query: Boosting Heart Nerve Control

positive: Fruit, vegetable, and fish consumption and heart rate variability: the Veterans Administration Normative Aging Study Background: Higher intakes of fruit, vegetables, and dark fish may prevent sudden cardiac death and arrhythmias, but the exact mechanisms are not fully understood. Objective: We examined whether high consumption of fruit, vegetables, and dark fish would be associated with beneficial changes in heart rate variability (HRV). Design: HRV variables were measured among 586 older men with 928 total observations from November 2000 to June 2007 in the Normative Aging Study, a community-based longitudinal study of aging. Dietary intake was evaluated with a self-administered semiquantitative food-frequency questionnaire and categorized into quartiles. Results: After controlling for potential confounders, intake of green leafy vegetables was positively associated with normalized high-frequency power and inversely associated with normalized low-frequency power (P for trend < 0.05). These significant associations were retained after further adjustment for healthy lifestyle factors, such as physical activity and use of multivitamins. No significant association was seen between HRV measures and intakes of other fruit and vegetables, vitamin C, carotenoids, tuna and dark-meat fish, or n–3 (omega-3) fatty acids. An effect modification of intake of noncitrus fruit by obesity and of total vegetables and cruciferous vegetables by cigarette smoking was seen, which warrants further investigation. Conclusion: These findings suggest that higher intake of green leafy vegetables may reduce the risk of cardiovascular disease through favorable changes in cardiac autonomic function.

positive: Diet and risk of ischemic heart disease in India. BACKGROUND: Ischemic heart disease (IHD) is a leading cause of death in India. Dietary changes could reduce risk, but few studies have addressed the association between diet and IHD risk in India. OBJECTIVE: The goal was to address the association between diet and IHD risk among Indians in New Delhi (northern India) and Bangalore (southern India). DESIGN: We collected data from 350 cases of acute myocardial infarction and 700 controls matched on the basis of age, sex, and hospital as part of a hospital-based case-control study in 8 hospitals. Long-term dietary intake was assessed by using food-frequency questionnaires developed for New Delhi and Bangalore. We used conditional logistic regression to control for the matching factors and other predictors of risk. RESULTS: We observed a significant and dose-dependent inverse association between vegetable intake and IHD risk. The inverse association was stronger for green leafy vegetables; in multivariate analysis, persons consuming a median of 3.5 servings/wk had a 67% lower relative risk (RR: 0.33; 95% CI: 0.17, 0.64; P for trend = 0.0001) than did those consuming 0.5 servings/wk. Controlling for other dietary covariates did not alter the association. Cereal intake was also associated with a lower risk. Use of mustard oil, which is rich in alpha-linolenic acid, was associated with a lower risk than was use of sunflower oil [for use in cooking: RR: 0.49 (95% CI: 0.24, 0.99); for use in frying, RR: 0.29 (95% CI: 0.13, 0.64)]. CONCLUSION: Diets rich in vegetables and use of mustard oil could contribute to the lower risk of IHD among Indians.

positive: Antioxidant intake and primary open-angle glaucoma: a prospective study. The relation between dietary antioxidant intake and primary open-angle glaucoma risk was examined in participants aged over 40 years in the Nurses' Health Study (n = 76,200) and the Health Professionals Follow-up Study (n = 40,284). They were followed biennially from 1980 and 1986, respectively, to 1996, during periods when they received an eye examination. Dietary intakes were measured repeatedly from 1980 in the Nurses' Health Study and from 1986 in the Health Professionals Follow-up Study using validated food frequency questionnaires. The authors analyzed 474 self-reported glaucoma cases confirmed by medical chart review to have primary open-angle glaucoma with visual field loss. The authors used Cox proportional hazards models for cohort-specific multivariate analyses, and results were pooled using random effects models. The pooled multivariate rate ratios for primary open-angle glaucoma comparing the highest versus lowest quintile of cumulative updated intake were 1.17 (95% confidence interval (CI): 0.87, 1.58) for alpha-carotene, 1.10 (95% CI: 0.82, 1.48) for beta-carotene, 0.95 (95% CI: 0.70, 1.29) for beta-cryptoxanthin, 0.82 (95% CI: 0.60, 1.12) for lycopene, 0.92 (95% CI: 0.69, 1.24) for lutein/zeaxanthin, 1.05 (95% CI: 0.59, 1.89) for vitamin C, 0.97 (95% CI: 0.62, 1.52) for vitamin E, and 1.11 (95% CI: 0.82, 1.51) for vitamin A. In conclusion, the authors did not observe any strong associations between antioxidant consumption and the risk of primary open-angle glaucoma.

positive: Glaucoma risk and the consumption of fruits and vegetables among older women in the study of osteoporotic fractures. PURPOSE: To explore the association between the consumption of fruits and vegetables and the presence of glaucoma. DESIGN: Cross-sectional cohort study. METHODS: In a sample of 1,155 women located in multiple centers in the United States, glaucoma specialists diagnosed glaucoma in at least one eye by assessing optic nerve head photographs and 76-point suprathreshold screening visual fields. Consumption of fruits and vegetables was assessed using the Block Food Frequency Questionnaire. The relationship between selected fruit and vegetable consumption and glaucoma was investigated using adjusted logistic regression models. RESULTS: Among 1,155 women, 95 (8.2%) were diagnosed with glaucoma. In adjusted analysis, the odds of glaucoma risk were decreased by 69% (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.11 to 0.91) in women who consumed at least one serving per month of green collards and kale compared with those who consumed fewer than one serving per month, by 64% (OR, 0.36; 95% CI, 0.17 to 0.77) in women who consumed more than two servings per week of carrots compared with those who consumed fewer than one serving per week, and by 47% (OR, 0.53; 95% CI, 0.29 to 0.97) in women who consumed at least one serving per week of canned or dried peaches compared with those who consumed fewer than one serving per month. CONCLUSIONS: A higher intake of certain fruits and vegetables may be associated with a decreased risk of glaucoma. More studies are needed to investigate this relationship.

positive: Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population. PURPOSE: Age and advanced disease in the fellow eye are the two most important risk factors for age-related macular degeneration (AMD). In this study, the authors investigated the relationship between these variables and the optical density of macular pigment (MP) in a group of subjects from a northern European population. METHODS: The optical density of MP was measured psychophysically in 46 subjects ranging in age from 21 to 81 years with healthy maculae and in 9 healthy eyes known to be at high-risk of AMD because of advanced disease in the fellow eye. Each eye in the latter group was matched with a control eye on the basis of variables believed to be associated with the optical density of MP (iris color, gender, smoking habits, age, and lens density). RESULTS: There was an age-related decline in the optical density of macular pigment among volunteers with no ocular disease (right eye: r(2) = 0.29, P = 0.0006; left eye: r(2) = 0.29, P < 0.0001). Healthy eyes predisposed to AMD had significantly less MP than healthy eyes at no such risk (Wilcoxon's signed rank test: P = 0.015). CONCLUSIONS: The two most important risk factors for AMD are associated with a relative absence of MP. These findings are consistent with the hypothesis that supplemental lutein and zeaxanthin may delay, avert, or modify the course of this disease.

positive: Iris color and macular pigment optical density. The present study was designed to assess the relationship between iris color and macular pigment optical density. Both melanin and carotenoids (responsible for iris color and macular pigment composition, respectively) appear to protect the retina through similar mechanisms and higher concentrations may reduce the incidence of retinal degenerations. To evaluate this relationship, 95 subjects were examined and the following variables were measured: iris color; macular pigment optical density (MP); plasma concentrations of lutein and zeaxanthin and beta-carotene; dietary intake of lutein and zeaxanthin and beta-carotene; and total fat intake. Iris color was determined by self assessment and classified as blue or gray (group I), green or hazel (group II) or brown or black (group III). MP density was measured psychophysically by measuring foveal and parafoveal sensitivities to lights of 460 and 550 nm, using the method of heterochromatic flicker photometry. Plasma carotenoid concentrations were measured using reverse-phase high-performance liquid chromatography. Dietary intake was determined by a detailed food-frequency questionnaire. Despite similarities in diet and in blood concentrations of carotenoids, significant differences in macular pigment density (P < 0.02) were found for different colored irises (group I, n = 38, MP = 0.25; group II, n = 26, MP = 0.32; group III, n = 31, MP = 0.38). The covariation of iris color and MP indicates that past epidemiologic studies have not adequately determined the independent effects of either factor. The relationship of MP and iris color may be the result of one or two factors: the evolution of a shared tendency to accumulate melanin and carotenoids due to similar environmental pressures (e.g. light and oxygen); and/or MP might be depleted due to the tendency for eyes with light irises to transmit more light than eyes with dark irises, thus causing increased oxidative stress.

positive: The Association of Consumption of Fruits/Vegetables with Decreased Risk of Glaucoma among Older African American Women in the Study of Osteoporotic Fractures Purpose To explore the association between consumption of fruits and vegetables and the presence of glaucoma in older African American women. Design Cross-sectional study. Methods Disc photographs and suprathreshold visual fields were obtained from the 662 African American participants in the Study of Osteoporotic Fractures. Masked, trained readers graded all discs, and two glaucoma specialists reviewed photos and visual fields. The Block Food Frequency Questionnaire assessed food consumption. Relationships between selected fruit/vegetable/nutrient consumption and glaucoma were evaluated using logistic regression models after adjusting for potential confounders. Results After excluding women missing Food Frequency Questionnaire and disc data, 584 African American women (88.2% of total African American cohort) were included. Glaucoma was diagnosed in at least one eye in 77 subjects (13%). Women who ate 3 or more servings/day of fruits/fruit juices were 79% (odds ratio [OR]=0.21; 95% confidence interval [CI]: 0.08–0.60) less likely to have glaucoma than women who ate less than one serving/day. Women who consumed more than 2 servings/week of fresh oranges (OR=0.18; 95%CI: 0.06–0.51) and peaches (OR=0.30; 95%CI: 0.13–0.67) had a decreased odds of glaucoma compared to those consuming less than one serving/week. For vegetables, >1 serving/week compared to ≤1 serving/month of collard-greens/kale decreased the odds of glaucoma by 57% (OR=0.43; 95%CI: 0.21–0.85). There was a protective trend against glaucoma in those consuming more fruit/fruit juices (p=0.023), fresh oranges (p=0.002), fresh peaches (p=0.002), and collard greens/kale (p=0.014). Higher consumption of carrots (p=0.061) and spinach (p=0.094) also showed some associations. Individual nutrient intake from food sources found protective trends with higher intakes of vitamin A (p=0.011), vitamin C (p=0.018), and α-carotene (p=0.021), and close to statistically significant trends with β-carotene (p=0.052), folate (p=0.056), and lutein/zeaxanthin (p=0.077). Conclusion Higher intake of certain fruits and vegetables high in Vitamins A and C and carotenoids may be associated with a decreased likelihood of glaucoma in older African American women. Randomized controlled trials are needed to determine whether the intake of specific nutrients changes the risk of glaucoma.

