Serum magnesium and calcium levels in relation to ischemic stroke : Mendelian randomization study

ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases).ResultsIn standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 7 10-4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 7 10-4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype.ConclusionsThis study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding: Bill & Melinda Gates Foundation

Culture and mental health in Nepal: an interdisciplinary scoping review

Efforts to address global mental health disparities have given new urgency to longstanding debates on the relevance of cultural variations in the experience and expression of distress for the design and delivery of effective services. This scoping review examines available information on culture and mental health in Nepal, a low-income country with a four-decade history of humanitarian mental health intervention. Structured searches were performed using PsycINFO, Web of Science, Medline, and Proquest Dissertation for relevant book chapters, doctoral theses, and journal articles published up to May 2017. A total of 38 publications met inclusion criteria (nine published since 2015). Publications represented a range of disciplines, including anthropology, sociology, cultural psychiatry, and psychology and explored culture in relation to mental health in four broad areas: (1) cultural determinants of mental illness; (2) beliefs and values that shape illness experience, including symptom experience and expression and help-seeking; (3) cultural knowledge of mental health and healing practices; and (4) culturally informed mental health research and service design. The review identified divergent approaches to understanding and addressing mental health problems. Results can inform the development of mental health systems and services in Nepal as well as international efforts to integrate attention to culture in global mental health

Indoor air pollution from solid fuels and risk of hypopharyngeal/ laryngeal and lung cancers: A multicentric case - Control study from India

Background: A recent monograph by the International Agency for Research on Cancer (IARC) has identified indoor air pollution from coal usage as a known human carcinogen, while that from biomass as a probable human carcinogen. Although as much as 74% of the Indian population relies on solid fuels for cooking, very little information is available on cancer risk associated with these fuels in India. Methods: Using data from a multicentric case-control study of 799 lung and 1062 hypopharyngeal/laryngeal cancer cases, and 718 controls, we investigated indoor air pollution from various solid fuels as risk factors for these cancers in India. Results: Compared with never users, individuals who always used coal had an increased risk of lung cancer [odds ratio (OR) 3.76, 95% confidence interval (CI) 1.64-8.63]. Long duration of coal usage (>50 years) was a risk factor for hypopharyngeal (OR 3.47, CI 0.95-12.69) and laryngeal (OR 3.65, CI 1.11-11.93) cancers. An increased risk of hypopharyngeal cancer was observed among lifelong users of wood (OR 1.62, CI 1.14-2.32), however this was less apparent among never-smokers. Increasing level of smokiness inside the home was associated with an increasing risk of hypopharyngeal and lung cancer (Ptrend< 0.05). Conclusion: This study showed differential risks associated with indoor air pollution from wood and coal burning, and provides novel evidence on cancer risks associated with solid fuel usage in India. Our findings suggest that reducing indoor air pollution from solid fuels may contribute to prevention of these cancers in India, in addition to tobacco and alcohol control programs. \ua9 The Author 2008; all rights reserved

Smokeless tobacco and increased risk of hypopharyngeal and laryngeal cancers: A multicentric case-control study from India

Hypopharyngeal and laryngeal cancers are among the most common cancers in India. In addition to smoking, tobacco chewing may be a major risk factor for some of these cancers in India. Using data from a multicentric case-control study conducted in India that included 513 hypopharyngeal cancer cases, 511 laryngeal cancer cases and 718 controls, we investigated smoking and chewing tobacco products as risk factors for these cancers. Bidi smoking was a stronger risk factor compared to cigarette smoking for cancer of the hypopharynx (OR bidi 6.80 vs. ORcig 3.82) and supraglottis (OR bidi 7.53 vs. ORcig 2.14), while the effect of the 2 products was similar for cancer of the glottis (ORbidi 5.32 vs. ORcig 5.74). Among never-smokers, tobacco chewing was a risk factor for hypopharyngeal cancer, but not for laryngeal cancer. In particular, the risk of hypopharyngeal cancer increased with the use of Khaini (OR 2.02, CI 0.81-5.05), Mawa (OR 3.17, CI 1.06-9.53), Pan (OR 3.34, CI 1.68-6.61), Zarda (OR 3.58, CI 1.20-10.68) and Gutkha (OR 4.59, CI 1.21-17.49). A strong dose-response relationship was observed between chewing frequency and the risk of hypopharyngeal cancer (ptrend < 0.001). An effect of alcohol on cancer of the hypopharynx and supraglottis was observed only among daily drinkers (OR 2.22, CI 1.11-4.45 and OR 3.76, CI 1.25-11.30, respectively). In summary, this study shows that chewing tobacco products commercially available in India are risk factors for hypopharyngeal cancer, and that the potency of Bidi smoking may be higher than that of cigarette smoking for hypopharyngeal and laryngeal cancers. \ua9 2007 Wiley-Liss, Inc

