month. There is a 100% probability that you will have to pay this premium. If you don't have insurance, there is a large chance that you will have no cost in any given month, and a small chance that you will have a large cost. Like my home-owners insurance costs me about $50 per month. If I didn't have insurance and my house burned down, I would be out something like $100,000. What's the chance that my house will burn down this month? Very small. But I'd rather pay $50 and not have to worry about it. On the other hand, I just bought a filing cabinet for $160 and the store offered me an \"\"extended warranty\"\" for something like $20 a year. What's the probability that some accident will happen that damages my filing cabinet? Pretty small. Even if it did, I think I could handle shelling out $160. I can imagine my stomach in knots and lying awake at nights worrying about the possibility of losing $100,000 or finding myself homeless. I can't imagine lying awake at nights worrying about losing $160 or being force to stuff my files under the bed. I'll take my chances. When I was young and had even less money than I have now, I bought cars that cost me a thousand dollars or. Even poor as I was, I knew that if the car was totaled I could dig up the cash to buy another. It wasn't worth paying the insurance premium. These days I'm driving a car that cost me $6,000. I have collision and comprehensive insurance, but I think it's debatable. I bought the car with cash to begin with, and if I had to I could scrape up the cash to replace it. Especially considering that my last payment for my daughter's college tuition is due next month and then that expense is gone. :-)\"",
"title": ""
},
{
"docid": "33914",
"text": "As you suspected, there is more than just car replacement taken care of by insurance (some of them are pointed out in Chad's story:",
"title": ""
},
{
"docid": "281040",
"text": "Insurance is to mitigate risk you can't handle yourself. (All insurance, not just car insurance.) The expected value of the insurance will always cost more than the expected value of your loss, that's how the insurance company makes money. But sometimes the known fixed cost is better for your ability to sleep at night than the unknown (though likely lower) variable cost. If you were suddenly hit with a bill the size of your car tomorrow, would you be ok? If so, then you can handle the risk yourself and don't need insurance. If not, then you need the insurance. The insurance company sells thousands of policies and it's much easier to predict the number out of 1000 people that will get in an accident tomorrow than the chance that you specifically will get in an accident tomorrow. So they can manage the risk by making a small amount of money from 999/1000 people and buying the other guy a new car.",
"title": ""
},
{
"docid": "147837",
"text": "\"One way to look at insurance is that it replaces an unpredictable expenses with a predictable fees. That is, you pay a set monthly amount (\"\"premium\"\") instead of the sudden costs associated with a collision or other covered event. Insurance works as a business, which means they intend to make a substantial profit for providing that service. They put a lot of effort in to measuring probabilities, and carefully set the premiums to get make a steady profit*. The odds are in their favor. You have to ask yourself: if X happened tomorrow, how would I feel about the financial impact? Also, how much will it cost me to buy insurance to cover X? If you have a lot of savings, plenty of available credit, a bright financial future, and you take the bus to work anyway, then totaling your car may not be a big deal, money wise. Skip the insurance. If you have no savings, plenty of debt, little prospects for that improving, and you depend on your car to get to work just so you can pay what you already owe, then totaling your car would probably be a big problem for you. Stick with insurance. There is a middle ground. You can adjust your deductible. Raise it as high as you can comfortably handle. You cover the small stuff out of pocket, and save the insurance for the big ticket items. *Insurance companies also invest the money they take as premiums, until they pay out a claim. That's not relevant to this discussion, though.\"",
"title": ""
},
{
"docid": "69495",
"text": "\"Here's what you do without, on the negative side, just for balance: A bill: When I last had comprehensive insurance, it cost something like 3-4% of the value of the car per annum. (Obviously ymmv enormously but I think that's somewhere near the middle of the range and I'm not especially risky.) So, compared to the total depreciation and running costs of the car, it's actually fairly substantial. Over the say 10 years I might keep that car, it adds up to a fair slice of what it will take to buy a replacement. Financial crisis costs: I don't know about you, but my insurance went up something like 30% in recent years, despite the value-insured and the risk going down, said by the insurer to be due to market turmoil. So, at least hundreds of dollars is just kind of frictional loss, and I'd rather not pay it. Wrangling with the insurer: if you have insurance and a loss, you have to persuade them to pay out, perhaps document the original conditions or the fault, perhaps argue about whether their payment is fair. I've done this for small (non-automotive) claims, and it added up to more hassle than the incident itself. Obviously all insurers will claim they're friendly to deal with but until you actually have a big claim you never know. Moral hazard: I know I'm solely responsible for not having my car crashed or stolen. Somehow that just feels better. Free riders: I've seen people \"\"fudge\"\" their insurance claims so that things that shouldn't have been covered were claimed to be. You might have too. Buy insurance and you're paying for them. Choice: Insurers are typically going to make the decision for you about whether a claim is repairable or not, and in my experience are reluctant or refuse to just give you the cash amount of the claim. (See also, moral hazard.) Do it yourself and you can choose whether to live with it, make a smaller or larger repair, or replace the whole vehicle with a second hand one or a brand new one, or indeed perhaps do without a vehicle. A distraction: Hopefully by the time you've been working for a while, a vehicle is not a really large fraction of your net worth. If you lose 10% of your net worth it's not really nice but - well, you could easily have lost that off the value of your house or your retirement portfolio in recent years. What you actually need to insure is genuinely serious risks that would seriously change your life if they were lost, such as your ability to work. For about the same cost as insuring a $x car, you can insure against $x income every year for the rest of your life, and I think it's far more important. If I have a write-off accident but walk away I'll be perfectly happy. And, obviously, liability insurance is important, because being hit for $millions of liabilities could also have a serious impact. Coverage for mechanical failures: If your 8yo car needs a new transmission, insurance isn't going to help, yet it may cost more than the typical minor collision. Save the money yourself and you can manage those costs out of the same bucket. Flexibility: If you save up to replace your car, but some other crisis occurs, you can choose to put the money towards that. If you have car insurance but you have a family medical thing it's no help. I think the bottom line is: insure against costs you couldn't cope with by yourself. There are people who need a car but can just barely afford it, but if you're fortunate enough not to be in that case you don't really need comprehensive insurance.\"",
"title": ""
},
{
"docid": "406036",
"text": "\"Convenience, and of course money. In case of an event, you'll have to spend the full worth of money to fix/replace, while if you're insured - you get the insurance to pay for it. It is up to you to decide, if the money saved on the lower premiums worth the risk of paying much more in case of an event. Of course, the cheaper the car the more it makes sense not to pay the premiums. Many people do that. Regarding the bargaining power, I actually think that you would pay less if it is not going through insurance than the bill the insurance pays. I fixed a nasty dent for like $300 at one shop, while at the other they said \"\"It's $1200, but what do you care, your insurance will cover it\"\" (I had $500 deductible, so in the end it was cheaper for me to pay $300 without the insurance at all).\"",
"title": ""
}
] |
[
{
"docid": "311252",
"text": "Your basic point is correct; the savvy move is to use insurance only to cover losses that would be painful or catastrophic for you. Otherwise, self-insure. In the specific example of car insurance, you may be missing that it doesn't only cover replacement of the car, it also covers liability, which is a hundreds-of-thousands-of-dollars risk. The liability coverage may well be legally required; it may also be required as a base layer if you want to get a separate umbrella policy up to millions in liability. So you have to be very rich before this insurance stops making sense. In the US at least you can certainly buy car insurance that doesn't cover loss of the car, or that has a high deductible. And in fact, if you can afford to self-insure up to a high deductible, on average as you say that should be a good idea. Same is true of most kinds of insurance, a high deductible is best as long as you can afford it, unless you know you'll probably file a claim. (Health insurance in particular is weird in many ways, and one is that you often can estimate whether you'll have claims.) On our auto policy, the liability and uninsured motorist coverage is about 60% of the cost while damage to the car coverage is 40%. I'm sure this varies a lot depending on the value of your cars and how much you drive and driving record, etc. On an aging car the coverage for the car itself should get cheaper and cheaper since the car is worth less, while liability coverage would not necessarily get cheaper.",
"title": ""
},
{
"docid": "217596",
"text": "This is going to be a philosophical answer, but here it goes. What is the purpose of an insurance? In my perspective, insurance is a way to protect yourself from risks in life you can not afford to take. Following this principle, most of the people do not have enough money to fix a Ferrari, or pay the medical expenses of a third party--so insurance against liabilities makes financial sense, but many can afford buying an equivalent car as they are insuring. If you have enough money to buy an equivalent car, you are paying for a risk you can take yourself. Then, instead of paying the comprehensive fee which is used to pay the different accidents, the company's administrative fees and the shareholder profits; I would save your money in a separate account and use it as a self-insurance. That is at least what I do. I even put other insurances and extended warranties, which respective risks I have decided to absorve; that way I diversify my fund.",
"title": ""
},
{
"docid": "147243",
"text": "\"While a lot of the answers focus on cost to replace and how much money you should have for tangible goods. There are a few more issues to consider. However before we get started, these issues are not related to ones net worth. They are related to other factors. Having money certainly helps, but someone worth only $10 may not need to insure their stuff under some circumstances. Insurance is a risk avoidance strategy. As such, it should be used to avoid risks that would otherwise cause issues for you. The normal example is a house. If you lost your house due to fire, would you be able to \"\"make it\"\" while you paid the mortgage off, and got a new mortgage to pay for a new house? This is a relatively simple view, but a good one. These days people tend to look at insurance as a savings account. I payed in X so I am entitled to Y. Heath insurance (a bit more on this later) is exacerbating the issue by selling it's self that way, but it simply isn't true. What your paying the premium for to avoid the risk of loss. Not so you can have a pool of money to draw from in time of need, but so that a time of need should never arise. Which brings us back to, should you get insurance? Tangible Assets Let's assume you have no legal or contractual obligation to have insurance. If you put the money you were spending aside would you have enough money to secure a new asset should your current one just vanish? This is the normal argument. But it has a second side. Do you need the asset at all, or can you just accept the loss. Lets pick on a red neck for a second. While certainly not millionaires, or \"\"well off\"\" by conventional means, the guy with 6 cars on bricks in his lawn does not need to insure 6 cars. If one were to vanish, it may make a hardship but hey, he's got 5 more. So with tangible goods it's more of a question of can you afford to replace the item, do you need to replace the item, and how big a risk is it to you to loose the item? What would you rather loose, the item, or the cost of the insurance? Non-tangible Assets I am going to try to keep this as un-rant like as I can manage, but be aware that I am biased. There are two big examples of non-tangible assets that are commonly insured. Life Insurance, and Health insurance. There are others, but it's very hard to get people to pay money to insure something that they don't actually have. Ideas can be insured, for example, but in order to insure an idea you have to spell it out, at that point why not just file for the patent etc. etc. Keep in mind that a lot of people and companies will insure against losses due to IP theft or other such intangible things. Largely these follow the same rules as tangible assets. This section is meant to focus on those insurances that do not. Life Insurance Life insurance is a bit odd. Were all going to die, so it seems like a \"\"good bet\"\" but what your insuring against with life insurance is an early death. For term life insurance it's a gamble. Will you die before your term runs out. For full life insurance (with no term) it's a different gamble. Will you die before you have paid in what they agreed to pay out. In many cases it's also a gamble that you will miss a payment or two and cancel the policy before you die. If the risk of your death worth the insurance. Usually while young the answer is yes. Do you leave your Family short one earner? Will they make it without the insurance? But as you get older, as life insurance becomes more of a sure thing it also becomes less needed. Your kids move out, there not dependent on you any more. You have retirement accounts setup so your partner need not worry should something happen. What risk exactly are your trying to avoid at this point. You will die. You have planned for that eventuality, it's not a risk anymore, it's a fact. Heath Insurance Is another beast all together. Historically you insured against some catastrophic event, that you couldn't really plan for. Say a heart attack. Surgery and treatment would run in the tens of thousands, so it would ruin you if you didn't have insurance to cover that. That was the risk that you were avoiding. A big, expensive event, causing financial ruin. However, over time it has shifted into something else. The general concept is still there, insure to avoid a risk. But the \"\"risk\"\" has been widened to include all manor of things that are not actually risks. For example a flu. You would go to your doctor, pay your co-pay, and your insurance would pay the rest of the visit. Then you would go to the drug store and get the drugs, pay your co-pay and the insurance pays the rest. But what risk, in this instance are you insuring against? That you can't cover the cost of a doctors visit? That you can't cover the cost of the medication? In this example, a common one, historically the \"\"mother of the house\"\" would go you have a flu, have some chicken noodle soup and go to bed. That would be the end of it. Cost of care is a day's lost wages (or maybe a weeks) and a few cans of soup. However today, because we choose to, the cost of care is much higher. We go to the doctor, pay our co-pays, the insurance has to pay it's part. The doctors office has to carry the cost of the staff it takes to see you, and the staff it takes to handle the claims with the insurance company. And now your flu, cost $1,500. But again that's not exactly true either. With heath insurance and \"\"normal\"\" medical care (like sprained ankles, and colds, etc.) the insurance only really covers the cost of having insurance. In that same flu example, if you went to the doctor as a \"\"self pay\"\" (no insurance) you would often time get a much lower, and reasonable rate. Frequently, under the cost of your standard co-pay. This seems like the doctors being \"\"bad\"\" but it's not. They don't have to file a claim, they don't have to keep track of it. They get immediate payment, not payment 6 months down the line that they need to share with other businesses. With \"\"critical\"\" or \"\"catastrophic\"\" care, heath insurance is still a good thing. If you have a big, unforeseen event, then heath insurance is great at helping you avoid that risk. With chronic (long term) care, your back in the same boat as the flu. Often times you can get better, and cheaper, care as a self pay patent, then as a insured patent. That is not always the case however. So you have to measure your own circumstance, and decide if insurance is right for you. But remember insurance is about risk avoidance, and not about paying less. You will ALWAYS pay more for insurance. It's designed that way. Even if the cost is hidden in many ways. (Taxes, spread out over visits, or prescriptions, etc.)\"",
"title": ""
},
{
"docid": "251065",
"text": "Indeed, there is conservation of money. If the insurance companies have those big buildings and television commercials and CEOs, then that money comes from only one place: the insurance premiums of customers. To say insurance is a good deal is either The benefit and cost of insurance for most: Indeed, of all the answers here, James Turner's is best. If you can't afford to lose something, it is vital to insure it. Ideally insurance would be a non-profit operation to best cover this. Such that people would as a whole lose nothing. Theoretically it could even be slightly for profit by making wise investment decisions, and benefiting from the future value of money by beating inflation. But they don't (see this writeup for slightly dated information on health, and this Wikipedia article for more direction). But even if you are taking an average loss (by using a profit-making insurance company), by taking insurance you avoid the situation where you're crippled by a catastrophe. You are paying a fee to hedge your losses. Like James said, insure what you cannot afford to lose. But realize you're going into a situation where the overall net is an average loss of between 10-50% of your money, on average. Basically you're playing the lottery, except your net losses mostly go to fund the company and the CEOs rather than nominally support education. But you sounded like you understood those ideas well, so... Can you self insure? As others noted, yes, there is the option of self insurance in most places. Even even often when insurance is considered as required. For example, in the US, basically car insurance coverage is required. But generally you are legally able to self insure to cover this requirement: The cost of self insuring: There is one cost to self-insure: time. It takes time to research the laws, time to to satisfy those requirements, and then time to find/setup all the care providers (doctors, mechanics, lawyers, etc). When is it worth it? First, again, you must satisfy the prerequisite: you are able to financially handle the loss of the topic under consideration. At a commenter's request, here is an attempt to better spell out this requirement (though it doesn't appear pertinent to the question asked, it is indeed very important not to mistakenly assume you satisfy this requirement). Can you comfortably cover the level of insurance you would otherwise be taking out. $50,000/$100,000/$50,000 is a common reasonable insurance level, so that would be $200,000. Basically, have enough money to cover the loss of your car, your possible injury expenses, and most importantly the damage and medical of anyone else you hit. You would need to have that value available, optimally in your accounts. Alternatively, you could weigh it against your assets, such that if you had low accounts but a paid off $200,000 house, you could conceivably sell your property and still be able to survive financially afterwards. However, it is indeed dangerous to make this assumption, as there may be additional costs and troubles in selling assets, and you may fail to recognize how precious the property is to you. Having at least double or triple in property you'd be willing to part with might be a more comfortable number. Again, the main idea is: can you afford to lose the insured value tomorrow? Though you hope it wouldn't happen, if someone came and took $200,000+ of yours tomorrow, would you be able to adjust to it relatively easily? If the answer is yes, you've satisfied this requirement. In many states it's easier to understand whether you can meet this requirement: it instead becomes can you take out the liability bond required. If you've met that requirement, then it comes down to the time you'd lose versus the savings you'd gain. To get a fair idea, you'll need: The premium you would pay to purchase the insurance: Since you are likely losing 10-50% of your premiums, it should be fair to make a rough estimate of value lost by using 25% for most purposes (especially given that this still ignores the future value/opportunity cost of your money, which could often be 5-10% if invested well) The value of your time: You must properly identify either: A rough estimate of how much time it will take you to research the legal requirements and meet them, and then to research/handle the subsequent needs that come up which the insurance would take care of in an average year. So try to balance those typical years where you wouldn't have a lot of work to do with a year where you'd need to call repair mechanics or find health practitioners. Perhaps aim high, research/calling usually takes more time than we think. Is this calculation positive? Your estimated net annual benefit (or cost) from self insuring is: 0.25 * (Insurance Premium Per Year) - (Estimated Value of Your Time)*(Estimated Hours Of Work\\Research to Self-Insure Per Year) This is a rough estimate. But if the result is quite positive (and you can afford to cover the hit the insurance would otherwise cover), you're likely better off self-insuring. If the result is quite negative (or you can't cover the possible costs insurance would cover), you're probably better off buying insurance. Finally, indeed there are still a few other factors on each side to consider... Most often those additional pluses and minuses probably are smaller than the primary cost/benefits spelt out earlier. But if you're rich enough to have the money, you're in a situation where you can likely sacrifice a little income to have your peace of mind. So there's certainly a lot to consider in it. But if you're a self starter, I believe you're right that you'll find it's more worthwhile to self-insure if you indeed have the resources.",
"title": ""
},
{
"docid": "393934",
"text": "\"In terms of how to make your decision, here are some considerations. Comprehensive insurance often covers other perils besides collision, including fire, theft, hail or other weather damage, additional liability coverage etc. It may be worth looking at your specific policy to see what is covered. No matter what you do, make sure you have some form of personal liability coverage in case you are sued (doesn't necessarily need to be through the auto policy). While it can make financial sense to drop comprehensive coverage once you can afford to self-insure against collision, this will only be the case if you are certain that you can set aside dedicated savings that you would only need to dip in to in the case of a collision or other major loss. For example, if you only have $5-$10,000 in the bank, and you happen to lose your job, and then the next month you happen to be hit in an accident and the car is totaled, could you afford to replace the car out of pocket? I would recommend looking at dropping comprehensive insurance as similar to a \"\"DNR\"\" (do not resuscitate) order for your car, i.e. under no circumstances would you choose repair the car were it totaled or damaged. For example, if your car's exterior were badly damaged in a hail storm (but still ran fine), would you pay $500 or more to repair it, or would you simply get a new car? Ultimately, this is going to be a judgement call based on how much financial risk you want to take on. Personally, I would continue to pay the extra $300 per year for now in order to insure a $6-8,000 asset (5% of the asset value) However, in the next few years the resale value of your car will continue to decline. If in a few years the car were worth $1,500, I would probably not pay the same $300 a year (or 20% of the asset's value). When you should make that choice depends on how many more years of service you expect to get from the car, which is a very localized question. Hope that helps!\"",
"title": ""
},
{
"docid": "184210",
"text": "Insurance is for events that are both and Unexpected and, for many people, catastrophic events are, for example, sickness, disability, death, car accidents, house fires, and burglaries, for which you may buy health, disability, life, auto, home, and renter's insurance. It may be catastrophic for a family relying on a very old earner for that earner to die, and you can buy life insurance up to a very old age, but the premiums will reflect the likelihood of someone of that age dying within the covered period. The more expected an event is, the more anything referred to as insurance is actually forced savings. Health insurance with no copays on regular checkups expects the insured to use them, so the cost of those checkups plus a profit for the insurance company is factored into the premiums ahead of time. A wooden pencil breaking may be unexpected. Regardless of foreseeability, no one buys insurance on wooden pencils, as the loss of a pencil is not catastrophic. What is catastrophic can be context dependent. Health-care needs are typically unforeseeable, as you don't know when you'll get sick. For a billionaire, needing health-care, while unforeseeable, the situation would not be catastrophic, and the billionaire can easily self-insure his or her health to the same extent as most caps offered by health insurance companies. If you're on a fixed budget buying a laptop, if it unexpectedly failed, that would be catastrophic to you, so budgeting in the cost of insurance or an extended warranty while buying your laptop would probably make sense. Especially if you need that $2000 laptop, spending an extra 17.5% would safeguard against you having to come out of pocket and depleting your savings to replace it, even though that brings you to a grand total of $2350 before taxes. However, if you're in that tight of a situation, I would strongly recommend you to find a less expensive option that would allow you to self-insure. If you found a used laptop for much less (I can even see Apple selling refurbished Macs for less than $1000) you might decide that your budget allows you to self-insure, and you could profit from being careful with your hardware and resolving to cover any issues with it yourself.",
"title": ""
},
{
"docid": "506194",
"text": "\"In general, if you can afford to replace something, you are able to \"\"self-insure\"\". You really want to understand a little of the statistics before you can make a generic call, but my rule of thumb is that insurance via \"\"extended warranty\"\" is rarely a good deal. Here is a simple expected value math formula you can apply (when the > is true, then you should buy it): replacement cost x likelihood of using warranty % > cost of insurance You can then back-compute, what is the likelihood that I'd need to lose this item to break even? Given your numbers: $2000 x Y > $350 or Y > (350/2000) or Y > 17.5% So if you think there is a 17.5% or greater chance that you'll need to have you system replaced (i.e. not just a simple fix) AND (as Scott pointed out) you'll be able to actually use the replacement warranty then the applecare is a good purchase. Note, this only applies to items you can replace out-of-pocket without significant burden, because if you didn't have the $10k to replace your car, it wouldn't matter if the insurance wasn't such a good deal (especially if you need the car to get to work, etc.) So the obvious question is: \"\"Why would a for-profit company ever offer insurance on something they are statistically likely to lose money on?\"\" The obvious answer is \"\"they wouldn't,\"\" but that doesn't mean you should never buy this type of insurance, because you may have statistically significant circumstances. For instance, I purchased a $40 remote helicopter as a gift for my children. I also paid the $5 for a \"\"no questions asked\"\" warranty on it because, knowing my kids, I knew there was a nearly 100% chance they would break it at least once. In this case, this warranty was well worth the $5, because they did break it! Presumably they make money on these warranties because most of the purchasers of the plan are more attentive (or too lazy to make the claim) than in this case. Edit note: I incorporated Scott's comment about likelihood of being able to utilize the warranty into a combined \"\"likelihood of using warranty\"\" term. This term could be broken up into likelihood of needing replacement x likelihood of actually getting company to replace it I didn't do this above because it makes it a little harder to understand, and may not be a major factor in all cases, but you can definitely add it after the fact (i.e. if there's only a 90% chance Applecare will pay out at all, then divide the 17.5% by 0.9 to get 19.4% likelihood of needing the replacement for it to be cost effective). More complete formulas can be derived also (including terms for full replacement costs vs repair costs and including terms for \"\"deductible\"\" type costs or shipping), but I'm trying to keep things relatively simple for those who aren't statistics nerds like I am.\"",
"title": ""
},
{
"docid": "496064",
"text": "If this will be your sole income for the year, going self-employed is the best way to do this: So, here's how to go at it: Total cash in: £2000 Total Tax paid: £0 Admin overhead: approx 3 hours. Legit: 100% :) Edit: Can you tell me that in my case what are the required fields on the invoice? If you're non-VAT registered, there are no legal requirements as to what information you need to put on the invoice -it literally can be a couple of numbers on a napkin, and still be legit. With that said, to make a professional appearance, my invoices are usually structured as follows: Left side: ( Sidenote: why client-specific incremental numbering? Why, so they can't make educated guesses to the number of clients I have at any given time :) ) Right side: Center table: And so far, none of my clients missed any fields, so this should have everything they need to :) Hope this helps, but keep in mind, all of the above is synthetic sugar on the top -ultimately, the relationship you share with your Clients is the thing you will (or will not) get paid for! Edit#2: The voices in my head just pointed out, that I've totally omitted National Insurance contributions in the above. However, and I quote HMRC: If your profits are expected to be less than £5,315 you may not have to pay Class 2 National Insurance contributions. Hence, this won't change the numbers above, either -just make sure to point this out during your registration in the office.",
"title": ""
},
{
"docid": "595152",
"text": "I had my car seized last year and I was charged thousands and had a ton of hardships and almost lost my car and was without it for 2 months due to this. Also they didn't tell me what I was being charged. When I fell behind my car insurance, Wells Fargo automatically started charging me without notifying me. Also what pissed me off was they never told me about the charges when I went into the bank to pay my car note every month. I paid my car note in person every month and I ASKED them every month what my payment was and they never once told me about any additional charges. That's what pissed me off. The fact that I walked into the bank every month, made my payment, and NO ONE informed me of any additional charges. Every month I walked in, verified my payment, and paid in full. I was livid when I received a phone call months later that I owed thousands and when I asked if I could set up a payment plan because I couldn't pay all at once, I was threatened and insulted. Then a week or so later my car is missing from in front of my house and I began the long tedious process of getting it back. It totally fucked up my finances and mental health. I hate Wells Fargo. So fucking shady. This stuff really affects real people.",
"title": ""
},
{
"docid": "210187",
"text": "Back when I was 25 and living near Kansas City, I would put 500-700 miles on my car almost every weekend traveling to other places like Omaha, St. Louis, Iowa City, occasionally Minneapolis, once to Fargo, and one longer trip all the way to Virginia... There's a whole lot of nothing out there so road trips are quite naturally long. They're also quite attractive and I still wouldn't miss an opportunity to get up and drive somewhere for the weekend. But, I have spent less money on cars in my entire lifetime than you have on this single car. I preferred then, and still do, to buy older cars for a few thousand dollars (or even less) and drive them until they die or can no longer pass inspection. Changing the oil is usually the most maintenance I'll do. Since I've spent so little on each car, I don't really care if it suffers some minor damage, or even gets totaled in an accident (which fortunately has never happened), so I would only carry the mandatory liability insurance. This is going to be much cheaper than the full coverage you will have on your car. If something did happen I would just go buy another junker. One such car I bought cost me a grand total of $150 excluding gas and gave me almost 10,000 miles until its transmission fell out. Another that I paid $100 for had difficulty getting over 60 miles an hour, but it did those 500-mile trips almost every weekend for two years before the engine threw a rod. This might not be something you want to do. Perhaps you don't want to be seen driving what one of my exes called a ****mobile because people will misjudge you. But consider that billionaire Sam Walton (of Wal-Mart) could afford any vehicle he wanted, but drove an old pickup truck. I present it as an option because it works for me, and might work for you. And my ex liked my old cars, especially the 1983 Mercury Zephyr station wagon with enough space in the back for a full size bed... Thus you have one possible way to cut your expenses significantly. The only thing left to deal with is parking and its attendant security issues. My ****mobiles have never been stolen, broken into or even looked at funny, though I have never left anything visible in them but the occasional bit of trash. Thieves don't seem to expect an old beater to contain valuables or even be drivable, and a chop shop certainly wouldn't want one. And as I noted in a comment earlier, it's possible to find cheaper monthly parking in NYC if you search carefully; the $130/month example in the Bronx being just the first one I found after 25 seconds on Google. I am pretty sure that if you do some more extensive research you can find cheaper parking that is reasonably secure and at least relatively convenient to your most common travel plans.",
"title": ""
},
{
"docid": "175693",
"text": "It seems like you are asking two different questions, one is, how do I know if I can afford a house? The other is, how do I know what type of mortage to get? The first question is fairly simple to answer, there's plenty of calculators out there that will tell you what you can afford, but rule of thumb is 30% of income can goto housing. Now what type of mortgage to get can be much more confusing, because the mortgage industry makes money off of these confusing products. The best thing to do in my opionion in situations like this is to keep it simple. You need to be careful buying a house. So much money is changing hands and there are so many parasites involved in the transaction I would be extremely wary of anybody who is going to tell you what mortgage to get. I've never heard of a fee only independent mortgage broker, and if I found one that claimed to be I wouldn't believe him. I would just ignore all the exotic non-conforming products and just answer one simple question. Are you the type of person that buys an insurance policy or that likes to self insure? If you like insurance, get a 30 year fixed mortgage. If you like to self insure, get a 7 year ARM. The average lenghth someone owns a house is 7 years, plus in 7 years time, it might not adjust up, and even if it does, you can just accelerate your payments and pay it off quickly (this is the self insurance part of it). If you're like me, I'm willing to pay an extra .5% for the 30 year so that my payment never changes and I'm never forced to move (which is admitedly extremely unlikely, but I like the safety). I don't like 15 year term loans because rates are so low, you can get way better returns in the stock market right now, so why pay off sooner then you need to. Heck, if I had a paid off house right now I'd refi into a 30 year and invest the money. In summary, pick 30 year or ARM, then just shop around to find the lowest rate (which is extremely easy).",
"title": ""
},
{
"docid": "519173",
"text": "\"I do not think you are missing much. One thing you have right is low cost cars depreciate almost nothing. One thing you are missing is your satisfaction index. Driving a 200K car for 4 years requires a bit of motivation when your friends are driving new cars. Typically you need a larger goal to keep you focused. That might be saving money, getting out of debt, or obtaining an education. Buying a car from a private party, Craigslist is only one source, can save both parties money as the \"\"middle man\"\" is cut out. If you have the ability to do so, one can save a lot of money by doing your own brakes. The info is up on youtube, and I typically \"\"earn\"\" between 100-300/hour doing this work myself. Most of the time warranties do not pay off. At the core, they are insurance and insurance companies are in the business to make money. If your car is likely to need repairs a policy may be unattainable or very high in price.\"",
"title": ""
},
{
"docid": "59687",
"text": "\"For the person being hired this is a tricky situation. Specially with the new laws. There is no real magic number that can be applied as a lot will depend on what benefits you want, and what is actually available. This will really shift the spectrum quite a bit. Under the affordibal care act, everyone has to have insurance or pay a ?fine? (were really not sure what to call this yet) but there are two provisions that really mess with the numbers you look at as an employee. First, the cost of heath care has skyrocketed. So the same benefits that you had 5 years ago now cost maybe 10-15 times as much as they used to. This gets swept under the rug a bit because the \"\"main costs\"\" of insurance has only increased a tiny amount. What this actually comes down to is does your new ACA approved heath plan cover exactly the benefits you need, or does it cut corners. Sorry this is complicated, and I don't mean it to come off as a speech against the ACA so I will give an example. My wife has RA, she really has it under control with the help of her RA doctor. This is not something she ever wants to change. Because she has had RA from the age of 15, and because it's degenerative, she doesn't want to spend 5 years working with a new doctor to get to the same place she is with her current doctor. In addition, the main drugs she takes for RA are not covered under any ACA plan, nor are the \"\"substitutions\"\" that her doctor makes (we are trying to have kids so she has to be off the main meds, and a couple of the things this doctor has tried has been meds that reduce inflammation, are pregnancy safe, but are not for the treatment of RA) You now have to take into effect rather the cost of health insurance + the cost of the things now not covered by the heath insurance + the out of pocket expenses is worth the insurance. Second the ACA has set up provisions to straight up trick those people that have lower income and are not paying close attention. When shopping for insurance, they get quotes like \"\"$50 a month\"\" or \"\"$100 a month\"\". The truth is that the remainder of the actual cost is deducted from their tax returns. This takes consideration, because if you thing your paying $50 a month for insurance but your really paying $650 then you need to make sure your doing your math right. Finally, you need to understand how messed up things are right now in the US with heath care. Largely this goes unreported. I'm not really sure why. But in order to do this I will have to give examples. For my wife to see a specialist (her RA doctor) the co-pay is $75. So she goes to the doctor, he charges her $75 and bills the insurance $200. The insurance pays the doctor $50. With out insurance, the visit costs $50. At first you want to blame the doctor for cheating the system, but the doctor has to pay for hours of labor to get the $50 back from the insurance company. From the doctors perspective it's cheaper to take the $50 then it is to charge the insurance company. And by charging the insurance company he has no control over the cost of the co pay. He essentially has to charge more to make the same money and the patient gets the shaft in the process. Another example, I got strep throat last year. I went to the walk in clinic, paid $75, saw the doctor got my Z-Pack for $15, went home crawled in bed and got better. My wife (who still had separate insurance from before the marriage) got strep throat (imagen that) went to the same clinic, they charged her $200 for the visit ($50 co-pay) and $250 for the z-pack ($3 co-pay). The insurance paid the clinic $90 for the visit and $3 for the drugs. Again the patient is left out in this scenario. In this case it worked better for my wife, unless you account for the fact that to get that coverage she had to pay $650/month. My point is that when comparing costs of heathcare with insurance, and without out insurance, its often times much cheaper for the practices to have you self pay then it is for them to go through the loops of trying to insurance to make them whole. This creates two rates. Self pay rates and Insured rates. When your trying to figure out the cost of not having insurance then you need to use the self pay rates. These can be vastly different. So as an employee you need to figure out your cost of heath care with insurance, and your cost of heath care without insurance. Then user those numbers when your trying to negotiate a salary. The problem is that there is no magic number to use for this because the cost will very a lot. For us, it was cheaper to not have insurance. Even with a pre-existing condition that takes constant attention, it's just better if we set aside $500 a month then it is to try to pay $750 a month. That might not hold true for everyone. For some people or conditions it may be better to pay the $750 then to try to handle it themselves. So for my negotiations I would go with x+$6,000 without insurance or x+$4,500 with insurance. Now as an employer it's a lot simpler. Usually you have a \"\"group plan\"\" that offers you a pretty straight $x per year per person or $y per year per family. So you can offer exactly that. Salary - $x or Salary - $y. AS a starting point. However this is where negotiations start. If your offering me $50,500 and insurance, I would rather just have $57,000 and no insurance. Of course your real cost is only $55,000 cause you don't care about my heath care costs only about insurance costs. So you try to negotiate down towards $55,000 and no insurance. But that's not good enough for me. So I either go else where and you loose talent, or I accept $50,500 and insurance (or somewhere in between).\"",
"title": ""
},
{
"docid": "516631",
"text": "I might be missing something, but I always understood that leasing is about managing cash-flow in a business. You have a fixed monthly out-going as opposed to an up-front payment. My accountant (here in Germany) recommended: pay cash, take a loan (often the manufactures offer good rates) or lease - in that order. The leasing company has to raise the cash from somewhere and they don't want to make a loss on the deal. They will probably know better than I how to manage that and will therefore be calculating in the projected resale value at the end of the leasing period. I can't see how an electric car would make any difference here. These people are probably better informed about the resale value of any type of car than I am. My feeling is to buy using a loan from the manufacturer. The rates are often good and I have also got good deals on insurance as a part of that package. Here in Germany the sales tax (VAT) can be immediately claimed back in full when the loan deal is signed.",
"title": ""
},
{
"docid": "80838",
"text": "Having recently been given basically the same question it hinges on a few major factors. What does your apartment provide (e.g. heating, internet/etc)? My (personal) example. With my numbers (which includes taxes, insurance estimates, minor repairs to home as needed), also ignoring all costs that are shared (e.g. food, internet, car insurance, etc), I am only making a difference around $450 per month. In 5 years I would save ($450 * 12 * 5) $27,000. However I also have to pay costs for buying the house (transfer deed, laywer fees, home inspections, etc) which in my case cost around $3000. Not to mention selling a home has some costs (I think around $1500+ in my area) as well as the realitor taking a cut (which I also think is around 2.5% = $7,225. So we can probably estimate you would lose around $15000 at most, buying and selling the home when all final costs come in. Which means in my case I would at most be saving around $12,000... probably less (assuming I did not miss anything). So basically 12,000/(12*5) = $200 per month saved. TLDR: I don't think its worthwhile, because there is a lot of risks involved, and houses tend to require a lot of extra work/money. With apartments you have little/no risk, and can freely leave at the end.",
"title": ""
},
{
"docid": "280805",
"text": "Some things you missed in your analysis: How will financing change your insurance costs? I.e. what is the difference between the insurance that you would buy for yourself and what they require? Note that it is possible that your insurance preferences are more stringent than the financing company's. If so, this isn't a big deal. But what's important is to consider if that's true. Because if you'd prefer to drive with only the legal minimum insurance and they insist that you have full coverage with no more than a $1000 deductible, that's a significant difference. Remember that you don't have $22.5k for six years. You have an average of $10.5k (($22.5k + -$1500)/2) for six years. Because you make payments ($24k) throughout. So you start with $22.5k and subtract $333.33 a month until you reach -$1500. That neglects both investment gains and potential losses. It's not the $333 payment that will freak out mortgage companies. It's the $24k debt. But that's offset by your $22.5k in assets at the beginning. And the car of course counts as an asset, albeit at lower than its sale value. I.e. from the bank's perspective, paying $22.5k for a car out of savings is almost as bad as borrowing $24k for a car. Both reduce your net worth. Watch out for hidden fees. In particular, 0% interest can often change into higher interest under certain circumstances. If we assume a 7% return for the six years, that's about $1400 the first year and less each year after. Perhaps $4500 over six years. But you aren't going to get a 7% return if you keep $24,000 in a bank account in case you have to pay off the loan. Instead, you'll get more like 1%, less than inflation. Even five year Certificates of Deposit are only about 2%, right around inflation (1.9% for previous twelve months). You can't keep the $24,000 in a securities account and be sure that it will be there when you need it. If the market crashes tomorrow, your $24,000 might be worth $12,000 instead. You'd have to throw in extra money from elsewhere. Instead of making $4500 at the cost of $1500, you'd have paid $25,500 for $12,000. Not a good deal. So for your plan to work, that $24,000 needs to be in an account that won't fall in value. You either need to compromise on the idea of a separate account that is always there when you need it, or you have to accept rather low returns. Personally, I would prefer not to have the debt and not to pay extra on the insurance. But that's me. The potential investment returns are not worth it to me. If you give up the separate account, you can make a few thousand dollars more. But your risk is higher.",
"title": ""
},
{
"docid": "370108",
"text": "\"You're making the assumption that a person would be aware, in advance, that they'd have enough resources to pay the costs of anything that might happen. Second, you're assuming the cost of insurance would outweigh what the person would have to pay out of pocket if they didn't have insurance. In other words as an example, if the insurance premiums on my car are so high that it would be cheaper for me to replace it myself in cash then it might make sense, but how likely is that to be the case? There's a gambling adage that I think applies here - \"\"Always bet with the house's money\"\". Why would I put my own money on the line in the event of some event rather than pay for an insurance policy that takes care of it for me? That way, my costs are predictable and manageable - I pay the premiums and perhaps a deductible, and that's it.\"",
"title": ""
},
{
"docid": "495874",
"text": "\"The two questions inherent in any decision to purchase an insurance plan is, \"\"how likely am I to need it?\"\", and \"\"what's the worst case scenario if I don't have it?\"\". The actuary that works for the insurance company is asking these same questions from the other end (with the second question thus being \"\"what would we be expected to have to pay out for a claim\"\"), using a lot of data about you and people like you to arrive at an answer. It really boils down to little more than a bet between you and the insurance company, and like any casino, the insurer has a house edge. The question is whether you think you'll beat that edge; if you're more likely than the insurer thinks you are to have to file a claim, then additional insurance is a good bet. So, the reasons you might decide against getting umbrella insurance include: Your everyday liability is low - Most people don't live in an environment where the \"\"normal\"\" insurance they carry won't pay for their occasional mistakes or acts of God. The scariest one for most is a car accident, but when you think of all the mistakes that have to be made by both sides in order for you to burn through the average policy's liability limits and still be ruined for life, you start feeling better. For instance, in Texas, minimum insurance coverage levels are 50/100/50; assuming neither party is hurt but the car is a total loss, your insurer will pay the fair market value of the car up to $50,000. That's a really nice car, to have a curbside value of 50 grand; remember that most cars take an initial hit of up to 25% of their sticker value and a first year depreciation of up to 50%. That 50 grand would cover an $80k Porsche 911 or top-end Lexus ES, and the owner of that car, in the U.S. at least, cannot sue to recover replacement value; his damages are only the fair market value of the car (plus medical, lost wages, etc, which are covered under your two personal injury liability buckets). If that's a problem, it's the other guy's job to buy his own supplemental insurance, such as gap insurance which covers the remaining payoff balance of a loan or lease above total loss value. Beyond that level, up into the supercars like the Bentleys, Ferraris, A-Ms, Rollses, Bugattis etc, the drivers of these cars know full well that they will never get the blue book value of the car from you or your insurer, and take steps to protect their investment. The guys who sell these cars also know this, and so they don't sell these cars outright; they require buyers to sign \"\"ownership contracts\"\", and one of the stipulations of such a contract is that the buyer must maintain a gold-plated insurance policy on the car. That's usually not the only stipulation; The total yearly cost to own a Bugatti Veyron, according to some estimates, is around $300,000, of which insurance is only 10%; the other 90% is obligatory routine maintenance including a $50,000 tire replacement every 10,000 miles, obligatory yearly detailing at $10k, fuel costs (that's a 16.4-liter engine under that hood; the car requires high-octane and only gets 3 mpg city, 8 highway), and secure parking and storage (the moguls in Lower Manhattan who own one of these could expect to pay almost as much just for the parking space as for the car, with a monthly service contract payment to boot). You don't have a lot to lose - You can't get blood from a turnip. Bankruptcy laws typically prevent creditors from taking things you need to live or do your job, including your home, your car, wardrobe, etc. For someone just starting out, that may be all you have. It could still be bad for you, but comparing that to, say, a small business owner with a net worth in the millions who's found liable for a slip and fall in his store, there's a lot more to be lost in the latter case, and in a hurry. For the same reason, litigious people and their legal representation look for deep pockets who can pay big sums quickly instead of $100 a month for the rest of their life, and so very few lawyers will target you as an individual unless you're the only one to blame (rare) or their client insists on making it personal. Most of your liability is already covered, one way or the other - When something happens to someone else in your home, your homeowner's policy includes a personal liability rider. The first two \"\"buckets\"\" of state-mandated auto liability insurance are for personal injury liability; the third is for property (car/house/signpost/mailbox). Health insurance covers your own emergency care, no matter who sent you to the ER, and life and AD&D insurance covers your own death or permanent disability no matter who caused it (depending on who's offering it; sometimes the AD&D rider is for your employer's benefit and only applies on the job). 99 times out of 100, people just want to be made whole when it's another Average Joe on the other side who caused them harm, and that's what \"\"normal\"\" insurance is designed to cover. It's fashionable to go after big business for big money when they do wrong (and big business knows this and spends a lot of money insuring against it), but when it's another little guy on the short end of the stick, rabidly pursuing them for everything they're worth is frowned on by society, and the lawyer virtually always walks away with the lion's share, so this strategy is self-defeating for those who choose it; no money and no friends. Now, if you are the deep pockets that people look for when they get out of the hospital, then a PLP or other supplemental liability insurance is definitely in order. You now think (as you should) that you're more likely to be sued for more than your normal insurance will cover, and even if the insurance company thinks the same as you and will only offer a rather expensive policy, it becomes a rather easy decision of \"\"lose a little every month\"\" or \"\"lose it all at once\"\".\"",
"title": ""
},
{
"docid": "252859",
"text": "Considering I'm putting 30% down and having my father cosign is there any chance I would be turned down for a loan on a $100k car? According to BankRate, the average credit score needed to buy a new car is 714, but they also show average interest rates at 6.39% for new-car loans to people with credit scores in the 601-660 range. High income certainly helps offset credit score to some extent. Not every bank/dealership does things the same way. Being self-employed you'd most likely be required to show 2 years of tax returns, and they'd use those as a basis for your income rather than whatever you have made recently. If using a co-signer, their income matters. Another key factor is debt to income ratio, if too much of someone's income is already spoken for by other debts a lender will shy away. So, yes, there's a chance, given all the information we don't know and the variability with lender policies, that you could be turned down for a car loan. How should I go about this? If you're set on pursuing the car loan, just go talk to some lenders. You'll want to shop around for a good rate anyway, so no need to speculate just go find out. Include the dealership as a potential financing option, they can have great rates. Personally, I'd get a much cheaper car. Your insurance premium on a 100k car will be quite high due to your age. You might be rightly confident in your earning potential, but nothing is guaranteed, situations can change wildly in short order. A new car is not a good investment or a value-retaining asset, so why bother going into debt for one if you don't have to? If you buy something in cash now, you could upgrade in a few years without financing if your earning prediction holds and would save quite a bit in car insurance and interest over the years between.",
"title": ""
},
{
"docid": "250672",
"text": "I respectfully disagree with @JohnFX's comment regarding new vs used. (John knows what is talking about though; he gave an awesome answer on buying a car: What are some tips for getting the upper hand in car price negotiations?) The answer to your question is based on whether or you not you can stand to have a small, loud, cheap but reliable car for the next 10 or 15 years. If you plan to keep your new car until it dies 20 years from now, then a new car can be a fine choice. I just bought a car and the difference between my 2013 Hyundai and a comparable 2012 Hyundai wasn't much. Furthermore, it was hard to even find a 2012 (which justifies the higher price from dealerships and the private market). Doing math in my head told me the reduced usage I will get out of the car wasn't offset by the slightly lower price. Depending on the specific age, insurance on newer cars can be cheaper than insurance on older cars. (But you have to have carry more insurance, so consider that as well.) There might not be a different between a 2010 and a 2012, but there will likely be for a 2005 and the 2013. New cars can be cheaper to operate. Lower fuel costs, better safety and possibly pollution costs. They are tuned up and you know everything about their history. Repairs and factory warranties might not be available on a used car, so if you car turns out to be a problem, your out of pocket is limited. These programs don't mean anything. Get an independent certified mechanic to check out any used car you buy. If the dealer won't let you get the car checked out, then they aren't worth your business. Certified cars don't justify their cost according to consumer reports, they are more for marketing than reliability. Don't waste money on a third party warranty. Either the car is good and doesn't need it, or it needs a warranty and you shouldn't buy it. If you new car comes with a factory warranty, that is fine. Radio host Clark Howard is indifferent if you want to purchase a factory warranty separately, but never a third party. Just out of college, you probably will be better off spending the least amount of money you can for a good used car. If for no other reason, this likely isn't going to be your car in the near future. (Only you can answer that) If you have a feeling you won't keep your tiny car well into your 30s, then definitely don't buy a new car. Also, my experience only applies to my make and model. Certain models of cars keep their value and the difference between new and used isn't much for the most recent model years. But there are many more makes and models that don't pan out that way.",
"title": ""
},
{
"docid": "545305",
"text": "Regarding auto insurance, you have to look at the different parts. In the United Sates most states do require a level of specific coverage for all drivers. That is to make sure that if you are at fault there is money available to pay the victims. That payment may be for damage to their car or other property, but it also covers medical costs. Many policies also cover you if the other driver doesn't have insurance. The policy that covers the loss of the vehicle is required if you have a loan or are leasing the car. Somebody else owns it while there is a loan, so they can and do require you to pay to protect the vehicle. If there i no loan you don't have to have that portion of a policy. Other parts such as towing, roadside assistance, and rental cars replacement may be required by the insurance standards for your state, or might be almost impossible to drop because all insurance companies include it to stay competitive with their competition. Dropping the non-required parts of the coverage is acceptable when you don't have a loan. Some people do drop it to save money. But that does mean you are self insuring. If you can afford to self insure a new car, great. The interesting thing is that some people have more than enough assets to self inure the non-required part of auto insurance. But then they realize that they do need to up their umbrella liability insurance. This is to protect them from somebody deciding that their resources make them a tempting target when they are involved in a collision.",
"title": ""
},
{
"docid": "4604",
"text": "This person could buy another car at any moment without any money problems, so I don't really see any point in insuring, especially with such a ridiculously high price compared to the extremely low risk. Convenience. If you self-insure, then an accident means that you have to make arrangements to get the car towed, fixed, evaluated, etc. If you buy insurance, your insurer would prefer to do all that. They argue with the mechanic over prices, the lawyer over liability, etc. And of course, rich people need more liability insurance than other people, not less. So part of that $1400 is probably money that your friend would have to pay regardless.",
"title": ""
},
{
"docid": "545800",
"text": "\"The general answer to this is \"\"yes\"\". When you're dealing with single-digit millionaires, the answer is that their insurance habits and needs are basically the same as everyone else. When you get into the double digit and triple digit millionaires, or people worth billions, they have additional options, but those basically boil down to using \"\"self-insurance\"\" rather than paying a company for an insurance policy. The following is based on both what I've read and a fair deal of personal experience working for or with various stripes of millionaire, and even one billionaire. Addressing the types of insurance you mention: This is generally used to provide survivors with a replacement for income you can no longer provide when dead, in addition to paying for costs associated with dying (funeral, hospital/hospice bills, etc). Even millionaires and billionaires have this, yes, but the higher your net worth, the less value it has. If you're worth 9 or 10 figures, you probably already have trust funds set up for your family members, so an extra payout from an insurance policy is probably going to represent a small fraction of the wealth you're leaving your survivors, and as has been noted, insurance makes a profit, so the expectation by the insurance company is that they'll make more money on the policy than they'll have to pay out on death. That being said, the members of the 9+ figure club I've worked for all had multi-million dollar life insurance policies on them, which were paid for or heavily subsidized by the companies they owned or worked for. I doubt they would have held those policies if they had to pay the full cost, but when it's free or cheap, why not? Absolutely. As health insurance in America is an untaxed employment benefit, owing to regulations from World War II, all the wealthy folks I've had contact with got outrageously good plans as part of the companies they work for or owned. Having said that, even their trust fund beneficiaries held health insurance, because this type of insurance (in America, at least) is actually not really insurance, it's more of a pre-payment plan for medical expenses, and as such, it provides broader access to health care than you'd get from simply having enough money to pay for whatever treatments you need. If you walk into a hospital as a millionaire and state that you'll definitely be able to pay for your open-heart surgery with cash, you'll get a very different response than if you walk in with your insurance card and your \"\"diamond-level\"\" coverage. So, in this case, it's not as much as about the monetary benefits (although this is a type of \"\"insurance\"\" that's generally free or heavily discounted to the individual, so that's a factor) as it is about easier access to health care. Although this is required by law, it's one of the common forms of insurance that the very wealthy can, and often do handle differently than the rest of us. Most (if not all) US states have a provision to allow motorists to self-insure themselves, which amount to putting up a bond to cover claims against them. Basically, you deposit the minimum amount the state determines is required for auto insurance with the responsible state organization, get a certificate of self-insurance and you're good to go. All the high wealth individuals I know when this route, for two reasons - first of all, they didn't have to deal with insurance companies (or pay sky-high rates on account of all the speeding tickets they picked up) and secondly, they made their deposit with government bonds they had in their portfolios anyway, and they could still collect the interest on their self-insurance deposits. Of course, this meant that if they wrecked or dinged up their Maserati or Bentley or whatever, they'd be out of pocket to repair or replace it... but I guess if you can afford one $200,000 car, you can afford to buy a second one if you wreck it, or get by riding one of your other luxury automobiles instead. Since someone else mentioned kidnapping insurance, I'll point out here that what Robert DeNiro did in Casino when he put a couple million dollars into a safety deposit box for his wife to use if he was kidnapped or needed to pay off a government official is essentially the same thing as \"\"self-insurance\"\". Putting money away somewhere for unexpected events in lieu of buying an insurance policy against them. In real life, the very wealthy will often do this with US treasuries, government bonds and other interest-bearing, safe investments. They make a little money, diversify their portfolios and at the same time, self-insure against a potential big loss. This is another insurance area where even the very wealthy are remarkably similar to the rest of us, in that they all generally have it, yes, although the reason is a little different. For normal folks, the home they own is generally the largest part of their net worth, or at least a very substantial fraction, for those older folks with retirement savings that exceed the value of their homes. So for us, we have home owners insurance to prevent a catastrophic event from wiping out the lion's share of our net worth. If you're an ultra-wealthy individual who can afford an 8 figure home, that's not really the case (at least with the ones I've dealt with, who made their fortunes in business and are good managing their wealth and diversifying their assets - could be different for sports stars or the entertainment industry), and these people generally own multiple homes anyway, so it's not as big a deal if they lose one. However, no one actually buys a multi-million dollar home by writing a multi-million dollar check. They get a mortgage, just like the rest of us. And to get a mortgage, insurance on the property is a requirement. So yes, even the ultra wealthy generally have insurance on their home(s). There is an element of not wanting to shell out another 20 million if the place burns down, or someone breaks in and steals your valuables, but the bigger part of the reason is that it's required to get a mortgage in the first place, which is generally done for financial reasons - interest on your mortgage is a tax deduction, and you don't want to sink millions of dollars all at once into buying a property that's not going to appreciate in value, when you can get a mortgage and invest those millions of dollars to make more money instead.\"",
"title": ""
},
{
"docid": "564420",
"text": "I haven't looked at that warranty in detail, but generally speaking this should help. What is GAP insurance? In the case of a total loss/write off gap insurance covers the outstanding finance after your regular insurance pay out. The two won't match up usually because of the depreciation right after you buy the car. For example, if you take out $20,000 finance and buy a car, then write it off after six months, your insurance company may only value it at $16,000 but it's unlikely you will have cleared $4,000 from your finance. Gap insurance will pay out the difference and settle the debt. Will Chrysler change the engine, if it comes to bhore? Yes, unless they identify misuse or deliberate damage. For instance, if you do 1000 miles and the engine explodes, it's a mechanical fault that the warranty would cover. If they open up the engine/look at diagnostics and find it's been thrashed to within an inch of it's life, they may claim it was your driving which has destroyed the engine and you would have to prove it was an underlying fault and would have blown either way. Will car dents be covered with this bumper to bumper insurance? Not likely, as I mentioned in the last point, if it's your fault it wouldn't be covered. I think you may be confusing the terms insurance and warranty at this point. Insurance would cover your dents but a warranty only covers the manufacturer's faults, even in the case of extended warranties. What does basic mean in terms of warranty? Sounds obvious, but whatever Chrysler want it to mean! There's no legal definition of 'basic' so you would need to check the documents thoroughly or ask them to explain exactly what is and isn't covered. If they're reluctant, it's probably because 'basic' covers very little...",
"title": ""
},
{
"docid": "502126",
"text": "As someone who has worked for both an insurance carrier and an insurance agent, the reason people buy insurance is two fold: to spread risk out, and to get the benefits (when applicable) of approaching risk as a group. What you are really doing when you buy insurance is you are buying in to a large group of people who are sharing risk. You put money in that will help people when they take a loss, and in exchange get a promise of having your losses covered. There is an administrative fee taken by the company that runs the group in order to cover their costs of doing business and their profits that they get for running the group well (or losses they take if they run it poorly.) Some insurances are for profit, some are non-profit; all work on the principle of spreading risk around though and taking risk as a larger group. So let's take a closer look at each of the advantages you get from participating in insurance. The biggest and most obvious is the protection from catastrophic loss. Yes, you could self-insure with a group size of one, by saving your money and having no overhead (other than your time and the time value of your money) but that has a cost in itself and also doesn't cover you against risk up front if you aren't already independently wealthy. A run of bad luck could wipe you out entirely since you don't have a large group to spread the risk around. The same thing can still happen to insurance companies as well when the group as a whole takes major losses, but it's less likely to occur because there are more rare things that have to go wrong. You pay an administrative overhead for the group to be run for you, but you have less exposure to your own risks in exchange for a small premium. Another significant but less visible advantage is the benefit of being part of a large group. Insurance companies represent a large group of people and lots of business, so they can get better rates on dealing with recovering from losses. They can negotiate for better health care rates or better repair rates or cheaper replacement parts. This can potentially save more than the administrative overhead and profit that they take off the top, even when compared to self-insuring. There is an element of gambling to it, but there are also very real financial benefits to having predictable costs. The value of that predictability (and the lesser need for liquid assets) is what makes insurance worth it for many people. The value of this group benefit does decrease a lot as the value of the insurance coverage (the amount it pays out) decreases. Insurance for minor losses has a much smaller impact on liquidity and is much easier to self insure. Cheaper items that have insurance also tend to be high risk items, so the costs tend to be very high relative to the amount of protection. If you are financially able, it may make more sense to self-insure in these cases, particularly if you tend to be more cautious. It may make sense for those who are more prone to accidents with their devices to buy insurance, but this selection bias also drives the cost up further. Generally, the reason to buy insurance on something like a cellphone is because you expect you will break it. You are going to end up paying for an entire additional phone over time anyway and most such policies stop paying out after the first replacement anyway. The reason why people buy the coverage anyway, even when it really isn't in their best interest is due to two factors: being risk averse, as base64 pointed out, and also being generally bad at dealing with large numbers. On the risk averse side, they think of how much they are spending on the item (even if it is less compared to large items like cars or houses) and don't want to lose that. On the bad at dealing with large numbers side, they don't think about the overall cost of the coverage and don't read the fine print as to what they are actually getting coverage for. (This is the same reason that you always see prices one cent under the dollar.) People often don't really subconsciously get that they are paying more even if they would be able to eat the loss, so they pay what feels like a small amount to offset a large risk. The risk of loss is a higher fear than the known small, easy payment that keeps the risk away and the overall value proposition isn't even considered.",
"title": ""
},
{
"docid": "265177",
"text": "\"In regards to purchasing full coverage on your car even if you can afford to replace it, consider the hassle you have to deal with an accident that is not just the cost. As an example, my sister's car was stolen and wrecked. It was her problem to go recover the car on the other side of the state such that she would not be paying the storage \"\"fees\"\" imposed by the sheriff of the other county. Had she had insurance they would have taken care of it call. Another story is that I rented a car and side swiped in the parking lot by a hit and run. I was responsible for the minor damage. I started down the path of paying out of pocket because it was small enough that I did not want to submit a claim. The rental car agency started to pile on extra fees such that it was worth it to turn in a claim. My insurance company was savvy enough to be able to dispute the extra charges. After I submitted it to the insurance company I basically did nothing. They took care of everything. So, in summary, when you buy full coverage on your car, it is not just a financial decision. It is also about not having to deal with a hassle.\"",
"title": ""
},
{
"docid": "528361",
"text": "You will be categorized as self employed. Will I have to register myself as a company or can go on unregistered and work You can register a company or can use an umbrella company or work as a sole trader. Remember as a sole trader you are legally responsible for you company's activities, an if a company sues you for your work he can take compensation from your personal assets. As a company your liability ends with the company, if your company is sued. Your personal assets are outside the purview of the lawsuit, but the court can attach that also but those are rare. This doesn't matter if you use an umbrella company. If you intend to be doing this for a short time(maybe a year or so), go for an umbrella company. Else register a company. will take you 5 minutes to form one. Depending on your earning you might need to register for VAT too. A comprehensive guide for self employed on HMRC. what would i need to be sound in uk and to be fit to work online as a freelancer? The same as above. Will it include paying any tax or paying any insurance Yes you have register for National Insurance(NI), before you can pay yourself a salary. The benefit of a company is you pay yourself a minimum salary, below the limit above which you have to contribute for NI, and take the rest as dividends. And pay no tax on it, till you don't exceed the limits. When the money comes in my account, will i be accountable to government of uk, to tell the source of income? If you are operating through a company, yes you would need to show your income(including source) and expenditure when you do your annual returns. What should i be knowing, like health insurance and things that are necessities in uk for a freelancer ? No health insurance as NHS exists. You can take out health insurance if you don't want to get into queues in NHS.",
"title": ""
},
{
"docid": "278611",
"text": "\"Since it's not tagged united-states, I'd like to offer a more general advice. Your emergency fund should match the financial risks that are relevant to you. The two main classes of financial risk are of course a sudden increase in costs or a decrease in income. You'd have to address both independently. First, loss of income. For most, this would simply equate to the loss of a job. How much benefits would you expect to get, and for how long? This is often the most important question; the 6 months advise in the US is based on a lack of benefits. With two incomes, you're less likely to lose both jobs at the same time. That's a general advise, though. If you both work for the same employer, the risk of losing two jobs at the same time is certainly real. Also, in countries with little protection against dismissal (such as the US), the chance of being layed off at the same time is also higher. On the debit side, there are also two main risks. The first is the loss or failure of an essential possession, i.e. one which requires immediate replacement. This could include a car, or a washing machine. You already paid for one before, so you should have a good idea how much it costs. The second expenditure risk is health-related costs. Those can suddenly crop up, but often you have some kind of insurance. If not, you'd need to account for some costs, but it's hard to come up with an objective number here. The two categories are dependent, of course. Health-related costs may very well coincide with a loss of income, especially if you're self-employed. Now, once you've figured out what the risks are, it's time to figure out how to insure against them. Insurance might be a better choice than an emergency fund, especially for the health costs. You might even discover that you don't need an emergency fund at all. In large parts of Europe, you could establish a credit margin that's not easily revoked (i.e. overdraft agreements), and unemployment benefits are sufficient to cover your regular cost of living. The main risk would then be a sudden lack of liquidity if your employer goes bankrupt and fails to pay the monthly wages, which means your credit should be guaranteed sufficient to borrow one month of expenses. (This of course assumes quite good credit; \"\"pay off my car\"\" doesn't suggest that.)\"",
"title": ""
},
{
"docid": "485318",
"text": "As a recent college grad who switched to his own car insurance, many of the things I did myself are reflected here. The #1 thing I did was find out what coverages I had, what coverages some friends of mine had (car enthusiasts mostly - they're the most informed on this stuff), and then figured out what kind of coverages I wanted. From there, I went around getting quotes from anyone and everyone and eventually built out a sizeable spreadsheet that made it obvious which company was going to offer me the best rate at a given coverage level. Something else to remember - not all insurance companies look at past accidents and violations (speeding, etc) the same. In my search, I found some have a 3-year scope on accidents and violations, while others were as much as 5 years. So, if your driving record isn't a shining example (mine isn't perfect), you could potentially save money by considering insurance through a company that will see fewer violations/incidents than another because of the size of their scope. I ended up saving $25/mo by choosing a company that had a 3-year scope, which was on the cusp of when my last violation/incident occurred. Insurance companies will also give out discounts for younger drivers based on GPA average. If you have kids and they maintain a high GPA, you might be able to get a discount there. Not all companies offer it, so if they do it's worth finding out how much it is",
"title": ""
},
{
"docid": "477552",
"text": "\"I wish I was in your shoes with the knowledge I have in my head. financial goal setting is a great plan at your age. In my humble opinion you don't want to save for anything... you want to invest as much as you can, create a corporation and have the corporation invest as much as possible. When there is enough monthly cash flow coming from your investments... have the corporation buy you a house, a car, take out an insurance policy on you as key employee... etc. As for the $11,000 laying around in cash as an emergency fund, no way! With returns as high as 1-3% per month invested properly keep it invested. Getting to your emergency cash reserve you have in a trading account is only a couple key strokes away. As for the 401k... If it is not making at least 25% yearly for the last 10 years (excluding your Contributions) do it yourself in a self directed IRA. Oh... I forgot to mention When your corporation buys your stuff... if set up correctly you can take them as a loss in the corporate ledger and you know any loss from one entity can offset profits from another, thus reducing any taxes you may have. My friend you are at the point of great beginnings, hard choices and an open door to what ever you want your future to look like. Decide what you want out of your money and don't take \"\"NO YOU CAN'T DO THAT\"\" as an answer. Find someone that will tell you these secrets, they are out there. Good luck.\"",
"title": ""
}
] |
PLAIN-2898
|
The Ice Diet
|
[
{
"docid": "MED-4768",
"text": "The rapid increase in obesity and the associated health care costs have prompted a search for better approaches for its prevention and management. Such efforts may be facilitated by better understanding the etiology of obesity. Of the several etiological factors, infection, an unusual causative factor, has recently started receiving greater attention. In the last two decades, 10 adipogenic pathogens were reported, including human and nonhuman viruses, scrapie agents, bacteria, and gut microflora. Some of these pathogens are associated with human obesity, but their causative role in human obesity has not been established. This chapter presents information about the natural hosts, signs and symptoms, and pathogenesis of the adipogenic microorganisms. If relevant to humans, \"Infectobesity\" would be a relatively novel, yet extremely significant concept. A new perspective about the infectious etiology of obesity may stimulate additional research to assess the contribution of hitherto unknown pathogens to human obesity and possibly to prevent or treat obesity of infectious origins.",
"title": "Infectobesity: obesity of infectious origin."
},
{
"docid": "MED-3771",
"text": "OBJECTIVE: Hyperosmotic stress on cells limits many aspects of cell function, metabolism and health. International data suggest that schoolchildren may be at risk of hyperosmotic stress on cells because of suboptimal water intake. The present study explored the cell hydration status of two samples of children in the USA. DESIGN: Cross-sectional study describing the urine osmolality (an index of hyperosmotic cell shrinkage) and water intake of convenience samples from Los Angeles (LA) and New York City (NYC). SETTING: Each participant collected a urine sample at an outpatient clinic on the way to school on a weekday morning in spring 2009. Each was instructed to wake, eat, drink and do as usual before school, and complete a dietary record form describing the type and amounts of all foods and beverages consumed after waking, before giving the sample. SUBJECTS: The children (9-11 years) in LA (n 337) and NYC (n 211) considered themselves healthy enough to go to school on the day they gave the urine sample. RESULTS: Elevated urine osmolality (>800 mmol/kg) was observed in 63 % and 66 % of participants in LA and NYC, respectively. In multivariable-adjusted logistic regression models, elevated urine osmolality was associated with not reporting intake of drinking water in the morning (LA: OR = 2·1, 95 % CI 1·2, 3·5; NYC: OR = 1·8, 95 % CI 1·0, 3·5). Although over 90 % of both samples had breakfast before giving the urine sample, 75 % did not drink water. CONCLUSIONS: Research is warranted to confirm these results and pursue their potential health implications.",
"title": "What is the cell hydration status of healthy children in the USA? Preliminary data on urine osmolality and water intake."
},
{
"docid": "MED-4264",
"text": "Domestic winter indoor temperatures in the USA, UK and other developed countries appear to be following an upwards trend. This review examines evidence of a causal link between thermal exposures and increases in obesity prevalence, focusing on acute and longer-term biological effects of time spent in thermal comfort compared with mild cold. Reduced exposure to seasonal cold may have a dual effect on energy expenditure, both minimizing the need for physiological thermogenesis and reducing thermogenic capacity. Experimental studies show a graded association between acute mild cold and human energy expenditure over the range of temperatures relevant to indoor heating trends. Meanwhile, recent studies of the role of brown adipose tissue (BAT) in human thermogenesis suggest that increased time spent in conditions of thermal comfort can lead to a loss of BAT and reduced thermogenic capacity. Pathways linking cold exposure and adiposity have not been directly tested in humans. Research in naturalistic and experimental settings is needed to establish effects of changes in thermal exposures on weight, which may raise possibilities for novel public health strategies to address obesity. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.",
"title": "Could increased time spent in a thermal comfort zone contribute to population increases in obesity?"
},
{
"docid": "MED-3774",
"text": "While dehydration has well-documented negative effects on adult cognition, there is little research on hydration and cognitive performance in children. We investigated whether having a drink of water improved children's performance on cognitive tasks. Fifty-eight children aged 7-9 years old were randomly allocated to a group that received additional water or a group that did not. Results showed that children who drank additional water rated themselves as significantly less thirsty than the comparison group (p=0.002), and they performed better on visual attention tasks (letter cancellation, p=0.02; spot the difference memory tasks, ps=0.019 and 0.014).",
"title": "Should children drink more water?: the effects of drinking water on cognition in children."
},
{
"docid": "MED-3776",
"text": "Little research has examined the effect of water consumption on cognition in children. We examined whether drinking water improves performance from baseline to test in twenty-three 6-7-year-old children. There were significant interactions between time of test and water group (water/no water), with improvements in the water group on thirst and happiness ratings, visual attention and visual search, but not visual memory or visuomotor performance. These results indicate that even under conditions of mild dehydration, not as a result of exercise, intentional water deprivation or heat exposure, children's cognitive performance can be improved by having a drink of water.",
"title": "Does having a drink help you think? 6-7-Year-old children show improvements in cognitive performance from baseline to test after having a drink of ..."
},
{
"docid": "MED-4278",
"text": "OBJECTIVE: To describe the lifestyle characteristics and nutrient intakes of the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: Cohort of men and women recruited through general practices or by post to include a high proportion of non meat-eaters. Dietary, anthropometric and lifestyle data were collected at baseline and four diet groups were defined. SETTING: United Kingdom. PARTICIPANTS: In total, 65 429 men and women aged 20 to 97 years, comprising 33 883 meat-eaters, 10 110 fish-eaters, 18 840 lacto-ovo vegetarians and 2596 vegans. RESULTS: Nutrient intakes and lifestyle factors differed across the diet groups, with striking differences between meat-eaters and vegans, and fish-eaters and vegetarians usually having intermediate values. Mean fat intake in each diet group was below the UK dietary reference value of 33% of total energy intake. The mean intake of saturated fatty acids in vegans was approximately 5% of energy, less than half the mean intake among meat-eaters (10-11%). Vegans had the highest intakes of fibre, vitamin B1, folate, vitamin C, vitamin E, magnesium and iron, and the lowest intakes of retinol, vitamin B12, vitamin D, calcium and zinc. CONCLUSIONS: The EPIC-Oxford cohort includes 31 546 non meat-eaters and is one of the largest studies of vegetarians in the world. The average nutrient intakes in the whole cohort are close to those currently recommended for good health. Comparisons of the diet groups show wide ranges in the intakes of major nutrients such as saturated fat and dietary fibre. Such variation should increase the ability of the study to detect associations of diet with major cancers and causes of death.",
"title": "EPIC-Oxford: lifestyle characteristics and nutrient intakes in a cohort of 33 883 meat-eaters and 31 546 non meat-eaters in the UK."
},
{
"docid": "MED-4276",
"text": "Propionate is produced along with acetate and butyrate as a result of fermentative activity of gut microflora on dietary fiber. It has long been known to exhibit hypophagic effects in ruminants, however, its potential physiological roles in non-ruminants as well as humans remained unnoticed over the years. In view of various studies pointing towards the hypophagic as well as hypocholesterolemic effects of propionate in humans, it may act as an important factor in amelioration of obesity, a lifestyle disease arising due to energy imbalance and growing at a startling rate globally. Short chain fatty acids have recently been ascribed as ligands to G-protein coupled receptors (GPRs) 41 and 43. Thus, propionate along with acetate may also be involved in the regulation of adipogenesis and adipokine release mediated via GPRs. The present review summarizes the evidence which collectively raise the possibility of propionate as a dietary factor to depress appetite and combat the obesity epidemic. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Propionate. Anti-obesity and satiety enhancing factor?"
},
{
"docid": "MED-4262",
"text": "Satiety, which is the inhibition of eating following the end of a meal, is influenced by a number of food characteristics, including compositional and structural factors. An increased understanding of these factors and the mechanisms whereby they exert their effects on satiety may offer a food-based approach to weight management. Water and gas, which are often neglected in nutrition, are major components of many foods and contribute to volume, and to sensory and other characteristics. A review of previous short-term studies that evaluated the effects of water or gas in foods on satiety showed that while satiety was generally increased, effects on subsequent intakes were not always apparent. These studies were diverse in terms of design, timings and food matrices, which precludes definitive conclusions. However, the results indicate that solids may be more effective at increasing satiety than liquids, but gas may be as effective as water. Although increased gastric distension may be the main mechanism underlying these effects, pre-ingestive and ingestive impacts on cognitive, anticipatory and sensory responses also appear to be involved. Furthermore, there is limited evidence that water on its own may be effective at increasing satiety and decreasing intakes when drunk before, but not with, a meal. Longer-term extrapolation suggests that increasing food volumes with water or gas may offer weight-management strategies. However, from a practical viewpoint, the effects of water and gas on satiety may be best exploited by using these non-nutrients to manipulate perceived portion sizes, without increasing energy contents.",
"title": "Satiety: have we neglected dietary non-nutrients?"
},
{
"docid": "MED-4266",
"text": "The relative proportion of Bacteroidetes to Firmicutes is decreased in obese people. This imbalance in gut microbiota generates signals controlling the expression of genes by the epithelial intestinal cells. Both dairy and non-dairy probiotics increase body weight, reportedly through Lactobacillus species growth in the gut. On the other hand, daily intake of some fruits and drinks such as three apples or three pears or grapefruit, or green tea, which all are rich in polyphenols, can significantly reduce body weight in obese people. Metabolism of polyphenols by microbiota involves the cleavage of glycosidic linkages. Glycans, which are the product of glycosidic cleavage, are necessary for survival of the intestinal microbiota as a nutrient foundation. There are two pivotal points: (i) Firmicutes possess a disproportionately smaller number of glycan-degrading enzymes than Bacteroidetes, (ii) Firmicutes are more repressed than the Bacteroidetes by phenolic compounds' antimicrobial properties. The Bacteroidetes community prevails following dietary polyphenol intake and its fermentation to phenolic compounds, due to having more glycan-degrading enzymes, so this may thus be a mechanism by which dietary polyphenols exert their weight lowering effect. I suggest that future studies utilize clone libraries and fingerprinting techniques enabling identification of the composition and community structure of the microbiota, and dot blot hybridization or fluorescent in situ hybridization to analyze abundance of particular taxa in obese and individuals. A supplementation with polyphenols with high bioavailability in obese individuals with higher Firmicutes/Bacteroides community ratio phenotype, when associated to a probiotic restricted diet, is proposed for weight loss; this hypothesis could have relevant implication in planning a successful dietary regimen and/or neutraceutical/pharmaceutical preparations for achieving and maintaining a normal body weight in obese individuals, especially including much more use of polyphenol-rich foodstuffs and/or polyphenol-rich syrups, and including low amounts of probiotic-rich foodstuffs like yogurt, soy yogurt, or as probiotic supplements. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.",
"title": "High polyphenol, low probiotic diet for weight loss because of intestinal microbiota interaction."
},
{
"docid": "MED-4313",
"text": "BACKGROUND: Population-based studies have shown that vegetarians have lower body mass index than nonvegetarians, suggesting that vegetarian diet plans may be an approach for weight management. However, a perception exists that vegetarian diets are deficient in certain nutrients. OBJECTIVE: To compare dietary quality of vegetarians, nonvegetarians, and dieters, and to test the hypothesis that a vegetarian diet would not compromise nutrient intake when used to manage body weight. DESIGN: Cross-sectional analysis of National Health and Nutrition Examination Survey (1999-2004) dietary and anthropometric data. Diet quality was determined using United States Department of Agriculture's Healthy Eating Index 2005. Participants included adults aged 19 years and older, excluding pregnant and lactating women (N = 13,292). Lacto-ovo vegetarian diets were portrayed by intakes of participants who did not eat meat, poultry, or fish on the day of the survey (n = 851). Weight-loss diets were portrayed by intakes of participants who consumed 500 kcal less than their estimated energy requirements (n = 4,635). Mean nutrient intakes and body mass indexes were adjusted for energy, sex, and ethnicity. Using analysis of variance, all vegetarians were compared to all nonvegetarians, dieting vegetarians to dieting nonvegetarians, and nondieting vegetarians to nondieting nonvegetarians. RESULTS: Mean intakes of fiber, vitamins A, C, and E, thiamin, riboflavin, folate, calcium, magnesium, and iron were higher for all vegetarians than for all nonvegetarians. Although vegetarian intakes of vitamin E, vitamin A, and magnesium exceeded that of nonvegetarians (8.3 ± 0.3 vs 7.0 ± 0.1 mg; 718 ± 28 vs 603 ± 10 μg; 322 ± 5 vs 281 ± 2 mg), both groups had intakes that were less than desired. The Healthy Eating Index score did not differ for all vegetarians compared to all nonvegetarians (50.5 ± 0.88 vs 50.1 ± 0.33, P = 0.6). CONCLUSIONS: These findings suggest that vegetarian diets are nutrient dense, consistent with dietary guidelines, and could be recommended for weight management without compromising diet quality. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.",
"title": "A vegetarian dietary pattern as a nutrient-dense approach to weight management: an analysis of the national health and nutrition examination survey..."
},
{
"docid": "MED-3775",
"text": "We investigated the beneficial effects of drinking supplementary water during the school day on the cognitive performance and transitory subjective states, such as fatigue or vigor, in 168 children aged between 9 and 11years who were living in a hot climate (South Italy, Sardinia). The classes were randomly divided into an intervention group, which received water supplementation, and a control group. Dehydration was determined by urine sampling and was defined as urine osmolality greater than 800mOsm/kg H(2)O (Katz, Massry, Agomn, & Toor, 1965). The change in the scores from the morning to the afternoon of hydration levels, cognitive performance and transitory subjective states were correlated. In line with a previous observational study that evaluated the hydration status of school children living in a country with a hot climate (Bar-David, Urkin, & Kozminsky, 2005), our results showed that a remarkable proportion of children were in a state of mild, voluntary dehydration at the beginning of the school day (84%). We found a significant negative correlation between dehydration and the auditory number span, which indicates a beneficial effect of drinking supplementary water at school on short-term memory. Moreover, there was a positive correlation between dehydration and performance in the verbal analogy task. The results are discussed in the light of the complexity of the neurobiological mechanisms involved in the relationship between hydration status and cognition. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Effects of drinking supplementary water at school on cognitive performance in children."
}
] |
[
{
"docid": "MED-3050",
"text": "Background: Weight gain leads to reduced reward-region responsivity to energy-dense food receipt, and consumption of an energy-dense diet compared with an isocaloric, low-energy-density diet leads to reduced dopamine receptors. Furthermore, phasic dopamine signaling to palatable food receipt decreases after repeated intake of that food, which collectively suggests that frequent intake of an energy-dense food may reduce striatal response to receipt of that food. Objective: We tested the hypothesis that frequent ice cream consumption would be associated with reduced activation in reward-related brain regions (eg, striatum) in response to receipt of an ice cream–based milkshake and examined the influence of adipose tissue and the specificity of this relation. Design: Healthy-weight adolescents (n = 151) underwent fMRI during receipt of a milkshake and during receipt of a tasteless solution. Percentage body fat, reported food intake, and food craving and liking were assessed. Results: Milkshake receipt robustly activated the striatal regions, yet frequent ice cream consumption was associated with a reduced response to milkshake receipt in these reward-related brain regions. Percentage body fat, total energy intake, percentage of energy from fat and sugar, and intake of other energy-dense foods were not related to the neural response to milkshake receipt. Conclusions: Our results provide novel evidence that frequent consumption of ice cream, independent of body fat, is related to a reduction in reward-region responsivity in humans, paralleling the tolerance observed in drug addiction. Data also imply that intake of a particular energy-dense food results in attenuated reward-region responsivity specifically to that food, which suggests that sensory aspects of eating and reward learning may drive the specificity.",
"title": "Frequent ice cream consumption is associated with reduced striatal response to receipt of an ice cream–based milkshake"
},
{
"docid": "MED-1627",
"text": "Sweetened beverages, coffee, and tea are the most consumed non-alcoholic beverages and may have important health consequences. We prospectively evaluated the consumption of various types of beverages assessed in 1995–1996 in relation to self-reported depression diagnosis after 2000 among 263,923 participants of the NIH-AARP Diet and Health Study. Odds ratios (OR) and 95% confidence intervals (CI) were derived from multivariate logistic regressions. The OR (95% CI) comparing ≥4 cans/cups per day with none were 1.30 (95%CI: 1.17–1.44) for soft drinks, 1.38 (1.15–1.65) for fruit drinks, and 0.91 (0.84–0.98) for coffee (all P for trend<0.0001). Null associations were observed for iced-tea and hot tea. In stratified analyses by drinkers of primarily diet versus regular beverages, the ORs were 1.31 (1.16–1.47) for diet versus 1.22 (1.03–1.45) for regular soft drinks, 1.51 (1.18–1.92) for diet versus 1.08 (0.79–1.46) for regular fruit drinks, and 1.25 (1.10–1.41) for diet versus 0.94 (0.83–1.08) for regular sweetened iced-tea. Finally, compared to nondrinkers, drinking coffee or tea without any sweetener was associated with a lower risk for depression, adding artificial sweeteners, but not sugar or honey, was associated with higher risks. Frequent consumption of sweetened beverages, especially diet drinks, may increase depression risk among older adults, whereas coffee consumption may lower the risk.",
"title": "Sweetened Beverages, Coffee, and Tea and Depression Risk among Older US Adults"
},
{
"docid": "MED-2570",
"text": "The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.",
"title": "In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ..."
},
{
"docid": "MED-3719",
"text": "Purpose The objective of this study was to formulate and evaluate freeze-dried black raspberry (FBR) ethanol extract (RE) loaded poly(DL-lactic-co-glycolic acid) (PLGA) and poly(DL-lactic acid) (PLA) injectable millicylindrical implants for sustained delivery of chemopreventive FBR anthocyanins (cyanidin-3-sambubioside (CS), cyanidin-3-glucoside (CG) and cyanidin-3-rutinoside (CR)). Methods Identification and quantitation of CS, CG, and CR in RE was performed by mass spectroscopy and HPLC. RE:triacetyl-β-cyclodextrin (TA-β-CD) inclusion complex (IC) was prepared by a kneading method and characterized by X-ray diffraction (XRD), nuclear magnetic resonance spectroscopy (NMR) and UV-visible spectroscopy. RE or RE:TA-β-CD IC-loaded PLGA or PLA implants were prepared by a solvent extrusion method. In vitro and in vivo controlled release studies were conducted in phosphate-buffered saline Tween-80 (pH 7.4, 37°C) and after subcutaneous administration in male Sprague-Dawley rats, respectively. Anthocyanins were quantified by HPLC at 520 nm. Results The content of CS, CG, and CR in RE was 0.2, 1.5, and 3.5 wt%, respectively. The chemical stability of anthocyanins in solution was determined to be pH-dependent, and their degradation rate increased with an increase in pH from 2.4 to 7.4. PLGA/PLA millicylindrical implants loaded with 5 or 10 wt% RE exhibited a high initial burst and short release duration of anthocyanins (35–52 and 80–100% CG + CR release after 1 and 14 days, respectively). The cause for rapid anthocyanins release was linked to higher polymer water uptake and porosity associated with the high osmolytic components of large non-anthocyanin fraction of RE. XRD, 1H NMR and UV-visible spectroscopy indicated that the non-anthocyanin fraction molecules of RE formed an IC with TA-β-CD, decreasing the hydrophilicity of RE. Formation of an IC with hydrophobic carrier, TA-β-CD, provided better in vitro/in vivo sustained release of FBR anthocyanins (16–24 and 97–99% CG + CR release, respectively, after 1 and 28 days from 20 wt% RE:TA-β-CD IC/PLA implants) over 1 month, owing to reduced polymer water uptake and porosity. Conclusion PLA injectable millicylindrical implants loaded with RE:TA-β-CD IC are optimal dosage forms for 1-month slow and continuous delivery of chemopreventive FBR anthocyanins.",
"title": "Formulation and In Vitro-In Vivo Evaluation of Black Raspberry Extract-Loaded PLGA/PLA Injectable Millicylindrical Implants for Sustained Delivery of Chemopreventive Anthocyanins"
},
{
"docid": "MED-1670",
"text": "The effect of polyphenols, phenolic acids and tannins (PPTs) from strawberry and apple on uptake and apical to basolateral transport of glucose was investigated using Caco-2 intestinal cell monolayers. Substantial inhibition on both uptake and transport was observed by extracts from both strawberry and apple. Using sodium-containing (glucose transporters SGLT1 and GLUT2 both active) and sodium-free (only GLUT2 active) conditions, we show that the inhibition of GLUT2 was greater than that of SGLT1. The extracts were analyzed and some of the constituent PPTs were also tested. Quercetin-3-O-rhamnoside (IC₅₀ =31 μM), phloridzin (IC₅₀=146 μM), and 5-caffeoylquinic acid (IC₅₀=2570 μM) contributed 26, 52 and 12%, respectively, to the inhibitory activity of the apple extract, whereas pelargonidin-3-O-glucoside (IC₅₀=802 μM) contributed 26% to the total inhibition by the strawberry extract. For the strawberry extract, the inhibition of transport was non-competitive based on kinetic analysis, whereas the inhibition of cellular uptake was a mixed-type inhibition, with changes in both V(max) and apparent K(m) . The results in this assay show that some PPTs inhibit glucose transport from the intestinal lumen into cells and also the GLUT2-facilitated exit on the basolateral side. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Polyphenols and phenolic acids from strawberry and apple decrease glucose uptake and transport by human intestinal Caco-2 cells."