positive: The Association between Glaucoma Prevalence and Supplementation with the Oxidants Calcium and Iron Purpose. To investigate the relationship between supplementary consumption of the oxidants calcium and iron and the prevalence of glaucoma. Methods. This cross-sectional study included 3833 participants in the National Health and Nutrition Examination Survey (NHANES) for 2007 and 2008, ≥40 years of age, who reported a presence or absence of glaucoma. Participants were interviewed regarding the use of dietary supplements and antacids during the preceding 30-day period. Data pertaining to the supplementary intake of calcium and iron was aggregated and divided into quintiles. Information regarding the presence or absence of glaucoma and demographics, comorbidities, and health-related behavior was obtained via interview. Results. Participants who consumed ≥800 mg/d of supplementary calcium or ≥18 mg/d of supplementary iron had significantly higher odds of having been diagnosed with glaucoma than did those who had not consumed supplementary calcium or iron, after adjustment for potential confounders (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.25–4.76 for calcium; OR 3.80, 95% CI 1.79–8.06 for iron). Concurrent consumption of both calcium and iron above these levels was associated with still greater odds of having been diagnosed with glaucoma (OR 7.24, 95% CI 2.42–21.62). A clear dose–response relationship between quintiles of supplementary calcium or iron intake and glaucoma prevalence was not found. Conclusions. These results suggest that there may be a threshold intake of iron and calcium above which there is an increased risk of development of glaucoma. Prospective longitudinal studies are needed, to assess whether oxidant intake is a risk factor for development and progression of glaucoma.

positive: Mediterranean diet improves sexual function in women with the metabolic syndrome. In the present study, we tested the effect of a Mediterranean-style diet on sexual function in women with the metabolic syndrome. Women were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of female sexual dysfunction (FSD) associated with a diagnosis of metabolic syndrome, a complete follow-up in the study trial and an intervention focused mainly on dietary changes. Fifty-nine women met the inclusion/exclusion criteria; 31 out of them were assigned to the Mediterranean-style diet and 28 to the control diet. After 2 years, women on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain and olive oil as compared with the women on the control diet. Female sexual function index (FSFI) improved in the intervention group, from a mean basal value of 19.7+/-3.1 to a mean post-treatment value of 26.1+/-4.1 (P=0.01), and remained stable in the control group. C-reactive protein (CRP) levels were significantly reduced in the intervention group (P<0.02). No single sexual domain (desire, arousal, lubrication, orgasm, satisfaction, pain) was significantly ameliorated by the dietary treatment, suggesting that the whole female sexuality may find benefit from lifestyle changes. A Mediterranean-style diet might be effective in ameliorating sexual function in women with metabolic syndrome.

positive: Adherence to Mediterranean diet and sexual function in women with type 2 diabetes. INTRODUCTION: There are no reported studies assessing the relation between diet and sexual function in women with diabetes. AIM: In the present study, we explored the relation between consumption of a Mediterranean-type diet and sexual function in a population of type 2 diabetic women. METHODS: Patients with type 2 diabetes were enrolled if they had a diagnosis of type 2 diabetes for at least six months but less than 10 years, age 35-70 years, body mass index (BMI) of 24 or higher, HbA1c of 6.5% or higher, treatment with diet or oral drugs. All diabetic patients were invited to complete a food-frequency questionnaire and self-report measures of sexual function. A total of 595 (90.2%) of the 659 women completed both questionnaires and were analyzed in the present study. MAIN OUTCOME MEASURES: Adherence to a Mediterranean diet was assessed by a 9-point scale that incorporated the salient characteristics of this diet (range of scores, 0-9, with higher scores indicating greater adherence). The Female Sexual Function Index (FSFI) was used for assessing the key dimensions of female sexual function. RESULTS: Diabetic women with the highest scores (6-9) had lower BMI, waist circumference, and waist-to-hip ratio, a lower prevalence of depression, obesity and metabolic syndrome, a higher level of physical activity, and better glucose and lipid profiles than the diabetic women who scored <3 points on the scale. The proportion of sexually active women showed a significant increase across tertiles of adherence to Mediterranean diet (from 54.2% to 65.1%, P = 0.01). Based on the FSFI cutoff score for female sexual dysfunction (FSD) of 23, women with the highest score of adherence had a lower prevalence of sexual dysfunction as compared with women of lower tertiles (47.6%, 53.9%, and 57.8%, higher, middle, and lower tertile, respectively, P = 0.01). These associations remained significant after adjustment for many potential confounders. CONCLUSIONS: In women with type 2 diabetes, greater adherence to Mediterranean diet is associated with a lower prevalence of FSD.

positive: Subclinical endothelial dysfunction and low-grade inflammation play roles in the development of erectile dysfunction in young men with low risk of ... The purpose of this study is to investigate the possible underlying pathogenesis of erectile dysfunction(ED) in young men with low risk of coronary heart disease and no well-known aetiology. To conduct this study, 122 patients with ED under the age of 40 were enrolled, along with 33 age-matched normal control subjects. The patients with ED had significantly higher levels of systolic blood pressure (SBP), total cholesterol and triglyceride, high sensitivity C-reactive protein (hs-CRP), greater carotid intima-media thickness (CIMT) and Framingham risk score (FRS) than the control group, though all of these values were within the respective normal range. Further, the brachial artery flow- mediated vasodilation (FMD) values were significantly lower in ED patients and correlated positively with the severity of ED (r = 0.714, p < 0.001). When these significant factors were studied in the multivariate logistic regression model, FMD, SBP, hs-CRP and FRS remained the statistical significance. The receiver-operating characteristic (ROC) analysis demonstrated that FMD had a high ability to predict ED in young male with low FRS [area under the curve (AUC) 0.921, p < 0.001]. The cutoff value of FMD <10.25% had sensitivity of 82.8% and specificity of 100% for diagnosis of ED. FRS and hs- CRP were also proven to be predictors of ED (AUC 0.812, p < 0.001; AUC 0.645, p = 0.011, respectively). The results of this study validated that subclinical endothelial dysfunction and low-grade inflammation may be the underlying pathogenesis of ED with no well-known aetiology. Young patients complaining of ED should be screened for cardiovascular risk factors and possible subclinical atherosclerosis. Measurement of FMD, hs-CRP and FRS can improve our ability to predict and treat ED, as well as subclinical cardiovascular disease early for young male. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.

positive: Heart disease risk factors predict erectile dysfunction 25 years later: the Rancho Bernardo Study. OBJECTIVES: We examined whether common coronary heart disease (CHD) risk factors measured in mid-life predict erectile dysfunction (ED) 25 years later. BACKGROUND: Retrospective and cross-sectional studies have suggested that ED is associated with classic CHD risk factors, but few prospective studies have studied these associations. METHODS: In this prospective study of community-dwelling men age 30 to 69 years, seven classic CHD risk factors (age, smoking, hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, and obesity) were assessed from 1972 to 1974. In 1998, after an average follow-up of 25 years, surviving male participants were asked to complete the International Index of Erectile Function (IIEF-5), which allows stratification of ED into five groups. RESULTS: Sixty-eight percent of the surviving men returned, and 60% completed the IIEF-5 questionnaire. Respondents had more favorable levels of all heart disease risk factors at baseline than non-respondents. At baseline, the average age of the 570 ED study participants was 46 years; at follow-up, their average age was 72 years. Mean age, body mass index, cholesterol, and triglycerides were each significantly associated with an increased risk of ED. Cigarette smoking was marginally more common in those with severe/complete ED, as compared with those without ED. Blood pressure and fasting blood glucose were not significantly associated with ED, likely due to selective mortality. CONCLUSIONS: Improving CHD risk factors in mid-life may decrease the risk of ED as well as CHD. Erectile dysfunction should be included as an outcome in clinical trials of lipid-lowering agents and lifestyle modifications.

positive: Subclinical coronary artery atherosclerosis in patients with erectile dysfunction. OBJECTIVES: The purpose of our study was to assess the prevalence and extent of coronary artery atherosclerosis in asymptomatic patients with vascular erectile dysfunction (ED). BACKGROUND: An association between ED and ischemic heart disease has been suggested, but it is unknown if it represents a marker of subclinical coronary atherosclerosis. METHODS: We studied 70 consecutive patients with vascular ED, evaluated by penile Doppler, and 73 control subjects with no history of coronary artery disease. We measured traditional coronary risk factors, circulating levels of C-reactive protein (CRP), endothelial function by ultrasound of brachial artery, and coronary artery calcification by multi-slice computed tomography. RESULTS: The patients and the control group were similar for age, race, and coronary risk score. Patients with ED had significantly higher high-sensitivity C-reactive protein levels (2.62 vs. 1.03 mg/l, p < 0.001). Flow-mediated dilation of the brachial artery was more impaired in patients with ED than in controls (2.36 vs. 3.92, p < 0.001). Coronary artery calcification was more frequent in individuals with ED than in control subjects (p = 0.01). Multiple logistic regression analysis showed that patients with ED had an overall odds ratio of 3.68 for having calcium score above the 75th percentile, compared to the controls. CONCLUSIONS: Coronary atherosclerosis is more severe in patients with vascular ED; ED predicts the presence and extent of subclinical atherosclerosis independent of traditional risk factors for cardiovascular disease. Thus, ED may be considered an additional, early warning sign of coronary atherosclerosis.