Dietary risk factors for hypopharyngeal cancer in India

Objective: The Indian subcontinent has among the highest rates of hypopharyngeal cancer worldwide. The purpose of this study was to examine the associations between the Indian diet and hypopharyngeal cancer. Methods: We used data from a hospital-based case-control study of 513 incident hypopharyngeal cancers and 718 controls from four centers in India. Dietary information was assessed using a 67-item semi-quantitative food frequency questionnaire. Intakes of related foods were combined across food groups and were categorized by quartile. We used unconditional logistic regression modeling, stratified by ever tobacco use, to analyze the association between food intakes and hypopharyngeal cancer. Results: Among persons who had ever smoked or chewed tobacco, protective associations were seen at the highest quartiles of total fruit intake (OR = 0.37, 0.20-0.69), curds (OR = 0.35, 0.17-0.69), and leafy green (OR = 0.25, 95% CI 0.13-0.51), root (OR = 0.22, 95% CI 0.11-0.43), and cruciferous vegetable intakes (OR = 0.41, 0.20-0.84). Results were similar, although not as robust, among persons who had never smoked or chewed tobacco. An increased risk of disease was seen among tobacco users who drank milk daily (OR = 1.84, 1.14-2.98). Conclusions: Dietary factors might contribute to the high risk of hypopharyngeal cancer observed in India. © 2008 Springer Science+Business Media B.V

Sustainable intensification influences soil quality, biota, and productivity in cereal-based agroecosystems

Monotonous rice-wheat cropping system with conventional management practices have resulted in declining soil quality and biota in addition to low input factor productivity and farmer’s profitability in western Indo-Gangetic plains (IGP) of India. Conservation agriculture (CA) based sustainable intensification (SI) is required to improve the soil quality while improving the productivity and profitability. A field experiment was conducted to evaluate the effects of CA based management practices such as zero tillage (ZT), direct seeding of rice (DSR), crop di- versification, residue recycling and legume integration for SI in comparison to conventional management on soil quality and biota in cereal (rice and maize) based cropping systems. Fourteen treatments were included in which four treatments (T1–T4) with rice–wheat and two treatments (T11–T12) with maize-wheat system were based on conventional management, while six treatments (T5–T10) with rice–wheat and two (T13–T14) with maize-wheat were based on CA management practices. Conservation agriculture based SI of maize-wheat-mungbean (T14) recorded lower soil bulk density (1.33 Mg m−3). Soil organic carbon (OC) was increased by 83% and 72% with CA based rice-wheat-mungbean (T10) and maize-wheat-mungbean (T14) system, respectively and it was at par with T9 and T12 compared to farmer’s practice (T1) (4.6 g kg−1). Mean microbial biomass carbon (MBC) and microbial biomass nitrogen (MBN) were 213% and 293% higher with T14 over T1 (646 and 201 μg g−1 dry soil), respectively. However, T10 recorded 117% and 171% higher MBC and MBN, respectively compared to T1. Dehydrogenase activity (DHA) and alkaline phosphatase activity (APA) were improved by 210% and 49% under T14; 140% and 42% under T10 compared to T1 (180 μg TPF g−1 soil 24 h−1 and 144 μg p-nitrophenol g−1h−1), respectively. Mean number of bacteria, fungi and actinomycetes were increased by 28%, 68%, 98% respectively, under T14 relative to T1, and at par with T12 and T10. Most abundant micro-arthropod group belonged to Collembola followed by Acari and Protura, irrespective of treatments. Higher soil quality index (SQI) was ob- served in T10 (0.82), followed by T14 and T6 treatment (0.76). Sustainable intensification of rice and maize based systems (T10 and T14) recorded 39% higher system yield compared to T1 (11.12 Mg ha−1). CA-based sustainable intensification of rice/maize systems improved soil quality and biota, hence resulted higher system yield in alluvial soils of IGP. Conservation agriculture based SI of maize-wheat-mungbean system was found to be the best alternative option than rice–wheat system to achieve sustainable productivity while improving the soil quality index (35%) and conservation of natural resources