},
{
"docid": "MED-4705",
"text": "Several studies suggest that regular consumption of nuts, mostly walnuts, may have beneficial effects against oxidative stress mediated diseases such as cardiovascular disease and cancer. Walnuts contain several phenolic compounds which are thought to contribute to their biological properties. The present study reports the total phenolic contents and antioxidant properties of methanolic and petroleum ether extracts obtained from walnut (Juglans regia L.) seed, green husk and leaf. The total phenolic contents were determined by the Folin-Ciocalteu method and the antioxidant activities assessed by the ability to quench the stable free radical 2,2'-diphenyl-1-picrylhydrazyl (DPPH) and to inhibit the 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative hemolysis of human erythrocytes. Methanolic seed extract presented the highest total phenolic content (116 mg GAE/g of extract) and DPPH scavenging activity (EC(50) of 0.143 mg/mL), followed by leaf and green husk. In petroleum ether extracts, antioxidant action was much lower or absent. Under the oxidative action of AAPH, all methanolic extracts significantly protected the erythrocyte membrane from hemolysis in a time- and concentration-dependent manner, although leaf extract inhibitory efficiency was much stronger (IC(50) of 0.060 mg/mL) than that observed for green husks and seeds (IC(50) of 0.127 and 0.121 mg/mL, respectively). Walnut methanolic extracts were also assayed for their antiproliferative effectiveness using human renal cancer cell lines A-498 and 769-P and the colon cancer cell line Caco-2. All extracts showed concentration-dependent growth inhibition toward human kidney and colon cancer cells. Concerning A-498 renal cancer cells, all extracts exhibited similar growth inhibition activity (IC(50) values between 0.226 and 0.291 mg/mL), while for both 769-P renal and Caco-2 colon cancer cells, walnut leaf extract showed a higher antiproliferative efficiency (IC(50) values of 0.352 and 0.229 mg/mL, respectively) than green husk or seed extracts. The results obtained herein strongly indicate that walnut tree constitute an excellent source of effective natural antioxidants and chemopreventive agents. Copyright 2009 Elsevier Ltd. All rights reserved.",
"title": "Human cancer cell antiproliferative and antioxidant activities of Juglans regia L."
},
{
"docid": "MED-3100",
"text": "Dioxins invade the body mainly through the diet, and produce toxicity through the transformation of aryl hydrocarbon receptor (AhR). An inhibitor of the transformation should therefore protect against the toxicity and ideally be part of the diet. We examined flavonoids ubiquitously expressed in plant foods as one of the best candidates, and found that the subclasses flavones and flavonols suppressed antagonistically the transformation of AhR induced by 1 nM of 2,3,7,8-tetrachlorodibenzo-p-dioxin, without exhibiting agonistic effects that transform AhR. The antagonistic IC(50) values ranged from 0.14 to 10 microM, close to the physiological levels in human.",
"title": "Flavones and flavonols at dietary levels inhibit a transformation of aryl hydrocarbon receptor induced by dioxin."
},
{
"docid": "MED-5105",
"text": "Food, especially dairy products, meat, and fish, is the primary source of environmental exposure to dioxins in the general population. Little data exists on dioxin levels in the popular and widely consumed \"fast foods\". Data presented in a previously published pilot study was limited to measuring only the levels of dioxins and dibenzofurans in three types of U.S. fast food. This study adds to the previous paper by presenting data, in addition to dioxins and dibenzofurans, on the closely related dioxin-like polychlorinated biphenyls (PCBs), and the persistent metabolite of DDT, 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (DDE), in four types of popular U.S. fast food. These include McDonald's Big Mac Hamburger, Pizza Hut's Personal Pan Pizza Supreme, Kentucky Fried Chicken (KFC) three piece original recipe mixed dark and white meat luncheon package, and Häagen-Daz chocolate-chocolate chip ice cream. Dioxin plus dibenzofuran dioxin toxic equivalents (TEQ) ranged from 0.03 to 0.28 TEQ pg/g wet or whole weight for the Big Mac, from 0.03 to 0.29 for the Pizza, from 0.01 to 0.31 for the KFC, and from 0.03 to 0.49 TEQ pg/g for the ice cream. Daily TEQ consumption per kilogram body weight (kg/BW), assuming an average 65 kg adult and a 20 kg child, from one serving of each of these fast food ranged between 0.046 and 1.556 pg/kg in adults whereas in children the values were between 0.15 and 5.05 pg/kg. Total measured PCDD/Fs in the Big Mac, Personal Pan Pizza, KFC, and the Häagen-Daz ice cream varied from 0.58 to 9.31 pg/g. Measured DDE levels in the fast foods ranged from 180 to 3170 pg/g. Total mono-ortho PCB levels ranged up to 500 pg/g or 1.28 TEQ pg/g for the KFC and for di-ortho PCBs up to 740 pg/g or 0.014 TEQ pg/g for the pizza sample. Total PCB values in the four samples ranged up to 1170 pg/g or 1.29 TEQ pg/g for the chicken sample.",
"title": "Dioxins, dibenzofurans, dioxin-like PCBs, and DDE in U.S. fast food, 1995."
},
{
"docid": "MED-4881",
"text": "The effects of microbial transglutaminase (MTGase) at different levels (0 to 0.8 units/g sample) on the properties of gels from lizardfish (Saurida undosquamis) mince set at 25 degrees C for 2 h or 40 degrees C for 30 min prior to heating at 90 degrees C for 20 min were studied. Breaking force and deformation of gels increased with increasing MTGase amount added (P<0.05). At the same MTGase level used, gels with the prior setting at 40 degrees C for 30 min showed a higher breaking force compared with those subjected to prior setting at 25 degrees C for 2 h (P<0.05). Sodium dodecyl sulfate-polyacrylamide gel electrophoretic study revealed that myosin heavy chain (MHC) underwent polymerization to a higher extent in the presence of MTGase. Regardless of setting condition, microstructure of gel added with MTGase was finer with a smaller void compared with that of gel without MTGase. Therefore, setting temperature affected the property of gels added with MTGase. Gel properties of mince obtained from lizardfish stored in ice for different times (0 to 10 d) with and without MTGase at a level 0.6 units/g were determined. Irrespective of MTGase addition, breaking force and deformation of all gels decreased as the storage time of lizardfish increased (P<0.05). The addition of MTGase was able to increase both breaking force and deformation of the resulting gel produced from lizardfish kept in ice for all storage times used. Therefore, both freshness and MTGase addition had the direct impact on gel properties of lizardfish mince.",
"title": "Improvement of gelling properties of lizardfish mince as influenced by microbial transglutaminase and fish freshness."
},
{
"docid": "MED-1838",
"text": "The determination of Al, B, Cu, Fe, Mn, Ni, P, Zn and Ca, K, Mg by inductively coupled plasma optical emission spectrometry (ICP-OES) and flame atomic absorption spectroscopy (FAAS), respectively, in digests and infusions of Hibiscus sabdariffa (petals), Rosa canina (receptacles), Ginkgo biloba (leaves), Cymbopogon citratus (leaves), Aloe vera (leaves) and Panax ginseng (roots) was carried out in this study. Particular attention has been given to Al and heavy metals for the identification of possible raw material contaminants, their transformation into the infusion and for predicting their eventual role in the human diet during daily consumption. Additionally, Ion Chromatography (IC) speciation of Al in the leachates was carried out. In dry herbs, hibiscus and ginkgo appeared to contain the greatest contents of Al, Fe, K, Mn, Ni, Zn and B, Mg, P, respectively. A. vera contained the highest amount of Ca and highest values of Cu and P were observed in ginseng. In infusions, the topmost concentrations of Al, B, Cu, Fe, P, K, Mn, Ni, Zn were detected in those prepared from hibiscus petals, Ca from aloe leaves and Mg from leaves of ginkgo. According to a possible daily consumption exceeding 1 L, hibiscus decoction was identified as potentially dietetically significant in the content of certain elements. It seems to be possibly one of the top contributors of B from food (up to 5.5±0.2 mg/L). The Mg contained in the infusion (up to 106±5 mg/L) may be a contributor in the attenuation of blood pressure. A high amount of accessible Mn (up to 17.4±1.1 mg/L) can probably have an adverse effect in humans. The total Al allowance (up to 1.2±0.1 mg/L) suggests that no more than 1 L of the hibiscus infusion should be consumed per day by sensitive individuals including pregnant women and should be completely excluded from the diet of children under 6 months of age and children with chronic renal failure. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Aluminium and other elements in selected herbal tea plant species and their infusions."
},
{
"docid": "MED-4864",
"text": "To elucidate the health benefit of herbal teas on the cytotoxicity induced by H(2)O(2) in V79-4 cells, herbal extracts and its flavonoids were tested using lactate dehydrogenase release and determining intracellular reactive oxygen species generation and antioxidant activity with superoxide radical scavenging assay. Significant decrease in cell viability was observed on V79-4 cells treated with H(2)O(2) (1 mM), while herbal extracts and its flavonoids including catechin and epigallocatechin gallate prevented the LDH release from H(2)O(2) cytotoxicity. Total catechin contents of green tea (65.6 mg/g of dry matter) were significantly higher than other herbal teas (35.8 to 1.2 mg/g of DM). The relative concentration of the 4 major tea catechins ranked EGCG > EGC > EC > C. Green tea exhibited the lowest IC(50) values (2 g fresh herb/100 mL) of superoxide radical scavenging activity among the tested herbal tea, which indicates powerful antioxidant activity in O(2)(*-) radicals scavenging, followed by black tea, dandelion, hawthorn, rose hip, chamomile.",
"title": "Comparative flavonoids contents of selected herbs and associations of their radical scavenging activity with antiproliferative actions in V79-4 cells."
},
{
"docid": "MED-905",
"text": "ETHNOPHARMACOLOGICAL RELEVANCE: The beverages of Hibiscus sabdariffa calyces are widely used in Mexico as diuretic, for treating gastrointestinal disorders, liver diseases, fever, hypercholesterolemia and hypertension. Different works have demonstrated that Hibiscus sabdariffa extracts reduce blood pressure in humans, and recently, we demonstrated that this effect is due to angiotensin converting enzyme (ACE) inhibitor activity. AIM OF THE STUDY: The aim of the current study was to isolate and characterizer the constituents responsible of the ACE activity of the aqueous extract of Hibiscus sabdariffa. MATERIALS AND METHODS: Bioassay-guided fractionation of the aqueous extract of dried calyces of Hibiscus sabdariffa using preparative reversed-phase HPLC, and the in vitro ACE Inhibition assay, as biological monitor model, were used for the isolation. The isolated compounds were characterized by spectroscopic methods. RESULTS: The anthocyanins delphinidin-3-O-sambubioside (1) and cyanidin-3-O-sambubioside (2) were isolated by bioassay-guided purification. These compounds showed IC(50) values (84.5 and 68.4 microg/mL, respectively), which are similar to those obtained by related flavonoid glycosides. Kinetic determinations suggested that these compounds inhibit the enzyme activity by competing with the substrate for the active site. CONCLUSIONS: The competitive ACE inhibitor activity of the anthocyanins 1 and 2 is reported for the first time. This activity is in good agreement with the folk medicinal use of Hibiscus sabdariffa calyces as antihypertensive. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.",
"title": "Inhibition of angiotensin convertin enzyme (ACE) activity by the anthocyanins delphinidin- and cyanidin-3-O-sambubiosides from Hibiscus sabdariffa."
},
{
"docid": "MED-2573",
"text": "A significant anticancer activity of the naturally occurring carbohydrate inositol hexaphosphate (IP(6)) has been reported against numerous cancer models. Since tumors require angiogenesis for growth and metastasis, we hypothesize that IP(6) reduces tumor growth by inhibiting angiogenesis. Because angiogenesis depends on the interaction between endothelial and tumor cells, we investigated the effect of IP(6) on both. IP(6) inhibited the proliferation and induced the differentiation of endothelial cells in vitro; the growth of bovine aortic endothelial cells (BAECs) evaluated by MTT proliferation assay was inhibited in a dose-dependent manner (IC(50) = 0.74 mM). The combination of IP(6) and vasostatin, a calreticulin fragment with anti-angiogenic activity, was synergistically superior in growth inhibition than either compound. IP(6) inhibited human umbilical vein endothelial cell (HUVEC) tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel, and disrupted pre-formed tubes. IP(6) significantly reduced basic fibroblast growth factor (bFGF)-induced vessel formation (P < 0.01) in vivo in Matrigel plug assay. Exposure of HepG2, a human hepatoma cell line, to IP(6) for 8 h, resulted in a dose-dependent decrease in the mRNA levels of vascular endothelial growth factor (VEGF), as assessed by RT-PCR. IP(6) treatment of HepG2 cells for 24 h also significantly reduced the VEGF protein levels in conditioned medium, in a concentration-dependent manner (P = 0.012). Thus, IP(6) has an inhibitory effect on induced angiogenesis.",
"title": "Anti-angiogenic activity of inositol hexaphosphate (IP6)."
},
{
"docid": "MED-873",
"text": "BACKGROUND: Vanillin is responsible for the flavor and smell of vanilla, a widely used flavoring agent. Previous studies showed that vanillin could enhance the repair of mutations and thus function as an anti-mutagen. However, its role in cancer, a disease that is closely related to mutation has not yet been fully elucidated. METHODS: Hence, this study investigated the cytolytic and cytostatic properties of vanillin against HT-29, a human colorectal cancer cell line. Methods used including cell viability assay, acridine orange (AO)-ethidium bromide (EB) double staining cell morphological analysis, Cell cycle analysis, annexin V-propidium iodide apoptosis test and 5-bromo-2-deoxyuridine (BrdU)-labeling cell proliferation assay. RESULTS: Results showed that apoptosis was induced by vanillin and the IC(50) for HT-29 and NIH/3T3 normal cell lines were 400 microg/ml and 1000 microg/ml, respectively. Different concentrations of vanillin arrest cell cycle at different checkpoints. 5-Bromo-2-deoxyuridine-labeling cell proliferation assay showed that G0/G1 arrest was achieved at lower concentration of vanillin (200 microg/ml) while cell cycle analysis by flow cytometer showed that G2/M arrest occurs at higher concentration of vanillin (1000 microg/ml). CONCLUSION: Cytolytic and cytostatic effects shown by vanillin showed that it could be a useful colorectal cancer preventive agent. Further in vivo study should be carried out to confirm that similar effects could happen in animals.",
"title": "Apoptosis and cell cycle arrest of human colorectal cancer cell line HT-29 induced by vanillin."
},
{
"docid": "MED-5077",
"text": "Due to the increased demand and consumption of bottled water in the United States, there has been a growing concern about the quality of this product. Retail outlets sell local as well as imported bottled water to consumers. Three bottles for each of 35 different brands of bottled water were randomly collected from local grocery stores in the greater Houston area. Out of the 35 different brands, 16 were designated as spring water, 11 were purified and/or fortified tap water, 5 were carbonated water and 3 were distilled water. Chemical, microbial and physical properties of all samples were evaluated including pH, conductivity, bacteria counts, anion concentration, trace metal concentration, heavy metal and volatile organics concentration were determined in all samples. Inductively coupled plasma/mass spectrometry (ICPMS) was used for elemental analysis, gas chromatography with electron capture detector (GCECD) as well as gas chromatography mass spectrometry (GCMS) were used for analysis of volatile organics, ion chromatography (IC) and selective ion electrodes were used for the analysis of anions. Bacterial identification was performed using the Biolog software (Biolog, Inc., Hayward, Ca, USA). The results obtained were compared with guidelines of drinking water recommended by the International Bottled Water Association (IBWA), United States Food and Drug Administration (FDA), United States Environmental Protection Agency (EPA) and the World Health Organization (WHO) drinking water standard. The majority of the analyzed chemicals were below their respective drinking water standards for maximum admissible concentrations (MAC). Volatile organic chemicals were found to be below detection limits. Four of the 35 brands of the bottled water samples analyzed were found to be contaminated with bacteria.",
"title": "Chemical, microbial and physical evaluation of commercial bottled waters in greater Houston area of Texas."
},
{
"docid": "MED-5318",
"text": "Brown adipose tissue (BAT) can be identified by (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in adult humans. Thirteen healthy male volunteers aged 20-28 years underwent FDG-PET after 2-h cold exposure at 19 °C with light-clothing and intermittently putting their legs on an ice block. When exposed to cold, 6 out of the 13 subjects showed marked FDG uptake into adipose tissue of the supraclavicular and paraspinal regions (BAT-positive group), whereas the remaining seven showed no detectable uptake (BAT-negative group). The BMI and body fat content were similar in the two groups. Under warm conditions at 27 °C, the energy expenditure of the BAT-positive group estimated by indirect calorimetry was 1,446 ± 97 kcal/day, being comparable with that of the BAT-negative group (1,434 ± 246 kcal/day). After cold exposure, the energy expenditure increased markedly by 410 ± 293 (P < 0.05) and slightly by 42 ± 114 kcal/day (P = 0.37) in the BAT-positive and -negative groups, respectively. A positive correlation (P < 0.05) was found between the cold-induced rise in energy expenditure and the BAT activity quantified from FDG uptake. After cold exposure, the skin temperature in the supraclavicular region close to BAT deposits dropped by 0.14 °C in the BAT-positive group, whereas it dropped more markedly (P < 0.01) by 0.60 °C in the BAT-negative group. The skin temperature drop in other regions apart from BAT deposits was similar in the two groups. These results suggest that BAT is involved in cold-induced increases in whole-body energy expenditure, and, thereby, the control of body temperature and adiposity in adult humans.",
"title": "Brown adipose tissue, whole-body energy expenditure, and thermogenesis in healthy adult men."
},
{
"docid": "MED-3816",
"text": "Most of adult women exhibit cellulite on the hips, buttock and thighs. Although extracellular matrix and lymphatic system disorders can increase its appearance, cellulite basically results from an excessive fat storage in the adipose tissue which exerts considerable pressure on the surrounding skin tissue and creates a dimpled irregular appearance. Caffeine, the most widely used anti-cellulite ingredient, favours fat break-down by inhibiting the phosphodiesterase enzyme and encouraging a high intracellular level of cAMP. A series of studies has shown that spermine and spermidine, two ubiquitous polyamines, encouraged fat storage and slowed fat break-down in the adipose tissue. Besides, it was shown that heparan sulfate glycosaminoglycans had a strong affinity for polyamines. To design a new cosmetic ingredient with anti-cellulite properties, we used molecular modelling to screen several ingredients with a structure similar to that of heparan sulfate glycosaminoglycans. This way, we identified sulfo-carrabiose as a potent molecule for trapping spermine and spermidine. These virtual results were first confirmed in tubo where sulfo-carrabiose was shown to dose-dependently inactivate spermine and spermidine. In vitro, adipocytes cultured with sulfo-carrabiose exhibited a significant reduction of lipogenesis and a significant increase of lipolysis. When sulfo-carrabiose was incorporated in a cosmetic formula, significant improvements were observed in thigh circumference, with better results than those obtained with caffeine after 28 days of use. Furthermore, a combination of caffeine and sulfo-carrabiose led to results significantly better than those obtained with caffeine alone. As measured by fringe projection, thigh volume was also significantly reduced after sulfo-carrabiose treatment. Finally, the appearance of cellulite assessed by clinical evaluation was also significantly reduced within 28 days. © 2010 BASF Beauty Care Solutions. ICS © 2010 Society of Cosmetic Scientists and the Société Française de Cosmétologie.",
"title": "In vitro and in vivo efficacy of sulfo-carrabiose, a sugar-based cosmetic ingredient with anti-cellulite properties."
},
{
"docid": "MED-4532",
"text": "The cytotoxic effects of Triphala (TPL), an Indian Ayurvedic formulation with known anti-cancer properties, has been investigated on two human breast cancer cell lines differing in their p53 status. In vitro studies showed that MCF 7 with wild type p53 was more sensitive to TPL than T 47 D, which is p53 negative. TPL induced loss of cell viability was determined by MTT assay. After 72h incubation, the IC 50 values for MCF 7 was found to be approximately 8microg/ml and that for T 47 D was approximately 26microg/ml. Moreover, TPL inhibited the clonogenic growth of MCF 7 cells, which was significantly recovered by pifithrin-alpha, the p53 inhibitor. However, pifithrin-alpha, did not modify TPL induced cytotoxicity in T 47 D cells. Exogenous addition of antioxidants, glutathione (GSH) and N-Acetyl-Cysteine (NAC) inhibited the anti-proliferative ability of TPL in both MCF 7 and T47 D. Annexin-V and propidium iodide double staining of cells treated with TPL for 2h revealed that TPL induced significant apoptosis in both the cell lines in a dose dependant manner but magnitude of apoptosis was significantly higher in MCF 7 than in T 47-D cells. TPL was also found to induce dose and time dependent increase in intracellular reactive oxygen species in both the cell lines. Present results have demonstrated that MCF 7 and T 47 D cells exhibited differential sensitivity to TPL, which seems to be dependant on their p53 status. Inhibition of anti-proliferative ability of TPL by antioxidants suggests a role for TPL induced ROS in the induction of apoptosis. It is concluded that p53 status of cancer cells formed an important factor in predicting the response of cancer cells to prooxidant drugs.",
"title": "Cytotoxic response of breast cancer cell lines, MCF 7 and T 47 D to triphala and its modification by antioxidants."
},
{
"docid": "MED-1098",
"text": "The first U.S. nationwide food sampling with measurement of dioxins, dibenzofurans, and coplanar, mono-ortho and di-ortho polychlorinated biphenyls (PCBs) is reported in this study. Twelve separate analyses were conducted on 110 food samples divided into pooled lots by category. The samples were purchased in 1995 in supermarkets in Atlanta, GA, Binghamton, NY, Chicago, IL, Louisville, KY, and San Diego, CA. Human milk also was collected to estimate nursing infants' consumption. The food category with highest World Health Organization (WHO) dioxin toxic equivalent (TEQ) concentration was farm-grown freshwater fish fillet with 1.7 pg/g, or parts per trillion (ppt), wet, or whole, weight. The category with the lowest TEQ level was a simulated vegandiet, with 0.09 ppt. TEQ concentrations in ocean fish, beef, chicken, pork, sandwich meat, eggs, cheese, and ice cream, as well as human milk, were in the range O.33 to 0.51 ppt, wet weight. In whole dairy milk TEQ was 0.16 ppt, and in butter 1.1 ppt. Mean daily intake of TEQ for U.S. breast-fed infants during the first year of life was estimated at 42 pg/kg body weight. For children aged 1-11 yr the estimated daily TEQ intake was 6.2 pg/kg body weight. For males and females aged 12-19 yr, the estimated TEQ intake was 3.5 and 2.7 pg/kg body weight, respectively. For adult men and women aged 20-79 yr, estimated mean daily TEQ intakes were 2.4 and 2.2 pg/kg body weight, respectively. Estimated mean daily intake of TEQ declined with age to a low of 1.9 pg/kg body weight at age 80 yr and older. For all ages except 80 yr and over, estimates were higher for males than females. For adults, dioxins, dibenzofurans, and PCBs contributed 42%, 30%, and 28% of dietary TEQ intake, respectively. DDE was also analyzed in the pooled food samples.",
"title": "Intake of dioxins and related compounds from food in the U.S. population."
},
{
"docid": "MED-2468",
"text": "BACKGROUND AND METHODS: We estimated the prevalence of self-reported asthma in adult Indians and examined several risk factors influencing disease prevalence. Analysis is based on 99 574 women and 56 742 men aged 20–49 years included in India’s third National Family Health Survey, 2005–2006. Multiple logistic regression analysis was used to estimate the prevalence odds ratios for asthma, adjusting for various risk factors. RESULTS: The prevalence of self-reported asthma was 1.8% (95%CI 1.6–2.0) among men and 1.9% (95%CI 1.8–2.0) among women, with higher rates in rural than in urban areas and marked geographic differences. After adjustment for known asthma risk factors, women were 1.2 times more likely to have asthma than men. Daily/weekly consumption of milk/milk products, green leafy vegetables and fruits were associated with a lower asthma risk, whereas consumption of chicken/meat, a lower body mass index (BMI; <16 kg/m2, OR 2.08, 95%CI 1.73–2.50) as well as a higher BMI (>30 kg/m2, OR 1.67, 95%CI 1.36–2.06), current tobacco smoking (OR 1.30, 95%CI 1.12–1.50) and ever use of alcohol (OR 1.21, 95%CI 1.05–1.39) were associated with an increased asthma risk. CONCLUSIONS: There are wide regional variations in the prevalence of asthma in India. With the exception of the findings for BMI, however, most of the associations of asthma with the risk factors are relatively weak and account for only a small proportion of cases. RÉSUMÉ CONTEXTE ET MÉTHODES: Nous avons estimé la prévalence auto-rapportée de l’asthme chez les Indiens adultes et examiné plusieurs facteurs de risque influençant la prévalence de la maladie. L’analyse repose sur 99 574 femmes et 56 742 hommes âgés de 20 à 49 ans et inclus dans la troisième Enquête Nationale des Familles en Inde, 2005–2006. On a utilisé l’analyse de régression logistique multiple pour estimer les odds ratio de prévalence pour l’asthme, après ajustement pour divers facteurs de risque. RÉSULTATS: La prévalence auto-rapportée de l’asthme est de 1,8% (IC95% 1,6–2,0) parmi les hommes et de 1,9% (IC95% 1,8–2,0) parmi les femmes, les taux étant plus élevés dans les zones rurales que dans les zones urbaines, et les différences géographiques étant marquées. Après ajustement pour les facteurs de risque d’asthme connus, les femmes sont 1,2 fois plus susceptibles de souffrir de l’asthme que les hommes. La consommation quotidienne ou hebdomadaire de lait/produits laitiers, de légumes à feuilles vertes et de fruits est en association avec un risque plus faible d’asthme alors que la consommation de poulet ou de viande, un index de masse corporelle (BMI) plus bas (<16 kg/m2, OR 2,08 ; IC95% 1,73–2,50) ainsi qu’un BMI plus élevé (>30 kg/m2, OR 1,67 ; IC95% 1,36–2,06), le fait de fumer du tabac actuellement (OR 1,30 ; IC95% 1,12–1,50) et l’utilisation de l’alcool à un moment quelconque (OR 1,21 ; IC95% 1,05–1,39) sont en association avec un risque accru d’asthme. La prévalence de l’asthme en Inde varie largement selon les régions. Toutefois, à l’exception des observations sur le BMI, l’association de l’asthme avec les facteurs de risque est relativement faible et ne rend compte que d’une petite proportion des cas seulement. RESUMEN MARCO DE REFERENCIA Y MÉTODOS: Se calculó la prevalencia de asma autorreferida en los adultos en la India y se evaluaron varios factores de riesgo que influyen sobre la prevalencia de la enfermedad. El estudio se basó en las 99 574 mujeres y los 56 742 hombres de 20 a 49 años de edad que participaron en la tercera Encuesta Nacional sobre la Salud de la Familia en la India entre el 2005 y el 2006. Mediante un análisis de regresión logística multifactorial se calculó la prevalencia de asma y el cociente de posibilidades de padecerla, al corregir diversos factores de riesgo. RESULTADOS: La prevalencia de asma autorreferida fue 1,8% en los hombres (intervalo de confianza [IC] del 95% 1,6 a 2,0) y 1,9% en las mujeres (IC95% 1,8 a 2,0); se observaron tasas más altas en las zonas rurales que en las zonas urbanas y se presentaron diferencias geográficas considerables. Tras corregir en función de algunos factores de riesgo de padecer asma conocidos, las mujeres presentaron una probabilidad 1,2 veces superior a los hombres de sufrir la enfermedad. El consumo diario o semanal de leche o productos lácteos, hortalizas de hojas verdes y frutas se asoció con un menor riesgo de asma y el consumo de carne de pollo o de res, un bajo índice de masa corporal (<16 kg/m2; OR 2,08; IC95% 1,73 a 2,50) igual que un alto índice de masa corporal (>30 kg/m2; OR 1,67; IC95% 1,36 a 2,06), el tabaquismo actual (OR 1,30; IC95% 1,12 a 1,50) y el consumo de alcohol en algún momento de la vida (OR 1,21; IC95% 1,05 a 1,39) se asociaron con un mayor riesgo de padecer la enfermedad. CONCLUSIÓN: Existen amplias variaciones geográficas en la prevalencia de asma en la India. Sin embargo, con la excepción del índice de masa corporal, la mayor parte de las asociaciones del asma con los factores de riesgo fueron débiles y explican solo una pequeña proporción de los casos.",
"title": "Prevalence and risk factors for self-reported asthma in an adult Indian population: a cross-sectional survey"
},
{
"docid": "MED-4848",
"text": "We have previously reported that a significant improvement can be obtained in rheumatoid arthritis patients by fasting followed by an individually adjusted vegetarian diet for one year. The patients who changed their diet could be divided into diet responders and diet nonresponders. After the clinical trial the patients were free to change diet or medication and after approximately one year they were asked to attend a new clinical examination. We compared the change from baseline (i.e. at the time of study entry) to the time of the follow-up examination for diet responders, diet nonresponders and controls who ate an omnivorous diet. The following variables favoured diet responders: pain score, duration of morning stiffness, Stanford Health Assessment Questionnaire index, number of tender joints, Ritchie's articular index, number of swollen joints, ESR and platelet count [corrected]. The difference between the three groups were significant for all the clinical variables, except for grip strength. There was no significant difference between the groups with regard to laboratory or anthropometric variables. At the time of the follow-up examination all diet responders but only half of the diet nonresponders still followed a diet. Our findings indicate that a group of patients with rheumatoid arthritis benefit from dietary manipulations and that the improvement can be sustained through a two-year period.",
"title": "Vegetarian diet for patients with rheumatoid arthritis--status: two years after introduction of the diet."
},
{
"docid": "MED-5267",
"text": "BACKGROUND: The regulatory function of the endothelium is altered in hypercholesterolemia, and the subsequent endothelial dysfunction plays a central role in the development of atherosclerosis. OBJECTIVE: To determine whether endothelial function in hypercholesterolemic patients is affected by replacing a saturated fat-enriched diet with a low-fat, low-saturated fat diet (the U.S. National Cholesterol Education Program stage 1 [NCEP-1] diet) or a diet rich in monounsaturated fat (such as that common in Mediterranean countries). DESIGN: Intervention dietary study with a baseline phase and two randomized crossover dietary periods. SETTING: Hospital Universitario Reina Sofía, Córdoba, Spain. PATIENTS: 22 hypercholesterolemic men. INTERVENTION: Patients followed a diet high in saturated fat, then were assigned in a crossover design to the NCEP-1 diet or a Mediterranean diet. Each dietary period lasted 28 days. MEASUREMENTS: Plasma P-selectin levels, lipid concentrations, and endothelial function. RESULTS: Compared with the saturated fat diet, flow-mediated dilatation increased during the Mediterranean diet but not during the NCEP-1 diet. In addition, levels of plasma cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and P-selectin decreased during the NCEP-1 and Mediterranean diets. CONCLUSION: In hypercholesterolemic men, diets low in fat (especially saturated fat) and diets rich in monounsaturated fats improve endothelial function.",
"title": "Mediterranean and low-fat diets improve endothelial function in hypercholesterolemic men."
},
{
"docid": "MED-825",
"text": "BACKGROUND: Some evidence has suggested that a diet with a higher ratio of protein to carbohydrates has metabolic advantages in the treatment of polycystic ovary syndrome (PCOS). OBJECTIVE: The objective of this study was to compare the effect of a high-protein (HP) diet to a standard-protein (SP) diet in women with PCOS. DESIGN: A controlled, 6-mo trial was conducted in 57 PCOS women. The women were assigned through rank minimization to one of the following 2 diets without caloric restriction: an HP diet (>40% of energy from protein and 30% of energy from fat) or an SP diet (<15% of energy from protein and 30% of energy from fat). The women received monthly dietary counseling. At baseline and 3 and 6 mo, anthropometric measurements were performed, and blood samples were collected. RESULTS: Seven women dropped out because of pregnancy, 23 women dropped out because of other reasons, and 27 women completed the study. The HP diet produced a greater weight loss (mean: 4.4 kg; 95% CI: 0.3, 8.6 kg) and body fat loss (mean: 4.3 kg; 95% CI: 0.9, 7.6 kg) than the SP diet after 6 mo. Waist circumference was reduced more by the HP diet than by the SP diet. The HP diet produced greater decreases in glucose than did the SP diet, which persisted after adjustment for weight changes. There were no differences in testosterone, sex hormone-binding globulin, and blood lipids between the groups after 6 mo. However, adjustment for weight changes led to significantly lower testosterone concentrations in the SP-diet group than in the HP-diet group. CONCLUSION: Replacement of carbohydrates with protein in ad libitum diets improves weight loss and improves glucose metabolism by an effect that seems to be independent of the weight loss and, thus, seems to offer an improved dietary treatment of PCOS women.",
"title": "Effects of increased dietary protein-to-carbohydrate ratios in women with polycystic ovary syndrome."
},
{
"docid": "MED-1669",
"text": "One of the proposed causes of obesity and metabolic syndrome is the excessive intake of products containing added sugars, in particular, fructose. Although the ability of excessive intake of fructose to induce metabolic syndrome is mounting, to date, no study has addressed whether a diet specifically lowering fructose but not total carbohydrates can reduce features of metabolic syndrome. A total of 131 patients were randomized to compare the short-term effects of 2 energy-restricted diets-a low-fructose diet vs a moderate natural fructose diet-on weight loss and metabolic syndrome parameters. Patients were randomized to receive 1500, 1800, or 2000 cal diets according to sex, age, and height. Because natural fructose might be differently absorbed compared with fructose from added sugars, we randomized obese subjects to either a low-fructose diet (<20 g/d) or a moderate-fructose diet with natural fruit supplements (50-70 g/d) and compared the effects of both diets on the primary outcome of weight loss in a 6-week follow-up period. Blood pressure, lipid profile, serum glucose, insulin resistance, uric acid, soluble intercellular adhesion molecule-1, and quality of life scores were included as secondary outcomes. One hundred two (78%) of the 131 participants were women, mean age was 38.8 ± 8.8 years, and the mean body mass index was 32.4 ± 4.5 kg/m(2). Each intervention diet was associated with significant weight loss compared with baseline. Weight loss was higher in the moderate natural fructose group (4.19 ± 0.30 kg) than the low-fructose group (2.83 ± 0.29 kg) (P = .0016). Compared with baseline, each intervention diet was associated with significant improvement in secondary outcomes. Reduction of energy and added fructose intake may represent an important therapeutic target to reduce the frequency of obesity and diabetes. For weight loss achievement, an energy-restricted moderate natural fructose diet was superior to a low-fructose diet. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "The effect of two energy-restricted diets, a low-fructose diet versus a moderate natural fructose diet, on weight loss and metabolic syndrome param..."
},
{
"docid": "MED-4347",
"text": "BACKGROUND: The nutritional composition of the dietary intake could produce specific effects on metabolic variables and inflammatory marker concentrations. This study assessed the effects of two hypocaloric diets (legume-restricted- vs. legume-based diet) on metabolic and inflammatory changes, accompanying weight loss. METHODS: Thirty obese subjects (17 M/13F; BMI: 32.5 ± 4.5 kg/m(2); 36 ± 8 years) were randomly assigned to one of the following hypocaloric treatments (8 weeks): Calorie-restricted legume-free diet (Control: C-diet) or calorie-restricted legume-based diet (L-diet), prescribing 4 weekly different cooked-servings (160-235 g) of lentils, chickpeas, peas or beans. Body composition, blood pressure (BP), blood biochemical and inflammatory marker concentrations as well as dietary intake were measured at baseline and after the nutritional intervention. RESULTS: The L-diet achieved a greater body weight loss, when compared to the C-diet (-7.8 ± 2.9% vs. -5.3 ± 2.7%; p = 0.024). Total and LDL cholesterol levels and systolic BP were improved only when consuming the L-diet (p < 0.05). L-diet also resulted in a significant higher reduction in C-reactive protein (CRP) and complement C3 (C3) concentrations (p < 0.05), compared to baseline and C-diet values. Interestingly, the reduction in the concentrations of CRP and C3 remained significantly higher to L-diet group, after adjusting by weight loss (p < 0.05). In addition, the reduction (%) in CRP concentrations was positively associated with decreases (%) in systolic BP and total cholesterol concentration specifically in the L-diet group, independent from weight loss (p < 0.05). CONCLUSION: The consumption of legumes (4 servings/week) within a hypocaloric diet resulted in a specific reduction in proinflammatory markers, such as CRP and C3 and a clinically significant improvement of some metabolic features (lipid profile and BP) in overweight/ obese subjects, which were in some cases independent from weight loss.",
"title": "A legume-based hypocaloric diet reduces proinflammatory status and improves metabolic features in overweight/obese subjects."
},
{
"docid": "MED-4985",
"text": "Background: Low-fat vegetarian and vegan diets are associated with weight loss, increased insulin sensitivity, and improved cardiovascular health. Objective: We compared the effects of a low-fat vegan diet and conventional diabetes diet recommendations on glycemia, weight, and plasma lipids. Design: Free-living individuals with type 2 diabetes were randomly assigned to a low-fat vegan diet (n = 49) or a diet following 2003 American Diabetes Association guidelines (conventional, n = 50) for 74 wk. Glycated hemoglobin (Hb A1c) and plasma lipids were assessed at weeks 0, 11, 22, 35, 48, 61, and 74. Weight was measured at weeks 0, 22, and 74. Results: Weight loss was significant within each diet group but not significantly different between groups (−4.4 kg in the vegan group and −3.0 kg in the conventional diet group, P = 0.25) and related significantly to Hb A1c changes (r = 0.50, P = 0.001). Hb A1c changes from baseline to 74 wk or last available values were −0.34 and −0.14 for vegan and conventional diets, respectively (P = 0.43). Hb A1c changes from baseline to last available value or last value before any medication adjustment were −0.40 and 0.01 for vegan and conventional diets, respectively (P = 0.03). In analyses before alterations in lipid-lowering medications, total cholesterol decreased by 20.4 and 6.8 mg/dL in the vegan and conventional diet groups, respectively (P = 0.01); LDL cholesterol decreased by 13.5 and 3.4 mg/dL in the vegan and conventional groups, respectively (P = 0.03). Conclusions: Both diets were associated with sustained reductions in weight and plasma lipid concentrations. In an analysis controlling for medication changes, a low-fat vegan diet appeared to improve glycemia and plasma lipids more than did conventional diabetes diet recommendations. Whether the observed differences provide clinical benefit for the macro- or microvascular complications of diabetes remains to be established. This trial was registered at clinicaltrials.gov as NCT00276939.",
"title": "A low-fat vegan diet and a conventional diabetes diet in the treatment of type 2 diabetes: a randomized, controlled, 74-wk clinical trial"
},
{
"docid": "MED-5272",
"text": "Traditional cardiovascular risk factors are associated with endothelial dysfunction. The vascular endothelium plays a key role in local vascular tone regulation and can be modulated by dietary fat. We propose to determine the chronic effect of three diets with different fat compositions on postprandial endothelial function and inflammatory biomarkers. Twenty healthy men followed three 4-week diets in a randomised cross-over design: a Western diet, rich in saturated fat (22% SFA, 12% MUFA and 0.4% alpha-linolenic acid (ALA), all fractions are % of energy); a Mediterranean diet, rich in MUFA ( < 10 % SFA, 24 % MUFA and 0.4% ALA); a low-fat diet enriched in ALA ( < 10% SFA, 12% MUFA and 2% ALA). At the end of each dietary period all subjects underwent a postprandial study. Plasma concentrations of lipid parameters, soluble intercellular cell-adhesion molecule-1, soluble vascular cell-adhesion molecule-1 (sVCAM-1), nitrates and nitrites (NOx) and endothelial function studied by laser Doppler were examined at 0, 2, 4, 6 and 8 h. The endothelium-dependent vasodilatory response was greater 4 h after the ingestion of the MUFA-rich diet than after the SFA or ALA low-fat diets (P = 0.031). The 4 h postprandial plasma sVCAM-1 levels were lower after the MUFA meals than after the ALA low-fat diet (P = 0.043). The bioavailability of NOx was higher following the MUFA diet than after the SFA and ALA low-fat diets (P = 0.027). We found no differences in the other parameters measured. Chronic ingestion of a Mediterranean diet avoids the postprandial deterioration of endothelial function associated with Westernised diets in healthy individuals.",
"title": "Chronic effects of a high-fat diet enriched with virgin olive oil and a low-fat diet enriched with alpha-linolenic acid on postprandial endothelial..."
},
{
"docid": "MED-5200",
"text": "We studied the effect on fecal hydrolytic activities of adopting an uncooked extreme vegan diet and readopting a conventional diet. Eighteen subjects were randomly divided into test and control groups. In the test group subjects adopted the uncooked extreme vegan diet for 1 mo and then resumed a conventional diet for a second month. Controls consumed a conventional diet throughout the study. Phenol and p-cresol concentrations in serum and daily output in urine and fecal enzyme activities were measured. The activity of fecal urease significantly decreased (by 66%) as did cholylglycine hydrolase (55%), beta-glucuronidase (33%) and beta-glucosidase (40%) within 1 wk of beginning the vegan diet. The new level remained throughout the period of consuming this diet. Phenol and p-cresol concentrations in serum and daily outputs in urine significantly declined. The fecal enzyme activities returned to normal values within 2 wk of resuming the conventional diet. Concentrations of phenol and p-cresol in serum and daily output in urine had returned to normal after 1 mo of consuming the conventional diet. No changes were observed in the control group during the study. Results suggest that this uncooked extreme vegan diet causes a decrease in bacterial enzymes and certain toxic products that have been implicated in colon cancer risk.",
"title": "Shifting from a conventional diet to an uncooked vegan diet reversibly alters fecal hydrolytic activities in humans."
},
{
"docid": "MED-1454",
"text": "AIMS/HYPOTHESIS: The amount and quality of fat in the diet could be of importance for development of insulin resistance and related metabolic disorders. Our aim was to determine whether a change in dietary fat quality alone could alter insulin action in humans. METHODS: The KANWU study included 162 healthy subjects chosen at random to receive a controlled, isoenergetic diet for 3 months containing either a high proportion of saturated (SAFA diet) or monounsaturated (MUFA diet) fatty acids. Within each group there was a second assignment at random to supplements with fish oil (3.6 g n-3 fatty acids/d) or placebo. RESULTS: Insulin sensitivity was significantly impaired on the saturated fatty acid diet (-10%, p = 0.03) but did not change on the monounsaturated fatty acid diet (+2%, NS) (p = 0.05 for difference between diets). Insulin secretion was not affected. The addition of n-3 fatty acids influenced neither insulin sensitivity nor insulin secretion. The favourable effects of substituting a monounsaturated fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only seen at a total fat intake below median (37E%). Here, insulin sensitivity was 12.5% lower and 8.8% higher on the saturated fatty acid diet and monounsaturated fatty acid diet respectively (p = 0.03). Low density lipoprotein cholesterol (LDL) increased on the saturated fatty acid diet (+4.1%, p < 0.01) but decreased on the monounsaturated fatty acid diet (MUFA) (-5.2, p < 0.001), whereas lipoprotein (a) [Lp(a)] increased on a monounsaturated fatty acid diet by 12% (p < 0.001). CONCLUSIONS/INTERPRETATION: A change of the proportions of dietary fatty acids, decreasing saturated fatty acid and increasing monounsaturated fatty acid, improves insulin sensitivity but has no effect on insulin secretion. A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake (> 37E%).",
"title": "Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study."
},
{
"docid": "MED-2459",
"text": "BACKGROUND: Free radical-mediated oxidative damage to lipids is thought to be an important process in the pathogenesis of atherosclerosis. Although previous studies have demonstrated a beneficial impact of antioxidant vitamin supplements on lipid peroxidation, the effect of dietary patterns on lipid peroxidation is unknown. METHODS AND RESULTS: During the 3-week run-in period of a randomized trial, 123 healthy individuals were fed a control diet, low in fruits, vegetables, and dairy products, with 37% of calories from fat. Participants were then randomized to consume for 8 weeks: (1) the control diet, (2) a diet rich in fruits and vegetables but otherwise similar to the control diet, and (3) a combination diet rich in fruits, vegetables, and low-fat dairy products and reduced in fat. Serum oxygen radical-absorbing capacity, malondialdehyde (an in vitro measure of lipid peroxidation), and breath ethane (an in vivo measure of lipid peroxidation) were measured at the end of run-in and intervention periods. Between run-in and intervention, mean (95% CI) change in oxygen radical-absorbing capacity (U/mL) was -35 (-93, 13) in the control diet, 26 (-15, 67) in the fruits and vegetables diet (P=0.06 compared with control), and 19 (-22, 54) in the combination diet (P=0.10 compared with control). Median (interquartile range) change in ethane was 0.84 (0.10, 1.59) in the control diet, 0.02 (-0.61, 0.83) in the fruits and vegetables diet (P=0.04 compared with control), and -1.00 (-1.97, 0.25) in the combination diet (P=0.005 compared with control). Change in malondialdehyde did not differ between diets. CONCLUSIONS: This study demonstrates that modification of diet can favorably affect serum antioxidant capacity and protect against lipid peroxidation.",
"title": "Effect of dietary patterns on measures of lipid peroxidation: results from a randomized clinical trial."
}
] |
115390
|
Martin Scorsese completely avoided involving himself in the making of Cape Fear.
|
[
{
"docid": "Cape_Fear_(1991_film)",
"text": "Cape Fear is a 1991 American psychological thriller film directed by Martin Scorsese and a remake of the 1962 film of the same name . It stars Robert De Niro , Nick Nolte , Jessica Lange , and Juliette Lewis , and features cameos from Gregory Peck , Robert Mitchum , and Martin Balsam , who all appeared in the original film . It was Peck 's final theatrical film . The film tells the story of a convicted rapist who , using mostly his newfound knowledge of the law and its numerous loopholes , seeks vengeance against a former public defender whom he blames for his 14-year imprisonment due to purposefully faulty defense tactics used during his trial . Cape Fear marks the seventh of eight collaborations between Scorsese and De Niro , the others being Mean Streets ( 1973 ) , Taxi Driver ( 1976 ) , New York , New York ( 1977 ) , Raging Bull ( 1980 ) , The King of Comedy ( 1982 ) , Goodfellas ( 1990 ) and Casino ( 1995 ) . The film received positive reviews and received Academy Award and Golden Globe nominations for Best Actor ( De Niro ) and Best Supporting Actress ( Lewis ) .",
"title": ""
}
] |
[
{
"docid": "Cape_Fear_(1962_film)",
"text": "Cape Fear is a 1962 American psychological thriller film starring Robert Mitchum , Gregory Peck , Martin Balsam , and Polly Bergen . It was adapted by James R. Webb from the novel The Executioners by John D. MacDonald . It was initially storyboarded by Alfred Hitchcock ( slated to direct but quit over a dispute ) , subsequently directed by J. Lee Thompson , and released on April 12 , 1962 . The movie concerns an attorney whose family is stalked by a criminal he helped to send to jail . Cape Fear was remade in 1991 by Martin Scorsese . Peck , Mitchum , and Balsam all appeared in the remake .",
"title": ""
},
{
"docid": "Max_Cady",
"text": "Max Cady is a fictional character and the primary antagonist of the John D. MacDonald novel The Executioners . He was portrayed by Robert Mitchum in Cape Fear ( 1962 film ) and Robert De Niro in Martin Scorsese 's Cape Fear ( 1991 film ) .",
"title": ""
},
{
"docid": "Careful_(film)",
"text": "Careful ( 1992 ) is the third feature film directed by Guy Maddin . It is Maddin 's first colour film , shot on 16mm for a budget of $ 1.1 million . At one point , Martin Scorsese had agreed to act in the film , as Count Knotkers , but bowed out to complete Cape Fear . Maddin pursued casting hockey star Bobby Hull , but ended up casting Paul Cox .",
"title": ""
},
{
"docid": "Wesley_Strick",
"text": "Wesley Strick ( born February 11 , 1954 ) is an American screenwriter who has written such films as the comic-horror hit Arachnophobia , the Martin Scorsese remake of Cape Fear and the videogame adaptation Doom .",
"title": ""
},
{
"docid": "The_Audition_(2015_film)",
"text": "The Audition is a 2015 short film directed by Martin Scorsese . It stars Robert De Niro and Leonardo DiCaprio , playing fictionalized versions of themselves , who travel through Asia and compete against each other for a potential role in Scorsese 's next film . The short film was created as a promotional piece for the Studio City Macau Resort and Casino . It is Scorsese 's first film to feature both De Niro and DiCaprio . Both actors had individually worked with Scorsese several times in the past ( De Niro with eight films , DiCaprio with five ) , but the three had never collaborated together . Brad Pitt , also playing a fictionalized version of himself , makes a cameo appearance .",
"title": ""
},
{
"docid": "Casino_(film)",
"text": "Casino is a 1995 American epic crime drama film directed by Martin Scorsese and starring Robert De Niro , Joe Pesci , and Sharon Stone . It is based on the non-fiction book Casino : Love and Honor in Las Vegas by Nicholas Pileggi , who also co-wrote the screenplay for the film with Scorsese . The two previously collaborated on the hit film Goodfellas ( 1990 ) . The film marks the eighth collaboration between director Scorsese and actor Robert De Niro , following Mean Streets ( 1973 ) , Taxi Driver ( 1976 ) , New York , New York ( 1977 ) , Raging Bull ( 1980 ) , The King of Comedy ( 1982 ) , Goodfellas ( 1990 ) , and Cape Fear ( 1991 ) . In Casino , De Niro stars as Sam `` Ace '' Rothstein , a Jewish American top gambling handicapper who is called by the Italian Mob to oversee the day-to-day operations at the Tangiers Casino in Las Vegas . His character is based on Frank Rosenthal , who ran the Stardust , Fremont , and Hacienda casinos in Las Vegas for the Chicago Outfit from the 1970s until the early 1980s . Pesci plays Nicholas `` Nicky '' Santoro , based on real-life Mob enforcer Anthony Spilotro , a made man . Nicky is sent to Vegas to make sure that money from the Tangiers is skimmed off the top and the mobsters in Vegas are kept in line . Sharon Stone plays Ginger McKenna , Ace 's scheming , self-absorbed wife , based on Geri McGee . Casino was released on November 22 , 1995 , to a mostly positive critical response and was a box office success . Stone 's performance was unanimously praised , earning her a Golden Globe Award for Best Actress in a Motion Picture -- Drama and a nomination for the Academy Award for Best Actress .",
"title": ""
},
{
"docid": "The_Last_Temptation_of_Christ_(film)",
"text": "The Last Temptation of Christ is a 1988 American epic drama film directed by Martin Scorsese . Written by Paul Schrader with uncredited rewrites from Scorsese and Jay Cocks , the film is an adaptation of Nikos Kazantzakis ' controversial 1955 novel of the same name . The film , starring Willem Dafoe , Harvey Keitel , Barbara Hershey , Andre Gregory , Harry Dean Stanton and David Bowie , was shot entirely in Morocco . Like the novel , the film depicts the life of Jesus Christ and his struggle with various forms of temptation including fear , doubt , depression , reluctance and lust . This results in the book and film depicting Christ being tempted by imagining himself engaged in sexual activities , a notion that has caused outrage from some Christians . The film includes a disclaimer explaining that it departs from the commonly accepted biblical portrayal of Jesus 's life and is not based on the Gospels . The film received polarized reviews from critics on its release but Scorsese received an Academy Award nomination for Best Director . Hershey 's performance as Mary Magdalene earned her a nomination for the Golden Globe for Best Supporting Actress . Peter Gabriel 's music score also received acclaim , including a nomination for the Golden Globe Award for Best Original Score .",
"title": ""
},
{
"docid": "Martin_Scorsese",
"text": "Martin Charles Scorsese ( -LSB- skɔːrˈsɛsi -RSB- -LSB- skorˈseːze -RSB- ; born November 17 , 1942 ) is an American director , producer , screenwriter , and film historian , whose career spans more than 50 years . Scorsese 's body of work addresses such themes as Sicilian-American identity , Roman Catholic concepts of guilt and redemption , faith , machismo , modern crime , and gang conflict . Many of his films are also known for their depiction of violence and liberal use of profanity . Part of the New Hollywood wave of filmmaking , he is widely regarded as one of the most significant and influential filmmakers in cinematic history . In 1990 , he founded The Film Foundation , a nonprofit organization dedicated to film preservation , and in 2007 he founded the World Cinema Foundation . He is a recipient of the AFI Life Achievement Award for his contributions to the cinema , and has won an Academy Award , a Palme d'Or , Cannes Film Festival Best Director Award , Silver Lion , Grammy Award , Emmys , Golden Globes , BAFTAs , and DGA Awards . He has directed works such as the crime film Mean Streets ( 1973 ) , the vigilante-thriller Taxi Driver ( 1976 ) , the biographical sports drama Raging Bull ( 1980 ) , the black comedy The King of Comedy ( 1983 ) , the religious epic drama The Last Temptation of Christ ( 1988 ) , the crime film Goodfellas ( 1990 ) , the psychological thriller Cape Fear ( 1991 ) and the crime film Casino ( 1995 ) , some of which he collaborated on with actor and close friend Robert De Niro . Scorsese has also been noted for his successful collaborations with actor Leonardo DiCaprio , having directed him in five films , beginning with Gangs of New York ( 2002 ) and most recently The Wolf of Wall Street ( 2013 ) . Their third film together , The Departed , won Scorsese the Academy Award for Best Director in addition to the film winning the award for Best Picture . Their collaborations have resulted in numerous Academy Award nominations for both as well as them winning several other prestigious awards . Scorsese 's other film work includes the concert film The Last Waltz ( 1978 ) , the black comedy After Hours ( 1985 ) , the biographical drama The Aviator ( 2004 ) , the psychological thriller Shutter Island ( 2010 ) , the historical adventure drama Hugo ( 2011 ) and the religious epic Silence ( 2016 ) . His work in television includes the pilot episode of the HBO series Boardwalk Empire and Vinyl , the latter of which he also co-created . He won the Academy Award for Best Director for the crime drama The Departed ( 2006 ) . With eight Best Director nominations , he is the most nominated living director and is tied with Billy Wilder for the second most nominations overall .",
"title": ""
},
{
"docid": "I_Am_Cuba",
"text": "I Am Cuba ( Soy Cuba Я Куба , Ya Kuba ) is a 1964 Soviet-Cuban film directed by Mikhail Kalatozov at Mosfilm . The film was not received well by either the Russian or Cuban public and was almost completely forgotten until it was re-discovered by filmmakers in the United States thirty years later . The acrobatic tracking shots and idiosyncratic mise en scene prompted Hollywood directors like Martin Scorsese to begin a campaign to restore the film in the early 1990s . The film is shot in black and white , sometimes using infrared film obtained from the Soviet military to exaggerate contrast ( making trees and sugar cane almost white , and skies very dark but still obviously sunny ) . Most shots are in extreme wide-angle and the camera passes very close to its subjects , whilst still largely avoiding having those subjects ever look directly at the camera .",
"title": ""
},
{
"docid": "Juliette_Lewis",
"text": "Juliette L. Lewis ( born June 21 , 1973 ) is an American actress and singer . She gained fame for her role in Martin Scorsese 's 1991 remake of the thriller Cape Fear for which she was nominated for both an Academy Award and Golden Globe for Best Supporting Actress . This followed with major roles in What 's Eating Gilbert Grape , Natural Born Killers , Strange Days , The Evening Star , Kalifornia , From Dusk till Dawn , and The Other Sister . Her work in television has resulted in two Emmy nominations . Lewis launched a career as a singer and musician , leading the American rock band Juliette and the Licks until 2009 when she launched a solo career .",
"title": ""
},
{
"docid": "Martin_Scorsese_and_Robert_De_Niro",
"text": "Film director Martin Scorsese and actor Robert De Niro have frequently collaborated throughout their careers , making a grand total of eight feature films together since 1973 , along with one short film . Most of the pair 's films were in the crime genre . Some of the pair 's films are often ranked among the greatest films of all time .",
"title": ""
},
{
"docid": "The_Age_of_Innocence_(1993_film)",
"text": "The Age of Innocence is a 1993 American romantic period piece directed by Martin Scorsese . It is a film adaptation of Edith Wharton 's 1920 novel of the same name . The story takes place during the Gilded Age , portraying New York 's high society . The film was released by Columbia Pictures and stars Daniel Day-Lewis , Michelle Pfeiffer , Winona Ryder and Miriam Margolyes The Age of Innocence won the Academy Award for Best Costume Design , and was nominated for Academy Awards for Best Actress in a Supporting Role ( Winona Ryder ) , Best Adapted Screenplay , Best Original Score and Best Art Direction . The film was dedicated to Martin Scorsese 's father , Luciano Charles Scorsese , who died before it was completed .",
"title": ""
},
{
"docid": "Martin_Scorsese_bibliography",
"text": "A list of books and essays about Martin Scorsese : Scorsese , Martin",
"title": ""
},
{
"docid": "Martin_Scorsese_and_Leonardo_DiCaprio",
"text": "Film director Martin Scorsese and actor Leonardo DiCaprio have frequently collaborated , making a total of five feature films and one short film since 2002 . The pair 's films explore a variety of genres , including crime , thriller , biopic and comedy . Several have been listed on many critics ' year-end top ten and best-of-decade lists . The duo 's films have been nominated for thirty-one Academy Awards , winning nine . In 2013 , the duo was awarded National Board of Review Spotlight award for career collaboration . Scorsese 's work with DiCaprio is considered to be as vital as his work with Robert De Niro . Their movie The Wolf of Wall Street was included in the BBC 's 100 Greatest Films of the 21st Century .",
"title": ""
},
{
"docid": "Italianamerican",
"text": "For Italians and their descendents living in the United States , see Italian American . Italianamerican is a 1974 documentary directed by Martin Scorsese and featuring Scorsese 's parents , Catherine and Charles . The Scorseses talk about their experiences as Italian immigrants in New York City among other things , while having dinner at their flat on Elizabeth Street . Scorsese 's mother also instructs how to cook her meatballs , a recipe later featured in the credits of the film . Among the subjects discussed in the film are family , religion , their origins , Italian ancestors , life in Italy after the war and the hardships of poor Sicilian immigrants in America striving to make money .",
"title": ""
},
{
"docid": "Robert_De_Niro",
"text": "Robert Anthony De Niro ( -LSB- dəˈnɪroʊ -RSB- born August 17 , 1943 ) is an American actor , producer and director . He has both Italian and American citizenship . He was cast as the young Vito Corleone in the 1974 film The Godfather Part II , for which he won the Academy Award for Best Supporting Actor . His longtime collaboration with director Martin Scorsese earned him the Academy Award for Best Actor for his portrayal of Jake La Motta in the 1980 film Raging Bull . He received the AFI Life Achievement Award in 2003 , the Golden Globe Cecil B. DeMille Award in 2010 , and the Presidential Medal of Freedom from President Barack Obama in 2016 . De Niro 's first major film roles were in the sports drama , Bang the Drum Slowly ( 1973 ) and Scorsese 's crime film Mean Streets ( 1973 ) . He earned Academy Award nominations for the psychological thrillers Taxi Driver ( 1976 ) and Cape Fear ( 1991 ) , both directed by Scorsese . De Niro received additional nominations for Michael Cimino 's Vietnam war drama , The Deer Hunter ( 1978 ) , Penny Marshall 's drama Awakenings ( 1990 ) , and David O. Russell 's romantic comedy-drama , Silver Linings Playbook ( 2012 ) . His portrayal of gangster Jimmy Conway in Scorsese 's crime film , Goodfellas ( 1990 ) , and his role as Rupert Pupkin in the black comedy film The King of Comedy ( 1983 ) , earned him BAFTA Award nominations . De Niro has earned four nominations for the Golden Globe Award for Best Actor -- Motion Picture Musical or Comedy , for his work in the musical drama New York , New York ( 1977 ) , the action comedy Midnight Run ( 1988 ) , the gangster comedy Analyze This ( 1999 ) , and the comedy Meet the Parents ( 2000 ) . Other notable performances include roles in Once Upon a Time in America ( 1984 ) , Brazil ( 1985 ) , The Mission ( 1986 ) , The Untouchables ( 1987 ) , Heat ( 1995 ) , and Casino ( 1995 ) . He has directed and starred in films such as the crime drama A Bronx Tale ( 1993 ) and the spy film The Good Shepherd ( 2006 ) .",
"title": ""
},
{
"docid": "Catherine_Scorsese",
"text": "Catherine Scorsese ( née Cappa ; April 16 , 1912 -- January 6 , 1997 ) was an American actress , and the mother of director Martin Scorsese . Of Italian descent , she began acting when her son Martin Scorsese cast her in his film It 's Not Just You , Murray ! . She frequently played the role of an Italian mother , and is perhaps most well known for her appearance in her son 's film Goodfellas . She acted in films other than her son 's . She was married to Charles Scorsese . Her father , Martin Cappa , was a stage co-ordinator and her mother , Domenica , was a shop owner . She published a recipe book , Italianamerican : The Scorsese Family Cookbook .",
"title": ""
},
{
"docid": "Martin_Scorsese_Presents_the_Blues:_Keb'_Mo'",
"text": "Martin Scorsese Presents The Blues : Keb ' Mo ' is a blues album by Keb ' Mo ' , it was released in 2003 as part of Martin Scorsese 's The Blues documentary series .",
"title": ""
},
{
"docid": "Charles_Scorsese",
"text": "Luciano Charles `` Charlie '' Scorsese ( May 8 , 1913 -- August 23 , 1993 ) was an American film actor and the father of film director Martin Scorsese . Scorsese was born in New York City , the son of Teresa and Francesco Scorsese , Sicilian immigrants from Polizzi Generosa , a small town near Palermo . He married film actress Catherine Scorsese in 1933 . He was the father of Academy Award-winning film director Martin Scorsese . In 1980 he made his first film appearance in Raging Bull , playing `` Charlie '' . He featured in the gangster film Goodfellas in 1990 , portraying `` Vinnie '' who was based on the real-life gangster , Thomas Agro .",
"title": ""
},
{
"docid": "Cape_Fear_Academy",
"text": "Cape Fear Academy is a PK3-12 school located in Wilmington , North Carolina . It is a coeducational day school with 600 students and is a non-profit organization unaffiliated with any other institution , group , or church . Cape Fear Academy strives to be `` a learning community sharing a commitment to respect , integrity , academic excellence , and service to others . '' The school was incorporated in 1966 and opened its doors in September 1967 . It was named for the original Cape Fear Academy , an independent school for boys in Wilmington that operated from 1868 until 1916 . The present school 's first class graduated in 1971 . In the present enrollment model , there is one Prekindergarten ( ages 3.5 to 5 ) of 18 students , and Kindergarten through Grade 5 classes have two sections of 20 students each . Middle School ( grades 6-8 ) and Upper School ( grades 9-12 ) academic sections are composed of no more than 21 students , with up to 60 students enrolled in each of those grades . Cape Fear Academy has enjoyed a stable enrollment ; 93 % of its students re-enrolled after the 2009-2010 school year . The school is situated on a 27-acre ( 110,000 m2 ) campus . Present facilities include two classroom buildings , a gymnasium with 6 classrooms , and the Beane-Wright Student Center , as well as athletic fields and a tennis facility . Additionally , athletic fields , including a synthetic-turf field and the John B. Meehl Field House are located across from the campus entrance on College Road on a 9-acre ( 36,000 m2 ) tract . Cape Fear Academy is accredited by the Southern Association of Colleges and Schools and also by the Southern Association of Independent Schools . The school is also an active member of the National Association of Independent Schools , the Southern Association of Independent Schools , the North Carolina Association of Independent Schools , the Educational Records Bureau , the Independent School Management Consortium , and the College Entrance Examination Board . Cape Fear Academy offers two types of financial aid : need-based and merit . Approximately 18 % of the student body receives some type of financial aid , with the bulk of the awards benefiting students in the Middle and Upper School . Beginning in seventh grade , students may participate in interscholastic athletics . Approximately 89 % of the Middle School students play at least one sport during their tenure . In Upper School , about 93 % of the student body plays on at least one team and 60 % participate in two or more sports . The athletic program makes it possible for all students to have an opportunity in at least one sport per season . Upper School has an extensive list of clubs for students ranging from the Beta Club and the Diversity Club to the Surfing Club . Students are encouraged to create clubs where there are groups of interest and a faculty sponsor , A highly successful element of the Upper School program is theater . Approximately 30 % of the student body participates in drama as performers or in technology support . Drama presentations include a range of original and well-known pieces from Shakespeare to musical theater . Performances are held on campus , as well as in local community venues , such as Thalian Hall . The Upper School has an active student-government association , which includes a branch devoted to community service . Students in Upper School must complete 72 hours of service . One of the student-government vice presidents is charged with facilitating this part of student life . A student judicial council makes recommendations for minor disciplinary infractions . Cape Fear Academy has a long history of 100 % of its graduates being accepted to four-year colleges . The school offers an array of Advanced Placement ( AP ® ) courses and 90 % of the student body in Upper School takes an AP class before graduation . CFA students taking AP courses are required to take the course exam ; 94 % of the exams taken by CFA students in May 2012 scored as 3 , 4 , or 5 ( the level most colleges accept for credit ) . Graduates of CFA have a positive track record in college with a 66 % rate of CFA alumni completing their college careers in 4 years or fewer ( national average 29 % ) . Over 1,000 CFA alums are located around the world in a variety of careers and educational pursuits .",
"title": ""
},
{
"docid": "Martin_Scorsese_Presents_the_Blues:_Piano_Blues",
"text": "Martin Scorsese Presents the Blues : Piano Blues is the soundtrack to the documentary film directed by Clint Eastwood . This is the seventh part of the critically acclaimed television documentary series Martin Scorsese Presents The Blues shown on PBS in September 2003 . This collection of music represents what Clint said '' ... in my film Piano Blues I 'm trying to investigate who influenced everyone , and who the great players were . ''",
"title": ""
},
{
"docid": "Martin_Scorsese_Presents_the_Blues:_A_Musical_Journey",
"text": "Martin Scorsese Presents the Blues : A Musical Journey is a 2003 box set released on Hip-O Records . It is the soundtrack to the Martin Scorsese PBS documentary series The Blues . The box set attempts to present a history of the blues from the dawning of recorded music to the present day . It offers a survey of many different blues subgenres and tangential music styles , as well as a survey of almost all the most notable blues performers over time . In 2004 , the box set won two Grammy Awards for Best Historical Album and Best Album Notes . The previous year it was number 2 on the Billboards Top Blues Albums chart . Martin Scorsese Presents the Blues : A Musical Journey is also the title of a 2003 companion book to the series . Writers/editors include Peter Guralnick , Robert Santelli , Holly George-Warren and Christopher John Farley .",
"title": ""
},
{
"docid": "Geri_McGee",
"text": "Geraldine `` Geri '' McGee ( May 16 , 1936 -- November 9 , 1982 ) was an American model , socialite , and Las Vegas showgirl . Her involvement with criminal activity in Las Vegas , along with her husband Frank Rosenthal , was chronicled in the 1995 Martin Scorsese film Casino . The screenplay for Casino was written by Nicholas Pileggi and Scorsese , based on Pileggi 's biography about Geri and Frank Rosenthal titled Casino : Love and Honor in Las Vegas . Sharon Stone portrayed McGee in the film , with her name changed to ` Ginger McKenna ' , and was nominated for the Academy Award for Best Actress for her performance .",
"title": ""
},
{
"docid": "Scorsese_(surname)",
"text": "Scorsese is an Italian surname . Notable people with the surname include : Catherine Scorsese ( 1912 -- 1997 ) , American actress Charles Scorsese ( 1913 -- 1993 ) , American actor Martin Scorsese ( b. 1942 ) , American film director , writer , and producer Category : Italian-language surnames",
"title": ""
},
{
"docid": "Joseph_Minion",
"text": "Joseph Minion ( born 1957 in Teaneck , New Jersey ) is an American film director and screenwriter , best known for Martin Scorsese 's After Hours ( 1985 ) . Born in New Jersey in 1957 , Minion briefly attended NYU Film School before finishing his studies at Columbia University , then renowned for its screenwriting program . In 1984 , Minion 's script for After Hours was optioned by Griffin Dunne and Amy Robinson , the latter a former actress who 'd appeared as Harvey Keitel 's damaged girlfriend in Scorsese 's Mean Streets ( 1973 ) . Robinson sent Minion 's screenplay to Scorsese , whose Last Temptation of Christ had recently fallen through ; production on After Hours started shortly afterward . Later , it surfaced that Minion had plagiarized portions of After Hours from radio host Joe Frank , who sued and settled for an undisclosed sum . Minion continued his screenwriting career with 1987 's Julia and Julia starring Kathleen Turner ; 1989 's Vampire 's Kiss , starring Nicolas Cage ; Motorama ( 1991 ) ; and On the Run ( 1999 ) . He also worked again with Martin Scorsese in 1986 for an episode of Amazing Stories , `` Mirror , Mirror '' . As a director , Minion made his debut for producer Roger Corman with 1987 's Daddy 's Boys , said to have been thrown together at the last minute to make use of standing sets for Big Bad Mama II . His last outing as director was for another low-budget feature , Trafficking ( 1999 ) .",
"title": ""
},
{
"docid": "Eat_the_Document",
"text": "Eat the Document is a documentary of Bob Dylan 's 1966 tour of the United Kingdom with the Hawks . It was shot under Dylan 's direction by D. A. Pennebaker , whose groundbreaking documentary Dont Look Back chronicled Dylan 's 1965 British tour . The film was originally commissioned for the ABC television series ABC Stage 67 . Though shooting had completed for the film , Dylan 's July 1966 motorcycle accident delayed the editing process . Once well enough to work again , Dylan edited the film himself . ABC rejected the film as incomprehensible for a mainstream audience . It has never been released on home video and prints are rarely screened in theaters . Some footage from Eat the Document was used in Martin Scorsese 's 2005 documentary on Bob Dylan , No Direction Home and 3 song excerpts are Special Features on the DVD .",
"title": ""
},
{
"docid": "Martin_Scorsese_filmography",
"text": "Martin Scorsese ( born November 17 , 1942 ) is an American director , producer , screenwriter , actor , and film historian whose career spans more than fifty years . Scorsese has directed twenty-four narrative films to date . His movies Taxi Driver , Raging Bull , and Goodfellas are often cited among the greatest films ever made .",
"title": ""
},
{
"docid": "Gideon_Nieuwoudt",
"text": "Gideon Nieuwoudt ( 1951-2005 ) was a former apartheid-era security policeman involved in the torture and murder of several anti-apartheid activists , including Steve Biko . Nieuwoudt , nicknamed `` Notorious '' , was one of the most feared security policemen in the Eastern Cape for his interrogation methods including wet bags , poison , torture machines and often disguised himself as a priest , dubbing him the `` Priest from hell '' . Nieuwoudt has had up to five hearings at the Truth and Reconciliation Commission ( TRC ) , in connection with the murders of numerous political activists .",
"title": ""
},
{
"docid": "Sandy_Powell_(costume_designer)",
"text": "Sandy Powell OBE ( born 7 April 1960 ) is a British costume designer . She has won three Academy Awards for Best Costume Design for Shakespeare in Love ( 1998 ) , The Aviator ( 2004 ) , and The Young Victoria ( 2009 ) , and has been nominated 12 times for the award . She has also received 13 BAFTA Award nominations , winning for Velvet Goldmine and The Young Victoria . She won many other awards in costume design for the latter film . Powell is often associated with Martin Scorsese and Todd Haynes , having designed the costumes for six of Scorsese 's films and three of Haynes ' . Powell left Saint Martin 's School of Art in London , before completing her degree , due to offers of work from , amongst others , Derek Jarman . She was appointed Officer of the Order of the British Empire ( OBE ) in the 2011 New Year Honours for services to the film industry .",
"title": ""
},
{
"docid": "Martin_Scorsese_Presents_the_Blues_–_Taj_Mahal",
"text": "Martin Scorsese Presents the Blues -- Taj Mahal is an album by American blues artist Taj Mahal .",
"title": ""
}
] |
10553
|
How to report “foreign tax paid” from 1099-DIV?