positive: The link between erectile and cardiovascular health: the canary in the coal mine. Lifestyle and nutrition have been increasingly recognized as central factors influencing vascular nitric oxide (NO) production and erectile function. This review underscores the importance of NO as the principal mediator influencing cardiovascular health and erectile function. Erectile dysfunction (ED) is associated with smoking, excessive alcohol intake, physical inactivity, abdominal obesity, diabetes, hypertension, and decreased antioxidant defenses, all of which reduce NO production. Better lifestyle choices; physical exercise; improved nutrition and weight control; adequate intake of or supplementation with omega-3 fatty acids, antioxidants, calcium, and folic acid; and replacement of any testosterone deficiency will all improve vascular and erectile function and the response to phosphodiesterase-5 inhibitors, which also increase vascular NO production. More frequent penile-specific exercise improves local endothelial NO production. Excessive intake of vitamin E, calcium, l-arginine, or l-citrulline may impart significant cardiovascular risks. Interventions discussed also lower blood pressure or prevent hypertension. Certain angiotensin II receptor blockers improve erectile function and reduce oxidative stress. In men aged <60 years and in men with diabetes or hypertension, erectile dysfunction can be a critical warning sign for existing or impending cardiovascular disease and risk for death. The antiarrhythmic effect of omega-3 fatty acids may be particularly crucial for these men at greatest risk for sudden death. In conclusion, by better understanding the complex factors influencing erectile and overall vascular health, physicians can help their patients prevent vascular disease and improve erectile function, which provides more immediate motivation for men to improve their lifestyle habits and cardiovascular health. Copyright © 2011 Elsevier Inc. All rights reserved.

positive: Erectile dysfunction prevalence, time of onset and association with risk factors in 300 consecutive patients with acute chest pain and angiographic... OBJECTIVES: The aim of this study was to assess erectile dysfunction prevalence, time of onset and association with risk factors in patients with acute chest pain and angiographically documented coronary artery disease. METHODS: 300 consecutive patients with acute chest pain and angiographically documented coronary artery disease were assessed using a semi-structured interview investigating their medical and sexual histories, the International Index of Erectile Function and other instruments. RESULTS: Patient mean age was 62.5+/-8 years (range 33-86 years). Mean duration of symptoms or signs of myocardial ischaemia prior to enrollment in the study was 49 months (range 1-200). Coronary angiography showed 1-, 2- and 3-vessel disease in 98 (32.6%), 88 (29.3%) and 114 (38%) patients, respectively. The prevalence of ED among all patients was 49% (147/300). Erectile dysfunction was scored as mild, mild to moderate, moderate and severe in 21 (14%), 31 (21%), 20 (14%), and 75 (51%) of patients, respectively. There was no significant difference between patients with ED (n=147) or without ED (n=153) as far as clinical and angiographic characteristics were concerned. In the 147 patients with co-existing ED and CAD, ED symptoms were reported as having become clinically evident prior to CAD symptoms by 99/147 (67%) patients. The mean time interval between the onset of ED and CAD was 38.8 months (range 1-168). There was no significant difference in terms of risk factor distribution and clinical and angiographic characteristics between patients with the onset of ED before vs. after CAD diagnosis. Interestingly, all patients with type I diabetes and ED actually developed sexual dysfunction before CAD onset (p<0.001). CONCLUSIONS: Our study suggests that a significant proportion of patients with angiographically documented coronary artery disease have erectile dysfunction and that this latter condition may become evident prior to angina symptoms in almost 70% of cases. Future studies including a control group of patients with coronary artery disease and normal erectile function are required in order to verify whether erectile dysfunction may be considered a real predictor of ischemic heart disease.

positive: The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative tradition dedicated to optimizing sexual function and preserving cardiovascular health. The third Princeton Consensus met November 8 to 10, 2010, and had 2 primary objectives. The first objective focused on the evaluation and management of cardiovascular risk in men with erectile dysfunction (ED) and no known cardiovascular disease (CVD), with particular emphasis on identification of men with ED who may require additional cardiologic work-up. The second objective focused on reevaluation and modification of previous recommendations for evaluation of cardiac risk associated with sexual activity in men with known CVD. The Panel's recommendations build on those developed during the first and second Princeton Consensus Conferences, first emphasizing the use of exercise ability and stress testing to ensure that each man's cardiovascular health is consistent with the physical demands of sexual activity before prescribing treatment for ED, and second highlighting the link between ED and CVD, which may be asymptomatic and may benefit from cardiovascular risk reduction.

positive: Lifestyle/dietary recommendations for erectile dysfunction and female sexual dysfunction. Sexual problems are diffuse in both genders. Although epidemiologic evidence seems to support a role for lifestyle factors in erectile dysfunction, limited data are available suggesting the treatment of underlying risk factors may improve erectile dysfunction. The results are sparse regarding associations between lifestyle factors and female sexual dysfunction, and conclusions regarding influence of healthy behaviors on female sexual dysfunction cannot be made before more studies have been performed. Beyond the specific effects on sexual dysfunctions in men and women, adoption of these measures promotes a healthier life and increased well-being, which may help reduce the burden of sexual dysfunction. Copyright © 2011 Elsevier Inc. All rights reserved.

positive: The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: a systematic review and meta-analysis. BACKGROUND: Erectile dysfunction (ED) shares similar modifiable risks factors with coronary artery disease (CAD). Lifestyle modification that targets CAD risk factors may also lead to improvement in ED. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating the effect of lifestyle interventions and pharmacotherapy for cardiovascular (CV) risk factors on the severity of ED. METHODS: A comprehensive search of multiple electronic databases through August 2010 was conducted using predefined criteria. We included randomized controlled clinical trials with follow-up of at least 6 weeks of lifestyle modification intervention or pharmacotherapy for CV risk factor reduction. Studies were selected by 2 independent reviewers. The main outcome measure of the study is the weighted mean differences in the International Index of Erectile Dysfunction (IIEF-5) score with 95% confidence intervals (CIs) using a random effects model. RESULTS: A total of 740 participants from 6 clinical trials in 4 countries were identified. Lifestyle modifications and pharmacotherapy for CV risk factors were associated with statistically significant improvement in sexual function (IIEF-5 score): weighted mean difference, 2.66 (95% CI, 1.86-3.47). If the trials with statin intervention (n = 143) are excluded, the remaining 4 trials of lifestyle modification interventions (n = 597) demonstrate statistically significant improvement in sexual function: weighted mean difference, 2.40 (95% CI, 1.19-3.61). CONCLUSION: The results of our study further strengthen the evidence that lifestyle modification and pharmacotherapy for CV risk factors are effective in improving sexual function in men with ED.

positive: Mediterranean diet improves erectile function in subjects with the metabolic syndrome. Men with the metabolic syndrome demonstrate an increased prevalence of erectile dysfunction (ED). In the present study, we tested the effect of a Mediterranean-style diet on ED in men with the metabolic syndrome. Men were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of ED associated with a diagnosis of metabolic syndrome, complete follow-up in the study trial, and intervention focused mainly on dietary changes. Sixty-five men with the metabolic syndrome met the inclusion/exclusion criteria; 35 out of them were assigned to the Mediterranean-style diet and 30 to the control diet. After 2 years, men on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain, and olive oil as compared with men on the control diet. Endothelial function score and inflammatory markers (C-reactive protein) improved in the intervention group, but remained stable in the control group. There were 13 men in the intervention group and two in the control group (P=0.015) that reported an IIEF score of 22 or higher. Mediterranean-style diet rich in whole grain, fruits, vegetables, legumes, walnut, and olive oil might be effective per se in reducing the prevalence of ED in men with the metabolic syndrome.

positive: Erectile dysfunction and risk of cardiovascular disease: meta-analysis of prospective cohort studies. 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.

positive: Dietary factors, Mediterranean diet and erectile dysfunction. INTRODUCTION: Although epidemiological evidence seems to support a role for lifestyle factors in the pathogenesis of erectile dysfunction (ED), limited data are available suggesting that dietary changes may improve ED. AIM: To provide an update on clinical evidence regarding the role of dietary factors in ED. METHODS: A systematic literature search was performed using MEDLINE and other database (EMBASE, SCOPUS) with MeSH terms and keywords for "erectile dysfunction", "diet", "dietary patterns", "Mediterranean diet", and "lifestyle". MAIN OUTCOME MEASURES: To examine the data relating to erectile dysfunction with dietary factors, its relationship and the impact of dietary treatment. RESULTS: Only few studies assessed the role or the effect of diet on ED. A dietary pattern which is high in fruit, vegetables, nuts, whole grains, and fish but low in red and processed meat and refined grains is more represented in subjects without ED. Mediterranean diet has been proposed as a healthy dietary pattern based on evidence that greater adherence to this diet is associated with lower all-cause and disease-specific survival. In type 2 diabetic men, those with the highest adherence to the Mediterranean diet had the lowest prevalence of ED and were more likely to be sexually active. In clinical trials, Mediterranean diet was more effective than a control diet in ameliorating ED or restoring absent ED in people with obesity or metabolic syndrome. CONCLUSION: The adoption of a Mediterranean diet may be associated with an improvement of erectile dysfunction.

positive: Increased risk of stroke among men with erectile dysfunction: a nationwide population-based study. INTRODUCTION: Previous cross-sectional studies have suggested that erectile dysfunction (ED) represents an independent risk factor for future cardiovascular events. However, very few studies have attempted to examine the association between ED and subsequent stroke. AIM: The aim of this study is to estimate the risk of stroke during a 5-year follow-up period after the first ambulatory care visit for the treatment of ED using nationwide, population-based data and a retrospective case-control cohort design in Taiwan. METHODS: This study used data sourced from the "Longitudinal Health Insurance Database." The study cohort comprised 1,501 patients who received a principal diagnosis of ED between 1997 and 2001 and 7,505 randomly selected subjects as the comparison cohort. Each patient (N = 9,006) was then individually tracked for 5 years from their index ambulatory care visit to identify those who had diagnosed episodes of stroke. MAIN OUTCOME MEASURE: Stratified Cox proportional hazard regressions were performed as a means of comparing the 5-year stroke-free survival rate for the two cohorts. RESULTS: Of the sampled patients, 918 (10.2%) developed stroke within the 5-year follow-up period, that is, 188 individuals (12.5% of the patients with ED) from the study cohort and 730 individuals (9.7% of patients in the comparison cohort) from the comparison cohort. The log-rank test indicated that patients with ED had significantly lower 5-year stroke-free survival rates than those in the comparison cohort (P < 0.001). After adjusting for the patient's monthly income, geographical location, hypertension, diabetes, coronary heart disease, peripheral vascular disease, atrial fibrillation, and hyperlipidemia, patients with ED were more likely to have a stroke during the 5-year follow-up period than patients in the comparison cohort (hazard ratio = 1.29, 95% confidence interval = 1.08 - 1.54, P < 0.01). CONCLUSIONS: These results suggest that ED is a surrogate marker for future stroke in men. © 2010 International Society for Sexual Medicine.

positive: How to save a life during a clinic visit for erectile dysfunction by modifying cardiovascular risk factors. Erectile dysfunction (ED) is an early marker for systemic atherosclerosis and is a predictor for coronary artery disease and cardiac events. The aim of this paper is to convey the importance of addressing cardiovascular risk factors in patients with ED and to inform urologists as well as other physicians who are not specialized in cardiology how to carry out a basic cardiovascular evaluation, including history, physical examination and objective data. We review the evidence and pathophysiology linking ED to cardiovascular disease, and then describe how to carry out a basic cardiovascular evaluation. We present data from the literature showing that appropriate use of lifestyle modifications and medical therapy has a positive effect on mortality, on numerous cardiovascular end points and on ED. Suggestions of when to refer the ED patient to an internist or cardiologist are provided. Identifying and treating cardiovascular risk factors may not only benefit the patient's ED, but it might also save the patient's life.

positive: Penile doppler ultrasound in patients with erectile dysfunction (ED): role of peak systolic velocity measured in the flaccid state in predicting ar... INTRODUCTION: The use of the penile peak systolic velocity (PSV) measured in the flaccid state during penile color Doppler ultrasound (PCDU) examination has been questioned without substantial evidence. AIM: To assess the validity of PSV measured in the flaccid state during PCDU, in patients consulting for erectile dysfunction (ED). METHODS: A consecutive series of 1,346 (mean age 55.0 +/- 12.0 years) male patients was studied. MAIN OUTCOMES MEASURES: All patients underwent PCDU performed both in the flaccid state and dynamic (after prostaglandin E1 stimulation) conditions. A subset of 20 subjects with uncomplicated type 2 diabetes underwent diagnostic testing for silent coronary heart disease by means of adenosine stress myocardial perfusion scintigraphy (SPECT). In these subjects penile arterial flow was simultaneously assessed by PCDU before and after systemic adenosine administration. RESULTS: Flaccid PSV showed a significant (r = 0.513, P < 0.0001) correlation with dynamic PSV. Receiver operating characteristic (ROC) curve analysis demonstrated that when a threshold of 13 cm/seconds was chosen, flaccid PSV was predictive for dynamic PSV < 25 and <35 cm/seconds with an accuracy of 89% and 82%, respectively. Among the subset of patients who underwent SPECT, an impaired coronary flow reserve (ICFR) occurred in nine cases (45%). When the same threshold of <13 cm/seconds was chosen, PSV before SPECT was predictive of ICFR with an accuracy of 80% (area under the ROC curve = 0.798 +/- 0.10; P < 0.05). After adjustment for confounders, anxiety symptoms were related to dynamic PSV (Adj. r = -0.154, P < 0.05) but not to flaccid PSV. CONCLUSIONS: Our results show that flow in the cavernosal arteries can be routinely evaluated by PCDU in the flaccid state. Performing PCDU only in the flaccid state allows identifying subjects with pathological dynamic PSV with accuracy higher than 80%. Furthermore, our preliminary data suggest that the same examination could identify diabetic subjects with ICFR with an accuracy of 80%.

positive: The artery size hypothesis: a macrovascular link between erectile dysfunction and coronary artery disease. Erectile dysfunction (ED) is defined as the inability to achieve or maintain an erection satisfactory for sexual performance. Evidence is accumulating to consider ED as a vascular disorder. Common risk factors for atherosclerosis are frequently found in association with ED, and ED is frequently reported in vascular syndromes, such as coronary artery disease (CAD), hypertension, cerebrovascular disease, peripheral arterial disease, and diabetes mellitus. Finally, similar early impairment of endothelium-dependent vasodilatation and late obstructive vascular changes has been reported in both ED and other vascular syndromes. Recently, we proposed a pathophysiologic mechanism to explain the link between ED and CAD called the artery size hypothesis. Given the systemic nature of atherosclerosis, all major vascular beds should be affected to the same extent. However, symptoms rarely become evident at the same time. This difference in rate of occurrence of different symptoms is proposed to be caused by the different size of the arteries supplying different vascular beds that allow a larger vessel to better tolerate the same amount of plaque compared with a smaller one. According to this hypothesis, because penile arteries are smaller in diameter than coronary arteries, patients with ED will seldom have concomitant symptoms of CAD, whereas patients with CAD will frequently complain of ED. Available clinical evidence appears to support this hypothesis.

positive: Correlation between penile duplex findings and stress electrocardiography in men with erectile dysfunction. The aim of this work is to assess the association between vasculogenic erectile dysfunction (ED) and coronary artery disease in men above the age of 40 y. The study included 40 patients above 40 y of age with vasculogenic ED of more than 3 months duration. A dynamic duplex study after intracavernosal injection of a bimix solution (60 mg papaverine + 2 mg phentolamine mesylate) was carried out using a color ultrasound machine. The patients underwent a stress ECG test, carried out on a motor-driven treadmill according to the 'Bruce Protocol'. A total of 12 patients were diagnosed with positive ischemic heart disease (IHD). Their mean peak systolic velocity (PSV) was PSV = 19.58 cm/s. In all, patients were diagnosed with negative IHD; their mean PSV was 36.21 cm/s. A statistically significant difference was observed between patients with positive IHD and patients with negative IHD regarding PSV (P = 0.003). The sensitivity of a PSV of less than 35 cm/s in predicting IHD was 50% with a specificity of 100%. Positive predictive value for abnormal stress ECG to predict a PSV of less than 35 cm/s was 100%. In conclusion, the PSV of cavernosal arteries is a reliable measure for predicting IHD in patients with vasculogenic ED. Patients with a PSV of less than 35 cm/s should be referred for cardiologic assessment as they carry a real risk of having silent IHD.

positive: Erectile dysfunction and coronary disease: evaluating the link. Erectile dysfunction (ED) is common, affecting 40% of men over 40 years of age (so-called 40 over 40) and 1 in 3 men over 70 years of age. It is predominantly a vascular condition, often preceding a cardiovascular event by 3-5 years. ED is associated as a consequence with acute coronary syndromes and increased cardiovascular and all-cause mortality. Its early identification therefore offers a window of opportunity for cardiovascular risk reduction. ED has for many a devastating impact on a couple's relationship. Its treatment is often successful, maintaining quality of life in the middle aged and elderly. ED should always be queried as part of the ongoing health care worker and patient relationship - its early detection may prevent early death. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

positive: Cardiovascular mortality in men with erectile dysfunction: increased risk but not inevitable. INTRODUCTION: It is unclear whether men with erectile dysfunction (ED) ultimately die of cardiovascular (CV) causes. AIM: This study examined the causes of death in men with ED and their risk of CV death. METHODS: Based on statutory death registrations and hospital morbidity data, the risk of CV death in men with ED in a linked-data study was assessed against the CV mortality risk in a reference male population. MAIN OUTCOME MEASURES: Deaths from CV causes as proportions of all deaths. Age-specific rate, mortality rate ratio (MRR), standardized mortality rate ratio (SMRR), and adjusted hazard ratio (HR). RESULTS: CV mortality was 4.0%. Compared with the reference population, the risk of CV death was higher in men with ED (SMRR 2.2; 95% confidence interval [CI] 1.6, 3.0). Risk of CV mortality was higher in men with CV disease prior to ED (adjusted HR 1.7; 95% CI 1.1, 2.6) or with history of hospital admissions for CV events (adjusted HR 2.2; 95% CI 1.3, 3.8), compared with those without the respective history. MRR was significantly increased in the 40-69 years age group (MRR 4.1; 95% CI 3.2, 5.2). The median time interval between manifestation of ED and CV death was 10.0 years. A greater proportion of deaths from oncological than from CV causes (25.0% vs. 10.8%) occurred within the first 5 years of the manifestation of ED. CONCLUSIONS: Although the risk of CV mortality is greater in men with ED, almost as many men die of oncological as of CV causes, with a higher proportion of oncological deaths occurring sooner subsequent to the first manifestation of ED. © 2011 International Society for Sexual Medicine.

positive: Erectile Dysfunction and Mortality Introduction Erectile dysfunction (ED) and cardiovascular disease (CVD) share pathophysiological mechanisms and often co-occur. Yet it is not known whether ED provides an early warning for increased CVD or other causes of mortality. Aim We sought to examine the association of ED with all-cause and cause-specific mortality. Methods Prospective, population-based study of 1,709 men (of 3,258 eligible) aged 40–70 years. ED was measured by self-report. Subjects were followed for a mean of 15 years. Hazard ratios (HR) were calculated using the Cox proportional hazards regression model. Main outcome measures Mortality due to all causes, CVD, malignant neoplasms, and other causes. Results Of 1,709 men, 1,284 survived to the end of 2004 and had complete ED and age data. Of 403 men who died, 371 had complete data. After adjustment for age, body mass index, alcohol consumption, physical activity, cigarette smoking, self-assessed health, and self-reported heart disease, hypertension, and diabetes, ED was associated with HRs of 1.26 [95% confidence interval (CI), 1.01–1.57] for all-cause mortality and 1.43 (95% CI, 1.00–2.05) for CVD mortality. The HR for CVD mortality associated with ED is of comparable magnitude to HRs of some conventional CVD risk factors. Conclusions These findings demonstrate that ED is significantly associated with increased all-cause mortality, primarily through its association with CVD mortality.