|
[
{
"docid": "475410",
"text": "You can always take deduction for foreign tax paid on Schedule A, or calculate foreign tax credit using form 1116. Credit is usually more beneficial, but in some cases you will be better of with a deduction. However, in very specific cases, you can claim the credit directly on your 1040 without using the form 1116. Look at the 1040 instructions for line 47: Exception. You do not have to complete Form 1116 to take this credit if all of the following apply. All of your foreign source gross income was from interest and dividends and all of that income and the foreign tax paid on it were reported to you on Form 1099-INT, Form 1099-DIV, or Schedule K-1 (or substitute statement). The total of your foreign taxes was not more than $300 (not more than $600 if married filing jointly). You held the stock or bonds on which the dividends or interest were paid for at least 16 days and were not obligated to pay these amounts to someone else. You are not filing Form 4563 or excluding income from sources within Puerto Rico. All of your foreign taxes were: Legally owed and not eligible for a refund or reduced tax rate under a tax treaty, and Paid to countries that are recognized by the United States and do not support terrorism. For more details on these requirements, see the Instructions for Form 1116.",
"title": ""
}
] |
[
{
"docid": "496820",
"text": "When you invest (say $1000) in (say 100 shares) of a mutual fund at $10 per share, and the price of the shares changes, you do not have a capital gain or loss, and you do not have to declare anything to the IRS or make any entry on any line on Form 1040 or tell anyone else about it either. You can brag about it at parties if the share price has gone up, or weep bitter tears into your cocktail if the price has gone down, but the IRS not only does not care, but it will not let you deduct the paper loss or pay taxes on the paper gain. What you put down on Form 1040 Schedules B and D is precisely what the mutual fund will tell you on Form 1099-DIV (and Form 1099-B), no more, no less. If you did not report any of these amounts on your previous tax returns, you need to file amended tax returns, both Federal as well as State, A stock mutual fund invests in stocks and the fund manager may buy and sell some stocks during the course of the year. If he makes a profit, that money will be distributed to the share holders of the mutual fund. That money can be re-invested in more shares of the same mutual fund or taken as cash (and possibly invested in some other fund). This capital gain distribution is reported to you on Form 1099-DIV and you have to report sit on your tax return even if you re-invested in more share of the same mutual fund, and the amount of the distribution is taxable income to you. Similarly, if the stocks owned by the mutual fund pay dividends, those will be passed on to you as a dividend distribution and all the above still applies. You can choose to reinvest, etc, the amount will be reported to you on Form 1099-DIV, and you need to report it to the IRS and include it in your taxable income. If the mutual fund manager loses money in the buying and selling he will not tell you that he lost money but it will be visible as a reduction in the price of the shares. The loss will not be reported to you on Form 1099-DIV and you cannot do anything about it. Especially important, you cannot declare to the IRS that you have a loss and you cannot deduct the loss on your income tax returns that year. When you finally sell your shares in the mutual fund, you will have a gain or loss that you can pay taxes on or deduct. Say the mutual fund paid a dividend of $33 one year and you re-invested the money into the mutual fund, buying 3 shares at the then cost of $11 per share. You declare the $33 on your tax return that year and pay taxes on it. Two years later, you sell all 103 shares that you own for $10.50 per share. Your total investment was $1000 + $33 = $1033. You get $1081.50 from the fund, and you will owe taxes on $1081.50 - $1033 = $48.50. You have a profit of $50 on the 100 shares originally bought and a loss of $1.50 on the 3 shares bought for $11: the net result is a gain of $48.50. You do not pay taxes on $81.50 as the profit from your original $1000 investment; you pay taxes only on $48.50 (remember that you already paid taxes on the $33). The mutual fund will report on Form 1099-B that you sold 103 shares for $1081.50 and that you bought the 103 shares for an average price of $1033/103 = $10.029 per share. The difference is taxable income to you. If you sell the 103 shares for $9 per share (say), then you get $927 out of an investment of $1033 for a capital loss of $106. This will be reported to you on Form 1099-B and you will enter the amounts on Schedule D of Form 1040 as a capital loss. What you actually pay taxes on is the net capital gain, if any, after combining all your capital gains and losses for the year. If the net is a loss, you can deduct up to $3000 in a year, and carry the rest forward to later years to offset capital gains in later years. But, your unrealized capital gains or losses (those that occur because the mutual fund share price goes up and down like a yoyo while you grin or grit your teeth and hang on to your shares) are not reported or deducted or taxed anywhere. It is more complicated when you don't sell all the shares you own in the mutual fund or if you sell shares within one year of buying them, but let's stick to simple cases.",
"title": ""
},
{
"docid": "196399",
"text": "I can't find specific information for Form 1099-DIV for this tax year. However, I found this quote for next tax season that talks about Form 1099-B: Due date for certain statements sent to recipients. The due date for furnishing statements to recipients for Forms 1099-B, 1099-S, and 1099-MISC (if amounts are reported in box 8 or 14) is February 15, 2018. [emphasis added] I know many brokerages bundle the 1099-DIV with the 1099-B, so one might assume that the deadlines are the same. February 15 seems consistent with the messages I got from my brokerages that said the forms will be mailed by mid-February.",
"title": ""
},
{
"docid": "42665",
"text": "I believe it's not only legal, but correct and required. A 1099 is how a business reports payments to others, and they're required by the IRS to send them for payments of $600 or more (for miscalleneous payments like this). The payment is an expense to the landlord and income to you, and the 1099 is how that's documented (although note that if they don't send you a 1099, it's still income to you and you still need to report it as such). It's similar to getting a 1099-INT for interest payments or a 1099-DIV for dividend payments. You'll get a 1099-MISC for a miscellaneous payment. If you were an employee they'd send you a W-2, not a 1099.",
"title": ""
},
{
"docid": "490997",
"text": "Why was I sent both 1042-S and 1099. Which amount is the right amount that has been withheld. Generally, each tax form you get will be about a separate income; for instance, you might get a 1099-DIV for dividends you earned from an investment and then a 1099-B for the profit or loss on selling that investment, in which case you'd report them both to the IRS. In this case, you've also had money withheld as a non-resident alien, which is why you've been issued a 1042-S. So you need to report both amounts to the IRS.",
"title": ""
},
{
"docid": "212394",
"text": "\"I'll try to answer using your original example. First, let me restate your assumptions, slightly modified: The mutual fund has: Note that I say the \"\"mutual fund has\"\" those gains and losses. That's because they occur inside the mutual fund and not directly to you as a shareholder. I use \"\"realized\"\" gains and losses because the only gains and losses handled this way are those causes by actual asset (stock) sales within the fund (as directed by fund management). Changes in the value of fund holdings that are not sold are not included in this. As a holder of the fund, you learn the values of X, Y, and Z after the end of the year when the fund management reports the values. For gains, you will also typically see the values reported on your 1099-DIV under \"\"capital gains distributions\"\". For example, your 1099-DIV for year 3 will have the value Z for capital gains (besides reporting any ordinary dividends in another box). Your year 1 1099 will have $0 \"\"capital gains distributions\"\" shown because of the rule you highlighted in bold: net realized losses are not distributed. This capital loss however can later be used to the mutual fund holder's tax advantage. The fund's internal accounting carries forward the loss, and uses it to offset later realized gains. Thus your year 2 1099 will have a capital gain distribution of (Y-X), not Y, thus recognizing the loss which occurred. Thus the loss is taken into account. Note that for capital gains you, the holder, pay no tax in year 1, pay tax in year 2 on Y-X, and pay tax in year 3 on Z. All the above is the way it works whether or not you sell the shares immediately after the end of year 3 or you hold the shares for many more years. Whenever you do sell the shares, you will have a gain or loss, but that is different from the fund's realized losses we have been talking about (X, Y, and Z).\"",
"title": ""
},
{
"docid": "227518",
"text": "I am using the same logic as the two answers above. I got almost the same result ($46.60 instead of $46.59 per share) using the sold fractional share basis. However, the JCI Qualified Dividend (on the 1099-DIV, not the 1099-B) divided by the number of shares spun off yields a basis per share of only $40.97 That compares to $45.349 in answer two above. It seems that we should get the approximately same basis per share using the same arithmetic, and I do not know why we don't. For my tax files, I plan to use the Adient basis equal to the dividend from the 2016 1099-DIV of JCI (the PLC after the merger). My reasoning is that I cannot use an amount for the Adient basis that is greater than the dividend I paid taxes on. [In case this part of the question comes up again, you can get historical quotes at various websites such as https://finance.yahoo.com/quote, which does show $45.51 as the Adient closing price on 10/31/16.]",
"title": ""
},
{
"docid": "350555",
"text": "Capital gain distribution is not capital gain on sale of stock. If you have stock sales (Schedule D) you should be filing 1040, not 1040A. Capital gain distributions are distributions from mutual funds/ETFs that are attributed to capital gains of the funds (you may not have actually received the distribution, but you still may have gain attributed to you). It is reported on 1099-DIV, and if it is 0 - then you don't have any. If you sold a stock, your broker should have given you 1099-B (which is not the same as 1099-DIV, but may be consolidated by your broker into one large PDF and not provided separately). On 1099-B the sales proceeds are recorded, and if you purchased the stock after 2011 - the cost basis is also recorded. The difference between the proceeds and the cost basis is your gain (or loss, if it is negative). Fees are added to cost basis.",
"title": ""
},
{
"docid": "480949",
"text": "\"It is true, as farnsy noted, that you generally do not know when stock that you're holding has been loaned by your broker to someone for a short sale, that you generally consent to that when you sign up somewhere in the small print, and that the person who borrows has to make repay and dividends. The broker is on the hook to make sure that your stock is available for you to sell when you want, so there's limited risk there. There are some risks to having your stock loaned though. The main one is that you don't actually get the dividend. Formally, you get a \"\"Substitute Payment in Lieu of Dividends.\"\" The payment in lieu will be taxed differently. Whereas qualified dividends get reported on Form 1099-DIV and get special tax treatment, substitute payments get reported on Form 1099-MISC. (Box 8 is just for this purpose.) Substitute payments get taxed as regular income, not at the preferred rate for dividends. The broker may or may not give you additional money beyond the dividend to compensate you for the extra tax. Whether or not this tax difference matters, depends on how much you're getting in dividends, your tax bracket, and to some extent your general perspective. If you want to vote your shares and exercise your ownership rights, then there are also some risks. The company only issues ballots for the number of shares issued by them. On the broker's books, however, the short sale may result in more long positions than there are total shares of stock. Financially the \"\"extra\"\" longs are offset by shorts, but for voting this does not balance. (I'm unclear how this is resolved - I've read that the the brokers essentially depend on shareholder apathy, but I'd guess there's more to it than that.) If you want to prevent your broker from loaning out your shares, you have some options:\"",
"title": ""
},
{
"docid": "417866",
"text": "\"Payment gateways such as Square do not normally withhold tax. It is up to you to pay the appropriate tax at tax time. That having been said, Square does report your payments to the IRS on a form 1099-K if your payments are large enough. According to Square, you'll get a 1099-K from them if your total payments for the year add up to $20,000 AND more than 200 transactions. Whether or not they report on a 1099-K, you are required to pay the appropriate taxes on your income. So now the question becomes, \"\"Do I have to pay income tax on the proceeds from my garage sale?\"\" And the answer to that question is usually not. When you sell something that you previously purchased, if you sell it for more than you paid for it, you have a capital gain and need to pay tax on that. However, generally you sell things in a garage sale at a loss, meaning that there is no tax due. If you make more than $20,000 at your garage sale and the IRS gets a 1099-K, the IRS might be curious as to how you did that with no capital gain. So if you sell any big ticket items (a bulldozer, for example), you should keep a record of what you paid for it, so you can show the loss to the IRS in the event of an audit.\"",
"title": ""
},
{
"docid": "64672",
"text": "\"Income code 09 is dividends, so yes - it is the same as line 1 of the US form 1099-DIV. 1a or 1b however depends on whether the requirements for qualified dividends are met. If they're met - its 1b, if not - 1a. These are treated and taxed differently. See here on what are the qualification requirements. Note that Canada has a tax treaty with the US making Canadian corporations \"\"qualified foreign corporations\"\".\"",
"title": ""
},
{
"docid": "347723",
"text": "\"I don't see why you would need an \"\"international tax specialist\"\". You need a tax specialist to give you a consultation and training on your situation, but it doesn't seem too complicated to me. You invoice your client and get paid - you're a 1099 contractor. They should issue you a 1099 at the end of the year on everything they paid you. Once you become full-time employee - you become a W2 employee and will get a W2 at the end of the year on the amounts paid as such. From your perspective there's nothing international here, regular business. You have to pay your own taxes on the 1099 income (including SE taxes), they have to withhold taxes from your W2 income (including FICA). Since they're foreign employers, they might not do that latter part, and you'll have to deal with that on your tax return, any decent EA/CPA will be able to accommodate you with that. For the employer there's an issue of international taxation. They might have to register as a foreign business in your state, they might be liable for some payroll taxes and State taxes, etc etc. They might not be aware of all that. They might also be liable (or exempt) for Federal taxes, depending on the treaty provisions. But that's their problem. Your only concern is whether they're going to issue you a proper W2 and do all the withholdings or not when the time comes.\"",
"title": ""
},
{
"docid": "276411",
"text": "This is a complicated question that relies on the US-India Tax Treaty to determine whether the income is taxable to the US or to India. The relevant provision is likely Article 15 on Personal Services. http://www.irs.gov/pub/irs-trty/india.pdf It seems plausible that your business is personal services, but that's a fact-driven question based on your business model. If the online training is 'personal services' provided by you from India, then it is likely foreign source income under the treaty. The 'fixed base' and '90 days' provisions in Article 15 would not apply to an India resident working solely outside the US. The question is whether your US LLC was a US taxpayer. If the LLC was a taxpayer, then it has an obligation to pay US tax on any worldwide income and it also arguably disqualifies you from Article 15 (which applies to individuals and firms of individuals, but not companies). If you were the sole owner of the US LLC, and you did not make a Form 8832 election to be treated as subject to entity taxation, then the LLC was a disregarded entity. If you had other owners, and did not make an election, then you are a partnership and I suspect but cannot conclude that the treaty analysis is still valid. So this is fact-dependent, but you may be exempt from US tax under the tax treaty. However, you may have still had an obligation to file Forms 1099 for your worker. You can also late-file Forms 1099 reporting the nonemployee compensation paid to your worker. Note that this may have tax consequences on the worker if the worker failed to report the income in those years.",
"title": ""
},
{
"docid": "350317",
"text": "Generally, ETFs and mutual funds don't pay taxes (although there are some cases where they do, and some countries where it is a common case). What happens is, the fund reports the portion of the gain attributed to each investor, and the investor pays the tax. In the US, this is reported to you on 1099-DIV as capital gains distribution, and can be either short term (as in the scenario you described), long term, or a mix of both. It doesn't mean you actually get a distribution, though, but if you don't - it reduces your basis.",
"title": ""
},
{
"docid": "368938",
"text": "\"Answers: 1: No, Sections 1291-1298 of the IRC were passed in the Reagan adminstration. 2: Not only can a foreign company like a chocolate company fall afoul of the definition of PFIC because of the \"\"asset test\"\", which you cite, but it can also be called a PFIC because of the \"\"income test\"\". For example, I have shares in a development-stage Canadian biotech which is considered a PFIC because it has no income at all, except for a minor amount of bank interest on its working capital. This company is by no means \"\"passive\"\" (it has run 31 clinical trials in over 1100 human research subjects, burning $250M of investor's money in the process) nor is it an \"\"investment company\"\", but the stupid IRS considers it to be a \"\"passive foreign investment company\"\"! The IRS looks at it and sees only the bank account, and assumes it is a foreign shell corporation set up to shield the bank interest from them. 3: Yes, a foreign mutual fund is EXACTLY what congress intended to be a PFIC when passed IRC 1291-1298. (Biotechs, candy factories, ect got nailed as innocent bystanders.) Note that if you hold a US mutual fund then every year you'll get a form 1099 in the mail. The 1099 will report your share of the mutual fund's own income and capital gains, which you must report on your taxes. (You can also have capital gains from selling your shares of the mutual fund, but that's a different thing.) Now suppose that there was no PFIC law. Then the US investors in the mutual fund would do better if the mutual fund were in a foreign country, for two reasons: a) The fund would no longer distribute 1099's. That means the shareholders wouldn't have to pay tax every year on their proportions of the fund's own income/gains. The money that would have sooner gone to the IRS can sit around for years earning interest. b) The fund could return profits to shareholders exclusively through capital gains rather than dividends, thus ensuring that all of the investors' income on the fund would be taxed at <15%-20% rather than up to 39%. The fund could do this by returning cash to shareholders exclusively through buybacks. However, the US mutual fund industry doesn't want to move the industry to Canada, and it only takes a few newspaper articles about a foreign loophole to make congress spring to action. 4) It depends. If you have a PEDIGREED QEF election in place (as I do for my biotech shares) then form 8621 takes a few minutes by hand. However, this requires both the company and the investor to fully cooperate with congress's vision for PFICs. The company cooperates by providing a so-called \"\"PFIC annual information sheet\"\", which replaces the 1099 form for a US mutual fund. The investor cooperates by having a \"\"QEF election\"\" in place for EACH AND EVERY TAX YEAR in which he held the stock and by reporting the numbers from the PFIC annual information sheet on his return. (Note that the QEF election persists once made, until revoked. There are subtleties here that I am glossing over, since \"\"deemed sale\"\" elections and other means may be used to modify a share's holding period to come into compliance.) Note that there is software coming out to handle PFICs, and that the software makers will already run their software to make your form 8621 for $75 or so. I should also warn you that the blogs of tax accountants and tax lawyers all contradict each other on the basic issue of whether you can take capital losses on PFICs for which you have no form 8621 elections. (See section 2.3 of my notes http://tinyurl.com/mh9vlnr for commentary on this mess.) I do not know if the software people will tell you which elections are best made on form 8621, though, or advise you if it's time to simply dump your investment. The professional software is at 8621.com, and the individual 8621 preparation is at http://expattaxtools.com/?page_id=242. BTW, in case you're interested, I wrote up a very careful analysis of how to deal with the PFIC situation for the small biotech I invested in in certain cases. It is posted http://tinyurl.com/mh9vlnr. (For tax reasons it was quite fortunate that the share price dipped to near an all-time low on Jan 1, 2015, making the (next) 2015 tax year ripe for a so-called \"\"deemed sale\"\" election. This was only possible because the company provides the necessary \"\"PFIC annual information statements\"\", which your chocolate factory may or may not do.)\"",
"title": ""
},
{
"docid": "251394",
"text": "The capital gain is either short-term or long-term and will be indicated on the 1099-DiV. You pay taxes on this amount as the capital gain was received in a taxable account (assuming since you received a 1099-DIV). More info here: https://www.mutualfundstore.com/brokerage-account/capital-gains-distributions-taxable",
"title": ""
},
{
"docid": "489898",
"text": "\"Whenever you do paid work for a company, you will need to fill out some sort of paperwork so that the company knows how to pay you, and also how to report how much they paid you to the appropriate government agencies. You should not think of this as a \"\"hurdle\"\" and you shouldn't worry that you haven't been employed for a long time. The two most common ways a company pays an individual are via employee wages, or \"\"independent contractor\"\" payments. When you start a relationship with a company, if you are going to become an employee, then you will out a W4 form, and at the end of the year you will receive a W2 form. If you are an independent contractor, (which you would be considered in this case), you will fill out form W9 and at the end of the year you will receive a 1099. This is completely normal and you have nothing to worry about. All it means is that if you make more than a certain amount (typically $600) in a year, you will receive a 1099 in the mail or electronically. The 1099 form basically means that they are reporting that amount to the IRS, and it also helps you file your tax return by showing you all the numbers you need on one form. Please remember that when you are paid as an independent contractor, no taxes are withheld on your behalf, so you may owe some tax on the money you make. It's best to set aside some of your income so you are prepared to pay it come tax time next year.\"",
"title": ""
},
{
"docid": "254151",
"text": "\"If you receive a 1099-MISC from YouTube, that tells you what they stated to the IRS and leads into most tax preparation software guided interviews or wizards as a topic for you to enter. Whether or not you have a 1099-MISC, this discussion from the IRS is pertinent to your question. You could probably elect to report the income as a royalty on your copyrighted work of art on Schedule E, but see this note: \"\"In most cases you report royalties in Part I of Schedule E (Form 1040). However, if you ... are in business as a self-employed writer, inventor, artist, etc., report your income and expenses on Schedule C or Schedule C-EZ (Form 1040).\"\" Whether reporting on Schedule E or C is more correct or better for your specific circumstances is beyond the advice you should take from strangers on the internet based on a general question - however, know that there are potentially several paths for you. Note that this is revenue from a business, so if you paid for equipment or services that are 100% dedicated to your YouTubing (PC, webcam, upgraded broadband, video editing software, vehicle miles to a shoot, props, etc.) then these are a combination of depreciable capital investments and expenses you can report against the income, reducing the taxes you may owe. If the equipment/services are used for business and personal use, there are further guidelines from the IRS as to estimating the split. These apply whether you report on Sch. E, Sch. C, or Sch C-EZ. Quote: \"\"Self-Employment Income It is a common misconception that if a taxpayer does not receive a Form 1099-MISC or if the income is under $600 per payer, the income is not taxable. There is no minimum amount that a taxpayer may exclude from gross income. All income earned through the taxpayer’s business, as an independent contractor or from informal side jobs is self-employment income, which is fully taxable and must be reported on Form 1040. Use Form 1040, Schedule C, Profit or Loss from Business, or Form 1040, Schedule C-EZ, Net Profit from Business (Sole Proprietorship) to report income and expenses. Taxpayers will also need to prepare Form 1040 Schedule SE for self-employment taxes if the net profit exceeds $400 for a year. Do not report this income on Form 1040 Line 21 as Other Income. Independent contractors must report all income as taxable, even if it is less than $600. Even if the client does not issue a Form 1099-MISC, the income, whatever the amount, is still reportable by the taxpayer. Fees received for babysitting, housecleaning and lawn cutting are all examples of taxable income, even if each client paid less than $600 for the year. Someone who repairs computers in his or her spare time needs to report all monies earned as self-employment income even if no one person paid more than $600 for repairs.\"\"\"",
"title": ""
},
{
"docid": "57229",
"text": "Your clients should not send you 1099-MISC if they paid with a credit card. You can refer them to this text in the instructions for the form 1099-MISC: Payments made with a credit card or payment card and certain other types of payments, including third party network transactions, must be reported on Form 1099-K by the payment settlement entity under section 6050W and are not subject to reporting on Form 1099-MISC. See the separate Instructions for Form 1099-K. By sending out the 1099-MISC, your clients are essentially saying that they paid you directly (check or cash) in addition to the payment they made with a credit card (which will be reported on 1099-K). In case of an audit, you'll have trouble convincing the IRS that it didn't happen. I suggest asking the clients not to do this to you, since it may cost you significant amounts to fight the IRS later on. In any case, you report on your tax return what you really got, not what the 1099 says. If you have two 1099's covering the same income - there's no legal obligation to report the income twice. You do not have to pay twice the tax just because you have stupid clients. But you may have troubles explaining it to the IRS, especially if you're dealing with cash in your business. If you want to avoid matching issues, consider reporting all the 1099s, and then subtracting the duplicates and attaching a statement (the software will do it automatically when you add the description in the miscellaneous item) about what it is.",
"title": ""
},
{
"docid": "332626",
"text": "\"The IRS taxes worldwide income of its citizens and green card holders. Generally, for those Americans genuinely living/working overseas the IRS takes the somewhat reasonable position of being in \"\"2nd place\"\" tax-wise. That is, you are expected to pay taxes in the country you are living in, and these taxes can reduce the tax you would have owed in the USA. Unfortunately, all of this has to be documented and tax returns are still required every year. Your European friends may find this quite surprising as I've heard, for instance, that France will not tax you if you go live and work in Germany. A foreign company operating in a foreign country under foreign law is not typically required to give you a W-2, 1099, or any of the forms you are used to. Indeed, you should be paying taxes in the place where you live and work, which is probably somewhat different than the USA. Keep all these records as they may be useful for your USA taxes as well. You are required to total up what you were paid in Euros and convert them to US$. This will go on the income section of a 1040. You should be paying taxes in the EU country where you live. You can also total those up and convert to US$. This may be useful for a foreign tax credit. If you are living in the EU long term, like over 330 days/year or you have your home and family there, then you might qualify for a very large exemption from your income for US tax purposes, called the Foreign Earned Income Exclusion. This is explained in IRS Publication 54. The purpose of this is primarily to avoid double taxation. FBAR is a serious thing. In past years, the FBAR form went to a Financial Crimes unit in Detroit, not the regular IRS address. Also, getting an extension to file taxes does not extend the deadline for the FBAR. Some rich people have paid multi-million dollar fines over FBAR and not paying taxes on foreign accounts. I've heard you can get a $10,000 FBAR penalty for inadvertent, non-willful violations so be sure to send those in and it goes up from there to $250k or half the value of the account, whichever is more. You also need to know about whether you need to do FATCA reporting with your 1040. There are indeed, a lot of obnoxious things you need to know about that came into existence over the years and are still on the law books -- because of the perpetual 'arms race' between the government and would be cheaters, non-payers and their advisors. http://www.irs.gov/publications/p54/ http://americansabroad.org/\"",
"title": ""
},
{
"docid": "404840",
"text": "Profit after tax can have multiple interpretations, but a common one is the EPS (Earnings Per Share). This is frequently reported as a TTM number (Trailing Twelve Months), or in the UK as a fiscal year number. Coincidentally, it is relatively easy to find the total amount of dividends paid out in that same time frame. That means calculating div cover is as simple as: EPS divided by total dividend. (EPS / Div). It's relatively easy to build a Google Docs spreadsheet that pulls both values from the cloud using the GOOGLEFINANCE() function. I suspect the same is true of most spreadsheet apps. With a proper setup, you can just fill down along a column of tickers to get the div cover for a number of companies at once.",
"title": ""
},
{
"docid": "406042",
"text": "Are the amounts in those boxes taxes that have already been removed? Yes. If they are, how do I report these totals? When I entered the information from the 1099-MISC, it only asked for the total, and didn't ask for (what I thought were) the taxes already taken out. It should appear on your 1040 line 64 (and similar line on your State tax return). If the program doesn't ask for all the 1099 fields (which is stupid), you can add it as additional taxes paid in the Credits section, somewhere in the area where they ask about estimated payments etc.",
"title": ""
},
{
"docid": "466213",
"text": "\"You file taxes as usual. W2 is a form given to you, you don't need to fill it. Similarly, 1099. Both report moneys paid to you by your employers. W2 is for actual employer (the one where you're on the payroll), 1099 is for contractors (where you invoice the entity you provide services to and get paid per contract). You need to look at form 1040 and its instructions as to how exactly to fill it. That would be the annual tax return. It has various schedules (A, B, C, D, E, F, H, etc) which you should familiarize yourself with, and various additional forms that you attach to it. If you're self employed, you're expected to make quarterly estimate payments, but if you're a salaried employee you can instruct your employer to withhold the amounts you expect to owe for taxes from your salary, instead. If you're using a tax preparation software (like TurboTax or TaxAct), it will \"\"interview\"\" you to get all the needed information and provide you with the forms filled accordingly. Alternatively you can pay someone to prepare the tax return for you.\"",
"title": ""
},
{
"docid": "530596",
"text": "Many of the custodians (ie. Schwab) file for an extension on 1099s. They file for an extension as many of their accounts have positions with foreign income which creates tax reporting issues. If they did not file for extension they would have to send out 1099s at the end of January and then send out corrected forms. Obviously sending out one 1099 is cheaper and less confusing to all. Hope that helps,",
"title": ""
},
{
"docid": "562776",
"text": "I would at least encrypt the part of the drive you keep forms like that, but not to protect myself from the odd villain who works for the IRS. Your broker does report your capital gains to the IRS, whether in sales or dividends. I received a bill last month from the IRS for dividends I forgot to report on my 2013 return. The bill contained a partial duplicate of my 1099-DIV form from the brokerage, and included account numbers and SSN. Therefore it's safe to say IRS employees don't need to hack your laptop in order to get that info. :) As for minimum information, it depends on your broker. Call them and ask; they'll tell you everything you need to know. Vanguard, for example, has some security questions, among other things.",
"title": ""
},
{
"docid": "28633",
"text": "\"I think I found the answer, at least in my specific case. From the heading \"\"Questar/Dominion Resources Merger\"\" in this linked website: Q: When will I receive tax forms showing the stock and dividend payments? A: You can expect a Form 1099-B in early February 2017 showing the amount associated with payment of your shares. You also will receive a Form 1099-DIV by Jan. 31, 2017, with your 2016 dividends earned.\"",
"title": ""
},
{
"docid": "122012",
"text": "In a taxable account you're going to owe taxes when you sell the shares for a gain. You're also going to owe taxes on any distributions you receive from the holdings in the account; these distributions can happen one or more times a year. Vanguard has a writeup on mutual fund taxation. Note: for a fund like you linked, you will owe taxes annually, regardless of whether you sell it. The underlying assets will pay dividends and those are distributed to you either in cash, or more beneficially as additional shares of the mutual fund (look into dividend reinvestment.) Taking VFIAX's distributions as an example, if you bought 1 share of the fund on March 19, 2017, on March 20th you would have been given $1.005 that would be taxable. You'd owe taxes on that even if you didn't sell your share during the year. Your last paragraph is based on a false premise. The mutual fund does report to you at the end of the year the short and long term capital gains, along with dividends on a 1099-DIV. You get to pay taxes on those transactions, that's why it's advantageous to hold low turnover mutual funds in taxable accounts.",
"title": ""
},
{
"docid": "559884",
"text": "The dividend quoted on a site like the one you linked to on Yahoo shows what 1 investor owning 1 share received from the company. It is not adjusted at all for taxes. (Actually some dividend quotes are adjusted but not for taxes... see below.) It is not adjusted because most dividends are taxed as ordinary income. This means different rates for different people, and so for simplicity's sake the quotes just show what an investor would be paid. You're responsible for calculating and paying your own taxes. From the IRS website: Ordinary Dividends Ordinary (taxable) dividends are the most common type of distribution from a corporation or a mutual fund. They are paid out of earnings and profits and are ordinary income to you. This means they are not capital gains. You can assume that any dividend you receive on common or preferred stock is an ordinary dividend unless the paying corporation or mutual fund tells you otherwise. Ordinary dividends will be shown in box 1a of the Form 1099-DIV you receive. Now my disclaimer... what you see on a normal stock quote for dividend in Yahoo or Google Finance is adjusted. (Like here for GE.) Many corporations actually pay out quarterly dividends. So the number shown for a dividend will be the most recent quarterly dividend [times] 4 quarters. To find out what you would receive as an actual payment, you would need to divide GE's current $0.76 dividend by 4 quarters... $0.19. So you would receive that amount for each share of stock you owned in GE.",
"title": ""
},
{
"docid": "481459",
"text": "Do you get cash (or a deposit into your bank account) of your PhD stipend and then you immediately send the university a check to pay the tuition fee (which might be more than the cash you get from the University)? Or does the University simply keep the stipend money, transferring it from one pocket to another in essence, and say, OK, you have paid your tuition except for $X that you still owe us? Or does the university grant you a tuition waiver as part of your assistantship and reports this as income on Form 1099-MISC? In all of these cases, the money reported on Form 1099-MISC is not taxable income to you, and it is neither subject to Self-Employment tax (basically, Social Security and Medicare tax -- both the employee's share and the employer's share) nor to (Federal) income tax.",
"title": ""
},
{
"docid": "65040",
"text": "As the owner of the S-corp, it is far easier for you to move money in/out of the company as contributions and distributions rather than making loans to the company. Loans require interest payments, 1099-INT forms, and have tax consequences, whereas the distributions don't need to be reported because you pay taxes on net profits regardless of whether the money was distributed. If you were paid interest, disregard this answer. I don't know if or how you could re-categorize the loan once there's a 1099-INT involved. If no interest was ever paid, you just need to account for it properly: If the company didn't pay you any interest and never issued you a 1099-INT form (i.e. you wrote a check to the company, no promissory note, no tax forms, no payments, no interest, etc.) then you can categorize that money as a capital contribution. You can likewise take that money back out of the company as a capital distribution and neither of these events are taxable nor do they need to be reported to the IRS. In Quickbooks, create the following Equity accounts -- one for each shareholder making capital contributions and distributions: When putting money into the company, deposit into your corporate bank account and use the Capital Contribution equity account. When taking money out of the company, write yourself a check and use the Distributions account. At the end of every tax year, you can close out your Contributions and Distributions to Retained Earnings by making a general journal entry. For example, debit retained earnings and credit distributions on Dec 31 every year to zero-out the distributions account. For contributions, do the reverse and credit retained earnings. There are other ways of recording these transactions -- for example I think some people just use a Member Capital equity account instead of separate accounts for contributions and distributions -- and QB might warn you about posting journal entries to the special Retained Earnings account at the end of the year. In any case, this is how my CPA set up my books and it's been working well enough for many years. Still, never a bad idea to get a second opinion from your CPA. Be sure to pay yourself a reasonable salary, you can't get out of payroll taxes and just distribute profits -- that's a big red flag that can trigger an audit. If you're simply distributing back the money you already put into the company, that should be fine.",
"title": ""
},
{
"docid": "454563",
"text": "If you are tax-resident in the US, then you must report income from sources within and without the United States. Your foreign income generally must be reported to the IRS. You will generally be eligible for a credit for foreign income taxes paid, via Form 1116. The question of the stock transfer is more complicated, but revolves around the beneficial owner. If the stocks are yours but held by your brother, it is possible that you are the beneficial owner and you will have to report any income. There is no tax for bringing the money into the US. As a US tax resident, you are already subject to income tax on the gain from the sale in India. However, if the investment is held by a separate entity in India, which is not a US domestic entity or tax resident, then there is a separate analysis. Paying a dividend to you of the sale proceeds (or part of the proceeds) would be taxable. Your sale of the entity containing the investments would be taxable. There are look-through provisions if the entity is insufficiently foreign (de facto US, such as a Subpart-F CFC). There are ways to structure that transaction that are not taxable, such as making it a bona fide loan (which is enforceable and you must pay back on reasonable terms). But if you are holding property directly, not through a foreign separate entity, then the sale triggers US tax; the transfer into the US is not meaningful for your taxes, except for reporting foreign accounts. Please review Publication 519 for general information on taxation of resident aliens.",
"title": ""
}
] |
PLAIN-1612
|
meta-analysis
|
[
{
"docid": "MED-4840",
"text": "OBJECTIVE: To evaluate the evidence for and against the effectiveness of homeopathy. DATA SOURCES: The Cochrane Database of Systematic Reviews (generally considered to be the most reliable source of evidence) was searched in January 2010. STUDY SELECTION: Cochrane reviews with the term \"homeopathy\" in the title, abstract or keywords were considered. Protocols of reviews were excluded. Six articles met the inclusion criteria. DATA EXTRACTION: Each of the six reviews was examined for specific subject matter; number of clinical trials reviewed; total number of patients involved; and authors' conclusions. The reviews covered the following conditions: cancer, attention-deficit hyperactivity disorder, asthma, dementia, influenza and induction of labour. DATA SYNTHESIS: The findings of the reviews were discussed narratively (the reviews' clinical and statistical heterogeneity precluded meta-analysis). CONCLUSIONS: The findings of currently available Cochrane reviews of studies of homeopathy do not show that homeopathic medicines have effects beyond placebo.",
"title": "Homeopathy: what does the \"best\" evidence tell us?"
}
] |
[
{
"docid": "MED-2429",
"text": "Emerging evidence suggests that statins' may decrease the risk of cancers. However, available evidence on breast cancer is conflicting. We, therefore, examined the association between statin use and risk of breast cancer by conducting a detailed meta-analysis of all observational studies published regarding this subject. PubMed database and bibliographies of retrieved articles were searched for epidemiological studies published up to January 2012, investigating the relationship between statin use and breast cancer. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Combined relative risk (RR) and 95 % confidence interval (CI) were calculated using a random-effects model (DerSimonian and Laird method). Subgroup analyses, sensitivity analysis, and cumulative meta-analysis were also performed. A total of 24 (13 cohort and 11 case-control) studies involving more than 2.4 million participants, including 76,759 breast cancer cases contributed to this analysis. We found no evidence of publication bias and evidence of heterogeneity among the studies. Statin use and long-term statin use did not significantly affect breast cancer risk (RR = 0.99, 95 % CI = 0.94, 1.04 and RR = 1.03, 95 % CI = 0.96, 1.11, respectively). When the analysis was stratified into subgroups, there was no evidence that study design substantially influenced the effect estimate. Sensitivity analysis confirmed the stability of our results. Cumulative meta-analysis showed a change in trend of reporting risk of breast cancer from positive to negative in statin users between 1993 and 2011. Our meta-analysis findings do not support the hypothesis that statins' have a protective effect against breast cancer. More randomized clinical trials and observational studies are needed to confirm this association with underlying biological mechanisms in the future.",
"title": "Statin use and risk of breast cancer: a meta-analysis of observational studies."
},
{
"docid": "MED-1400",
"text": "BACKGROUND: The Mediterranean diet has long been reported to be protective against the occurrence of several different health outcomes. OBJECTIVE: We aimed to update our previous meta-analysis of published cohort prospective studies that investigated the effects of adherence to the Mediterranean diet on health status. DESIGN: We conducted a comprehensive literature search through electronic databases up to June 2010. RESULTS: The updated review process showed 7 prospective studies published in the past 2 y that were not included in the previous meta-analysis (1 study for overall mortality, 3 studies for cardiovascular incidence or mortality, 1 study for cancer incidence or mortality, and 2 studies for neurodegenerative diseases). These recent studies included 2 health outcomes not previously investigated (ie, mild cognitive impairment and stroke). The meta-analysis for all studies with a random-effects model that was conducted after the inclusion of these recent studies showed that a 2-point increase in adherence to the Mediterranean diet was associated with a significant reduction of overall mortality [relative risk (RR) = 0.92; 95% CI: 0.90, 0.94], cardiovascular incidence or mortality (RR = 0.90; 95% CI: 0.87, 0.93), cancer incidence or mortality (RR = 0.94; 95% CI: 0.92, 0.96), and neurodegenerative diseases (RR = 0.87; 95% CI: 0.81, 0.94). The meta-regression analysis showed that sample size was the most significant contributor to the model because it significantly influenced the estimate of the association for overall mortality. CONCLUSION: This updated meta-analysis confirms, in a larger number of subjects and studies, the significant and consistent protection provided by adherence to the Mediterranean diet in relation to the occurrence of major chronic degenerative diseases.",
"title": "Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis."
},
{
"docid": "MED-5253",
"text": "Background Fractures are important causes of healthy damage and economic loss nowadays. The conclusions of observational studies on tea consumption and fracture risk are still inconsistent. The objective of this meta-analysis is to determine the effect of tea drinking on the risk of fractures. Methods A comprehensive literature search was conducted in PubMed, Embase and reference lists of the relevant articles. Observational studies that reported an estimate of the association between tea drinking and incidence of fractures were included. A meta-analysis was conducted by the STATA software. Results A total of 9 studies involving 147,950 individuals that examined the association between tea consumption and risk of fractures were included in this meta-analysis. The odds risks (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects model. The pooled OR of 9 observational studies for the tea consumption on risk of fracture was 0.89 (95% CI, 0.78-1.04). In the subgroup analyses, no significant association was detected in neither cohort studies (n = 3; OR, 0.97; 95% CI, 0.89-1.06) nor case–control studies (n = 6; OR, 0.91; 95% CI, 0.70-1.19), respectively. No significant association was detected in the dose–response meta-analysis. Conclusions Tea consumption might not be associated with the risk of fractures. The following large-sample and well-designed studies are required to confirm the existing conclusions. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5309904231178427.",
"title": "Tea consumption didn’t modify the risk of fracture: a dose–response meta-analysis of observational studies"
},
{
"docid": "MED-5371",
"text": "We conducted a meta-analysis of randomized, placebo-controlled trials of omega-3 fatty acid treatment of major depressive disorder in order to determine efficacy and to examine sources of heterogeneity between trials. PubMED (1965-May 2010) was searched for randomized, placebo-controlled trials of omega-3 fatty acids for major depressive disorder. Our primary outcome measure was standardized mean difference in a clinical measure of depression severity. In stratified meta-analysis we examined the effects of trial duration, trial methodological quality, baseline depression severity, diagnostic indication, dose of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in omega-3 preparations, and whether omega-3 fatty acid was given as monotherapy or augmentation. In 13 randomized, placebo-controlled trials examining the efficacy of omega-3 fatty acids involving 731 participants, meta-analysis demonstrated no significant benefit of omega-3 fatty acid treatment compared to placebo (SMD=0.11, 95% CI: -0.04, 0.26). Meta-analysis demonstrated significant heterogeneity and publication bias. Nearly all evidence of omega-3 benefit was removed after adjusting for publication bias using the trim-and-fill method (SMD=0.01, 95% CI: -0.13, 0.15). Secondary analyses suggested a trend towards increased efficacy of omega-3 fatty acids in trials of lower methodological quality, trials of shorter duration, trials, which utilized completers rather than intention-to-treat analysis, and trials in which study participants had greater baseline depression severity, Current published trials suggest a small, non-significant benefit of omega-3 fatty acids for major depression. Nearly all of the treatment efficacy observed in the published literature may be attributable to publication bias.",
"title": "Omega-3 Fatty Acids for the Treatment of Depression: Systematic Review and Meta-Analysis"
},
{
"docid": "MED-3433",
"text": "OBJECTIVES: Our goal was to evaluate the association between erectile dysfunction (ED) and risk of cardiovascular disease (CVD) and all-cause mortality by conducting a meta-analysis of prospective cohort studies. BACKGROUND: Observational studies suggest an association between ED and the incidence of CVD. However, whether ED is an independent risk factor of CVD remains controversial. METHODS: The PubMed database was searched through January 2011 to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Two authors independently extracted information on the designs of the studies, the characteristics of the study participants, exposure and outcome assessments, and control for potential confounding factors. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. RESULTS: Twelve prospective cohort studies involving 36,744 participants were included in the meta-analysis. The overall combined relative risks for men with ED compared with the reference group were 1.48 (95% confidence interval [CI]: 1.25 to 1.74) for CVD, 1.46 (95% CI: 1.31 to 1.63) for coronary heart disease, 1.35 (95% CI: 1.19 to 1.54) for stroke, and 1.19 (95% CI: 1.05 to 1.34) for all-cause mortality. Sensitivity analysis restricted to studies with control for conventional cardiovascular risk factors yielded similar results. No evidence of publication bias was observed. CONCLUSIONS: This meta-analysis of prospective cohort studies suggests that ED significantly increases the risk of CVD, coronary heart disease, stroke, and all-cause mortality, and the increase is probably independent of conventional cardiovascular risk factors. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.",
"title": "Erectile dysfunction and risk of cardiovascular disease: meta-analysis of prospective cohort studies."
},
{
"docid": "MED-2158",
"text": "Background Epidemiologic studies have reported inconsistent results regarding coffee consumption and the risk of liver cancer. We performed a meta-analysis of published case–control and cohort studies to investigate the association between coffee consumption and liver cancer. Methods We searched Medline, EMBASE, ISI Web of Science and the Cochrane library for studies published up to May 2012. We performed a meta-analysis of nine case–control studies and seven cohort studies. Results The summary odds ratio (OR) for high vs no/almost never drinkers was 0.50 (95% confidence interval (CI): 0.42–0.59), with no significant heterogeneity across studies (Q = 16.71; P = 0.337; I2 = 10.2%). The ORs were 0.50 (95% CI: 0.40–0.63) for case–control studies and 0.48 (95% CI: 0.38–0.62) for cohort studies. The OR was 0.38 (95% CI: 0.25–0.56) in males and 0.60 (95% CI: 0.33–1.10) in females. The OR was 0.45 (95% CI: 0.36–0.56) in Asian studies and 0.57 (95% CI: 0.44–0.75) in European studies. The OR was 0.39 (95% CI: 0.28–0.54) with no adjustment for a history of liver disease and 0.54 (95% CI: 0.46–0.66) after adjustment for a history of liver disease. Conclusions The results of this meta-analysis suggested an inverse association between coffee consumption and liver cancer. Because of the small number of studies, further prospective studies are needed.",
"title": "Consumption of coffee associated with reduced risk of liver cancer: a meta-analysis"
},
{
"docid": "MED-951",
"text": "BACKGROUND: Vitamin supplementation is used for many purposes with mainly alleged benefits. One of these is the use of various vitamins for the prevention of prostate cancer. METHODS: We conducted a systematic review and meta-analysis on this topic. Pubmed, Embase and the Cochrane Database were searched; as well, we hand searched the references in key articles. Randomized controlled trials (RCTs), cohort studies and case-control studies were included. The review assessed the effect of supplemental vitamins on the risk of prostate cancer and on disease severity and death in men with prostate cancer. RESULTS: Fourteen articles were included in the final assessment. Individually, a few of these studies showed a relationship between the ingestion of supplemental vitamins or minerals and the incidence or severity of prostate cancer, especially in smokers. However, neither the use of multivitamin supplementation nor the use of individual vitamin/mineral supplementation affected the overall occurrence of prostate cancer or the occurrence of advanced/metastatic prostate cancer or death from prostate cancer when the results of the studies were combined in a meta-analysis. We also conducted several sensitivity analyses by running meta-analysis using just the higher quality studies and just the RCTs. There were still no associations found. CONCLUSIONS: There is no convincing evidence that the use of supplemental multivitamins or any specific vitamin affects the occurrence or severity of prostate cancer. There was high heterogeneity among the studies so it is possible that unidentified subgroups may benefit or be harmed by the use of vitamins.",
"title": "The effect of supplemental vitamins and minerals on the development of prostate cancer: a systematic review and meta-analysis."
},
{
"docid": "MED-3758",
"text": "Homeopathy remains one of the most controversial subjects in therapeutics. This article is an attempt to clarify its effectiveness based on recent systematic reviews. Electronic databases were searched for systematic reviews/meta-analysis on the subject. Seventeen articles fulfilled the inclusion/exclusion criteria. Six of them related to re-analyses of one landmark meta-analysis. Collectively they implied that the overall positive result of this meta-analysis is not supported by a critical analysis of the data. Eleven independent systematic reviews were located. Collectively they failed to provide strong evidence in favour of homeopathy. In particular, there was no condition which responds convincingly better to homeopathic treatment than to placebo or other control interventions. Similarly, there was no homeopathic remedy that was demonstrated to yield clinical effects that are convincingly different from placebo. It is concluded that the best clinical evidence for homeopathy available to date does not warrant positive recommendations for its use in clinical practice.",
"title": "A systematic review of systematic reviews of homeopathy"
},
{
"docid": "MED-2893",
"text": "Lutein and zeaxanthin are thought to decrease the incidence of age-related macular degeneration (AMD); however, findings have been inconsistent. We conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. Relevant studies were identified by searching five databases up to April 2010. Reference lists of articles were retrieved, and experts were contacted. Literature search, data extraction and study quality assessment were performed independently by two reviewers and results were pooled quantitatively using meta-analysis methods. The potential sources of heterogeneity and publication bias were also estimated. The search yielded six longitudinal cohort studies. The pooled relative risk (RR) for early AMD, comparing the highest with the lowest category of lutein and zeaxanthin intake, was 0·96 (95 % CI 0·78, 1·17). Dietary intake of these carotenoids was significantly related with a reduction in risk of late AMD (RR 0·74; 95 % CI 0·57, 0·97); and a statistically significant inverse association was observed between lutein and zeaxanthin intake and neovascular AMD risk (RR 0·68; 95 % CI 0·51, 0·92). The results were essentially consistent among subgroups stratified by participant characteristics. The findings of the present meta-analysis indicate that dietary lutein and zeaxanthin is not significantly associated with a reduced risk of early AMD, whereas an increase in the intake of these carotenoids may be protective against late AMD. However, additional studies are needed to confirm these relationships.",
"title": "Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis."
},
{
"docid": "MED-3987",
"text": "Background: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D]. Objective: The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans. Design: The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials. Results: A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation. Conclusions: This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3 could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.",
"title": "Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis"
},
{
"docid": "MED-5036",
"text": "We evaluated long-term use of mobile phones and the risk for brain tumours in case-control studies published so far on this issue. We identified ten studies on glioma and meta-analysis yielded OR = 0.9, 95% CI = 0.8-1.1. Latency period of > or =10-years gave OR = 1.2, 95% CI = 0.8-1.9 based on six studies, for ipsilateral use (same side as tumour) OR = 2.0, 95% CI = 1.2-3.4 (four studies), but contralateral use did not increase the risk significantly, OR = 1.1, 95% CI = 0.6-2.0. Meta-analysis of nine studies on acoustic neuroma gave OR = 0.9, 95% CI = 0.7-1.1 increasing to OR = 1.3, 95% CI = 0.6-2.8 using > or =10-years latency period (four studies). Ipsilateral use gave OR = 2.4, 95% CI = 1.1-5.3 and contra-lateral OR = 1.2, 95% CI = 0.7-2.2 in the > or =10-years latency period group (three studies). Seven studies gave results for meningioma yielding overall OR = 0.8, 95% CI = 0.7-0.99. Using > or =10-years latency period OR = 1.3, 95% CI = 0.9-1.8 was calculated (four studies) increasing to OR = 1.7, 95% CI = 0.99-3.1 for ipsilateral use and OR = 1.0, 95% CI = 0.3-3.1 for contralateral use (two studies). We conclude that this meta-analysis gave a consistent pattern of an association between mobile phone use and ipsilateral glioma and acoustic neuroma using > or =10-years latency period.",
"title": "Meta-analysis of long-term mobile phone use and the association with brain tumours."
},
{
"docid": "MED-4855",
"text": "OBJECTIVE: Meta-analysis of randomized controlled trials (RCTs)--of a hip powder of Rosa canina (rosehip) preparation for symptomatic treatment of osteoarthritis (OA), in order to estimate the empirical efficacy as a pain reducing compound. METHOD: RCTs from systematic searches were included if they explicitly stated that OA patients were randomized to either rosehip or placebo. The primary outcome was reduction in pain calculated as effect size (ES), defined as the standardized mean difference (SMD). As secondary analysis the number of responders to therapy was analyzed as Odds Ratios (OR), and expressed as the Number Needed to Treat (NNT). Restricted Maximum Likelihood (REML) methods were applied for the meta-analyses using mixed effects models. RESULTS: The three studies (287 patients and a median trial-duration of 3 months)--all supported by the manufacturer (Hyben-Vital International)--showed a reduction in pain scores by rosehip powder (145 patients) compared to placebo (142 patients): ES of 0.37 [95% confidence interval (CI): 0.13-0.60], P=0.002. Test for homogeneity seemed to support that the efficacy was consistent across trials (I(2)=0%). Thus it seems reasonable to assume that the three studies were measuring the same overall effect. It seemed twice as likely that a patient allocated to rosehip powder would respond to therapy, compared to placebo (OR=2.19; P=0.0009); corresponding to a NNT of six (95% CI: 4-13) patients. CONCLUSIONS: Although based on a sparse amount of data, the results of the present meta-analysis indicate that rosehip powder does reduce pain; accordingly it may be of interest as a nutraceutical, although its efficacy and safety need evaluation and independent replication in a future large-scale/long-term trial.",
"title": "Does the hip powder of Rosa canina (rosehip) reduce pain in osteoarthritis patients?--a meta-analysis of randomized controlled trials."
},
{
"docid": "MED-5009",
"text": "OBJECTIVE: To evaluate the efficacy of preparations with avocado-soybean unsaponifiables (ASUs) in osteoarthritis (OA) patients using meta-analysis on randomized controlled trials (RCTs). METHOD: RCTs from systematic searches were included if they explicitly stated that hip and/or knee OA patients were randomized to either ASU or placebo. The co-primary outcome was reduction in pain and Lequesne index, leading to effect size (ES), calculated as the standardized mean difference. As secondary analysis, the number of responders to therapy was analyzed as odds ratios (ORs). Restricted maximum likelihood methods were applied for the meta-analyses, using mixed effects models. RESULTS: Four trials--all supported by the manufacturer--were included, with 664 OA patients with either hip (41.4%) or knee (58.6%) OA allocated to either 300 mg ASU (336) or placebo (328). Average trial duration was 6 months (range: 3-12 months). Though based on heterogeneous results, the combined pain reduction favored ASU (I(2) = 83.5%, ES = 0.39 [95% confidence intervals: 0.01-0.76], P=0.04). Applying the Lequesne index also favored ASU (I(2) = 61.0%, ES = 0.45 [0.21-0.70], P = 0.0003). Secondarily, the number of responders following ASU compared to placebo (OR = 2.19, P = 0.007) corresponded to a number needed to treat of six (4-21) patients. CONCLUSIONS: Based on the available evidence, patients may be recommended to give ASU a chance for e.g., 3 months. Meta-analysis data support better chances of success in patients with knee OA than in those with hip OA.",
"title": "Symptomatic efficacy of avocado-soybean unsaponifiables (ASU) in osteoarthritis (OA) patients: a meta-analysis of randomized controlled trials."
},
{
"docid": "MED-5255",
"text": "BACKGROUND: The association between habitual caffeine intake with incident atrial fibrillation (AF) was unknown. We conducted a meta-analysis to investigate the association between chronic exposure of caffeine and the risk of AF and to evaluate the potential dose-response relation. METHODS: We searched PubMed, EMBASE, and the Cochrane Library up to November 2013 and references of relevant retrieved articles. Prospective cohort studies were included with relative risk (RR) or hazard ratio and 95% confidence intervals (CIs) for AF according to coffee/caffeine intake. RESULTS: Six prospective cohort studies with 228,465 participants were included. In the primary meta-analysis, caffeine exposure was weakly associated with a reduced risk of AF (RR, 0.90; 95% CI, 0.81-1.01; P = 0.07; I(2) = 73%). In subgroup analyses, pooled results from studies with adjustment of potential confounders showed an 11% reduction for low doses (RR, 0.89; 95% CI, 0.80-0.99, P = 0.032; I(2) = 30.9%, P = 0.227) and 16% for high doses (RR, 0.84; 95% CI, 0.75-0.94, P = 0.002; I(2) = 24.1%, P = 0.267) of caffeine consumption in AF risk. An inverse relation was found between habitual caffeine intake and AF risk (P for overall trend = 0.015; P for nonlinearity = 0.27) in dose-response meta-analysis and the incidence of AF decreased by 6% (RR, 0.94; 95% CI, 0.90-0.99) for every 300 mg/d increment in habitual caffeine intake. CONCLUSIONS: It is unlikely that caffeine consumption causes or contributes to AF. Habitual caffeine consumption might reduce AF risk. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.",
"title": "Caffeine intake and atrial fibrillation incidence: dose response meta-analysis of prospective cohort studies."
},
{
"docid": "MED-1170",
"text": "OBJECTIVE: To examine the potential association between parental occupational exposure to pesticides and the occurrence of brain tumors in children and young adults. METHODS: Studies identified from a MEDLINE search through 15 January 2013 and from the reference lists of identified publications were submitted to a systematic review and meta-analysis. Relative risk estimates were extracted from 20 studies published between 1974 and 2010. Most of the retrieved studies involved farm/agricultural jobs. Summary ratio estimates (SR) were calculated according to fixed and random-effect meta-analysis models. Separate analyses were conducted after stratification for study design, exposure parameters, disease definition, geographic location and age at diagnosis. RESULTS: Statistically significant associations were observed for parents potentially exposed to pesticides in occupational settings and the occurrence of brain tumor in their offspring after combining all case-control studies (summary odds ratio [SOR]: 1.30; 95%: 1.11, 1.53) or all cohort studies (summary rate ratio [SRR]: 1.53; 95% CI: 1.20, 1.95). Significantly increased risks were seen for prenatal exposure windows, for either exposed parent, for exposure defined as to pesticides as well as by occupational/industry title, for astroglial brain tumors and after combining case-control studies from North America or cohort studies from Europe. CONCLUSIONS: This meta-analysis supports an association between parental occupational exposure to pesticides and brain tumors in children and young adults, and adds to the evidence leading to the recommendation of minimizing (parental) occupational exposure to pesticides. These results must, however, be interpreted with caution because the impact of work-related factors others than pesticide exposure is not known. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Parental occupational exposure to pesticides as risk factor for brain tumors in children and young adults: a systematic review and meta-analysis."
},
{
"docid": "MED-4228",
"text": "Insulin-like growth factors (IGF-I, IGF-II) and their binding proteins (IGFBP-1-6) play a key role in cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis. Several epidemiological studies show associations of IGFs with prostate cancer. We searched the published literature for all studies relating levels of IGFs or IGFBPs with prostate cancer. We performed random effects meta-analysis to calculate summary odds ratios. The number of studies (prostate cancer cases) included in each meta-analysis were 42 (7,481) IGF-I; 10 (923) IGF-II; 3 (485) IGFBP-1; 5 (577) IGFBP-2; 29 (6,541) IGFBP-3; and 11 (3,545) IGF-1:IGFBP-3 ratio. The pooled odds ratios (95% confidence intervals) per standard deviation increase in peptide, were: IGF-I, OR = 1.21 (1.07, 1.36); IGF-II, OR = 1.17 (0.93, 1.47); IGFBP-1, OR = 1.21 (0.62, 2.33); IGFBP-2, OR = 1.18 (0.90, 1.54); IGFBP-3, OR = 0.88 (0.79, 0.98); IGFI:IGFBP-3 ratio, OR = 1.10 (0.97, 1.24). For all exposures, there was substantial heterogeneity (all I2 > 75%), partly explained by study design: the magnitude of associations was smaller in prospective versus retrospective studies, and for IGFBP-3 the inverse association with prostate cancer risk was seen in retrospective but not prospective studies. There was weak evidence that associations of IGF-I and IGFBP-3 with prostate cancer were stronger for advanced disease. Our meta-analysis confirms that raised circulating lGF-I is positively associated with prostate cancer risk. Associations between IGFBP-3 and prostate cancer were inconsistent, and there was little evidence for a role of IGF-II, IGFBP-1 or IGFBP-2 in prostate cancer risk.",
"title": "Circulating insulin-like growth factor (IGF) peptides and prostate cancer risk: a systematic review and meta-analysis"
},
{
"docid": "MED-1656",
"text": "Background Low back pain (LBP) is common in children and adolescents, and it is becoming a public health concern. In recent years there has been a considerable increase in research studies that examine the prevalence of LBP in this population, but studies exhibit great variability in the prevalence rates reported. The purpose of this research was to examine, by means of a meta-analytic investigation, the prevalence rates of LBP in children and adolescents. Methods Studies were located from computerized databases (ISI Web of Knowledge, MedLine, PEDro, IME, LILACS, and CINAHL) and other sources. The search period extended to April 2011. To be included in the meta-analysis, studies had to report a prevalence rate (whether point, period or lifetime prevalence) of LBP in children and/or adolescents (≤ 18 years old). Two independent researchers coded the moderator variables of the studies, and extracted the prevalence rates. Separate meta-analyses were carried out for the different types of prevalence in order to avoid dependence problems. In each meta-analysis, a random-effects model was assumed to carry out the statistical analyses. Results A total of 59 articles fulfilled the selection criteria. The mean point prevalence obtained from 10 studies was 0.120 (95% CI: 0.09 and 0.159). The mean period prevalence at 12 months obtained from 13 studies was 0.336 (95% CI: 0.269 and 0.410), whereas the mean period prevalence at one week obtained from six studies was 0.177 (95% CI: 0.124 and 0.247). The mean lifetime prevalence obtained from 30 studies was 0.399 (95% CI: 0.342 and 0.459). Lifetime prevalence exhibited a positive, statistically significant relationship with the mean age of the participants in the samples and with the publication year of the studies. Conclusions The most recent studies showed higher prevalence rates than the oldest ones, and studies with a better methodology exhibited higher lifetime prevalence rates than studies that were methodologically poor. Future studies should report more information regarding the definition of LBP and there is a need to improve the methodological quality of studies.",
"title": "Prevalence of low back pain in children and adolescents: a meta-analysis"
},
{
"docid": "MED-3811",
"text": "Cinnamon, the dry bark and twig of Cinnamomum spp., is a rich botanical source of polyphenolics that has been used for centuries in Chinese medicine and has been shown to affect blood glucose and insulin signaling. Cinnamon's effects on blood glucose have been the subject of many clinical and animal studies; however, the issue of cinnamon intake's effect on fasting blood glucose (FBG) in people with type 2 diabetes and/or prediabetes still remains unclear. A meta-analysis of clinical studies of the effect of cinnamon intake on people with type 2 diabetes and/or prediabetes that included three new clinical trials along with five trials used in previous meta-analyses was done to assess cinnamon's effectiveness in lowering FBG. The eight clinical studies were identified using a literature search (Pub Med and Biosis through May 2010) of randomized, placebo-controlled trials reporting data on cinnamon and/or cinnamon extract and FBG. Comprehensive Meta-Analysis (Biostat Inc., Englewood, NJ, USA) was performed on the identified data for both cinnamon and cinnamon extract intake using a random-effects model that determined the standardized mean difference ([i.e., Change 1(control) - Change 2(cinnamon)] divided by the pooled SD of the post scores). Cinnamon intake, either as whole cinnamon or as cinnamon extract, results in a statistically significant lowering in FBG (-0.49±0.2 mmol/L; n=8, P=.025) and intake of cinnamon extract only also lowered FBG (-0.48 mmol/L±0.17; n=5, P=.008). Thus cinnamon extract and/or cinnamon improves FBG in people with type 2 diabetes or prediabetes.",
"title": "Cinnamon intake lowers fasting blood glucose: meta-analysis."
},
{
"docid": "MED-4416",
"text": "Cinnamon, the dry bark and twig of Cinnamomum spp., is a rich botanical source of polyphenolics that has been used for centuries in Chinese medicine and has been shown to affect blood glucose and insulin signaling. Cinnamon's effects on blood glucose have been the subject of many clinical and animal studies; however, the issue of cinnamon intake's effect on fasting blood glucose (FBG) in people with type 2 diabetes and/or prediabetes still remains unclear. A meta-analysis of clinical studies of the effect of cinnamon intake on people with type 2 diabetes and/or prediabetes that included three new clinical trials along with five trials used in previous meta-analyses was done to assess cinnamon's effectiveness in lowering FBG. The eight clinical studies were identified using a literature search (Pub Med and Biosis through May 2010) of randomized, placebo-controlled trials reporting data on cinnamon and/or cinnamon extract and FBG. Comprehensive Meta-Analysis (Biostat Inc., Englewood, NJ, USA) was performed on the identified data for both cinnamon and cinnamon extract intake using a random-effects model that determined the standardized mean difference ([i.e., Change 1(control) - Change 2(cinnamon)] divided by the pooled SD of the post scores). Cinnamon intake, either as whole cinnamon or as cinnamon extract, results in a statistically significant lowering in FBG (-0.49±0.2 mmol/L; n=8, P=.025) and intake of cinnamon extract only also lowered FBG (-0.48 mmol/L±0.17; n=5, P=.008). Thus cinnamon extract and/or cinnamon improves FBG in people with type 2 diabetes or prediabetes.",
"title": "Cinnamon intake lowers fasting blood glucose: meta-analysis."
},
{
"docid": "MED-2772",
"text": "Prostate cancer has become the most common cancer among men in the United States. Although milk consumption is considered to be a risk factor in some epidemiological studies, the results are inconsistent. A meta-analysis method was conducted to estimate the combined odds ratio (OR) between milk consumption and prostate cancer from case-control studies published between 1984 and 2003 using commercial software (comprehensive meta-analysis). The combined OR was 1.68 (95% confidence interval = 1.34-2.12) in the 11 published case-control studies. The combined OR varied little by study stratification. Additionally, we evaluated the possible risk factors in milk for prostate cancer. In conclusion, we found a positive association between milk consumption and prostate cancer. The underlying mechanisms, including fat, calcium, hormones, and other factors, should be investigated further. Copyright 2004 Lawrence Erlbaum Associates, Inc.",
"title": "Milk consumption is a risk factor for prostate cancer: meta-analysis of case-control studies."
},
{
"docid": "MED-5243",
"text": "PURPOSE: The data on the association between coffee consumption and the risk of fractures are inconclusive. We performed a comprehensive literature review and meta-analysis to better quantify this association. METHODS: We identified all potentially relevant articles by searching MEDLINE, EMBASE, Cochrane Library, Web of Science, SCOPUS, and CINAHL (until February 2013). The keywords \"coffee,\" \"caffeine,\" \"drink,\" and \"beverage\" were used as the exposure factors, and the keyword \"fracture\" was used as the outcome factor. We determined the overall relative risk (RR) and confidence interval (CI) for the highest and lowest levels of coffee consumption. A dose-response analysis was performed to assess the risk of fractures based on the level of coffee consumption. RESULTS: We included 253,514 participants with 12,939 fracture cases from 9 cohort and 6 case-control studies. The estimated RR of fractures at the highest level of coffee consumption was 1.14 (95% CI: 1.05-1.24; I(2)=0.0%) in women and 0.76 (95% CI: 0.62-0.94; I(2)=7.3%) in men. In the dose-response analysis, the pooled RRs of fractures in women who consumed 2 and 8 cups of coffee per day were 1.02 (95% CI: 1.01-1.04) and 1.54 (95% CI: 1.19-1.99), respectively. CONCLUSIONS: Our meta-analysis suggests that daily consumption of coffee is associated with an increased risk of fractures in women and a contrasting decreased risk in men. However, future well-designed studies should be performed to confirm these findings. Copyright © 2014 Elsevier Inc. All rights reserved.",
"title": "Coffee consumption and risk of fractures: a systematic review and dose-response meta-analysis."
},
{
"docid": "MED-1192",
"text": "Objectives To determine the quantitative efficacy of different classes of blood pressure lowering drugs in preventing coronary heart disease (CHD) and stroke, and who should receive treatment. Design Meta-analysis. Data source Medline (1966-2007). Study selection Randomised trials of blood pressure lowering drugs recording CHD events and strokes. 108 trials studied differences in blood pressure between study drug and placebo (or control group not receiving the study drug) (“blood pressure difference trials”), and 46 trials compared drugs (“drug comparison trials”). Seven trials with three randomised groups fell into both categories. The results were interpreted in the context of those expected from the largest published meta-analysis of cohort studies, totalling 958 000 people. Participants 464 000 people defined into three mutually exclusive categories: participants with no history of vascular disease, a history of CHD, or a history of stroke. Results In the blood pressure difference trials β blockers had a special effect over and above that due to blood pressure reduction in preventing recurrent CHD events in people with a history of CHD: risk reduction 29% (95% confidence interval 22% to 34%) compared with 15% (11% to 19%) in trials of other drugs. The extra effect was limited to a few years after myocardial infarction, with a risk reduction of 31% compared with 13% in people with CHD with no recent infarct (P=0.04). In the other blood pressure difference trials (excluding CHD events in trials of β blockers in people with CHD), there was a 22% reduction in CHD events (17% to 27%) and a 41% (33% to 48%) reduction in stroke for a blood pressure reduction of 10 mm Hg systolic or 5 mm Hg diastolic, similar to the reductions of 25% (CHD) and 36% (stroke) expected for the same difference in blood pressure from the cohort study meta-analysis, indicating that the benefit is explained by blood pressure reduction itself. The five main classes of blood pressure lowering drugs (thiazides, β blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers) were similarly effective (within a few percentage points) in preventing CHD events and strokes, with the exception that calcium channel blockers had a greater preventive effect on stroke (relative risk 0.92, 95% confidence interval 0.85 to 0.98). The percentage reductions in CHD events and stroke were similar in people with and without cardiovascular disease and regardless of blood pressure before treatment (down to 110 mm Hg systolic and 70 mm Hg diastolic). Combining our results with those from two other studies (the meta-analyses of blood pressure cohort studies and of trials determining the blood pressure lowering effects of drugs according to dose) showed that in people aged 60-69 with a diastolic blood pressure before treatment of 90 mm Hg, three drugs at half standard dose in combination reduced the risk of CHD by an estimated 46% and of stroke by 62%; one drug at standard dose had about half this effect. The present meta-analysis also showed that drugs other than calcium channel blockers (with the exception of non-cardioselective β blockers) reduced the incidence of heart failure by 24% (19% to 28%) and calcium channel blockers by 19% (6% to 31%). Conclusions With the exception of the extra protective effect of β blockers given shortly after a myocardial infarction and the minor additional effect of calcium channel blockers in preventing stroke, all the classes of blood pressure lowering drugs have a similar effect in reducing CHD events and stroke for a given reduction in blood pressure so excluding material pleiotropic effects. The proportional reduction in cardiovascular disease events was the same or similar regardless of pretreatment blood pressure and the presence or absence of existing cardiovascular disease. Guidelines on the use of blood pressure lowering drugs can be simplified so that drugs are offered to people with all levels of blood pressure. Our results indicate the importance of lowering blood pressure in everyone over a certain age, rather than measuring it in everyone and treating it in some.",
"title": "Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies"
},
{
"docid": "MED-2255",
"text": "Background Diet is a major source of cadmium intake among the non-smoking general population. Recent studies have determined that cadmium exposure may produce adverse health effects at lower exposure levels than previously predicted. We conducted a meta-analysis to combine and analyze the results of previous studies that have investigated the association of dietary cadmium intake and cancer risk. Methods We searched PubMed, EMBASE, and MEDLINE database for case-control and cohort studies that assessed the association of dietary cadmium intake and cancer risk. We performed a meta-analysis using eight eligible studies to summarize the data and summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random effects model. Results Overall, dietary cadmium intake showed no statistically significant association with cancer risk (RR = 1.10; 95% CI: 0.99–1.22, for highest vs. lowest dietary cadmium group). However, there was strong evidence of heterogeneity, and subgroup analyses were conducted using the study design, geographical location, and cancer type. In subgroup analyses, the positive associations between dietary cadmium intake and cancer risk were observed among studies with Western populations (RR = 1.15; 95% CI: 1.08–1.23) and studies investigating some hormone-related cancers (prostate, breast, and endometrial cancers). Conclusion Our analysis found a positive association between dietary cadmium intake and cancer risk among studies conducted in Western countries, particularly with hormone-related cancers. Additional experimental and epidemiological studies are required to verify our findings.",
"title": "Dietary Cadmium Intake and the Risk of Cancer: A Meta-Analysis"
},
{
"docid": "MED-3858",
"text": "BACKGROUND: Observational and preclinical studies suggest that dietary fiber intake may reduce the risk of breast cancer, but the results are inconclusive. OBJECTIVE: We aimed to examine the association between dietary fiber intake and risk of breast cancer by conducting a meta-analysis of prospective cohort studies. DESIGN: Relevant studies were identified by a PubMed database search through January 2011. Reference lists from retrieved articles were also reviewed. We included prospective cohort studies that reported RRs with 95% CIs for the association between dietary fiber intake and breast cancer risk. Both fixed- and random-effects models were used to calculate the summary risk estimates. RESULTS: We identified 10 prospective cohort studies of dietary fiber intake and risk of breast cancer involving 16,848 cases and 712,195 participants. The combined RR of breast cancer for the highest compared with the lowest dietary fiber intake was 0.89 (95% CI: 0.83, 0.96), and little evidence of heterogeneity was observed. The association between dietary fiber intake and risk of breast cancer did not significantly differ by geographic region, length of follow-up, or menopausal status of the participants. Omission of any single study had little effect on the combined risk estimate. Dose-response analysis showed that every 10-g/d increment in dietary fiber intake was associated with a significant 7% reduction in breast cancer risk. Little evidence of publication bias was found. CONCLUSION: This meta-analysis provides evidence of a significant inverse dose-response association between dietary fiber intake and breast cancer risk.",
"title": "Dietary fiber intake and risk of breast cancer: a meta-analysis of prospective cohort studies."
},
{
"docid": "MED-1563",
"text": "OBJECTIVE: Lifestyle factors are related to mortality. Although much is known about the impact of single factors, the current evidence about the combined effects of lifestyle behaviors on mortality has not yet been systematically compiled. METHOD: We searched Medline, Embase, Global Health, and Somed up to February 2012. Prospective studies were selected if they reported the combined effects of at least three of five lifestyle factors (obesity, alcohol consumption, smoking, diet, and physical activity). The mean effect sizes that certain numbers of combined lifestyle factors have on mortality were compared to the group with the least number of healthy lifestyle factors by meta-analysis. Sensitivity analyses were conducted to explore the robustness of the results. RESULTS: 21 studies (18 cohorts) met the inclusion criteria of which 15 were included in the meta-analysis that comprised 531,804 people with a mean follow-up of 13.24 years. The relative risks decreased proportionate to a higher number of healthy lifestyle factors for all cause mortality. A combination of at least four healthy lifestyle factors is associated with a reduction of the all cause mortality risk by 66% (95% confidence interval 58%-73%). CONCLUSION: Adherence to a healthy lifestyle is associated with a lower risk of mortality. Copyright © 2012. Published by Elsevier Inc.",
"title": "The combined effects of healthy lifestyle behaviors on all cause mortality: a systematic review and meta-analysis."
},
{
"docid": "MED-1796",
"text": "Background Several studies have shown that Adenovirus 36 (Ad36) influences the risk of obesity in humans. Clarifying the relationship between Ad36 infection and obesity could lead to more effective approaches for the management of obesity. The objective of this study was to conduct a meta-analysis to confirm the influence of Ad36 infection on obesity and metabolic markers. Methodology/Principal Findings We searched MEDLINE and the Cochrane Library for pertinent articles (including their references) published between 1951 and April 22, 2012. Only English language reports of original observational studies were included in this meta-analysis. Data extraction was performed independently by two reviewers. Weighted mean differences (WMDs) and pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated using the random effects model. Of 237 potentially relevant studies, 10 cross-sectional studies (n = 2,870) conformed to the selection criteria. Pooled analysis showed that the WMD for BMI of Ad36 infection compared with non-infection was 3.19 (95% CI 1.44–4.93; P<0.001). Sensitivity analysis restricted to studies of adults yielded a similar result of 3.18 (95% CI 0.78–5.57; P = 0.009). The increased risk of obesity associated with Ad36 infection was also significant (OR: 1.9; 95% CI: 1.01–3.56; P = 0.047). No significant differences were found in relation to total cholesterol (P = 0.83), triglycerides (P = 0.64), HDL (P = 0.69), blood glucose (P = 0.08), waist circumstance (P = 0.09), and systolic blood pressure (P = 0.25). Conclusion/Significance Ad36 infection was associated with the risk of obesity and weight gain, but was not associated with abnormal metabolic markers including waist circumstance. It suggests that Ad36 infection is more associated with accumulation of subcutaneous fat than that of visceral fat. The relationship between Ad36 and obesity should be assessed by further studies, including well-designed prospective studies, to gain a better understanding of whether Ad36 plays a role in the etiology of human obesity.",
"title": "Association of Adenovirus 36 Infection with Obesity and Metabolic Markers in Humans: A Meta-Analysis of Observational Studies"
},
{
"docid": "MED-1348",
"text": "Background Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression scores. The purpose of this analysis is to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials. Methods and Findings We obtained data on all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available. We then used meta-analytic techniques to assess linear and quadratic effects of initial severity on improvement scores for drug and placebo groups and on drug–placebo difference scores. Drug–placebo differences increased as a function of initial severity, rising from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category. Meta-regression analyses indicated that the relation of baseline severity and improvement was curvilinear in drug groups and showed a strong, negative linear component in placebo groups. Conclusions Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication. Editors' Summary Background. Everyone feels miserable occasionally. But for some people—those with depression—these sad feelings last for months or years and interfere with daily life. Depression is a serious medical illness caused by imbalances in the brain chemicals that regulate mood. It affects one in six people at some time during their life, making them feel hopeless, worthless, unmotivated, even suicidal. Doctors measure the severity of depression using the “Hamilton Rating Scale of Depression” (HRSD), a 17–21 item questionnaire. The answers to each question are given a score and a total score for the questionnaire of more than 18 indicates severe depression. Mild depression is often treated with psychotherapy or talk therapy (for example, cognitive–behavioral therapy helps people to change negative ways of thinking and behaving). For more severe depression, current treatment is usually a combination of psychotherapy and an antidepressant drug, which is hypothesized to normalize the brain chemicals that affect mood. Antidepressants include “tricyclics,” “monoamine oxidases,” and “selective serotonin reuptake inhibitors” (SSRIs). SSRIs are the newest antidepressants and include fluoxetine, venlafaxine, nefazodone, and paroxetine. Why Was This Study Done? Although the US Food and Drug Administration (FDA), the UK National Institute for Health and Clinical Excellence (NICE), and other licensing authorities have approved SSRIs for the treatment of depression, some doubts remain about their clinical efficacy. Before an antidepressant is approved for use in patients, it must undergo clinical trials that compare its ability to improve the HRSD scores of patients with that of a placebo, a dummy tablet that contains no drug. Each individual trial provides some information about the new drug's effectiveness but additional information can be gained by combining the results of all the trials in a “meta-analysis,” a statistical method for combining the results of many studies. A previously published meta-analysis of the published and unpublished trials on SSRIs submitted to the FDA during licensing has indicated that these drugs have only a marginal clinical benefit. On average, the SSRIs improved the HRSD score of patients by 1.8 points more than the placebo, whereas NICE has defined a significant clinical benefit for antidepressants as a drug–placebo difference in the improvement of the HRSD score of 3 points. However, average improvement scores may obscure beneficial effects between different groups of patient, so in the meta-analysis in this paper, the researchers investigated whether the baseline severity of depression affects antidepressant efficacy. What Did the Researchers Do and Find? The researchers obtained data on all the clinical trials submitted to the FDA for the licensing of fluoxetine, venlafaxine, nefazodone, and paroxetine. They then used meta-analytic techniques to investigate whether the initial severity of depression affected the HRSD improvement scores for the drug and placebo groups in these trials. They confirmed first that the overall effect of these new generation of antidepressants was below the recommended criteria for clinical significance. Then they showed that there was virtually no difference in the improvement scores for drug and placebo in patients with moderate depression and only a small and clinically insignificant difference among patients with very severe depression. The difference in improvement between the antidepressant and placebo reached clinical significance, however, in patients with initial HRSD scores of more than 28—that is, in the most severely depressed patients. Additional analyses indicated that the apparent clinical effectiveness of the antidepressants among these most severely depressed patients reflected a decreased responsiveness to placebo rather than an increased responsiveness to antidepressants. What Do These Findings Mean? These findings suggest that, compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression, but show significant effects only in the most severely depressed patients. The findings also show that the effect for these patients seems to be due to decreased responsiveness to placebo, rather than increased responsiveness to medication. Given these results, the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective. In addition, the finding that extremely depressed patients are less responsive to placebo than less severely depressed patients but have similar responses to antidepressants is a potentially important insight into how patients with depression respond to antidepressants and placebos that should be investigated further. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050045.",
"title": "Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration"
},
{
"docid": "MED-2594",
"text": "BACKGROUND: Epidemiologic studies have shown an inverse association between the frequency of nut consumption and body mass index (BMI) and risk of obesity. However, clinical trials that evaluated nut consumption on adiposity have been scarce and inconclusive. OBJECTIVE: We performed a systematic review and meta-analysis of published, randomized nut-feeding trials to estimate the effect of nut consumption on adiposity measures. DESIGN: MEDLINE and the Cochrane Central Register of Controlled Trials databases were searched for relevant clinical trials of nut intake that provided outcomes of body weight, BMI (in kg/m(2)), or waist-circumference measures and were published before December 2012. There were no language restrictions. Two investigators independently selected and reviewed eligible studies. The weighted mean difference (WMD) between nut or control diets was estimated by using a random-effects meta-analysis with 95% CIs. RESULTS: Thirty-three clinical trials met our inclusion criteria. Pooled results indicated a nonsignificant effect on body weight (WMD: -0.47 kg; 95% CI: -1.17, 0.22 kg; I(2) = 7%), BMI (WMD: -0.40 kg/m(2); 95% CI: -0.97, 0.17 kg/m(2); I(2) = 49%), or waist circumference (WMD: -1.25 cm; 95% CI: -2.82, 0.31 cm; I(2) = 28%) of diets including nuts compared with control diets. These findings were remarkably robust in the sensitivity analysis. No publication bias was shown. CONCLUSION: Compared with control diets, diets enriched with nuts did not increase body weight, body mass index, or waist circumference in controlled clinical trials.",
"title": "Nut intake and adiposity: meta-analysis of clinical trials."
},
{
"docid": "MED-2757",
"text": "BACKGROUND: Multivitamins are the most commonly used supplement in the developed world. Recent epidemiologic findings suggest that multivitamin use increases the risk of mortality. OBJECTIVE: We aimed to determine whether multivitamin-multimineral treatment, used for primary or secondary prevention, increases the risk of mortality in independently living adults. DESIGN: We performed a meta-analysis of randomized controlled trials. Multiple electronic databases were systematically searched from March to October 2012. Randomized controlled primary or secondary prevention trials were considered for inclusion. Eligible trials investigated daily multivitamin-multimineral supplementation for ≥1 y. Cohorts described as institutionalized or as having terminal illness (tertiary prevention) were excluded. The number of deaths and the sample size of each study arm were extracted independently by 2 researchers. Twenty-one articles were included in the analysis, which generated a total pooled sample of 91,074 people and 8794 deaths. These trials were pooled in a meta-analysis, and the outcomes were expressed as RRs and 95% CIs. RESULTS: The average age of the pooled sample was 62 y, and the average duration of supplementation was 43 mo. Across all studies, no effect of multivitamin-multimineral treatment on all-cause mortality (RR: 0.98; 95% CI: 0.94, 1.02) was observed. There was a trend for a reduced risk of all-cause mortality across primary prevention trials (RR: 0.94; 95% CI: 0.89, 1.00). Multivitamin-multimineral treatment had no effect on mortality due to vascular causes (RR: 1.01; 95% CI: 0.93, 1.09) or cancer (RR: 0.96; 95% CI: 0.88, 1.04). No statistical evidence of heterogeneity or publication bias was observed. CONCLUSION: Multivitamin-multimineral treatment has no effect on mortality risk.",
"title": "Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials."
},
{
"docid": "MED-1556",
"text": "Background: A reduction in dietary saturated fat has generally been thought to improve cardiovascular health. Objective: The objective of this meta-analysis was to summarize the evidence related to the association of dietary saturated fat with risk of coronary heart disease (CHD), stroke, and cardiovascular disease (CVD; CHD inclusive of stroke) in prospective epidemiologic studies. Design: Twenty-one studies identified by searching MEDLINE and EMBASE databases and secondary referencing qualified for inclusion in this study. A random-effects model was used to derive composite relative risk estimates for CHD, stroke, and CVD. Results: During 5–23 y of follow-up of 347,747 subjects, 11,006 developed CHD or stroke. Intake of saturated fat was not associated with an increased risk of CHD, stroke, or CVD. The pooled relative risk estimates that compared extreme quantiles of saturated fat intake were 1.07 (95% CI: 0.96, 1.19; P = 0.22) for CHD, 0.81 (95% CI: 0.62, 1.05; P = 0.11) for stroke, and 1.00 (95% CI: 0.89, 1.11; P = 0.95) for CVD. Consideration of age, sex, and study quality did not change the results. Conclusions: A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat.",
"title": "Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease"
}
] |
1026
|
Reduced phosphorylation of PP2A increases HDAC4 dephosphorylation by enhancing PP2A-HDAC4 interaction.
|
[
{
"docid": "3113630",
"text": "Ataxia telangiectasia is a neurodegenerative disease caused by mutation of the Atm gene. Here we report that ataxia telangiectasia mutated (ATM) deficiency causes nuclear accumulation of histone deacetylase 4 (HDAC4) in neurons and promotes neurodegeneration. Nuclear HDAC4 binds to chromatin, as well as to myocyte enhancer factor 2A (MEF2A) and cAMP-responsive element binding protein (CREB), leading to histone deacetylation and altered neuronal gene expression. Blocking either HDAC4 activity or its nuclear accumulation blunts these neurodegenerative changes and rescues several behavioral abnormalities of ATM-deficient mice. Full rescue of the neurodegeneration, however, also requires the presence of HDAC4 in the cytoplasm, suggesting that the ataxia telangiectasia phenotype results both from a loss of cytoplasmic HDAC4 as well as its nuclear accumulation. To remain cytoplasmic, HDAC4 must be phosphorylated. The activity of the HDAC4 phosphatase, protein phosphatase 2A (PP2A), is downregulated by ATM-mediated phosphorylation. In ATM deficiency, enhanced PP2A activity leads to HDAC4 dephosphorylation and the nuclear accumulation of HDAC4. Our results define a crucial role of the cellular localization of HDAC4 in the events leading to ataxia telangiectasia neurodegeneration.",
"title": "Nuclear accumulation of HDAC4 in ATM deficiency promotes neurodegeneration in ataxia-telangiectasia"
}
] |
[
{
"docid": "22185730",
"text": "Abnormal hyperphosphorylation of tau appears to be crucial in neurofibrillary degeneration in Alzheimer's disease (AD). Previous studies suggest that a down-regulation of protein phosphatase 2A (PP2A), the major tau phosphatase in human brain, contributes to tau hyperphosphorylation in AD. However, the effects of PP2A down-regulation on site-specific tau hyperphosphorylation is not well understood. In the present study, we showed that PP2A dephosphorylated tau at several phosphorylation sites with different efficiencies. Among the sites studied, Thr205, Thr212, Ser214, and Ser262 were the most favorable sites, and Ser199 and Ser404 were the least favorable sites for PP2A in vitro. Inhibition of PP2A with okadaic acid in metabolically active rat brain slices caused inhibition of glycogen synthase kinase-3beta (GSK-3beta) via an increase in its phosphorylation at Ser9. GSK-3beta phosphorylated tau at many sites, with Ser199, Thr205, and Ser396 being the most favorable sites in cells. The overall alterations in tau phosphorylation induced by PP2A inhibition were the result of the combined effects of both reduced tau dephosphorylation due to PP2A inhibition directly and reduced phosphorylation by GSK-3beta due to its inhibition. Because the impacts of tau phosphorylation on its biological activity and on neurofibrillary degeneration are site-specific, this study provides a new insight into the role of PP2A down-regulation in neurofibrillary degeneration in AD.",
"title": "PP2A regulates tau phosphorylation directly and also indirectly via activating GSK-3beta."
},
{
"docid": "29806339",
"text": "Targeting mitotic exit has been recently proposed as a relevant therapeutic approach against cancer. By using genetically engineered mice, we show that the APC/C cofactor Cdc20 is essential for anaphase onset in vivo in embryonic or adult cells, including progenitor/stem cells. Ablation of Cdc20 results in efficient regression of aggressive tumors, whereas current mitotic drugs display limited effects. Yet, Cdc20 null cells can exit from mitosis upon inactivation of Cdk1 and the kinase Mastl (Greatwall). This mitotic exit depends on the activity of PP2A phosphatase complexes containing B55α or B55δ regulatory subunits. These data illustrate the relevance of critical players of mitotic exit in mammals and their implications in the balance between cell death and mitotic exit in tumor cells.",
"title": "Targeting mitotic exit leads to tumor regression in vivo: Modulation by Cdk1, Mastl, and the PP2A/B55α,δ phosphatase."
},
{
"docid": "665817",
"text": "AIMS Frontotemporal lobar degeneration (FTLD) is clinically and pathologically heterogeneous. Although associated with variations in MAPT, GRN and C9ORF72, the pathogenesis of these, and of other nongenetic, forms of FTLD, remains unknown. Epigenetic factors such as histone regulation by histone deacetylases (HDAC) may play a role in the dysregulation of transcriptional activity, thought to underpin the neurodegenerative process. METHODS The distribution and intensity of HDACs 4, 5 and 6 was assessed semi-quantitatively in immunostained sections of temporal cortex with hippocampus, and cerebellum, from 33 pathologically confirmed cases of FTLD and 27 controls. RESULTS We found a significantly greater intensity of cytoplasmic immunostaining for HDAC4 and HDAC6 in granule cells of the dentate gyrus in cases of FTLD overall compared with controls, and specifically in cases of FTLD tau-Picks compared with FTLD tau-MAPT and controls. No differences were noted between FTLD-TDP subtypes, or between the different genetic and nongenetic forms of FTLD. No changes were seen in HDAC5 in any FTLD or control cases. CONCLUSIONS Dysregulation of HDAC4 and/or HDAC6 could play a role in the pathogenesis of FTLD-tau associated with Pick bodies, although their lack of immunostaining implies that such changes do not contribute directly to the formation of Pick bodies.",
"title": "Histone deacetylases (HDACs) in frontotemporal lobar degeneration."
},
{
"docid": "16605494",
"text": "BACKGROUND Whereas many causes and mechanisms of neurodegenerative diseases have been identified, very few therapeutic strategies have emerged in parallel. One possible explanation is that successful treatment strategy may require simultaneous targeting of more than one molecule of pathway. A new therapeutic approach to have emerged recently is the engagement of microRNAs (miRNAs), which affords the opportunity to target multiple cellular pathways simultaneously using a single sequence. METHODOLOGY/PRINCIPAL FINDINGS We identified miR-22 as a potentially neuroprotective miRNA based on its predicted regulation of several targets implicated in Huntington's disease (histone deacetylase 4 (HDAC4), REST corepresor 1 (Rcor1) and regulator of G-protein signaling 2 (Rgs2)) and its diminished expression in Huntington's and Alzheimer's disease brains. We then tested the hypothesis that increasing cellular levels of miRNA-22 would achieve neuroprotection in in vitro models of neurodegeneration. As predicted, overexpression of miR-22 inhibited neurodegeneration in primary striatal and cortical cultures exposed to a mutated human huntingtin fragment (Htt171-82Q). Overexpression of miR-22 also decreased neurodegeneration in primary neuronal cultures exposed to 3-nitropropionic acid (3-NP), a mitochondrial complex II/III inhibitor. In addition, miR-22 improved neuronal viability in an in vitro model of brain aging. The mechanisms underlying the effects of miR-22 included a reduction in caspase activation, consistent with miR-22's targeting the pro-apoptotic activities of mitogen-activated protein kinase 14/p38 (MAPK14/p38) and tumor protein p53-inducible nuclear protein 1 (Tp53inp1). Moreover, HD-specific effects comprised not only targeting HDAC4, Rcor1 and Rgs2 mRNAs, but also decreasing focal accumulation of mutant Htt-positive foci, which occurred via an unknown mechanism. CONCLUSIONS These data show that miR-22 has multipartite anti-neurodegenerative activities including the inhibition of apoptosis and the targeting of mRNAs implicated in the etiology of HD. These results motivate additional studies to evaluate the feasibility and therapeutic efficacy of manipulating miR-22 in vivo.",
"title": "MicroRNA-22 (miR-22) Overexpression Is Neuroprotective via General Anti-Apoptotic Effects and May also Target Specific Huntington’s Disease-Related Mechanisms"
},
{
"docid": "22500262",
"text": "During fasting, mammals maintain normal glucose homeostasis by stimulating hepatic gluconeogenesis. Elevations in circulating glucagon and epinephrine, two hormones that activate hepatic gluconeogenesis, trigger the cAMP-mediated phosphorylation of cAMP response element-binding protein (Creb) and dephosphorylation of the Creb-regulated transcription coactivator-2 (Crtc2)--two key transcriptional regulators of this process. Although the underlying mechanism is unclear, hepatic gluconeogenesis is also regulated by the circadian clock, which coordinates glucose metabolism with changes in the external environment. Circadian control of gene expression is achieved by two transcriptional activators, Clock and Bmal1, which stimulate cryptochrome (Cry1 and Cry2) and Period (Per1, Per2 and Per3) repressors that feed back on Clock-Bmal1 activity. Here we show that Creb activity during fasting is modulated by Cry1 and Cry2, which are rhythmically expressed in the liver. Cry1 expression was elevated during the night-day transition, when it reduced fasting gluconeogenic gene expression by blocking glucagon-mediated increases in intracellular cAMP concentrations and in the protein kinase A-mediated phosphorylation of Creb. In biochemical reconstitution studies, we found that Cry1 inhibited accumulation of cAMP in response to G protein-coupled receptor (GPCR) activation but not to forskolin, a direct activator of adenyl cyclase. Cry proteins seemed to modulate GPCR activity directly through interaction with G(s)α. As hepatic overexpression of Cry1 lowered blood glucose concentrations and improved insulin sensitivity in insulin-resistant db/db mice, our results suggest that compounds that enhance cryptochrome activity may provide therapeutic benefit to individuals with type 2 diabetes.",
"title": "Cryptochrome Mediates Circadian Regulation of cAMP Signaling and Hepatic Gluconeogenesis"
},
{
"docid": "8417211",
"text": "HP1 is an essential heterochromatin-associated protein in Drosophila. HP1 has dosage-dependent effects on the silencing of euchromatic genes that are mislocalized to heterochromatin and is required for the normal expression of at least two heterochromatic genes. HP1 is multiply phosphorylated in vivo, and HP1 hyperphosphorylation is correlated with heterochromatin assembly during development. The purpose of this study was to test whether HP1 phosphorylation modifies biological activity and biochemical properties of HP1. To determine sites of HP1 phosphorylation in vivo and whether phosphorylation affects any biochemical properties of HP1, we expressed Drosophila HP1 in lepidopteran cultured cells using a recombinant baculovirus vector. Phosphopeptides were identified by matrix-assisted laser desorption ionization/time of flight mass spectroscopy; these peptides contain target sites for casein kinase II, protein tyrosine kinase, and PIM-1 kinase. Purified HP1 from bacterial (unphosphorylated) and lepidopteran (phosphorylated) cells has similar secondary structure. Phosphorylation has no effect on HP1 self-association but alters the DNA binding properties of HP1, suggesting that phosphorylation could differentially regulate HP1-dependent interactions. Serine-to-alanine and serine-to-glutamate substitutions at consensus protein kinase motifs resulted in reduction or loss of silencing activity of mutant HP1 in transgenic flies. These results suggest that dynamic phosphorylation/dephosphorylation regulates HP1 activity in heterochromatic silencing.",
"title": "Phosphorylation site mutations in heterochromatin protein 1 (HP1) reduce or eliminate silencing activity."