positive: Male sexuality and cardiovascular risk. A cohort study in patients with erectile dysfunction. INTRODUCTION: Although penile blood flow (PBF) has been recommended as an additional diagnostic test in identifying erectile dysfunction (ED) patients at risk for latent cardiovascular disease, no study has ever assessed the possible association of PBF and the relational component of sexual function with incident major cardiovascular events (MACE). AIM: The aim of this study is to investigate whether severity of ED, PBF, and other factors related to a couple's relationship predict incident MACE. METHODS: A consecutive series of 1,687 patients was studied. Different clinical, biochemical, and instrumental (penile flow at color Doppler ultrasound) parameters were evaluated. MAIN OUTCOME MEASURES: Information on MACE was obtained through the City of Florence Registry Office. RESULTS: During a mean follow-up of 4.3 +/- 2.6 years, 139 MACE, 15 of which were fatal, were observed. Cox regression analysis, after adjustment for age and Chronic Disease Score, showed that severe ED predicted MACE (hazard ratio [HR] 1.75; 95% confidence interval 1.10-2.78; P < 0.05). In addition, lower PBF, evaluated both in flaccid (before) and dynamic (after prostaglandin-E1 stimulation) conditions, was associated with an increased risk of MACE (HR = 2.67 [1.42-5.04] and 1.57 [1.01-2.47], respectively, for flaccid [<13 cm/second] and dynamic [<25 cm/second] peak systolic velocity; both P < 0.05). Reported high sexual interest in the partner and low sexual interest in the patient proved to have a protective effect against MACE. CONCLUSIONS: The investigation of male sexuality, and in particular PBF, and sexual desire, could provide insights not only into present cardiovascular status but also into prospective risk.

positive: Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today. The 1950s saw the clinical introduction of the first two specifically antidepressant drugs: iproniazid, a monoamine-oxidase inhibitor that had been used in the treatment of tuberculosis, and imipramine, the first drug in the tricyclic antidepressant family. Iproniazid and imipramine made two fundamental contributions to the development of psychiatry: one of a social-health nature, consisting in an authentic change in the psychiatric care of depressive patients; and the other of a purely pharmacological nature, since these agents have constituted an indispensable research tool for neurobiology and psychopharmacology, permitting, among other things, the postulation of the first aetiopathogenic hypotheses of depressive disorders. The clinical introduction of fluoxetine, a selective serotonin reuptake inhibitor, in the late 1980s, once again revolutionized therapy for depression, opening the way for new families of antidepressants. The present work reviews, from a historical perspective, the entire process that led to the discovery of these drugs, as well as their contribution to the development of the neuroscientific disciplines. However, all of these antidepressants, like the rest of those currently available for clinical practice, share the same action mechanism, which involves the modulation of monoaminergic neurotransmission at a synaptic level, so that the future of antidepressant therapy would seem to revolve around the search for extraneuronal non-aminergic mechanisms or mechanisms that modulate the intraneuronal biochemical pathways.

positive: Frequent consumption of vegetables predicts lower risk of depression in older Taiwanese - results of a prospective population-based study. OBJECTIVE: The study evaluated the association between consumption frequencies of the major food categories and the risk of new depression four years later in older Taiwanese. DESIGN: A prospective cohort study with multistage random sampling. Logistic regression analysis evaluated the significance of the longitudinal associations of intake frequencies of the major food categories with future (4 years later) risk of new depression, controlled for possible confounding factors with or without adjustment for cognitive status. SETTING: Population-based free-living elderly. SUBJECTS: Men and women (n 1609) ≥65 years of age. RESULTS: In a regression model that controlled for demographic, socio-economic, lifestyle and disease/health-related variables but not cognitive status, both fruits (OR = 0·66, 95 % CI 0·45, 0·98, P = 0·038) and vegetables (OR = 0·38, 95 % CI 0·17, 0·86, P = 0·021) were protective against depressive symptoms 4 years later. However, when the same regression model was also adjusted for cognitive status, only vegetables (OR = 0·40, 95 % CI 0·17, 0·95, P = 0·039) were protective against depressive symptoms. Higher consumption of eggs was close to being significant in both regression models (P = 0·087 and 0·069, respectively). Other food categories including meat/poultry, fish, seafood, dairy, legumes, grains and tea showed no significant associations. CONCLUSIONS: Results suggest that although confounding factors cannot be totally ruled out, more frequent consumption of vegetables seems to be protective against depressive symptoms in the elderly. Further studies are needed to elucidate the causal role and the mechanism of the association.

positive: Monoamine oxidase inhibitors and the cheese effect. The behavior of inhibitors of monoamine oxidase-A (MAO-A) is considered in terms of the possibility of having an effective antidepressant that does not give rise to hypertensive interactions with dietary tyramine. Studies with punch-biopsy samples of human intestine and rat intestinal samples show MAO-A to be the predominant form of the enzyme in both species. Transport studies with everted rat intestinal preparations indicate that tyramine is extensively metabolized during transport through the intestine. Selective inhibition of MAO-A by clorgyline results in a large increase in the amount of unchanged tyramine transported, whereas selective inhibition of MAO-B with L-deprenyl (selegiline) has no significant effect. The behavior of reversible MAO-A inhibitors can significantly reduce, but not entirely eliminate, these effects on the intestinal metabolism of tyramine, but only if the inhibition is competitive in nature.

positive: Dietary inhibitors of monoamine oxidase A. Inhibition of monoamine oxidase is one way to treat depression and anxiety. The information now available on the pharmacokinetics of flavonoids and of the components of tobacco prompted an exploration of whether a healthy diet (with or without smoking) provides active compounds in amounts sufficient to partially inhibit monoamine oxidase. A literature search was used to identify dietary monoamine oxidase inhibitors, the levels of these compounds in foods, the pharmacokinetics of the absorption and distribution, and tissue levels observed. An estimated daily intake and the expected tissue concentrations were compared with the measured efficacies of the compounds as inhibitors of monoamine oxidases. Norharman, harman and quercetin dietary presence, pharmacokinetics, and tissue levels were consistent with significant levels reaching neuronal monoamine oxidase from the diet or smoking; 1,2,3,4-tetrahydroisoquinoline, eugenol, 1-piperoylpiperidine, and coumarin were not. Quercetin was equipotent with norharman as a monoamine oxidase A inhibitor and its metabolite, isorhamnetin, also inhibits. Total quercetin was the highest of the compounds in the sample diet. Although bioavailability was variable depending on the source, a healthy diet contains amounts of quercetin that might give sufficient amounts in brain to induce, by monoamine oxidase A inhibition, a small decrease in neurotransmitter breakdown.

positive: Contribution of monoamine oxidase (MAO) inhibition to tobacco and alcohol addiction. Whole-body PET-scan studies in brains of tobacco smokers have shown a decrease in monoamine oxidase (MAO) activity, which reverts to control level when they quit smoking. The observed decrease in MAO activity in smokers is presumably due to their exposure to tobacco constituents that possess MAO-inhibiting properties. The inhibition of MAO activity seems, however, not to be a unique feature of tobacco smoking as subjects with Type II alcoholism have been reported to show a similar decrease in MAO activity that reverses when they cease to use alcohol. The present review summarizes the data on MAO-inhibiting tobacco constituents and explains that the decrease in MAO activity observed in alcoholics is probably due to concomitant tobacco use. It is concluded that the inhibition of MAO by constituents contained in tobacco and tobacco smoke, enhances the addiction induced by tobacco smoking.

positive: Restriction of meat, fish, and poultry in omnivores improves mood: A pilot randomized controlled trial Background Omnivorous diets are high in arachidonic acid (AA) compared to vegetarian diets. Research shows that high intakes of AA promote changes in brain that can disturb mood. Omnivores who eat fish regularly increase their intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), fats that oppose the negative effects of AA in vivo. In a recent cross-sectional study, omnivores reported significantly worse mood than vegetarians despite higher intakes of EPA and DHA. This study investigated the impact of restricting meat, fish, and poultry on mood. Findings Thirty-nine omnivores were randomly assigned to a control group consuming meat, fish, and poultry daily (OMN); a group consuming fish 3-4 times weekly but avoiding meat and poultry (FISH), or a vegetarian group avoiding meat, fish, and poultry (VEG). At baseline and after two weeks, participants completed a food frequency questionnaire, the Profile of Mood States questionnaire and the Depression Anxiety and Stress Scales. After the diet intervention, VEG participants reduced their EPA, DHA, and AA intakes, while FISH participants increased their EPA and DHA intakes. Mood scores were unchanged for OMN or FISH participants, but several mood scores for VEG participants improved significantly after two weeks. Conclusions Restricting meat, fish, and poultry improved some domains of short-term mood state in modern omnivores. To our knowledge, this is the first trial to examine the impact of restricting meat, fish, and poultry on mood state in omnivores.

positive: Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression. CONTEXT: The monoamine theory of depression proposes that monoamine levels are lowered, but there is no explanation for how monoamine loss occurs. Monoamine oxidase A (MAO-A) is an enzyme that metabolizes monoamines, such as serotonin, norepinephrine, and dopamine. OBJECTIVE: To determine whether MAO-A levels in the brain are elevated during untreated depression. SETTING: Tertiary care psychiatric hospital. PATIENTS: Seventeen healthy and 17 depressed individuals with major depressive disorder that met entry criteria were recruited from the care of general practitioners and psychiatrists. All study participants were otherwise healthy and nonsmoking. Depressed individuals had been medication free for at least 5 months. MAIN OUTCOME MEASURE: Harmine labeled with carbon 11, a radioligand selective for MAO-A and positron emission tomography, was used to measure MAO-A DVS (specific distribution volume), an index of MAO-A density, in different brain regions (prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, caudate, putamen, thalamus, anterior temporal cortex, midbrain, hippocampus, and parahippocampus). RESULTS: The MAO-A DVS was highly significantly elevated in every brain region assessed (t test; P=.001 to 3x10(-7)). The MAO-A DVS was elevated on average by 34% (2 SDs) throughout the brain during major depression. CONCLUSIONS: The sizable magnitude of this finding and the absence of other compelling explanations for monoamine loss during major depressive episodes led to the conclusion that elevated MAO-A density is the primary monoamine-lowering process during major depression.

positive: Monoamine theories of depression: historical impact on biomedical research. Monoamine theories associate depression with reduced brain monoamine levels. These theories achieved broad popularity in the mid-1960s. The present article reviews the historical development of monoamine theories and their subsequent impact on biomedical research. Alleged divisions between West European and US researchers over competing versions of the theories are investigated using bibliometrics. Subsequently, the application of monoamine theories in the NIMH Collaborative Program on the Psychobiology of Depression is covered. The article argues that the impact of monoamine theories is best explained by the ability of researchers, governmental agencies, and pharmaceutical companies to invoke theories that advance various projects and agendas.

positive: Mortality from Western cancers rose dramatically among African-Americans during the 20th century: are dietary animal products to blame? Statistics compiled by the National Cancer Institute indicate that, between 1935 and 1974, age-adjusted mortality from most 'Western' cancers (those of the breast, colon, prostate, pancreas, ovary, and kidney) rose dramatically in African-Americans. This phenomenon is paralleled by marked increases in the incidence of these cancers in Asia and Southern Europe during the latter 20th century, in conjunction with increased intakes of dietary animal products. A credible case can be made that diets rich in animal products work in various complementary ways to up-regulate serum levels of insulin, free IGF-I, and free sex hormones: hormones that appear to have important promotional activity for Western cancers. It seems likely that dietary animal product intake by black Americans increased substantially during the 20th century, and that this fact is primarily responsible for their concurrent marked increase in mortality from Western cancers. A whole-food vegan diet rich in fruits and vegetables, especially if coupled with regular exercise and smoking avoidance, could be expected to have a remarkably positive impact on African-American cancer risk, reversing the increases in cancer risk incurred during the 20th century. Copyright 2001 Harcourt Publishers Ltd.

negative: Surgical interruption of pelvic nerve pathways in dysmenorrhea: a systematic review of effectiveness. 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.

negative: An outbreak of neurological autoimmunity with polyradiculoneuropathy in workers exposed to aerosolised porcine neural tissue: a descriptive study. 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.

negative: Strategies for preventing type 2 diabetes: an update for clinicians Diabetes is a major and growing public health challenge which threatens to overwhelm medical services in the future. Type 2 diabetes confers significant morbidity and mortality, most notably with target organ damage to the eyes, kidneys, nerves and heart. The magnitude of cardiovascular risk associated with diabetes is best illustrated by its position as a coronary heart disease risk equivalent. Complications related to neuropathy are also vast, often working in concert with vascular abnormalities and resulting in serious clinical consequences such as foot ulceration. Increased understanding of the natural history of this disorder has generated the potential to intervene and halt pathological progression before overt disease ensues, after which point management becomes increasingly challenging. The concept of prediabetes as a formal diagnosis has begun to be translated from the research setting to clinical practice, but with continually updated guidelines, varied nomenclature, emerging pharmacotherapies and an ever-changing evidence base, clinicians may be left uncertain of best practice in identifying and managing patients at the prediabetic stage. This review aims to summarize the epidemiological data, new concepts in disease pathogenesis and guideline recommendations in addition to lifestyle, pharmacological and surgical therapies targeted at stopping progression of prediabetes to diabetes. While antidiabetic medications, with newer anti-obesity medications and interventional bariatric procedures have shown some promising benefits, diet and therapeutic lifestyle change remains the mainstay of management to improve the metabolic profile of individuals with glucose dysregulation. New risk stratification tools to identify at-risk individuals, coupled with unselected population level intervention hold promise in future practice.

negative: Health benefits of nut consumption with special reference to body weight control. Nuts are an integral part of the Mediterranean food patterns, and their incorporation into the regular diets of human beings is believed to provide many health benefits. The recent recognition of nuts as "heart-healthy" foods by the U.S. Food and Drug Administration has given a major boost to the positive image of nuts. Nut consumption has been associated with several health benefits, such as antioxidant, hypocholesterolemic, cardioprotective, anticancer, anti-inflammatory, and antidiabetic benefits, among other functional properties. However, although nuts possess these many health benefits, their consumption has been hampered by a lack of adequate information regarding those benefits. In addition, because nuts are energy-dense foods with high-fat content, there is a misconception among consumers that increased consumption may lead to unwanted gain in body weight with the risk of developing overweight/obesity. Nonetheless, available epidemiologic studies and short-term controlled feeding trials have supported the theory that the inclusion of nuts in the typical diet does not induce weight gain, despite an expected increase in total caloric intake. To address the misperception about nuts and body weight gain, the present review focuses mainly on the relation between nut consumption and body weight gain, in the context of the many health benefits of nuts. Copyright © 2012 Elsevier Inc. All rights reserved.

negative: Auto-immune polyradiculoneuropathy and a novel IgG biomarker in workers exposed to aerosolized porcine brain. 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.

negative: The role of nerve blocks and botulinum toxin injections in the management of cluster headaches. Cluster headache (CH) is a primary headache syndrome that is classified with the trigeminal autonomic cephalalgias. CH treatment involves three steps: acute attack management, transitional therapy, and preventive therapy. Greater occipital nerve block has been shown to be an effective alternative bridge therapy to oral steroids in CH. Botulinum toxin type A has recently been studied as a new preventive treatment for patients with chronic CH, with limited success.

negative: Dysmenorrhea. 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.

negative: Guillain-barré syndrome: modern theories of etiology. Guillain-Barré syndrome (GBS) is a classic failure of the immune system with a life-threatening attack upon a critical self-component. The active phase of the disease is short, concordant with the latency of a primary adaptive immune response. Triggers for GBS include infection and (rarely) vaccination; cross-reactivity between infectious and neural epitopes has been well demonstrated, particularly for Campylobacter jejuni and motor axonal forms of GBS in which non-protein gangliosides are antigenic. Most people are probably exposed to a GBS trigger, but only rarely does the disease develop. We propose that GBS illustrates competing determinants of the immune system's decision about whether to mount a response, and that in unlucky affected individuals, co-presentation of cross-reactive antigens with danger signals activating pattern-recognition receptors overcomes normal self-recognition such that a primary response is initiated that attacks the nerve. Then, in most cases of GBS, the response rapidly turns off, and second attacks rarely occur. This suggests active restoration of tolerance, and specific privileged site attributes of nerve and declining danger signals as the trigger wanes may contribute to this restoration. Standard immunosuppression has not been effective in GBS. We suggest this is because immune tolerance is already being restored by the time such therapies are initiated. This in turn suggests that improvements in GBS outcomes are likely to come from better protection of the nerve cells under attack while normal resumption of tolerance is permitted to proceed rather than exploring more aggressive immunosuppressive approaches.

negative: Outbreak of progressive inflammatory neuropathy following exposure to aerosolized porcine neural tissue. 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.

negative: Insulin secretion as a determinant of pancreatic cancer risk. 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.

negative: The autopsy of chicken nuggets reads "chicken little". PURPOSE: To determine the contents of chicken nuggets from 2 national food chains. BACKGROUND: Chicken nuggets have become a major component of the American diet. We sought to determine the current composition of this highly processed food. METHODS: Randomly selected nuggets from 2 different national fast food chains were fixed in formalin, sectioned and stained for microscopic analysis. RESULTS: Striated muscle (chicken meat) was not the predominate component in either nugget. Fat was present in equal or greater quantities along with epithelium, bone, nerve, and connective tissue. CONCLUSION: Chicken nuggets are mostly fat, and their name is a misnomer. Copyright © 2013 Elsevier Inc. All rights reserved.

negative: Baker's yeast β-glucan supplementation increases monocytes and cytokines post-exercise: implications for infection risk? Strenuous aerobic exercise is known to weaken the immune system, and while many nutritional supplements have been proposed to boost post-exercise immunity, few are known to be effective. The purpose of the present study was to evaluate whether 10 d of supplementation with a defined source of baker's yeast β-glucan (BG, Wellmune WGP®) could minimise post-exercise immunosuppression. Recreationally active men and women (n 60) completed two 10 d trial conditions using a cross-over design with a 7 d washout period: placebo (rice flour) and baker's yeast BG (250 mg/d of β-1,3/1,6-glucans derived from Saccharomyces cerevisiae) before a bout of cycling (49 ± 6 min) in a hot (38 ± 2°C), humid (45 ± 2 % relative humidity) environment. Blood was collected at baseline (before supplement), pre- (PRE), post- (POST) and 2 h (2H) post-exercise. Total and subset monocyte concentration was measured by four-colour flow cytometry. Plasma cytokine levels and lipopolysaccharide (LPS)-stimulated cytokine production were measured using separate multiplex assays. Total (CD14⁺) and pro-inflammatory monocyte concentrations (CD14⁺/CD16⁺) were significantly greater at POST and 2H (P<0·05) with BG supplementation. BG supplementation boosted LPS-stimulated production of IL-2, IL-4, IL-5 and interferon-γ (IFN-γ) at PRE and POST (P<0·05). Plasma IL-4, IL-5 and IFN-γ concentrations were greater at 2H following BG supplementation. It appears that 10 d of supplementation with BG increased the potential of blood leucocytes for the production of IL-2, IL-4, IL-5 and IFN-γ. The key findings of the present study demonstrate that BG may have potential to alter immunity following a strenuous exercise session.