},
{
"docid": "6157371",
"text": "Actin and its key regulatory component, cofilin, are found together in large rod-shaped assemblies in neurons subjected to energy stress. Such inclusions are also enriched in Alzheimer's disease brain, and appear in transgenic models of neurodegeneration. Neuronal insults, such as energy loss and/or oxidative stress, result in rapid dephosphorylation of the cellular cofilin pool prior to its assembly into rod-shaped inclusions. Although these events implicate a role for phosphatases in cofilin rod formation, a mechanism linking energy stress, phosphocofilin turnover, and subsequent rod assembly has been elusive. We demonstrate the ATP-sensitive interaction of the cofilin phosphatase chronophin (CIN) with the chaperone hsp90 to form a biosensor that mediates cofilin/actin rod formation. Our results suggest a model whereby attenuated interactions between CIN and hsp90 during ATP depletion enhance CIN-dependent cofilin dephosphorylation and consequent rod assembly, thereby providing a mechanism for the formation of pathological actin/cofilin aggregates during neurodegenerative energy flux.",
"title": "Chronophin mediates an ATP-sensing mechanism for cofilin dephosphorylation and neuronal cofilin-actin rod formation."
},
{
"docid": "31311495",
"text": "We have previously demonstrated that, following acquisition of endocrine resistance, breast cancer cells display an altered growth rate together with increased aggressive behaviour in vitro. Since dysfunctional cell-cell adhesive interactions can promote an aggressive phenotype, we investigated the integrity of this protein complex in our breast cancer model of tamoxifen resistance. In culture, tamoxifen-resistant MCF7 (TamR) cells grew as loosely packed colonies with loss of cell-cell junctions and demonstrated altered morphology characteristic of cells undergoing epithelial-to-mesenchymal transition (EMT). Neutralising E-cadherin function promoted the invasion and inhibited the aggregation of endocrine-sensitive MCF7 cells, whilst having little effect on the behaviour of TamR cells. Additionally, TamR cells had increased levels of tyrosine-phosphorylated beta-catenin, whilst serine/threonine-phosphorylated beta-catenin was decreased. These cells also displayed loss of association between beta-catenin and E-cadherin, increased cytoplasmic and nuclear beta-catenin and elevated transcription of beta-catenin target genes known to be involved in tumour progression and EMT. Inhibition of EGFR kinase activity in TamR cells reduced beta-catenin tyrosine phosphorylation, increased beta-catenin-E-cadherin association and promoted cell-cell adhesion. In such treated cells, the association of beta-catenin with Lef-1 and the transcription of c-myc, cyclin-D1, CD44 and COX-2 were also reduced. These results suggest that homotypic adhesion in tamoxifen-resistant breast cancer cells is dysfunctional due to EGFR-driven modulation of the phosphorylation status of beta-catenin and may contribute to an enhanced aggressive phenotype and transition towards a mesenchymal phenotype in vitro.",
"title": "Tamoxifen resistance in MCF7 cells promotes EMT-like behaviour and involves modulation of beta-catenin phosphorylation."
},
{
"docid": "10607877",
"text": "Cell surface receptors have been extensively studied because they initiate and regulate signal transduction cascades leading to a variety of functional cellular outcomes. An important class of immune receptors (e.g., T-cell antigen receptors) whose ligands are anchored to the surfaces of other cells remain poorly understood. The mechanism by which ligand binding initiates receptor phosphorylation, a process termed \"receptor triggering\", remains controversial. Recently, direct measurements of the (two-dimensional) receptor-ligand complex lifetimes at cell-cell interface were found to be smaller than (three-dimensional) lifetimes in solution but the underlying mechanism is unknown. At the cell-cell interface, the receptor-ligand complex spans a short intermembrane distance (15 nm) compared to long surface molecules (LSMs) whose ectodomains span >40 nm and these LSMs include phosphatases (e.g., CD45) that dephosphorylate the receptor. It has been proposed that size-based segregation of LSMs from a receptor-ligand complex is a mechanism of receptor triggering but it is unclear whether the mechanochemistry supports such small-scale segregation. Here we present a nanometer-scale mathematical model that couples membrane elasticity with the compressional stiffness and lateral mobility of LSMs. We find robust supradiffusive segregation of LSMs from a single receptor-ligand complex. The model predicts that LSM redistribution will result in a time-dependent tension on the complex leading to a decreased two-dimensional lifetime. Interestingly, the model predicts a nonlinear relationship between the three- and two-dimensional lifetimes, which can enhance the ability of receptors to discriminate between similar ligands.",
"title": "Mechanical modulation of receptor-ligand interactions at cell-cell interfaces."
},
{
"docid": "21307488",
"text": "HER-2/neu amplification or overexpression can make cancer cells resistant to apoptosis and promotes their growth. p53 is crucial in regulating cell growth and apoptosis, and is often mutated or deleted in many types of tumour. Moreover, many tumours with a wild-type gene for p53 do not have normal p53 function, suggesting that some oncogenic signals suppress the function of p53. In this study, we show that HER-2/neu-mediated resistance to DNA-damaging agents requires the activation of Akt, which enhances MDM2-mediated ubiquitination and degradation of p53. Akt physically associates with MDM2 and phosphorylates it at Ser166 and Ser186. Phosphorylation of MDM2 enhances its nuclear localization and its interaction with p300, and inhibits its interaction with p19ARF, thus increasing p53 degradation. Our study indicates that blocking the Akt pathway mediated by HER-2/neu would increase the cytotoxic effect of DNA-damaging drugs in tumour cells with wild-type p53.",
"title": "HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation"
},
{
"docid": "4688340",
"text": "BACKGROUND Resistance to radiotherapy continues to be a limiting factor in the treatment of cancer including head and neck squamous cell carcinoma (HNSCC). Simultaneous targeting of β1 integrin and EGFR was shown to have a higher radiosensitizing potential than mono-targeting in the majority of tested HNSCC cancer models. As tumor-initiating cells (TIC) are thought to play a key role for therapy resistance and recurrence and can be enriched in sphere forming conditions, this study investigated the efficacy of β1 integrin/EGFR targeting without and in combination with X-ray irradiation on the behavior of sphere-forming cells (SFC). METHODS HNSCC cell lines (UTSCC15, UTSCC5, Cal33, SAS) were injected subcutaneously into nude mice for tumor up-take and plated for primary and secondary sphere formation under non-adhesive conditions which is thought to reflect the enrichment of SFC and their self-renewal capacity, respectively. Treatment was accomplished by inhibitory antibodies for β1 integrin (AIIB2) and EGFR (Cetuximab) as well as X-ray irradiation (2 - 6 Gy single doses). Further, flow cytometry for TIC marker expression and cell cycling as well as Western blotting for DNA repair protein expression and phosphorylation were employed. RESULTS We found higher primary and secondary sphere forming capacity of SAS cells relative to other HNSCC cell lines, which was in line with the tumor up-take rates of SAS versus UTSCC15 cells. AIIB2 and Cetuximab administration had minor cytotoxic and no radiosensitizing effects on SFC. Intriguingly, secondary SAS spheres, representing the fraction of surviving SFC upon passaging, showed greatly enhanced radiosensitivity compared to primary spheres. Intriguingly, neither AIIB2 nor Cetuximab significantly altered basal sphere forming capacity and radiosensitivity. While an increased accumulation of G0/G1 phase cells was observable in secondary SAS spheres, DNA double strand break repair indicated no difference on the basis of significantly enhanced ATM and Chk2 dephosphorylation upon irradiation. CONCLUSIONS In the HNSCC model, sphere-forming conditions select for cells, which are unsusceptible to both anti-β1 integrin and anti-EGFR inhibitory antibodies. With regard to primary and secondary sphere formation, our data suggest that both of these SFC fractions express distinct survival strategies independent from β1 integrin and EGFR and that future work is warranted to better understand SFC survival and enrichment before and after treatment to untangle the underlying mechanisms for identifying novel, druggable cancer targets in SFC.",
"title": "Efficacy of Beta1 Integrin and EGFR Targeting in Sphere-Forming Human Head and Neck Cancer Cells"
},
{
"docid": "33063763",
"text": "MAP kinase signaling modules serve to transduce extracellular signals to the nucleus of eukaryotic cells, but little is known about how signals cross the nuclear envelope. Exposure of yeast cells to increases in extracellular osmolarity activates the HOG1 MAP kinase cascade, which is composed of three tiers of protein kinases, namely the SSK2, SSK22 and STE11 MAPKKKs, the PBS2 MAPKK, and the HOG1 MAPK. Using green fluorescent protein (GFP) fusions of these kinases, we found that HOG1, PBS2 and STE11 localize to the cytoplasm of unstressed cells. Following osmotic stress, HOG1, but neither PBS2 nor STE11, translocates into the nucleus. HOG1 translocation occurs very rapidly, is transient, and correlates with the phosphorylation and activation of the MAP kinase by its MAPKK. HOG1 phosphorylation is necessary and sufficient for nuclear translocation, because a catalytically inactive kinase when phosphorylated is translocated to the nucleus as efficiently as the wild-type. Nuclear import of the MAPK under stress conditions requires the activity of the small GTP binding protein Ran-GSP1, but not the NLS-binding importin alpha/beta heterodimer. Rather, HOG1 import requires the activity of a gene, NMD5, that encodes a novel importin beta homolog. Similarly, export of dephosphorylated HOG1 from the nucleus requires the activity of the NES receptor XPO1/CRM1. Our findings define the requirements for the regulated nuclear transport of a stress-activated MAP kinase.",
"title": "Regulated nucleo/cytoplasmic exchange of HOG1 MAPK requires the importin beta homologs NMD5 and XPO1."
},
{
"docid": "17194716",
"text": "In this study, the mechanisms of actin-bundling in filopodia were examined. Analysis of cellular localization of known actin cross-linking proteins in mouse melanoma B16F1 cells revealed that fascin was specifically localized along the entire length of all filopodia, whereas other actin cross-linkers were not. RNA interference of fascin reduced the number of filopodia, and remaining filopodia had abnormal morphology with wavy and loosely bundled actin organization. Dephosphorylation of serine 39 likely determined cellular filopodia frequency. The constitutively active fascin mutant S39A increased the number and length of filopodia, whereas the inactive fascin mutant S39E reduced filopodia frequency. Fluorescence recovery after photobleaching of GFP-tagged wild-type and S39A fascin showed that dephosphorylated fascin underwent rapid cycles of association to and dissociation from actin filaments in filopodia, with t1/2 < 10 s. We propose that fascin is a key specific actin cross-linker, providing stiffness for filopodial bundles, and that its dynamic behavior allows for efficient coordination between elongation and bundling of filopodial actin filaments.",
"title": "Role of fascin in filopodial protrusion"
},
{
"docid": "2481032",
"text": "Sirt1 is a NAD(+)-dependent class III deacetylase that functions as a cellular energy sensor. In addition to its well-characterized effects in peripheral tissues, emerging evidence suggests that neuronal Sirt1 activity plays a role in the central regulation of energy balance and glucose metabolism. To assess this idea, we generated Sirt1 neuron-specific knockout (SINKO) mice. On both standard chow and HFD, SINKO mice were more insulin sensitive than Sirt1(f/f) mice. Thus, SINKO mice had lower fasting insulin levels, improved glucose tolerance and insulin tolerance, and enhanced systemic insulin sensitivity during hyperinsulinemic euglycemic clamp studies. Hypothalamic insulin sensitivity of SINKO mice was also increased over controls, as assessed by hypothalamic activation of PI3K, phosphorylation of Akt and FoxO1 following systemic insulin injection. Intracerebroventricular injection of insulin led to a greater systemic effect to improve glucose tolerance and insulin sensitivity in SINKO mice compared with controls. In line with the in vivo results, insulin-induced AKT and FoxO1 phosphorylation were potentiated by inhibition of Sirt1 in a cultured hypothalamic cell line. Mechanistically, this effect was traced to a reduced effect of Sirt1 to directly deacetylate and repress IRS-1 function. The enhanced central insulin signaling in SINKO mice was accompanied by increased insulin receptor signal transduction in liver, muscle, and adipose tissue. In summary, we conclude that neuronal Sirt1 negatively regulates hypothalamic insulin signaling, leading to systemic insulin resistance. Interventions that reduce neuronal Sirt1 activity have the potential to improve systemic insulin action and limit weight gain on an obesigenic diet.",
"title": "Neuronal Sirt1 deficiency increases insulin sensitivity in both brain and peripheral tissues."
},
{
"docid": "21622715",
"text": "Transcriptional factors binding to cAMP-responsive elements (CREs) in the promoters of various genes belong to the basic domain-leucine zipper superfamily and are composed of three genes in mammals, CREB, CREM, and ATF-1. A large number of CREB, CREM, and ATF-1 proteins are generated by posttranscriptional events, mostly alternative splicing, and regulate gene expression by acting as activators or repressors. Activation is classically brought about by signaling-dependent phosphorylation of a key acceptor site (Ser133 in CREB) by a number of possible kinases, including PKA, CamKIV, and Rsk-2. Phosphorylation is the prerequisite for the interaction of CBP (CREB-binding protein), a co-activator that has also histone acetyltransferase activity. Repression may involve dynamic dephosphorylation of the activators and thus decreased association with CBP. Another pathway of transcriptional repression on CRE sites implicates the inducible repressor ICER (inducible cAMP early repressor), a product of the CREM gene. Being an inducible repressor, ICER is involved in autoregulatory feedback loops of transcription that govern the down-regulation of early response genes, such as the proto-oncogene c-fos. The liver represents a remarkable physiological setting where cAMP-responsive signaling plays a major role. Indeed, a finely tuned program of gene expression is triggered by partial hepatectomy, so that through specific checkpoints a coordinated regeneration of the tissue is obtained. Temporal kinetics of transcriptional activation after hepatectomy reveals a pattern of early induction for several genes, some of them controlled by the CREB/CREM transcription factors. An important role of CREM in liver physiology was suggested by the robust induction of ICER after partial hepatectomy. The delay in tissue regeneration in CREM-deficient mice confirmed the important function of this factor in regulating hepatocyte proliferation. As gene induction is accompanied by critical changes in chromatin organization, the deciphering of the specific modification codes that histones display during liver regeneration and physiology will provide exciting new insights into the dynamics of chromatin architecture.",
"title": "Coupling cAMP signaling to transcription in the liver: pivotal role of CREB and CREM."
},
{
"docid": "52873726",
"text": "The Hippo pathway controls organ size and tissue homeostasis, with deregulation leading to cancer. The core Hippo components in mammals are composed of the upstream serine/threonine kinases Mst1/2, MAPK4Ks and Lats1/2. Inactivation of these upstream kinases leads to dephosphorylation, stabilization, nuclear translocation and thus activation of the major functional transducers of the Hippo pathway, YAP and its paralogue TAZ. YAP/TAZ are transcription co-activators that regulate gene expression primarily through interaction with the TEA domain DNA-binding family of transcription factors (TEAD). The current paradigm for regulation of this pathway centres on phosphorylation-dependent nucleocytoplasmic shuttling of YAP/TAZ through a complex network of upstream components. However, unlike other transcription factors, such as SMAD, NF-κB, NFAT and STAT, the regulation of TEAD nucleocytoplasmic shuttling has been largely overlooked. In the present study, we show that environmental stress promotes TEAD cytoplasmic translocation via p38 MAPK in a Hippo-independent manner. Importantly, stress-induced TEAD inhibition predominates YAP-activating signals and selectively suppresses YAP-driven cancer cell growth. Our data reveal a mechanism governing TEAD nucleocytoplasmic shuttling and show that TEAD localization is a critical determinant of Hippo signalling output.",
"title": "Regulation of Hippo pathway transcription factor TEAD by p38 MAPK-induced cytoplasmic translocation"
},
{
"docid": "20054396",
"text": "In animal cells, most microtubules are nucleated at centrosomes. At the onset of mitosis, centrosomes undergo a structural reorganization, termed maturation, which leads to increased microtubule nucleation activity. Centrosome maturation is regulated by several kinases, including Polo-like kinase 1 (Plk1). Here, we identify a centrosomal Plk1 substrate, termed Nlp (ninein-like protein), whose properties suggest an important role in microtubule organization. Nlp interacts with two components of the gamma-tubulin ring complex and stimulates microtubule nucleation. Plk1 phosphorylates Nlp and disrupts both its centrosome association and its gamma-tubulin interaction. Overexpression of an Nlp mutant lacking Plk1 phosphorylation sites severely disturbs mitotic spindle formation. We propose that Nlp plays an important role in microtubule organization during interphase, and that the activation of Plk1 at the onset of mitosis triggers the displacement of Nlp from the centrosome, allowing the establishment of a mitotic scaffold with enhanced microtubule nucleation activity.",
"title": "Polo-like kinase 1 regulates Nlp, a centrosome protein involved in microtubule nucleation."
},
{
"docid": "1225513",
"text": "UNLABELLED Two-component systems (TCS) comprise histidine kinases and their cognate response regulators and allow bacteria to sense and respond to a wide variety of signals. Histidine kinases (HKs) phosphorylate and dephosphorylate their cognate response regulators (RRs) in response to stimuli. In general, these reactions appear to be highly specific and require an appropriate association between the HK and RR proteins. The Myxococcus xanthus genome encodes one of the largest repertoires of signaling proteins in bacteria (685 open reading frames [ORFs]), including at least 127 HKs and at least 143 RRs. Of these, 27 are bona fide NtrC-family response regulators, 21 of which are encoded adjacent to their predicted cognate kinases. Using system-wide profiling methods, we determined that the HK-NtrC RR pairs display a kinetic preference during both phosphotransfer and phosphatase functions, thereby defining cognate signaling systems in M. xanthus. Isothermal titration calorimetry measurements indicated that cognate HK-RR pairs interact with dissociation constants (Kd) of approximately 1 µM, while noncognate pairs had no measurable binding. Lastly, a chimera generated between the histidine kinase, CrdS, and HK1190 revealed that residues conferring phosphotransfer and phosphatase specificity dictate binding affinity, thereby establishing discrete protein-protein interactions which prevent cross talk. The data indicate that binding affinity is a critical parameter governing system-wide signaling fidelity for bacterial signal transduction proteins. IMPORTANCE Using in vitro phosphotransfer and phosphatase profiling assays and isothermal titration calorimetry, we have taken a system-wide approach to demonstrate specificity for a family of two-component signaling proteins in Myxococcus xanthus. Our results demonstrate that previously identified specificity residues dictate binding affinity and that phosphatase specificity follows phosphotransfer specificity for cognate HK-RR pairs. The data indicate that preferential binding affinity is the basis for signaling fidelity in bacterial two-component systems.",
"title": "Specificity Residues Determine Binding Affinity for Two-Component Signal Transduction Systems"
},
{
"docid": "11532659",
"text": "Nucleosomes, the fundamental units of chromatin structure, are regulators and barriers to transcription, replication and repair. Post-translational modifications (PTMs) of the histone proteins within nucleosomes regulate these DNA processes. Histone H3(T118) is a site of phosphorylation [H3(T118ph)] and is implicated in regulation of transcription and DNA repair. We prepared H3(T118ph) by expressed protein ligation and determined its influence on nucleosome dynamics. We find H3(T118ph) reduces DNA-histone binding by 2 kcal/mol, increases nucleosome mobility by 28-fold and increases DNA accessibility near the dyad region by 6-fold. Moreover, H3(T118ph) increases the rate of hMSH2-hMSH6 nucleosome disassembly and enables nucleosome disassembly by the SWI/SNF chromatin remodeler. These studies suggest that H3(T118ph) directly enhances and may reprogram chromatin remodeling reactions.",
"title": "Phosphorylation of histone H3(T118) alters nucleosome dynamics and remodeling"
},
{
"docid": "12640810",
"text": "Invadopodia are matrix-degrading membrane protrusions in invasive carcinoma cells. The mechanisms regulating invadopodium assembly and maturation are not understood. We have dissected the stages of invadopodium assembly and maturation and show that invadopodia use cortactin phosphorylation as a master switch during these processes. In particular, cortactin phosphorylation was found to regulate cofilin and Arp2/3 complex-dependent actin polymerization. Cortactin directly binds cofilin and inhibits its severing activity. Cortactin phosphorylation is required to release this inhibition so cofilin can sever actin filaments to create barbed ends at invadopodia to support Arp2/3-dependent actin polymerization. After barbed end formation, cortactin is dephosphorylated, which blocks cofilin severing activity thereby stabilizing invadopodia. These findings identify novel mechanisms for actin polymerization in the invadopodia of metastatic carcinoma cells and define four distinct stages of invadopodium assembly and maturation consisting of invadopodium precursor formation, actin polymerization, stabilization, and matrix degradation.",
"title": "Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation"
},
{
"docid": "3973445",
"text": "Adenosine 5′-monophosphate–activated protein kinase (AMPK) is a pivotal regulator of metabolism at cellular and organismal levels. AMPK also suppresses inflammation. We found that pharmacological activation of AMPK rapidly inhibited the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway in various cells. In vitro kinase assays revealed that AMPK directly phosphorylated two residues (Ser515 and Ser518) within the Src homology 2 domain of JAK1. Activation of AMPK enhanced the interaction between JAK1 and 14-3-3 proteins in cultured vascular endothelial cells and fibroblasts, an effect that required the presence of Ser515 and Ser518 and was abolished in cells lacking AMPK catalytic subunits. Mutation of Ser515 and Ser518 abolished AMPK-mediated inhibition of JAK-STAT signaling stimulated by either the sIL-6Rα/IL-6 complex or the expression of a constitutively active V658F-mutant JAK1 in human fibrosarcoma cells. Clinically used AMPK activators metformin and salicylate enhanced the inhibitory phosphorylation of endogenous JAK1 and inhibited STAT3 phosphorylation in primary vascular endothelial cells. Therefore, our findings reveal a mechanism by which JAK1 function and inflammatory signaling may be suppressed in response to metabolic stress and provide a mechanistic rationale for the investigation of AMPK activators in a range of diseases associated with enhanced activation of the JAK-STAT pathway.",
"title": "Phosphorylation of Janus kinase 1 (JAK1) by AMP-activated protein kinase (AMPK) links energy sensing to anti-inflammatory signaling"
},
{
"docid": "29788648",
"text": "NuA4, the major H4 lysine acetyltransferase (KAT) complex in Saccharomyces cerevisiae, is recruited to promoters and stimulates transcription initiation. NuA4 subunits contain domains that bind methylated histones, suggesting that histone methylation should target NuA4 to coding sequences during transcription elongation. We show that NuA4 is cotranscriptionally recruited, dependent on its physical association with elongating polymerase II (Pol II) phosphorylated on the C-terminal domain by cyclin-dependent kinase 7/Kin28, but independently of subunits (Eaf1 and Tra1) required for NuA4 recruitment to promoters. Whereas histone methylation by Set1 and Set2 is dispensable for NuA4's interaction with Pol II and targeting to some coding regions, it stimulates NuA4-histone interaction and H4 acetylation in vivo. The NuA4 KAT, Esa1, mediates increased H4 acetylation and enhanced RSC occupancy and histone eviction in coding sequences and stimulates the rate of transcription elongation. Esa1 cooperates with the H3 KAT in SAGA, Gcn5, to enhance these functions. Our findings delineate a pathway for acetylation-mediated nucleosome remodeling and eviction in coding sequences that stimulates transcription elongation by Pol II in vivo.",
"title": "NuA4 lysine acetyltransferase Esa1 is targeted to coding regions and stimulates transcription elongation with Gcn5."
},
{
"docid": "18758057",
"text": "Direct molecular imaging of nano-spatial relationship between T cell receptor (TCR)/CD3 and CD4 or CD8 co-receptor before and after activation of a primary T cell has not been reported. We have recently innovated application of near-field scanning optical microscopy (NSOM) and immune-labeling quantum dots (QD) to image Ag-specific TCR response during in vivo clonal expansion, and now up-graded the NSOM/QD-based nanotechnology through dipole-polarization and dual-color imaging. Using this imaging system scanning cell-membrane molecules at a best-optical lateral resolution, we demonstrated that CD3, CD4 or CD8 molecules were distinctly distributed as single QD-bound molecules or nano-clusters equivalent to 2-4 QD fluorescence-intensity/size on cell-membrane of un-stimulated primary T cells, and approximately 6-10% of CD3 were co-clustering with CD4 or CD8 as 70-110 nm nano-clusters without forming nano-domains. The ligation of TCR/CD3 on CD4 or CD8 T cells led to CD3 nanoscale co-clustering or interaction with CD4 or CD8 co-receptors forming 200-500 nm nano-domains or >500 nm micro-domains. Such nano-spatial co-clustering of CD3 and CD4 or CD3 and CD8 appeared to be an intrinsic event of TCR/CD3 ligation, not purely limited to MHC engagement, and be driven by Lck phosphorylation. Importantly, CD28 co-stimulation remarkably enhanced TCR/CD3 nanoscale co-clustering or interaction with CD4 co-receptor within nano- or micro-domains on the membrane. In contrast, CD28 co-stimulation did not enhance CD8 clustering or CD3-CD8 co-clustering in nano-domains although it increased molecular number and density of CD3 clustering in the enlarged nano-domains. These nanoscale findings provide new insights into TCR/CD3 interaction with CD4 or CD8 co-receptor in T-cell activation.",
"title": "NSOM/QD-Based Direct Visualization of CD3-Induced and CD28-Enhanced Nanospatial Coclustering of TCR and Coreceptor in Nanodomains in T Cell Activation"
},
{
"docid": "40590358",
"text": "The pro-drug FTY720 is undergoing phase III clinical trials for prevention of allograft rejection. After phosphorylation, FTY720 targets the G protein-coupled-sphingosine-1-phosphate receptor 1 (S1PR1) on lymphocytes, thereby inhibiting their egress from lymphoid organs and their recirculation to inflammatory sites. Potential effects on dendritic cell (DC) trafficking have not been evaluated. Here, we demonstrate the expression of all five S1PR subtypes (S1PR1-5) by murine DCs. Administration of FTY720 to C57BL/10 mice markedly reduced circulating T and B lymphocytes within 24 h, but not blood-borne DCs, which were enhanced significantly for up to 96 h, while DCs in lymph nodes and spleen were reduced. Numbers of adoptively transferred, fluorochrome-labeled syngeneic or allogeneic DCs in blood were increased significantly in FTY720-treated animals, while donor-derived DCs and allostimulatory activity for host naïve T cells within the spleen were reduced. Administration of the selective S1PR1 agonist SEW2871 significantly enhanced circulating DC numbers. Flow analysis revealed that CD11b, CD31/PECAM-1, CD54/ICAM-1 and CCR7 expression on blood-borne DCs was downregulated following FTY720 administration. Transendothelial migration of FTY720-P-treated immature DCs to the CCR7 ligand CCL19 was reduced. These novel data suggest that modulation of DC trafficking by FTY720 may contribute to its immunosuppressive effects.",
"title": "The sphingosine-1-phosphate receptor agonist FTY720 modulates dendritic cell trafficking in vivo."
},
{
"docid": "29429111",
"text": "Forkhead box transcription factor, class O (FOXO) is a mammalian homologue of DAF-16, which is known to regulate the lifespan of Caenorhabditis elegans and includes subfamilies of forkhead transcription factors such as AFX, FKHRL1, and FKHR. FKHR is phosphorylated on three sites (Thr-24, Ser-256, and Ser-319) in a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent manner, thereby inhibiting death signals. We here documented dephosphorylation of FKHR following transient forebrain ischemia with its concomitant translocation into the nucleus in neurons in gerbil and mouse brains. The activation of FKHR preceded delayed neuronal death in the vulnerable hippocampal regions following ischemic brain injury. The FKHR activation was accompanied by an increase in DNA binding activity for FKHR-responsive element on the Fas ligand promoter. We also defined FKHR-induced downstream targets such as Fas ligand and Bim in brain ischemia. Therefore, we propose a new strategy to rescue neurons from delayed neuronal death by promoting the survival signaling. Sodium orthovanadate, a protein tyrosine phosphatase inhibitor, up-regulated Akt activity in the brain and in turn rescue neurons from delayed neuronal death by inhibiting FKHR-dependent or -independent death signals in neurons.",
"title": "Transcriptional regulation of neuronal genes and its effect on neural functions: expression and function of forkhead transcription factors in neurons."
},
{
"docid": "9588931",
"text": "Vascular calcification is a strong independent predictor of increased cardiovascular morbidity and mortality and has a high prevalence among patients with chronic kidney disease. The present study investigated the effects of quercetin on vascular calcification caused by oxidative stress and abnormal mitochondrial dynamics both in vitro and in vivo. Calcifying vascular smooth muscle cells (VSMCs) treated with inorganic phosphate (Pi) exhibited mitochondrial dysfunction, as demonstrated by decreased mitochondrial potential and ATP production. Disruption of mitochondrial structural integrity was also observed in a rat model of adenine-induced aortic calcification. Increased production of reactive oxygen species, enhanced expression and phosphorylation of Drp1, and excessive mitochondrial fragmentation were also observed in Pi-treated VSMCs. These effects were accompanied by mitochondria-dependent apoptotic events, including release of cytochrome c from the mitochondria into the cytosol and subsequent activation of caspase-3. Quercetin was shown to block Pi-induced apoptosis and calcification of VSMCs by inhibiting oxidative stress and decreasing mitochondrial fission by inhibiting the expression and phosphorylation of Drp1. Quercetin also significantly ameliorated adenine-induced aortic calcification in rats. In summary, our findings suggest that quercetin attenuates calcification by reducing apoptosis of VSMCs by blocking oxidative stress and inhibiting mitochondrial fission.",
"title": "Quercetin attenuates vascular calcification by inhibiting oxidative stress and mitochondrial fission."
},
{
"docid": "38401028",
"text": "1. The changes in the metabolite content in freeze-clamped livers of fed rats occurring on perfusion with 10mm-d-fructose have been examined. 2. The most striking effects of fructose were an accumulation of fructose 1-phosphate, as already known, up to 8.7mumol/g of liver within 10min, a loss of total adenine nucleotides (up to 35% after 40min) with a decrease in the ATP content to 23% within 10min, a sevenfold rise in the concentration of IMP to 1.1mumol/g and an eightfold rise of alpha-glycerophosphate to 1.1mumol/g. 3. There was a transient decrease in P(i) from 4.2 to 1.7mumol/g. Within 40min the P(i) content recovered to the normal value, probably because of an uptake of P(i) from the perfusion medium. 4. The degradation of the adenine nucleotides beyond the stage of AMP can be accounted for by the decrease of ATP and P(i). As ATP inhibits 5-nucleotidase, and as P(i) inhibits AMP deaminase any AMP arising in the tissue is liable to undergo dephosphorylation or deamination under the conditions occurring after fructose loading. 5. The content of lactate increased to 4.3mumol/g at 80min; pyruvate also increased and the [lactate]/[pyruvate] ratio remained within physiological limits. 6. The concentration of free fructose within the liver remained much below that in the perfusion medium, indicating that the rate of penetration of fructose into the tissue was lower than the rate of utilization. 7. The fission of fructose 1-phosphate by liver aldolase is inhibited by several phosphorylated intermediates, especially by IMP. This inhibition is competitive with a K(i) of 0.1mm. 8. The maximal rates of the enzymes synthesizing and splitting fructose 1-phosphate are about equal. The accumulation of fructose 1-phosphate on fructose loading is due to the inhibition of the fission of fructose 1-phosphate by the IMP arising from the degradation of the adenine nucleotides.",
"title": "The cause of hepatic accumulation of fructose 1-phosphate on fructose loading."
},
{
"docid": "38751591",
"text": "The DELLA proteins GAI, RGA, RGL1 and RGL2 in Arabidopsis are plant growth repressors, repressing diverse developmental processes. Studies have shown that gibberellin (GA) attenuates the repressive function of DELLA proteins by triggering their degradation via the proteasome pathway. However, it is not known if GA-induced protein degradation is the only pathway for regulating the bioactivity of DELLA proteins. We show here that tobacco BY2 cells represent a suitable system for studying GA signaling. RGL2 exists in a phosphorylated form in BY2 cells. RGL2 undergoes GA-induced degradation, and this process is blocked by proteasome inhibitors and serine/threonine phosphatase inhibitors; however, serine/threonine kinase inhibitors had no detectable effect, suggesting that dephosphorylation of serine/threonine is probably a prerequisite for degradation of RGL2 via the proteasome pathway. Site-directed substitution of all 17 conserved serine and threonine residues showed that six mutants (RGL2(S441D, RGL2(S542D), RGL2(T271E), RGL2(T319E), RGL2(T411E) and RGL2(T535E)) mimicking the status of constitutive phosphorylation are resistant to GA-induced degradation. This suggests that these sites are potential phosphorylation sites. A functional assay based on the expression of GA 20-oxidase revealed that RGL2(T271E) is probably a null mutant, RGL2(S441D), RGL2(S542D), RGL2(T319E) and RGL2(T411E) only retained about 4-17% of the activity of the wild type RGL2, whereas RGL2(T535E) retained about 66% of the activity of the wild type RGL2. However, expression of GA 20-oxidase in BY2 cells expressing these mutant proteins is still responsive to GA, suggesting that the stabilization of RGL2 protein is not the only pathway for regulating its bioactivity.",
"title": "Identification of the conserved serine/threonine residues important for gibberellin-sensitivity of Arabidopsis RGL2 protein."
},
{
"docid": "10669582",
"text": "The protein cross-linking enzyme tissue transglutaminase binds in vitro with high affinity to fibronectin via its 42-kD gelatin-binding domain. Here we report that cell surface transglutaminase mediates adhesion and spreading of cells on the 42-kD fibronectin fragment, which lacks integrin-binding motifs. Overexpression of tissue transglutaminase increases its amount on the cell surface, enhances adhesion and spreading on fibronectin and its 42-kD fragment, enlarges focal adhesions, and amplifies adhesion-dependent phosphorylation of focal adhesion kinase. These effects are specific for tissue transglutaminase and are not shared by its functional homologue, a catalytic subunit of factor XIII. Adhesive function of tissue transglutaminase does not require its cross-linking activity but depends on its stable noncovalent association with integrins. Transglutaminase interacts directly with multiple integrins of β1 and β3 subfamilies, but not with β2 integrins. Complexes of transglutaminase with integrins are formed inside the cell during biosynthesis and accumulate on the surface and in focal adhesions. Together our results demonstrate that tissue transglutaminase mediates the interaction of integrins with fibronectin, thereby acting as an integrin-associated coreceptor to promote cell adhesion and spreading.",
"title": "Tissue Transglutaminase Is an Integrin-Binding Adhesion Coreceptor for Fibronectin"
},
{
"docid": "35884026",
"text": "Phosphorylation of AMPA receptors is a major mechanism for the regulation of receptor function and underlies several forms of synaptic plasticity in the CNS. Although serine and threonine phosphorylation of AMPA receptors has been well studied, the potential role of tyrosine phosphorylation of AMPA receptors has not been investigated. Here, we show that the GluR2 subunit of AMPA receptors is tyrosine phosphorylated in vitro and in vivo by Src family tyrosine kinases on tyrosine 876 near its C terminus. In addition, GluR agonist treatment of cultured cortical neurons increased phosphorylation of tyrosine 876. The association with GluR2-interacting molecules GRIP1/2 was decreased by tyrosine phosphorylation of GluR2, whereas PICK1 interaction was not influenced. Moreover, mutation of tyrosine 876 eliminated AMPA- and NMDA-induced internalization of the GluR2 subunit. These data indicate that tyrosine phosphorylation of tyrosine 876 on the GluR2 C terminus by Src family tyrosine kinases is important for the regulation of AMPA receptor function and may be important for synaptic plasticity.",
"title": "Tyrosine phosphorylation and regulation of the AMPA receptor by SRC family tyrosine kinases."
}
] |
PLAIN-170
|
Treating Breast Pain with Flax Seeds
|
[
{
"docid": "MED-5327",
"text": "OBJECTIVE: To investigate the associations between dietary patterns and mental health in early adolescence. METHOD: The Western Australian Pregnancy Cohort (Raine) Study is a prospective study of 2900 pregnancies recruited from 1989-1992. At 14 years of age (2003-2006; n=1324), the Child Behaviour Checklist (CBCL) was used to assess behaviour (characterising mental health status), with higher scores representing poorer behaviour. Two dietary patterns (Western and Healthy) were identified using factor analysis and food group intakes estimated by a 212-item food frequency questionnaire. Relationships between dietary patterns, food group intakes and behaviour were examined using general linear modelling following adjustment for potential confounding factors at age 14: total energy intake, body mass index, physical activity, screen use, family structure, income and functioning, gender and maternal education at pregnancy. RESULTS: Higher total (b=2.20, 95% CI=1.06, 3.35), internalizing (withdrawn/depressed) (b=1.25, 95% CI=0.15, 2.35) and externalizing (delinquent/aggressive) (b=2.60, 95% CI=1.51, 3.68) CBCL scores were significantly associated with the Western dietary pattern, with increased intakes of takeaway foods, confectionary and red meat. Improved behavioural scores were significantly associated with higher intakes of leafy green vegetables and fresh fruit (components of the Healthy pattern). CONCLUSION: These findings implicate a Western dietary pattern in poorer behavioural outcomes for adolescents. Better behavioural outcomes were associated with a higher intake of fresh fruit and leafy green vegetables.",
"title": "The association between dietary patterns and mental health in early adolescence."
},
{
"docid": "MED-4598",
"text": "OBJECTIVE: The present study aimed to evaluate the knowledge and practices of public-sector primary-care health professionals and final-year students regarding the role of nutrition, physical activity and smoking cessation (lifestyle modification) in the management of chronic diseases of lifestyle within the public health-care sector. DESIGN: A comparative cross-sectional descriptive quantitative study was conducted in thirty primary health-care facilities and four tertiary institutions offering medical and/or nursing programmes in Cape Town in the Western Cape Metropole. Stratified random sampling, based on geographical location, was used to select the health facilities while convenience sampling was used to select students at the tertiary institutions. A validated self-administered knowledge test was used to obtain data from the health professionals. RESULTS: Differential lifestyle modification knowledge exists among both health professionals and students, with less than 10 % achieving the desired scores of 80 % or higher. The majority of health professionals seem to be promoting the theoretical concepts of lifestyle modification but experience difficulty in providing practical advice to patients. Of the health professionals evaluated, doctors appeared to have the best knowledge of lifestyle modification. Lack of time, lack of patient adherence and language barriers were given as the main barriers to providing lifestyle counselling. CONCLUSIONS: The undergraduate curricula of medical and nursing students should include sufficient training on lifestyle modification, particularly practical advice on diet, physical activity and smoking cessation. Health professionals working at primary health-care facilities should be updated by providing lifestyle modification education as part of continuing medical education.",
"title": "They think they know but do they? Misalignment of perceptions of lifestyle modification knowledge among health professionals."
},
{
"docid": "MED-5341",
"text": "The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.",
"title": "Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro."
},
{
"docid": "MED-3801",
"text": "21 patients with severe persistent cyclical mastopathy of at least 5 years' duration were randomised to a control group who received general dietary advice or to an intervention group who were taught how to reduce the fat content of their diet to 15% of calories while increasing complex carbohydrate consumption to maintain caloric intake. Both groups were followed for 6 months with food records and measurement of plasma hormone and lipid levels. Severity of symptoms was recorded with daily diaries and patients were assessed at the beginning and end of the study by a physician who was unaware of their dietary regimen. After 6 months there was a significant reduction in the intervention group in the severity of premenstrual breast tenderness and swelling. Physical examination showed reduced breast swelling, tenderness, and nodularity in 6 of 10 patients in the intervention group and 2 of 9 patients in the control group.",
"title": "Effect of a low-fat high-carbohydrate diet on symptoms of cyclical mastopathy."
},
{
"docid": "MED-3793",
"text": "OBJECTIVES: To determine cross-cultural and other effects on women's experiences of premenstrual symptoms and their impact on activities of daily life (ADL). STUDY DESIGN: Cross-sectional survey. Sample A total of 7226 women aged 15-49 recruited by random sampling with approximately 400 each from France, Germany, Hungary, Italy, Spain, UK, Brazil, Mexico, Hong Kong, Pakistan and Thailand. Approximately 1000 women in Japan and Korea and 500 Australian women were found using Internet panels. MAIN OUTCOME MEASURES: Questionnaire of 23 premenstrual symptoms, sociodemographic and lifestyle variables, ADL and women's knowledge of premenstrual terms. RESULTS: The most prevalent symptoms were abdominal bloating, cramps or abdominal pain, irritability, mastalgia and joint/muscle/back pains. Severity of symptoms was directly proportional to duration (number of affected cycles) (R = 0.78). A linear model found that symptom prevalence (duration × severity) was associated with age (linear and quadratic effects), parity, current smoking and country. Premenstrual physical and mental symptom domains had similar negative effects on ADL. Impact on ADL was affected by education and exercise participation. Women's knowledge of the terms premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) varied by symptom intensity, age, education and country. CONCLUSIONS: Four of the five most prevalent premenstrual symptoms were physical. There was a great deal of similarities of women's experiences of these symptoms across countries and regions. Women's knowledge of PMS terms is highly dependent on the country in which they live.",
"title": "Global study of women's experiences of premenstrual symptoms and their effects on daily life."
},
{
"docid": "MED-5339",
"text": "Recently, it has been suggested that the Escherichia coli causing urinary tract infection (UTI) may come from meat and animals. The purpose was to investigate if a clonal link existed between E. coli from animals, meat and UTI patients. Twenty-two geographically and temporally matched B2 E. coli from UTI patients, community-dwelling humans, broiler chicken meat, pork, and broiler chicken, previously identified to exhibit eight virulence genotypes by microarray-detection of approximately 300 genes, were investigated for clonal relatedness by PFGE. Nine isolates were selected and tested for in vivo virulence in the mouse model of ascending UTI. UTI and community-dwelling human strains were closely clonally related to meat strains. Several human derived strains were also clonally interrelated. All nine isolates regardless of origin were virulent in the UTI model with positive urine, bladder and kidney cultures. Further, isolates with the same gene profile also yielded similar bacterial counts in urine, bladder and kidneys. This study showed a clonal link between E. coli from meat and humans, providing solid evidence that UTI is zoonosis. The close relationship between community-dwelling human and UTI isolates may indicate a point source spread, e.g. through contaminated meat.",
"title": "Is Escherichia coli urinary tract infection a zoonosis? Proof of direct link with production animals and meat."
},
{
"docid": "MED-4609",
"text": "Two pandemics of heart attack deaths have plagued the world's population during the past 130 years. The first pandemic, induced by beriberi, was caused by the industrial revolution altering the nutritional composition of rice. By 1892 a simple working knowledge, then at hand, could have terminated the beriberi plague; however, orthodox medicine being then enchanted with the false concept that all disease was caused by germs, permitted millions of Asians to die needlessly of beriberi by refusing to tell them to eat rice bran or to drink rice bran tea. A second pandemic of heart attack deaths, called myocardial infarction (MI), struck the developed nations of the Western World in full force after 1930. As a hypothesis, it is suggested that this MI pandemic, still raging today, was caused by a change in food processing that occurred after 1920, when the new oil seed industry introduced into our food three greatly harmful lipid substances. The unnatural trans-trans isomer of linoleic acid, which had never been in human food prior to 1920 and which entered our food in margarines and refined oils, blocked the conversion of natural cis-cis linoleic acid to prostaglandin E1, which tends to prevent MI, both by acting as a vasodilator and by minimizing platelet aggregation. Harmful lactones were also introduced into our food, increasing the risk of MI by decreasing the fibrinolytic activity of our blood. The oil seed industry also introduced into our diet free radical lipid peroxides that make the myocardium more vulnerable to infarction. It is suggested that except for the one in 500 of us who is afflicted by familial hypercholesterolemia, the cholesterol concept of MI is as false today as was the concept in 1900 that germs caused beriberi. It is further suggested that a working knowledge is at hand today that can make death from MI just as rare as death is now from a beriberi-induced heart attack.",
"title": "The beriberi analogy to myocardial infarction."
},
{
"docid": "MED-4674",
"text": "Purpose To quantify the number of required hours of nutrition education at U.S. medical schools and the types of courses in which the instruction was offered, and to compare these results with results from previous surveys. Method The authors distributed to all 127 accredited U.S. medical schools (that were matriculating students at the time of this study) a two-page online survey devised by the Nutrition in Medicine Project at the University of North Carolina at Chapel Hill. From August 2008 through July 2009, the authors asked their contacts, most of whom were nutrition educators, to report the nutrition contact hours that were required for their medical students and whether those actual hours of nutrition education occurred in a designated nutrition course, within another course, or during clinical rotations. Results Respondents from 109 (86%) of the targeted medical schools completed some part of the survey. Most schools (103/109) required some form of nutrition education. Of the 105 schools answering questions about courses and contact hours, only 26 (25%) required a dedicated nutrition course; in 2004, 32 (30%) of 106 schools did. Overall, medical students received 19.6 contact hours of nutrition instruction during their medical school careers (range: 0–70 hours); the average in 2004 was 22.3 hours. Only 28 (27%) of the 105 schools met the minimum 25 required hours set by the National Academy of Sciences; in 2004, 40 (38%) of 104 schools did so. Conclusions The amount of nutrition education that medical students receive continues to be inadequate.",
"title": "Nutrition Education in U.S. Medical Schools: Latest Update of a National Survey"
},
{
"docid": "MED-3794",
"text": "OBJECTIVE: To test the hypothesis that a low-fat, vegetarian diet reduces dysmenorrhea and premenstrual symptoms by its effect on serum sex-hormone binding globulin concentration and estrogen activity. METHODS: In a crossover design, 33 women followed a low-fat, vegetarian diet for two menstrual cycles. For two additional cycles, they followed their customary diet while taking a supplement placebo pill. Dietary intake, serum sex-hormone binding globulin concentration, body weight, pain duration and intensity, and premenstrual symptoms were assessed during each study phase. RESULTS: Mean (+/- standard deviation [SD]) serum sex-hormone binding globulin concentration was higher during the diet phase (46.7 +/- 23.6 nmol/L) than during the supplement phase (39.3 +/- 19.8 nmol/L, P < .001). Mean (+/- SD) body weight was lower during the diet (66.1 +/- 11.3 kg) compared with the supplement phase (67.9 +/- 12.1 kg, P < .001). Mean dysmenorrhea duration fell significantly from baseline (3.9 +/- 1.7 days) to diet phase (2.7 +/- 1.9 days) compared with change from baseline to supplement phase (3.6 +/- 1.7 days, P < .01). Pain intensity fell significantly during the diet phase, compared with baseline, for the worst, second-worst, and third-worst days, and mean durations of premenstrual concentration, behavioral change, and water retention symptoms were reduced significantly, compared with the supplement phase. CONCLUSION: A low-fat vegetarian diet was associated with increased serum sex-hormone binding globulin concentration and reductions in body weight, dysmenorrhea duration and intensity, and premenstrual symptom duration. The symptom effects might be mediated by dietary influences on estrogen activity.",
"title": "Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms."
},
{
"docid": "MED-5335",
"text": "Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Does a vegan diet reduce risk for Parkinson's disease?"
},
{
"docid": "MED-5322",
"text": "BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%) and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks. Copyright 2009 S. Karger AG, Basel.",
"title": "Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting."
},
{
"docid": "MED-5324",
"text": "Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.",
"title": "Effects of a high-fat meal on pulmonary function in healthy subjects."
},
{
"docid": "MED-4612",
"text": "Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.",
"title": "Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity."
},
{
"docid": "MED-5342",
"text": "Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.",
"title": "Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults"
},
{
"docid": "MED-5337",
"text": "PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.",
"title": "Intensive lifestyle changes may affect the progression of prostate cancer."
},
{
"docid": "MED-3798",
"text": "The Moos Menstrual Distress Questionnaire (MMDQ) was completed by thirty healthy premenopausal women randomized into one of two sets of weight-maintaining diets, those with a ratio of polyunsaturated to saturated fatty acids (P/S ratio) of 1.0 and those with a P/S ratio of 0.3. After a baseline interval of one menstrual cycle, both groups were fed a high fat diet (40% energy from fat) for four menstrual cycles per subject, followed by a similar interval on a low fat diet (20% energy from fat). There were no significant differences in self-reported menstrual symptoms between the two P/S groups. During both menses and the premenstrual week of the low fat dietary period there were significant decreases in self-reported symptoms associated with water retention. A decrease in symptoms in the group labelled \"arousal\" during the rest of the menstrual cycle was also reported.",
"title": "Influence of dietary fat on self-reported menstrual symptoms."
},
{
"docid": "MED-5330",
"text": "Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05 compared with low-fat meal data). No changes in lipoproteins or flow-mediated vasoactivity were observed after the low-fat meal. Fasting low-density lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results demonstrate that a single high-fat meal transiently impairs endothelial function. These findings identify a potential process by which a high-fat diet may be atherogenic independent of induced changes in cholesterol.",
"title": "Effect of a single high-fat meal on endothelial function in healthy subjects."
},
{
"docid": "MED-3796",
"text": "Lignans are a group of phytochemicals shown to have weakly estrogenic and antiestrogenic properties. Two specific lignans, enterodiol and enterolactone, are absorbed after formation in the intestinal tract from plant precursors particularly abundant in fiber-rich food and are excreted in the urine. We evaluated the effect of the ingestion of flax seed powder, known to produce high concentrations of urinary lignans, on the menstrual cycle in 18 normally cycling women, using a balanced randomized cross-over design. Each subject consumed her usual omnivorous, low fiber (control) diet for 3 cycles and her usual diet supplemented with flax seed for another 3 cycles. The second and third flax cycles were compared to the second and third control cycles. Three anovulatory cycles occurred during the 36 control cycles, compared to none during the 36 flax seed cycles. Compared to the ovulatory control cycles, the ovulatory flax cycles were consistently associated with longer luteal phase (LP) lengths (mean +/- SEM, 12.6 +/- 0.4 vs. 11.4 +/- 0.4 days; P = 0.002). There were no significant differences between flax and control cycles for concentrations of either estradiol or estrone during the early follicular phase, midfollicular phase, or LP. Although flax seed ingestion had no significant effect on LP progesterone concentrations, the LP progesterone/estradiol ratios were significantly higher during the flax cycles. Midfollicular phase testosterone concentrations were slightly higher during flax cycles. Flax seed ingestion had no effect on early follicular phase concentrations of DHEA-S, PRL, or sex hormone-binding globulin. Our data suggest a significant specific role for lignans in the relationship between diet and sex steroid action, and possibly between diet and the risk of breast and other hormonally dependent cancers.",
"title": "Effect of flax seed ingestion on the menstrual cycle."
},
{
"docid": "MED-5363",
"text": "OBJECTIVE: Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. METHODS: Subjects were 521 municipal employees (309 men and 212 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D >or=16) with adjustment for potential confounding variables. RESULTS: We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62-1.59) and 0.44 (0.25-0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms. CONCLUSIONS: Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status.",
"title": "Dietary patterns and depressive symptoms among Japanese men and women."
},
{
"docid": "MED-5325",
"text": "Objective Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores. Design Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Setting Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire. Subjects Five hundred white subjects representing the AHS-2 cohort. Results Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β =−6·8, P<0·05 and β = −6·9, P<0·001). Findings for lacto-ovo vegetarians (β = −9·1, P<0·001 and β = −5·8, P<0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI. Conclusions We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.",
"title": "Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2)"
},
{
"docid": "MED-5328",
"text": "Aim To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. Methods and Results Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses. Conclusion Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.",
"title": "Vegetarian diets and incidence of diabetes in the Adventist Health Study-2"
},
{
"docid": "MED-5323",
"text": "This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta-hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.",
"title": "Endocrine-disrupting chemicals and obesity development in humans: a review."
},
{
"docid": "MED-3792",
"text": "Basal serum prolactin and serum oestradiol-17-beta concentrations were measured four times during one menstrual cycle in 20 women with severe cyclical mastalgia and normal to slightly fibroadenotic breasts. A group of 10 normal women who had never experienced mastalgia served as controls. Basal serum prolactin was significantly elevated in patients compared to normals, although within the normal range. Serum oestradiol concentrations did not differ in the two groups and were also within the normal range. A significant positive correlation between oestradiol and prolactin was found in patients and normals, but with larger prolactin levels in patients. The results point towards a prolactin secretory hypersensitivity for oestradiol in patients with cyclical mastalgia. Prolactin is considered a central factor in the eliciting of cyclical mastalgia.",
"title": "Serum prolactin and oestradiol levels in women with cyclical mastalgia."
},
{
"docid": "MED-3797",
"text": "A double blind crossover trial of the prolactin inhibitor bromocriptine in painful benign breast disease is reported. Twenty-nine women with cyclical mastalgia and 11 with non-cyclical pain were treated with bromocriptine, 5 mg daily, and placebo over six menstrual cycels. Assessment of response to treatment was made by a linear analogue system and clinical examination together with plasma prolactin estimations. Bromocriptine produced a significant improvement in breast symptoms and a significant fall in prolactin levels in the cyclical pain group, but had no effect in the non-cyclical group. These results suggest that bromocriptine offers a new and effective approach in the management of cyclical breast pain.",
"title": "A double blind trial of the prolactin inhibitor bromocriptine in painful benign breast disease."
},
{
"docid": "MED-5331",
"text": "A global health transition is currently underway. The burden of non-communicable diseases (NCDs) is increasing rapidly in the developing world, very much as a result of changes in lifestyles. In addition to changes in tobacco use and physical activity, major changes are taking place in diets, contributing greatly to the growing epidemic of NCD. Thus, a huge global public health challenge is how to influence the trends in diet and nutrition for effective global NCD prevention. The health transition took place rapidly in Finland after World War II and mortality from cardiovascular disease (CVD) was exceptionally high. The North Karelia Project was launched in 1972 as a community-based, and later as a national, programme to influence diet and other lifestyles that are crucial in the prevention of CVD. The intervention had a strong theory base and it employed comprehensive strategies. Broad community organisation and the strong participation of people were the key elements. Evaluation has shown how the diet (particularly fat consumption) has changed and how these changes have led to a major reduction in population serum cholesterol and blood pressure levels. It has also shown how ischaemic heart disease mortality in a working-age population has declined by 73% in North Karelia and by 65% in the whole country from 1971 to 1995. Although Finland is an industrialised country, North Karelia was rural, of rather low socio-economic level and with many social problems in the 1970s and 1980s. The project was based on low-cost intervention activities, where people's participation and community organisations played a key role. Comprehensive interventions in the community were eventually supported by national activities--from expert guidelines and media activities to industry collaboration and policy. Similar principles for nutrition intervention programmes could be used in developing countries, obviously tailored to the local conditions. This paper discusses the experiences of the North Karelia Project in the light of needs from the less-industrialised countries and makes some general recommendations.",
"title": "Influencing public nutrition for non-communicable disease prevention: from community intervention to national programme--experiences from Finland."
},
{
"docid": "MED-5340",
"text": "In Asia, vegetarianism is a well-established eating behavior. It appears that the adoption of a vegan diet leads to a lessening of several health risk factors. Although vegetarianism has some notable effects on the hematological system, the effect on the nephrological system has not been well clarified. The pattern of renal function parameters was studied in 25 Thai vegans compared with 25 non-vegetarians. Of the studied parameters, it was found that urine protein was significantly different (p < 0.05) in vegans and controls. Vegans had significantly lower urine protein level.",
"title": "Renal function parameters of Thai vegans compared with non-vegans."
},
{
"docid": "MED-3779",
"text": "The question of whether menstrual disturbances are more common in vegetarian than in nonvegetarian women is complex. Disturbances of the cycle may be clinical (ie, amenorrhea or oligomenorrhea) or subclinical (i.e., normal-length cycles with anovulation or a short or defective luteal phase). Detection of the latter requires that the menstrual cycle be monitored, but may help prevent recruitment bias in studies comparing vegetarians with nonvegetarians because vegetarians with menstrual disturbances may be more likely to volunteer for a study on menstrual disturbances and vegetarianism. Three general mechanisms that could contribute to menstrual disturbances that may differ between vegetarians and nonvegetarians include energy imbalances associated with body-weight disturbances or exercise, psychosocial and cognitive factors, and dietary components. Evidence for each of these mechanisms is reviewed and studies comparing menstrual function between vegetarians and nonvegetarians are described in this article. Although results from several cross-sectional studies suggest that clinical menstrual disturbances may be more common in vegetarians, a prospective study that controlled for many potential confounders found that subclinical disturbances were less common in weight-stable, healthy vegetarian women. Because the sample studied may not be representative of all vegetarian women, however, these results cannot be generalized. Population studies are needed to draw definitive conclusions.",
"title": "Vegetarianism and menstrual cycle disturbances: is there an association?"
},
{
"docid": "MED-3795",
"text": "Mastalgia affects up to two-thirds of women at some time during their reproductive lives. It is usually benign, but thefear of underlying breast cancer is why many women present for evaluation. Mastalgia can be associated with premenstrual syndrome, fibrocystic breast disease, psychologic disturbance and, rarely, breast cancer. Occasionally, extramammary conditions, like Tietzie syndrome, present as mastalgia. A thorough clinical evaluation is required to assess the cause. The majority of women can be reassured after a clinical evaluation. Approximately 15% require pain-relieving therapy. Mechanical breast support; a low-fat, high-carbohydrate diet; and topical nonsteroidal antiinflammatory agents are reasonable first-line treatments. Hormonal agents, such as bromocriptine, tamoxifen and danazol, have all demonstrated efficacy in the treatment of mastalgia. Side effects, however, limit their extensive use. Danazol is the only FDA-approved hormonal treatment and is best used in cyclic form to limit the adverse effects. Lisuride maleate is a new agent recently studied for the treatment of mastalgia. Initial data on this medication are encouraging. Sixty percent of cyclic mastalgia recurs after treatment. Noncyclic mastalgia responds poorly to treatment but resolves spontaneously in up to 50% of cases.",
"title": "Mastalgia: a review of management."
},
{
"docid": "MED-3778",
"text": "Ovulatory function was prospectively assessed over 6 mo in 23 vegetarians and 22 nonvegetarians with clinically normal menstrual cycles. Subjects were 20-40 y of age, of stable weight (body mass index, in kg/m2, of 18-25), on current diets for > or = 2 y, and not using oral contraceptives. Quantitative analysis of basal body temperature records classified cycles as normally ovulatory, short luteal phase (< 10 d), or anovulatory. Subjects completed the Three-Factor Eating Questionnaire (subjects completed the Three-Factor Eating Questionnaire (subscales for restraint, hunger, and disinhibition) and kept three 3-d food records. Vegetarians had lower BMIs (21.1 +/- 2.3 vs 22.7 +/- 1.9, P < 0.05), percentage body fat (24.0 +/- 5.5% vs 27.4 +/- 5.1%, P < 0.05), and restraint scores (6.4 +/- 4.4 vs 9.5 +/- 3.7, P < 0.05). Mean cycle lengths were similar, but vegetarians had longer luteal phase lengths (11.2 +/- 2.6 vs 9.1 +/- 3.8 d, P < 0.05). Cycle types also differed (chi 2 = 9.64, P < 0.01): vegetarians had fewer anovulatory cycles (4.6% vs 15.1% of cycles). Compared with those with restraint scores below the median, highly restrained women had fewer ovulatory cycles (3.6 +/- 2.3 vs 5.0 +/- 1.4, P < 0.05) and shorter mean luteal phase lengths (7.4 +/- 4.1 vs 10.7 +/- 3.1 d, P < 0.05). We conclude that ovulatory disturbances and restrained eating are less common among vegetarians, and that restraint influences ovulatory function.",
"title": "Vegetarian vs nonvegetarian diets, dietary restraint, and subclinical ovulatory disturbances: prospective 6-mo study."
},
{
"docid": "MED-5333",
"text": "BACKGROUND/AIM: A vegetarian diet is known to prevent a series of diseases but may influence the balance of carbohydrate and fat metabolism as well as collagen synthesis. This study compares expression patterns of relevant genes in oral mucosa of omnivores and vegetarians. METHODS: Quantitative reverse transcriptase polymerase chain reaction was applied for analysis of mRNA levels from carnitine transporter OCTN2, hepatic CPT1A and nonhepatic CPT1B isoforms of carnitine palmitoyltransferase and collagen (CCOL2A1) in oral mucosa. RESULTS: Compared with volunteers with traditional eating habits, carbohydrate consumption was significantly higher (+22%) in vegetarians. This was associated with a significant stimulation of CPT1A (+50%) and OCTN2 (+10%) and a lowered collagen synthesis (-10%). CONCLUSION: These novel findings provide further insight into the association of a changed fat metabolism and reduced collagen synthesis in vegetarians, which could also play a role in the aging process. Copyright 2008 S. Karger AG, Basel.",
"title": "Vegetarian diet affects genes of oxidative metabolism and collagen synthesis."
},
{
"docid": "MED-4617",
"text": "The need for consistent and current data describing the true incidence of SCA and/or SCD was highlighted during the most recent Sudden Cardiac Arrest Thought Leadership Alliance’s (SCATLA) Think Tank meeting of national experts with broad representation of key stakeholders including thought leaders and representatives from the American College of Cardiology, American Heart Association, and the Heart Rhythm Society. As such, to evaluate the true magnitude of this public health problem, we performed a systematic literature search in MEDLINE using the MeSH headings, “death, sudden” OR the terms “sudden cardiac death” OR “sudden cardiac arrest” OR “cardiac arrest” OR “cardiac death” OR “sudden death” OR “arrhythmic death.” Study selection criteria included peer-reviewed publications of primary data used to estimate SCD incidence in the U.S. We used Web of Science®’s Cited Reference Search to evaluate the impact of each primary estimate on the medical literature by determining the number of times each “primary source” has been cited. The estimated U.S. annual incidence of SCD varied widely from 180,000 to > 450,000 among 6 included studies. These different estimates were in part due to different data sources (with data age ranging from 1980 to 2007), definitions of SCD, case ascertainment criteria, methods of estimation/extrapolation, and sources of case ascertainment. The true incidence of SCA and/or SCD in the U.S. remains unclear with a wide range in the available estimates, which are badly dated. As reliable estimates of SCD incidence are important for improving risk stratification and prevention, future efforts are clearly needed to establish uniform definitions of SCA and SCD and then to prospectively and precisely capture cases of SCA and SCD in the overall U.S. population.",
"title": "Systematic Review of the Incidence of Sudden Cardiac Death in the United States"
},
{
"docid": "MED-3800",
"text": "OBJECTIVE: To review the current management of women with breast pain. OPTIONS: The effect of various treatment modes and health practices, including medications, was considered for the management of both cyclical and noncyclical breast pain. OUTCOMES: Effective and timely management of the woman with breast pain and improved quality of life. EVIDENCE: A literature search was performed to identify reports published in English between 1975 and July 2003 using MEDLINE and Cochrane Database of Systematic Reviews. VALUES: Levels of evidence, as outlined, have been determined using the criteria outlined by the Canadian Task Force on the Periodic Health Examination. Participants were the principal authors: a clinical dietitian, a surgeon oncologist, and a nurse. BENEFITS, HARMS, AND COSTS: Utilizing the information will increase knowledge, enabling a consistent approach, which will reduce the number of ineffective interventions and ensure appropriate use medications. VALIDATION: Comparison has been made with management protocols in the literature, but no clinical guidelines have been located. No formal clinical testing has taken place. SPONSOR: The Society of Obstetricians and Gynaecologists of Canada (SOGC). Work on these guidelines was initiated by team members to fill a need for practice guidelines at Winnipeg Regional Health Authority Breast Health Centre, Winnipeg, MB. RECOMMENDATIONS: 1. Education and reassurance is an integral part of the management of mastalgia and should be the first-line treatment. (II-1 A) 2. The use of a well-fitting bra that provides good support should be considered for the relief of cyclical and noncyclical mastalgia. (II-3 B) 3. A change in dose, formulation, or scheduling should be considered for women on HRT. HRT may be discontinued if appropriate. (III C) 4. Women with breast pain should not be advised to reduce caffeine intake. (1 E) 5. Vitamin E should not be considered for the treatment of mastalgia. (1 E) 6. There is presently insufficient evidence to recommend the use of evening primrose oil (EPO) in the treatment of breast pain. (II-2 C) 7. Flaxseed should be considered as a first-line treatment for cyclical mastalgia. (I A) 8. Topical non-steroidal anti-inflammatory gel, such as diclofenac 2% in pluronic lethicin organogel, should be considered for pain control for localized treatment of mastalgia. (I A) 9. Tamoxifen 10 mg daily or danazol 200 mg daily should be considered when first-line treatments are ineffective. (I A) 10. Mastectomy or partial mastectomy should not be considered an effective treatment for mastalgia. (III E).",
"title": "Mastalgia."
},
{
"docid": "MED-5332",
"text": "The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.",
"title": "Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age."
},
{
"docid": "MED-5334",
"text": "Until recently, intact protein that is rich in tryptophan was not seen as an alternative to pharmaceutical-grade tryptophan because protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a rich source of tryptophan with approximately 22 mg/g protein) is combined with glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective and subjective measures of anxiety in those suffering from social phobia (also known as social anxiety disorder) were employed to measure changes in anxiety in response to a stimulus as part of a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between study sessions. Subjects were randomly assigned to start with either (i) protein-source tryptophan (deoiled gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week after the initial session, subjects returned for a follow-up session and received the opposite treatment of that received at the first session. All 7 subjects who began the study completed the 2-week protocol. Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement on an objective measure of anxiety. Protein-source tryptophan combined with a high glycemic carbohydrate is a potential anxiolytic to those suffering from social phobia.",
"title": "Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study."
},
{
"docid": "MED-5326",
"text": "The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Red meat and colon cancer: should we become vegetarians, or can we make meat safer?"
},
{
"docid": "MED-3799",
"text": "Modifiable factors, including diet, might alter breast cancer risk. We used the WHI Dietary Modification (DM) trial to test the effect of the intervention on risk of benign proliferative breast disease, a condition associated with increased risk of and considered to be on the pathway to invasive breast cancer. The WHI DM trial was a randomized, controlled, primary prevention trial conducted in 40 US clinical centers from 1993–2005. 48,835 postmenopausal women, aged 50–79 years, without prior breast cancer, were enrolled. Participants were randomly assigned to the DM intervention group or to the comparison group. The intervention was designed to reduce total dietary fat intake to 20% of total energy intake, and to increase fruit and vegetable intake to ≥5 servings/day and intake of grain products to ≥6 servings/day, but resulted in smaller, albeit significant changes in practice. Participants had biennial mammograms and regular clinical breast exams. We identified women who reported breast biopsies free of cancer, obtained the histologic sections, and subjected them to standardized central review. During follow-up (average, 7.7 years), 570 incident cases of benign proliferative breast disease were ascertained in the intervention group and 793 in the comparison group. The hazard ratio for the association between DM and benign proliferative breast disease was 1.09 (95%CI, 0.98–1.23). Risk varied by levels of baseline total vitamin D intake but it varied little by levels of other baseline variables. These results suggest that a modest reduction in fat intake and increase in fruit, vegetable, and grain intake does not alter the risk of benign proliferative breast disease.",
"title": "Low-fat dietary pattern and risk of benign proliferative breast disease: a randomized, controlled dietary modification trial"
},
{
"docid": "MED-5338",
"text": "Summary Background and objectives Patients with advanced chronic kidney disease (CKD) are in positive phosphorus balance, but phosphorus levels are maintained in the normal range through phosphaturia induced by increases in fibroblast growth factor-23 (FGF23) and parathyroid hormone (PTH). This provides the rationale for recommendations to restrict dietary phosphate intake to 800 mg/d. However, the protein source of the phosphate may also be important. Design, setting, participants, & measurements We conducted a crossover trial in nine patients with a mean estimated GFR of 32 ml/min to directly compare vegetarian and meat diets with equivalent nutrients prepared by clinical research staff. During the last 24 hours of each 7-day diet period, subjects were hospitalized in a research center and urine and blood were frequently monitored. Results The results indicated that 1 week of a vegetarian diet led to lower serum phosphorus levels and decreased FGF23 levels. The inpatient stay demonstrated similar diurnal variation for blood phosphorus, calcium, PTH, and urine fractional excretion of phosphorus but significant differences between the vegetarian and meat diets. Finally, the 24-hour fractional excretion of phosphorus was highly correlated to a 2-hour fasting urine collection for the vegetarian diet but not the meat diet. Conclusions In summary, this study demonstrates that the source of protein has a significant effect on phosphorus homeostasis in patients with CKD. Therefore, dietary counseling of patients with CKD must include information on not only the amount of phosphate but also the source of protein from which the phosphate derives.",
"title": "Original Articles: Vegetarian Compared with Meat Dietary Protein Source and Phosphorus Homeostasis in Chronic Kidney Disease"
},
{
"docid": "MED-3791",
"text": "Experimental and epidemiological evidence suggest that a diet with dietary fat as low as 20% of kcal may be necessary to reduce the risk of breast cancer. Two groups of women, postmenopausal women treated for breast cancer and premenopausal women with cystic breast disease accompanied by cyclical mastaligia, participated in an intervention program to determine the feasibility of such a low-fat diet. After 3 mo of intervention both groups were consuming a low-fat diet; in the premenopausal groups serum estrogen levels decreased in response to the fat reduction. Other nutrition-education programs in research institutions, restaurants, and schools are attempting to influence the public's knowledge and behavior regarding the importance of dietary fat reduction.",
"title": "Recommendations for the prevention of chronic disease: the application for breast disease."
},
{
"docid": "MED-4613",
"text": "The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations. (c)2001 CHF, Inc.",
"title": "Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition."
},
{
"docid": "MED-4599",
"text": "Purpose To quantify the number of required hours of nutrition education at U.S. medical schools and the types of courses in which the instruction was offered, and to compare these results with results from previous surveys. Method The authors distributed to all 127 accredited U.S. medical schools (that were matriculating students at the time of this study) a two-page online survey devised by the Nutrition in Medicine Project at the University of North Carolina at Chapel Hill. From August 2008 through July 2009, the authors asked their contacts, most of whom were nutrition educators, to report the nutrition contact hours that were required for their medical students and whether those actual hours of nutrition education occurred in a designated nutrition course, within another course, or during clinical rotations. Results Respondents from 109 (86%) of the targeted medical schools completed some part of the survey. Most schools (103/109) required some form of nutrition education. Of the 105 schools answering questions about courses and contact hours, only 26 (25%) required a dedicated nutrition course; in 2004, 32 (30%) of 106 schools did. Overall, medical students received 19.6 contact hours of nutrition instruction during their medical school careers (range: 0–70 hours); the average in 2004 was 22.3 hours. Only 28 (27%) of the 105 schools met the minimum 25 required hours set by the National Academy of Sciences; in 2004, 40 (38%) of 104 schools did so. Conclusions The amount of nutrition education that medical students receive continues to be inadequate.",
"title": "Nutrition Education in U.S. Medical Schools: Latest Update of a National Survey"
},
{
"docid": "MED-4673",
"text": "OBJECTIVE: The present study aimed to evaluate the knowledge and practices of public-sector primary-care health professionals and final-year students regarding the role of nutrition, physical activity and smoking cessation (lifestyle modification) in the management of chronic diseases of lifestyle within the public health-care sector. DESIGN: A comparative cross-sectional descriptive quantitative study was conducted in thirty primary health-care facilities and four tertiary institutions offering medical and/or nursing programmes in Cape Town in the Western Cape Metropole. Stratified random sampling, based on geographical location, was used to select the health facilities while convenience sampling was used to select students at the tertiary institutions. A validated self-administered knowledge test was used to obtain data from the health professionals. RESULTS: Differential lifestyle modification knowledge exists among both health professionals and students, with less than 10 % achieving the desired scores of 80 % or higher. The majority of health professionals seem to be promoting the theoretical concepts of lifestyle modification but experience difficulty in providing practical advice to patients. Of the health professionals evaluated, doctors appeared to have the best knowledge of lifestyle modification. Lack of time, lack of patient adherence and language barriers were given as the main barriers to providing lifestyle counselling. CONCLUSIONS: The undergraduate curricula of medical and nursing students should include sufficient training on lifestyle modification, particularly practical advice on diet, physical activity and smoking cessation. Health professionals working at primary health-care facilities should be updated by providing lifestyle modification education as part of continuing medical education.",
"title": "They think they know but do they? Misalignment of perceptions of lifestyle modification knowledge among health professionals."
},
{
"docid": "MED-5329",
"text": "OBJECTIVE: This study was conducted to demonstrate the effectiveness of a strictly vegetarian, very low-fat diet on cardiac risk factor modification. METHODS: Five hundred men and women, participants in an intensive 12-day live-in program, were studied. The program focused on dietary modification, moderate exercise, and stress management at a hospital-based health-center. RESULTS: During this short time period, cardiac risk factors improved: there was an average reduction of total serum cholesterol of 11% (p < 0.001), of blood pressure of 6% (p < 0.001) and a weight loss of 2.5 kg for men and 1 kg for women. Serum triglycerides did not increase except for two subgroups: females age > or = 65 years with serum cholesterol < 6.5 mmol/L and for females 50 to 64 years with baseline serum cholesterol between 5.2-6.5 mmol/L. High-density lipoprotein cholesterol measured on 66 subjects decreased by 19%. CONCLUSION: A strict, very low-fat vegetarian diet free from all animal products combined with lifestyle changes that include exercise and weight loss is an effective way to lower serum cholesterol and blood pressure.",
"title": "Rapid reduction of serum cholesterol and blood pressure by a twelve-day, very low fat, strictly vegetarian diet."
}
] |
[
{
"docid": "MED-1825",
"text": "Background. Flax is a food and dietary supplement commonly used for menopausal symptoms. Flax is known for its lignan, α-linolenic acid, and fiber content, components that may possess phytogestrogenic, anti-inflammatory, and hormone modulating effects, respectively. We conducted a systematic review of flax for efficacy in improving menopausal symptoms in women living with breast cancer and for potential impact on risk of breast cancer incidence or recurrence. Methods. We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to January 2013 for human interventional or observational data pertaining to flax and breast cancer. Results. Of 1892 records, we included a total of 10 studies: 2 randomized controlled trials, 2 uncontrolled trials, 1 biomarker study, and 5 observational studies. Nonsignificant (NS) decreases in hot flash symptomatology were seen with flax ingestion (7.5 g/d). Flax (25 g/d) increased tumor apoptotic index (P < .05) and decreased HER2 expression (P < .05) and cell proliferation (Ki-67 index; NS) among newly diagnosed breast cancer patients when compared with placebo. Uncontrolled and biomarker studies suggest beneficial effects on hot flashes, cell proliferation, atypical cytomorphology, and mammographic density, as well as possible anti-angiogenic activity at doses of 25 g ground flax or 50 mg secoisolariciresinol diglycoside daily. Observational data suggests associations between flax and decreased risk of primary breast cancer (adjusted odds ratio [AOR] = 0.82; 95% confidence interval [CI] = 0.69-0.97), better mental health (AOR = 1.76; 95% CI = 1.05-2.94), and lower mortality (multivariate hazard ratio = 0.69; 95% CI = 0.50-0.95) among breast cancer patients. Conclusions. Current evidence suggests that flax may be associated with decreased risk of breast cancer. Flax demonstrates antiproliferative effects in breast tissue of women at risk of breast cancer and may protect against primary breast cancer. Mortality risk may also be reduced among those living with breast cancer. © The Author(s) 2013.",
"title": "Flax and Breast Cancer: A Systematic Review."
},
{
"docid": "MED-1826",
"text": "PURPOSE: To investigate the association between intake of flaxseed-the richest source of dietary lignans (a class of phytoestrogens)-and breast cancer risk. METHODS: A food frequency questionnaire was used to measure the consumption of flaxseed and flax bread by 2,999 women with breast cancer and 3,370 healthy control women who participated in the Ontario Women's Diet and Health Study (2002-2003). Logistic regression was used to investigate associations between consumption of flaxseed and flax bread and breast cancer risk. Confounding by established and suspected breast cancer risk factors, as well as dietary factors, was assessed. RESULTS: Flaxseed or flax bread was consumed at least weekly by 21 % of control women. None of the 19 variables assessed were identified as confounders of the associations between flaxseed or flax bread and breast cancer risk. Consumption of flaxseed was associated with a significant reduction in breast cancer risk (odds ratio (OR) = 0.82, 95 % confidence interval (CI) 0.69-0.97), as was consumption of flax bread (OR = 0.77, 95 % CI 0.67-0.89). CONCLUSIONS: This Canadian study is, to our knowledge, the first to report on the association between flaxseed alone and breast cancer risk and has found that flaxseed intake is associated with a reduction in breast cancer risk. As dietary intake of flaxseed is modifiable, this finding may be of public health importance with respect to breast cancer prevention.",
"title": "Consumption of flaxseed, a rich source of lignans, is associated with reduced breast cancer risk."
},
{
"docid": "MED-1827",
"text": "BACKGROUND: Actin cytoskeleton is involved in actin-based cell adhesion, cell motility, and matrix metalloproteinases(MMPs) MMP2, MMP9, MMP11 and MMP14 are responsible for cell invasion in breast cancer metastasis. The dietary intake of lignan from flax seed gets converted to enterolactone (EL) and enterodiol in the human system. Here we show that the enterolactone has a very significant anti-metastatic activity as demonstrated by its ability to inhibit adhesion and invasion and migration in MCF-7 and MDA MB231 cell lines. MATERIALS AND METHODS: Migration inhibition assay, actin-based cell motility assay along with reverse transcriptase polymerase chain reaction (RT-PCR) for MMP2, MMP9, MMP11 and MMP14 genes were performed in MCF-7 and MDA MB 231 cell lines. RESULTS: Enterolactone seems to inhibit actin-based cell motility as evidenced by confocal imaging and photo documentation of cell migration assay. The results are supported by the observation that the enterolactone in vitro significantly down-regulates the metastasis-related metalloproteinases MMP2, MMP9 and MMP14 gene expressions. No significant alteration in the MMP11 gene expression was found. CONCLUSIONS: Therefore we suggest that the anti-metastatic activity of EL is attributed to its ability to inhibit cell adhesion, cell invasion and cell motility. EL affects normal filopodia and lamellipodia structures, polymerization of actin filaments at their leading edges and thereby inhibits actin-based cell adhesion and cell motility. The process involves multiple force-generating mechanisms of actin filaments i.e. protrusion, traction, deadhesion and tail-retraction. By down-regulating the metastasis-related MMP2, MMP9 and MMP14 gene expressions, EL may be responsible for cell invasion step of metastasis.",
"title": "In vitro anti-metastatic activity of enterolactone, a mammalian lignan derived from flax lignan, and down-regulation of matrix metalloproteinases i..."
},
{
"docid": "MED-3869",
"text": "Diabetes mellitus is characterized by hyperglycemia and associated with aberrations in the metabolism of carbohydrate, protein, and lipid that result in development of secondary complications. Extensive studies have indicated that nutritional therapy plays a pivotal role in the controlling or postponing of development of these secondary complications. Several functional foods have been shown to possess hypoglycemic and hypolipidemic properties. Flax seed (FS) is a functional food that is rich in omega 3 fatty acids and antioxidants and is low in carbohydrates. In exploratory studies, FS was incorporated in recipes, which resulted in a reduction in the glycemic index of the food items. These observations prompted us to investigate the efficacy of FS supplementation in type 2 diabetics (n = 29). Subjects were assigned to the experimental (n = 18) or the control group (n = 11) on the basis of their desire to participate in the study. The experimental group's diet was supplemented daily with 10 g of FS powder for a period of 1 month. The control group received no supplementation or placebo. During the study, diet and drug intake of the subjects remained unaltered. The efficacy of supplementation with FS was evaluated through a battery of clinico-biochemical parameters. Supplementation with FS reduced fasting blood glucose by 19.7% and glycated hemoglobin by 15.6%. A favorable reduction in total cholesterol (14.3%), triglycerides (17.5%), low-density lipoprotein cholesterol (21.8%), and apolipoprotein B and an increase in high-density lipoprotein cholesterol (11.9%) were also noticed. These observations suggest the therapeutic potential of FS in the management of diabetes mellitus.",
"title": "An open-label study on the effect of flax seed powder (Linum usitatissimum) supplementation in the management of diabetes mellitus."
},
{
"docid": "MED-666",
"text": "Breast pain is a common condition affecting most women at some stage in their reproductive life. Mastalgia is resistant to treatment in 6% of cyclical and 26% non-cyclical patients. Surgery is not widely used to treat this condition and only considered in patients with severe mastalgia resistant to medication. The aims of this study were to audit the efficacy of surgery in severe treatment resistant mastalgia and to assess patient satisfaction following surgery. This is a retrospective review of the medical records of all patients seen in mastalgia clinic in the University Hospital of Wales, Cardiff since 1973. A postal questionnaire was distributed to all patients who had undergone surgery. Results showed that of the 1054 patients seen in mastalgia clinic, 12 (1.2%) had undergone surgery. Surgery included 8 subcutaneous mastectomies with implants (3 bilateral, 5 unilateral), 1 bilateral simple mastectomy and 3 quadrantectomies (1 having a further simple mastectomy). The median duration of symptoms was 6.5 years (range 2-16 years). Five patients (50%) were pain free following surgery, 3 developed capsular contractures and 2 wound infections with dehiscence. Pain persisted in both patients undergoing quadrantectomy. We conclude that surgery for mastalgia should only be considered in a minority of patients. Patients should be informed of possible complications inherent of reconstructive surgery and warned that in 50% cases their pain will not be improved.",
"title": "Is there a role for surgery in the treatment of mastalgia?"
},
{
"docid": "MED-3664",
"text": "OBJECTIVE: To evaluate the efficacy and safety of acetaminophen 1000 mg for the treatment of episodic migraine headache. BACKGROUND: While acetaminophen is commonly used to treat migraine, there have been limited published clinical trial efficacy results. DESIGN/METHODS: Ten investigators at 13 private, ambulatory, primary care sites in the United States enrolled and treated 346 outpatient adults 18-72 years of age with migraine headache of moderate to severe intensity into a randomized, placebo-controlled, double-blind clinical trial of 6 hours duration. Each patient was randomly assigned to a single dose of study medication of acetaminophen 1000 mg (n = 177) or placebo (n = 169). The percentage of patients with a reduction in baseline headache pain intensity from severe or moderate to mild or none 2 hours after treatment and the headache pain intensity difference from baseline at 2 hours were the primary efficacy measures. Other measures of pain relief, severity differences from baseline for migraine-associated symptoms of nausea, photophobia, phonophobia, and functional disability, and percentage of patients with migraine-associated symptoms reduced to none were also assessed. RESULTS: Significantly (P = .001) more patients treated with acetaminophen 1000 mg reported mild to no pain after 2 hours (52.0%) compared with those treated with placebo (32.0%). The mean pain intensity difference from baseline measured at 2 hours was significantly (P < .001) greater for patients treated with acetaminophen 1000 mg (0.82) compared with those treated with placebo (0.46). A significant difference in favor of acetaminophen 1000 mg over placebo was also observed at 1 hour after treatment for the percentage of patients with mild to no pain and for mean pain intensity difference from baseline. Acetaminophen 1000 mg was significantly more effective than placebo for all but 1 (pain reduced to none at 2 hours) clinically important secondary pain relief outcomes. Mean severity changes from baseline in migraine-associated symptoms of nausea, photophobia, phonophobia, and functional disability at 2 and 6 hours were significantly (P < .001) in favor of acetaminophen over placebo; the percentage of patients with no symptoms at 2 and 6 hours statistically significantly favored acetaminophen in 6 of 8 comparisons. Adverse events, overall, and specifically for nausea, were reported more frequently in the placebo group. CONCLUSIONS: Acetaminophen 1000 mg, a nonprescription drug, is an effective and well-tolerated treatment for episodic and moderate migraine headache. In addition, acetaminophen generally provided a beneficial effect on associated symptoms of migraine including nausea, photophobia, phonophobia, and functional disability.",
"title": "A randomized, placebo-controlled trial of acetaminophen for treatment of migraine headache."
},
{
"docid": "MED-2438",
"text": "Phytoestrogens are structurally similar to estrogens and may affect breast cancer risk by mimicking estrogenic/antiestrogenic properties. In Western societies, whole grains and possibly soy foods are rich sources of phytoestrogens. A population-based case-control study in German postmenopausal women was used to evaluate the association of phytoestrogen-rich foods and dietary lignans with breast cancer risk. Dietary data were collected from 2,884 cases and 5,509 controls using a validated food-frequency questionnaire, which included additional questions phytoestrogen-rich foods. Associations were assessed using conditional logistic regression. All analyses were adjusted for relevant risk and confounding factors. Polytomous logistic regression analysis was performed to evaluate the associations by estrogen receptor (ER) status. High and low consumption of soybeans as well as of sunflower and pumpkin seeds were associated with significantly reduced breast cancer risk compared to no consumption (OR = 0.83, 95% CI = 0.70-0.97; and OR = 0.66, 95% CI = 0.77-0.97, respectively). The observed associations were not differential by ER status. No statistically significant associations were found for dietary intake of plant lignans, fiber, or the calculated enterolignans. Our results provide evidence for a reduced postmenopausal breast cancer risk associated with increased consumption of sunflower and pumpkin seeds and soybeans.",
"title": "The association between dietary lignans, phytoestrogen-rich foods, and fiber intake and postmenopausal breast cancer risk: a German case-control st..."
},
{
"docid": "MED-2378",
"text": "Background Polyunsaturated fatty acids (PUFA) have beneficial effects on cardiovascular risk, although the mechanisms are incompletely understood. In a previous article, we showed significant reductions in low-density lipoprotein cholesterol and several markers of inflammation with increasing intake of alpha-linolenic acid (ALA) from walnuts and flax. Objective To examine effects of ALA on cardiovascular responses to acute stress, flow-mediated dilation (FMD) of the brachial artery, and blood concentrations of endothelin-1 and arginine-vasopressin (AVP). Design Using a randomized, crossover study design, cardiovascular responses to acute stress were assessed in 20 hypercholesterolemic subjects, a subset of whom also underwent FMD testing (n = 12). Participants were fed an average American diet (AAD) and 2 experimental diets that varied in the amount of ALA and linoleic acid (LA) that they contained. The AAD provided 8.7% energy from PUFA (7.7% LA, 0.8% ALA). On the LA diet, saturated fat was reduced, and PUFA from walnuts and walnut oil provided 16.4% of energy (12.6% LA, 3.6% ALA). On the ALA diet, walnuts, walnut oil, and flax oil provided 17% energy from PUFA (10.5% LA, 6.5% ALA). Results The ALA and LA diets significantly reduced diastolic blood pressure (−2 to −3 mm Hg) and total peripheral resistance (−4%), and this effect was evident at rest and during stress (main effect of diet, p < 0.02). FMD increased (+34%) on the diet containing additional ALA. AVP also increased by 20%, and endothelin-1 was unchanged. Conclusions These results suggest novel mechanisms for the cardioprotective effects of walnuts and flax, and further work is needed to identify the bioactives responsible for these effects.",
"title": "Effects of Diets High in Walnuts and Flax Oil on Hemodynamic Responses to Stress and Vascular Endothelial Function"
},
{
"docid": "MED-4621",
"text": "The aqueous seed extract of Persea americana Mill (Lauraceae) is used by herbalists in Nigeria for the management of hypertension. As part of our on-going scientific evaluation of the extract, we designed the present study to assess its acute and sub-acute toxicity profiles in rats. Experiments were conducted to determine the oral median lethal dose (LD50) and other gross toxicological manifestations on acute basis. In the sub-acute experiments, the animals were administered 2.5 g/kg (p.o) per day of the extract for 28 consecutive days. Animal weight and fluid intake were recorded during the 28 days period. Terminally, kidneys, hearts, blood/sera were obtained for weight, haematological and biochemical markers of toxicity. Results show that the LD50 could not be determined after a maximum dose of 10 g/kg. Sub-acute treatment with the extract neither affected whole body weight nor organ-to-body weight ratios but significantly increased the fluid intake (P < 0.0001). Haematological parameters and the levels of ALT, AST, albumin and creatinine were not significantly altered. However, the concentration of total proteins was significantly increased in the treated group. In conclusion, the aqueous seed extract of P. americana is safe on sub-acute basis but extremely high doses may not be advisable.",
"title": "Acute and Sub-Acute Toxicological Assessment of the Aqueous Seed Extract of Persea Americana Mill (Lauraceae) in Rats"
},
{
"docid": "MED-4855",
"text": "OBJECTIVE: Meta-analysis of randomized controlled trials (RCTs)--of a hip powder of Rosa canina (rosehip) preparation for symptomatic treatment of osteoarthritis (OA), in order to estimate the empirical efficacy as a pain reducing compound. METHOD: RCTs from systematic searches were included if they explicitly stated that OA patients were randomized to either rosehip or placebo. The primary outcome was reduction in pain calculated as effect size (ES), defined as the standardized mean difference (SMD). As secondary analysis the number of responders to therapy was analyzed as Odds Ratios (OR), and expressed as the Number Needed to Treat (NNT). Restricted Maximum Likelihood (REML) methods were applied for the meta-analyses using mixed effects models. RESULTS: The three studies (287 patients and a median trial-duration of 3 months)--all supported by the manufacturer (Hyben-Vital International)--showed a reduction in pain scores by rosehip powder (145 patients) compared to placebo (142 patients): ES of 0.37 [95% confidence interval (CI): 0.13-0.60], P=0.002. Test for homogeneity seemed to support that the efficacy was consistent across trials (I(2)=0%). Thus it seems reasonable to assume that the three studies were measuring the same overall effect. It seemed twice as likely that a patient allocated to rosehip powder would respond to therapy, compared to placebo (OR=2.19; P=0.0009); corresponding to a NNT of six (95% CI: 4-13) patients. CONCLUSIONS: Although based on a sparse amount of data, the results of the present meta-analysis indicate that rosehip powder does reduce pain; accordingly it may be of interest as a nutraceutical, although its efficacy and safety need evaluation and independent replication in a future large-scale/long-term trial.",
"title": "Does the hip powder of Rosa canina (rosehip) reduce pain in osteoarthritis patients?--a meta-analysis of randomized controlled trials."
},
{
"docid": "MED-3868",
"text": "OBJECTIVE: To determine the effects of dietary consumption of milled flaxseed or flaxseed oil on glycemic control, n-3 fatty acid status, anthropometrics, and adipokines in individuals with type 2 diabetes. DESIGN: Thirty-four participants were randomized into a parallel, controlled trial. SUBJECTS: The participants were adults with type 2 diabetes (age 52.4 +/- 1.5 years, body mass index 32.4 +/- 1.0 kg/m(2), n = 17 men and 17 women). INTERVENTIONS: Participants consumed a selection of bakery products containing no flax (control group [CTL], n = 9), milled flaxseed (FXS, n = 13; 32 g/d), or flaxseed oil (FXO, n = 12; 13 g/d) daily for 12 weeks. The FXS and FXO groups received equivalent amounts of alpha-linolenic acid (ALA; 7.4 g/day). MEASURES OF OUTCOME: The primary outcome measures were fasting plasma hemoglobin A(1c), glucose, insulin, and phospholipid fatty acid composition. The secondary outcome measures were fasting circulating leptin and adiponectin, as well as body weight, body mass index, and waist circumference. Dietary intake assessment and calculations for homeostasis model assessment for insulin resistance and quantified insulin sensitivity check were also completed. RESULTS: The FXS and FXO groups had increases in plasma phospholipid n-3 fatty acids (ALA, eicosapentaenoic acid [EPA], or decosapentaenoic acid [DPA], but not docosahexaenoic acid), and the FXO group had more EPA and DPA in plasma phospholipids compared to the FXS group. All groups had similar caloric intakes; however, the CTL group experienced a 4% weight gain compared to baseline (p < 0.05), while both flax groups had constant body weights during the study period. All other parameters, including glycemic control, were unchanged by dietary treatment. CONCLUSIONS: Milled FXS and FXO intake does not affect glycemic control in adults with well-controlled type 2 diabetes. Possible prevention of weight gain by flax consumption warrants further investigation.",
"title": "Dietary milled flaxseed and flaxseed oil improve N-3 fatty acid status and do not affect glycemic control in individuals with well-controlled type ..."
},
{
"docid": "MED-5080",
"text": "Bioactivity-guided fractionation of black bean (Phaseolus vulgaris) seed coats was used to determine the chemical identity of bioactive constituents, which showed potent antiproliferative and antioxidative activities. Twenty-four compounds including 12 triterpenoids, 7 flavonoids, and 5 other phytochemicals were isolated using gradient solvent fractionation, silica gel and ODS columns, and semipreparative and preparative HPLC. Their chemical structures were identified using MS, NMR, and X-ray diffraction analysis. Antiproliferative activities of isolated compounds against Caco-2 human colon cancer cells, HepG2 human liver cancer cells, and MCF-7 human breast cancer cells were evaluated. Among the compounds isolated, compounds 1, 2, 6, 7, 8, 13, 14, 15, 16, 19, and 20 showed potent inhibitory activities against the proliferation of HepG2 cells, with EC50 values of 238.8 +/- 19.2, 120.6 +/- 7.3, 94.4 +/- 3.4, 98.9 +/- 3.3, 32.1 +/- 6.3, 306.4 +/- 131.3, 156.9 +/- 11.8, 410.3 +/- 17.4, 435.9 +/- 47.7, 202.3 +/- 42.9, and 779.3 +/- 37.4 microM, respectively. Compounds 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 14, 15, 19, and 20 showed potent antiproliferative activities against Caco-2 cell growth, with EC50 values of 179.9 +/- 16.9, 128.8 +/- 11.6, 197.8 +/- 4.2, 105.9 +/- 4.7, 13.9 +/- 2.8, 35.1 +/- 2.9, 31.2 +/- 0.5, 71.1 +/- 11.9, 40.8 +/- 4.1, 55.7 +/- 8.1, 299.8 +/- 17.3, 533.3 +/- 126.0, 291.2 +/- 1.0, and 717.2 +/- 104.8 microM, respectively. Compounds 5, 7, 8, 9, 11, 19, 20 showed potent antiproliferative activities against MCF-7 cell growth in a dose-dependent manner, with EC50 values of 129.4 +/- 9.0, 79.5 +/- 1.0, 140.1 +/- 31.8, 119.0 +/- 7.2, 84.6 +/- 1.7, 186.6 +/- 21.1, and 1308 +/- 69.9 microM, respectively. Six flavonoids (compounds 14-19) showed potent antioxidant activity. These results showed the phytochemical extracts of black bean seed coats have potent antioxidant and antiproliferative activities.",
"title": "Phytochemicals of black bean seed coats: isolation, structure elucidation, and their antiproliferative and antioxidative activities."
},
{
"docid": "MED-4830",
"text": "Muscle pain and weakness are frequent complaints in patients receiving 3-hydroxymethylglutaryl coenzymeA (HMG CoA) reductase inhibitors (statins). Many patients with myalgia have creatine kinase levels that are either normal or only marginally elevated, and no obvious structural defects have been reported in patients with myalgia only. To investigate further the mechanism that mediates statin-induced skeletal muscle damage, skeletal muscle biopsies from statin-treated and non-statin-treated patients were examined using both electron microscopy and biochemical approaches. The present paper reports clear evidence of skeletal muscle damage in statin-treated patients, despite their being asymptomatic. Though the degree of overall damage is slight, it has a characteristic pattern that includes breakdown of the T-tubular system and subsarcolemmal rupture. These characteristic structural abnormalities observed in the statin-treated patients were reproduced by extraction of cholesterol from skeletal muscle fibres in vitro. These findings support the hypothesis that statin-induced cholesterol lowering per se contributes to myocyte damage and suggest further that it is the specific lipid/protein organization of the skeletal muscle cell itself that renders it particularly vulnerable. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.",
"title": "Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia."
},
{
"docid": "MED-3658",
"text": "The triptans, selective serotonin 5-HT1B/1D agonists, are very effective acute migraine drugs. Soon, seven different triptans will be clinically available at 13 different oral doses, making evidence-based selection guidelines necessary. Triptan trials have similar designs, facilitating meta-analysis. We wished to provide an evidence-based foundation for using triptans in clinical practice, and to review the methodological issues surrounding triptan trials. We asked pharmaceutical companies and the principal investigators of company-independent trials for the 'raw patient data' of all double-blind, randomized, controlled, clinical trials with oral triptans in migraine. All data were cross-checked with published or presented data. We calculated summary estimates across studies for important efficacy and tolerability parameters, and compared these with those from direct, head-to-head, comparator trials. Out of 76 eligible clinical trials, 53 (12 not yet published) involving 24089 patients met the criteria for inclusion. Mean results (and 95% confidence intervals) for sumatriptan 100 mg, the first available and most widely prescribed oral triptan, are 59% (57-60) for 2 h headache response (improvement from moderate or severe to mild or no pain); 29% (27-30) for 2 h pain free (improvement to no pain); 20% (18-21) for sustained pain free (pain free by 2 h and no headache recurrence or use of rescue medication 2-24 h post-dose), and 67% (63-70) for consistency (response in at least two out of three treated attacks); placebo-subtracted proportions for patients with at least one adverse event (AE) are 13% (8-18), for at least one central nervous system AE 6% (3-9), and for at least one chest AE 1.9% (1.0-2.7). Compared with these data: rizatriptan 10 mg shows better efficacy and consistency, and similar tolerability; eletriptan 80 mg shows better efficacy, similar consistency, but lower tolerability; almotriptan 12.5 mg shows similar efficacy at 2 h but better sustained pain-free response, consistency, and tolerability; sumatriptan 25 mg, naratriptan 2.5 mg and eletriptan 20 mg show lower efficacy and better tolerability; zolmitriptan 2.5 mg and 5 mg, eletriptan 40 mg, and rizatriptan 5 mg show very similar results. The results of the 22 trials that directly compared triptans show the same overall pattern. We received no data on frovatriptan, but publicly available data suggest substantially lower efficacy. The major methodological issues involve the choice of the primary endpoint, consistency over multiple attacks, how to evaluate headache recurrence, use of placebo-subtracted proportions to control for across-study differences, and the difference between tolerability and safety. In addition, there are a number of methodological issues specific for direct comparator trials, including encapsulation and patient selection. At marketed doses, all oral triptans are effective and well tolerated. Differences among them are in general relatively small, but clinically relevant for individual patients. Rizatriptan 10 mg, eletriptan 80 mg and almotriptan 12.5 mg provide the highest likelihood of consistent success. Sumatriptan features the longest clinical experience and the widest range of formulations. All triptans are contra-indicated in the presence of cardiovascular disease.",
"title": "Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials."
},
{
"docid": "MED-1008",
"text": "INTRODUCTION: The use of peppermint oil in treating the irritable bowel syndrome has been studied with variable results probably due to the presence of patients affected by small intestinal bacterial overgrowth, lactose intolerance or celiac disease that may have symptoms similar to irritable bowel syndrome. AIM: The aim of the study was to test the effectiveness of enteric-coated peppermint oil in patients with irritable bowel syndrome in whom small intestinal bacterial overgrowth, lactose intolerance and celiac disease were excluded. METHODS: Fifty-seven patients with irritable bowel syndrome according to the Rome II criteria, with normal lactose and lactulose breath tests and negative antibody screening for celiac disease, were treated with peppermint oil (two enteric-coated capsules twice per day or placebo) for 4 weeks in a double blind study. The symptoms were assessed before therapy (T(0)), after the first 4 weeks of therapy (T(4)) and 4 weeks after the end of therapy (T(8)). The symptoms evaluated were: abdominal bloating, abdominal pain or discomfort, diarrhoea, constipation, feeling of incomplete evacuation, pain at defecation, passage of gas or mucus and urgency at defecation. For each symptom intensity and frequency from 0 to 4 were scored. The total irritable bowel syndrome symptoms score was also calculated as the mean value of the sum of the average of the intensity and frequency scores of each symptom. RESULTS: At T(4), 75% of the patients in the peppermint oil group showed a >50% reduction of basal (T(0)) total irritable bowel syndrome symptoms score compared with 38% in the placebo group (P<0.009). With peppermint oil at T(4) and at T(8) compared with T(0) a statistically significant reduction of the total irritable bowel syndrome symptoms score was found (T(0): 2.19+/-0.13, T(4): 1.07+/-0.10*, T(8): 1.60+/-0.10*, *P<0.01 compared with T(0), mean+/-S.E.M.), while no change was found with the placebo. CONCLUSION: A 4 weeks treatment with peppermint oil improves abdominal symptoms in patients with irritable bowel syndrome.",
"title": "Peppermint oil (Mintoil) in the treatment of irritable bowel syndrome: a prospective double blind placebo-controlled randomized trial."
},
{
"docid": "MED-4850",
"text": "Plants are rich natural sources of antioxidants in addition to other nutrients. Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food (LF) have been carried out. We have clarified the efficacy of LF in rheumatoid diseases as an example of a health problem where inflammation is one of the main concerns. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts, i.e. rich sources of carotenoids, vitamins C and E. The subjects eating LF showed highly increased levels of beta and alfa carotenes, lycopen and lutein in their sera. Also the increases of vitamin C and vitamin E (adjusted to cholesterol) were statistically significant. As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin, myricetin and kaempherol was much higher than in the omnivorous controls. The LF diet is rich in fibre, substrate of lignan production, and the urinary excretion of polyphenols like enterodiol and enterolactone as well as secoisolaricirecinol were much increased in subjects eating LF. The shift of fibromyalgic subjects to LF resulted in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health. The rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding. The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms. In conclusion the rheumatoid patients subjectively benefited from the vegan diet rich in antioxidants, lactobacilli and fibre, and this was also seen in objective measures.",
"title": "Antioxidants in vegan diet and rheumatic disorders."
},
{
"docid": "MED-2571",
"text": "Background Prospective, randomized, pilot clinical study was conducted to evaluate the beneficial effects of inositol hexaphosphate (IP6) + Inositol in breast cancer patients treated with adjuvant therapy. Patients and methods Patients with invasive ductal breast cancer where polychemotherapy was indicated were monitored in the period from 2005-2007. Fourteen patients in the same stage of ductal invasive breast cancer were involved in the study, divided in two randomized groups. One group was subjected to take IP6 + Inositol while the other group was taking placebo. In both groups of patients the same laboratory parameters were monitored. When the treatment was finished, all patients have filled questionnaires QLQ C30 and QLQ-BR23 to determine the quality of life. Results Patients receiving chemotherapy, along with IP6 + Inositol did not have cytopenia, drop in leukocyte and platelet counts. Red blood cell counts and tumor markers were unaltered in both groups. However, patients who took IP6 + Inositol had significantly better quality of life (p = 0.05) and functional status (p = 0.0003) and were able to perform their daily activities. Conclusion IP6 + Inositol as an adjunctive therapy is valuable help in ameliorating the side effects and preserving quality of life among the patients treated with chemotherapy.",
"title": "Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study"
},
{
"docid": "MED-5066",
"text": "Context Evidence is lacking that a dietary pattern high in vegetables, fruit, and fiber and low in total fat can influence breast cancer recurrence or survival. Objective To assess whether a major increase in vegetable, fruit, and fiber intake and a decrease in dietary fat intake reduces the risk of recurrent and new primary breast cancer and all-cause mortality among women with previously treated early stage breast cancer. Design, Setting, and Participants Multi-institutional randomized controlled trial of dietary change in 3088 women previously treated for early stage breast cancer who were 18 to 70 years old at diagnosis. Women were enrolled between 1995 and 2000 and followed up through June 1, 2006. Intervention The intervention group (n=1537) was randomly assigned to receive a telephone counseling program supplemented with cooking classes and newsletters that promoted daily targets of 5 vegetable servings plus 16 oz of vegetable juice; 3 fruit servings; 30 g of fiber; and 15% to 20% of energy intake from fat. The comparison group (n=1551) was provided with print materials describing the \"5-A-Day\" dietary guidelines. Main Outcome Measures Invasive breast cancer event (recurrence or new primary) or death from any cause. Results From comparable dietary patterns at baseline, a conservative imputation analysis showed that the intervention group achieved and maintained the following statistically significant differences vs the comparison group through 4 years: servings of vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake from fat, −13%. Plasma carotenoid concentrations validated changes in fruit and vegetable intake. Throughout the study, women in both groups received similar clinical care. Over the mean 7.3-year follow-up, 256 women in the intervention group (16.7%) vs 262 in the comparison group (16.9%) experienced an invasive breast cancer event (adjusted hazard ratio, 0.96; 95% confidence interval, 0.80–1.14; P=.63), and 155 intervention group women (10.1%) vs 160 comparison group women (10.3%) died (adjusted hazard ratio, 0.91; 95% confidence interval, 0.72–1.15; P=.43). No significant interactions were observed between diet group and baseline demographics, characteristics of the original tumor, baseline dietary pattern, or breast cancer treatment. Conclusion Among survivors of early stage breast cancer, adoption of a diet that was very high in vegetables, fruit, and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period. Trial Registration clinicaltrials.gov Identifier: NCT00003787",
"title": "Influence of a Diet Very High in Vegetables, Fruit, and Fiber and Low in Fat on Prognosis Following Treatment for Breast Cancer"
},
{
"docid": "MED-3503",
"text": "BACKGROUND: Dysmenorrhoea is a common gynaecological complaint consisting of painful cramps accompanying menstruation, which in the absence of any underlying abnormality is known as primary dysmenorrhoea. Research has shown that women with dysmenorrhoea have high levels of prostaglandins, hormones known to cause cramping abdominal pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs which act by blocking prostaglandin production. OBJECTIVES: The purpose of this review is to compare all nonsteroidal anti-inflammatory drugs used in the treatment of primary dysmenorrhoea with placebo, with paracetamol and with each other to evaluate their effectiveness and safety. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (11 April 2003), Cochrane Central Register of Controlled Trials (1st quarter 2003), MEDLINE (1966-April 2003), and EMBASE (1980 - Week 15 2003). Attempts were also made to identify trials from the National Research Register and the Clinical Trials Register. Citation lists of relevant publications, review articles, abstracts of major scientific meetings and included studies were also searched. SELECTION CRITERIA: All randomised controlled comparisons of NSAID therapies versus placebo, versus other NSAIDs or versus paracetamol when used to treat primary dysmenorrhoea. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for quality and extracted data, calculating odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Crossover trial data were presented in additional tables and other data were summarised descriptively. MAIN RESULTS: In women with dysmenorrhoea, NSAIDs were found significantly more effective for pain relief than placebo (OR 7.91, 95% CI 5.65 to 11.09), though overall adverse effects were also significantly more common (OR 1.52 95% CI 1.09 to 2.12). When NSAIDs were compared with each other or with paracetamol, there was little evidence of the superiority of any individual NSAID with regard to either efficacy or safety. However the available evidence had little power to detect such differences, as most individual comparisons were based on very few small trials, most of which were unsuitable for meta-analysis. REVIEWER'S CONCLUSIONS: NSAIDs are an effective treatment for dysmenorrhoea, though women using them need to be aware of the significant risk of adverse effects. There is insufficient evidence to determine which (if any) individual NSAID is the most safe and effective for the treatment of dysmenorrhoea.",
"title": "Nonsteroidal anti-inflammatory drugs for primary dysmenorrhoea."
},
{
"docid": "MED-3517",
"text": "Preliminary studies have shown that repeated nasal applications of capsaicin prevented the occurrence of cluster headache attacks. The present study was designed to verify the difference in efficacy of treatment with nasal capsaicin, depending on the side of application. Fifty-two patients affected by episodic form were divided into 2 groups, one receiving the treatment on the same side where the attacks occurred (ipsilateral side), the other on the controlateral side. Eighteen patients with a chronic form alternately received both ipsilateral and controlateral treatments. Seventy percent of the episodic patients, treated on the ipsilateral side, showed a marked amelioration whereas no improvement was noted in the patients treated on the contralateral side. The efficacy of ipsilateral treatment was emphasized by the results obtained in chronic patients. However, in these patients, the maximum period of amelioration lasted no more than 40 days. The difference between the effects of the 2 treatments (contralateral and ipsilateral) was statistically significant in both episodic and chronic sufferers. The efficacy of repeated nasal applications of capsaicin in cluster headache is congruent with previous reports on the therapeutic effect of capsaicin in other pain syndromes (post-herpetic neuralgia, diabetic neuropathy, trigeminal neuralgia) and supports the use of the drug to produce a selective analgesia.",
"title": "Preventative effect of repeated nasal applications of capsaicin in cluster headache."
},
{
"docid": "MED-1049",
"text": "Bowel movements provide vital information on how the body is functioning, and constipation among older adults is especially problematic. Although we do not like hearing the details of someone else's bowel movement, it is a function that nurses need to assess, support, and treat with the same attitude as when caring for patients with pain.",
"title": "Bowel movement: the sixth vital sign."
},
{
"docid": "MED-946",
"text": "BACKGROUND: Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder. The role of pharmacotherapy for IBS is limited and focused mainly on symptom control. OBJECTIVES: The objective of this systematic review was to evaluate the efficacy of bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. SEARCH STRATEGY: Computer assisted structured searches of MEDLINE, EMBASE, The Cochrane library, CINAHL and PsychInfo were conducted for the years 1966-2009. An updated search in April 2011 identified 10 studies which will be considered for inclusion in a future update of this review. SELECTION CRITERIA: Randomized controlled trials comparing bulking agents, antispasmodics or antidepressants with a placebo treatment in patients with irritable bowel syndrome aged over 12 years were considered for inclusion. Only studies published as full papers were included. Studies were not excluded on the basis of language. The primary outcome had to include improvement of abdominal pain, global assessment or symptom score. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from the selected studies. Risk Ratios (RR) and Standardized Mean Differences (SMD) with 95% confidence intervals (CI) were calculated. A proof of practice analysis was conducted including sub-group analyses for different types of bulking agents, spasmolytic agents or antidepressant medication. This was followed by a proof of principle analysis where only the studies with adequate allocation concealment were included. MAIN RESULTS: A total of 56 studies (3725 patients) were included in this review. These included 12 studies of bulking agents (621 patients), 29 of antispasmodics (2333 patients), and 15 of antidepressants (922 patients). The risk of bias was low for most items. However, selection bias is unclear for many of the included studies because the methods used for randomization and allocation concealment were not described. No beneficial effect for bulking agents over placebo was found for improvement of abdominal pain (4 studies; 186 patients; SMD 0.03; 95% CI -0.34 to 0.40; P = 0.87), global assessment (11 studies; 565 patients; RR 1.10; 95% CI 0.91 to 1.33; P = 0.32) or symptom score (3 studies; 126 patients SMD -0.00; 95% CI -0.43 to 0.43; P = 1.00). Subgroup analyses for insoluble and soluble fibres also showed no statistically significant benefit. Separate analysis of the studies with adequate concealment of allocation did not change these results. There was a beneficial effect for antispasmodics over placebo for improvement of abdominal pain (58% of antispasmodic patients improved compared to 46% of placebo; 13 studies; 1392 patients; RR 1.32; 95% CI 1.12 to 1.55; P < 0.001; NNT = 7), global assessment (57% of antispasmodic patients improved compared to 39% of placebo; 22 studies; 1983 patients; RR 1.49; 95% CI 1.25 to 1.77; P < 0.0001; NNT = 5) and symptom score (37% of antispasmodic patients improved compared to 22% of placebo; 4 studies; 586 patients; RR 1.86; 95% CI 1.26 to 2.76; P < 0.01; NNT = 3). Subgroup analyses for different types of antispasmodics found statistically significant benefits for cimteropium/ dicyclomine, peppermint oil, pinaverium and trimebutine. Separate analysis of the studies with adequate allocation concealment found a significant benefit for improvement of abdominal pain. There was a beneficial effect for antidepressants over placebo for improvement of abdominal pain (54% of antidepressants patients improved compared to 37% of placebo; 8 studies; 517 patients; RR 1.49; 95% CI 1.05 to 2.12; P = 0.03; NNT = 5), global assessment (59% of antidepressants patients improved compared to 39% of placebo; 11 studies; 750 patients; RR 1.57; 95% CI 1.23 to 2.00; P < 0.001; NNT = 4) and symptom score (53% of antidepressants patients improved compared to 26% of placebo; 3 studies; 159 patients; RR 1.99; 95% CI 1.32 to 2.99; P = 0.001; NNT = 4). Subgroup analyses showed a statistically significant benefit for selective serotonin releasing inhibitors (SSRIs) for improvement of global assessment and for tricyclic antidepressants (TCAs) for improvement of abdominal pain and symptom score. Separate analysis of studies with adequate allocation concealment found a significant benefit for improvement of symptom score and global assessment. Adverse events were not assessed as an outcome in this review. AUTHORS' CONCLUSIONS: There is no evidence that bulking agents are effective for treating IBS. There is evidence that antispasmodics are effective for the treatment of IBS. The individual subgroups which are effective include: cimetropium/dicyclomine, peppermint oil, pinaverium and trimebutine. There is good evidence that antidepressants are effective for the treatment of IBS. The subgroup analyses for SSRIs and TCAs are unequivocal and their effectiveness may depend on the individual patient. Future research should use rigorous methodology and valid outcome measures.",
"title": "Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome."
},
{
"docid": "MED-1012",
"text": "GOALS: The aim of this study was to assess the efficacy and safety of enteric-coated peppermint oil capsules compared with placebo for the treatment of active irritable bowel syndrome (IBS). BACKGROUND: IBS is a common disorder that is often encountered in clinical practice. Medical interventions are limited and the focus is on symptom control. STUDY: Randomized placebo-controlled trials with a minimum treatment duration of 2 weeks were considered for inclusion. Cross-over studies that provided outcome data before the first cross-over were included. A literature search upto February 2013 identified all applicable randomized-controlled trials. Study quality was evaluated using the Cochrane risk of bias tool. Outcomes included global improvement of IBS symptoms, improvement in abdominal pain, and adverse events. Outcomes were analyzed using an intention-to-treat approach. RESULTS: Nine studies that evaluated 726 patients were identified. The risk of bias was low for most of the factors assessed. Peppermint oil was found to be significantly superior to placebo for global improvement of IBS symptoms (5 studies, 392 patients, relative risk 2.23; 95% confidence interval, 1.78-2.81) and improvement in abdominal pain (5 studies, 357 patients, relative risk 2.14; 95% confidence interval, 1.64-2.79). Although peppermint oil patients were significantly more likely to experience an adverse event, such events were mild and transient in nature. The most commonly reported adverse event was heartburn. CONCLUSIONS: Peppermint oil is a safe and effective short-term treatment for IBS. Future studies should assess the long-term efficacy and safety of peppermint oil and its efficacy relative to other IBS treatments including antidepressants and antispasmodic drugs.",
"title": "Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis."
},
{
"docid": "MED-5009",
"text": "OBJECTIVE: To evaluate the efficacy of preparations with avocado-soybean unsaponifiables (ASUs) in osteoarthritis (OA) patients using meta-analysis on randomized controlled trials (RCTs). METHOD: RCTs from systematic searches were included if they explicitly stated that hip and/or knee OA patients were randomized to either ASU or placebo. The co-primary outcome was reduction in pain and Lequesne index, leading to effect size (ES), calculated as the standardized mean difference. As secondary analysis, the number of responders to therapy was analyzed as odds ratios (ORs). Restricted maximum likelihood methods were applied for the meta-analyses, using mixed effects models. RESULTS: Four trials--all supported by the manufacturer--were included, with 664 OA patients with either hip (41.4%) or knee (58.6%) OA allocated to either 300 mg ASU (336) or placebo (328). Average trial duration was 6 months (range: 3-12 months). Though based on heterogeneous results, the combined pain reduction favored ASU (I(2) = 83.5%, ES = 0.39 [95% confidence intervals: 0.01-0.76], P=0.04). Applying the Lequesne index also favored ASU (I(2) = 61.0%, ES = 0.45 [0.21-0.70], P = 0.0003). Secondarily, the number of responders following ASU compared to placebo (OR = 2.19, P = 0.007) corresponded to a number needed to treat of six (4-21) patients. CONCLUSIONS: Based on the available evidence, patients may be recommended to give ASU a chance for e.g., 3 months. Meta-analysis data support better chances of success in patients with knee OA than in those with hip OA.",
"title": "Symptomatic efficacy of avocado-soybean unsaponifiables (ASU) in osteoarthritis (OA) patients: a meta-analysis of randomized controlled trials."
},
{
"docid": "MED-4055",
"text": "Heterocyclic amines (HCAs) are formed when meat products such as beef, chicken, pork and fish are cooked at high temperatures. The most abundant HCA found in the human diet is 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP). PhIP causes mammary carcinomas in female rats and mice, and is associated with an increased risk of developing colon, breast, and prostate cancer in humans. PhIP is metabolized by cytochrome P-450s producing N-OH-PhIP. The N-OH-PhIP can be esterified by phase II enzymes forming an arylnitrenium ion that binds to DNA causing adducts. Furthermore, N-OH-PhIP may be reduced by cytochrome b5 reductase producing superoxide anions and hydroxyl radicals causing DNA strand breaks. Diallyl sulfide (DAS) has been shown to prevent cancer in several animal models, presumably by metabolic modulation. We hypothesize that PhIP produces reactive oxygen species causing DNA strand breaks and that DAS will inhibit the formation of PhIP induced DNA strand breaks. To test this hypothesis we treated normal breast epithelial (MCF-10A) cells with PhIP, DAS and a combination of PhIP and DAS. The detection of lipid peroxides was used as a surrogate for ROS. Lipid peroxides were detected using a PeroxiDetect kit (Sigma). PhIP increased the production of lipid peroxides and DAS decreased the PhIP-induced peroxidation by 47%. To determine if PhIP causes DNA strand breaks in MCF-10A cells, cells were treated for 3, 6, 9, and 24 h with PhIP (100 microM), DAS (100 microM) and a combination of PhIP (100 microM) and DAS (100 microM). DNA strand breaks were evaluated using the Comet assay. PhIP produced DNA strand breaks in a dose- and time-dependent fashion. We have shown that DAS inhibits PhIP-induced DNA strand breaks by inhibiting the production of reactive oxygen species. Therefore, we propose that DAS can prevent PhIP-induced breast cancer.",
"title": "Diallyl sulfide inhibits PhIP-induced DNA strand breaks in normal human breast epithelial cells."
},
{
"docid": "MED-3832",
"text": "Oestrogen is an important determinant of breast cancer risk. Oestrogen-mimicking plant compounds called phytoestrogens can bind to oestrogen receptors and exert weak oestrogenic effects. Despite this activity, epidemiological studies suggest that the incidence of breast cancer is lower in countries where the intake of phytoestrogens is high, implying that these compounds may reduce breast cancer risk, and possibly have an impact on survival. Isoflavones and lignans are the most common phytoestrogens in the diet. In this article, we present findings from human observational and intervention studies related to both isoflavone and lignan exposure and breast cancer risk and survival. In addition, the clinical implications of these findings are examined in the light of a growing dietary supplement market. An increasing number of breast cancer patients seek to take supplements together with their standard treatment in the hope that these will either prevent recurrence or treat their menopausal symptoms. Observational studies suggest a protective effect of isoflavones on breast cancer risk and the case may be similar for increasing lignan consumption although evidence so far is inconsistent. In contrast, short-term intervention studies suggest a possible stimulatory effect on breast tissue raising concerns of possible adverse effects in breast cancer patients. However, owing to the dearth of human studies investigating effects on breast cancer recurrence and survival the role of phytoestrogens remains unclear. So far, not enough clear evidence exists on which to base guidelines for clinical use, although raising patient awareness of the uncertain effect of phytoestrogens is recommended.",
"title": "Do phytoestrogens reduce the risk of breast cancer and breast cancer recurrence? What clinicians need to know."
},
{
"docid": "MED-2055",
"text": "BACKGROUND: Chronic diarrhea is the most common gastrointestinal symptom of intolerance of cow's milk among children. On the basis of a prior open study, we hypothesized that intolerance of cow's milk can also cause severe perianal lesions with pain on defecation and consequent constipation in young children. METHODS: We performed a double-blind, crossover study comparing cow's milk with soy milk in 65 children (age range, 11 to 72 months) with chronic constipation (defined as having one bowel movement every 3 to 15 days). All had been referred to a pediatric gastroenterology clinic and had previously been treated with laxatives without success; 49 had anal fissures and perianal erythema or edema. After 15 days of observation, the patients received cow's milk or soy milk for two weeks. After a one-week washout period, the feedings were reversed. A response was defined as eight or more bowel movements during a treatment period. RESULTS: Forty-four of the 65 children (68 percent) had a response while receiving soy milk. Anal fissures and pain with defecation resolved. None of the children who received cow's milk had a response. In all 44 children with a response, the response was confirmed with a double-blind challenge with cow's milk. Children with a response had a higher frequency of coexistent rhinitis, dermatitis, or bronchospasm than those with no response (11 of 44 children vs. 1 of 21, P=0.05); they were also more likely to have anal fissures and erythema or edema at base line (40 of 44 vs. 9 of 21, P<0.001), evidence of inflammation of the rectal mucosa on biopsy (26 of 44 vs. 5 of 21, P=0.008), and signs of hypersensitivity, such as specific IgE antibodies to cow's-milk antigens (31 of 44 vs. 4 of 21, P<0.001). CONCLUSIONS: In young children, chronic constipation can be a manifestation of intolerance of cow's milk.",
"title": "Intolerance of cow's milk and chronic constipation in children."
},
{
"docid": "MED-3447",
"text": "To investigate the chemopreventive effects of seaweed on breast cancer, we have been studying the relationship between iodine and breast cancer. We found earlier that the seaweed, wakame, showed a suppressive effect on the proliferation of DMBA (dimethylbenz(a)anthracene)-induced rat mammary tumors, possibly via apoptosis induction. In the present study, powdered mekabu was placed in distilled water, and left to stand for 24 h at 4 degrees C. The filtered supernatant was used as mekabu solution. It showed an extremely strong suppressive effect on rat mammary carcinogenesis when used in daily drinking water, without toxicity. In vitro, mekabu solution strongly induced apoptosis in 3 kinds of human breast cancer cells. These effects were stronger than those of a chemotherapeutic agent widely used to treat human breast cancer. Furthermore, no apoptosis induction was observed in normal human mammary cells. In Japan, mekabu is widely consumed as a safe, inexpensive food. Our results suggest that mekabu has potential for chemoprevention of human breast cancer.",
"title": "Seaweed prevents breast cancer?"
},
{
"docid": "MED-4536",
"text": "The cytotoxic effects of aqueous extract of Triphala, an ayurvedic formulation, were investigated on human breast cancer cell line (MCF-7) and a transplantable mouse thymic lymphoma (barcl-95). The viability of treated cells was found to decrease with the increasing concentrations of Triphala. On the other hand, treatment of normal breast epithelial cells, MCF-10 F, human peripheral blood mononuclear cells, mouse liver and spleen cells, with similar concentrations of Triphala did not affect their cytotoxicity significantly. The drug treatment was found to induce apoptosis in MCF-7 and barcl-95 cells in vitro as determined by annexin-V fluorescence and proportion of apoptotic cells was found dependent on Triphala concentration. MCF-7 cells treated with Triphala when subjected to single cell gel electrophoresis, revealed a pattern of DNA damage, characteristic of apoptosis. Studies on Triphala treated MCF-7 and barcl-95 cells showed significant increase in intracellular reactive oxygen species (ROS) in a concentration dependent manner. ROS increase was, however, found to be insignificant in MCF-10 F as well as in murine spleen and liver normal cells. In vivo, direct oral feeding of Triphala to mice (40 mg/kg body weight) transplanted with barcl-95 produced significant reduction in tumor growth as evaluated by tumor volume measurement. It was also found that apoptosis was significantly higher in the excised tumor tissue of Triphala fed mice as compared to the control, suggesting the involvement of apoptosis in tumor growth reduction. These results suggest that Triphala possessed ability to induce cytotoxicity in tumor cells but spared the normal cells. The differential effect of Triphala on normal and tumor cells seems to be related to its ability to evoke differential response in intracellular ROS generation. The differential response of normal and tumor cells to Triphala in vitro and the substantial regression of transplanted tumor in mice fed with Triphala points to its potential use as an anticancer drug for clinical treatment.",
"title": "Potential of traditional ayurvedic formulation, Triphala, as a novel anticancer drug."
},
{
"docid": "MED-948",
"text": "Sprouted vegetable seeds used as food have been implicated as sources of outbreaks of Salmonella and Escherichia coli O157:H7 infections. We profiled the microbiological quality of sprouts and seeds sold at retail shops in Seoul, Korea. Ninety samples of radish sprouts and mixed sprouts purchased at department stores, supermarkets, and traditional markets and 96 samples of radish, alfalfa, and turnip seeds purchased from online stores were analyzed to determine the number of total aerobic bacteria (TAB) and molds or yeasts (MY) and the incidence of Salmonella, E. coli O157:H7, and Enterobacter sakazakii. Significantly higher numbers of TAB (7.52 log CFU/g) and MY (7.36 log CFU/g) were present on mixed sprouts than on radish sprouts (6.97 and 6.50 CFU/g, respectively). Populations of TAB and MY on the sprouts were not significantly affected by location of purchase. Radish seeds contained TAB and MY populations of 4.08 and 2.42 log CFU/g, respectively, whereas populations of TAB were only 2.54 to 2.84 log CFU/g and populations of MY were 0.82 to 1.69 log CFU/g on alfalfa and turnip seeds, respectively. Salmonella and E. coli O157:H7 were not detected on any of the sprout and seed samples tested. E. sakazakii was not found on seeds, but 13.3% of the mixed sprout samples contained this potentially pathogenic bacterium.",
"title": "Microbiological examination of vegetable seed sprouts in Korea."
}
] |
189500
|
Karl Malone played for the Los Angeles Lakers.
|
[
{
"docid": "Karl_Malone",
"text": "Karl Anthony Malone ( born July 24 , 1963 ) is an American retired professional basketball player . Nicknamed `` The Mailman '' , Malone played the power forward position and spent his first 18 seasons ( 1985 -- 2003 ) in the National Basketball Association ( NBA ) with the Utah Jazz and formed a formidable duo with his teammate John Stockton . Malone also played one season for the Los Angeles Lakers . Malone was a two-time NBA Most Valuable Player , a 14-time NBA All-Star , and an 11-time member of the All-NBA first team . He scored the second most career points in NBA history ( 36,928 ) ( second behind Kareem Abdul-Jabbar ) , and holds the records for most free throws attempted and made , in addition to co-holding the record for the most first team All-NBA elections in history ( tied with Kobe Bryant and LeBron James ) . He is considered one of the best power forwards in NBA history . Malone played college basketball at Louisiana Tech University . In his three seasons with Louisiana Tech , he helped the Bulldogs basketball team to its first-ever NCAA tournament in 1984 and to first place in the Southland Conference in 1985 . The Utah Jazz drafted Malone in 1985 with the 13th overall pick in the first round . Malone appeared in the playoffs every season in his career , including the NBA Finals in 1997 and 1998 with the Jazz . He played his final season with the Los Angeles Lakers , with whom he played his third Finals in 2004 . However , Malone has the most career postseason losses of any NBA player ever , with 95 . Malone also competed with the United States national team in the Summer Olympic Games of 1992 and 1996 ; in both years he won gold medals . After retiring from the NBA , Malone joined the staff of the Louisiana Tech Bulldogs basketball team in 2007 and was inducted into the Naismith Memorial Basketball Hall of Fame in 2010 ( twice -- for his individual career , and as a member of the 1992 United States men 's Olympic basketball team ) .",
"title": ""
}
] |
[
{
"docid": "2003–04_Los_Angeles_Lakers_season",
"text": "The 2003 -- 04 NBA season was the Lakers ' 56th season in the NBA and 44th in the city of Los Angeles . During the offseason , the Lakers signed veteran free agents and former All-Stars Karl Malone and Gary Payton , who were recruited by Superstar center Shaquille O'Neal , plus re-signing free agent Horace Grant . Payton struggled with coach Phil Jackson 's triangle offense , which limited his ball-handling and post-up opportunities . The off-season is notable for seeing Superstar guard Kobe Bryant getting accused of sexual assault in Colorado , which proved to be an ongoing distraction during the season . The Lake Show started the season 18-3 . However , they ran into struggles when Malone went down with a knee injury in December , soon followed by ailments to Shaq and Kobe . The `` Big Four '' of O'Neal , Bryant , Malone , and Payton played in only 20 games together . Despite all of this , the injury-depleted Lakers still managed a 56 -- 26 record and entered the playoffs as the number 2 seed in the Western Conference . They defeated a Houston Rockets team featuring Steve Francis and a young Yao Ming in five games in the first round . The second round pitted the Lakers against the defending NBA champions the San Antonio Spurs , who defeated the Lakers in last year 's playoffs . Though the Spurs took the first two games , the Lakers won the next four games , including Derek Fisher 's miracle shot with 0.4 seconds left in Game 5 ( a 74 -- 73 Lakers victory ) and a Game 6 88 -- 76 victory at home to advance to the Western Conference Finals against the Kevin Garnett-led Minnesota Timberwolves . The Lakers managed to get through a tough Minnesota team , defeating them in six games to advance to the NBA Finals where they would meet the Detroit Pistons . Though the Lakers were heavily favored to win the title , the heavy-underdog Pistons proved too much for the Lakers as they easily went on to win the series in five games . Game 4 of the NBA Finals was Karl Malone 's final NBA game as injuries forced him to sit out the fifth and final game of the series . Grant also retired the following season . Game 5 was the last time that O'Neal and Bryant would play together as teammates as O'Neal would be traded to the Miami Heat following the season after an acrimonious relationship between the duo . Meanwhile , Fisher signed as a free agent with the Golden State Warriors and Payton , who only spent one season with the Lakers , and Rick Fox were both traded to the Boston Celtics . For head coach Phil Jackson , he left the team at the conclusion of the Finals and later wrote a book about the team 's season in which he voiced disdain for Kobe Bryant , calling him `` uncoachable '' . 2004 was the first time the Lakers had lost the NBA Finals under Jackson . He returned for the 2005-06 season and led the team to another NBA Finals appearance in 2008 , where they fell to the Boston Celtics in six games . However , the Lakers won two more titles the following two seasons before Jackson retired from coaching in 2011 .",
"title": ""
},
{
"docid": "2004–05_Los_Angeles_Lakers_season",
"text": "The 2004 -- 05 Los Angeles Lakers season was the 57th in the National Basketball Association ( NBA ) and 59th overall . The Los Angeles Lakers finished fifth in the Pacific Division . The season is best remembered as a tough one for the Lakers , starting with a crushing defeat to the Detroit Pistons in last year 's NBA Finals in five games despite being the heavily favored team to win the Finals , winning only 34 games , missing the playoffs for the first time in 11 years . The off-season marked changes for the Lakers , who lost several members from the famed 2004 team : Rick Fox and Gary Payton were traded to the Boston Celtics , but Fox would retire before the season instead of suiting up for Boston , Shaquille O'Neal was traded to the Miami Heat in exchange for Brian Grant , Caron Butler , and Lamar Odom after bad blood between himself and teammate Kobe Bryant culminated after the loss to the Detroit Pistons in the NBA Finals , Derek Fisher left for the Golden State Warriors , though he would return to the Lakers in 2007 and would eventually win two more championships in 2009 and 2010 , and Karl Malone retired in February 2005 after spending half of the season unsigned . The team hired Rudy Tomjanovich , who was well known for his tenure with the Houston Rockets , to be their new head coach for the upcoming season . But midseason , Tomjanovich once again resigned and Frank Hamblen took over for the rest of the season . Kobe Bryant , for the sixth time in his career , did not make the All-NBA First Team .",
"title": ""
},
{
"docid": "The_Last_Season:_A_Team_in_Search_of_Its_Soul",
"text": "The Last Season : A Team in Search of Its Soul is a book by the former American basketball coach Phil Jackson , originally published by the Penguin Press in 2004 . The book deals with the ups and downs of the Los Angeles Lakers ' 2003-04 season and offers Jackson 's insight into the team 's season that ended in a breakup but not a championship , despite boasting four potential future Hall of Famers : Shaquille O'Neal , Kobe Bryant , Karl Malone and Gary Payton .",
"title": ""
},
{
"docid": "1988_NBA_All-Star_Game",
"text": "The 38th National Basketball Association All-Star Game was played on February 7 , 1988 , at Chicago Stadium in Chicago . The East won the game 138-133 and Michael Jordan ( who scored a game-high 40 points ) was named the game 's MVP . The Eastern Conference team featured Jordan and Dominique Wilkins , who had faced each other the preceding night in the slam dunk contest , along with Boston Celtics trio Larry Bird , Danny Ainge and Kevin McHale , plus Patrick Ewing of the New York Knicks , Maurice Cheeks and Charles Barkley of the Philadelphia 76ers , Moses Malone of the Washington Bullets , Isiah Thomas of the Detroit Pistons , Doc Rivers of the Atlanta Hawks , and Brad Daugherty of the Cleveland Cavaliers . The Western Conference team was led by Magic Johnson of the Los Angeles Lakers , Clyde Drexler of the Portland Trail Blazers , the Utah Jazz 's power forward Karl Malone and the Houston Rockets ' center Akeem Olajuwon . Joining them were James Worthy and Kareem Abdul-Jabbar of the Lakers , Fat Lever and Alex English of the Denver Nuggets , Xavier McDaniel of the Seattle SuperSonics , Alvin Robertson of the San Antonio Spurs and Mark Aguirre and James Donaldson of the Dallas Mavericks . In this game , Abdul-Jabbar would become the all-time leading scorer in NBA All-Star Game history , a distinction he held for 15 years . The Eastern Conference was coached by Mike Fratello of the Atlanta Hawks , and the Western Conference by Pat Riley of the Lakers . The game was telecast by CBS Sports , with Dick Stockton and Billy Cunningham commentating , and Pat O'Brien and Lesley Visser reporting from the sidelines . On radio , ABC Radio broadcast their fourth consecutive All-Star game , with Lakers announcer Chick Hearn working alongside Celtics announcer Johnny Most , and the two trading roles on play-by-play and color analysis . ABC 's regular NBA announcer Fred Manfra served as a sideline reporter .",
"title": ""
},
{
"docid": "2001–02_Utah_Jazz_season",
"text": "The 2001 -- 02 NBA season was the Jazz 's 28th season in the National Basketball Association , and 23rd season in Salt Lake City , Utah . During the offseason , the Jazz signed free agent John Amaechi . John Stockton continued to set new standards with 15,000 career assists and 3,000 career steals , as Karl Malone scored his 34,000 th career point . However , the Jazz began to show their age as they played mediocre basketball all season finishing fourth in the Midwest Division with a 44 -- 38 record . The Jazz also beat the Los Angeles Lakers ' record of sixteen consecutive winning seasons , set between 1976 -- 77 and 1991 -- 92 . Malone was selected for the 2002 NBA All-Star Game , but did not play due to an injury . Rookie Andre Kirilenko was selected to the All-Rookie First Team . In the first round of the playoffs , they lost in four games to the Sacramento Kings . Following the season , Bryon Russell signed as a free agent with the Washington Wizards , Donyell Marshall signed with the Chicago Bulls and John Starks retired .",
"title": ""
},
{
"docid": "2001–02_Los_Angeles_Lakers_season",
"text": "The 2001 -- 02 NBA season was the Lakers ' 54th season in the National Basketball Association , and 42nd in the city of Los Angeles . During the offseason , the Lakers signed All-Star guard Mitch Richmond and free agent Samaki Walker , while acquiring Lindsey Hunter from the Milwaukee Bucks . The team got off to a fast start winning 16 of their first 17 games , and finished second in the Pacific Division with a 58 -- 24 record . Kobe Bryant and Shaquille O'Neal were both selected for the 2002 NBA All-Star Game in which Bryant won MVP honors , but O'Neal did not participate in the All-Star game due to an injury . After sweeping the Portland Trail Blazers 3 -- 0 in the first round of the playoffs , then defeating the San Antonio Spurs 4 -- 1 in the semifinals , the Lakers where pushed to the brink once more in the Western Conference Finals by their archrivals the Sacramento Kings , who they narrowly defeated in a deciding seventh game . They then went on to win the NBA Finals , defeating and sweeping the New Jersey Nets in four straight games for their second three-peat in franchise history , the first since 1952 -- 54 . Following the season , Richmond retired and Hunter was traded to the Toronto Raptors . This would be the third and final consecutive NBA Championship the Lakers won in the early 2000s , as in the next season , their quest for a fourth consecutive NBA Championship ended with a playoff elimination by the San Antonio Spurs in six games in the semifinals , who would then go on to win the NBA Finals that season and their second NBA Championship . Although the Lakers returned to the Finals in 2004 , the Lakers would lose to the Detroit Pistons in five games , despite being the heavy favorites to win and having former All-Stars and veterans Gary Payton and Karl Malone , leading to O'Neal 's departure from the Lakers amidst boiling points between the Lakers staff and management and Kobe Bryant , culminating in his trade to the Miami Heat , ending the early 2000s Lakers dynasty . The Lakers would not win another title until 2009 , in which they defeated the Orlando Magic in five games .",
"title": ""
},
{
"docid": "2002–03_Utah_Jazz_season",
"text": "The 2002 -- 03 NBA season was the Jazz 's 29th season in the National Basketball Association , and 24th season in Salt Lake City , Utah . During the offseason , the Jazz signed free agents Matt Harpring , Calbert Cheaney and Mark Jackson . The team finished third in the Midwest Division with a 47 -- 35 record , and qualified for the playoffs for the twentieth straight season . However , the Jazz once again failed to make it out of the first round , losing to the Sacramento Kings in five games . This season also marked the end of the Stockton and Malone era . John Stockton and Karl Malone were both given a long standing ovation after Game 4 at the Delta Center , and another one after Game 5 at the ARCO Arena . Following the season , Stockton retired while Malone signed as a free agent with the Los Angeles Lakers . Also following the season , Cheaney signed with the Golden State Warriors and Jackson was released . The Jazz would not return to the playoffs until 2007 .",
"title": ""
},
{
"docid": "2003–04_San_Antonio_Spurs_season",
"text": "The 2003-04 NBA season was the Spurs ' 28th season in the NBA , the 31st in San Antonio , and 37th season as a franchise . During the offseason , the Spurs acquired Hedo Turkoglu from the Sacramento Kings in a three-team trade and signed free agent Robert Horry . Despite the retirement of David Robinson , the Spurs still managed a 57 -- 25 record , finishing 3rd in the West . They swept the Memphis Grizzlies in four straight games in the first round , and though the Spurs took the first two games in a second round rematch against the team they eliminated in the previous season 's semifinals and eventual Western Conference champion Los Angeles Lakers , led by their `` big four '' of Karl Malone , Shaquille O'Neal , Kobe Bryant , and Gary Payton , the Lakers responded by taking the next four games to eliminate the defending champions . Following the season , Turkoglu signed as a free agent with the Orlando Magic .",
"title": ""
},
{
"docid": "List_of_National_Basketball_Association_franchise_career_scoring_leaders",
"text": "The National Basketball Association ( NBA ) is a professional men 's basketball league , consisting of 30 teams in North America ( 29 in the United States and one in Canada ) . The NBA was founded in New York City on June 6 , 1946 , as the Basketball Association of America ( BAA ) . It adopted the name National Basketball Association at the start of the 1949 -- 50 season when it merged with the National Basketball League ( NBL ) . The NBA is an active member of USA Basketball , which is recognized by the International Basketball Federation ( FIBA ) as the National Governing Body ( NGB ) for basketball in the country . The league is considered to be one of the four major professional sports leagues of North America . There have been 15 defunct franchises in NBA history . In basketball , points are the sum of the score accumulated through free throw or field goal . The NBA introduced three-point field goals in the 1979 -- 80 season as a bonus for field goals made from a longer distance . Karl Malone scored 36,374 points with the Utah Jazz , the most points by a player for a single franchise . Kareem Abdul-Jabbar , the NBA 's all-time leading scorer , is the Milwaukee Bucks leader with 14,211 points . He scored more points with the Los Angeles Lakers ( 24,176 ) , where he ranks third in Lakers ' history . Kobe Bryant leads the Lakers , scoring the most points in the NBA while playing for only one team in an entire career . Dirk Nowitzki of the Dallas Mavericks is second behind Bryant in scoring while playing for only one team . Statistics accurate as of the conclusion of the regular 2016 -- 17 NBA season .",
"title": ""
},
{
"docid": "Los_Angeles_Lakers",
"text": "The Los Angeles Lakers are an American professional basketball team based in Los Angeles . The Lakers compete in the National Basketball Association ( NBA ) , as a member of the league 's Western Conference Pacific Division . The Lakers play their home games at Staples Center , an arena shared with the NBA 's Los Angeles Clippers , the Los Angeles Sparks of the Women 's National Basketball Association , and the Los Angeles Kings of the National Hockey League . The Lakers are one of the most successful teams in the history of the NBA , and have won 16 NBA championships , their last being in 2010 . As of 2015 , the Lakers are the second most valuable franchise in the NBA according to Forbes , having an estimated value of $ 2.7 billion . The franchise began with the 1947 purchase of a disbanded team , the Detroit Gems of the National Basketball League ( NBL ) . The new team began playing in Minneapolis , calling themselves the Minneapolis Lakers in honor of the state 's nickname , `` Land of 10,000 Lakes '' . Initially a member of the NBL , the Lakers won the 1948 NBL championship before joining the rival Basketball Association of America and winning five of the next six BAA and NBA championships in Minneapolis after the NBA formed in 1949 . The team was propelled by center George Mikan , who is described by the NBA 's official website as the league 's `` first superstar '' . After struggling financially in the late 1950s following Mikan 's retirement , they relocated to Los Angeles before the 1960 -- 61 season . Led by Hall of Famers Elgin Baylor and Jerry West , Los Angeles made the NBA Finals six times in the 1960s , but lost each series to the Boston Celtics , beginning their long and storied rivalry . In 1968 , the Lakers acquired four-time NBA Most Valuable Player ( MVP ) Wilt Chamberlain to play center , and after losing in the Finals in 1969 and 1970 , they won their sixth NBA title -- and first in Los Angeles -- in 1972 , led by new head coach Bill Sharman . After the retirement of West and Chamberlain , the team acquired another center , Kareem Abdul-Jabbar , who had won multiple MVP awards , but was unable to make the Finals in the late 1970s . The 1980s Lakers were nicknamed `` Showtime '' due to their Magic Johnson-led fast break-offense , and won five championships in a 9-year span , including their first ever Finals championship against the Celtics in 1985 . This team featured Hall of Famers in Johnson , Abdul-Jabbar , and James Worthy , and a Hall of Fame coach , Pat Riley . After Abdul-Jabbar and Johnson 's retirement , the team struggled in the early 1990s before acquiring Shaquille O'Neal and Kobe Bryant in 1996 . Led by O'Neal , Bryant , and another Hall of Fame coach , Phil Jackson , Los Angeles won three consecutive titles between 2000 to 2002 , securing the franchise its second `` three-peat '' . After losing both the 2004 and 2008 NBA Finals , the Lakers won two more championships by defeating the Orlando Magic in 2009 and Boston in 2010 . The Lakers hold the record for NBA 's longest winning streak , 33 straight games , set during the 1971 -- 72 season . 21 Hall of Famers have played for Los Angeles , while four have coached the team . Four Lakers -- Abdul-Jabbar , Johnson , O'Neal , and Bryant -- have won the NBA MVP Award for a total of eight awards .",
"title": ""
},
{
"docid": "Los_Angeles_Lakers_accomplishments_and_records",
"text": "This page details the all-time statistics , records , and other achievements pertaining to the Los Angeles Lakers . The Los Angeles Lakers are an American professional basketball team currently playing in the National Basketball Association .",
"title": ""
},
{
"docid": "1982–83_Los_Angeles_Lakers_season",
"text": "In the 1982-83 NBA season , the Lakers were attempting to become the first team since the Boston Celtics in 1969 to repeat as NBA Champions . However , on April 10 , 1983 , rookie James Worthy injured his leg while attempting a putback in a home loss against Phoenix , ending his rookie season . Even without Worthy for the playoffs , the Lakers did make it to the NBA Finals , only to be swept in four games by the Julius Erving and Moses Malone led Philadelphia 76ers .",
"title": ""
},
{
"docid": "1987_NBA_All-Star_Game",
"text": "The 37th National Basketball Association All-Star Game was played on February 8 , 1987 , at Seattle 's Kingdome . Seattle SuperSonics power forward Tom Chambers was the game 's MVP . The Eastern Conference team consisted of the Washington Bullets ' Moses Malone and Jeff Malone , the Philadelphia 76ers ' Julius Erving , Maurice Cheeks and Charles Barkley , the Boston Celtics ' Larry Bird , Robert Parish and Kevin McHale , the Detroit Pistons ' Isiah Thomas and Bill Laimbeer , the Atlanta Hawks ' Dominique Wilkins and the Chicago Bulls ' Michael Jordan . In addition to game MVP Tom Chambers , the Western Conference team featured the Los Angeles Lakers ' Magic Johnson , James Worthy and Kareem Abdul-Jabbar , the Golden State Warriors ' Sleepy Floyd and Joe Barry Carroll , the Dallas Mavericks ' Rolando Blackman and Mark Aguirre , the San Antonio Spurs ' Alvin Robertson , the Phoenix Suns ' Walter Davis , the Denver Nuggets ' Alex English and the Houston Rockets ' Akeem Olajuwon . Houston 's Ralph Sampson was selected but unable to play due to injury . The coach of the Eastern team was Boston 's K.C. Jones . The coach of the Western team was the Lakers ' Pat Riley .",
"title": ""
},
{
"docid": "2011_NBA_All-Star_Game",
"text": "The 2011 NBA All-Star Game was an exhibition basketball game that was played on February 20 , 2011 at Staples Center in Los Angeles , California , home of the Los Angeles Clippers and the Los Angeles Lakers . This game was the 60th edition of the National Basketball Association ( NBA ) All-Star Game and was played during the 2010 -- 11 NBA season . The Los Angeles Clippers and Los Angeles Lakers served as the hosts . The Clippers and Lakers were both awarded the All-Star Game in an announcement by commissioner David Stern on June 9 , 2009 . This was the second time that the Staples Center had hosted the All-Star Game ; the arena had previously hosted the event in 2004 . This will be the fifth time that Los Angeles had hosted the All-Star Game ; before Staples Center opened in 1999 , the city had previously hosted the event in 1963 , 1972 , and 1983 . Rihanna , Kanye West and Drake were the halftime performers , while Keri Hilson , Lenny Kravitz and Bruno Mars were the entertainment for pre-show festivities .",
"title": ""
},
{
"docid": "1983_NBA_Playoffs",
"text": "The 1983 NBA Playoffs was the postseason tournament of the National Basketball Association 's 1982 -- 83 season . This was the final postseason using the 12-team format , before the NBA expanded the postseason to 16 teams the next season . The tournament concluded with the Eastern Conference champion Philadelphia 76ers defeating the Western Conference champion Los Angeles Lakers 4 games to 0 in the NBA Finals . Moses Malone was named NBA Finals MVP . Malone made a famous prediction about the Sixers ' chances prior to the playoffs , saying `` Fo ' , fo ' , fo ' '' -- predicting that the Sixers would win 4 games in each of the three series they would play . They nearly accomplished a sweep of all three rounds , only losing one game ( to Milwaukee in the Eastern Conference Finals ) en route to the championship . The Sixers set a record for highest winning percentage in the playoffs that was not broken until the Lakers went 15 -- 1 in 2001 . The Lakers ' mark , however , came after the expansion to the current 16-team , four-round playoff format , which was first implemented in the 1984 playoffs , while the Sixers avoided the first round by virtue of their top seeding . It was the third time in four years that the Lakers and 76ers had met in the NBA Finals , with the Lakers winning the previous two series . After missing the playoffs the previous year , the Blazers began a string of 21 straight playoff appearances in 1983 lasting until 2003 . They made the playoffs 25 out of 26 years from their title-winning season of 1977 -- 2003 . The record was just one season shy of the 22-year playoff run set by the Syracuse Nationals/Philadelphia 76ers from 1950 -- 1971 . The Celtics were swept out of the playoffs for the first time in team history , losing 4 -- 0 to the Bucks in the second round . This was the Spurs ' last appearance in the Conference Finals until 1995 . However , for players such as George Gervin and Artis Gilmore , the 6-game loss to the Lakers was the last chance they got at reaching the NBA Finals , let alone an NBA Championship ( Gilmore did return to the conference finals with the Celtics in 1988 , but played sparingly ) .",
"title": ""
},
{
"docid": "Lakers–Clippers_rivalry",
"text": "The Los Angeles Lakers and Los Angeles Clippers are rival teams in the National Basketball Association ( NBA ) . The two Pacific Division teams both play their home games at Staples Center in Los Angeles , inspiring their matchups to sometimes be called the `` Hallway Series '' . The Lakers relocated from Minneapolis in 1960 , while the Clippers moved from San Diego in 1984 . Los Angeles fans have historically favored the Lakers . But the Clippers have sold out every home game at Staples Center since Feb. 2011 and entered the 2016-17 season with the sixth-longest active sellout streak in the NBA . The Lakers have won 11 of their 16 NBA championships since moving to Los Angeles . Meanwhile , the Clippers have made the playoffs only nine times since 1984 and were long considered the laughingstock of the NBA ; in the history of the franchise , they have never advanced past the second round of the playoffs . Some contended that the term rivalry was inaccurate until the Clippers became more successful . For the first time in 20 years , the Clippers won the season series against the Lakers in 2012 -- 13 . This was the first of five straight season series victories for the Clippers , which included season sweeps in both 2014-15 and 2015-16 . With the Clippers ' 3-1 series win in 2016-17 , the Lakers have now won the season series just four times in the past 13 seasons , with five Clippers wins , four Lakers wins , and four ties . The Lakers hold a 99 -- 47 advantage in the all-time series against the Clippers . The two teams have never met in the playoffs .",
"title": ""
},
{
"docid": "Los_Angeles_Clippers",
"text": "The Los Angeles Clippers , often abbreviated as the LA Clippers , are an American men 's professional basketball team based in Los Angeles . The Clippers compete in the National Basketball Association ( NBA ) as a member of the league 's Western Conference Pacific Division . The Clippers play their home games at Staples Center in downtown Los Angeles , an arena shared with the Los Angeles Lakers of the NBA , the Los Angeles Sparks of the Women 's National Basketball Association ( WNBA ) , and the Los Angeles Kings of the National Hockey League ( NHL ) . The franchise was founded in 1970 as the Buffalo Braves , one of three expansion teams to join the NBA that year . The Braves moved from Buffalo , New York to San Diego , California in 1978 and became known as the San Diego Clippers . In 1984 , the Clippers moved to Los Angeles . Through much of its history , the franchise failed to see significant regular season or playoff success . The Clippers were frequently seen as an example of a perennial loser in American professional sports , drawing unfavorable comparisons to the historically successful Lakers , with whom they have shared a market since 1984 and an arena since 1999 . The Clippers ' fortunes turned in the early 2010s with the acquisition of core players Blake Griffin , DeAndre Jordan , and Chris Paul . In 2013 , the franchise won its first division title , as the team made the playoffs for the ninth time in franchise history and the third time in the previous eight seasons . They also added to their budding rivalry with the Lakers , as they finished with a better record than the Lakers for the fifth time and won the season series for the second time since moving to Los Angeles in 1984 , this time in a sweep . They repeated as division champions in 2014 .",
"title": ""
},
{
"docid": "Lakers–Pistons_rivalry",
"text": "The Lakers -- Pistons rivalry is an American professional basketball rivalry between the Los Angeles Lakers and Detroit Pistons . This rivalry , which was showcased 3 times in the NBA Finals ( 1988 , 1989 , 2004 ) , pitted the high-flying , All-Star filled Lakers teams against the blue collar , team-first oriented Pistons squads . Despite playing the role of underdog in all 3 of their final round meetings with Los Angeles , Detroit enjoyed significant success against the Lakers , claiming the NBA title against them twice .",
"title": ""
},
{
"docid": "List_of_Los_Angeles_Lakers_seasons",
"text": "The Los Angeles Lakers are a professional basketball team based in Los Angeles , California that competes in the National Basketball Association ( NBA ) , which was formerly called the Basketball Association of America ( BAA ) . Since 1999 , the Lakers have played their home games at Staples Center . The Lakers ' franchise was founded in 1947 in Minneapolis , Minnesota . The first owners purchased the disbanded Gems from Detroit , Michigan , then renamed and moved the team . It was in Minneapolis where the Lakers received their official title from Minnesota 's nickname , Land of 10,000 Lakes . The Lakers won five championships before relocating to Los Angeles for the 1960 -- 61 NBA season . The Lakers went on to lose all of their eight appearances in the NBA Finals in the 1960s , despite the presence of Elgin Baylor and Jerry West . In , the Lakers compiled a 33-game winning streak , the longest streak in U.S. professional team sports , and won their sixth title , under coach Bill Sharman . The Lakers ' popularity soared in the 1980s when they won five additional championships during a nine-year span with the help of Hall of Famers Magic Johnson , Kareem Abdul-Jabbar , James Worthy and coach Pat Riley , the franchise 's all-time leader in both regular season and playoff games coached and wins . Two of those championships during that span were against their arch-rivals , the Boston Celtics . With the help of Shaquille O'Neal , Kobe Bryant , and Hall of Fame coach Phil Jackson , the Lakers played in seven NBA Finals between 2000 and 2010 , winning three of them consecutively from 2000 to 2002 , losing the next two in 2004 and 2008 , and winning in 2009 and 2010 ; the last three appearances were without O'Neal . The Lakers hold records for having ( at the end of the 2014 -- 15 NBA season ) the most wins ( 3,125 ) , the highest winning percentage ( .620 ) , the most NBA Finals appearances ( 31 ) of any NBA franchise , second-fewest non-playoff seasons with seven and are second NBA championships with 16 , behind the Boston Celtics ' 17 .",
"title": ""
},
{
"docid": "Los_Angeles_Lakers_all-time_roster",
"text": "The Los Angeles Lakers are an American professional basketball team based in Los Angeles , California . They play in the Pacific Division of the Western Conference in the National Basketball Association ( NBA ) . The Lakers ' franchise was founded in 1947 in Detroit , Michigan before moving to Minneapolis , Minnesota , where the team got its official title from the state 's nickname , `` Land of 10,000 Lakes '' . The Minneapolis Lakers won five NBA Finals before relocating to Los Angeles in the 1960 -- 61 NBA season , becoming the first West Coast team in league history . In the 1960s , the Lakers reached the NBA Finals six times , but lost every series to the Boston Celtics , beginning their long and storied rivalry . In 1972 , with future Hall of Famers Wilt Chamberlain , Gail Goodrich , and Jerry West , the Lakers compiled a 33-game winning streak , the longest streak in U.S. professional team sports , and won their sixth title under coach Bill Sharman . The Lakers ' popularity soared in the 1980s when they won five additional championships during a nine-year span with the help of Hall of Famers Magic Johnson , Kareem Abdul-Jabbar , James Worthy and coach Pat Riley , the franchise 's all-time leader in both regular season and playoff games coached and wins . Two of those championships during that span were against their arch-rivals , the Boston Celtics . With the team of Shaquille O'Neal , Kobe Bryant , Toby Tincher , and Hall of Fame coach Phil Jackson , the Lakers played in four of the first five NBA Finals of the 21st century ; winning three consecutively from 2000 to 2002 , and losing the fourth in 2004 . The Lakers would then conclude the decade with three straight Finals appearances ; losing to the Boston Celtics in 2008 but then prevailing with back-to-back championships against the Orlando Magic in 2009 and the Boston Celtics in 2010 . The 2010 championship marks the 16th NBA championship in Lakers franchise history . There have been 339 past and current players who has appeared in at least one game for the Lakers franchise . __ NOTOC __",
"title": ""
},
{
"docid": "List_of_Los_Angeles_Lakers_head_coaches",
"text": "The Los Angeles Lakers are an American professional basketball team based in Los Angeles , California , formerly known as the Minneapolis Lakers from 1948 to 1960 . They play in the Pacific Division of the Western Conference in the National Basketball Association ( NBA ) The Lakers have played their home games at the Staples Center since 1999 . The franchise took its official name from Minnesota 's nickname , the Land of 10,000 Lakes . At the time the name was revealed , the Lakers were in Minneapolis . In their franchise history , the team has only missed the NBA playoffs five times . According to Forbes magazine , the Lakers are the second most valuable basketball franchise in the NBA , valued at approximately US$ 1 billion , surpassed only by the New York Knicks . The Lakers are majority-owned by Jerry Buss 's family trust , while Mitch Kupchak is the general manager . There have been 24 head coaches for the Lakers since joining the NBA . The franchise 's first head coach while in the NBA was John Kundla , who coached for 11 seasons with the Lakers . The Lakers won four additional NBA championships in the next five years under Kundla . Phil Jackson is the franchise 's all-time leader for the most regular-season games coached ( 820 ) , most playoff games coached ( 181 ) , most regular-season game wins ( 553 ) , and most playoff wins ( 118 ) . The Lakers have won 16 championships ; five with Kundla , five with Phil Jackson , four with Riley , one with Bill Sharman , and one with Paul Westhead . With the Lakers , Sharman , Riley , and Del Harris have won the NBA Coach of the Year Award , in , , and respectively . Kundla , Bill Sharman , Riley and Jackson have been inducted into the Basketball Hall of Fame as a coach . George Mikan , Jim Pollard , Jerry West , Riley , Magic Johnson , Kurt Rambis , Byron Scott and Luke Walton have all played and head coached for the Lakers .",
"title": ""
},
{
"docid": "List_of_Los_Angeles_Lakers_first_and_second_round_draft_picks",
"text": "The Los Angeles Lakers joined the National Basketball Association ( NBA ) in the 1948 -- 49 BAA season as the Minneapolis Lakers , but moved to Los Angeles for the 1959 -- 60 NBA season , where they have been located ever since . They play their home games at Staples Center , which they share with fellow NBA team the Los Angeles Clippers . The Minneapolis Lakers took its official name from Minnesota 's nickname , Land of 10,000 Lakes . The NBA started as the Basketball Association of America ( BAA ) . To help teams acquire local players , territorial picks were instituted from its inception in 1950 until 1965 . Territorial picks were used as a type of special draft choice used in the NBA Draft . Prior to the league 's draft , a team could forfeit its first round draft pick and select a player from within 50 mi . Territorial picks were then eliminated when the draft was revamped in 1966 . Before the 1989 NBA draft , the draft had more than two rounds . After 1989 , the NBA agreed with the National Basketball Players ' Association to limit drafts to two rounds . Teams can also trade their picks , so some years a team could have more than or less than two picks . The Lakers selected Chuck Hanger with their first pick , ninth overall in the 1948 BAA draft . The Lakers got their first overall draft pick in 1958 by choosing Elgin Baylor , who went on to be selected as the only NBA Rookie of the Year to be on the Lakers . The Lakers also drafted Magic Johnson in 1979 with their second first overall pick , who was rated the greatest NBA point guard of all time by ESPN in 2007 . The Lakers had no first round draft picks in 1967 , 1976 , 1978 , 1980 , 2008 , 2010 , 2011 , 2012 and 2013 . The Lakers had no first or second round draft picks from 1983 , 1987 , and 2001 . Throughout the years , the Lakers had traded away some of their picks as well as traded for other teams ' picks . As a result of the various trades , the Los Angeles Lakers had five first and second round picks in 1979 .",
"title": ""
},
{
"docid": "Spectrum_SportsNet_(Los_Angeles)",
"text": "Spectrum SportsNet and Spectrum Deportes , formerly Time Warner Cable SportsNet and Time Warner Cable Deportes , ( abbreviated as TWC SportsNet and TWC Deportes ) are American regional sports cable and satellite television networks that are owned by Charter Communications through its acquisition of Time Warner Cable in May 2016 , with the Los Angeles Lakers maintaining editorial control over the content , including team-assigned reporters and anchors , as well as team-related programming . The networks are based near the Lakers ' team headquarters in the Los Angeles suburb of El Segundo , California . Spectrum SportsNet -- which broadcasts in English -- and Spectrum Deportes -- which is the first U.S. regional sports network with a 24-hour Spanish feed -- launched at 7:00 p.m. Pacific Time on October 1 , 2012 . Spectrum SportsNet and Spectrum Deportes serve the Los Angeles and San Diego metropolitan areas , the Coachella Valley , the Central Coast of California , Las Vegas , and Hawaii . Lakers game broadcasts serve as the centerpiece of both networks . Spectrum SportsNet and Spectrum Deportes have been the exclusive home of all Lakers games that are not televised nationally since the 2012 -- 13 NBA season . Other sports events aired on the networks include Los Angeles Galaxy soccer and Los Angeles Sparks basketball games . Game broadcasts are carried in high definition in both English and Spanish . A Korean language audio track is also provided via the second audio program function available on most television sets and cable receiver boxes ; as a result , Spectrum SportsNet holds the distinction of being the first English-language television network to offer Asian-language play-by-play audio of sporting events .",
"title": ""
},
{
"docid": "1997–98_Utah_Jazz_season",
"text": "The 1997 -- 98 NBA season was the Jazz 's 24th season in the National Basketball Association , and 19th season in Salt Lake City , Utah . Without John Stockton for the first 18 games due to a knee injury , the Jazz slowly got off to an 11 -- 7 start to the season . However , Stockton would eventually return as the Jazz won 31 of their final 36 games after the All-Star break , and finished first place in the Midwest Division with a 62 -- 20 record . The Jazz 's top scorer Karl Malone , who averaged 27.0 points per game , was part of a Jazz offense that had two other players , Stockton and Jeff Hornacek , averaging double-digits in points . Malone was the only member of the team to play in the 1998 NBA All-Star Game . In the first round of the playoffs , the Jazz trailed 2 -- 1 to the 8th-seeded Houston Rockets . However , they won the series in five games . In the semifinals , they defeated the San Antonio Spurs in five games . After that , the Jazz swept the Los Angeles Lakers in the Western Conference Finals in four straight games to advance to the NBA Finals for the second consecutive year , and once again , met the Chicago Bulls in a rematch of last year 's NBA Finals , in which they lost to the Bulls in six games . In the Finals , just like last year 's NBA Finals , they lost in six games to the Chicago Bulls . Following the season , Antoine Carr signed as a free agent with the Houston Rockets , and Chris Morris signed with the Phoenix Suns . The team 's season roster is featured in the video games NBA 2K16 and NBA 2K17 .",
"title": ""
},
{
"docid": "1972_NBA_Finals",
"text": "The 1972 NBA Finals was the championship series played at the conclusion of the 1971 -- 72 National Basketball Association ( NBA ) season . The Western Conference champion Los Angeles Lakers defeated the Eastern Conference champion New York Knicks in five games . The Los Angeles Lakers got their first NBA championship since the Lakers moved to Los Angeles from Minneapolis . This season 's edition of the Los Angeles Lakers had won an NBA-record 69 regular season games , including 33 wins in a row . They were led by Wilt Chamberlain , the NBA 's top rebounder that season . Guards Gail Goodrich and Jerry West were each among the NBA 's top ten scorers that season , spearheading the NBA 's top offense at 121 points per game . West also led the NBA in assists . The Lakers as a team led all NBA teams in rebounds and assists that season . Los Angeles had swept a solid 57-win Chicago Bulls team in the playoff 's opening round , then defeated the defending champion Milwaukee Bucks ( record of 63-19 ) in six games to win the Western Conference . That historic series had matched Chamberlain against Kareem Abdul-Jabbar , and West against Oscar Robertson . Having defeated tough Milwaukee , 48-win New York figured to be an easy formality for the Lakers . New York was a top defensive team that allowed just 98.2 points per game and made 47 % of their shots as a team . They had defeated the 38-win Baltimore Bullets and then upset the 56-win Boston Celtics to win the Eastern Conference final .",
"title": ""
},
{
"docid": "1984_NBA_Finals",
"text": "The 1984 NBA Finals , also known as Showdown ' 84 , was the championship round of the 1983-84 NBA season . In 1984 , the Boston Celtics defeated the Los Angeles Lakers in a seven-game Finals , winning Game 7 111-102 . Larry Bird averaged 27 points and 14 rebounds a game during the series , earning the Finals Most Valuable Player ( MVP ) . Bird was also named the league regular season MVP for that year . This series was the long-awaited rematch of the Los Angeles Lakers and Boston Celtics after their rivalry was revived in 1979 with the Magic Johnson-Larry Bird pair entering the league . After the Lakers won Game 1 , a crucial steal in Game 2 led to a tie game and the Celtics were able to win in overtime to tie the series . The Lakers won Game 3 easily and almost won Game 4 , but were again thwarted . Now tied 2-2 , the Lakers and Celtics each held serve at their home court to send the series to Boston for Game 7 . Game 5 was a classic , with Bird coming up with a huge game in one of the ( literally ) hottest games ever ( 97 ° F ) in the non-air conditioned Boston Garden . Game 7 was also contested in hot temperatures that hovered around 91 ° F . The score was close but the contest eventually went to the Celtics . Cedric Maxwell scored 24 points against the Los Angeles Lakers in the decisive Game 7 victory . Los Angeles won all three games played on Sunday afternoons . Boston won the games played on Tuesday night , Wednesday night , Thursday night , and Friday night . The Series schedule was an odd schedule , due entirely to the whims of television . Game One was played on a Sunday afternoon in Boston , about 36 hours after the Lakers had eliminated the Phoenix Suns in the Western Finals . The teams then had three plus days off , not playing until Thursday night . Then , after Game 3 on Sunday afternoon in Los Angeles , the teams had two plus days off , not playing again until Wednesday night . That in turn started a wearying back-and-forth across the country ... Wednesday night at LA , Friday night at Boston , Sunday afternoon at LA , and Tuesday night at Boston ... to end the series . The following year , the Finals format switched to 2-3-2 , where Games 1 , 2 , 6 , and 7 were hosted by the team with the best record . The change in format came after Red Auerbach complained about the constant travelling during the finals . The 2-2-1-1-1 format would return for the 2014 NBA Finals .",
"title": ""
},
{
"docid": "Laker_Band",
"text": "The Los Angeles Laker Band is a subset of the USC Trojan Marching Band that plays at Lakers home games . Created in 1979 at the request of Lakers owner Dr. Jerry Buss , this brass and rhythm ensemble performs at every Laker home game , including the playoffs , and regularly performs the national anthem before the game on the Staples Center court . The group is the only one of its kind in the NBA : a dedicated band that performs at every game in its own section . The band sits and performs in section 308 . The Laker Band comprises nine trumpets , six or seven trombones , a bass guitar , and a drum set . The band has been featured in the championship parade in downtown Los Angeles when the Lakers win the NBA title . Band members and the Laker Girls ride atop firetrucks for the parade down Figueroa Blvd. .",
"title": ""
},
{
"docid": "1991–92_Portland_Trail_Blazers_season",
"text": "The 1991 -- 92 NBA season was the 22nd season for the Portland Trail Blazers in the National Basketball Association . After losing three of their first four games , the Blazers would quickly recover as they continued to lead the way in the West posting a 57 -- 25 record , earning their second straight Pacific Division championship and 10th consecutive trip to the NBA Playoffs . Clyde Drexler led the way averaging 25.0 points per game while being named to the All-NBA First Team , selected for the 1992 NBA All-Star Game , and finishing a distant second to Michael Jordan in the MVP ballot . The Blazers began their postseason run by defeating the Los Angeles Lakers 3 -- 1 in the first round , eliminating the Lakers for the first time since Portland 's championship season of 1977 ; the Lakers had beaten the Blazers in four playoff series since then , including most recently the 1991 Western Conference Finals . The Blazers proceeded to defeat the Phoenix Suns 4 -- 1 in the second round and Karl Malone 's Utah Jazz 4 -- 2 in the Western Conference Finals , earning their second trip to the NBA Finals in three years , and a matchup with the defending champion Chicago Bulls . The Blazers ' dream of winning their second NBA title , however , was stifled by the Michael Jordan and Scottie Pippen-led Bulls , who defeated the Blazers 4 -- 2 and won their second straight NBA title . Following the season , Danny Ainge signed as a free agent with the Phoenix Suns . For the season , the Blazers changed their logo and uniforms . Both would last until 2002 .",
"title": ""
},
{
"docid": "1991–92_Los_Angeles_Lakers_season",
"text": "The 1991 -- 92 NBA season was the Lakers ' 44th season in the National Basketball Association , and 32nd in the city of Los Angeles . This was the start of a new era for the Los Angeles Lakers , as they had to cope with the sudden retirement of their longtime superstar , Magic Johnson , due to an HIV infection . However , he would make a brief return playing in the 1992 NBA All-Star Game winning the All-Star MVP award . During the offseason , the Lakers acquired Sedale Threatt from the Seattle SuperSonics . Without Johnson for the first time since 1979 , the Lakers won 10 of their first 13 games including a nine-game winning streak . However , they struggled in February losing seven straight games with a 3 -- 9 record during the month . The Lakers struggled to make the playoffs as they finished sixth in the Pacific Division with a 43 -- 39 record . It would be considered their worst record since the 1975 -- 76 season . As the # 8 seed in the Western Conference , the Lakers were eliminated from the first round of the NBA playoffs in four games by the Portland Trail Blazers . Following the season , Mike Dunleavy left and took a coaching job with the Milwaukee Bucks .",
"title": ""
},
{
"docid": "Andrew_Bynum",
"text": "Andrew Bynum ( born October 27 , 1987 ) is an American professional basketball player who is currently a free agent . Bynum has played for the Los Angeles Lakers , Cleveland Cavaliers , and Indiana Pacers of the National Basketball Association ( NBA ) . The 7 ft center is a two-time NBA champion , winning in 2009 and 2010 with the Lakers . He was named an All-Star and was selected to the All-NBA team in 2012 . Bynum was an All-American player in high school before he decided to forgo college and enter the 2005 NBA draft . He was selected with the 10th overall pick by the Los Angeles Lakers , and he became the youngest player ever to play in an NBA game . In 2012 , he was traded after 7 seasons with the Lakers to the Philadelphia 76ers as part of a four-team deal that also sent All-Star center Dwight Howard to Los Angeles . Bynum missed the entire 2012 -- 13 season because of knee problems . He signed as a free agent with Cleveland , where he briefly played before being traded to the Chicago Bulls , who subsequently released him . He then signed with the Indiana Pacers for the remainder of the 2013 -- 14 season .",
"title": ""
}
] |
1703
|
Is it possible to borrow money to accrue interest, and then use that interest to pay back the borrower + fees?