negative: A comparative review of thermography as a breast cancer screening technique. Breast cancer is the most frequently diagnosed cancer of women in North America. Despite advances in treatment that have reduced mortality, breast cancer remains the second leading cause of cancer induced death. Several well established tools are used to screen for breast cancer including clinical breast exams, mammograms, and ultrasound. Thermography was first introduced as a screening tool in 1956 and was initially well accepted. However, after a 1977 study found thermography to lag behind other screening tools, the medical community lost interest in this diagnostic approach. This review discusses each screening tool with a focus brought to thermography. No single tool provides excellent predictability; however, a combination that incorporates thermography may boost both sensitivity and specificity. In light of technological advances and maturation of the thermographic industry, additional research is required to confirm the potential of this technology to provide an effective non-invasive, low risk adjunctive tool for the early detection of breast cancer.

negative: Dietary intake and the risk of coronary heart disease among the coconut-consuming Minangkabau in West Sumatra, Indonesia. Several nutrition and non-nutritional pathways are recognised in the development and occurrence of cardiovascular disease. In many populations, high intakes of saturated fat are associated with elevated serum cholesterol concentrations and increased coronary heart disease (CHD) mortality. However, several studies report that hyperlipidaemia and heart diseases are not common among populations who consume coconut, a source of saturated fat. A case-control study was conducted among the Minangkabau known to be high coconut consumers to examine the difference in food patterns and risk of coronary heart disease (CHD) between the coronary cases and their gender- and age-matched apparently healthy counterparts serving as controls. Eligible subjects with CHD were identified through the co-operation of five participating hospitals located in Padang and Bukittinggi in West Sumatra, Indonesia. A total of 93 eligible cases (62 men and 31 women) in the Case group and 189 subjects (113 men and 76 women) in the Control group were recruited. Information on the intakes of individual foods and dishes over the preceding 12 months was obtained using a semi-quantitative food frequency questionnaire. The Case groups had significantly higher intakes of meats, eggs, sugar, tea, coffee and fruits, but lower intakes of soy products, rice and cereals compared to the controls. Coconut consumption as flesh or milk was not different between cases and controls. The cases had significantly higher intakes of protein and cholesterol, but lower intake of carbohydrate. Similar intakes of saturated and unsaturated fatty acids between the cases and controls indicated that the consumption of total fat or saturated fat, including that from coconut, was not a predictor for CHD in this food culture. However, the intakes of animal foods, total protein, dietary cholesterol and less plant derived carbohydrates were predictors of CHD.

negative: A wholly nutritional 'multifocal angiostatic therapy' for control of disseminated cancer. 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.

negative: Patient expectations on lipid-lowering drugs. OBJECTIVE: The objective of this study was to assess expectations of effect when using statins in a treatment population. Further the aim was to examine factors, including history and concurrent risk of coronary heart disease, associated with a higher and lower treatment belief. METHODS: Eight hundred and twenty-nine (829) Swedish patients using statins completed postal questionnaires about their health, life style, cardiovascular risk factors and expectation of the treatment. Expected treatment benefit was used as outcome measurement. RESULTS: A medical history of coronary heart disease did not affect treatment expectations. Patients with a high risk of cardiovascular disease reported a slightly lower expectation of the treatment effect at a 10-year perspective (p<0.01) but not at shorter time perspectives. Low satisfaction with the explanation of the purpose of the treatment and a poor perceived control of own health was associated with a more negative view on treatment benefit. CONCLUSION: The rationale applied by physicians prescribing statins does not seem to relate to the patients' expectations, whereas factors relating to the patient-physician relationship, the social situation and the perceived control of health seem to affect patient belief. PRACTICE IMPLICATIONS: The association between patients' poor satisfaction of treatment explanation and a low belief in treatment benefits emphasizes the importance of the patient-physician communication. It is suggested that clinical tools are developed in order to identify patients with poor belief in treatment benefit since tailored education for this group might reduce the risk of non-compliance and subsequently reduce the risk of coronary heart disease.

negative: Several culinary and medicinal herbs are important sources of dietary antioxidants. We assessed the contribution of culinary and medicinal herbs to the total intake of dietary antioxidants. Our results demonstrate that there is more than a 1000-fold difference among antioxidant concentrations of various herbs. Of the dried culinary herbs tested, oregano, sage, peppermint, garden thyme, lemon balm, clove, allspice and cinnamon as well as the Chinese medicinal herbs Cinnamomi cortex and Scutellariae radix all contained very high concentrations of antioxidants (i.e., >75 mmol/100 g). In a normal diet, intake of herbs may therefore contribute significantly to the total intake of plant antioxidants, and be an even better source of dietary antioxidants than many other food groups such as fruits, berries, cereals and vegetables. In addition, the herbal drug, Stronger Neo-Minophagen C, a glycyrrhizin preparation used as an intravenous injection for the treatment of chronic hepatitis, boosts total antioxidant intake. It is tempting to speculate that several of the effects due to these herbs are mediated by their antioxidant activities.

negative: Effects of Aerobic Exercise on Mild Cognitive Impairment 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.

negative: Platelets in atherosclerosis. Beyond obvious functions in haemostasis and thrombosis, platelets are considered to be essential in proinflammatory surroundings such as atherosclerosis, allergy, rheumatoid arthritis and even cancer. In atherosclerosis, platelets facilitate the recruitment of inflammatory cells towards the lesion sites and release a plethora of inflammatory mediators, thereby enriching and boosting the inflammatory milieu. Platelets do so by interacting with endothelial cells, circulating leukocytes (monocytes, neutrophils, dendritic cells, T-cells) and progenitor cells. This cross-talk enforces leukocyte activation, adhesion and transmigration. Furthermore, platelets are known to function in innate host defense through the release of antimicrobial peptides and the expression of pattern recognition receptors. In severe sepsis, platelets are able to trigger the formation of neutrophil extracellular traps (NETs), which bind and clear pathogens. The present antiplatelet therapies that target key pathways of platelet activation and aggregation therefore hold the potential to modulate platelet-derived immune functions by reducing cellular interactions of platelets with other immune components and by reducing the secretion of inflammatory proteins into the milieu. The objective of this review is to update and discuss the current perceptions of the platelet immune constituents and their prospect as therapeutic targets in an atherosclerotic setting.

negative: Immunity: plants as effective mediators. 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.

negative: The effect of vegetarian diets on plasma lipid and platelet levels. Vegetarians have an apparent diminished risk for the development of ischemic coronary heart disease. This may be secondary to dietary effects of plasma lipids and lipoproteins, but platelets, which may also play a role, have also been observed to have aberrant functions in vegetarians. We measured plasma lipid and lipoprotein levels, platelet function, platelet fatty acid levels, and platelet active prostaglandins in ten strict vegetarians (vegans), 15 lactovegetarians, and 25 age- and sex-matched omnivorous controls. The most striking observations were a highly significant rise in platelet linoleic acid concentration and a decline in platelet arachidonic acid concentration in both vegetarian subgroups as compared with omnivorous controls. Serum thromboxane and prostacyclin levels as well as results of platelet aggregation studies did not differ among the groups tested. Cholesterol levels were significantly lower in both vegetarian groups as compared with controls, but plasma high- and low-density lipoprotein levels were lower only in the vegan subgroup as compared with omnivores. If diet produces these changes in platelet fatty acid and plasma lipid levels it may contribute to the decreased risk of coronary heart disease and possibly atherosclerosis in vegetarians.

negative: Treatment of migraine: update on new therapies. PURPOSE OF REVIEW: This review provides a comprehensive selection of the latest clinical trial results in antimigraine treatment. RECENT FINDINGS: The oral calcitonine gene-related peptide antagonist telcagepant is efficacious in acute treatment. Compared to triptans, its efficacy is almost comparable but its tolerance is superior. The same is true for the 5HT-1F agonist lasmiditan, another agent devoid of vascular effects. Triptans, as other drugs, are more efficient if taken early but nonsteroidal anti-inflammatory drugs and analgesics remain useful for acute treatment, according to several meta-analyses. Single-pulse transcranial magnetic stimulation during the aura rendered more patients pain-free (39%) than sham stimulation (22%) in one study. Topiramate could be effective for migrainous vertigo, but it did not prevent transformation to chronic migraine in patients with high attack frequency. Onabotulinumtoxin A was effective for chronic migraine and well tolerated, but the therapeutic gain over placebo was modest; the clinical profile of responders remains to be determined before widespread use. Occipital nerve stimulation was effective in intractable chronic migraine with 39% of responders compared to 6% after sham stimulation. This and other neuromodulation techniques, such as sphenopalatine ganglion stimulation, are promising treatments for medically refractory patients but large controlled trials are necessary. One study suggests that outcome of patent foramen ovale closure in migraine might depend on anatomic and functional characteristics. SUMMARY: Drugs with a better efficacy or side-effect profile than triptans may soon become available for acute treatment. The future may also look brighter for some of the very disabled chronic migraineurs thanks to novel drug and neuromodulation therapies.

negative: Diabetic retinopathy. Diabetic retinopathy is a common and specific microvascular complication of diabetes, and remains the leading cause of preventable blindness in working-aged people. It is identified in a third of people with diabetes and associated with increased risk of life-threatening systemic vascular complications, including stroke, coronary heart disease, and heart failure. Optimum control of blood glucose, blood pressure, and possibly blood lipids remains the foundation for reduction of risk of retinopathy development and progression. Timely laser therapy is effective for preservation of sight in proliferative retinopathy and macular oedema, but its ability to reverse visual loss is poor. Vitrectomy surgery might occasionally be needed for advanced retinopathy. New therapies, such as intraocular injection of steroids and antivascular endothelial growth-factor agents, are less destructive to the retina than are older therapies, and could be useful in patients who respond poorly to conventional therapy. The outlook for future treatment modalities, such as inhibition of other angiogenic factors, regenerative therapy, and topical therapy, is promising. Copyright 2010 Elsevier Ltd. All rights reserved.