|
[
{
"docid": "149723",
"text": "\"With (1), it's rather confusing as to where \"\"interest\"\" refers to what you're paying and where it refers to what you're being paid, and it's confusing what you expect the numbers to work out to be. If you have to pay normal interest on top of sharing the interest you receive, then you're losing money. If the lending bank is receiving less interest than the going market rate, then they're losing money. If the bank you've deposited the money with is paying more than the going market rate, they're losing money. I don't see how you imagine a scenario where someone isn't losing money. For (2) and (3), you're buying stocks on margin, which certainly is something that happens, but you'll have to get an account that is specifically for margin trading. It's a specific type of credit with specific rules, and you if you want to engage in this sort of trading, you should go through established channels rather than trying to convert a regular loan into margin trading. If you get a personal loan that isn't specifically for margin trading, and buy stocks with the money, and the stocks tank, you can be in serious trouble. (If you do it through margin trading, it's still very risky, but not nearly as risky as trying to game the system. In some cases, doing this makes you not only civilly but criminally liable.) The lending bank absolutely can lose if your stocks tank, since then there will be nothing backing up the loan.\"",
"title": ""
},
{
"docid": "121590",
"text": "\"There are many flaws with your idea. Say I want to borrow $225,000.00 to accrue interest on a 1.20% APY account. I promise ... that I cannot withdraw nor touch the account by legal contract. If you break the contract and lose the money, the lender is out the money. They can take you to court and will win, but if you don't have the money, then they don't get paid. (You can't squeeze water out of a rock even if a judge orders you to.) By sharing the interest with me on a loan, they keep a percentage that they'd normally get... If you're \"\"investing\"\" the money at 1.2%, and the lender gets some amount less than that, then they are getting much less than they \"\"normally\"\" get. Lenders typically get somewhere from 5-15% on loans. The money can also be used to fund a stock/trading account. Regardless of whether I profit, I pay interest on the loan and split the profit shares 24/7. How can the lender lose with legal enforcing? Again, if you lose the money, no amount of legal enforcing can force you to pay money that you don't have. Even if you go to jail for fraud the lender still doesn't get paid. Simply, no bank would ever agree to this.\"",
"title": ""
},
{
"docid": "392980",
"text": "\"Your plan as proposed will not work, because it goes against how banks make money. Banks make money in two ways: (1) Fees [including account fees, investment advice fees, mortgage application fees, etc.]; and (2) Interest Rate Spread. They borrow money for x%, and they lend it out for x+y%. In a simple form, someone gives the bank a deposit, and earns 1%. The bank turns around to the next person in line and loans the money to them for 4%. You are asking them to turn the interest rate spread into a cost instead of their main source of profit: You are asking the bank to borrow money from another person paying them 1.2% interest, and then loan the money to you, paying you 0.6% interest and keeping 0.6% for themselves. The bank would lose money doing this. Technically yes, you can borrow from a bank and invest it in something earning above the 4% interest they will charge you. You can then pay the bank's interest off of your earnings, and make some profit for yourself. BUT this carries an inherent risk: If your investment loses money, you still owe the bank, effectively increasing the negative impact of your investment. This tactic is called \"\"Leveraging\"\"; you can look it up on this site or on google. It is not something you should do if you do not fully understand the risks you are taking on. Given that you are asking this question, I would suggest tactfully that you are not yet well informed enough to make this sort of investment. You run serious risk of losing everything if you over-leverage (assuming the banks will even lend you money in the first place).\"",
"title": ""
},
{
"docid": "52343",
"text": "No. The WSJ prime rate is 4.25%, even the Fed prime rate is 1.75%, way above the 1.20% you'll be making from your savings account. If you are high worth individual with great credit history, the bank might give you a personal loan at 4.25%. They won't care what you do with it as long as they get their payments. If you are not that creditworthy, they'll ask for a collateral, you can mortgage your house for example. It ends up being the sames thing, you get your money and do what you want with it. If you can make more than the interest rate the bank gave you, great, you made profit. The bank however won't agree to lend you money at 0.6% (1/2 of the 1.2% APY your savings account will bring). Why would they when they can loan that at prime rate of 4.25%?? The closest you can get to something like this is if you are a hot-shot wall street money manager with track record of making big profits. In that case the bank might put some money in your fund for you to manage, but that's not something a regular person can do.",
"title": ""
}
] |
[
{
"docid": "550457",
"text": "\"Outstanding principal balance is the amount you owe at any given time, not including the amount of interest you need to pay as soon as possible. The \"\"capitalized interest\"\" shown is consistent with an average of 13.5 months between when each dollar is borrowed and when the repayment period begins. Suppose you borrow the first half of the money on September 1, 2017 and the second half of the money on February 1, 2017 (5 months later). At that point, half the money has been accruing interest for 5 months. On January 1, 2018, half the money accrued interest for 16 months, and half the money accrued interest for 11 months. The lender now expects you to start repaying the loan, with the first payment due at the end of January 2018 or the beginning of February 2018. If you make the minimum payments on time, the lender expects you to make 120 monthly payments. The last monthly payment would be at the end of December 2027 or the beginning of January 2028. The lender (or the website) should provide details about the actual payment plan, grace periods, provisions for handling inability to pay due to unemployment, and other terms. In the United States, most installment loans pretend that (for purposes of calculating interest) every month has 30 days -- even February and July! Each month, 1/12 of the \"\"annual percentage rate\"\" (APR) is charged as interest. If you do the compounding, a 6.8 percent APR corresponds to (1 + 0.068 / 12)^12 - 1 = 7.016 percent \"\"annual percentage yield\"\" (APY). Also, the APR is understated. The 6.8 percent applies to the full balance (including the loan fees), even though the borrower only gets the amount minus the loan fees. The 6.8 percent rate is useful for doing calculations after the loan fees have been charged, though. These calculations include the capitalized interest and the monthly payment amounts. A true calculation of the APR would take the loan fees into account, and give a higher number than 6.8 percent. But the corrected APR would not be useful for calculating the capitalized interest, nor for calculating the monthly payment amounts.\"",
"title": ""
},
{
"docid": "444941",
"text": "\"This election only applies to payments that you make within 120 days of your having received loan money. These wouldn't be required payments, which is why they are called \"\"early\"\" payments. For example, let's say that you've just received $10,000 from your lender for a new loan. One month later, you pay $500 back. This election decides how that $500 will be applied. The first choice, \"\"Apply as Refund,\"\" means that you are essentially returning some of the money that you initially borrowed. It's like you never borrowed it. Instead of a $10,000 loan, it is now a $9,500 loan. The accrued interest will be recalculated for the new loan amount. The second choice, \"\"Apply as Payment,\"\" means that your payment will first be applied to any interest that has accrued, then applied to the principal. While you are in school, you don't need to make payments on student loans. However, interest is accruing from the day you get the money. This interest is simple interest, which means that the interest is only based on the loan principal; the interest is not compounding, and you are not paying interest on interest. After you leave school and your grace period expires, you enter repayment, and you have to start making payments. At this point, all the interest that has accrued from the time you first received the money until now is capitalized. This means that the interest is added to your loan principal, and interest will now be calculated on this new, larger amount. To avoid this, you can pay the interest as you go before it is capitalized, which will save you from having to pay even more interest later on. As to which method is better, just as they told you right on the form, the \"\"Apply as Refund\"\" method will save you the most money in the long run. However, as I said at the beginning, this election only applies if you make a payment within 120 days from receiving loan funds. Since you are already out of school and in repayment, I don't think it matters at all what you select here. For any students reading this and thinking about loans, I want to issue a warning. Student loans can ruin people later in life. If you truly feel that taking out a loan is the only way you'll be able to get the education you need, minimize these as much as possible. Borrow as little as possible, pay as much as you can as early as you can, and plan on knocking these out ASAP. Great Lakes has a few pages that discuss these topics:\"",
"title": ""
},
{
"docid": "503723",
"text": "When you pay off a loan early, you pay the remaining principal, and you save all of the remaining interest. So you do save on interest, but it's the interest you would have paid in the future, not the interest you have paid in the past. (Your remaining balance when you pay off the loan only includes the principal, not the projected interest.) Interest is a factor of the amount borrowed, the interest rate and the amount of time you borrow the money. The sooner you repay the money, the less interest you pay. Imagine if you had taken a 30 year loan at 4% interest but were allowed to make no payments until the loan term ended. If you waited 15 years to make your first payment, you wouldn't owe the same money as if you'd made payments every month. No, instead of owing ~$64k, you'd owe ~$182k, because you had borrowed $100k for 15 years (plus the interest due) rather than borrowing a declining sum. So that's why you don't get a refund on interest for previous months. If you had started with a 16 year loan, then you would have been paying more principal every month, and your monthly amount due would have been higher to reflect that. As you paid the principal off faster, the interest each month would drop faster. Paying a huge portion of the principal at the end of the loan is not the same as steadily paying it down in the same time frame. You will pay a lot more interest in the former case, and rightfully so. It might help to consider a credit card payment in comparison. If you run up a balance and pay only the minimum each month, you pay a lot of interest over time, because your principal goes down slowly. If you suddenly pay off your credit card, you don't have to pay any more interest, but you also don't get any interest back for previous months. That's because the interest accrued each month is based on your current balance, just like your mortgage. The minimum payments are calculated differently, but the interest accrued each month uses essentially the same mechanism.",
"title": ""
},
{
"docid": "436331",
"text": "I suggest rolling it over to the 401(k) with your new employer. Particularly if they match any percentage of your contribution, it would be in your interest to take as much of that money as possible. When it comes to borrowing money from your 401(k), it looks like the issues AbraCadaver mentioned only apply if you don't pay back the money (http://www.kiplinger.com/article/real-estate/T010-C000-S002-borrowing-from-your-retirement-plan-to-buy-a-home.html). The reasonable argument against taking money out of your 401(k) to buy a home is that it leaves a dent in your retirement nest egg (and its earning power) during key earning years. On the plus side for borrowing from your 401(k), it's very low interest--and it's interest you're paying back to yourself over a 5-year period. At its current value, the most you could borrow from your 401(k) is $35K. If you're fortunate in where you live, that could be most or all of the downpayment. In my own experience, my wife borrowed against her 401(k) balance for the earnest money when we purchased a new home. Fortunately for us, an investor snapped up my previous home within 4 days of us listing it, so she was able to pay back her loan in full right away.",
"title": ""
},
{
"docid": "293897",
"text": "\"Let me run some simplistic numbers, ignoring inflation. You have the opportunity to borrow up to 51K. What matters (and varies) is your postgraduation salary. Case 1 - you make 22K after graduation. You pay back 90 a year for 30 years, paying off at most 2700 of the loan. In this case, whether you borrow 2,800 or 28,000 makes no difference to the paying-off. You would do best to borrow as much as you possibly can, treating it as a grant. Case 2 - you make 100K after graduation. You pay back over 7K a year. If you borrowed the full 51, after 7 or 8 years it would be paid off (yeah, yeah, inflation, interest, but maybe that might make it 9 years.) In this case, the more you borrow the more you have to pay back, but you can easily pay it back, so you don't care. Invest your sponsorships and savings into something long term since you know you won't be needing to draw on them. Case 3 - you make 30K after graduation. Here, the payments you have to make actually impact how much disposable income you have. You pay back 810 a year, and over 30 years that's about 25K of principal. It will be less if you account for some (even most) of the payment going to interest, not principal. Anything you borrow above 25K (or the lower, more accurate amount) is \"\"free\"\". If you borrow substantially less than that (by using your sponsorship, savings, and summer job) you may be able to stop paying sooner than 30 years. But even if you borrow only 12K (or half the more accurate number), it will still be 15 years of payments. Running slightly more realistic versions of these calculations where your salary goes up, and you take interest into account, I think you will discover, for each possible salary path, a number that represents how much of your loan is really loan: everything above that is actually a grant you do not pay back. The less you are likely to make, the more of it is really grant. On top of that, it seems to me that no matter the loan/grant ratio, \"\"borrow as much as you can from this rather bizarre source\"\" appears to be the correct answer. In the cases where it's all loan, you have a lot of income and don't care much about this loan payment. Borrowing the whole 51K lets you invest all the money you get while you're a student, and you can use the returns on those investments to make the loan payments.\"",
"title": ""
},
{
"docid": "559745",
"text": "\"@fredsbend, Hope this helps! \"\"I understand that a reverse mortgage can be paid out in two ways: A lump sum and monthly payments. I figure that if you take the lump sum, eventually, the bank wants you to start paying it back.\"\" Answer: Actually, there are 3 payout options, or 4 if you consider a combination payout as another one. There's a lump sum, a line of credit, or the monthly payout, or a combination. \"\"I figure that if you take the monthly payments, eventually, the bank stops paying out and wants you to pay it back. In both situations, interest accrues and this is how the bank makes money off of the deal\"\". Answer: The only time the monthly payments would stop would be if the borrower defaults on the lenders' terms or they no longer live at home. You are right though, and interest does accrue on whichever payment is decided on. I'm not sure how the lender makes money, probably by the interest, but I know borrowers are protected against high rates and owing more than your house. Here's an article I found that goes over the protections more in detail: https://www.americanadvisorsgroup.com/news/6-consumer-protections-reverse-mortgage-loan-borrowers. \"\"But what determines when you have to begin paying back the reverse mortgage? Some sources online seem to say that it's based only on if you die or would like to sell/move. That can't be right in all situations, because you could end up with a massive debt on a property more than its value.\"\" Answer: There are a lot of protections or regulations in place to protect anyone who takes out a reverse mortgage. One being, you can't owe MORE than your house is valued at during the time of repayment, a reverse mortgage is a non-recourse loan. In the instance that your house is less than you owe, you either sell the home and the proceeds are used to pay the loan and you keep the rest OR if you owe more than the house proceeds of the home go to the lender. Either way, you're not left paying for a \"\"mortgage\"\" without the house. In the case the parent, grandparent passes, then the heirs would have a choice of either paying back the reverse mortgage in payments, OR they can sell the house, heirs are protected during this as well to make sure they're not left with major debt in case of anything. Is there a formula to figure out when the bank stops the monthly payments and then wants it back? **Answer:**The amount becomes due if loan terms are not met, but the lender will discuss the options if it comes to that. Is there a different formula for when the lump sum would have to be paid back?\"\" Answer: Each payout option has the same terms and the same pay back terms. As long as terms are met, the lender can't ask for early repayment.\"",
"title": ""
},
{
"docid": "479240",
"text": "I like the answers others gave, if it's some substantial debt you definitely could go the bankruptcy route but it damages your future, also it's morally unethical to borrow all that money and not intend to pay. Second, if you can pay off the entire balance and clear out the 23% interest than I'd do that first. One less bill to concern yourself with. Now let's say you've been making $100 payments monthly on each card (my assumption for this examples sale) now instead of paying $100 to the remaining cards balance each month and saving the other $100, pay $200 against the remaining credit cards balance. By not taking home any money this way you are tackling the liability that is costing you money every month. Unless you have a great investment opportunity on that remaining $1000 or haven't created much of an emergency fund yet, I'd consider putting more of that money towards the debt. Gaining 0.01% on savings interest still means you're eating 25.99% in debt monthly. If you're able to I'd venture out to open a zero interest card and do a balance transfer over to that new card, there will be a minimal transfer fee but you may get some cash back out of it and also that zero interest for a year would help hold off more interest accruing while you're tackling the balance.",
"title": ""
},
{
"docid": "171339",
"text": "\"One of the factors of a credit score is the \"\"length of time revolving accounts have been established\"\". Having a credit card with any line of credit will help in this regard. The account will age regardless of your use or utilization. If you are having issues with credit limits and no credit history, you may have trouble getting financing for the purchase. You should be sure you're approved for financing, and not just that the financing option is \"\"available\"\" (potentially with the caveat of \"\"for well qualified borrowers\"\"). Generally, if you've gotten approved for financing, that will come in the form of another credit card account (many contracting and plumbing companies will do this in hopes you will use the card for future purchases) or a bank loan account (more common for auto and home loans). With the credit card account, you might be able to perform a balance transfer, but there are usually fees associated with that. For bank loan accounts, you probably can't pay that off with a credit card. You'll need to transfer money to the account via ACH or send in a check. In short: I wouldn't bet on paying with your current credit card to get any benefit. IANAL. Utilizing promotional offers, whether interest-free for __ months, no balance transfer fees, or whatever, and passing your debt around is not illegal, not fraudulent, and in many cases advised (this is a link), though that is more for people to distribute utilization across multiple cards, and to minimize interest accrued. Many people, myself included, use a credit card for purchasing EVERYTHING, then pay it off in full every month (or sometimes immediately) to reap the benefit of cash back rewards and other cardholder benefits. I've also made a major payment (tuition, actually) on a Discover card, and opened up a new Visa card with 18-months of no interest and no balance transfer fees to let the bill sit for 12 months while I finished school and got a job.\"",
"title": ""
},
{
"docid": "360003",
"text": "My opinion is that in general, it is probably not a good idea to borrow at a cost in order to make your RRSP contribution. Banks, of course, have an interest in loaning you money. Don't expect their literature to be objective on the matter! They are selling you a product and the advice is biased. What better way to double-dip than to get guaranteed interest payments from you, as well as ongoing fees for (probably also) getting your loan money invested in their high-fee mutual funds? A year's RRSP contribution room allowance isn't use it or lose it — unlike 401k contribution allowances in the U.S.. That is, unused RRSP contribution room accumulates and you can take advantage of it in later years. If we couldn't carry our RRSP contribution room over, I might feel different about the general case for RRSP loans. Yet there are two specific cases I can think of where it may make sense to borrow and pay back: (a possible case) ... if your tax rate is currently in a high bracket (e.g. 46%), and you anticipate being in a lower income and bracket next year (e.g. 35%), then it would make sense to take advantage of the higher tax savings in the current tax year. If you waited until the following year to take the deduction, you'd lose out on 11% of the deducted amount. For a typical person whose income is level or increasing from year to year, this isn't likely to be applicable, but it could help somebody who is going on leave or otherwise has irregular income. (a foolish case) ... if you knew, somehow, that you could realize a return on your invested RRSP money exceeding the pre-tax earnings required to pay the interest on the RRSP loan. However, I would suggest this is foolish bet to make. The interest you pay is guaranteed, but the return you are expected to get is probably not (or if it is, it is probably a return lower than what your bank wants to charge on the loan.) If for some reason it does make sense for you, take the money and invest it somewhere better than the high-fee mutual funds the bank is also pushing.",
"title": ""
},
{
"docid": "365342",
"text": "If you intend to flip this property, you might consider either a construction loan or private money. A construction loan allows you to borrow from a bank against the value of the finished house a little at a time. As each stage of the construction/repairs are completed, the bank releases more funds to you. Interest accrues during the construction, but no payments need to be made until the construction/repairs are complete. Private money works in a similar manner, but the full amount can be released to you at once so you can get the repairs done more quickly. The interest rate will be higher. If you are flipping, then this higher interest rate is simply a cost of doing business. Since it's a private loan, you ca structure the deal any way you want. Perhaps accruing interest until the property is sold and then paying it back as a single balloon payment on sale of the property. To find private money, contact a mortgage broker and tell them what you have in mind. If you're intending to keep the property for yourself, private money is still an option. Once the repairs are complete, have the bank reassess the property value and refinance based on the new amount. Pay back the private loan with equity pulled from the house and all the shiny new repairs.",
"title": ""
},
{
"docid": "150607",
"text": "\"In England, currently and for most of the last fifty years, the standard length of the mortgage term is 25 years. A mortgage can be either a capital-and-interest mortgage, or interest-only. In the former, you pay off part of the original loan each month, plus the interest on the amount borrowed. In the latter, you only pay interest each month, and the original amount borrowed never reduces: you pay premiums on a life insurance policy, additionally, which is designed to pay off the original sum borrowed at the end of the 25 years. No one in England thinks that a 25 year loan has any drawbacks. The main point to appreciate is that the longer the period of the loan, the less you need to pay each month, because you are repaying the original loan - the capital - over a longer period of time. Thus, in principle, a mortgage is easier to repay the longer the term is, because the monthly payment is less. If you have a 12 year mortgage, you must pay back the original amount borrowed in half the time: the capital element in your payment each month is double what it would be if repaid over 25 years - i.e. if repaid over a period twice as long. Only if the borrower is less than 25 years away from retirement is a 25 years mortgage seen as a bad idea, by the lender - because, obviously, the lender relies on the borrower having an income sufficient to keep up the repayments. There are many complicating factors: an interest-only mortgage, where you pay back the original amount borrowed from the maturity proceeds from a life policy, puts you in a situation where the original capital sum never reduces, so you always pay the same each month. But on a straight repayment mortgage, the traditional type, you pay less and less each month as time goes by, for you are reducing the capital outstanding each month, and because that is reducing so is the amount of interest you pay each month (as this is calculated on the outstanding capital amount). There are snags to avoid, if you can. For example, some mortgage contracts impose penalties if the borrower repays more than the due monthly amount, hence in effect the borrower faces a - possibly heavy - financial penalty for early repayment of the loan. But not all mortgages include such a condition. If house prices are on a rising trend, the market value of the property will soon be worth considerably more than the amount owed on the mortgage, especially where the mortgage debt is reducing every month, as each repayment is made; so the bank or other lender will not be worried about lending over a 25 year term, because if it forecloses there should normally be no difficulty in recovering the outstanding amount from the sale proceeds. If the borrower falls behind on the repayments, or house prices fall, he may soon get into difficulties; but this could happen to anyone - it is not a particular problem of a 25 year term. Where a default in repayment occurs, the bank will often suggest lengthening the mortgage term, from 25 years to 30 years, in order to reduce the amount of the monthly repayment, as a means of helping the borrower. So longer terms than 25 years are in fact a positive solution in a case of financial difficulty. Of course, the longer the term the greater the amount that the borrower will pay in total. But the longer the term, the less he will pay each month - at least on a traditional capital-and-interest mortgage. So it is a question of balancing those two competing factors. As long as you do not have a mortgage condition that penalises the borrower for paying off the loan more quickly, it can make sense to have as long a term as possible, to begin with, which can be shortened by increasing the monthly repayment as fast as circumstances allow. In England, we used to have tax relief on mortgage payments, and so in times gone by it did make sense to let the mortgage run the full 25 years, in order to get maximum tax relief - the rules were very complex, but it tended to maximise your tax relief by paying over the longest possible period. But today, with no income tax relief given on mortgage payments, that is no longer a consideration in this country. The practical position is, of course, that you can never tell how long it might take you to pay off a mortgage. It is a gamble as to whether your income will rise in future years, and whether your job will last until your mortgage is paid off. You might fall ill, you might be made redundant, you might be demoted. Mortgage interest rates might rise. It is never possible to say that you \"\"can\"\" pay off the loan in a short time. If you hope to do so, the only matters that actually fall within your control are the conditions of the mortgage contract itself. Get a good lawyer. Tell him to watch out for early-redemption penalties. Get a good financial adviser. Tell him to work out what you will need to pay in additional premiums on your life policy if you are considering taking an interest-only mortgage. Try to fix your mortgage rate in the first few years, for as long as possible, so that in your most vulnerable period, with the greatest amount owing, you are insulated against unexpected interest rate fluctuations. Only the initial conditions can be controlled, so it might be prudent to take as long a term as possible, even though a prudent borrower will leave himself room to reduce that term, and a prudent lender will leave room to extend it, in case of unpredictable changes in the financial circumstances. In England, most lenders are, in my experience, reluctant to grant mortgages for less than 25 years. That is simply a policy. Rightly or wrongly, the borrower usually has no choice about the length of the mortgbage term. Hence, in the UK it can be difficult to find a choice of interest rates based on differing mortgage terms. I am aware that the situation in the USA is rather different, but if I personally were faced with the choice I would be uncomfortable about taking on a short term mortgage, because of the factors I have outlined above.\"",
"title": ""
},
{
"docid": "10873",
"text": "\"This answer is better served as a comment but I don't have enough rep. It is not guaranteed that they 'do not accrue interest while you are a full time student'. Some student loans can capitalize the interest - before pursuing leveraged investing, be sure that your student loan is not capitalizing. https://www.salliemae.com/student-loans/manage-your-private-student-loan/understand-student-loan-payments/learn-about-interest-and-capitalization/ Capitalized interest Capitalized interest is a second reason your loan may end up costing more than the amount you originally borrowed. Interest starts to accrue (grow) from the day your loan is disbursed (sent to you or your school). At certain points in time—when your separation or grace period ends, or at the end of forbearance or deferment—your Unpaid Interest may capitalize. That means it is added to your loan’s Current Principal. From that point, your interest will now be calculated on this new amount. That’s capitalized interest.\"\" https://www.navient.com/loan-customers/interest-and-taxes/how-student-loan-interest-works/ Capitalized Interest If you accrue interest while you are in school – as with Direct Unsubsidized, FFELP Unsubsidized, Direct and FFELP PLUS Loans, and Private Loans – you will have capitalized interest if it is unpaid. Unpaid accrued interest is added to the principal amount of your loan after you leave school and finish any applicable grace period. Simply put, there will be interest to be paid on both the principal of the loan and on the interest that has already accumulated. To minimize the effects of the capitalized interest on the amount you will pay overall, you can pay the interest during college instead of waiting until after graduation. That way, you start with the original principal balance (minus any fees) when you begin repayment.\"",
"title": ""
},
{
"docid": "543811",
"text": "\"I think to some extent you may be confusing the terms margin and leverage. From Investopedia Two concepts that are important to traders are margin and leverage. Margin is a loan extended by your broker that allows you to leverage the funds and securities in your account to enter larger trades. In order to use margin, you must open and be approved for a margin account. The loan is collateralized by the securities and cash in your margin account. The borrowed money doesn't come free, however; it has to be paid back with interest. If you are a day trader or scalper this may not be a concern; but if you are a swing trader, you can expect to pay between 5 and 10% interest on the borrowed money, or margin. Going hand-in-hand with margin is leverage; you use margin to create leverage. Leverage is the increased buying power that is available to margin account holders. Essentially, leverage allows you to pay less than full price for a trade, giving you the ability to enter larger positions than would be possible with your account funds alone. Leverage is expressed as a ratio. A 2:1 leverage, for example, means that you would be able to hold a position that is twice the value of your trading account. If you had $25,000 in your trading account with 2:1 leverage, you would be able to purchase $50,000 worth of stock. Margin refers to essentially buying with borrowed money. This must be paid back, with interest. You also may have a \"\"margin call\"\" forcing you to liquidate assets if you go beyond your margin limits. Leverage can be achieved in a number of ways when investing, one of which is investing with a margin account.\"",
"title": ""
},
{
"docid": "521418",
"text": "\"A credit card is basically a \"\"revolving\"\" loan, in which you're allowed to borrow up to a certain amount (the limit), and any time you borrow, you pay interest. If you were to *borrow* $100 to pay for something via a credit card, you'd have a $100 balance on the card. If you then pay $70 cash to the card, there would be $30 remaining. That $30 balance could accrue interest. The timing of that interest charge could vary. The 20% you've quoted is almost certainly \"\"APR,\"\" of which the \"\"A\"\" stands for \"\"annual,\"\" so that 20% would be an annual rate. It makes the most sense, mind you, to keep a minimal balance on a credit card, as the interest rate is higher than most other loans.\"",
"title": ""
},
{
"docid": "559618",
"text": "\"Somehow I just stumbled onto this thread... > You essentially robbed the person holding the debt (since you promised to pay it off). Depends on leverage, with fractional reserve lending. Banks are permitted to loan out 30x their actual assets, or more. If I have $1 but can loan out $30, and anything more than $1 gets paid back, I haven't lost any money. In addition, I can write off the amount defaulted, *and the government will pay me back* for certain types of loans. With student loans, since they are almost impossible to discharge, gov't will pursue the borrower for years and decades, and ultimately collect more interest. Here is an article on it: http://online.wsj.com/article/SB10001424052748704723104576061953842079760.html > According to Kantrowitz, the government stands to earn $2,010.44 more in interest from a $10,000 loan that defaulted than if it had been paid in full over a 20-year term, and $6,522.00 more than if it had been paid back in 10 years. Alan Collinge, founder of borrowers' rights advocacy Student Loan Justice, said the high recovery rates provide a \"\"perverted incentive\"\" for the government to allow loans to go into default. Kantrowitz estimates the recovery rate would need to fall to below 50% in order for default prevention efforts to become more lucrative than defaults themselves. Not to mention: http://studentloanjustice.org/defaults-making-money.html > So essentially, the Department is given a choice: Either do nothing and get nothing, or outlay cash with the knowledge that this outlay will realize a 22 percent return, ultimately (minus the governments cost of money and collection costs). From this perspective, it is clear that based solely on financial motivations, and without specific detailed knowledge of the loan (i.e. borrower characteristics, etc.), the chooser would clearly favor the default scenario, for not only the return, but perhaps the potential savings in subsidy payment as well, And don't forget the penalties accruing to the person defaulting; they will probably have to move out of the country in order to escape collection. And let's factor in the huge ROI the lender sees by creating an indentured servant class. Plus, the gov't will issue as much currency as it wants, to make *itself* whole. And how much of a loss IS the loss, when the whole of the loan amount went right back into the local economy, paying professors, janitors, landlords, grocery stores, etc.? And don't forget all THOSE taxes (income and sale) that the gov't collects. Government will collect ~30%-50% of the loan immediately as income and sales tax, plus a portion of it every time the money changes hands (I pay income tax, then use some of my after-tax money to pay you for a product or service, and you still have to pay tax on that money, and so on). So it's more complicated than having \"\"robbed the person holding the debt\"\". Banks at 30x leverage don't lose money as long as they get back 1/30th of the total amount lent out, including interest, fees, and penalties, before considering write-offs and government repayment. In fact, the point of over-leverage is so you CAN make loans that have risk attached. If you could only lend what you actually had, you would have to stay away from anything risky because it would be too easy to lose money. Having virtual $ to bet means you can serve market segments that have higher risk. This makes MORE money for the banks, that's why they do it. They are already playing with funny money, so they don't lose any even if you default and move to another country. And the money you \"\"spent\"\" has also made its way back to them in various amounts, such as your professor's mortgage payments, auto loan, etc. Your taking on debt already helped the bank get its OTHER loans repaid. So, roughly speaking, if you took out $90,000 and $3,000 of that made its way back to the bank through various means, they haven't lost any money, because it only cost them $3,000 actual dollars in the first place.\"",
"title": ""
},
{
"docid": "421743",
"text": "\"never carry a balance on a credit card. there is almost always a cheaper way to borrow money. the exception to that rule is when you are offered a 0% promotion on a credit card, but even then watch out for cash advance fees and how payments are applied (typically to promotional balances first). paying interest on daily spending is a bad idea. generally, the only time you should pay interest is on a home loan, car loan or education loan. basically that's because those loans can either allow you to reduce an expense (e.g. apartment rent, taxi fair), or increase your income (by getting a better job). you can try to make an argument about the utility of a dollar, but all sophistry aside you are better off investing than borrowing under normal circumstances. that said, using a credit card (with no annual fee) can build credit for a future car or home loan. the biggest advantage of a credit card is cash back. if you have good credit you can get a credit card that offers at least 1% cash back on every purchase. if you don't have good credit, using a credit card with no annual fee can be a good way to build credit until you can get approved for a 2% card (e.g. citi double cash). additionally, technically, you can get close to 10% cash back by chasing sign up bonuses. however, that requires applying for new cards frequently and keeping track of minimum spend etc. credit cards also protect you from fraud. if someone uses your debit card number, you can be short on cash until your bank fixes it. but if someone uses your credit card number, you can simply dispute the charge when you get the bill. you don't have to worry about how to make rent after an unexpected 2k$ charge. side note: it is a common mis-conception that credit card issuers only make money from cardholder interest and fees. card issuers make a lot of revenue from \"\"interchange fees\"\" paid by merchants every time you use your card. some issuers (e.g. amex) make a majority of their revenue from merchants.\"",
"title": ""
},
{
"docid": "249831",
"text": "\"Ditto mhoran_psprep. I'm not quite sure what you're asking. Where does the money come from? When someone starts a bank, they normally get together a bunch of investors -- perhaps people they know personally, perhaps they sell stock -- to raise initial capital. But most of the money in the bank comes from depositors. Fundamentally, what a bank does is take money from depositors and loan it to borrowers. (Banks also borrow money from other banks and from the government.) They charge the borrowers interest on the loan, and they pay depositors interest on their deposits. The difference between those two interest rates is where the bank gets their profit. Where does the money go when you pay it back? As mhoran_psprep said, some of it goes to pay interest to the depositors; some of it goes to pay the bank's expenses like employee salaries, cost of the building, etc; and some of it goes as profit to the owners or stockholders of the bank. If you're thinking, \"\"Wow, I'm paying back a whole lot more than I borrowed\"\", well, yes. But remember you're borrowing that money for 20 or 30 years. The bank isn't making very much money on the loan each year that you have it -- these days something like 4 or 5% in the U.S., I don't know what the going rates are in other countries.\"",
"title": ""
},
{
"docid": "42475",
"text": "\"The interest rate offered by a bond is called the nominal interest rate. The so-called real interest rate is the nominal interest rate minus the rate of inflation. If inflation is equal to or greater than the nominal rate at any given time, the REAL interest rate is zero or negative. We're talking about a ten year bond. It's possible for the real interest rate to be negative for one or two years of the bond's life, and positive for eight or nine. On the other hand, if we have a period of rising inflation, as in the 1970s, the inflation rate will exceed the (original) interest rate in most years, meaning that the real interest rate on the ten year bond will be negative over its whole life. People lost \"\"serious\"\" money on bonds (and loans) in the 1970s. In such situations, the BORROWERS make out. That is, they borrow money at low rates, earn inflation (plus a little more) pay back inflated dollars, and pocket the difference. For them, the money is \"\"free.\"\"\"",
"title": ""
},
{
"docid": "191508",
"text": "Forget about terms. Think about loans in terms of months. To simplify things, let's consider a $1000 loan with .3% interest per month. This looks like a ten month term, but it's equally reasonable to think about it on a month-to-month basis. In the first month, you borrowed $1000 and accrued $3 interest. With the $102 payment, that leaves $901 which you borrow for another month. So on and so forth. The payoff after five payments would by $503.54 ($502.03 principal plus $1.51 interest). You'd save $2.99 in interest after paying $13.54. The reason why most of the interest was already paid is that you already did most of the borrowing. You borrowed $502.03 for six months and about $100 each for five, four, three, two, and one month. So you borrowed about $4500 months (you borrowed $1000 for the first month, $901 for the second month, etc.). The total for a ten month $1000 loan is about $5500 months of borrowing. So you've done 9/11 of the borrowing. It's unsurprising that you've paid about 9/11 of the interest. If you did this as a six month loan instead, then the payments look different. Say You borrow $1000 for one month. Then 834 for one month. So on and so forth. Adding that together, you get about $168.50 * 21 or $3538.50 months borrowed. Since you only borrow about 7/9 as much, you should pay 7/9 the interest. And if we adding things up, we get $10.54 in interest, about 7/9 of $13.54. That's how I would expect your mortgage to work in the United States (and I'd expect it to be similar elsewhere). Mortgages are pretty straight-jacketed by federal and state regulations. I too once had a car loan that claimed that early payment didn't matter. But to get rid of the loan, I made extra payments. And they ended up crediting me with an early release. In fact, they rebated part of my last payment. I saved several hundred dollars through the early release. Perhaps your loan did not work the same way. Perhaps it did. But in any case, mortgages don't generally work like you describe.",
"title": ""
},
{
"docid": "239611",
"text": "\"The most important thing in my view is flexibility, to avoid running into problems. One useful thing in the UK would be an arranged overdraft. You go to your bank, and they'll agree that you can overdraw your account by a certain number of pounds, depending on your income etc. It will cost you a very high interest rate, but only for each day where you are overdrawn. So paying a bill two days before your salary comes in isn't too bad. Obviously avoid using the overdraft if you can, having an overdraft while not using it is free. It's meant for an emergency; being regularly overdrawn is expensive. But once it is arranged with your bank, an arranged overdraft is much much cheaper than bouncing cheques etc. and possibly high fees for overdrawing your account. And it takes the pressure of you. Now things to need before you get a loan (again, UK): The real interest rate that you are paying is called APR. That's the number that counts, and that cannot be manipulated. No \"\"payday loans\"\" to avoid getting yourself into deep, deep trouble. No loan sharks, obviously. If you buy things with \"\"interest free credit\"\", that's (a) included in the price, so you pay more, and (b) if you miss paying by one day they'll hit you with huge interest payments, and some will try this intentionally. Interest rate depends on loan amount. I once had to borrow 20% more than I needed because it reduced the interest rate by half... The 20% went straight into a savings account. Credit cards and overdrafts are much more expensive than loans. Mortgage is again cheaper than a loan usually. Make sure that you only use money from sources that charge the least amount. Make sure you pay back regularly so cheap sources stay available to you. Just do yourself a favour and if at all possible, spend less instead of getting a loan.\"",
"title": ""
},
{
"docid": "362468",
"text": "\"I've never heard of a loan product like that. Yes, if they keep the funds in an account, it is no risk to the bank, but they would essentially need to go through the loan process twice for the same loan: when you pick a house, they need to reevaluate everything, along with appraising and approving the house. Even if you did find a bank that would do this for you, there are a few problems with this scheme. You would be paying interest before you have a need for this money, negating the savings you might achieve if the interest rates go up. In addition, your \"\"balance\"\" will go down as \"\"payments\"\" are deducted from your loan, and when you finally find a home to buy, you might not have enough for the house you want. You'll need to borrow more than you need, which will further negate any possible savings. It is impossible to know how fast rates will climb. If I were you, I would stick to saving for your down payment, and just get the best rate you can when you are ready to buy. Another potential idea for you is to lock an interest rate. When you apply for a mortgage, the interest rate is often locked for as much as 60 days, to protect the borrower in the event that the rates go up. You could ask the bank if you can pay a fee to lock the rate even longer. I don't know if that is possible or not. And, of course, the fee would eat into your potential savings.\"",
"title": ""
},
{
"docid": "17110",
"text": "Because this is Money.SE and you're connecting it to offspring, I'd think about a discussion with them to get their agreements. From my perspective, anything (my wife and) I have will go to offspring in the end. As such, everything borrowed and not repaid simply reduces the estate by that much. Among multiple offspring, such reductions should be against the borrower rather than spreading it out. That should be accounted for in whatever will is created. This would be the discussion point. It might also be discussed how or even if any interest should accrue for unpaid amounts. If, for example, a 1% APR is agreed upon for unpaid loans, then the final principle+interest amount is taken off of the borrower's inheritance. Existing outstanding loans might (or might not!) be useful examples for sample calculations if desired or needed. (If nothing else, they might serve as reminders that loans were not forgotten.) By having such a discussion, you can show that you are trying to plan for a fair distribution of your estate, perhaps thereby sidestepping any concern about charging interest to offspring for repaid loans. At the same time, you're handing over some financial responsibility, giving them a power of personal choice, which seems to be a part of what you're concerned about. Once such a discussion is started, it's possible that any question of interest will resolve itself naturally. The discussion almost necessarily must include all offspring at once. One will find it harder to negotiate from a standpoint of pure self-interest without objection from another. Think beforehand about what will be said and about what responses might come. Think things through as much as you can.",
"title": ""
},
{
"docid": "22268",
"text": "\"They don't actually need to. They accept deposits for historical reasons and because they make money doing so, but there's nothing key to their business that requires them to do so. Here's a decent summary, but I'll explain in great detail below. By making loans, banks create money. This is what we mean when we say the monetary supply is endogenous. (At least if you believe Sir Mervyn King, who used to run England's central bank...) The only real checks on this are regulatory--capitalization requirements and reserve requirements, which impose a sort of tax on a bank's circulating loans. I'll get into that later. Let's start with Why should you believe that story--that loans create deposits? It seems like a bizarre assertion. But it actually matches how banks behave in practice. If you go borrow money from a bank, the loan officer will do many things. She'll want to look at your credit history. She'll want to look at your income and assets. She'll want to look at what kind of collateral or guarantees you're providing that the loan will be repaid. What she will not do is call down to the vaults and make sure that there's enough bills stacked up for them to lend out. Loans are judged based on a profitability function determined by the interest rate and the loan risk. If those add up to \"\"profitable\"\", the bank makes the loan. So the limiting factor on the loans a bank makes are the available creditworthy borrowers--not the bank's stock of cash. Further, the story makes sense because loans are how banks make money. If a bank that was short of money suddenly stopped making loans, it'd be screwed: no new loans = no way to make money to pay back depositors and also keep the lights on = no more bank. And the story is believable because of the way banks make so little effort to solicit commercial deposit business. Oh sure, they used to give you a free toaster if you opened an account; but now it's really quite challenging to find a no-fee checking account that doesn't impose a super-high deposit limit. And the interest paid on savings deposits is asymptotically approaching zero. If banks actually needed your deposits, they'd be making a lot more of effort to get them. I mean, they won't turn up their noses; your deposited allowance is a couple basis points cheaper to the bank than borrowing from the Fed; but banks seem to value small-potatoes depositors more as a source of fees and sales opportunities for services and consumer credit than as a source of cash. (It's a bit different if you get north of seven figures, but smaller depositors aren't really worth the hassle just for their cash.) This is where someone will mention the regulatory requirements of fractional reserve banking: banks are obliged by regulators to keep enough cash on hand to pay out a certain percentage of deposits. Note nothing about loans was said in that statement: this requirement does not serve as a check on the bank making bad loans, because the bank is ultimately liable to all its depositors for the full value of their deposits; it's more making sure they have enough liquidity to prevent bank runs, the self-fulfilling prophecy in which an undercapitalized bank could be forced into bankruptcy. As you noted in your question, banks can always borrow from the Fed at the Fed Discount Rate (or from other banks at the interbank overnight rate, which is a little lower) to meet this requirement. They do have to pledge collateral, but loans themselves are collateral, so this doesn't present much of a problem. In terms of paying off depositors if the bank should collapse (and minimizing the amount of FDIC insurance payout from the government), it's really capital requirements that are actually important. I.E. the bank has to have investors who don't have a right to be paid back and whose investment is on the hook if the bank goes belly-up. But that's just a safeguard for the depositors; it doesn't really have anything to do with loans other than that bad loans are the main reason a bank might go under. Banks, like any other private business, have assets (things of value) and liabilities (obligations to other people). But banking assets and liabilities are counterintuitive. The bank's assets are loans, because they are theoretically recoverable (the principal) and also generate a revenue stream (the interest payments). The money the bank holds in deposits is actually a liability, because it has to pay that money out to depositors on demand, and the deposited money will never (by itself) bring the bank any revenue at all. In fact, it's a drain, because the bank needs to pay interest to its depositors. (Well, they used to anyway.) So what happens when a bank makes a loan? From a balance sheet perspective, strangely enough, the answer is nothing at all. If I grant you a loan, the minute we shake hands and you sign the paperwork, a teller types on a keyboard and money appears in your account. Your account with my bank. My bank has simultaneously created an asset (the loan you now have to repay me) and an equal-sized liability (the funds I loaned you, which are now deposited in your account). I'll make money on the deal, because the interest you owe me is a much higher rate than the interest I pay on your deposits, or the rate I'd have to pay if I need to borrow cash to cover your withdrawal. (I might just have the cash on hand anyway from interest and origination fees and whatnot from previous loans.) From an accounting perspective, nothing has happened to my balance sheet, but suddenly you owe me closing costs and a stream of extraneous interest payments. (Nice work if you can get it...) Okay, so I've exhaustively demonstrated that I don't need to take deposits to make loans. But we live in a world where banks do! Here's a few reasons: You can probably think of more, but at the end of the day, a bank should be designed so that if every single (non-borrowing) depositor withdrew their deposits, the bank wouldn't collapse or cease to exist.\"",
"title": ""
},
{
"docid": "444637",
"text": "Putting debt out long means to borrow a sum of money paid back over a longer period of time than you could reasonably pay it back. It should be important to note that this advice only applies for fixed rate loans (meaning your rate can't change for the life of the loan without you explicitly changing it). The logic is that if you can borrow money when interest rates are really low, there is a good chance you can find an investment that has a return higher than the interest rate on the loan. It also means that when/if interest rates go up in the future, a simple savings account may even have a greater return than your loans interest. The advice suggests to borrow over a long period so you are paying less interest per payment, and gives you time to find a proper investment without having to pay too much interest during that time.",
"title": ""
},
{
"docid": "474318",
"text": "\"If the government prints money recklessly and causes inflation, people will come to expect inflation, and the value of the currency will plummet, and you'll end up like Zimbabwe where a trillion dollars won't buy a loaf of bread. If the government actually pays people for the money they borrow, they don't have this problem - and as it turns out, the US government can get pretty good rates on borrowing in general, in part because they're extraordinarily good about paying them back. (Also, inflation expectations are low, so people will accept 1-2% interest rates. If you expected inflation of 10%, you'd see people demanding something more like 12% interest rates.) (The downside of too much of this sort of borrowing is that it \"\"crowds out\"\" other borrowing, which may harm the economy. Who would lend money to / invest in a small business, if the government is paying good money and there's almost no risk at all?) Now, inflation can come into play afterward, if the Fed decides it needs to maintain \"\"easy money\"\" policies to stimulate the economy (because taxes are too high because we're paying off the debt, or because we've crowded out smaller borrowers, or something). -- In general, you can count on the the principle that if you, as the government, try to play too many games with people's money... well, people aren't stupid; they will eventually catch on, and adjust their behavior to compensate, and then you're right back where you started, but with less trust.\"",
"title": ""
},
{
"docid": "580147",
"text": "When you get a loan (car, home, student) the lending company (bank) give the (auto dealer, previous home owner, school) money. You as the borrow promise to pay this money back with interest. So in your case the 100,000 you borrow requires a payment for principal and interest of ~965 per month. After 240 payments you will have paid the bank ~231,605. So who got the ~131,000 in interest. The bank did. It was used to pay interest to the people who made deposits into the bank. It was also used to pay the expenses of the bank: salaries, retirement, rent, electricity, computers, etc. If the bank is a company with investors they may have to pay dividends to them to. Of course not all loans are successfully paid back, so some of the payment goes to cover the loans that are in default. In many cases loans are also refinanced, or the house is sold long before the 20-30 year term is up. In these cases the amount of interest received for that loan is much less than anticipated, but the good news is that it can be loaned out again.",
"title": ""
},
{
"docid": "285176",
"text": "The assumption that bonds have been issued with a negative coupon is not correct, or at least is has not occurred thus far. We'll look at this future possibility in the final paragraph. For now, lets look at the current bond market. The issuance of government bonds which carry a negative gross redemption yield is the result of governments issuing bonds at an issue price which exceed the nominal/redemption price and any coupon yield receivable over the life of the bond. I can find no instances of bonds with a negative coupon, though many have tiny positive coupon yields. The short seller of a bond with a negative gross redemption yield will be liable to pay the buyer the interest amount determined by the coupon. If the short seller has borrowed the bonds in order to sell them, then the short seller will receive the interest due from the lender to offset the interest paid to the buyer. If the short seller has not borrowed the bonds, but has sold them using some sort of synthetic contract such as a Contract for Difference, then the short seller will pay the coupon without receiving any offsetting payment. I thought this was an interesting question and it will be interesting to see if, at some time in the future, governments do ever issue bonds with a negative coupon. To date, this does not appear to have happened. So what would happen if we assume that a government issues a bond with a negative coupon. The buyer of the bond would be required to pay the equivalent yield to the government according to the bond contract specification. If an investor sells short such a bond, they would then become entitled to receive the interest from the buyer. If they have borrowed the bonds in order to sell them short, then they would pay any interest received back to the lender - this chain should eventually end with the ultimate owner/lender paying the government their dues. If they have sold short using a synthetic contract, then presumably they would keep the interest from themselves.",
"title": ""
},
{
"docid": "41312",
"text": "You must mean the current debt ceiling debacle. The meaning of it is: US government is constantly borrowing money (by issuing treasury bonds) and constantly repaying some of the bonds that come to maturity, and also has other obligations it has to meet by law all the time - such as Social Security checks, bonds interest, federal employees' salaries and pensions, etc. By law, total amount of money that can be borrowed at the same time is capped. That means, there can be situation where the government needs to borrow money to pay, say, interest on existing bonds, but can not, since the limit is reached. Such situation is called a default, since the government promised to pay the interest, but is unable to do so. That does not mean the government has no money at all and will completely collapse or couldn't raise money on the market if it were permitted by law to do so (currently, the market is completely willing to buy the debt issued by US government, and with interest that is not very high, though of course that may change). It also does not mean the economy ceases to function, dollars cease to have value or banks instantly go bankrupt. But if the government breaks its promises to investors, it has various consequences such as raising the costs of borrowing in the future. Breaking promises to other people - like Social Security recipients - would also look bad and probably hurt many of them. Going back to your bank account, most probably nothing would happen to the money you store there. Even if the bank had invested 100% of the money in US treasury bonds (which doesn't really happen) they still can be sold on the open market, even if with some discount in the event of credit rating downgrade, so most probably your account would not be affected. As stated in another answer, even if the fallout of all these calamities causes a bank to fail, there's FDIC and if your money is under insured maximums you'll be getting your money back. But if your bank is one of the big ones, nothing of the sort would happen anyway - as we have seen in the past years, government would do practically anything to not allow any big bank failures.",
"title": ""
},
{
"docid": "28809",
"text": "\"Most likely that's the amount of interest that accrued on the loan while you were in school. If you had paid that amount before 6/21, you would have just paid off accrued interest and your loan balance would have stayed the same. Since you did not pay the interest, it will be added to your loan balance and you will just pay it off as part of the loan (plus compounded interest). If you pay off your loan at 5% over 30 years (hopefully you won't, but that's what they're amortized for), that $350 will compound and become $1,563. Essentially you're \"\"borrowing\"\" $350 at 5% interest for 30 years. Hopefully that motivates you to pay it off sooner that that...\"",
"title": ""
},
{
"docid": "557324",
"text": "There are a few reasons, particularly for businesses. The first is opportunity cost. That chunk of money they have could be used to get higher returns somewhere else. If they can borrow from a bank at low interest rates to finance their ongoing operations, they can use their cash to get a higher return somewhere else. The second is credit rating. For public companies, ratings companies give high emphasis to companies with large reserves. This strengthens their ability to pay back the loan should it become necessary. A good credit rating in turn let's the company borrow money at lower rates. When a company can borrow money at low rates, it circles back to the first point where they can now put their reserves to better use. The third is leverage. Companies can use the cash they have built up to leverage into a larger investment. Assuming the investment works out, it will pay for the cost of borrowing over time. For instance let's say I have $1 million to invest. I can pay all cash for a $1 million apartment building or I can leverage that into a $3 million building. Assuming I run it well, the tenants will pay for the cost of borrowing $2 million and at the end of the term I'll be left with my $3 million building.",
"title": ""
}
] |
771
|
Metastatic colorectal cancer treated with a single agent fluoropyrimidines resulted in similar efficacy and better quality of life when compared with oxaliplatin-based chemotherapy in elderly patients.
|
[
{
"docid": "15476777",
"text": "BACKGROUND Elderly and frail patients with cancer, although often treated with chemotherapy, are under-represented in clinical trials. We designed FOCUS2 to investigate reduced-dose chemotherapy options and to seek objective predictors of outcome in frail patients with advanced colorectal cancer. METHODS We undertook an open, 2 × 2 factorial trial in 61 UK centres for patients with previously untreated advanced colorectal cancer who were considered unfit for full-dose chemotherapy. After comprehensive health assessment (CHA), patients were randomly assigned by minimisation to: 48-h intravenous fluorouracil with levofolinate (group A); oxaliplatin and fluorouracil (group B); capecitabine (group C); or oxaliplatin and capecitabine (group D). Treatment allocation was not masked. Starting doses were 80% of standard doses, with discretionary escalation to full dose after 6 weeks. The two primary outcome measures were: addition of oxaliplatin ([A vs B] + [C vs D]), assessed with progression-free survival (PFS); and substitution of fluorouracil with capecitabine ([A vs C] + [B vs D]), assessed by change from baseline to 12 weeks in global quality of life (QoL). Analysis was by intention to treat. Baseline clinical and CHA data were modelled against outcomes with a novel composite measure, overall treatment utility (OTU). This study is registered, number ISRCTN21221452. FINDINGS 459 patients were randomly assigned (115 to each of groups A-C, 114 to group D). Factorial comparison of addition of oxaliplatin versus no addition suggested some improvement in PFS, but the finding was not significant (median 5·8 months [IQR 3·3-7·5] vs 4·5 months [2·8-6·4]; hazard ratio 0·84, 95% CI 0·69-1·01, p=0·07). Replacement of fluorouracil with capecitabine did not improve global QoL: 69 of 124 (56%) patients receiving fluorouracil reported improvement in global QoL compared with 69 of 123 (56%) receiving capecitabine. The risk of having any grade 3 or worse toxic effect was not significantly increased with oxaliplatin (83/219 [38%] vs 70/221 [32%]; p=0·17), but was higher with capecitabine than with fluorouracil (88/222 [40%] vs 65/218 [30%]; p=0·03). In multivariable analysis, fewer baseline symptoms (odds ratio 1·32, 95% CI 1·14-1·52), less widespread disease (1·51, 1·05-2·19), and use of oxaliplatin (0·57, 0·39-0·82) were predictive of better OTU. INTERPRETATION FOCUS2 shows that with an appropriate design, including reduced starting doses of chemotherapy, frail and elderly patients can participate in a randomised controlled trial. On balance, a combination including oxaliplatin was preferable to single-agent fluoropyrimidines, although the primary endpoint of PFS was not met. Capecitabine did not improve QoL compared with fluorouracil. Comprehensive baseline assessment holds promise as an objective predictor of treatment benefit. FUNDING Cancer Research UK and the Medical Research Council.",
"title": "Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial"
}
] |
[
{
"docid": "2492146",
"text": "Metastatic colorectal cancer (mCRC) is increasingly treated using targeted therapies. Post-marketing safety of these agents is understudied, especially in the elderly. This study aimed to compare, according to age, the adverse drug reactions (ADRs) of targeted therapies used for mCRC in real life. An extraction of VigiBase, which contains World Health Organization individual case safety reports (ICSRs), was performed. All ADR reports with aflibercept, bevacizumab, cetuximab, panitumumab, or regorafenib used in CRC were considered. For all drugs, chi-square tests were used to compare frequencies of serious ADRs between patients aged ≥75 and <75 years. For selected ADRs and each drug, the drug-ADR association compared to other anticancer drugs was estimated through the proportional reporting ratio (PRR) in both age groups. There were 21,565 ICSRs included, among which 74% were serious and 11% were fatal. Median age was 64 years (Inter Quartile Range = 56–71) and 15% of patients were aged ≥75; 57% were male. Serious ICSRs accounted for 47,292 ADRs. Neutropenia was not more reported in elderly for all drugs while diarrhea was more reported in elderly for panitumumab. Cardiac disorders were more reported in elderly patients, in particular heart failure, especially for bevacizumab, cetuximab, and regorafenib, as were respiratory, thoracic, and mediastinal disorders. Most of PRR were not different between the two groups, except encephalopathies, which were significantly associated with bevacizumab in the elderly only. ADRs related to targeted therapies used for mCRC treatment were different across age groups; yet, not systematically more reported or worse in elderly patients. Selected elderly patients could, therefore, be treated with these targeted therapies.",
"title": "Comparative Safety of Targeted Therapies for Metastatic Colorectal Cancer between Elderly and Younger Patients: a Study Using the International Pharmacovigilance Database"
},
{
"docid": "13256155",
"text": "BACKGROUND Molecularly targeted agents have been reported to have anti-tumour activity for patients whose tumours harbour the matching molecular alteration. These results have led to increased off-label use of molecularly targeted agents on the basis of identified molecular alterations. We assessed the efficacy of several molecularly targeted agents marketed in France, which were chosen on the basis of tumour molecular profiling but used outside their indications, in patients with advanced cancer for whom standard-of-care therapy had failed. METHODS The open-label, randomised, controlled phase 2 SHIVA trial was done at eight French academic centres. We included adult patients with any kind of metastatic solid tumour refractory to standard of care, provided they had an Eastern Cooperative Oncology Group performance status of 0 or 1, disease that was accessible for a biopsy or resection of a metastatic site, and at least one measurable lesion. The molecular profile of each patient's tumour was established with a mandatory biopsy of a metastatic tumour and large-scale genomic testing. We only included patients for whom a molecular alteration was identified within one of three molecular pathways (hormone receptor, PI3K/AKT/mTOR, RAF/MEK), which could be matched to one of ten regimens including 11 available molecularly targeted agents (erlotinib, lapatinib plus trastuzumab, sorafenib, imatinib, dasatinib, vemurafenib, everolimus, abiraterone, letrozole, tamoxifen). We randomly assigned these patients (1:1) to receive a matched molecularly targeted agent (experimental group) or treatment at physician's choice (control group) by central block randomisation (blocks of size six). Randomisation was done centrally with a web-based response system and was stratified according to the Royal Marsden Hospital prognostic score (0 or 1 vs 2 or 3) and the altered molecular pathway. Clinicians and patients were not masked to treatment allocation. Treatments in both groups were given in accordance with the approved product information and standard practice protocols at each institution and were continued until evidence of disease progression. The primary endpoint was progression-free survival in the intention-to-treat population, which was not assessed by independent central review. We assessed safety in any patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT01771458. FINDINGS Between Oct 4, 2012, and July 11, 2014, we screened 741 patients with any tumour type. 293 (40%) patients had at least one molecular alteration matching one of the 10 available regimens. At the time of data cutoff, Jan 20, 2015, 195 (26%) patients had been randomly assigned, with 99 in the experimental group and 96 in the control group. All patients in the experimental group started treatment, as did 92 in the control group. Two patients in the control group received a molecularly targeted agent: both were included in their assigned group for efficacy analyses, the patient who received an agent that was allowed in the experimental group was included in the experimental group for the purposes of safety analyses, while the other patient, who received a molecularly targeted agent and chemotherapy, was kept in the control group for safety analyses. Median follow-up was 11·3 months (IQR 5·8-11·6) in the experimental group and 11·3 months (8·1-11·6) in the control group at the time of the primary analysis of progression-free survival. Median progression-free survival was 2·3 months (95% CI 1·7-3·8) in the experimental group versus 2·0 months (1·8-2·1) in the control group (hazard ratio 0·88, 95% CI 0·65-1·19, p=0·41). In the safety population, 43 (43%) of 100 patients treated with a molecularly targeted agent and 32 (35%) of 91 patients treated with cytotoxic chemotherapy had grade 3-4 adverse events (p=0·30). INTERPRETATION The use of molecularly targeted agents outside their indications does not improve progression-free survival compared with treatment at physician's choice in heavily pretreated patients with cancer. Off-label use of molecularly targeted agents should be discouraged, but enrolment in clinical trials should be encouraged to assess predictive biomarkers of efficacy.",
"title": "Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial."
},
{
"docid": "20606520",
"text": "OBJECTIVES To assess mortality, quality of life (QOL), and quality-adjusted life-years (QALYs) for critically ill elderly patients. DESIGN Cross-sectional survey. SETTING A ten-bed medical-surgical intensive care unit (ICU) in a tertiary care university hospital. PATIENTS The study group included 882 elderly patients (> or =65 yrs of age) and 1,827 controls (<65 yrs of age) treated during the period of 1995 to 2000. INTERVENTION None. MEASUREMENTS AND MAIN RESULTS Mortality was assessed during the ICU and hospital stays, and 12, 24, and 36 months after ICU discharge. The cumulative 3-yr mortality rate among the elderly (57%) was higher (p < .05) than that among the controls (40%). The majority (66%) of the elderly nonsurvivors died within 1 month after intensive care discharge. All elderly patients with day-1 Sequential Organ Failure (SOFA) scores >15 died during the ICU stay. QOL was assessed with EQ-5D and RAND-36 measures from 10 months to 7 yrs after discharge. The majority (88%) of the elderly survivors assessed their present health state as good or satisfactory; 66% found it to be similar or better than 12 months earlier, and 48% similar or better than their preadmission state. QOL measures by RAND-36 revealed that aging decreased their competencies most in physical functioning, physical role limitations, and vitality, but the elderly had better values in mental health than the controls. However, QALYs of the elderly respondents were 21% to 35% lower than the mean QALY minus 2 sd units of the age- and gender-adjusted general population. CONCLUSIONS High age alone is not a valid reason to refuse intensive care, but the benefits perceived by intensive care seem to decrease with aging, if reflected as QALYs. However, 97% of the elderly survivors lived at home and 88% of them considered their QOL satisfactory or good after hospital discharge. Therefore, more reliable information on the outcome for the elderly is clearly needed.",
"title": "Long-term survival, quality of life, and quality-adjusted life-years among critically ill elderly patients."
},
{
"docid": "7165938",
"text": "PURPOSE The circadian clock gene Bmal1 is involved in cancer cell proliferation and DNA damage sensitivity. The aim of this study was to explore the effect of Bmal1 on oxaliplatin sensitivity and to determine its clinical significance in colorectal cancer. EXPERIMENTAL DESIGN Three colorectal cancer cell lines, HCT116, THC8307 and HT29, were used. The Bmal1-mediated control of colorectal cancer cell proliferation was tested in vitro and in vivo. MTT and colony formation assays were performed to determine the sensitivity of colorectal cancer cells to oxaliplatin. Flow cytometry was used to examine changes in the cell-cycle distribution and apoptosis rate. Proteins expressed downstream of Bmal1 upon its overexpression were determined by Western blotting. Immunohistochemistry was used to analyze Bmal1 expression in 82 archived colorectal cancer tumors from patients treated with oxaliplatin-based regimens. RESULTS Bmal1 overexpression inhibited colorectal cancer cell proliferation and increased colorectal cancer sensitivity to oxaliplatin in three colorectal cancer cell lines and HCT116 cells model in vivo. Furthermore, the overall survival of patients with colorectal cancer with high Bmal1 levels in their primary tumors was significantly longer than that of patients with low Bmal1 levels (27 vs. 19 months; P = 0.043). The progression-free survival of patients with high Bmal1 expression was also significantly longer than that of patients with low Bmal1 expression (11 vs. 5 months; P = 0.015). Mechanistically, the effect of Bmal1 was associated with its ability to regulate G2-M arrest by activating the ATM pathway. CONCLUSION Bmal1 shows the potential as a novel prognostic biomarker and may represent a new therapeutic target in colorectal cancer.",
"title": "Overexpression of the circadian clock gene Bmal1 increases sensitivity to oxaliplatin in colorectal cancer."
},
{
"docid": "9929089",
"text": "BACKGROUND Patients with advanced or metastatic non-small cell lung cancer (NSCLC) can develop acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib. Here, we report the successful treatment with alternating chemotherapy and TKIs of two cases of advanced NSCLC who developed resistance to TKI. CASE PRESENTATION Two patients with advanced or metastatic NSCLC were treated with palliative chemotherapy followed by erlotinib/gefitinib. When TKI therapy failed, two cycles of chemotherapy were provided, which were followed by re-challenge with erlotinib or gefitinib. CONCLUSION NSCLC patients with acquired TKI resistance should be managed aggressively whenever possible. Subsequent chemotherapy and target treatment is one of the reasonable choices for those with an initial dramatic clinical response with erlotinib/gefitinib treatment. Further studies are warranted to substantiate the association of erlotinib /gefitinib treatment with the efficacy of NSCLC patients with acquired TKI failure.",
"title": "Subsequent chemotherapy reverses acquired tyrosine kinase inhibitor resistance and restores response to tyrosine kinase inhibitor in advanced non-small-cell lung cancer"
},
{
"docid": "24974080",
"text": "New blood vessel formation (angiogenesis) is a fundamental event in the process of tumor growth and metastatic dissemination. Hence, the molecular basis of tumor angiogenesis has been of keen interest in the field of cancer research. The vascular endothelial growth factor (VEGF) pathway is well established as one of the key regulators of this process. The VEGF/VEGF-receptor axis is composed of multiple ligands and receptors with overlapping and distinct ligand-receptor binding specificities, cell-type expression, and function. Activation of the VEGF-receptor pathway triggers a network of signaling processes that promote endothelial cell growth, migration, and survival from pre-existing vasculature. In addition, VEGF mediates vessel permeability, and has been associated with malignant effusions. More recently, an important role for VEGF has emerged in mobilization of endothelial progenitor cells from the bone marrow to distant sites of neovascularization. The well-established role of VEGF in promoting tumor angiogenesis and the pathogenesis of human cancers has led to the rational design and development of agents that selectively target this pathway. Studies with various anti-VEGF/VEGF-receptor therapies have shown that these agents can potently inhibit angiogenesis and tumor growth in preclinical models. Recently, an anti-VEGF antibody (bevacizumab), when used in combination with chemotherapy, was shown to significantly improve survival and response rates in patients with metastatic colorectal cancer and thus, validate VEGF pathway inhibitors as an important new treatment modality in cancer therapy.",
"title": "Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis."
},
{
"docid": "24873253",
"text": "Patients with metastatic bone disease are at risk for developing skeletal-related events that can negatively influence quality of life, contributing to loss of autonomy and functional capabilities. Bisphosphonates have become an important component in the treatment of patients with bone metastases as they delay the onset and reduce the risk of skeletal-related events and also palliate or control bone pain in multiple cancer types, thus preserving quality of life. Zoledronic acid has proven efficacy and safety in patients with bone lesions from breast cancer, prostate cancer, lung cancer, and other solid tumors, as well as in patients with multiple myeloma. Current data suggest that early treatment with zoledronic acid (before the onset of bone pain) may provide additional clinical benefits and also positive effects on survival in subsets of patients who have elevated levels of N-telopeptide of type I collagen (NTX), a biochemical marker of bone resorption. Studies have shown that in patients with breast cancer, prostate cancer, lung cancer, or other solid tumors, normalization of elevated levels of NTX was observed in the majority of patients who received zoledronic acid. Furthermore, normalization of NTX values correlated with extended survival.",
"title": "Clinical benefits and considerations of bisphosphonate treatment in metastatic bone disease."
},
{
"docid": "25589047",
"text": "CONTEXT Fatal adverse events (FAEs) have been reported in cancer patients treated with the widely used angiogenesis inhibitor bevacizumab in combination with chemotherapy. Currently, the role of bevacizumab in treatment-related mortality is not clear. OBJECTIVE To perform a systematic review and meta-analysis of published randomized controlled trials (RCTs) to determine the overall risk of FAEs associated with bevacizumab. DATA SOURCES PubMed, EMBASE, and Web of Science databases as well as abstracts presented at American Society of Clinical Oncology conferences from January 1966 to October 2010 were searched to identify relevant studies. STUDY SELECTION AND DATA EXTRACTION Eligible studies included prospective RCTs in which bevacizumab in combination with chemotherapy or biological therapy was compared with chemotherapy or biological therapy alone. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. DATA SYNTHESIS A total of 10,217 patients with a variety of advanced solid tumors from 16 RCTs were included in the analysis. The overall incidence of FAEs with bevacizumab was 2.5% (95% CI, 1.7%-3.9%). Compared with chemotherapy alone, the addition of bevacizumab was associated with an increased risk of FAEs, with an RR of 1.46 (95% CI, 1.09-1.94; P = .01; incidence, 2.5% vs 1.7%). This association varied significantly with chemotherapeutic agents (P = .045) but not with tumor types (P = .13) or bevacizumab doses (P = .16). Bevacizumab was associated with an increased risk of FAEs in patients receiving taxanes or platinum agents (RR, 3.49; 95% CI, 1.82-6.66; incidence, 3.3% vs 1.0%) but was not associated with increased risk of FAEs when used in conjunction with other agents (RR, 0.85; 95% CI, 0.25-2.88; incidence, 0.8% vs 0.9%). The most common causes of FAEs were hemorrhage (23.5%), neutropenia (12.2%), and gastrointestinal tract perforation (7.1%). CONCLUSION In a meta-analysis of RCTs, bevacizumab in combination with chemotherapy or biological therapy, compared with chemotherapy alone, was associated with increased treatment-related mortality.",
"title": "Treatment-related mortality with bevacizumab in cancer patients: a meta-analysis."
},
{
"docid": "9558539",
"text": "Cancer stem cells drive tumor formation and metastasis, but how they acquire metastatic traits is not well understood. Here, we show that all colorectal cancer stem cells (CR-CSCs) express CD44v6, which is required for their migration and generation of metastatic tumors. CD44v6 expression is low in primary tumors but demarcated clonogenic CR-CSC populations. Cytokines hepatocyte growth factor (HGF), osteopontin (OPN), and stromal-derived factor 1α (SDF-1), secreted from tumor associated cells, increase CD44v6 expression in CR-CSCs by activating the Wnt/β-catenin pathway, which promotes migration and metastasis. CD44v6(-) progenitor cells do not give rise to metastatic lesions but, when treated with cytokines, acquire CD44v6 expression and metastatic capacity. Importantly, phosphatidylinositol 3-kinase (PI3K) inhibition selectively killed CD44v6 CR-CSCs and reduced metastatic growth. In patient cohorts, low levels of CD44v6 predict increased probability of survival. Thus, the metastatic process in colorectal cancer is initiated by CSCs through the expression of CD44v6, which is both a functional biomarker and therapeutic target.",
"title": "CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis."
},
{
"docid": "20127522",
"text": "PURPOSE Five or more circulating tumor cells (CTCs) per 7.5 mL of blood predicts for poorer progression-free survival (PFS) in patients with metastatic breast cancer (MBC). We conducted a prospective study to demonstrate that CTC results correlate strongly with radiographic disease progression at the time of and in advance of imaging. PATIENTS AND METHODS Serial CTC levels were obtained in patients starting a new treatment regimen for progressive, radiographically measurable MBC. Peripheral blood was collected for CTC enumeration at baseline and at 3- to 4-week intervals. Clinical outcomes were based on radiographic studies performed in 9- to 12-week intervals. RESULTS Sixty-eight patients were evaluable for the CTC-imaging correlations, and 74 patients were evaluable for the PFS analysis. Median follow-up was 13.3 months. A statistically significant correlation was demonstrated between CTC levels and radiographic disease progression in patients receiving chemotherapy or endocrine therapy. This correlation applied to CTC results obtained at the time of imaging (odds ratio [OR], 6.3), 3 to 5 weeks before imaging (OR, 3.1), and 7 to 9 weeks before imaging (OR, 4.9). Results from analyses stratified by type of therapy remained statistically significant. Shorter PFS was observed for patients with five or more CTCs at 3 to 5 weeks and at 7 to 9 weeks after the start of treatment. CONCLUSION We provide, to our knowledge, the first evidence of a strong correlation between CTC results and radiographic disease progression in patients receiving chemotherapy or endocrine therapy for MBC. These findings support the role of CTC enumeration as an adjunct to standard methods of monitoring disease status in MBC.",
"title": "Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer."
},
{
"docid": "6334188",
"text": "BACKGROUND Chemotherapy-induced febrile neutropenia (FN) is a clinically important complication that affects patient outcome by delaying chemotherapy doses or reducing dose intensity. Risk of FN depends on chemotherapy- and patient-level factors. We sought to determine the effects of chronic comorbidities on risk of FN. DESIGN We conducted a cohort study to examine the association between a variety of chronic comorbidities and risk of FN in patients diagnosed with six types of cancer (non-Hodgkin lymphoma and breast, colorectal, lung, ovary, and gastric cancer) from 2000 to 2009 who were treated with chemotherapy at Kaiser Permanente Southern California, a large managed care organization. We excluded those patients who received primary prophylactic granulocyte colony-stimulating factor. History of comorbidities and FN events were identified using electronic medical records. Cox models adjusting for propensity score, stratified by cancer type, were used to determine the association between comorbid conditions and FN. Models that additionally adjusted for cancer stage, baseline neutrophil count, chemotherapy regimen, and dose reduction were also evaluated. RESULTS A total of 19 160 patients with mean age of 60 years were included; 963 (5.0%) developed FN in the first chemotherapy cycle. Chronic obstructive pulmonary disease [hazard ratio (HR) = 1.30 (1.07-1.57)], congestive heart failure [HR = 1.43 (1.00-1.98)], HIV infection [HR = 3.40 (1.90-5.63)], autoimmune disease [HR = 2.01 (1.10-3.33)], peptic ulcer disease [HR = 1.57 (1.05-2.26)], renal disease [HR = 1.60 (1.21-2.09)], and thyroid disorder [HR = 1.32 (1.06-1.64)] were all associated with a significantly increased FN risk. CONCLUSIONS These results provide evidence that history of several chronic comorbidities increases risk of FN, which should be considered when managing patients during chemotherapy.",
"title": "History of chronic comorbidity and risk of chemotherapy-induced febrile neutropenia in cancer patients not receiving G-CSF prophylaxis."
},
{
"docid": "22635278",
"text": "From April 1986 to September 2000, 122 MRCC patients were treated by monthly intralymphatic injections (containing a mean of 573 IL-2 U and 26 x 10(6) LAK cells) and i.m. administration of IFN and TF; 71 patients also received a 3-day cycle of monthly IL-2 inhalations with a mean of 998 daily U. MRCC cases not treated by immunotherapy (n = 89) represent our historical controls. Adverse clinical side effects related to treatment were negligible. CR (n = 11) and PR (n = 13) were noticed in 24/122 patients. Of 24 responding patients, 17 resumed progression, whereas 7 remain in remission 11-69 months later. The overall median survival of treated patients (28 months) was 3.5-fold higher than the median survival of historical controls (7.5 months), and a Kaplan-Meier curve showed 25% survival 11 years after the beginning of immunotherapy. Apparently, the addition of IL-2 by inhalation improved survival. The present immunotherapy protocol appears to be efficacious, safe, devoid of adverse side effects, far less costly than others and able to offer a good quality of life to MRCC patients; if confirmed in a multicenter trial, it could set the basis for developing low-dose immunomodulatory treatments.",
"title": "Immunotherapy of metastatic kidney cancer."
},
{
"docid": "5912283",
"text": "CONTEXT Insomnia is a common condition in older adults and is associated with a number of adverse medical, social, and psychological consequences. Previous research has suggested beneficial outcomes of both psychological and pharmacological treatments, but blinded placebo-controlled trials comparing the effects of these treatments are lacking. OBJECTIVE To examine short- and long-term clinical efficacy of cognitive behavioral therapy (CBT) and pharmacological treatment in older adults experiencing chronic primary insomnia. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blinded, placebo-controlled trial of 46 adults (mean age, 60.8 y; 22 women) with chronic primary insomnia conducted between January 2004 and December 2005 in a single Norwegian university-based outpatient clinic for adults and elderly patients. INTERVENTION CBT (sleep hygiene, sleep restriction, stimulus control, cognitive therapy, and relaxation; n = 18), sleep medication (7.5-mg zopiclone each night; n = 16), or placebo medication (n = 12). All treatment duration was 6 weeks, and the 2 active treatments were followed up at 6 months. MAIN OUTCOME MEASURES Ambulant clinical polysomnographic data and sleep diaries were used to determine total wake time, total sleep time, sleep efficiency, and slow-wave sleep (only assessed using polysomnography) on all 3 assessment points. RESULTS CBT resulted in improved short- and long-term outcomes compared with zopiclone on 3 out of 4 outcome measures. For most outcomes, zopiclone did not differ from placebo. Participants receiving CBT improved their sleep efficiency from 81.4% at pretreatment to 90.1% at 6-month follow-up compared with a decrease from 82.3% to 81.9% in the zopiclone group. Participants in the CBT group spent much more time in slow-wave sleep (stages 3 and 4) compared with those in other groups, and spent less time awake during the night. Total sleep time was similar in all 3 groups; at 6 months, patients receiving CBT had better sleep efficiency using polysomnography than those taking zopiclone. CONCLUSION These results suggest that interventions based on CBT are superior to zopiclone treatment both in short- and long-term management of insomnia in older adults. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00295386.",
"title": "Cognitive behavioral therapy vs zopiclone for treatment of chronic primary insomnia in older adults: a randomized controlled trial."
},
{
"docid": "24341590",
"text": "CONTEXT The growth inhibitory effect of tamoxifen, which is used for the treatment of hormone receptor-positive breast cancer, is mediated by its metabolites, 4-hydroxytamoxifen and endoxifen. The formation of active metabolites is catalyzed by the polymorphic cytochrome P450 2D6 (CYP2D6) enzyme. OBJECTIVE To determine whether CYP2D6 variation is associated with clinical outcomes in women receiving adjuvant tamoxifen. DESIGN, SETTING, AND PATIENTS Retrospective analysis of German and US cohorts of patients treated with adjuvant tamoxifen for early stage breast cancer. The 1325 patients had diagnoses between 1986 and 2005 of stage I through III breast cancer and were mainly postmenopausal (95.4%). Last follow-up was in December 2008; inclusion criteria were hormone receptor positivity, no metastatic disease at diagnosis, adjuvant tamoxifen therapy, and no chemotherapy. DNA from tumor tissue or blood was genotyped for CYP2D6 variants associated with reduced (*10, *41) or absent (*3, *4, *5) enzyme activity. Women were classified as having an extensive (n=609), heterozygous extensive/intermediate (n=637), or poor (n=79) CYP2D6 metabolism. MAIN OUTCOME MEASURES Time to recurrence, event-free survival, disease-free survival, and overall survival. RESULTS Median follow-up was 6.3 years. At 9 years of follow-up, the recurrence rates were 14.9% for extensive metabolizers, 20.9% for heterozygous extensive/intermediate metabolizers, and 29.0% for poor metabolizers, and all-cause mortality rates were 16.7%, 18.0%, and 22.8%, respectively. Compared with extensive metabolizers, there was a significantly increased risk of recurrence for heterozygous extensive/intermediate metabolizers (time to recurrence adjusted hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.04-1.90) and for poor metabolizers (time to recurrence HR, 1.90; 95% CI, 1.10-3.28). Compared with extensive metabolizers, those with decreased CYP2D6 activity (heterozygous extensive/intermediate and poor metabolism) had worse event-free survival (HR, 1.33; 95% CI, 1.06-1.68) and disease-free survival (HR, 1.29; 95% CI, 1.03-1.61), but there was no significant difference in overall survival (HR, 1.15; 95% CI, 0.88-1.51). CONCLUSION Among women with breast cancer treated with tamoxifen, there was an association between CYP2D6 variation and clinical outcomes, such that the presence of 2 functional CYP2D6 alleles was associated with better clinical outcomes and the presence of nonfunctional or reduced-function alleles with worse outcomes.",
"title": "Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen."
},
{
"docid": "42731834",
"text": "Functional studies on colorectal cancer cells indicated a protective role of the interferon-inducible dsDNA sensor Absent in Melanoma 2 (AIM2) in cancer progression. Given that a high mutation rate and lack of AIM2 expression was previously detected in a subset of colorectal cancers, we here investigated the association of AIM2 expression in tumor cells and patient prognosis (5-year follow-up). A tissue microarray analysis of 476 matched tissue pairs (colorectal tumor and adjacent normal colon epithelium) was performed by two independent observers. Samples from 62 patients were excluded because of missing follow-up information or due to neo-adjuvant therapy before tissue sampling. Out of the remaining 414 tissue pairs, 279 (67.4%) displayed reduced AIM2 expression in cancer cells when compared to epithelial cells of their normal counterpart. Thirty-eight patients (9.18%) had completely lost AIM2 expression in tumor cells. After adjustment for sex, age, cancer stage, tumor site, tumor grade and chemotherapy, complete lack of AIM2 expression was associated with an up to 3-fold increase in overall mortality (HR=2.40; 95% CI=1.44-3.99) and disease specific mortality (HR=3.14; 95% CI=1.75-5.65) in comparison to AIM2-positive tumor samples. Our results demonstrate that lack of AIM2 expression is closely associated with poor outcome in colorectal cancer. The data thus strongly substantiate a protective role of AIM2 against progression of colorectal tumors. Further studies are required to assess whether lack of AIM2 expression may be used as a biomarker for the identification of colorectal cancer patients with poor prognosis.",
"title": "Lack of Absent in Melanoma 2 (AIM2) expression in tumor cells is closely associated with poor survival in colorectal cancer patients."
},
{
"docid": "25690516",
"text": "The aim of the study was to evaluate whether treatment with recombinant human growth hormone (rhGH) affects the quality of life of young adults who were diagnosed as idiopathic short stature (ISS) during childhood, and whether their quality of life and aspects of the personality are different from normal. Experiences and expectations concerning rhGH treatment of the subjects and their parents were also investigated. Eighty-nine subjects were included into the study: 24 subjects (16M, 8F) were treated with rhGH from childhood, whereas 65 subjects (40M, 25F) were never treated. At the time of the interview all subjects had attained final height [mean (SD) -2.3 (0.9) SDS for Dutch references], and the age of the treated subjects was 20.5 (1.0) y, and 25.7 (3.5) y of the control subjects (p < 0.001). The level of education was similar, but the treated subjects had less often a partner compared to the control subjects (adjusted for age and gender, p < 0.001). The Nottingham Health Profile and Short Form 36 Health Survey showed no difference in general health state between treated and control subjects, and the healthy Dutch age-specific references (norm group). Although 74% of the subjects reported one or more negative events related to their height, and 61% would like to be taller, only 22% and 11% were willing to trade-off at Time Trade-Off and Standard Gamble, respectively. The personality of the subjects, which was measured by the Minnesota Multiphasic Personality Inventory, was not different from the norm group. The satisfaction with the rhGH treatment was high, as it had caused 12 (8) cm and 13 (7) cm gain in final height according to the subjects and parents, respectively. Based on initial predicted adult height (Bayley & Pinneau), this gain was only 3.3 (5.6) cm. We concluded that although the treated subjects had a partner less often when compared to the control subjects, the quality of life of subjects with ISS at adult age is normal and appears not to be affected by rhGH therapy, The treated subjects were very satisfied with the treatment, probably by overestimation of the final height gain.",
"title": "Quality of life of young adults with idiopathic short stature: effect of growth hormone treatment. Dutch Growth Hormone Working Group."
},
{
"docid": "15041758",
"text": "OBJECTIVE To evaluate the effectiveness of integrated care for chronic physical diseases and depression in reducing disability and improving quality of life. DESIGN A randomised controlled trial of multi-condition collaborative care for depression and poorly controlled diabetes and/or risk factors for coronary heart disease compared with usual care among middle aged and elderly people SETTING Fourteen primary care clinics in Seattle, Washington. PARTICIPANTS Patients with diabetes or coronary heart disease, or both, and blood pressure above 140/90 mm Hg, low density lipoprotein concentration >3.37 mmol/L, or glycated haemoglobin 8.5% or higher, and PHQ-9 depression scores of ≥ 10. INTERVENTION A 12 month intervention to improve depression, glycaemic control, blood pressure, and lipid control by integrating a \"treat to target\" programme for diabetes and risk factors for coronary heart disease with collaborative care for depression. The intervention combined self management support, monitoring of disease control, and pharmacotherapy to control depression, hyperglycaemia, hypertension, and hyperlipidaemia. MAIN OUTCOME MEASURES Social role disability (Sheehan disability scale), global quality of life rating, and World Health Organization disability assessment schedule (WHODAS-2) scales to measure disabilities in activities of daily living (mobility, self care, household maintenance). RESULTS Of 214 patients enrolled (106 intervention and 108 usual care), disability and quality of life measures were obtained for 97 intervention patients at six months (92%) and 92 at 12 months (87%), and for 96 usual care patients at six months (89%) and 92 at 12 months (85%). Improvements from baseline on the Sheehan disability scale (-0.9, 95% confidence interval -1.5 to -0.2; P = 0.006) and global quality of life rating (0.7, 0.2 to 1.2; P = 0.005) were significantly greater at six and 12 months in patients in the intervention group. There was a trend toward greater improvement in disabilities in activities of daily living (-1.5, -3.3 to 0.4; P = 0.10). CONCLUSIONS Integrated care that covers chronic physical disease and comorbid depression can reduce social role disability and enhance global quality of life. Trial registration Clinical Trials NCT00468676.",
"title": "Functional outcomes of multi-condition collaborative care and successful ageing: results of randomised trial"
},
{
"docid": "52180874",
"text": "OBJECTIVE To evaluate the relative efficacy of programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors versus conventional drugs in patients with cancer that were PD-L1 positive and PD-L1 negative. DESIGN Meta-analysis of randomised controlled trials. DATA SOURCES PubMed, Embase, Cochrane database, and conference abstracts presented at the American Society of Clinical Oncology and European Society of Medical Oncology up to March 2018. REVIEW METHODS Studies of PD-1 or PD-L1 inhibitors (avelumab, atezolizumab, durvalumab, nivolumab, and pembrolizumab) that had available hazard ratios for death based on PD-L1 positivity or negativity were included. The threshold for PD-L1 positivity or negativity was that PD-L1 stained cell accounted for 1% of tumour cells, or tumour and immune cells, assayed by immunohistochemistry staining methods. RESULTS 4174 patients with advanced or metastatic cancers from eight randomised controlled trials were included in this study. Compared with conventional agents, PD-1 or PD-L1 inhibitors were associated with significantly prolonged overall survival in both patients that were PD-L1 positive (n=2254, hazard ratio 0.66, 95% confidence interval 0.59 to 0.74) and PD-L1 negative (1920, 0.80, 0.71 to 0.90). However, the efficacies of PD-1 or PD-L1 blockade treatment in patients that were PD-L1 positive and PD-L1 negative were significantly different (P=0.02 for interaction). Additionally, in both patients that were PD-L1 positive and PD-L1 negative, the long term clinical benefits from PD-1 or PD-L1 blockade were observed consistently across interventional agent, cancer histotype, method of randomisation stratification, type of immunohistochemical scoring system, drug target, type of control group, and median follow-up time. CONCLUSIONS PD-1 or PD-L1 blockade therapy is a preferable treatment option over conventional therapy for both patients that are PD-L1 positive and PD-L1 negative. This finding suggests that PD-L1 expression status alone is insufficient in determining which patients should be offered PD-1 or PD-L1 blockade therapy.",
"title": "Efficacy of PD-1 or PD-L1 inhibitors and PD-L1 expression status in cancer: meta-analysis"
},
{
"docid": "52188256",
"text": "This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.",
"title": "Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries."
},
{
"docid": "24575065",
"text": "CONTEXT The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) altered reimbursements for outpatient chemotherapy drugs and drug administration services. Anecdotal reports suggest that these adjustments may have negatively affected access to chemotherapy for Medicare beneficiaries. OBJECTIVE To compare patient wait times and travel distances for chemotherapy before and after the enactment of the MMA. DESIGN, SETTING, AND PATIENTS Analysis of a nationally representative 5% sample of claims from the Centers for Medicare & Medicaid Services for the period 2003 through 2006. Patients were Medicare beneficiaries with incident breast cancer, colorectal cancer, leukemia, lung cancer, or lymphoma who received chemotherapy in inpatient hospital, institutional outpatient, or physician office settings. MAIN OUTCOME MEASURES Days from incident diagnosis to first chemotherapy visit and distance traveled for treatment, controlling for age, sex, race/ethnicity, cancer type, geographic region, comorbid conditions, and year of diagnosis and treatment. RESULTS There were 5082 incident cases of breast cancer, colorectal cancer, leukemia, lung cancer, or lymphoma in 2003; 5379 cases in 2004; 5116 cases in 2005; and 5288 cases in 2006. Approximately 70% of patients received treatment in physician office settings in each year. Although the distribution of treatment settings in 2004 and 2005 was not significantly different from 2003 (P = .24 and P = .72, respectively), there was a small but significant change from 2003 to 2006 (P = .02). The proportion of patients receiving chemotherapy in inpatient settings decreased from 10.2% in 2003 to 8.8% in 2006 (P = .03), and the proportion in institutional outpatient settings increased from 21.1% to 22.5% (P = .004). The proportion in physician offices remained at 68.7% (P = .29). The median time from diagnosis to initial chemotherapy visit was 28 days in 2003, 27 days in 2004, 29 days in 2005, and 28 days in 2006. In multivariate analyses, average wait times for chemotherapy were 1.96 days longer in 2005 than in 2003 (95% confidence interval [CI], 0.11-3.80 days; P = .04) but not significantly different in 2006 (0.88 days; 95% CI, -0.96 to 2.71 days; P = .35). Median travel distance was 7 miles (11.2 km) in 2003 and 8 miles (12.8 km) in 2004 through 2006. After adjustment, average travel distance remained slightly longer in 2004 (1.47 miles [2.35 km]; 95% CI, 0.87-2.07 miles [1.39-3.31 km]; P < .001), 2005 (1.19 miles [1.90 km]; 95% CI, 0.58-1.80 miles [0.93-2.88 km]; P < .001), and 2006 (1.30 miles [2.08 km]; 95% CI, 0.69-1.90 miles [1.10-3.04 km]; P < .001) compared with 2003. CONCLUSION There have not been major changes in travel distance and patient wait times for chemotherapy in the Medicare population since 2003, the year before MMA-related changes in reimbursement.",
"title": "Association between the Medicare Modernization Act of 2003 and patient wait times and travel distance for chemotherapy."
},
{
"docid": "5151024",
"text": "BACKGROUND The diagnosis of hypertension has traditionally been based on blood-pressure measurements in the clinic, but home and ambulatory measurements better correlate with cardiovascular outcome, and ambulatory monitoring is more accurate than both clinic and home monitoring in diagnosing hypertension. We aimed to compare the cost-effectiveness of different diagnostic strategies for hypertension. METHODS We did a Markov model-based probabilistic cost-effectiveness analysis. We used a hypothetical primary-care population aged 40 years or older with a screening blood-pressure measurement greater than 140/90 mm Hg and risk-factor prevalence equivalent to the general population. We compared three diagnostic strategies-further blood pressure measurement in the clinic, at home, and with an ambulatory monitor-in terms of lifetime costs, quality-adjusted life years, and cost-effectiveness. FINDINGS Ambulatory monitoring was the most cost-effective strategy for the diagnosis of hypertension for men and women of all ages. It was cost-saving for all groups (from -£56 [95% CI -105 to -10] in men aged 75 years to -£323 [-389 to -222] in women aged 40 years) and resulted in more quality-adjusted life years for men and women older than 50 years (from 0·006 [0·000 to 0·015] for women aged 60 years to 0·022 [0·012 to 0·035] for men aged 70 years). This finding was robust when assessed with a wide range of deterministic sensitivity analyses around the base case, but was sensitive if home monitoring was judged to have equal test performance to ambulatory monitoring or if treatment was judged effective irrespective of whether an individual was hypertensive. INTERPRETATION Ambulatory monitoring as a diagnostic strategy for hypertension after an initial raised reading in the clinic would reduce misdiagnosis and save costs. Additional costs from ambulatory monitoring are counterbalanced by cost savings from better targeted treatment. Ambulatory monitoring is recommended for most patients before the start of antihypertensive drugs. FUNDING National Institute for Health Research and the National Institute for Health and Clinical Excellence.",
"title": "Cost-effectiveness of options for the diagnosis of high blood pressure in primary care: a modelling study."
},
{
"docid": "20610557",
"text": "In recent years, the immune-potentiating effects of some widely used chemotherapeutic agents have been increasingly appreciated. This provides a rationale for combining conventional chemotherapy with immunotherapy strategies to achieve durable therapeutic benefits. Previous studies have implicated the immunomodulatory effects of melphalan, an alkylating agent commonly used to treat multiple myeloma, but the underlying mechanisms remain obscure. In the present study, we investigated the impact of melphalan on endogenous immune cells as well as adoptively transferred tumor-specific CD4(+) T cells in tumor-bearing mice. We showed that melphalan treatment resulted in a rapid burst of inflammatory cytokines and chemokines during the cellular recovery phase after melphalan-induced myelodepletion and leukodepletion. After melphalan treatment, tumor cells exhibited characteristics of immunogenic cell death, including membrane translocation of the endoplasmic reticulum-resident calreticulin and extracellular release of high-mobility group box 1. Additionally, there was enhanced tumor Ag uptake by dendritic cells in the tumor-draining lymph node. Consistent with these immunomodulatory effects, melphalan treatment of tumor-bearing mice led to the activation of the endogenous CD8(+) T cells and, more importantly, effectively drove the clonal expansion and effector differentiation of adoptively transferred tumor-specific CD4(+) T cells. Notably, the combination of melphalan and CD4(+) T cell adoptive cell therapy was more efficacious than either treatment alone in prolonging the survival of mice with advanced B cell lymphomas or colorectal tumors. These findings provide mechanistic insights into melphalan's immunostimulatory effects and demonstrate the therapeutic potential of combining melphalan with adoptive cell therapy utilizing antitumor CD4(+) T cells.",
"title": "Alkylating agent melphalan augments the efficacy of adoptive immunotherapy using tumor-specific CD4+ T cells."
},
{
"docid": "195680777",
"text": "BACKGROUND Moderate differences in efficacy between adjuvant chemotherapy regimens for breast cancer are plausible, and could affect treatment choices. We sought any such differences. METHODS We undertook individual-patient-data meta-analyses of the randomised trials comparing: any taxane-plus-anthracycline-based regimen versus the same, or more, non-taxane chemotherapy (n=44,000); one anthracycline-based regimen versus another (n=7000) or versus cyclophosphamide, methotrexate, and fluorouracil (CMF; n=18,000); and polychemotherapy versus no chemotherapy (n=32,000). The scheduled dosages of these three drugs and of the anthracyclines doxorubicin (A) and epirubicin (E) were used to define standard CMF, standard 4AC, and CAF and CEF. Log-rank breast cancer mortality rate ratios (RRs) are reported. FINDINGS In trials adding four separate cycles of a taxane to a fixed anthracycline-based control regimen, extending treatment duration, breast cancer mortality was reduced (RR 0·86, SE 0·04, two-sided significance [2p]=0·0005). In trials with four such extra cycles of a taxane counterbalanced in controls by extra cycles of other cytotoxic drugs, roughly doubling non-taxane dosage, there was no significant difference (RR 0·94, SE 0·06, 2p=0·33). Trials with CMF-treated controls showed that standard 4AC and standard CMF were equivalent (RR 0·98, SE 0·05, 2p=0·67), but that anthracycline-based regimens with substantially higher cumulative dosage than standard 4AC (eg, CAF or CEF) were superior to standard CMF (RR 0·78, SE 0·06, 2p=0·0004). Trials versus no chemotherapy also suggested greater mortality reductions with CAF (RR 0·64, SE 0·09, 2p<0·0001) than with standard 4AC (RR 0·78, SE 0·09, 2p=0·01) or standard CMF (RR 0·76, SE 0·05, 2p<0·0001). In all meta-analyses involving taxane-based or anthracycline-based regimens, proportional risk reductions were little affected by age, nodal status, tumour diameter or differentiation (moderate or poor; few were well differentiated), oestrogen receptor status, or tamoxifen use. Hence, largely independently of age (up to at least 70 years) or the tumour characteristics currently available to us for the patients selected to be in these trials, some taxane-plus-anthracycline-based or higher-cumulative-dosage anthracycline-based regimens (not requiring stem cells) reduced breast cancer mortality by, on average, about one-third. 10-year overall mortality differences paralleled breast cancer mortality differences, despite taxane, anthracycline, and other toxicities. INTERPRETATION 10-year gains from a one-third breast cancer mortality reduction depend on absolute risks without chemotherapy (which, for oestrogen-receptor-positive disease, are the risks remaining with appropriate endocrine therapy). Low absolute risk implies low absolute benefit, but information was lacking about tumour gene expression markers or quantitative immunohistochemistry that might help to predict risk, chemosensitivity, or both. FUNDING Cancer Research UK; British Heart Foundation; UK Medical Research Council.",
"title": "Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials."
},
{
"docid": "32852283",
"text": "BACKGROUND Although zoledronic acid (ZOL), a third-generation nitrogen-containing bisphosphonate, has been identified as an attractive therapeutic agent against breast cancer, prostate cancer, multiple myeloma as well as small-cell lung cancer (SCLC), as best as we are aware, the anti-tumor effect of ZOL upon non-small-cell lung cancer (NSCLC) remains to be effectively investigated. This study examined the effects of ZOL upon the line-1 tumor cell, using a murine lung adenocarcinoma cell line similar to the behavior of human lung adenocarcinoma. METHODS We investigated the anti-tumor effects of ZOL (3-100 microM) on line-1 tumor cells in vitro, including cellular proliferation, by means of an MTT assay, cell-cycle analysis by flow cytometry and by assessing the level of apoptosis by annexin V/propidium iodide (PI) and 4'-6-diamidino-2-phenylindole (DAPI) staining. Further, we evaluated the growth and survival of line-1 tumor cells following ZOL treatment (1 microg/kg/week) using an animal model. We also examined the in vivo cell-cycle pattern using lacZ-expressing line-1 cells (line-1/lacZ). RESULTS ZOL significantly slowed the line-1 tumor growth in a dose-dependent manner in vitro. The treated line-1 tumor cells typically arrested at the S/G2/M-phase of the cell-cycle following ZOL exposure, but no apoptotic cells could be detected by either annexin V/PI or DAPI staining. When the ZOL was washed out, the drug-inhibited cells continued to proliferate again and the cell-cycle prolongation elicited earlier by the drug, then disappeared. Within 72-96 h following drug removal, the cell-cycle of the treated cells revealed a similar distribution to that of the untreated controls. In vivo studies demonstrated that ZOL significantly slowed the line-1 tumor growth. Indeed, mice lived significantly longer when they had been ZOL-treated than was the case for untreated mice (p<0.05). Using line-1/lacZ cells, the in vivo cell-cycle distribution of line-1 tumor cells subsequent to ZOL exposure revealed S/G2/M-phase arrest that was identical to the in vitro culture. CONCLUSIONS ZOL maintains the potential to reduce tumor burden and prolong survival for murine pulmonary adenocarcinoma. The flow cytometrical analysis of cell-cycle demonstrated that ZOL induces no apoptosis but is able to arrest line-1 tumor cells at the S/G2/M-phase. Although the clinical relevance of these results warrants verification for human lung cancer patients, ZOL combined with chemotherapy and/or radiotherapy appears to be a new therapeutic strategy for the effective treatment of NSCLC.",
"title": "Zoledronic acid is unable to induce apoptosis, but slows tumor growth and prolongs survival for non-small-cell lung cancers."
},
{
"docid": "2328272",
"text": "INTRODUCTION With the growing number of adult cancer survivors, there is increasing need for information that links potential late and long term effects with specific treatment regimens. Few adult cancer patients are treated on clinical trials; however, patients previously enrolled in these trials are an important source of information about treatment-related late effects. METHODS Focusing on colorectal cancer survivors, we used the database from five phase III randomized clinical trials from the National Surgical Adjuvant Breast & Bowel Project (NSABP) to recruit and enroll long term survivors in a study of late health outcomes and quality of life. We describe the challenges to recruitment of patients more than 5 -20 years after treatment. RESULTS Sixty-five NSABP treatment sites were invited to enroll patients in the study. Sixty participated with the potential to recruit 2,408 patients. We received registration forms on only 976 patients (41%) of whom 744 (76%) expressed interest in participating and 708 completed interviews (95% of those expressing interest; 29% of total potential sample). There were multiple barriers to recruitment (difficulty locating patients, lack of institutional commitment, lack of patient interest). CONCLUSIONS Patients treated on clinical trials are an important potential source for examining the late effects of cancer treatments. Retrospective recruitment has substantial limitations. In the future, mechanisms should be established for prospective long-term follow-up to identify and understand the frequency and type of late effects associated with cancer treatments. IMPLICATIONS FOR CANCER SURVIVORS As cancer patients are living longer, it will be important to learn from participants in clinical trials whether or not specific treatment regimens are associated with any serious late effects.",
"title": "Cancer survivorship research: the challenge of recruiting adult long term cancer survivors from a cooperative clinical trials group"
},
{
"docid": "32421068",
"text": "Objective To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe. Design Retrospective cohort study. Setting Publicly accessible regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013.Main outcome measures Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after market entry. Validated European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) used to assess the clinical value of the reported gains in published studies of cancer drugs. Results From 2009 to 2013, the EMA approved the use of 48 cancer drugs for 68 indications. Of these, eight indications (12%) were approved on the basis of a single arm study. At the time of market approval, there was significant prolongation of survival in 24 of the 68 (35%). The magnitude of the benefit on overall survival ranged from 1.0 to 5.8 months (median 2.7 months). At the time of market approval, there was an improvement in quality of life in seven of 68 indications (10%). Out of 44 indications for which there was no evidence of a survival gain at the time of market authorisation, in the subsequent postmarketing period there was evidence for extension of life in three (7%) and reported benefit on quality of life in five (11%). Of the 68 cancer indications with EMA approval, and with a median of 5.4 years' follow-up (minimum 3.3 years, maximum 8.1 years), only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (49%) remained uncertain. Of 23 indications associated with a survival benefit that could be scored with the ESMO-MCBS tool, the benefit was judged to be clinically meaningful in less than half (11/23, 48%).Conclusions This systematic evaluation of oncology approvals by the EMA in 2009-13 shows that most drugs entered the market without evidence of benefit on survival or quality of life. At a minimum of 3.3 years after market entry, there was still no conclusive evidence that these drugs either extended or improved life for most cancer indications. When there were survival gains over existing treatment options or placebo, they were often marginal.",
"title": "Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13"
},
{
"docid": "26067999",
"text": "The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms. It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment. The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms. Summary of Recommendation and Evidence The USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) See the Clinical Considerations section for suggestions for implementation in practice. See the Figure for a summary of the recommendation and suggestions for clinical practice. Figure. Screening for lung cancer: clinical summary of U.S. Preventive Services Task Force recommendation. Appendix Table 1 describes the USPSTF grades, and Appendix Table 2 describes the USPSTF classification of levels of certainty about net benefit. Appendix Table 1. What the USPSTF Grades Mean and Suggestions for Practice Appendix Table 2. USPSTF Levels of Certainty Regarding Net Benefit Supplement. Consumer Fact Sheet. Rationale Importance Lung cancer is the third most common cancer and the leading cause of cancer-related death in the United States (1). The most important risk factor for lung cancer is smoking, which results in approximately 85% of all U.S. lung cancer cases (2). Although the prevalence of smoking has decreased, approximately 37% of U.S. adults are current or former smokers (2). The incidence of lung cancer increases with age and occurs most commonly in persons aged 55 years or older. Increasing age and cumulative exposure to tobacco smoke are the 2 most common risk factors for lung cancer. Lung cancer has a poor prognosis, and nearly 90% of persons with lung cancer die of the disease. However, early-stage nonsmall cell lung cancer (NSCLC) has a better prognosis and can be treated with surgical resection. Detection Most lung cancer cases are NSCLC, and most screening programs focus on the detection and treatment of early-stage NSCLC. Although chest radiography and sputum cytologic evaluation have been used to screen for lung cancer, LDCT has greater sensitivity for detecting early-stage cancer (3). Benefits of Detection and Early Treatment Although lung cancer screening is not an alternative to smoking cessation, the USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancerrelated deaths. Direct evidence from a large, well-conducted, randomized, controlled trial (RCT) provides moderate certainty of the benefit of lung cancer screening with LDCT in this population (4). The magnitude of benefit to the person depends on that person's risk for lung cancer because those who are at highest risk are most likely to benefit. Screening cannot prevent most lung cancerrelated deaths, and smoking cessation remains essential. Harms of Detection and Early Intervention and Treatment The harms associated with LDCT screening include false-negative and false-positive results, incidental findings, overdiagnosis, and radiation exposure. False-positive LDCT results occur in a substantial proportion of screened persons; 95% of all positive results do not lead to a diagnosis of cancer. In a high-quality screening program, further imaging can resolve most false-positive results; however, some patients may require invasive procedures. The USPSTF found insufficient evidence on the harms associated with incidental findings. Overdiagnosis of lung cancer occurs, but its precise magnitude is uncertain. A modeling study performed for the USPSTF estimated that 10% to 12% of screen-detected cancer cases are overdiagnosedthat is, they would not have been detected in the patient's lifetime without screening. Radiation harms, including cancer resulting from cumulative exposure to radiation, vary depending on the age at the start of screening; the number of scans received; and the person's exposure to other sources of radiation, particularly other medical imaging. USPSTF Assessment The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT is of moderate net benefit in asymptomatic persons who are at high risk for lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. The moderate net benefit of screening depends on limiting screening to persons who are at high risk, the accuracy of image interpretation being similar to that found in the NLST (National Lung Screening Trial), and the resolution of most false-positive results without invasive procedures (4). Clinical Considerations Patient Population Under Consideration The risk for lung cancer increases with age and cumulative exposure to tobacco smoke and decreases with time since quitting smoking. The best evidence for the benefit of screening comes from the NLST, which enrolled adults aged 55 to 74 years who had at least a 30 pack-year smoking history and were current smokers or had quit within the past 15 years. As with all screening trials, the NLST tested a specific intervention over a finite period. Because initial eligibility extended through age 74 years and participants received 3 annual screening computed tomographic scans, the oldest participants in the trial were aged 77 years. The USPSTF used modeling studies to predict the benefits and harms of screening programs that use different screening intervals, age ranges, smoking histories, and times since quitting. A program that annually screens adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years is projected to have a reasonable balance of benefits and harms. The model assumes that persons who achieve 15 years of smoking cessation during the screening program discontinue screening. This model predicts the outcomes of continuing the screening program used in the NLST through age 80 years. Screening may not be appropriate for patients with substantial comorbid conditions, particularly those at the upper end of the screening age range. The NLST excluded persons who were unlikely to complete curative lung cancer surgery and those with medical conditions that posed a substantial risk for death during the 8-year trial. The baseline characteristics of the NLST showed a relatively healthy sample, and fewer than 10% of enrolled participants were older than 70 years (5). Persons with serious comorbid conditions may experience net harm, no net benefit, or at least substantially less net benefit. Similarly, persons who are unwilling to have curative lung surgery are unlikely to benefit from a screening program. Assessment of Risk Age, total exposure to tobacco smoke, and years since quitting smoking are important risk factors for lung cancer and were used to determine eligibility in the NLST. Other risk factors include specific occupational exposures, radon exposure, family history, and history of pulmonary fibrosis or chronic obstructive lung disease. The incidence of lung cancer is relatively low in persons younger than 50 years but increases with age, especially after age 60 years. In current and former smokers, age-specific incidence rates increase with age and cumulative exposure to tobacco smoke. Smoking cessation substantially reduces a person's risk for developing and dying of lung cancer. Among persons enrolled in the NLST, those who were at highest risk because of additional risk factors or a greater cumulative exposure to tobacco smoke experienced most of the benefit (6). A validated multivariate model showed that persons in the highest 60% of risk accounted for 88% of all deaths preventable by screening. Screening Tests Low-dose computed tomography has shown high sensitivity and acceptable specificity for the detection of lung cancer in high-risk persons. Chest radiography and sputum cytologic evaluation have not shown adequate sensitivity or specificity as screening tests. Therefore, LDCT is currently the only recommended screening test for lung cancer. Treatment Surgical resection is the current standard of care for localized NSCLC. This type of cancer is treated with surgical resection when possible and also with radiation and chemotherapy. Annual LDCT screening may not be useful for patients with life-limiting comorbid conditions or poor functional status who may not be candidates for surgery. Other Approaches to Prevention Smoking cessation is the most important intervention to prevent NSCLC. Advising smokers to stop smoking and preventing nonsmokers from being exposed to tobacco smoke are the most effective ways to decrease the morbidity and mortality associated with lung cancer. Current smokers should be informed of their continuing risk for lung cancer and offered cessation treatments. Screening with LDCT should be viewed as an adjunct to tobacco cessation interventions. Useful Resources Clinicians have many resources to help patients stop smoking. The Centers for Disease Control and Prevention has developed a Web site with many such resources, including information on tobacco quit lines, available in several languages (www.cdc.gov/tobacco/campaign/tips). Quit l",
"title": "Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation Statement"
},
{
"docid": "6407356",
"text": "Coxibs, including celecoxib, and other nonsteroidal anti-inflammatory drugs (NSAID), including aspirin, are among the most promising cancer chemopreventive agents in development today. This article examines the data on the efficacy of these agents in animal model studies of cancer prevention carried out by the authors. The studies evaluated here are restricted to our rodent models of colon/intestinal, bladder, and nonmelanoma skin cancer, in which celecoxib and other NSAIDs were administered as either cancer preventive or therapeutic agents. These studies may shed light on several questions. Is celecoxib unique compared with other NSAIDs, and if so, what implications would this have for human use? Are standard NSAIDs (which inhibit both COX-1 and COX-2) as effective as celecoxib in animal studies? Is the efficacy of celecoxib in particular or NSAIDs in general due to their off-target effects or to their effects on COX-1 and COX-2? What is the likely efficacy of low-dose aspirin? Some questions raised by human trials and epidemiology are discussed and related to our observations in animal model studies. We also discuss the problem of cardiovascular (CV) events associated with coxibs and certain other NSAIDs and whether results in animal models are predictive of efficacy in humans. On the basis of epidemiologic studies and its CV profile, aspirin seems to be the most promising NSAID for preventing human colorectal, bladder, and skin cancer, although the animal data for aspirin are less clear. A comprehensive understanding of the results of coxibs and other NSAIDs in animal studies may help inform and shape human trials of these commonly employed, relatively inexpensive, and highly effective compounds.",
"title": "Coxibs and other nonsteroidal anti-inflammatory drugs in animal models of cancer chemoprevention."
},
{
"docid": "38886345",
"text": "BACKGROUND JX-594 is a targeted oncolytic poxvirus designed to selectively replicate in and destroy cancer cells with cell-cycle abnormalities and epidermal growth factor receptor (EGFR)-ras pathway activation. Direct oncolysis plus granulocyte-macrophage colony-stimulating factor (GM-CSF) expression also stimulates shutdown of tumour vasculature and antitumoral immunity. We aimed to assess intratumoral injection of JX-594 in patients with refractory primary or metastatic liver cancer. METHODS Between Jan 4, 2006, and July 4, 2007, 14 patients with histologically confirmed refractory primary or metastatic liver tumours (up to 10.9 cm total diameter) that were amenable to image-guided intratumoral injections were enrolled into this non-comparative, open-label, phase I dose-escalation trial (standard 3x3 design; two to six patients for each dose with 12-18 estimated total patients). Patients received one of four doses of intratumoral JX-594 (10(8) plaque-forming units [pfu], 3x10(8) pfu, 10(9) pfu, or 3x10(9) pfu) every 3 weeks at Dong-A University Hospital (Busan, South Korea). Patients were monitored after treatment for at least 48 h in hospital and for at least 4 weeks as out-patients. Adverse event-monitoring according to the National Cancer Institute Common Toxicity Criteria (version 3) and standard laboratory toxicity grading for haematology, liver and renal function, coagulation studies, serum chemistry, and urinalysis were done. The primary aims were to ascertain the maximum-tolerated dose (MTD) and safety of JX-594 treatment. Data were also collected on pharmacokinetics, pharmacodynamics, and efficacy. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00629759. FINDINGS Of 22 patients with liver tumours who were assessed for eligibility, eight patients did not meet inclusion criteria. Therefore, 14 patients, including those with hepatocellular, colorectal, melanoma, and lung cancer, were enrolled. Patients were heavily pretreated (5.6 previous treatments, SD 2.8, range 2.0-12.0) and had large tumours (7.0 cm diameter, SD 2.7, range 1.8-10.9). Patients received a mean of 3.4 (SD 2.2, range 1.0-8.0) cycles of JX-594. All patients were evaluable for toxicity. All patients experienced grade I-III flu-like symptoms, and four had transient grade I-III dose-related thrombocytopenia. Grade III hyperbilirubinaemia was dose-limiting in both patients at the highest dose; the MTD was therefore 1x10(9) pfu. JX-594 replication-dependent dissemination in blood was shown, with resultant infection of non-injected tumour sites. GM-CSF expression resulted in grade I-III increases in neutrophil counts in four of six patients at the MTD. Tumour responses were shown in injected and non-injected tumours. Ten patients were radiographically evaluable for objective responses; non-evaluable patients had contraindications to contrast medium (n=2) or no post-treatment scans (n=2). According to Response Evaluation Criteria in Solid Tumors (RECIST), three patients had partial response, six had stable disease, and one had progressive disease. INTERPRETATION Intratumoral injection of JX-594 into primary or metastatic liver tumours was generally well-tolerated. Direct hyperbilirubinaemia was the dose-limiting toxicity. Safety was acceptable in the context of JX-594 replication, GM-CSF expression, systemic dissemination, and JX-594 had anti-tumoral effects against several refractory carcinomas. Phase II trials are now underway.",
"title": "Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial."
},
{
"docid": "35301079",
"text": "BACKGROUND In uveal melanoma (UM) with metastatic disease limited to the liver, the effect of an intrahepatic treatment on survival is unknown. We investigated prospectively the efficacy and toxicity of hepatic intra-arterial (HIA) versus systemic (IV) fotemustine in patients with liver metastases from UM. PATIENTS AND METHODS Patients were randomly assigned to receive either IV or HIA fotemustine at 100 mg/m(2) on days 1, 8, 15 (and 22 in HIA arm only) as induction, and after a 5-week rest period every 3 weeks as maintenance. Primary end point was overall survival (OS). Response rate (RR), progression-free survival (PFS) and safety were secondary end points. RESULTS Accrual was stopped after randomization of 171 patients based on the results of a futility OS analysis. A total of 155 patients died and 16 were still alive [median follow-up 1.6 years (range 0.25-6 years)]. HIA did not improve OS (median 14.6 months) when compared with the IV arm (median 13.8 months), hazard ratio (HR) 1.09; 95% confidence interval (CI) 0.79-1.50, log-rank P = 0.59. However, there was a significant benefit on PFS for HIA compared with IV with a median of 4.5 versus 3.5 months, respectively (HR 0.62; 95% CI 0.45-0.84, log-rank P = 0.002). The 1-year PFS rate was 24% in the HIA arm versus 8% in the IV arm. An improved RR was seen in the HIA (10.5%) compared with IV treatment (2.4%). In the IV arm, the most frequent grade ≥3 toxicity was thrombocytopenia (42.1%) and neutropenia (62.6%), compared with 21.2% and 28.7% in the HIA arm. The main grade ≥3 toxicity related to HIA was catheter complications (12%) and liver toxicity (4.5%) apart from two toxic deaths. CONCLUSION HIA treatment with fotemustine did not translate into an improved OS compared with IV treatment, despite better RR and PFS. Intrahepatic treatment should still be considered as experimental. EUDRACT NUMBER AND CLINICALTRIALSGOV IDENTIFIER 2004-002245-12 and NCT00110123.",
"title": "Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial."
}
] |
835
|
NR5A2 does not play a role in development of endometrial tissues.
|
[
{
"docid": "15928989",
"text": "Successful pregnancy requires coordination of an array of signals and factors from multiple tissues. One such element, liver receptor homolog-1 (Lrh-1), is an orphan nuclear receptor that regulates metabolism and hormone synthesis. It is strongly expressed in granulosa cells of ovarian follicles and in the corpus luteum of rodents and humans. Germline ablation of Nr5a2 (also called Lrh-1), the gene coding for Lrh-1, in mice is embryonically lethal at gastrulation. Depletion of Lrh-1 in the ovarian follicle shows that it regulates genes required for both steroid synthesis and ovulation. To study the effects of Lrh-1 on mouse gestation, we genetically disrupted its expression in the corpus luteum, resulting in luteal insufficiency. Hormone replacement permitted embryo implantation but was followed by gestational failure with impaired endometrial decidualization, compromised placental formation, fetal growth retardation and fetal death. Lrh-1 is also expressed in the mouse and human endometrium, and in a primary culture of human endometrial stromal cells, reduction of NR5A2 transcript abundance by RNA interference abrogated decidualization. These findings show that Lrh-1 is necessary for maintenance of the corpus luteum, for promotion of decidualization and for formation of the placenta. It therefore has multiple, indispensible roles in establishing and sustaining pregnancy.",
"title": "Liver receptor homolog-1 is essential for pregnancy"
}
] |
[
{
"docid": "1780819",
"text": "BACKGROUND Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development. METHODS AND FINDINGS Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64) and control samples (n = 23) revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma) is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A). Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to develop precancerous endometrial lesions with increasing age, and these lesions also demonstrated a lack of PTEN expression. CONCLUSIONS HAND2 methylation is a common and crucial molecular alteration in endometrial cancer that could potentially be employed as a biomarker for early detection of endometrial cancer and as a predictor of treatment response. The true clinical utility of HAND2 DNA methylation, however, requires further validation in prospective studies. Please see later in the article for the Editors' Summary.",
"title": "Role of DNA Methylation and Epigenetic Silencing of HAND2 in Endometrial Cancer Development"
},
{
"docid": "6121668",
"text": "OBJECTIVES To investigate the expressions of survivin and Cyclooxygenase-2 (COX-2), and their possible correlations in the development of endometrial adenocarcinoma (EC). We also looked at their association with classical prognostic factors in EC. To our knowledge, this is the first time survivin expression is investigated in terms of its relation to COX-2 in the developmental pathway of EC. METHODS Archived tissue samples of 50 EC, 30 endometrial hyperplasia and 20 proliferative endometrium were selected and immunohistochemically analyzed for survivin and COX-2 expression. RESULTS Both survivin and COX-2 were overexpressed in hyperplasia and endometrial adenocarcinoma cases compared to proliferative endometrium, which was statistically significant (p=0.01, p=0.02, respectively). Among EC cases, survivin and COX-2 were strongly positive in 38 (76%) and 30 (60%) patients, respectively. Furthermore, we found survivin and COX-2 to be positively correlated, which was also statistically significant (p=0.0001, r=0.46). Neither survivin nor COX-2 expression was correlated with classical prognostic factors of endometrial carcinoma such as myometrial invasion, grade or lymph node metastasis (p>0.05). Neither COX-2 nor survivin had an impact on overall survival (p>0.05). CONCLUSIONS Both survivin and COX-2 are overexpressed, and they seem to be early events in the occurrence of EC. Moreover, protein products of these two genes are positively correlated. COX-2 and survivin might share a common molecular pathway or enhance each other's actions in the developmental pathway of EC. Molecular basis of such a relationship should be further investigated in endometrial carcinogenesis.",
"title": "COX-2 and survivin are overexpressed and positively correlated in endometrial carcinoma."
},
{
"docid": "30369606",
"text": "Obtaining primary human endometrial stromal cells (HESCs) for in vitro studies is limited by the scarcity of adequate human material and the inability to passage these cells in culture for long periods. Immortalization of these cells would greatly facilitate studies; however, the process of immortalization often results in abnormal karyotypes and aberrant functional characteristics. To meet this need, we have introduced telomerase into cultured HESCs to prevent the normal shortening of telomeres observed in adult somatic cells during mitosis. We have now developed and analyzed a newly immortalized HESC line that contains no clonal chromosomal structural or numerical abnormalities. In addition, when compared with the primary unpassaged parent cells, the new cell line displayed similar biochemical endpoints after treatment with ovarian steroids. Classical decidualization response to estradiol plus medroxyprogesterone acetate were seen in both morphologically, and progestin was seen to induce or regulate the expression of IGF binding protein-1, fibronectin, prolactin, tissue factor, plasminogen activator inhibitor-1, and Fas/Fas ligand. In summary, an immortalized HESC line has been developed that is karyotypically, morphologically, and phenotypically similar to the primary parent cells, and it is a powerful and consistent resource for in vitro work.",
"title": "A novel immortalized human endometrial stromal cell line with normal progestational response."
},
{
"docid": "24707550",
"text": "Macrophages play a pivotal role in innate and acquired immune responses to Schistosoma mansoni. Classical (M1) or alternative (M2) activation states of these cells further delineate their roles in tissue damage through innate immunity or fibrotic remodeling, respectively. In the present study, we addressed the following question: Does systemic Th2-type cytokine polarization evoked by S. mansoni affect macrophage differentiation and activation? To this end, we analyzed bone marrow-derived macrophages from mice with S. mansoni egg-induced pulmonary granulomas and unchallenged (or naïve) mice to determine their activation state and their response to specific TLR agonists, including S. mansoni egg antigens. Unlike naïve macrophages, macrophages from Th2-polarized mice constitutively expressed significantly higher \"found in inflammatory zone-1\" (FIZZ1) and ST2 (M2 markers) and significantly lower NO synthase 2, CCL3, MIP-2, TNF-alpha, and IL-12 (M1 markers). Also, compared with naïve macrophages, Th2-polarized macrophages exhibited enhanced responses to the presence of specific TLR agonists, which consistently induced significantly higher levels of gene and protein levels for M2 and M1 markers in these cells. Together, these data show that signals received by bone marrow precursors during S. mansoni egg-induced granuloma responses dynamically alter the development of macrophages and enhance the TLR responsiveness of these cells, which may ultimately have a significant effect on the pulmonary granulomatous response.",
"title": "A systemic granulomatous response to Schistosoma mansoni eggs alters responsiveness of bone-marrow-derived macrophages to Toll-like receptor agonists."
},
{
"docid": "8771704",
"text": "Acute skeletal muscle injury triggers an expansion of fibro/adipogenic progenitors (FAPs) and a transient stage of fibrogenesis characterized by extracellular matrix deposition. While the perpetuation of such phase can lead to permanent tissue scarring, the consequences of its suppression remain to be studied. Using a model of acute muscle damage we were able to determine that pharmacological inhibition of FAP expansion by Nilotinib, a tyrosine kinase inhibitor with potent antifibrotic activity, exerts a detrimental effect on myogenesis during regeneration. We found that Nilotinib inhibits the damage-induced expansion of satellite cells in vivo, but it does not affect in vitro proliferation, suggesting a non cell-autonomous effect. Nilotinib impairs regenerative fibrogenesis by preventing the injury-triggered expansion and differentiation of resident CD45(-):CD31(-):α7integrin(-):Sca1(+) mesenchymal FAPs. Our data support the notion that the expansion of FAPs and transient fibrogenesis observed during regeneration play an important trophic role toward tissue-specific stem cells.",
"title": "Pharmacological blockage of fibro/adipogenic progenitor expansion and suppression of regenerative fibrogenesis is associated with impaired skeletal muscle regeneration."
},
{
"docid": "45015767",
"text": "BACKGROUND Adenocarcinoma of the endometrium is the most common gynecologic malignancy in the United States, accounting for approximately 36,000 diagnoses of invasive carcinoma annually. The most common histologic type, endometrioid adenocarcinoma (EC), accounts for 75-80% of patients. The objective of this work was to estimate the prevalence of concurrent carcinoma in women with a biopsy diagnosis of the precursor lesion, atypical endometrial hyperplasia (AEH). METHODS This prospective cohort study included women who had a community diagnosis of AEH. Diagnostic biopsy specimens were reviewed independently by three gynecologic pathologists who used International Society of Gynecologic Pathologists/World Health Organization criteria. Study participants underwent hysterectomy within 12 weeks of entry onto protocol without interval treatment. The hysterectomy slides also were reviewed by the study pathologists, and their findings were used in the subsequent analyses. RESULTS Between November 1998 and June 2003, 306 women were enrolled on the study. Of these, 17 women were not included in the analysis: Two patients had unreadable slides because of poor processing or insufficient tissue, 2 patients had only slides that were not endometrial, the slides for 5 patients were not available for review, and 8 of the hysterectomy specimens were excluded because they showed evidence of interval intervention, either progestin effect or ablation. In total, 289 patients were included in the current analysis. The study panel review of the AEH biopsy specimens was interpreted as follows: 74 of 289 specimens (25.6%) were diagnosed as less than AEH, 115 of 289 specimens (39.8%) were diagnosed as AEH, and 84 of 289 specimens (29.1%) were diagnosed as endometrial carcinoma. In 5.5% (16 of 289 specimens), there was no consensus on the biopsy diagnosis. The rate of concurrent endometrial carcinoma for analyzed specimens was 42.6% (123 of 289 specimens). Of these, 30.9% (38 of 123 specimens) were myoinvasive, and 10.6% (13 of 123 specimens) involved the outer 50% of the myometrium. Among the women who had hysterectomy specimens with carcinoma, 14 of 74 women (18.9%) had a study panel biopsy consensus diagnosis of less than AEH, 45 of 115 women (39.1%) had a study panel biopsy consensus diagnosis of AEH, and 54 of 84 women (64.3%) had a study panel diagnosis of carcinoma. Among women who had no consensus in their biopsy diagnosis, 10 of 16 women (62.5%) had carcinoma in their hysterectomy specimens. CONCLUSIONS The prevalence of endometrial carcinoma in patients who had a community hospital biopsy diagnosis of AEH was high (42.6%). When considering management strategies for women who have a biopsy diagnosis of AEH, clinicians and patients should take into account the considerable rate of concurrent carcinoma.",
"title": "Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study."
},
{
"docid": "10889845",
"text": "Obesity and insulin resistance, the key features of metabolic syndrome, are closely associated with a state of chronic, low-grade inflammation characterized by abnormal macrophage infiltration into adipose tissues. Although it has been reported that chemokines promote leukocyte migration by activating class IB phosphoinositide-3 kinase (PI3Kγ) in inflammatory states, little is known about the role of PI3Kγ in obesity-induced macrophage infiltration into tissues, systemic inflammation, and the development of insulin resistance. In the present study, we used murine models of both diet-induced and genetically induced obesity to examine the role of PI3Kγ in the accumulation of tissue macrophages and the development of obesity-induced insulin resistance. Mice lacking p110γ (Pik3cg(-/-)), the catalytic subunit of PI3Kγ, exhibited improved systemic insulin sensitivity with enhanced insulin signaling in the tissues of obese animals. In adipose tissues and livers of obese Pik3cg(-/-) mice, the numbers of infiltrated proinflammatory macrophages were markedly reduced, leading to suppression of inflammatory reactions in these tissues. Furthermore, bone marrow-specific deletion and pharmacological blockade of PI3Kγ also ameliorated obesity-induced macrophage infiltration and insulin resistance. These data suggest that PI3Kγ plays a crucial role in the development of both obesity-induced inflammation and systemic insulin resistance and that PI3Kγ can be a therapeutic target for type 2 diabetes.",
"title": "Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance."
},
{
"docid": "15836115",
"text": "Mitochondrial morphological and ultrastructural changes occur during apoptosis and autophagy, but whether they are relevant in vivo for tissue response to damage is unclear. Here we investigate the role of the optic atrophy 1 (OPA1)-dependent cristae remodeling pathway in vivo and provide evidence that it regulates the response of multiple tissues to apoptotic, necrotic, and atrophic stimuli. Genetic inhibition of the cristae remodeling pathway in vivo does not affect development, but protects mice from denervation-induced muscular atrophy, ischemic heart and brain damage, as well as hepatocellular apoptosis. Mechanistically, OPA1-dependent mitochondrial cristae stabilization increases mitochondrial respiratory efficiency and blunts mitochondrial dysfunction, cytochrome c release, and reactive oxygen species production. Our results indicate that the OPA1-dependent cristae remodeling pathway is a fundamental, targetable determinant of tissue damage in vivo.",
"title": "The Opa1-Dependent Mitochondrial Cristae Remodeling Pathway Controls Atrophic, Apoptotic, and Ischemic Tissue Damage"
},
{
"docid": "3210545",
"text": "BACKGROUND Three quarter of endometrial carcinomas are treated at early stage. Still, 15 to 20% of these patients experience recurrence, with little effect from systemic therapies. Homo sapiens v-Ki-ras2 Kirsten rat sarcoma viral oncogenes homologue (KRAS) mutations have been reported to have an important role in tumorigenesis for human cancers, but there is limited knowledge regarding clinical relevance of KRAS status in endometrial carcinomas. METHODS We have performed a comprehensive and integrated characterisation of genome-wide expression related to KRAS mutations and copy-number alterations in primary- and metastatic endometrial carcinoma lesions in relation to clinical and histopathological data. A primary investigation set and clinical validation set was applied, consisting of 414 primary tumours and 61 metastatic lesions totally. RESULTS Amplification and gain of KRAS present in 3% of the primary lesions and 18% of metastatic lesions correlated significantly with poor outcome, high International Federation of Gynaecology and Obstetrics stage, non-endometrioid subtype, high grade, aneuploidy, receptor loss and high KRAS mRNA levels, also found to be associated with aggressive phenotype. In contrast, KRAS mutations were present in 14.7% of primary lesions with no increase in metastatic lesions, and did not influence outcome, but was significantly associated with endometrioid subtype, low grade and obesity. CONCLUSION These results support that KRAS amplification and KRAS mRNA expression, both increasing from primary to metastatic lesions, are relevant for endometrial carcinoma disease progression.",
"title": "KRAS gene amplification and overexpression but not mutation associates with aggressive and metastatic endometrial cancer"
},
{
"docid": "19485649",
"text": "Transmembrane cadherins are calcium-dependent intercellular adhesion molecules. Recently, they have also been shown to be sites of actin assembly during adhesive contact formation. However, the roles of actin assembly on transmembrane cadherins during development are not fully understood. We show here, using the developing ectoderm of the Xenopus embryo as a model, that F-actin assembly is a primary function of both N-cadherin in the neural ectoderm and E-cadherin in the non-neural (epidermal) ectoderm, and that each cadherin is essential for the characteristic morphogenetic movements of these two tissues. However, depletion of N-cadherin and E-cadherin did not cause dissociation in these tissues at the neurula stage, probably owing to the expression of C-cadherin in each tissue. Depletion of each of these cadherins is not rescued by the other, nor by the expression of C-cadherin, which is expressed in both tissues. One possible reason for this is that each cadherin is expressed in a different domain of the cell membrane. These data indicate the combinatorial nature of cadherin function, the fact that N- and E-cadherin play primary roles in F-actin assembly in addition to roles in cell adhesion, and that this function is specific to individual cadherins. They also show how cell adhesion and motility can be combined in morphogenetic tissue movements that generate the form and shape of the embryonic organs.",
"title": "N- and E-cadherins in Xenopus are specifically required in the neural and non-neural ectoderm, respectively, for F-actin assembly and morphogenetic movements."
},
{
"docid": "29148743",
"text": "To determine the relative contributions of endothelial-derived nitric oxide (NO) vs. intravascular nitrogen oxide species in the regulation of human blood flow, we simultaneously measured forearm blood flow and arterial and venous levels of plasma nitrite, LMW-SNOs and HMW-SNOs, and red cell S-nitrosohemoglobin (SNO-Hb). Measurements were made at rest and during regional inhibition of NO synthesis, followed by forearm exercise. Surprisingly, we found significant circulating arterial-venous plasma nitrite gradients, providing a novel delivery source for intravascular NO. Further supporting the notion that circulating nitrite is bioactive, the consumption of nitrite increased significantly with exercise during the inhibition of regional endothelial synthesis of NO. The role of circulating S-nitrosothiols and SNO-Hb in the regulation of basal vascular tone is less certain. We found that low-molecular-weight S-nitrosothiols were undetectable and S-nitroso-albumin levels were two logs lower than previously reported. In fact, S-nitroso-albumin primarily formed in the venous circulation, even during NO synthase inhibition. Whereas SNO-Hb was measurable in the human circulation (brachial artery levels of 170 nM in whole blood), arterial-venous gradients were not significant, and delivery of NO from SNO-Hb was minimal. In conclusion, we present data that suggest (i) circulating nitrite is bioactive and provides a delivery gradient of intravascular NO, (ii) S-nitroso-albumin does not deliver NO from the lungs to the tissue but forms in the peripheral circulation, and (iii) SNO-Hb and S-nitrosothiols play a minimal role in the regulation of basal vascular tone, even during exercise stress.",
"title": "Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans."
},
{
"docid": "20960682",
"text": "BACKGROUND & AIMS GS-9620, an oral agonist of toll-like receptor 7 (TLR7), is in clinical development for the treatment of chronic hepatitis B (CHB). GS-9620 was previously shown to induce prolonged suppression of serum viral DNA and antigens in the woodchuck and chimpanzee models of CHB. Herein, we investigated the molecular mechanisms that contribute to the antiviral response to GS-9620 using in vitro models of hepatitis B virus (HBV) infection. METHODS Cryopreserved primary human hepatocytes (PHH) and differentiated HepaRG (dHepaRG) cells were infected with HBV and treated with GS-9620, conditioned media from human peripheral blood mononuclear cells treated with GS-9620 (GS-9620 conditioned media [GS-9620-CM]), or other innate immune stimuli. The antiviral and transcriptional response to these agents was determined. RESULTS GS-9620 had no antiviral activity in HBV-infected PHH, consistent with low level TLR7 mRNA expression in human hepatocytes. In contrast, GS-9620-CM induced prolonged reduction of HBV DNA, RNA, and antigen levels in PHH and dHepaRG cells via a type I interferon (IFN)-dependent mechanism. GS-9620-CM did not reduce covalently closed circular DNA (cccDNA) levels in either cell type. Transcriptional profiling demonstrated that GS-9620-CM strongly induced various HBV restriction factors - although not APOBEC3A or the Smc5/6 complex - and indicated that established HBV infection does not modulate innate immune sensing or signaling in cryopreserved PHH. GS-9620-CM also induced expression of immunoproteasome subunits and enhanced presentation of an immunodominant viral peptide in HBV-infected PHH. CONCLUSIONS Type I IFN induced by GS-9620 durably suppressed HBV in human hepatocytes without reducing cccDNA levels. Moreover, HBV antigen presentation was enhanced, suggesting additional components of the TLR7-induced immune response played a role in the antiviral response to GS-9620 in animal models of CHB. LAY SUMMARY GS-9620 is a drug currently being tested in clinical trials for the treatment of chronic hepatitis B virus (HBV) infection. GS-9620 has previously been shown to suppress HBV in various animal models, but the underlying antiviral mechanisms were not completely understood. In this study, we determined that GS-9620 does not directly activate antiviral pathways in human liver cells, but can induce prolonged suppression of HBV via induction of an antiviral cytokine called interferon. However, interferon did not destroy the HBV genome, suggesting that other parts of the immune response (e.g. activation of immune cells that kill infected cells) also play an important role in the antiviral response to GS-9620.",
"title": "Toll-like receptor 7 agonist GS-9620 induces prolonged inhibition of HBV via a type I interferon-dependent mechanism."
},
{
"docid": "18450716",
"text": "Adipose tissue dysfunction plays a pivotal role in the development of insulin resistance in obese individuals. Cell culture studies and gain-of-function mouse models suggest that canonical Wnt proteins modulate adipose tissue expansion. However, no genetic evidence supports a role for endogenous Wnt proteins in adipose tissue dysfunction, and the role of noncanonical Wnt signaling remains largely unexplored. Here we provide evidence from human, mouse, and cell culture studies showing that Wnt5a-mediated, noncanonical Wnt signaling contributes to obesity-associated metabolic dysfunction by increasing adipose tissue inflammation. Wnt5a expression is significantly upregulated in human visceral fat compared with subcutaneous fat in obese individuals. In obese mice, Wnt5a ablation ameliorates insulin resistance, in parallel with reductions in adipose tissue inflammation. Conversely, Wnt5a overexpression in myeloid cells augments adipose tissue inflammation and leads to greater impairments in glucose homeostasis. Wnt5a ablation or overexpression did not affect fat mass or adipocyte size. Mechanistically, Wnt5a promotes the expression of proinflammatory cytokines by macrophages in a Jun NH2-terminal kinase-dependent manner, leading to defective insulin signaling in adipocytes. Exogenous interleukin-6 administration restores insulin resistance in obese Wnt5a-deficient mice, suggesting a central role for this cytokine in Wnt5a-mediated metabolic dysfunction. Taken together, these results demonstrate that noncanonical Wnt signaling contributes to obesity-induced insulin resistance independent of adipose tissue expansion.",
"title": "Noncanonical Wnt Signaling Promotes Obesity-Induced Adipose Tissue Inflammation and Metabolic Dysfunction Independent of Adipose Tissue Expansion"
},
{
"docid": "25263942",
"text": "Endometrial polyps are very common benign endometrial lesions, but their pathogenesis is poorly understood, except for a few studies indicating the possibility of benign stromal neoplasm. Although the histopathological diagnosis of endometrial polyp on a surgical specimen is straightforward, it is often difficult to differentiate endometrial polyp from endometrial hyperplasia on a biopsy or curettage specimen. Presently, there is no immunohistochemical marker helpful in this differential diagnosis. In this study, we examined p16 expression in 35 endometrial polyps and 33 cases of endometrial hyperplasia that included 16 simple hyperplasias, 14 complex atypical hyperplasias, and 3 complex hyperplasias without atypia. Stromal p16 expression differed significantly between the two groups; it was seen in 31 (89 %) endometrial polyps, but in only 1 (3 %) endometrial hyperplasia. The percentage of p16-positive stromal cells ranged from 10 to 90 % (mean, 47 %) and the positive cells tended to be distributed around glands. Six cases of endometrial hyperplasia within an endometrial polyp were also examined and all cases showed stromal p16 expression. There was no difference in glandular p16 expression between endometrial polyps 33 (94 %) and hyperplasia 27 (82 %). The p16-immunoreactivity was mostly confined to metaplastic epithelial cells in both groups. Stromal p16 expression might be a peculiar characteristic of endometrial polyp and constitute a useful marker for the diagnosis, especially in fragmented specimens from biopsy or curettage. Stromal p16 expression might be a reflection of p16-induced cellular senescence, which has been documented in several benign mesenchymal neoplasms.",
"title": "Stromal p16 expression differentiates endometrial polyp from endometrial hyperplasia"
},
{
"docid": "14116046",
"text": "Retinoic acid-related orphan receptors RORα and RORγ play a regulatory role in lipid/glucose homeostasis and various immune functions, and have been implicated in metabolic syndrome and several inflammatory diseases. RORα-deficient mice are protected against age- and diet-induced obesity, hepatosteatosis, and insulin resistance. The resistance to hepatosteatosis in RORα-deficient mice is related to the reduced expression of several genes regulating lipid synthesis, transport, and storage. Adipose tissue-associated inflammation, which plays a critical role in the development of insulin resistance, is considerably diminished in RORα-deficient mice as indicated by the reduced infiltration of M1 macrophages and decreased expression of many proinflammatory genes. Deficiency in RORγ also protects against diet-induced insulin resistance by a mechanism that appears different from that in RORα deficiency. Recent studies indicated that RORs provide an important link between the circadian clock machinery and its regulation of metabolic genes and metabolic syndrome. As ligand-dependent transcription factors, RORs may provide novel therapeutic targets in the management of obesity and associated metabolic diseases, including hepatosteatosis, adipose tissue-associated inflammation, and insulin resistance.",
"title": "Retinoic acid-related orphan receptors α and γ: key regulators of lipid/glucose metabolism, inflammation, and insulin sensitivity"
},
{
"docid": "22705234",
"text": "The African green monkey (AGM) is one of many African species endemically infected with simian immunodeficiency virus (SIV). Like the other natural hosts, AGMs do not succumb to AIDS and understanding the basis for this resistance to disease progression would be of enormous theoretical and practical importance. Early efforts by our group that concentrated on identifying immune mechanisms presumed to keep the virus under control failed to find any obvious candidates. The presumption of virus control was invalidated by the finding that SIVagm replicates in AGMs with the same vigor as HIV-1 does in humans. Focus therefore shifted to identifying possible immunopathologic features present in disease susceptible hosts but absent in the AGM natural host. The apparent immunologic tolerance of AGMs to the SIVagm core protein led to the development of a hypothesis implicating anti-Gag antibodies in the formation of immune complexes, virus trapping in the lymph nodes and immune dysfunction. The idea proved difficult to test in vivo and present work focuses on the possibility that Gag tolerance at the T-cell level plays an important role in preventing the catastrophic demise of the immune system characteristic of immunodeficiency virus infection of the heterologous primate host.",
"title": "The role of the immune response during SIVagm infection of the African green monkey natural host."
},
{
"docid": "8538916",
"text": "The molecular chaperone CCT/TRiC plays a central role in maintaining cellular proteostasis as it mediates the folding of the major cytoskeletal proteins tubulins and actins. CCT/TRiC is also involved in the oncoprotein cyclin E, the Von Hippel-Lindau tumour suppressor protein, cyclin B and p21(ras) folding which strongly suggests that it is involved in cell proliferation and tumor genesis. To assess the involvement of CCT/TRiC in tumor genesis, we quantified its expression levels and activity in 18 cancer, one non-cancer human cell lines and a non-cancer human liver. We show that the expression levels of CCT/TRiC in cancer cell lines are higher than that in normal cells. However, CCT/TRiC activity does not always correlate with its expression levels. We therefore documented the expression levels of CCT/TRiC modulators and partners PhLP3, Hop/P60, prefoldin and Hsc/Hsp70. Our analysis reveals a functional interplay between molecular chaperones that might account for a precise modulation of CCT/TRiC activity in cell proliferation through changes in the cellular levels of prefoldin and/or Hsc/p70 and CCT/TRiC client protein availability. Our observation and approaches bring novel insights in the role of CCT/TRiC-mediated protein folding machinery in cancer cell development.",
"title": "The Cytosolic Chaperonin CCT/TRiC and Cancer Cell Proliferation"
},
{
"docid": "16346504",
"text": "BACKGROUND Growth arrest-specific 5 (GAS5) was reported to be implicated and aberrantly express in multiple cancers. However, the expression and mechanism of action of GAS5 were largely poor understood in endometrial carcinoma. RESULTS According to the result of real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and flow cytometry analysis, we identified that GAS5 was down-regulated in endometrial cancer cells and stimulated the apoptosis of endometrial cancer cells. To investigate the expression of GAS5, PTEN and miR-103, RT-PCR was performed. And we found that the expression of PTEN was up-regulated when endometrial cancer cells overexpressed GAS5. The prediction of bioinformatics online revealed that GAS5 could bind to miR-103, which was further found to be regulated by GAS5. Finally, we found that miR-103 mimic could decrease the mRNA and protein levels of PTEN through luciferase reporter assay and western blotting, and GAS5 plasmid may reverse this regulation effect in endometrial cancer cells. CONCLUSION In summary, we demonstrate that GAS5 acts as an tumor suppressor lncRNA in endometrial cancer. Through inhibiting the expression of miR-103, GAS5 significantly enhanced the expression of PTEN to promote cancer cell apoptosis, and, thus, could be an important mediator in the pathogenesis of endometrial cancer.",
"title": "LncRNA-GAS5 induces PTEN expression through inhibiting miR-103 in endometrial cancer cells"
},
{
"docid": "20456030",
"text": "Mitochondria play a pivotal role in energy metabolism, programmed cell death and oxidative stress. Mutated mitochondrial DNA in diseased cells compromises the structure of key enzyme complexes and, therefore, mitochondrial function, which leads to a myriad of health-related conditions such as cancer, neurodegenerative diseases, diabetes and aging. Early detection of mitochondrial and metabolic anomalies is an essential step towards effective diagnoses and therapeutic intervention. Reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) play important roles in a wide range of cellular oxidation-reduction reactions. Importantly, NADH and FAD are naturally fluorescent, which allows noninvasive imaging of metabolic activities of living cells and tissues. Furthermore, NADH and FAD autofluorescence, which can be excited using distinct wavelengths for complementary imaging methods and is sensitive to protein binding and local environment. This article highlights recent developments concerning intracellular NADH and FAD as potential biomarkers for metabolic and mitochondrial activities.",
"title": "Intracellular coenzymes as natural biomarkers for metabolic activities and mitochondrial anomalies."
},
{
"docid": "23577867",
"text": "Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer.",
"title": "Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer."
},
{
"docid": "1386103",
"text": "Tuberculosis, a major health problem in developing countries, has reemerged in recent years in many industrialized countries. The increased susceptibility of immunocompromised individuals to tuberculosis, and many experimental studies indicate that T cell-mediated immunity plays an important role in resistance. The lymphokine interferon gamma (IFN-gamma) is thought to be a principal mediator of macrophage activation and resistance to intracellular pathogens. Mice have been developed which fail to produce IFN-gamma (gko), because of a targeted disruption of the gene for IFN-gamma. Upon infection with Mycobacterium tuberculosis, although they develop granulomas, gko mice fail to produce reactive nitrogen intermediates and are unable to restrict the growth of the bacilli. In contrast to control mice, gko mice exhibit heightened tissue necrosis and succumb to a rapid and fatal course of tuberculosis that could be delayed, but not prevented, by treatment with exogenous recombinant IFN-gamma.",
"title": "An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection"
},
{
"docid": "9239963",
"text": "Excessive exposure to estradiol represents the main risk factor for endometrial cancer. The abnormally high estradiol levels in the endometrium of women with endometrial cancer are most likely due to overproduction by the tumour itself. Endometrial cancer cells express the genes encoding the steroidogenic enzymes involved in estradiol synthesis. Here we used RT-PCR and Western blot to show that the nuclear receptors SF1 and LRH1, two well-known regulators of steroidogenic gene expression in gonadal and adrenal cells, are also expressed in endometrial cancer cell lines. By transient transfections, we found that SF1 and LRH1, but not the related nuclear receptor NUR77, can activate the promoters of three human steroidogenic genes: STAR, HSD3B2, and CYP19A1 PII. Similarly, forskolin but not PMA, could activate all three promoters. In addition, we found that both SF1 and LRH1 can transcriptionally cooperate with the AP-1 family members c-JUN and c-FOS, known to be associated with enhanced proliferation of endometrial carcinoma cells, to further enhance activation of the STAR, HSD3B2, and CYP19A1 PII promoters. All together, our data provide novel insights into the mechanisms of steroidogenic gene expression in endometrial cancer cells and thus in the regulation of estradiol biosynthesis by tumour cells.",
"title": "The nuclear receptors SF1 and LRH1 are expressed in endometrial cancer cells and regulate steroidogenic gene transcription by cooperating with AP-1 factors."
},
{
"docid": "1428840",
"text": "BACKGROUND It has been suggested that identified risk factors for endometrial cancer operate through a single etiologic pathway, i.e., exposure to relatively high levels of unopposed estrogen (estrogen in the absence of progestins). Only a few studies, however, have addressed this issue directly. PURPOSE We assessed the risk of developing endometrial cancer among both premenopausal and postmenopausal women in relation to the circulating levels of steroid hormones and sex hormone-binding globulin (SHBG). The independent effect of hormones was assessed after adjustment for other known risk factors. METHODS The data used in the analysis are from a case-control study conducted in five geographic regions in the United States. Incident cases were newly diagnosed during the period from June 1, 1987, through May 15, 1990. The case patients, aged 20-74 years, were matched to control subjects by age, race, and geographic region. The community control subjects were obtained by random-digit-dialing procedures (for subjects 20-64 years old) and from files of the Health Care Financing Administration (for subjects > or = 65 years old). Additional control subjects who were having a hysterectomy performed for benign conditions were obtained from the participating centers. Women reporting use of exogenous estrogens or oral contraceptives within 6 months of interview were excluded, resulting in 68 case patients and 107 control subjects among premenopausal women and 208 case patients and 209 control subjects among postmenopausal women. The hormone analyses were performed on blood samples obtained from case patients or from hysterectomy control subjects before surgery. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of an unconditional logistic regression analysis after we controlled for matching variables and potential confounders. All P values were two-sided. RESULTS High circulating levels of androstenedione were associated with 3.6-fold and 2.8-fold increased risks among premenopausal and postmenopausal women, respectively, after adjustment for other factors (P for trend = .01 and < .001, respectively). Risks related to other hormone fractions varied by menopausal status. Among postmenopausal women, a reduced risk was associated with high SHBG levels and persisted after adjustment was made for obesity and other factors (OR = 0.51; 95% CI = 0.27-0.95). High estrone levels were associated with increased risk (OR = 3.8; 95% CI = 2.2-6.6), although adjustment for other risk factors (particularly body mass index) diminished the effect (OR = 2.2; 95% CI = 1.2-4.4). Albumin-bound estradiol (E2), a marker of the bioavailable fraction, also remained an important risk factor after adjustment was made for other factors (OR = 2.0; 95% CI = 1.0-3.9). In contrast, high concentrations of total, free, and albumin-bound E2 were unrelated to increased risk in premenopausal women. In both premenopausal and postmenopausal groups, risks associated with obesity and fat distribution were not affected by adjustment for hormones. CONCLUSION High endogenous levels of unopposed estrogen are related to increased risk of endometrial cancer, but their independence from other risk factors is inconsistent with being a common underlying biologic pathway through which all risk factors for endometrial cancer operate. IMPLICATIONS Further research should focus on alternative endocrinologic mechanisms for risk associated with obesity and body fat distribution and for the biologic relevance of the increased risk associated with androstenedione in both premenopausal and postmenopausal disease.",
"title": "Case-control study of endogenous steroid hormones and endometrial cancer."
},
{
"docid": "3952288",
"text": "Aire-expressing medullary thymic epithelial cells (mTECs) play a key role in preventing autoimmunity by expressing tissue-restricted antigens to help purge the emerging T cell receptor repertoire of self-reactive specificities. Here we demonstrate a novel role for a CD4+3− inducer cell population, previously linked to development of organized secondary lymphoid structures and maintenance of T cell memory in the functional regulation of Aire-mediated promiscuous gene expression in the thymus. CD4+3− cells are closely associated with mTECs in adult thymus, and in fetal thymus their appearance is temporally linked with the appearance of Aire+ mTECs. We show that RANKL signals from this cell promote the maturation of RANK-expressing CD80−Aire− mTEC progenitors into CD80+Aire+ mTECs, and that transplantation of RANK-deficient thymic stroma into immunodeficient hosts induces autoimmunity. Collectively, our data reveal cellular and molecular mechanisms leading to the generation of Aire+ mTECs and highlight a previously unrecognized role for CD4+3−RANKL+ inducer cells in intrathymic self-tolerance.",
"title": "RANK signals from CD4+3− inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla"
},
{
"docid": "39559521",
"text": "The negative selection of self-reactive thymocytes depends on the expression of tissue-specific antigens by medullary thymic epithelial cells. The autoimmune regulator (Aire) protein plays an important role in turning on these antigens, and the absence of even one Aire-induced tissue-specific antigen in the thymus can lead to autoimmunity in the antigen-expressing target organ. Recently, Aire protein has been detected in peripheral lymphoid organs, suggesting that peripheral Aire plays a complementary role here. In these peripheral sites, Aire was found to regulate the expression of a group of tissue-specific antigens that is distinct from those expressed in the thymus. Furthermore, transgenic antigen expression in extrathymic Aire-expressing cells (eTACs) can mediate deletional tolerance, but the immunological relevance of Aire-dependent, endogenous tissue-specific antigens remains to be determined.",
"title": "Control of central and peripheral tolerance by Aire."
},
{
"docid": "19332616",
"text": "Coronary atherosclerosis is by far the most frequent cause of ischemic heart disease, and plaque disruption with superimposed thrombosis is the main cause of the acute coronary syndromes of unstable angina, myocardial infarction, and sudden death.1 2 3 4 5 Therefore, for event-free survival, the vital question is not why atherosclerosis develops but rather why, after years of indolent growth, it suddenly becomes complicated by life-threatening thrombosis. The composition and vulnerability of plaque rather than its volume or the consequent severity of stenosis produced have emerged as being the most important determinants for the development of the thrombus-mediated acute coronary syndromes; lipid-rich and soft plaques are more dangerous than collagen-rich and hard plaques because they are more unstable and rupture-prone and highly thrombogenic after disruption.6 This review will explore potential mechanisms responsible for the sudden conversion of a stable atherosclerotic plaque to an unstable and life-threatening atherothrombotic lesion—an event known as plaque fissuring, rupture, or disruption.7 8 Atherosclerosis is the result of a complex interaction between blood elements, disturbed flow, and vessel wall abnormality, involving several pathological processes: inflammation, with increased endothelial permeability, endothelial activation, and monocyte recruitment9 10 11 12 13 14 ; growth, with smooth muscle cell (SMC) proliferation, migration, and matrix synthesis15 16 ; degeneration, with lipid accumulation17 18 ; necrosis, possibly related to the cytotoxic effect of oxidized lipid19 ; calcification/ossification, which may represent an active rather than a dystrophic process20 21 ; and thrombosis, with platelet recruitment and fibrin formation.1 22 23 Thrombotic factors may play a role early during atherogenesis, but a flow-limiting thrombus does not develop until mature plaques are present, which is why thrombosis often is classified as a complication rather than a genuine component of atherosclerosis. ### Mature Plaques: Atherosis and Sclerosis As the name atherosclerosis implies, mature …",
"title": "Coronary plaque disruption."
},
{
"docid": "2389574",
"text": "PURPOSE Overexpression of the oncogen Stathmin has been linked to aggressive endometrial carcinoma and a potential for PI3Kinase inhibitors in this disease. We wanted to validate the prognostic value of Stathmin expression in a large prospective multicenter setting. As lymph node sampling is part of current surgical staging, we also aimed to test if Stathmin expression in endometrial curettage specimens could predict lymph node metastasis. EXPERIMENTAL DESIGN A total of 1,076 endometrial cancer patients have been recruited from 10 centers to investigate the biological tumor marker Stathmin in relation to clinicopathologic variables, including lymph node status and survival. Stathmin immunohistochemical staining was carried out in 477 hysterectomy and 818 curettage specimens. RESULTS Seventy-one percent of the patients (n = 763) were subjected to lymph node sampling, of which 12% had metastatic nodes (n = 94). Overexpression of Stathmin was detected in 37% (302 of 818) of the curettage and in 18% (84 of 477) of the hysterectomy specimens investigated. Stathmin overexpression in curettage and hysterectomy specimens were highly correlated and significantly associated with nonendometrioid histology, high grade, and aneuploidy. Stathmin analysis in preoperative curettage samples significantly correlated with, and was an independent predictor of, lymph node metastases. High Stathmin expression was associated with poor disease-specific survival (P ≤ 0.002) both in curettage and hysterectomy specimens. CONCLUSIONS Stathmin immunohistochemical staining identifies endometrial carcinomas with lymph node metastases and poor survival. The value, as a predictive marker for response to PI3Kinase inhibition and as a tool to stratify patients for lymph node sampling in endometrial carcinomas, remains to be determined.",
"title": "Stathmin overexpression identifies high-risk patients and lymph node metastasis in endometrial cancer."
},
{
"docid": "16839245",
"text": "The basic biology of the cell division cycle and its control by protein kinases was originally studied through genetic and biochemical studies in yeast and other model organisms. The major regulatory mechanisms identified in this pioneer work are conserved in mammals. However, recent studies in different cell types or genetic models are now providing a new perspective on the function of these major cell cycle regulators in different tissues. Here, we review the physiological relevance of mammalian cell cycle kinases such as cyclin-dependent kinases (Cdks), Aurora and Polo-like kinases, and mitotic checkpoint regulators (Bub1, BubR1, and Mps1) as well as other less-studied enzymes such as Cdc7, Nek proteins, or Mastl and their implications in development, tissue homeostasis, and human disease. Among these functions, the control of self-renewal or asymmetric cell division in stem/progenitor cells and the ability to regenerate injured tissues is a central issue in current research. In addition, many of these proteins play previously unexpected roles in metabolism, cardiovascular function, or neuron biology. The modulation of their enzymatic activity may therefore have multiple therapeutic benefits in human disease.",
"title": "Physiological relevance of cell cycle kinases."
},
{
"docid": "9550981",
"text": "The adult Drosophila hindgut was recently reported to contain active, tissue-replenishing stem cells, like those of the midgut, but located within an anterior ring so as to comprise a single giant crypt. In contrast to this view, we observed no active stem cells and little cell turnover in adult hindgut tissue based on clonal marking and BrdU incorporation studies. Again contradicting the previous proposal, we showed that the adult hindgut is not generated by anterior stem cells during larval/pupal development. However, severe tissue damage within the hindgut elicits cell proliferation within a ring of putative quiescent stem cells at the anterior of the pylorus. Thus, the hindgut does not provide a model of tissue maintenance by constitutively active stem cells, but has great potential to illuminate mechanisms of stress-induced tissue repair.",
"title": "The Drosophila hindgut lacks constitutively active adult stem cells but proliferates in response to tissue damage."
},
{
"docid": "3514072",
"text": "Gene expression is controlled by the complex interaction of transcription factors binding to promoters and other regulatory DNA elements. One common characteristic of the genomic regions associated with regulatory proteins is a pronounced sensitivity to DNase I digestion. We generated genome-wide high-resolution maps of DNase I hypersensitive (DH) sites from both seedling and callus tissues of rice (Oryza sativa). Approximately 25% of the DH sites from both tissues were found in putative promoters, indicating that the vast majority of the gene regulatory elements in rice are not located in promoter regions. We found 58% more DH sites in the callus than in the seedling. For DH sites detected in both the seedling and callus, 31% displayed significantly different levels of DNase I sensitivity within the two tissues. Genes that are differentially expressed in the seedling and callus were frequently associated with DH sites in both tissues. The DNA sequences contained within the DH sites were hypomethylated, consistent with what is known about active gene regulatory elements. Interestingly, tissue-specific DH sites located in the promoters showed a higher level of DNA methylation than the average DNA methylation level of all the DH sites located in the promoters. A distinct elevation of H3K27me3 was associated with intergenic DH sites. These results suggest that epigenetic modifications play a role in the dynamic changes of the numbers and DNase I sensitivity of DH sites during development.",
"title": "High-resolution mapping of open chromatin in the rice genome."
}
] |
1119
|
Sympathetic nerve activity is elevated throughout normal pregnancy.
|
[
{
"docid": "13907928",
"text": "Baseline neurovascular transduction is reduced in normotensive pregnancy; however, little is known about changes to neurovascular transduction during periods of heightened sympathetic activation. We tested the hypothesis that, despite an exacerbated muscle sympathetic nerve activity (microneurography) response to cold pressor stimulation, the blunting of neurovascular transduction in normotensive pregnant women would result in similar changes in vascular resistance and mean arterial pressure (Finometer) relative to nonpregnant controls. Baseline neurovascular transduction was reduced in pregnant women relative to controls when expressed as the quotient of both total resistance and mean arterial pressure and sympathetic burst frequency (0.32±0.07 versus 0.58±0.16 mm Hg/L/min/bursts/min, P<0.001 and 2.4±0.7 versus 3.6±0.8 mm Hg/bursts/min, P=0.001). Sympathetic activation was greater across all 3 minutes of cold pressor stimulation in the pregnant women relative to the nonpregnant controls. Peak sympathoexcitation was also greater in pregnant than in nonpregnant women, whether expressed as sympathetic burst frequency (+17±13 versus +7±8 bursts/min, P=0.049), burst incidence (+17±9 versus +6±11 bursts/100 hb, P=0.03), or total activity (+950±660 versus +363±414 arbitrary units, P=0.04). However, neurovascular transduction during peak cold pressor-induced sympathoexcitation remained blunted in pregnant women (0.25±0.11 versus 0.45±0.08 mm Hg/L/min/bursts/min, P<0.001 and 1.9±1.0 versus 3.2±0.9 mm Hg/bursts/min, P=0.006). Therefore, mean arterial pressure (93±21 versus 99±6 mm Hg, P=0.4) and total peripheral resistance (12±3 versus 14±3 mm Hg/L/min) were not different between pregnant and nonpregnant women during peak sympathoexcitation. These data indicate that the third trimester of normotensive pregnancy is associated with reductions in neurovascular transduction, which result in the dissociation of sympathetic outflow from hemodynamic outcomes, even during cold pressor-induced sympathoexcitation.",
"title": "Regulation of sympathetic nerve activity during the cold pressor test in normotensive pregnant and nonpregnant women."
},
{
"docid": "5323845",
"text": "BACKGROUND Direct recordings from peripheral sympathetic nerves have shown an increased sympathetic drive in pregnancy-induced hypertension (PIH) and preeclampsia (PE). It is unknown whether sympathetic drive is altered in normal pregnancy, when arterial blood pressure can be normal or relatively low. The aim of this study was to measure and compare peripheral sympathetic discharge, its vasoconstrictor effect and its baroreceptor control, during pregnancy and postpartum in women with normal pregnancy (NP) and PIH and in normotensive nonpregnant (NN) women. METHODS AND RESULTS Twenty-one women with NP, 18 women with PIH, and 21 NN women had muscle sympathetic nerve activity assessed from multiunit discharges (MSNA) and from single units with defined vasoconstrictor properties (s-MSNA). The s-MSNA in NP (38+/-6.6 impulses/100 beats) was greater (P<0.05) than in NN women (19+/-1.8 impulses/100 beats) despite similar age and body weight but less than in PIH women (P<0.001) (146+/-23.5 impulses/100 beats). MSNA followed a similar trend. Cardiac baroreceptor reflex sensitivity (BRS) was impaired in NP and PIH women relative to NN. After delivery, sympathetic activity decreased to values similar to those obtained in NN, and there was an increase in BRS. In women with NP, the decrease in sympathetic output occurred despite an insignificant change in blood pressure. CONCLUSIONS Central sympathetic output was increased in women with normal pregnancy and was even greater in the hypertensive pregnant group. The findings suggest that the moderate sympathetic hyperactivity during the latter months of normal pregnancy may help to return the arterial pressure to nonpregnant levels, although when the increase in activity is excessive, hypertension may ensue.",
"title": "Sympathetic neural mechanisms in normal and hypertensive pregnancy in humans."