negative: The effect of inhaling peppermint odor and ethanol in women athletes. The purpose of this study was to determine whether inhaling peppermint odor has effects on time of running, maximum heart rate (MHR), maximum oxygen consumption (VO2max), oxygen consumption (VO2), minute ventilation (VE) and respiratory exchange ratio (RER) during acute intensive exercise or not. 36 women soccer player were chosen for participating in this research. They were randomly divided in 3 groups (control, inhaling peppermint, inhaling mixture of peppermint and ethanol). In order to be aware of similarity of groups, the subjects' BMI was determined and ANOVA did not show any significant differences (p < 0.05). The subjects of three groups ran on treadmill according to Bruce test. Heart rate, time of running, VO2max, VO2, VE and RER were measured by Gas Analyzer. After collecting the data, ANOVA was done (p < 0.05) and the results showed that in this study the inhaling of fragrant odors did not have any significant effect on the time of running, MHR, VO2max, VO2, VE and RER, which we think is due to the intensity and duration of training. Referring to our results of the present study; we suggest that inhaling peppermint odor during acute intensive exercise has no significant effect on pulmonary indexes and physical performance (Tab. 4, Fig. 1, Ref. 21).

negative: mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein ... Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin administration in transplant patients, and lifelong consumption of low-protein plant-based diets have all been linked to decreased risk for various cancers. These benefits may be mediated, at least in part, by down-regulated activity of the mTORC1 complex, a key regulator of protein translation. By boosting the effective availability of the translation initiator eIF4E, mTORC1 activity promotes the translation of a number of "weak" mRNAs that code for proteins, often up-regulated in cancer, that promote cellular proliferation, invasiveness, and angiogenesis, and that abet cancer promotion and chemoresistance by opposing apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly, may have utility not only for cancer prevention, but also for the treatment of many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in many cancers, strategies which target eIF4E directly--some of which are now being assessed clinically--may have the broadest efficacy in this regard. Many of the "weak" mRNAs coding for proteins that promote malignant behavior or chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which are active in a high proportion of cancers; thus, regimens concurrently targeting eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the transcriptional and translational levels, potentially achieving a very marked reduction in their expression. Copyright © 2011 Elsevier Ltd. All rights reserved.

negative: Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observational studies Objective To determine the comparative effects of the thiazolidinediones (rosiglitazone and pioglitazone) on myocardial infarction, congestive heart failure, and mortality in patients with type 2 diabetes. Design Systematic review and meta-analysis of observational studies. Data sources Searches of Medline and Embase in September 2010. Study selection Observational studies that directly compared the risk of cardiovascular outcomes for rosiglitazone and pioglitazone among patients with type 2 diabetes mellitus were included. Data extraction Random effects meta-analysis (inverse variance method) was used to calculate the odds ratios for cardiovascular outcomes with thiazolidinedione use. The I2 statistic was used to assess statistical heterogeneity. Results Cardiovascular outcomes from 16 observational studies (4 case-control studies and 12 retrospective cohort studies), including 810 000 thiazolidinedione users, were evaluated after a detailed review of 189 citations. Compared with pioglitazone, use of rosiglitazone was associated with a statistically significant increase in the odds of myocardial infarction (n=15 studies; odds ratio 1.16, 95% confidence interval 1.07 to 1.24; P<0.001; I2=46%), congestive heart failure (n=8; 1.22, 1.14 to 1.31; P<0.001; I2=37%), and death (n=8; 1.14, 1.09 to 1.20; P<0.001; I2=0%). Numbers needed to treat to harm (NNH), depending on the population at risk, suggest 170 excess myocardial infarctions, 649 excess cases of heart failure, and 431 excess deaths for every 100 000 patients who receive rosiglitazone rather than pioglitazone. Conclusion Among patients with type 2 diabetes, use of rosiglitazone is associated with significantly higher odds of congestive heart failure, myocardial infarction, and death relative to pioglitazone in real world settings.

negative: Postinfectious functional gastrointestinal disorders. Functional gastrointestinal disorders are associated with low health-related quality of life and high resource utilization. Postinfectious irritable bowel syndrome (PI-IBS) is a functional gastrointestinal disorder defined as the acute onset of new IBS symptoms in an individual who has not previously met the Rome criteria for IBS, immediately after an acute illness characterized by 2 or more of the following: fever, vomiting, diarrhea, or a positive bacterial stool culture. Although the pathophysiological mechanisms involved in PI-IBS are currently unknown, it is believed that a transitory inflammation leads to subtle but permanent changes in the structure and function of the digestive system that induce symptoms. This review considers recent evidence surrounding the role of inflammatory mediators in the development of hypersensitivity, along with the mediators and mechanisms of abdominal pain and discomfort once the acute inflammation has cleared. Recent data suggest that anatomic changes to mast cells-nerve fibers are necessary, but not sufficient to induce symptoms. It is now possible to estimate the risk of developing PI-FGID based on the presence and relative severity of different risk factors, including prolonged duration of initial illness, toxicity of infecting bacterial strain, smoking, mucosal markers of inflammation, female sex, depression, hypochondriasis, and adverse life events in the preceding 3 months.

negative: Plasma and erythrocyte biomarkers of dairy fat intake and risk of ischemic heart disease. 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.

negative: Flavanols, the Kuna, Cocoa Consumption, and Nitric Oxide The Kuna Indians who reside in an archipelago on the Caribbean Coast of Panama have very low blood pressure levels, live longer than other Panamanians, and have a reduced frequency of myocardial infarction, stroke, diabetes mellitus, and cancer -- at least on their death certificates. One outstanding feature of their diet includes a very high intake of flavanol-rich cocoa. Flavonoids in cocoa activate nitric oxide synthesis in healthy humans. The possibility that the high flavanol intake protects the Kuna against high blood pressure, ischemic heart disease, stroke, diabetes mellitus, and cancer is sufficiently intriguing and sufficiently important that large, randomized controlled clinical trials should be pursued.

negative: Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality. Coffee, after water, is the most widely consumed beverage in the United States, and is the principal source of caffeine intake among adults. The biological effects of coffee may be substantial and are not limited to the actions of caffeine. Coffee is a complex beverage containing hundreds of biologically active compounds, and the health effects of chronic coffee intake are wide ranging. From a cardiovascular (CV) standpoint, coffee consumption may reduce the risk of type 2 diabetes mellitus and hypertension, as well as other conditions associated with CV risk such as obesity and depression; but it may adversely affect lipid profiles depending on how the beverage is prepared. Regardless, a growing body of data suggests that habitual coffee consumption is neutral to beneficial regarding the risks of a variety of adverse CV outcomes including coronary heart disease, congestive heart failure, arrhythmias, and stroke. Moreover, large epidemiological studies suggest that regular coffee drinkers have reduced risks of mortality, both CV and all-cause. The potential benefits also include protection against neurodegenerative diseases, improved asthma control, and lower risk of select gastrointestinal diseases. A daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects for most of the studied health outcomes. However, most of the data on coffee's health effects are based on observational data, with very few randomized, controlled studies, and association does not prove causation. Additionally, the possible advantages of regular coffee consumption have to be weighed against potential risks (which are mostly related to its high caffeine content) including anxiety, insomnia, tremulousness, and palpitations, as well as bone loss and possibly increased risk of fractures. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

negative: Phospholipids in rice: significance in grain quality and health benefits: a review. Phospholipids (PLs) are a major class of lipid in rice grain. Although PLs are only a minor nutrient compared to starch and protein, they may have both nutritional and functional significance. We have systemically reviewed the literature on the class, distribution and variation of PLs in rice, their relation to rice end-use quality and human health, as well as available methods for analytical profiling. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and their lyso forms are the major PLs in rice. The deterioration of PC in rice bran during storage was considered as a trigger for the degradation of rice lipids with associated rancid flavour in paddy and brown rice. The lyso forms in rice endosperm represent the major starch lipid, and may form inclusion complexes with amylose, affecting the physicochemical properties and digestibility of starch, and hence its cooking and eating quality. Dietary PLs have a positive impact on several human diseases and reduce the side-effects of some drugs. As rice has long been consumed as a staple food in many Asian countries, rice PLs may have significant health benefits for those populations. Rice PLs may be influenced both by genetic (G) and environmental (E) factors, and resolving G×E interactions may allow future exploitation of PL composition and content, thus boosting rice eating quality and health benefits for consumers. We have identified and summarised the different methods used for rice PL analysis, and discussed the consequences of variation in reported PL values due to inconsistencies between methods. This review enhances the understanding of the nature and importance of PLs in rice and outlines potential approaches for manipulating PLs to improve the quality of rice grain and other cereals. Copyright © 2013 Elsevier Ltd. All rights reserved.

negative: Systemic immunity-enhancing effects in healthy subjects following dietary consumption of the lactic acid bacterium Lactobacillus rhamnosus HN001. OBJECTIVE: To determine the effects of the probiotic lactic acid bacterium, Lactobacillus rhamnosus HN001, on natural cellular immunity when delivered orally in normal low-fat milk (LFM) or lactose-hydrolyzed low-fat milk (LFM-LH). DESIGN: A three stage, pre-post intervention trial, spanning nine weeks. SETTING: Taipei Medical College Hospital, Taipei, Taiwan. SUBJECTS: Fifty-two healthy middle-aged and elderly volunteers (17 males, 35 females; median age 63.5, range 44-80). INTERVENTIONS: Stage 1 (run-in diet): 25 g/200 mL reconstituted LFM powder, twice daily for 3 weeks. Stage 2 (probiotic intervention): LFM or LFM-LH, supplemented with 10(9) CFUs/g L. rhamnosus HN001 in each case, for 3 weeks. Stage 3 (wash-out): LFM for 3 weeks. MEASURES OF OUTCOME: In vitro phagocytic capacity of peripheral blood polymorphonuclear (PMN) leukocytes; in vitro tumoricidal activity of natural killer (NK) leukocytes. RESULTS: Immunological responses were unaffected by the run-in diet of LFM alone. In contrast, the relative proportion of PMN cells showing phagocytic activity increased by 19% and 15%, respectively, following consumption of HN001 in either LFM or LFM-LH; the relative level of NK cell tumor killing activity increased by 71% and 147%. In most cases these levels declined following cessation, but remained above baseline. CONCLUSIONS: Dietary consumption of L. rhamnosus HN001, in a base of low-fat milk or lactose-hydrolyzed low-fat milk, appears to enhance systemic cellular immune responses and may be useful as a dietary supplement to boost natural immunity.