},
{
"docid": "18997216",
"text": "Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting. We hypothesized spontaneous sympathetic baroreflex gain would be reduced in normotensive pregnant women relative to nonpregnant matched controls. Integrated muscle sympathetic burst incidence and total sympathetic activity (microneurography), blood pressure (Finometer), and R-R interval (ECG) were assessed at rest in 11 pregnant women (33 ± 1 wk gestation, 31 ± 1 yr, prepregnancy BMI: 23.5 ± 0.9 kg/m(2)) and 11 nonpregnant controls (29 ± 1 yr; BMI: 25.2 ± 1.7 kg/m(2)). Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P < 0.01) relative to controls. Both mean (88 ± 3 vs. 91 ± 2 mmHg, P = 0.4) and diastolic (DBP) (72 ± 3 vs. 73 ± 2 mmHg, P = 0.7) pressures were similar between pregnant and nonpregnant women, respectively, indicating an upward resetting of the baroreflex set point with pregnancy. Baroreflex gain, calculated as the linear relationship between sympathetic burst incidence and DBP, was reduced in pregnant women relative to controls (-3.7 ± 0.5 vs. -5.4 ± 0.5 bursts·100 heart beats(-1)·mmHg(-1), P = 0.03), as was baroreflex gain calculated with total sympathetic activity (-294 ± 24 vs. -210 ± 24 au·100 heart beats(-1)·mmHg(-1); P = 0.03). Cardiovagal baroreflex gain (sequence method) was not different between nonpregnant controls and pregnant women (49 ± 8 vs. 36 ± 8 ms/mmHg; P = 0.2). However, sympathetic (burst incidence) and cardiovagal gains were negatively correlated in pregnant women (R = -0.7; P = 0.02). Together, these data indicate that the influence of the sympathetic nervous system over arterial blood pressure is reduced in normotensive pregnancy, in terms of both long-term and beat-to-beat regulation of arterial pressure, likely through a baroreceptor-dependent mechanism.",
"title": "Sympathetic baroreflex gain in normotensive pregnant women."
}
] |
[
{
"docid": "26710772",
"text": "Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min(-1), 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min(-1); main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm(-5); P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.(-1) min(-1); P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml(-1), P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml(-1), P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications.",
"title": "Sympathetic activation during early pregnancy in humans."
},
{
"docid": "8596837",
"text": "Women with a history of hypertensive pregnancy are at greater risk for future cardiovascular events; however, the mechanisms for this increased risk are unknown. Evidence suggests that an exercise stimulus unmasks latent hypertensive tendencies, identifying individuals at the greatest risk for developing cardiovascular disease. The current study examined the hypothesis that women with a hypertensive pregnancy history exhibit an augmented exercise pressor response. Normotensive women with a history of healthy pregnancy (CON; n = 9) and hypertensive pregnancy (HP+; n = 12) were studied during the mid-luteal phase of the menstrual cycle. Heart rate (HR), systolic and diastolic blood pressure (SBP, DBP), and muscle sympathetic nerve activity (MSNA) were measured during a cold pressor test (CPT), and, following a sufficient period of recovery, during static handgrip to fatigue (SHG) and post-exercise circulatory arrest (PECA). The BP, HR, and MSNA responses to the CPT were similar between groups. The SBP response to SHG and PECA was similar between groups, but DBP and HR were significantly greater in HP+ women (both p < 0.05). MSNA burst frequency, but not burst incidence or total activity, tended to be elevated in HP+ women during the stressor (peak Δ from baseline 31 ± 13 vs. 23 ± 13 bursts/min; p for group = 0.06). Despite no clinical signs of cardiovascular disease or hypertension, women with a history of hypertensive pregnancy display an enhanced cardiovascular reactivity to an exercise stimulus compared to women with a healthy pregnancy history. This response may be indicative of impaired cardiovascular control that precedes the clinical manifestation of hypertension or cardiovascular events.",
"title": "Sympathetic neural and cardiovascular responses during static handgrip exercise in women with a history of hypertensive pregnancy"
},
{
"docid": "58006489",
"text": "Whether sensory nerve can sense bone density or metabolic activity to control bone homeostasis is unknown. Here we found prostaglandin E2 (PGE2) secreted by osteoblastic cells activates PGE2 receptor 4 (EP4) in sensory nerves to regulate bone formation by inhibiting sympathetic activity through the central nervous system. PGE2 secreted by osteoblasts increases when bone density decreases as demonstrated in osteoporotic animal models. Ablation of sensory nerves erodes the skeletal integrity. Specifically, knockout of the EP4 gene in the sensory nerves or cyclooxygenase-2 (COX2) in the osteoblastic cells significantly reduces bone volume in adult mice. Sympathetic tone is increased in sensory denervation models, and propranolol, a β2-adrenergic antagonist, rescues bone loss. Furthermore, injection of SW033291, a small molecule to increase PGE2 level locally, significantly boostes bone formation, whereas the effect is obstructed in EP4 knockout mice. Thus, we show that PGE2 mediates sensory nerve to control bone homeostasis and promote regeneration.",
"title": "Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis"
},
{
"docid": "5107861",
"text": "Exposure to psychosocial stress is a risk factor for many diseases, including atherosclerosis. Although incompletely understood, interaction between the psyche and the immune system provides one potential mechanism linking stress and disease inception and progression. Known cross-talk between the brain and immune system includes the hypothalamic-pituitary-adrenal axis, which centrally drives glucocorticoid production in the adrenal cortex, and the sympathetic-adrenal-medullary axis, which controls stress-induced catecholamine release in support of the fight-or-flight reflex. It remains unknown, however, whether chronic stress changes hematopoietic stem cell activity. Here we show that stress increases proliferation of these most primitive hematopoietic progenitors, giving rise to higher levels of disease-promoting inflammatory leukocytes. We found that chronic stress induced monocytosis and neutrophilia in humans. While investigating the source of leukocytosis in mice, we discovered that stress activates upstream hematopoietic stem cells. Under conditions of chronic variable stress in mice, sympathetic nerve fibers released surplus noradrenaline, which signaled bone marrow niche cells to decrease CXCL12 levels through the β3-adrenergic receptor. Consequently, hematopoietic stem cell proliferation was elevated, leading to an increased output of neutrophils and inflammatory monocytes. When atherosclerosis-prone Apoe(-/-) mice were subjected to chronic stress, accelerated hematopoiesis promoted plaque features associated with vulnerable lesions that cause myocardial infarction and stroke in humans.",
"title": "Chronic variable stress activates hematopoietic stem cells"
},
{
"docid": "9197786",
"text": "Nerve growth factor (NGF) is a potent survival and axon growth factor for neuronal populations in the peripheral nervous system. Although the mechanisms by which target-derived NGF influences survival of innervating neurons have been extensively investigated, its regulation of axonal growth and target innervation are just being elucidated. Here, we identify Wnt5a, a member of the Wnt family of secreted growth factors, as a key downstream effector of NGF in mediating axonal branching and growth in developing sympathetic neurons. Wnt5a is robustly expressed in sympathetic neurons when their axons are innervating NGF-expressing targets. NGF:TrkA signaling enhances neuronal expression of Wnt5a. Wnt5a rapidly induces axon branching while it has a long-term effect on promoting axon extension. Loss of Wnt5a function revealed that it is necessary for NGF-dependent axonal branching and growth, but not survival, in vitro. Furthermore, Wnt5a(-/-) mice display reduced innervation of NGF-expressing target tissues, and a subsequent increase in neuronal apoptosis, in vivo. Wnt5a functions in developing sympathetic neurons by locally activating protein kinase C in axons. Together, our findings define a novel regulatory pathway in which Wnt5a, expressed in sympathetic neurons in response to target-derived NGF, regulates innervation of peripheral targets.",
"title": "Wnt5a mediates nerve growth factor-dependent axonal branching and growth in developing sympathetic neurons."
},
{
"docid": "1701063",
"text": "Semaphorin 3A (Sema3A) is a diffusible axonal chemorepellent that has an important role in axon guidance. Previous studies have demonstrated that Sema3a−/− mice have multiple developmental defects due to abnormal neuronal innervations. Here we show in mice that Sema3A is abundantly expressed in bone, and cell-based assays showed that Sema3A affected osteoblast differentiation in a cell-autonomous fashion. Accordingly, Sema3a−/− mice had a low bone mass due to decreased bone formation. However, osteoblast-specific Sema3A-deficient mice (Sema3acol1−/− and Sema3aosx−/− mice) had normal bone mass, even though the expression of Sema3A in bone was substantially decreased. In contrast, mice lacking Sema3A in neurons (Sema3asynapsin−/− and Sema3anestin−/− mice) had low bone mass, similar to Sema3a−/− mice, indicating that neuron-derived Sema3A is responsible for the observed bone abnormalities independent of the local effect of Sema3A in bone. Indeed, the number of sensory innervations of trabecular bone was significantly decreased in Sema3asynapsin−/− mice, whereas sympathetic innervations of trabecular bone were unchanged. Moreover, ablating sensory nerves decreased bone mass in wild-type mice, whereas it did not reduce the low bone mass in Sema3anestin−/− mice further, supporting the essential role of the sensory nervous system in normal bone homeostasis. Finally, neuronal abnormalities in Sema3a−/− mice, such as olfactory development, were identified in Sema3asynasin−/− mice, demonstrating that neuron-derived Sema3A contributes to the abnormal neural development seen in Sema3a−/− mice, and indicating that Sema3A produced in neurons regulates neural development in an autocrine manner. This study demonstrates that Sema3A regulates bone remodelling indirectly by modulating sensory nerve development, but not directly by acting on osteoblasts.",
"title": "Sema3A regulates bone-mass accrual through sensory innervations"
},
{
"docid": "34582256",
"text": "The object of this study was to assess the role of brown adipose tissue (BAT) and the sympathetic nervous system in the rise in heat production associated with endotoxin-induced fever. Oxygen consumption (VO2) was found to be significantly increased (28%) over a 4-h period after two doses of endotoxin (Escherichia coli lipopolysaccharide, 0.3 mg/100 g body wt) given 24 h apart. Injection of a mixed beta-adrenoceptor antagonist (propranolol) reduced VO2 by 14% in endotoxin-treated rats, whereas the selective beta 1- (atenolol) or beta 2- (ICI 118551) antagonists suppressed VO2 by 10%. These drugs did not affect VO2 in control animals. BAT thermogenic activity assessed from measurements of in vitro mitochondrial guanosine 5'-diphosphate (GDP) binding was elevated by 54% in interscapular BAT and by 171% in other BAT depots. Surgical denervation of one lobe of the interscapular depot prevented these responses. Endotoxin failed to stimulate GDP binding in rats fed protein-deficient diets. This may have been because BAT thermogenic activity was already elevated in control rats fed these diets or because endotoxin caused a marked suppression of food intake in the protein-deficient animals. The results indicate that sympathetic activation of BAT is involved in the thermogenic responses to endotoxin and that these can be modified by dietary manipulation.",
"title": "Involvement of sympathetic nervous system and brown fat in endotoxin-induced fever in rats."
},
{
"docid": "20544428",
"text": "Recent studies have highlighted the involvement of the peripheral immune system in delayed cellular degeneration after stroke. In the permanent middle cerebral artery occlusion (MCAO) model of stroke, the spleen decreases in size. This reduction occurs through the release of splenic immune cells. Systemic treatment with human umbilical cord blood cells (HUCBC) 24 h post-stroke blocks the reduction in spleen size while significantly reducing infarct volume. Splenectomy 2 weeks prior to MCAO also reduces infarct volume, further demonstrating the detrimental role of this organ in stroke-induced neurodegeneration. Activation of the sympathetic nervous system after MCAO results in elevated catecholamine levels both at the level of the spleen, through direct splenic innervation, and throughout the systemic circulation upon release from the adrenal medulla. These catecholamines bind to splenic alpha and beta adrenoreceptors. This study examines whether catecholamines regulate the splenic response to stroke. Male Sprague-Dawley rats either underwent splenic denervation 2 weeks prior to MCAO or received injections of carvedilol, a pan adrenergic receptor blocker, prazosin, an alpha1 receptor blocker, or propranolol, a beta receptor blocker. Denervation was confirmed by reduced splenic expression of tyrosine hydroxylase. Denervation prior to MCAO did not alter infarct volume or spleen size. Propranolol treatment also had no effects on these outcomes. Treatment with either prazosin or carvedilol prevented the reduction in spleen size, yet only carvedilol significantly reduced infarct volume (p < 0.05). These results demonstrate that circulating blood borne catecholamines regulate the splenic response to stroke through the activation of both alpha and beta adrenergic receptors.",
"title": "Blockade of adrenoreceptors inhibits the splenic response to stroke."
},
{
"docid": "12337611",
"text": "LIN28B regulates developmental processes by modulating microRNAs (miRNAs) of the let-7 family. A role for LIN28B in cancer has been proposed but has not been established in vivo. Here, we report that LIN28B showed genomic aberrations and extensive overexpression in high-risk neuroblastoma compared to several other tumor entities and normal tissues. High LIN28B expression was an independent risk factor for adverse outcome in neuroblastoma. LIN28B signaled through repression of the let-7 miRNAs and consequently resulted in elevated MYCN protein expression in neuroblastoma cells. LIN28B–let-7–MYCN signaling blocked differentiation of normal neuroblasts and neuroblastoma cells. These findings were fully recapitulated in a mouse model in which LIN28B expression in the sympathetic adrenergic lineage induced development of neuroblastomas marked by low let-7 miRNA levels and high MYCN protein expression. Interference with this pathway might offer therapeutic perspectives.",
"title": "LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression"
},
{
"docid": "13448422",
"text": "This review discusses some of the mechanisms inherent in diabetes that predispose patients to increased cardiac morbidity and mortality. Single photon emission computerized tomography or photon emission tomography with radioactive labeled analogues of norepinephrine have shown that cardiac sympathetic dysfunction and incompetence are early and also late abnormalities in patients with Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus. Furthermore, myocardial blood flow assessment with photon emission tomography has shown that in patients without myocardial perfusion deficits, endothelial-dependent vasodilatation is severely reduced in relation to cardiac sympathetic dysfunction. In addition, signs of endothelial activation have also been found early in patients with Type I and Type II diabetes in whom vascular disease has not been clinically detected. This activation in conjunction with glycaemic control is important in determining macrovascular mortality. Cardiac sympathetic dysfunction is partially restored to normal with near normalisation of glycaemia. Interpretations. Recently unrecognized “subtle” changes predispose the heart to failure, after ischaemia-induced remodelling, and arteriosclerotic plaques to instability and rupture. These changes act in conjunction with effects, driven by hyperglycaemia and diabetes, on the endothelium of large blood vessels, e. g. on nitric oxide release or on protein kinase-C β activation. Meticulous glucose control early on and rapid recompensation of hyperglycaemia in patients with acute coronary syndrome are part of a successful intensive multifactorial approach to prevent the heart in diabetes converting from ailing to failing. [Diabetologia (2000) 43: 1455–1469]",
"title": "A new look at the heart in diabetes mellitus: from ailing to failing"
},
{
"docid": "41131087",
"text": "Human placental lactogen and unconjugated estriol concentrations in maternal serum were evaluated in 100 uneventful twin pregnancies, and these values were compared with those observed in 16 twin pregnancies associated with intrauterine growth retardation or single intrauterine fetal death. In pregnancies associated with intrauterine growth retardation (n = 8), human placental lactogen levels were at the lower limit of normal range for singleton pregnancies, whereas estriol levels were normal in most cases. When one of the fetuses had died before week 33 of pregnancy (n = 5), both human placental lactogen and estriol levels were low and they were almost at the levels in singleton pregnancy. When intrauterine fetal death occurred after week 36 of pregnancy (n = 3), both hormone levels remained normal until term. Thus human placental lactogen rather than estriol is a good indicator of intrauterine growth retardation in twin pregnancy. Both human placental lactogen and estriol are useful for the monitoring of the surviving fetus in the case of single intrauterine fetal death.",
"title": "Human placental lactogen and unconjugated estriol concentrations in twin pregnancy: monitoring of fetal development in intrauterine growth retardation and single intrauterine fetal death."
},
{
"docid": "4409524",
"text": "In pregnancy, trophoblast invasion and uterine spiral artery remodelling are important for lowering maternal vascular resistance and increasing uteroplacental blood flow. Impaired spiral artery remodelling has been implicated in pre-eclampsia, a major complication of pregnancy, for a long time but the underlying mechanisms remain unclear. Corin (also known as atrial natriuretic peptide-converting enzyme) is a cardiac protease that activates atrial natriuretic peptide (ANP), a cardiac hormone that is important in regulating blood pressure. Unexpectedly, corin expression was detected in the pregnant uterus. Here we identify a new function of corin and ANP in promoting trophoblast invasion and spiral artery remodelling. We show that pregnant corin- or ANP-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice, trophoblast invasion and uterine spiral artery remodelling were markedly impaired. Consistent with this, the ANP potently stimulated human trophoblasts in invading Matrigels. In patients with pre-eclampsia, uterine Corin messenger RNA and protein levels were significantly lower than that in normal pregnancies. Moreover, we have identified Corin gene mutations in pre-eclamptic patients, which decreased corin activity in processing pro-ANP. These results indicate that corin and ANP are essential for physiological changes at the maternal–fetal interface, suggesting that defects in corin and ANP function may contribute to pre-eclampsia.",
"title": "Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy"
},
{
"docid": "6123521",
"text": "The brain interprets experiences and translates them into behavioral and physiological responses. Stressful events are those which are threatening or, at the very least, unexpected and surprising, and the physiological and behavioral responses are intended to promote adaptation via a process called \"allostasis. \" Chemical mediators of allostasis include cortisol and adrenalin from the adrenal glands, other hormones, and neurotransmitters, the parasympathetic and sympathetic nervous systems, and cytokines and chemokines from the immune system. Two brain structures, the amygdala and hippocampus, play key roles in interpreting what is stressful and determining appropriate responses. The hippocampus, a key structure for memories of events and contexts, expresses receptors that enable it to respond to glucocorticoid hormones in the blood, it undergoes atrophy in a number of psychiatric disorders; it also responds to stressors with changes in excitability, decreased dendritic branching, and reduction in number of neurons in the dentate gyrus. The amygdala, which is important for \"emotional memories, \" becomes hyperactive in posttraumatic stress disorder and depressive illness, in animal models of stress, there is evidence for growth and hypertrophy of nerve cells in the amygdala. Changes in the brain after acute and chronic stressors mirror the pattern seen in the metabolic, cardiovascular, and immune systems, that is, short-term adaptation (allostasis) followed by long-term damage (allostatic load), eg, atherosclerosis, fat deposition obesity, bone demineralization, and impaired immune function. Allostatic load of this kind is seen in major depressive illness and may also be expressed in other chronic anxiety and mood disorders.",
"title": "Structural plasticity of the adult brain: how animal models help us understand brain changes in depression and systemic disorders related to depression"
},
{
"docid": "30983338",
"text": "AIMS/HYPOTHESIS We assessed the association between congenital malformations and maternal hyperglycemia in pregnant women with pregestational (type 1 or type 2) diabetes and investigated if the rate of congenital malformations was similar in women with near-normal glycemic control compared to the background population. We also assessed the association between congenital malformations and maternal hyperglycemia in pregnant women with pregestational diabetes with special focus on women with near-normal HbA1c in early pregnancy. MATERIALS AND METHODS This is a literature review based on an electronic literature search of the databases PubMed, Cochrane, Embase and Web of Science conducted in July 2017 using the search terms diabetes, pregnancy, HbA1c or glycemic control and congenital anomaly or congenital anomaly. We included original papers in English published after 1997 with data on congenital malformations and HbA1c in at least 250 women with pregestational diabetes. RESULTS Nine papers with in total 6225 women with type 1 diabetes and 2334 women with type 2 diabetes were included. The prevalence of congenital malformations was 6.4% in women with type 1 diabetes and 4.3% in women with type 2 diabetes and for the combined group of women with pregestational diabetes, the relative risk compared to the background population was 3.2. In women with HbA1c < 53 mmol/mol (7.0%) in early pregnancy or HbA1c 53-64 mmol/mol (7.0-8.0%) the prevalence of congenital malformations was 4.3 and 3.7%, respectively, with a relative risk of 2.2 and 1.9, respectively. CONCLUSIONS In pregnant women with pregestational diabetes the prevalence of congenital abnormalities was threefold higher in women with pregestational diabetes compared to the background population. However, HbA1c below 53 mmol/mol (7.0%) in early pregnancy was also associated with a two times increased risk of congenital malformations compared to the background population.",
"title": "The prevalence of congenital malformations is still higher in pregnant women with pregestational diabetes despite near-normal HbA1c: a literature review."
},
{
"docid": "25182647",
"text": "Acute fatty liver of pregnancy (AFLP) and the syndrome of hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) are rare but major disorders of the third trimester of pregnancy. Over a 10-year period, 46 women (median age, 30 years; range, 17-41 years) developed hepatic dysfunction severe enough to require transfer to our Liver Failure Unit. Three quarters of the women were nulliparous, and 5 had twin pregnancies; the median gestational age was 35 weeks (range, 24-40 weeks). At admission, 32 patients (70%) were preeclamptic and 21 (46%) were encephalopathic and/or ventilated. Thirty-two patients (70%) had clinical features and laboratory values consistent with AFLP, and 7 (15%) had HELLP syndrome. One patient had preeclamptic liver rupture requiring liver transplantation. In 6 other patients, causes of severe liver dysfunction unrelated to pregnancy were found. Infectious complications occurred in 17 of the patients with AFLP (53%) and in 2 of those with HELLP syndrome (29%). Major intra-abdominal bleeding occurred in 12 women (10 with AFLP), 9 of whom required laparotomies for clot evacuation. Four patients with AFLP (12.5%) had a fatal outcome, with a corresponding perinatal mortality rate of 9%. There were no maternal or perinatal deaths associated with HELLP syndrome. In contrast to results of many previous studies, the results of this large series suggest a relatively favorable maternal and perinatal outcome in severe AFLP and HELLP syndrome. Further improvements in outcome are likely to be achieved through the prevention of the bleeding and infectious complications associated with these disorders.",
"title": "Maternal and perinatal outcome in severe pregnancy-related liver disease."
},
{
"docid": "5572127",
"text": "The role of ataxia telangiectasia mutated (ATM), a DNA double-strand break recognition and response protein, in inflammation and inflammatory diseases is unclear. We have previously shown that high levels of systemic DNA damage are induced by intestinal inflammation in wild-type mice. To determine the effect of Atm deficiency in inflammation, we induced experimental colitis in Atm(-/-), Atm(+/-), and wild-type mice via dextran sulfate sodium (DSS) administration. Atm(-/-) mice had higher disease activity indices and rates of mortality compared with heterozygous and wild-type mice. Systemic DNA damage and immune response were characterized in peripheral blood throughout and after three cycles of treatment. Atm(-/-) mice showed increased sensitivity to levels of DNA strand breaks in peripheral leukocytes, as well as micronucleus formation in erythroblasts, compared with heterozygous and wild-type mice, especially during remission periods and after the end of treatment. Markers of reactive oxygen and nitrogen species-mediated damage, including 8-oxoguanine and nitrotyrosine, were present both in the distal colon and in peripheral leukocytes, with Atm(-/-) mice manifesting more 8-oxoguanine formation than wild-type mice. Atm(-/-) mice showed greater upregulation of inflammatory cytokines and significantly higher percentages of activated CD69+ and CD44+ T cells in the peripheral blood throughout treatment. ATM, therefore, may be a critical immunoregulatory factor dampening the deleterious effects of chronic DSS-induced inflammation, necessary for systemic genomic stability and homeostasis of the gut epithelial barrier.",
"title": "Atm-deficient mice exhibit increased sensitivity to dextran sulfate sodium-induced colitis characterized by elevated DNA damage and persistent immune activation."
},
{
"docid": "68317730",
"text": "Objectives Corin, an atrial natriuretic peptide-converting enzyme, has been found to promote trophoblast invasion and spiral artery remodeling. Reduced maternal plasma atrial natriuretic peptide (ANP) levels and elevated corin levels have been reported in pregnancies complicated by PE. The aim of this study was to investigate longitudinal changes in maternal plasma levels of corin and midregional proatrial natriuretic peptide (MR-PANP) in pregnancies that develop preeclampsia (PE) and gestational hypertension (GH). Methods Nested case control study drawn from a larger prospective longitudinal study in singleton pregnancies identified by screening at 11 + 0 − 13 + 6 weeks’ gestation as being at high risk for PE. Blood samples were taken every four weeks until delivery. Values were compared in pregnancies that developed preterm-PE (requiring delivery before 37 weeks), term-PE, GH, and those that remained normotensive. The distribution of maternal plasma corin and PANP were made Gaussian after log 10 transformation. Analysis of repeated measures with multilevel mixed-effects linear model (fixed effects and random effects) was performed. The multilevel model was compared to one-level model by the likelihood radio (LR) test. Results A total of 471 samples were analyzed from 122 women, including 85 that remained normotensive, 12 that developed GH, 13 term-PE and 12 preterm-PE. In the normotensive group, log10corin levels were associated with gestational age ( p p = 0.001). In the GH and term-PE groups, corin did not differ significantly from the normotensive group ( p = 0.64 and p = 0.16, respectively). Compared to the normotensive group, MR-PANP levels were significantly higher in the pregnancies that developed preterm-PE and GH ( p = 0.046 and p = 0.019, respectively), but not term-PE ( p = 0.47). Conclusions Maternal plasma corin and MR-PANP could potentially be useful biomarkers for the prediction of preterm-PE. Disclosures A. Khalil: Research Support Recipient; Commercial Interests: USCOM, Roche, Alere, NICOM, Q-fFN; Speaker: Roche.",
"title": "Longitudinal changes in maternal corin and mid-regional proatrial natriuretic peptide in women at risk of pre-eclampsia"
},
{
"docid": "36838958",
"text": "Uncoupling protein 1 (Ucp1), which is localized in the mitochondrial inner membrane of mammalian brown adipose tissue (BAT), generates heat by uncoupling oxidative phosphorylation. Upon cold exposure or nutritional abundance, sympathetic neurons stimulate BAT to express Ucp1 to induce energy dissipation and thermogenesis. Accordingly, increased Ucp1 expression reduces obesity in mice and is correlated with leanness in humans. Despite this significance, there is currently a limited understanding of how Ucp1 expression is physiologically regulated at the molecular level. Here, we describe the involvement of Sestrin2 and reactive oxygen species (ROS) in regulation of Ucp1 expression. Transgenic overexpression of Sestrin2 in adipose tissues inhibited both basal and cold-induced Ucp1 expression in interscapular BAT, culminating in decreased thermogenesis and increased fat accumulation. Endogenous Sestrin2 is also important for suppressing Ucp1 expression because BAT from Sestrin2(-/-) mice exhibited a highly elevated level of Ucp1 expression. The redox-inactive mutant of Sestrin2 was incapable of regulating Ucp1 expression, suggesting that Sestrin2 inhibits Ucp1 expression primarily through reducing ROS accumulation. Consistently, ROS-suppressing antioxidant chemicals, such as butylated hydroxyanisole and N-acetylcysteine, inhibited cold- or cAMP-induced Ucp1 expression as well. p38 MAPK, a signaling mediator required for cAMP-induced Ucp1 expression, was inhibited by either Sestrin2 overexpression or antioxidant treatments. Taken together, these results suggest that Sestrin2 and antioxidants inhibit Ucp1 expression through suppressing ROS-mediated p38 MAPK activation, implying a critical role of ROS in proper BAT metabolism.",
"title": "Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species."
},
{
"docid": "25789730",
"text": "Both axon and myelin degeneration have significant impact on the long-term disability of patients with white matter disorder. However, the clinical manifestations of the neurological dysfunction caused by white matter disorders are not sufficient to determine the origin of neurological deficits. A noninvasive biological marker capable of detecting and differentiating axon and myelin degeneration would be a significant addition to currently available tools. Directional diffusivities derived from diffusion tensor imaging (DTI) have been previously proposed by this group as potential biological markers to detect and differentiate axon and myelin degeneration. To further test the hypothesis that axial (lambdaparallel) and radial (lambdaperpendicular) diffusivities reflect axon and myelin pathologies, respectively, the optic nerve was examined serially using DTI in a mouse model of retinal ischemia. A significant decrease of lambdaparallel, the putative DTI axonal marker, was observed 3 days after ischemia without concurrently detectable changes in lambdaperpendicular, the putative myelin marker. This result is consistent with histological findings of significant axonal degeneration with no detectable demyelination at 3 days after ischemia. The elevation of lambdaperpendicular observed 5 days after ischemia is consistent with histological findings of myelin degeneration at this time. These results support the hypothesis that lambdaparallel and lambdaperpendicular hold promise as specific markers of axonal and myelin injury, respectively, and, further, that the coexistence of axonal and myelin degeneration does not confound this utility.",
"title": "Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia."
},
{
"docid": "21297708",
"text": "1. Nitric oxide (NO) has been suggested as a gastrointestinal neurotransmitter, mediating the gastric receptive relaxation and the relaxation in the peristaltic reflex. The aim of the present study was to measure nerve-induced NO formation in vivo in the gastrointestinal tract. 2. Formation of the nitric oxide oxidation products nitrite and nitrate during vagal nerve stimulation were measured in the anaesthetized rabbit. Microdialysis probes were inserted into the wall of the stomach and proximal colon, and nitrite and nitrate in dialysate measured by capillary electrophoresis. 3. During bilateral vagal nerve stimulation there was an increase in nitrite and nitrate formation at the level of the stomach and in nitrite formation at the level of the colon. This increase was inhibited by intravenous administration of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME 30 mg kg-1). Furthermore, L-NAME significantly increased nerve-induced gastric and colonic contractions, as well as spontaneous colonic contractions. 4. In summary, we present a new methodological procedure for quantification of small changes in nitric oxide formation in vivo. This study provides evidence that nitric oxide is released in the stomach and colonic wall during vagal nerve activity, at concentrations able to cause inhibition of smooth muscle contractions in vivo.",
"title": "Nerve-induced release of nitric oxide in the rabbit gastrointestinal tract as measured by in vivo microdialysis."
},
{
"docid": "19843244",
"text": "BACKGROUND AND PURPOSE The PAR(2) receptors are involved in chronic arthritis by mechanisms that are as yet unclear. Here, we examined PAR(2) activation in the rat knee joint. EXPERIMENTAL APPROACH PAR(2) in rat knee joint dorsal root ganglia (DRG) cells at L3-L5, retrogradely labelled with Fluoro-gold (FG) were demonstrated immunohistochemically. Electrophysiological recordings from knee joint nerve fibres in urethane anaesthetized Wistar rats assessed the effects of stimulating joint PAR(2) with its activating peptide, 2-furoyl-LIGRLO-NH(2) (1-100 nmol·100 μL(-1) , via close intra-arterial injection). Fibre firing rate was recorded during joint rotations before and 15 min after administration of PAR(2) activating peptide or control peptide. Leukocyte kinetics in the synovial vasculature upon PAR(2) activation were followed by intravital microscopy for 60 min after perfusion of 2-furoyl-LIGRLO-NH(2) or control peptide. Roles for transient receptor potential vanilloid-1 (TRPV1) or neurokinin-1 (NK(1) ) receptors in the PAR(2) responses were assessed using the selective antagonists, SB366791 and RP67580 respectively. KEY RESULTS PAR(2) were expressed in 59 ± 5% of FG-positive DRG cells; 100 nmol 2-furoyl-LIGRLO-NH(2) increased joint fibre firing rate during normal and noxious rotation, maximal at 3 min (normal; 110 ± 43%, noxious; 90 ± 31%). 2-Furoyl-LIGRLO-NH(2) also significantly increased leukocyte rolling and adhesion over 60 min. All these effects were blocked by pre-treatment with SB366791 and RP67580 (P < 0.05 compared with 2-furoyl-LIGRLO-NH(2) alone). CONCLUSIONS AND IMPLICATIONS PAR(2) receptors play an acute inflammatory role in the knee joint via TRPV1- and NK(1) -dependent mechanisms involving both PAR(2) -mediated neuronal sensitization and leukocyte trafficking.",
"title": "Activation of PAR(2) receptors sensitizes primary afferents and causes leukocyte rolling and adherence in the rat knee joint."
},
{
"docid": "25687558",
"text": "The genetically obese (ob/ob) mouse exhibits defective thermoregulatory responses to cold exposure. Pathophysiological explanations for this phenomenon have focused on abnormalities in intracellular metabolism or insensitivity of peripheral tissues to the thermogenic effects of catecholamines. Because the sympathetic nervous system (SNS) is subject to feedback regulation, a peripheral impairment in thermogenesis should be associated with a compensatory increase in SNS activity. To examine SNS activity in the ob/ob mouse, norepinephrine (NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of ob/ob and lean mice. The results from studies utilizing radiolabeled NE or inhibition of NE biosynthesis with alpha-methyl-p-tyrosine to measure NE turnover demonstrated reductions in SNS activity of 33-56% in heart and of 45-73% in IBAT in ob/ob mice at ambient temperature (22 degrees C) compared with measurements in lean controls. During cold exposure (4 degrees C) NE turnover increased in heart and IBAT to a similar extent in both ob/ob and lean mice, but NE turnover rates in heart, and probably in IBAT as well, remained lower in the obese mice than in the lean despite the gradual development of hypothermia in the ob/ob mice during this period. Administration of naltrexone, a long-acting opiate antagonist, failed to reverse the suppression of SNS activity observed in the ob/ob mice. These data indicate that diminished SNS activity in ob/ob mice may be an additional factor contributing to the defective thermogenesis characteristic of these animals.",
"title": "Diminished sympathetic nervous system activity in genetically obese (ob/ob) mouse."
},
{
"docid": "39776978",
"text": "The maintenance of adequate bone mass is dependent upon the controlled and timely removal of old, damaged bone. This complex process is performed by the highly specialized, multinucleated osteoclast. Over the past 15 years, a detailed picture has emerged describing the origins, differentiation pathways and activation stages that contribute to normal osteoclast function. This information has primarily been obtained by the development and skeletal analysis of genetically modified mouse models. Mice harboring mutations in specific genetic loci exhibit bone defects as a direct result of aberrations in normal osteoclast recruitment, formation or function. These findings include the identification of the RANK–RANKL–OPG system as a primary mediator of osteoclastogenesis, the characterization of ion transport and cellular attachment mechanisms and the recognition that matrix-degrading enzymes are essential components of resorptive activity. This Review focuses on the principal observations in osteoclast biology derived from genetic mouse models, and highlights emerging concepts that describe how the osteoclast is thought to contribute to the maintenance of adequate bone mass and integrity throughout life.",
"title": "Advances in osteoclast biology: old findings and new insights from mouse models"
},
{
"docid": "21185923",
"text": "CD25+CD4+ regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance. We show here that glucocorticoid-induced tumor necrosis factor receptor family–related gene (GITR, also known as TNFRSF18)—a member of the tumor necrosis factor–nerve growth factor (TNF-NGF) receptor gene superfamily—is predominantly expressed on CD25+CD4+ T cells and on CD25+CD4+CD8− thymocytes in normal naïve mice. We found that stimulation of GITR abrogated CD25+CD4+ T cell–mediated suppression. In addition, removal of GITR-expressing T cells or administration of a monoclonal antibody to GITR produced organ-specific autoimmune disease in otherwise normal mice. Thus, GITR plays a key role in dominant immunological self-tolerance maintained by CD25+CD4+ regulatory T cells and could be a suitable molecular target for preventing or treating autoimmune disease.",
"title": "Stimulation of CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance"
},
{
"docid": "14419116",
"text": "Whole cell patch-clamp recordings were made from sympathetic preganglionic neurons (SPNs) in the intermediolateral cell column of thoracolumbar spinal cord slices of 12- to 16-day-old rats, and the effects of pituitary adenylate cyclase activating polypeptide (PACAP)-38 on N-methyl-D-aspartate (NMDA)- and kainate (KA)-induced inward currents were examined. PACAP, in concentrations (10-30 nM) that caused no significant change of holding currents, reversibly increased NMDA-induced currents but not KA-induced currents. At higher concentrations (>30 nM), the peptide produced a sustained inward current. The potentiating effect of PACAP was nullified by prior incubation of the slices with the adenylate cyclase inhibitor MDL-12,330A (25 microM). Further, superfusing the slices with the membrane-permeable cyclic AMP analogue N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (100-300 microM) in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (700 microM) increased the NMDA currents. This result suggests that PACAP selectively increases NMDA-receptor-mediated responses in the rat SPNs, probably via a cyclic-AMP-dependent mechanism, providing evidence that the peptide may be involved in synaptic plasticity.",
"title": "Potentiation of NMDA currents by pituitary adenylate cyclase activating polypeptide in neonatal rat sympathetic preganglionic neurons."
},
{
"docid": "25293721",
"text": "Placental oxidative stress plays a key role in the pathophysiology of placenta-related disorders, most notably preeclampsia (PE) and intrauterine growth restriction (IUGR). Oxidative stress occurs when accumulation of reactive oxygen species (ROS) damages DNA, proteins and lipids, an outcome that is limited by antioxidant enzymes; mitochondrial uncoupling protein 2 (UCP2) may also limit oxidative stress by reducing ROS production. Here we characterized placental antioxidant defenses during normal gestation and following glucocorticoid-induced IUGR. Placentas were collected on Days 16 and 22 of normal rat pregnancy (term = Day 23) and at Day 22 after dexamethasone treatment from Day 13. Expression of several genes encoding antioxidant enzymes (Sod1, Sod2, Sod3, Cat, Gpx3, Txn1, Txnrd1, Txnrd2, and Txnrd3) and Ucp2 was measured by quantitative RT-PCR in the labyrinth (LZ) and junctional zones (JZ) of the placenta. Expression of Sod1 and Ucp2 mRNAs and the activity of xanthine oxidase, a source of ROS, all increased from Days 16 to 22 in both placental zones, whereas Sod2 and Gpx3 increased only in the rapidly growing LZ. In contrast, Sod3 and Txnrd1 expression fell in the LZ over this period, whereas total superoxide dismutase activity remained stable. Dexamethasone treatment reduced fetal-placental growth and LZ expression of Ucp2 but increased JZ expression of Txn1. Indices of placental oxidative damage (TBARS, F2-isoprostanes, and 8-OHdG) did not change with gestational age or dexamethasone, indicative of adequate antioxidant protection. Overall, our data suggest that the rat placenta is protected from oxidative stress by the dynamic zone- and stage-dependent expression of antioxidant defense genes.",
"title": "Antioxidant Defenses in the Rat Placenta in Late Gestation: Increased Labyrinthine Expression of Superoxide Dismutases, Glutathione Peroxidase 3, and Uncoupling Protein 21"
},
{
"docid": "22820637",
"text": "The placental leucine aminopeptidase (P-LAP), adipocyte-derived leucine aminopeptidase (A-LAP) and leukocyte-derived aminopeptidase (L-RAP) belong to one distinct group of the M1 family of amimopeptidases, which we term the \"Oxytocinase subfamily\". They share HEXXH(X)18E Zn-binding and GAMEN motifs essential for the enzymatic activities. Intracellular localization is the characteristic feature of the subfamily members. While P-LAP is translocated from intracellular vesicles to plasma membrane in a stimulus-dependent manner, both A-LAP and L-RAP are retained in the endoplasmic reticulum. They contain sequences necessary for the specific localization in the cell. It is getting evident that the subfamily members play important roles in the maintenance of homeostasis including maintenance of normal pregnancy, memory retention, blood pressure regulation and antigen presentation. In this review, current situation of this newly identified subfamily is summarized.",
"title": "The oxytocinase subfamily of M1 aminopeptidases."
},
{
"docid": "16488405",
"text": "Physical activity induces a subclinical inflammatory response, mediated in part by leukocytes, and manifested by elevated concentrations of circulating proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). However, the source of the cytokines that appear during exercise remains unknown. In this study, we examined exercise-induced changes in plasma cytokine concentrations and their corresponding mRNA expression in peripheral blood mononuclear cells. Ten healthy [peak oxygen uptake = 48.8 ± 6.5 (SD) ml · kg−1 · min−1] but untrained men [age = 25 ± 5 (SD) yr] undertook 3 h of exercise (cycling and inclined walking) at 60–65% peak oxygen uptake. Circulating leukocyte subset counts were elevated during and 2 h postexercise but returned to normal within 24 h. Plasma concentrations of IL-1β, IL-6, and TNF-α peaked at the end of exercise and remained elevated at 2 h (IL-6) and up to 24 h (IL-1β and TNF-α) postexercise. Cytokine gene expression in circulating mononucl...",
"title": "Downloaded from"
},
{
"docid": "1686881",
"text": "BACKGROUND Patients with familial amyloid polyneuropathy, a rare hereditary form of amyloidosis, have progressive autonomic neuropathy. The disease usually does not induce heart failure but is associated with sudden death, conduction disturbances, and an increased risk of complications during anesthesia. Although cardiac sympathetic denervation has been clearly demonstrated, the postsynaptic status of the cardiac autonomic nervous system remains unelucidated. METHODS AND RESULTS Twenty-one patients were studied (age, 39+/-11 years; normal coronary arteries; left ventricular ejection fraction 68+/-9%). To evaluate the density and affinity constants of myocardial muscarinic receptors, PET with (11)C-MQNB (methylquinuclidinyl benzilate), a specific hydrophilic antagonist, was used. Cardiac beta-receptor functional efficiency was studied by the heart rate (HR) response to intravenous infusion of isoproterenol (5 minutes after 2 mg of atropine, 5, 10, and 15 ng/kg per minute during 5 minutes per step). The mean muscarinic receptor density was higher in patients than in control subjects (B'(max), 35.5+/-8.9 versus 26.1+/-6.7 pmol/mL, P=0.003), without change in receptor affinity. The increase in HR after injection of atropine as well as of MQNB was lower in patients compared with control subjects despite a similar basal HR (DeltaHR after atropine, 11+/-21% versus 62+/-17%; P<0.001), consistent with parasympathetic denervation. Incremental infusion of isoproterenol induced a similar increase in HR in patients and control subjects. CONCLUSIONS Cardiac autonomic denervation in familial amyloid polyneuropathy results in an upregulation of myocardial muscarinic receptors but without change in cardiac beta-receptor responsiveness to catecholamines.",
"title": "Myocardial muscarinic receptor upregulation and normal response to isoproterenol in denervated hearts by familial amyloid polyneuropathy."
},
{
"docid": "12631697",
"text": "Limited neural input results in muscle weakness in neuromuscular disease because of a reduction in the density of muscle innervation, the rate of neuromuscular junction activation or the efficiency of synaptic transmission. We developed a small-molecule fast-skeletal-troponin activator, CK-2017357, as a means to increase muscle strength by amplifying the response of muscle when neural input is otherwise diminished secondary to neuromuscular disease. Binding selectively to the fast-skeletal-troponin complex, CK-2017357 slows the rate of calcium release from troponin C and sensitizes muscle to calcium. As a consequence, the force-calcium relationship of muscle fibers shifts leftwards, as does the force-frequency relationship of a nerve-muscle pair, so that CK-2017357 increases the production of muscle force in situ at sub-maximal nerve stimulation rates. Notably, we show that sensitization of the fast-skeletal-troponin complex to calcium improves muscle force and grip strength immediately after administration of single doses of CK-2017357 in a model of the neuromuscular disease myasthenia gravis. Troponin activation may provide a new therapeutic approach to improve physical activity in diseases where neuromuscular function is compromised.",
"title": "Activation of fast skeletal muscle troponin as a potential therapeutic approach for treating neuromuscular diseases"
}
] |
365
|
ER-localized phosphatase Sac1 processes PI4P through coordination with OSBP and the endosome-localized protein sorting nexin 2.
|
[
{
"docid": "600437",
"text": "VAP (VAPA and VAPB) is an evolutionarily conserved endoplasmic reticulum (ER)-anchored protein that helps generate tethers between the ER and other membranes through which lipids are exchanged across adjacent bilayers. Here, we report that by regulating PI4P levels on endosomes, VAP affects WASH-dependent actin nucleation on these organelles and the function of the retromer, a protein coat responsible for endosome-to-Golgi traffic. VAP is recruited to retromer budding sites on endosomes via an interaction with the retromer SNX2 subunit. Cells lacking VAP accumulate high levels of PI4P, actin comets, and trans-Golgi proteins on endosomes. Such defects are mimicked by downregulation of OSBP, a VAP interactor and PI4P transporter that participates in VAP-dependent ER-endosomes tethers. These results reveal a role of PI4P in retromer-/WASH-dependent budding from endosomes. Collectively, our data show how the ER can control budding dynamics and association with the cytoskeleton of another membrane by direct contacts leading to bilayer lipid modifications.",
"title": "Endosome-ER Contacts Control Actin Nucleation and Retromer Function through VAP-Dependent Regulation of PI4P"
}
] |
[
{
"docid": "11250124",
"text": "Synaptic vesicle recycling involves AP-2/clathrin-mediated endocytosis, but it is not known whether the endosomal pathway is also required. Mice deficient in the tissue-specific AP-1-sigma1B complex have impaired synaptic vesicle recycling in hippocampal synapses. The ubiquitously expressed AP-1-sigma1A complex mediates protein sorting between the trans-Golgi network and early endosomes. Vertebrates express three sigma1 subunit isoforms: A, B and C. The expressions of sigma1A and sigma1B are highest in the brain. Synaptic vesicle reformation in cultured neurons from sigma1B-deficient mice is reduced upon stimulation, and large endosomal intermediates accumulate. The sigma1B-deficient mice have reduced motor coordination and severely impaired long-term spatial memory. These data reveal a molecular mechanism for a severe human X-chromosome-linked mental retardation.",
"title": "AP-1/sigma1B-adaptin mediates endosomal synaptic vesicle recycling, learning and memory."
},
{
"docid": "9680193",
"text": "The ubiquitin-binding protein Hrs and endosomal sorting complex required for transport (ESCRT)-I and ESCRT-III are involved in sorting endocytosed and ubiquitinated receptors to lysosomes for degradation and efficient termination of signaling. In this study, we have investigated the role of the ESCRT-II subunit Vps22/EAP30 in degradative protein sorting of ubiquitinated receptors. Vps22 transiently expressed in HeLa cells was detected in endosomes containing endocytosed epidermal growth factor receptors (EGFRs) as well as Hrs and ESCRT-I and ESCRT-III. Depletion of Vps22 by small interfering RNA, which was accompanied by decreased levels of other ESCRT-II subunits, greatly reduced degradation of EGFR and its ligand EGF as well as the chemokine receptor CXCR4. EGFR accumulated on the limiting membranes of early endosomes and aberrantly small multivesicular bodies in Vps22-depleted cells. Phosphorylation and nuclear translocation of extracellular-signal-regulated kinase1/2 downstream of the EGF-activated receptor were sustained by depletion of Hrs or the ESCRT-I subunit Tsg101. In contrast, this was not the case when Vps22 was depleted. These results indicate an important role for Vps22 in ligand-induced EGFR and CXCR4 turnover and suggest that termination of EGF signaling occurs prior to ESCRT-II engagement.",
"title": "Vps22/EAP30 in ESCRT-II mediates endosomal sorting of growth factor and chemokine receptors destined for lysosomal degradation."
},
{
"docid": "4429388",
"text": "The ESCRT (endosomal sorting complex required for transport) pathway is required for terminal membrane fission events in several important biological processes, including endosomal intraluminal vesicle formation, HIV budding and cytokinesis. VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly, possibly in conjunction with membrane fission. Here we show that the microtubule interacting and transport (MIT) domains of human VPS4A and VPS4B bind conserved sequence motifs located at the carboxy termini of the CHMP1–3 class of ESCRT-III proteins. Structures of VPS4A MIT–CHMP1A and VPS4B MIT–CHMP2B complexes reveal that the C-terminal CHMP motif forms an amphipathic helix that binds in a groove between the last two helices of the tetratricopeptide-like repeat (TPR) of the VPS4 MIT domain, but in the opposite orientation to that of a canonical TPR interaction. Distinct pockets in the MIT domain bind three conserved leucine residues of the CHMP motif, and mutations that inhibit these interactions block VPS4 recruitment, impair endosomal protein sorting and relieve dominant-negative VPS4 inhibition of HIV budding. Thus, our studies reveal how the VPS4 ATPases recognize their CHMP substrates to facilitate the membrane fission events required for the release of viruses, endosomal vesicles and daughter cells.",
"title": "ESCRT-III recognition by VPS4 ATPases"
},
{
"docid": "11289247",
"text": "The regulation and coordination of mitochondrial metabolism with hematopoietic stem cell (HSC) self-renewal and differentiation is not fully understood. Here we report that depletion of PTPMT1, a PTEN-like mitochondrial phosphatase, in inducible or hematopoietic-cell-specific knockout mice resulted in hematopoietic failure due to changes in the cell cycle and a block in the differentiation of HSCs. Surprisingly, the HSC pool was increased by ∼40-fold in PTPMT1 knockout mice. Reintroduction of wild-type PTPMT1, but not catalytically deficient PTPMT1 or truncated PTPMT1 lacking mitochondrial localization, restored differentiation capabilities of PTPMT1 knockout HSCs. Further analyses demonstrated that PTPMT1 deficiency altered mitochondrial metabolism and that phosphatidylinositol phosphate substrates of PTPMT1 directly enhanced fatty-acid-induced activation of mitochondrial uncoupling protein 2. Intriguingly, depletion of PTPMT1 from myeloid, T lymphoid, or B lymphoid progenitors did not cause any defects in lineage-specific knockout mice. This study establishes a crucial role of PTPMT1 in the metabolic regulation of HSC function.",
"title": "Metabolic regulation by the mitochondrial phosphatase PTPMT1 is required for hematopoietic stem cell differentiation."
},
{
"docid": "17017465",
"text": "The small GTPases, Rab5 and Rac, are essential for endocytosis and actin remodeling, respectively. Coordination of these processes is critical to achieve spatial restriction of intracellular signaling, which is essential for a variety of polarized functions. Here, we show that clathrin- and Rab5-mediated endocytosis are required for the activation of Rac induced by motogenic stimuli. Rac activation occurs on early endosomes, where the RacGEF Tiam1 is also recruited. Subsequent recycling of Rac to the plasma membrane ensures localized signaling, leading to the formation of actin-based migratory protrusions. Thus, membrane trafficking of Rac is required for the spatial resolution of Rac-dependent motogenic signals. We further demonstrate that a Rab5-to-Rac circuitry controls the morphology of motile mammalian tumor cells and primordial germinal cells during zebrafish development, suggesting that this circuitry is relevant for the regulation of migratory programs in various cells, in both in vitro settings and whole organisms.",
"title": "Endocytic Trafficking of Rac Is Required for the Spatial Restriction of Signaling in Cell Migration"
},
{
"docid": "19561411",
"text": "Orai1 and stromal interaction molecule 1 (STIM1) mediate store-operated Ca(2+) entry (SOCE) in immune cells. STIM1, an endoplasmic reticulum (ER) Ca(2+) sensor, detects store depletion and interacts with plasma membrane (PM)-resident Orai1 channels at the ER-PM junctions. However, the molecular composition of these junctions in T cells remains poorly understood. Here, we show that junctophilin-4 (JP4), a member of junctional proteins in excitable cells, is expressed in T cells and localized at the ER-PM junctions to regulate Ca(2+) signaling. Silencing or genetic manipulation of JP4 decreased ER Ca(2+) content and SOCE in T cells, impaired activation of the nuclear factor of activated T cells (NFAT) and extracellular signaling-related kinase (ERK) signaling pathways, and diminished expression of activation markers and cytokines. Mechanistically, JP4 directly interacted with STIM1 via its cytoplasmic domain and facilitated its recruitment into the junctions. Accordingly, expression of this cytoplasmic fragment of JP4 inhibited SOCE. Furthermore, JP4 also formed a complex with junctate, a Ca(2+)-sensing ER-resident protein, previously shown to mediate STIM1 recruitment into the junctions. We propose that the junctate-JP4 complex located at the junctions cooperatively interacts with STIM1 to maintain ER Ca(2+) homeostasis and mediate SOCE in T cells.",
"title": "Junctophilin-4, a component of the endoplasmic reticulum-plasma membrane junctions, regulates Ca2+ dynamics in T cells."
},
{
"docid": "18264714",
"text": "All cells perceive and respond to environmental stresses through elaborate stress-sensing networks. Yeast cells sense stress through diverse signaling pathways that converge on the transcription factors Msn2 and Msn4, which respond by initiating rapid, idiosyncratic cycles into and out of the nucleus. To understand the role of Msn2/4 nuclear localization dynamics, we combined time-lapse studies of Msn2-GFP localization in living cells with computational modeling of stress-sensing signaling networks. We find that several signaling pathways, including Ras/protein kinase A, AMP-activated kinase, the high-osmolarity response mitogen-activated protein kinase pathway, and protein phosphatase 1, regulate activation of Msn2 in distinct ways in response to different stresses. Moreover, we find that bursts of nuclear localization elicit a more robust transcriptional response than does sustained nuclear localization. Using stochastic modeling, we reproduce in silico the responses of Msn2 to different stresses, and demonstrate that bursts of localization arise from noise in the signaling pathways amplified by the small number of Msn2 molecules in the cell. This noise imparts diverse behaviors to genetically identical cells, allowing cell populations to \"hedge their bets\" in responding to an uncertain future, and to balance growth and survival in an unpredictable environment.",
"title": "Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses"
},
{
"docid": "4388082",
"text": "In a Drosophila follicle the oocyte always occupies a posterior position among a group of sixteen germline cells. Although the importance of this cell arrangement for the subsequent formation of the anterior-posterior axis of the embryo is well documented, the molecular mechanism responsible for the posterior localization of the oocyte was unknown. Here we show that the homophilic adhesion molecule DE-cadherin mediates oocyte positioning. During follicle biogenesis, DE-cadherin is expressed in germline (including oocyte) and surrounding follicle cells, with the highest concentration of DE-cadherin being found at the interface between oocyte and posterior follicle cells. Mosaic analysis shows that DE-cadherin is required in both germline and follicle cells for correct oocyte localization, indicating that germline-soma interactions may be involved in this process. By analysing the behaviour of the oocyte in follicles with a chimaeric follicular epithelium, we find that the position of the oocyte is determined by the position of DE-cadherin-expressing follicle cells, to which the oocyte attaches itself selectively. Among the DE-cadherin positive follicle cells, the oocyte preferentially contacts those cells that express higher levels of DE-cadherin. On the basis of these data, we propose that in wild-type follicles the oocyte competes successfully with its sister germline cells for contact to the posterior follicle cells, a sorting process driven by different concentrations of DE-cadherin. This is, to our knowledge, the first in vivo example of a cell-sorting process that depends on differential adhesion mediated by a cadherin.",
"title": "Drosophila oocyte localization is mediated by differential cadherin-based adhesion."
},
{
"docid": "2593298",
"text": "Receptor endocytosis is a fundamental step in controlling the magnitude, duration, and nature of cell signaling events. Confluent endothelial cells are contact inhibited in their growth and respond poorly to the proliferative signals of vascular endothelial growth factor (VEGF). In a previous study, we found that the association of vascular endothelial cadherin (VEC) with VEGF receptor (VEGFR) type 2 contributes to density-dependent growth inhibition (Lampugnani, G.M., A. Zanetti, M. Corada, T. Takahashi, G. Balconi, F. Breviario, F. Orsenigo, A. Cattelino, R. Kemler, T.O. Daniel, and E. Dejana. 2003. J. Cell Biol. 161:793–804). In the present study, we describe the mechanism through which VEC reduces VEGFR-2 signaling. We found that VEGF induces the clathrin-dependent internalization of VEGFR-2. When VEC is absent or not engaged at junctions, VEGFR-2 is internalized more rapidly and remains in endosomal compartments for a longer time. Internalization does not terminate its signaling; instead, the internalized receptor is phosphorylated, codistributes with active phospholipase C–γ, and activates p44/42 mitogen-activated protein kinase phosphorylation and cell proliferation. Inhibition of VEGFR-2 internalization reestablishes the contact inhibition of cell growth, whereas silencing the junction-associated density-enhanced phosphatase-1/CD148 phosphatase restores VEGFR-2 internalization and signaling. Thus, VEC limits cell proliferation by retaining VEGFR-2 at the membrane and preventing its internalization into signaling compartments.",
"title": "Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from intracellular compartments"
},
{
"docid": "12871002",
"text": "We have studied the function of a conserved germline-specific nucleotidyltransferase protein, CDE-1, in RNAi and chromosome segregation in C. elegans. CDE-1 localizes specifically to mitotic chromosomes in embryos. This localization requires the RdRP EGO-1, which physically interacts with CDE-1, and the Argonaute protein CSR-1. We found that CDE-1 is required for the uridylation of CSR-1 bound siRNAs, and that in the absence of CDE-1 these siRNAs accumulate to inappropriate levels, accompanied by defects in both meiotic and mitotic chromosome segregation. Elevated siRNA levels are associated with erroneous gene silencing, most likely through the inappropriate loading of CSR-1 siRNAs into other Argonaute proteins. We propose a model in which CDE-1 restricts specific EGO-1-generated siRNAs to the CSR-1 mediated, chromosome associated RNAi pathway, thus separating it from other endogenous RNAi pathways. The conserved nature of CDE-1 suggests that similar sorting mechanisms may operate in other animals, including mammals.",
"title": "CDE-1 Affects Chromosome Segregation through Uridylation of CSR-1-Bound siRNAs"
},
{
"docid": "15600979",
"text": "EMSY links the BRCA2 pathway to sporadic breast/ovarian cancer. It encodes a nuclear protein that binds to the BRCA2 N-terminal domain implicated in chromatin/transcription regulation, but when sporadically amplified/overexpressed, increased EMSY level represses BRCA2 transactivation potential and induces chromosomal instability, mimicking the activity of BRCA2 mutations in the development of hereditary breast/ovarian cancer. In addition to chromatin/transcription regulation, EMSY may also play a role in the DNA-damage response, suggested by its ability to localize at chromatin sites of DNA damage/repair. This implies that EMSY overexpression may also repress BRCA2 in DNA-damage replication/checkpoint and recombination/repair, coordinated processes that also require its interacting proteins: PALB2, the partner and localizer of BRCA2; RPA, replication/checkpoint protein A; and RAD51, the inseparable recombination/repair enzyme. Here, using a well-characterized recombination/repair assay system, we demonstrate that a slight increase in EMSY level can indeed repress these two processes independently of transcriptional interference/repression. Since EMSY, RPA and PALB2 all bind to the same BRCA2 region, these findings further support a scenario wherein: (a) EMSY amplification may mimic BRCA2 deficiency, at least by overriding RPA and PALB2, crippling the BRCA2/RAD51 complex at DNA-damage and replication/transcription sites; and (b) BRCA2/RAD51 may coordinate these processes by employing at least EMSY, PALB2 and RPA. We extensively discuss the molecular details of how this can happen to ascertain its implications for a novel recombination mechanism apparently conceived as checkpoint rather than a DNA repair system for cell division, survival, death, and human diseases, including the tissue specificity of cancer predisposition, which may renew our thinking about targeted therapy and prevention.",
"title": "EMSY overexpression disrupts the BRCA2/RAD51 pathway in the DNA-damage response: implications for chromosomal instability/recombination syndromes as checkpoint diseases"
},
{
"docid": "31851367",
"text": "Estrogens are key regulators of growth, differentiation, and the physiological functions of a wide range of target tissues, including the male and female reproductive tracts, breast, and skeletal, nervous, cardiovascular, digestive and immune systems. The majority of these biological activities of estrogens are mediated through two genetically distinct receptors, ERalpha and ERbeta, which function as hormone-inducible transcription factors. Over the past decade, it has become increasingly clear that the recruitment of coregulatory proteins to ERs is required for ER-mediated transcriptional and biological activities. These \"coactivator\" complexes enable the ERs to respond appropriately: 1) to hormones or pharmacological ligands, 2) interpret extra- and intra-cellular signals, 3) catalyze the process of chromatin condensation and 4) to communicate with the general transcription apparatus at target gene promoters. In addition to activating proteins, the existence of corepressors, proteins that function as negative regulators of ER activity in either physiological or pharmacological contexts, provides an additional level of complexity in ER action. This review also describes current efforts aimed at developing pharmaceutical agents that target ER-cofactor interactions as therapeutics for estrogen-associated pathologies.",
"title": "Coregulators in nuclear estrogen receptor action: from concept to therapeutic targeting."
},
{
"docid": "12800122",
"text": "Subdividing proliferating tissues into compartments is an evolutionarily conserved strategy of animal development [1-6]. Signals across boundaries between compartments can result in local expression of secreted proteins organizing growth and patterning of tissues [1-6]. Sharp and straight interfaces between compartments are crucial for stabilizing the position of such organizers and therefore for precise implementation of body plans. Maintaining boundaries in proliferating tissues requires mechanisms to counteract cell rearrangements caused by cell division; however, the nature of such mechanisms remains unclear. Here we quantitatively analyzed cell morphology and the response to the laser ablation of cell bonds in the vicinity of the anteroposterior compartment boundary in developing Drosophila wings. We found that mechanical tension is approximately 2.5-fold increased on cell bonds along this compartment boundary as compared to the remaining tissue. Cell bond tension is decreased in the presence of Y-27632 [7], an inhibitor of Rho-kinase whose main effector is Myosin II [8]. Simulations using a vertex model [9] demonstrate that a 2.5-fold increase in local cell bond tension suffices to guide the rearrangement of cells after cell division to maintain compartment boundaries. Our results provide a physical mechanism in which the local increase in Myosin II-dependent cell bond tension directs cell sorting at compartment boundaries.",
"title": "Increased Cell Bond Tension Governs Cell Sorting at the Drosophila Anteroposterior Compartment Boundary"
},
{
"docid": "6492658",
"text": "Weeble mutant mice have severe locomotor instability and significant neuronal loss in the cerebellum and in the hippocampal CA1 field. Genetic mapping was used to localize the mutation to the gene encoding inositol polyphosphate 4-phosphatase type I (Inpp4a), where a single nucleotide deletion results in a likely null allele. The substrates of INPP4A are intermediates in a pathway affecting intracellular Ca(2+) release but are also involved in cell cycle regulation through binding the Akt protooncogene; dysfunction in either may account for the neuronal loss of weeble mice. Although other mutations in phosphoinositide enzymes are associated with synaptic defects without neuronal loss, weeble shows that Inpp4a is critical for the survival of a subset of neurons during postnatal development in mice.",
"title": "A Null Mutation in Inositol Polyphosphate 4-Phosphatase Type I Causes Selective Neuronal Loss in Weeble Mutant Mice"
},
{
"docid": "6333347",
"text": "An emerging family of kinases related to the Drosophila Aurora and budding yeast Ipl1 proteins has been implicated in chromosome segregation and mitotic spindle formation in a number of organisms. Unlike other Aurora/Ipl1-related kinases, the Caenorhabditis elegans orthologue, AIR-2, is associated with meiotic and mitotic chromosomes. AIR-2 is initially localized to the chromosomes of the most mature prophase I–arrested oocyte residing next to the spermatheca. This localization is dependent on the presence of sperm in the spermatheca. After fertilization, AIR-2 remains associated with chromosomes during each meiotic division. However, during both meiotic anaphases, AIR-2 is present between the separating chromosomes. AIR-2 also remains associated with both extruded polar bodies. In the embryo, AIR-2 is found on metaphase chromosomes, moves to midbody microtubules at anaphase, and then persists at the cytokinesis remnant. Disruption of AIR-2 expression by RNA- mediated interference produces entire broods of one-cell embryos that have executed multiple cell cycles in the complete absence of cytokinesis. The embryos accumulate large amounts of DNA and microtubule asters. Polar bodies are not extruded, but remain in the embryo where they continue to replicate. The cytokinesis defect appears to be late in the cell cycle because transient cleavage furrows initiate at the proper location, but regress before the division is complete. Additionally, staining with a marker of midbody microtubules revealed that at least some of the components of the midbody are not well localized in the absence of AIR-2 activity. Our results suggest that during each meiotic and mitotic division, AIR-2 may coordinate the congression of metaphase chromosomes with the subsequent events of polar body extrusion and cytokinesis.",
"title": "AIR-2: An Aurora/Ipl1-related Protein Kinase Associated with Chromosomes and Midbody Microtubules Is Required for Polar Body Extrusion and Cytokinesis in Caenorhabditis elegans Embryos "
},
{
"docid": "4324278",
"text": "The rapamycin-sensitive TOR signalling pathway in Saccharomyces cerevisiae activates a cell-growth program in response to nutrients such as nitrogen and carbon. The TOR1 and TOR2 kinases (TOR) control cytoplasmic protein synthesis and degradation through the conserved TAP42 protein. Upon phosphorylation by TOR, TAP42 binds and possibly inhibits type 2A and type-2A-related phosphatases; however, the mechanism by which TOR controls nuclear events such as global repression of starvation-specific transcription is unknown. Here we show that TOR prevents transcription of genes expressed upon nitrogen limitation by promoting the association of the GATA transcription factor GLN3 with the cytoplasmic protein URE2. The binding of GLN3 to URE2 requires TOR-dependent phosphorylation of GLN3. Phosphorylation and cytoplasmic retention of GLN3 are also dependent on the TOR effector TAP42, and are antagonized by the type-2A-related phosphatase SIT4. TOR inhibits expression of carbon-source-regulated genes by stimulating the binding of the transcriptional activators MSN2 and MSN4 to the cytoplasmic 14-3-3 protein BMH2. Thus, the TOR signalling pathway broadly controls nutrient metabolism by sequestering several transcription factors in the cytoplasm.",
"title": "The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors."
},
{
"docid": "24555417",
"text": "In many species, oocyte meiosis is carried out in the absence of centrioles. As a result, microtubule organization, spindle assembly, and chromosome segregation proceed by unique mechanisms. Here, we report insights into the principles underlying this specialized form of cell division, through studies of C. elegans KLP-15 and KLP-16, two highly homologous members of the kinesin-14 family of minus-end-directed kinesins. These proteins localize to the acentriolar oocyte spindle and promote microtubule bundling during spindle assembly; following KLP-15/16 depletion, microtubule bundles form but then collapse into a disorganized array. Surprisingly, despite this defect we found that during anaphase, microtubules are able to reorganize into a bundled array that facilitates chromosome segregation. This phenotype therefore enabled us to identify factors promoting microtubule organization during anaphase, whose contributions are normally undetectable in wild-type worms; we found that SPD-1 (PRC1) bundles microtubules and KLP-18 (kinesin-12) likely sorts those bundles into a functional orientation capable of mediating chromosome segregation. Therefore, our studies have revealed an interplay between distinct mechanisms that together promote spindle formation and chromosome segregation in the absence of structural cues such as centrioles.",
"title": "Interplay between microtubule bundling and sorting factors ensures acentriolar spindle stability during C. elegans oocyte meiosis"
},
{
"docid": "24558930",
"text": "Although assembly of acentrosomal meiotic spindles has been extensively studied, little is known about the segregation of chromosomes on these spindles. Here, we show in Caenorhabditis elegans oocytes that the kinetochore protein, KNL-1, directs assembly of meiotic kinetochores that orient chromosomes. However, in contrast to mitosis, chromosome separation during meiotic anaphase is kinetochore-independent. Before anaphase, meiotic kinetochores and spindle poles disassemble along with the microtubules on the poleward side of chromosomes. During anaphase, microtubules then form between the separating chromosomes. Functional analysis implicated a set of proteins that localize to a ring-shaped domain between kinetochores during pre-anaphase spindle assembly and anaphase separation. These proteins are localized by the chromosomal passenger complex, which regulates the loss of meiotic chromosome cohesion. Thus, meiotic segregation in C. elegans is a two-stage process, where kinetochores orient chromosomes, but are then dispensable for their separation. We suggest that separation is controlled by a meiosis-specific chromosomal domain to coordinate cohesin removal and chromosome segregation.",
"title": "A kinetochore-independent mechanism drives anaphase chromosome separation during acentrosomal meiosis"
},
{
"docid": "25510546",
"text": "Increased lipid supply causes beta cell death, which may contribute to reduced beta cell mass in type 2 diabetes. We investigated whether endoplasmic reticulum (ER) stress is necessary for lipid-induced apoptosis in beta cells and also whether ER stress is present in islets of an animal model of diabetes and of humans with type 2 diabetes. Expression of genes involved in ER stress was evaluated in insulin-secreting MIN6 cells exposed to elevated lipids, in islets isolated from db/db mice and in pancreas sections of humans with type 2 diabetes. Overproduction of the ER chaperone heat shock 70 kDa protein 5 (HSPA5, previously known as immunoglobulin heavy chain binding protein [BIP]) was performed to assess whether attenuation of ER stress affected lipid-induced apoptosis. We demonstrated that the pro-apoptotic fatty acid palmitate triggers a comprehensive ER stress response in MIN6 cells, which was virtually absent using non-apoptotic fatty acid oleate. Time-dependent increases in mRNA levels for activating transcription factor 4 (Atf4), DNA-damage inducible transcript 3 (Ddit3, previously known as C/EBP homologous protein [Chop]) and DnaJ homologue (HSP40) C3 (Dnajc3, previously known as p58) correlated with increased apoptosis in palmitate- but not in oleate-treated MIN6 cells. Attenuation of ER stress by overproduction of HSPA5 in MIN6 cells significantly protected against lipid-induced apoptosis. In islets of db/db mice, a variety of marker genes of ER stress were also upregulated. Increased processing (activation) of X-box binding protein 1 (Xbp1) mRNA was also observed, confirming the existence of ER stress. Finally, we observed increased islet protein production of HSPA5, DDIT3, DNAJC3 and BCL2-associated X protein in human pancreas sections of type 2 diabetes subjects. Our results provide evidence that ER stress occurs in type 2 diabetes and is required for aspects of the underlying beta cell failure.",
"title": "Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes"
},
{
"docid": "42855554",
"text": "To clarify the fate of glycosylphosphatidylinositol (GPI) in mammals, we developed GPI-anchored enhanced green fluorescent protein (EGFP-GPI) and transgenic mice carrying this fusion construct. When it was introduced to culture cells, the EGFP-GPI protein was correctly sorted to plasma membranes and microsomes depending on GPI biosynthesis. Transgenic mice carrying EGFP-GPI were found to show a broad transgene expression. Histologically, a prominent polarized localization of EGFP-GPI protein was observed in various epithelia, the nervous system and liver and secreted from some exocrine glands, as well as non-polarized presence in non-epithelial tissues, demonstrating a tissue-inherent manner of GPI sorting.",
"title": "Tissue-inherent fate of GPI revealed by GPI-anchored GFP transgenesis."
},
{
"docid": "20460020",
"text": "Efficient local monocyte/macrophage recruitment is critical for tissue repair. Recruited macrophages are polarized toward classical (proinflammatory) or alternative (prohealing) activation in response to cytokines, with tight temporal regulation crucial for efficient wound repair. Estrogen acts as a potent anti-inflammatory regulator of cutaneous healing. However, an understanding of estrogen/estrogen receptor (ER) contribution to macrophage polarization and subsequent local effects on wound healing is lacking. Here we identify, to our knowledge previously unreported, a role whereby estrogen receptor α (ERα) signaling preferentially polarizes macrophages from a range of sources to an alternative phenotype. Cell-specific ER ablation studies confirm an in vivo role for inflammatory cell ERα, but not ERβ, in poor healing associated with an altered cytokine profile and fewer alternatively activated macrophages. Furthermore, we reveal intrinsic changes in ERα-deficient macrophages, which are unable to respond to alternative activation signals in vitro. Collectively, our data reveal that inflammatory cell-expressed ERα promotes alternative macrophage polarization, which is beneficial for timely healing. Given the diverse physiological roles of ERs, these findings will likely be of relevance to many pathologies involving excessive inflammation.",
"title": "Estrogen receptor-alpha promotes alternative macrophage activation during cutaneous repair."
},
{
"docid": "35231675",
"text": "CLIP-170 is a \"cytoplasmic linker protein\" implicated in endosome-microtubule interactions and in control of microtubule dynamics. CLIP-170 localizes dynamically to growing microtubule plus ends, colocalizing with the dynein activator dynactin and the APC-binding protein EB1. This shared \"plus-end tracking\" behavior suggests that CLIP-170 might interact with dynactin and/or EB1. We have used site-specific mutagenesis of CLIP-170 and a transfection/colocalization assay to address this question in mammalian tissue culture cells. Our results indicate that CLIP-170 interacts, directly or indirectly, with both dynactin and EB1. We find that the CLIP-170/dynactin interaction is mediated by the second metal binding motif of the CLIP-170 tail. In contrast, the CLIP-170/EB1 interaction requires neither metal binding motif. In addition, our experiments suggest that the CLIP-170/dynactin interaction occurs via the shoulder/sidearm subcomplex of dynactin and can occur in the cytosol (i.e., it does not require microtubule binding). These results have implications for the targeting of both dynactin and EB1 to microtubule plus ends. Our data suggest that the CLIP-170/dynactin interaction can target dynactin complex to microtubule plus ends, although dynactin likely also targets MT plus ends directly via the microtubule binding motif of the p150(Glued) subunit. We find that CLIP-170 mutants alter p150(Glued) localization without affecting EB1, indicating that EB1 can target microtubule plus ends independently of dynactin.",
"title": "CLIP-170 interacts with dynactin complex and the APC-binding protein EB1 by different mechanisms."
},
{
"docid": "37964706",
"text": "Ca2+ entry through store-operated Ca2+ channels drives the production of the pro-inflammatory molecule leukotriene C4 (LTC4) from mast cells through a pathway involving Ca2+-dependent protein kinase C, mitogen-activated protein kinases ERK1/2, phospholipase A2, and 5-lipoxygenase. Here we examine whether local Ca2+ influx through store-operated Ca2+ release-activated Ca2+ (CRAC) channels in the plasma membrane stimulates this signaling pathway. Manipulating the amplitude and spatial extent of Ca2+ entry by altering chemical and electrical gradients for Ca2+ influx or changing the Ca2+ buffering of the cytoplasm all impacted on protein kinase C and ERK activation, generation of arachidonic acid and LTC4 secretion, with little change in the bulk cytoplasmic Ca2+ rise. Similar bulk cytoplasmic Ca2+ concentrations were achieved when CRAC channels were activated in 0.25 mm external Ca2+ versus 2 mm Ca2+ and 100 nm La3+, an inhibitor of CRAC channels. However, despite similar bulk cytoplasmic Ca2+, protein kinase C activation and LTC4 secretion were larger in 2 mm Ca2+ and La3+ than in 0.25 mm Ca2+, consistent with the central involvement of a subplasmalemmal Ca2+ rise. The nonreceptor tyrosine kinase Syk coupled CRAC channel opening to protein kinase C and ERK activation. Recombinant TRPC3 channels also activated protein kinase C, suggesting that subplasmalemmal Ca2+ rather than a microdomain exclusive to CRAC channels is the trigger. Hence a subplasmalemmal Ca2+ increase in mast cells is highly versatile in that it triggers cytoplasmic responses through generation of intracellular messengers as well as long distance changes through increased secretion of paracrine signals.",
"title": "Local Ca2+ influx through Ca2+ release-activated Ca2+ (CRAC) channels stimulates production of an intracellular messenger and an intercellular pro-inflammatory signal."
},
{
"docid": "17194716",
"text": "In this study, the mechanisms of actin-bundling in filopodia were examined. Analysis of cellular localization of known actin cross-linking proteins in mouse melanoma B16F1 cells revealed that fascin was specifically localized along the entire length of all filopodia, whereas other actin cross-linkers were not. RNA interference of fascin reduced the number of filopodia, and remaining filopodia had abnormal morphology with wavy and loosely bundled actin organization. Dephosphorylation of serine 39 likely determined cellular filopodia frequency. The constitutively active fascin mutant S39A increased the number and length of filopodia, whereas the inactive fascin mutant S39E reduced filopodia frequency. Fluorescence recovery after photobleaching of GFP-tagged wild-type and S39A fascin showed that dephosphorylated fascin underwent rapid cycles of association to and dissociation from actin filaments in filopodia, with t1/2 < 10 s. We propose that fascin is a key specific actin cross-linker, providing stiffness for filopodial bundles, and that its dynamic behavior allows for efficient coordination between elongation and bundling of filopodial actin filaments.",
"title": "Role of fascin in filopodial protrusion"
},
{
"docid": "25623469",
"text": "A newly emerging family of phosphatases that are members of the haloacid dehalogenase superfamily contains the catalytic motif DXDX(T/V). A member of this DXDX(T/V) phosphatase family known as Dullard was recently shown to be a potential regulator of neural tube development in Xenopus [Satow R, Chan TC, Asashima M (2002) Biochem Biophys Res Commun 295:85-91]. Herein, we demonstrate that human Dullard and the yeast protein Nem1p perform similar functions in mammalian cells and yeast cells, respectively. In addition to similarity in primary sequence, Dullard and Nem1p possess similar domains and show similar substrate preferences, and both localize to the nuclear envelope. Additionally, we show that human Dullard can rescue the aberrant nuclear envelope morphology of nem1Delta yeast cells, functionally replacing Nem1p. Finally, Nem1p, has been shown to deposphorylate the yeast phosphatidic acid phosphatase Smp2p [Santos-Rosa H, Leung J, Grimsey N, Peak-Chew S, Siniossoglou S (2005) EMBO J 24:1931-1941], and we show that Dullard dephosphorylates the mammalian phospatidic acid phosphatase, lipin. Therefore, we propose that Dullard participates in a unique phosphatase cascade regulating nuclear membrane biogenesis, and that this cascade is conserved from yeast to mammals.",
"title": "A conserved phosphatase cascade that regulates nuclear membrane biogenesis."
},
{
"docid": "1991105",
"text": "Mitochondrial division is important for mitochondrial distribution and function. Recent data have demonstrated that ER-mitochondria contacts mark mitochondrial division sites, but the molecular basis and functions of these contacts are not understood. Here we show that in yeast, the ER-mitochondria tethering complex, ERMES, and the highly conserved Miro GTPase, Gem1, are spatially and functionally linked to ER-associated mitochondrial division. Gem1 acts as a negative regulator of ER-mitochondria contacts, an activity required for the spatial resolution and distribution of newly generated mitochondrial tips following division. Previous data have demonstrated that ERMES localizes with a subset of actively replicating mitochondrial nucleoids. We show that mitochondrial division is spatially linked to nucleoids and that a majority of these nucleoids segregate prior to division, resulting in their distribution into newly generated tips in the mitochondrial network. Thus, we postulate that ER-associated division serves to link the distribution of mitochondria and mitochondrial nucleoids in cells. DOI:http://dx.doi.org/10.7554/eLife.00422.001.",
"title": "ER-associated mitochondrial division links the distribution of mitochondria and mitochondrial DNA in yeast"
},
{
"docid": "13936152",
"text": "Partitioning tissues into compartments that do not intermix is essential for the correct morphogenesis of animal embryos and organs. Several hypotheses have been proposed to explain compartmental cell sorting, mainly differential adhesion, but also regulation of the cytoskeleton or of cell proliferation. Nevertheless, the molecular and cellular mechanisms that keep cells apart at boundaries remain unclear. Here we demonstrate, in early Drosophila melanogaster embryos, that actomyosin-based barriers stop cells from invading neighbouring compartments. Our analysis shows that cells can transiently invade neighbouring compartments, especially when they divide, but are then pushed back into their compartment of origin. Actomyosin cytoskeletal components are enriched at compartmental boundaries, forming cable-like structures when the epidermis is mitotically active. When MyoII (non-muscle myosin II) function is inhibited, including locally at the cable by chromophore-assisted laser inactivation (CALI), in live embryos, dividing cells are no longer pushed back, leading to compartmental cell mixing. We propose that local regulation of actomyosin contractibility, rather than differential adhesion, is the primary mechanism sorting cells at compartmental boundaries.",
"title": "An actomyosin-based barrier inhibits cell mixing at compartmental boundaries in Drosophila embryos"
},
{
"docid": "16557565",
"text": "Plants, compared to animals, exhibit an amazing adaptability and plasticity in their development. This is largely dependent on the ability of plants to form new organs, such as lateral roots, leaves, and flowers during postembryonic development. Organ primordia develop from founder cell populations into organs by coordinated cell division and differentiation. Here, we show that organ formation in Arabidopsis involves dynamic gradients of the signaling molecule auxin with maxima at the primordia tips. These gradients are mediated by cellular efflux requiring asymmetrically localized PIN proteins, which represent a functionally redundant network for auxin distribution in both aerial and underground organs. PIN1 polar localization undergoes a dynamic rearrangement, which correlates with establishment of auxin gradients and primordium development. Our results suggest that PIN-dependent, local auxin gradients represent a common module for formation of all plant organs, regardless of their mature morphology or developmental origin.",
"title": "Local, Efflux-Dependent Auxin Gradients as a Common Module for Plant Organ Formation"
},
{
"docid": "935538",
"text": "RNA-binding proteins are at the heart of posttranscriptional gene regulation, coordinating the processing, storage, and handling of cellular RNAs. We show here that GRSF1, previously implicated in the binding and selective translation of influenza mRNAs, is targeted to mitochondria where it forms granules that colocalize with foci of newly synthesized mtRNA next to mitochondrial nucleoids. GRSF1 preferentially binds RNAs transcribed from three contiguous genes on the light strand of mtDNA, the ND6 mRNA, and the long noncoding RNAs for cytb and ND5, each of which contains multiple consensus binding sequences. RNAi-mediated knockdown of GRSF1 leads to alterations in mitochondrial RNA stability, abnormal loading of mRNAs and lncRNAs on the mitochondrial ribosome, and impaired ribosome assembly. This results in a specific protein synthesis defect and a failure to assemble normal amounts of the oxidative phosphorylation complexes. These data implicate GRSF1 as a key regulator of posttranscriptional mitochondrial gene expression.",
"title": "The mitochondrial RNA-binding protein GRSF1 localizes to RNA granules and is required for posttranscriptional mitochondrial gene expression."
},
{
"docid": "3155374",
"text": "Binding interactions between the plasma membrane and the cytoskeleton define cell functions such as cell shape, formation of cell processes, cell movement, and endocytosis. Here we use optical tweezers tether force measurements and show that plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2) acts as a second messenger that regulates the adhesion energy between the cytoskeleton and the plasma membrane. Receptor stimuli that hydrolyze PIP2 lowered adhesion energy, a process that could be mimicked by expressing PH domains that sequester PIP2 or by targeting a 5'-PIP2-phosphatase to the plasma membrane to selectively lower plasma membrane PIP2 concentration. Our study suggests that plasma membrane PIP2 controls dynamic membrane functions and cell shape by locally increasing and decreasing the adhesion between the actin-based cortical cytoskeleton and the plasma membrane.",
"title": "Phosphatidylinositol 4,5-Bisphosphate Functions as a Second Messenger that Regulates Cytoskeleton–Plasma Membrane Adhesion"
}
] |
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