Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

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. © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY licens

Suplementação energética e proteica de um volumoso de baixa qualidade pela técnica de produção cumulativa de gás in vitro Energy and protein supplementation of a low quality roughage by the in vitro gas cumulative production technique

Um experimento foi conduzido utilizando-se a técnica semiautomática de produção cumulativa de gás in vitro com o objetivo de avaliar a combinação da suplementação energética com a proteica em dietas à base de um volumoso de baixa qualidade, feno de capim-tifton (Cynodon dactylon L.), com 7,69% de proteína bruta, 70,34% de fibra em detergente neutro e 57,98% de digestibilidade in vitro da matéria orgânica. Foram avaliadas duas fontes de proteína degradável no rúmen (ureia ou proteína isolada de soja); quatro níveis de grão de milho moído (0, 20, 40 e 60%) e quatro níveis suplementares de proteína degradável no rúmen (0; 2,8; 5,6 e 8,4%) em delineamento completamente casualizado em um fatorial 2 × 4 × 4. A digestibilidade in vitro da matéria orgânica aumentou linearmente em resposta à inclusão de milho com inclinação maior utilizando proteína isolada de soja. O fator de partição foi superior com proteína isolada de soja e foi detectado aumento linear em resposta ao aumento da proteína degradável com 20% de milho. A produção máxima de gás da fração de rápida (A) e de lenta (D) degradação aumentou linearmente em resposta à inclusão de milho, com proteína isolada de soja, e quadraticamente com ureia. A taxa de degradação de A aumentou com a inclusão de até 20% de milho e a taxa de degradação de D foi maior com ureia. O lag-time de A aumentou linearmente em resposta a inclusão de milho e no lag-time de D foi observada diminuição com até 20% de milho sem alterações em níveis superiores. A suplementação com até 60% de milho moído foi benéfica para a digestibilidade de dietas com volumoso de baixa qualidade. A associação entre energia e proteína foi benéfica em alguns parâmetros estudados. A ureia gerou melhores respostas em níveis moderados de grão de milho moído.<br>It was conducted an experiment using the semi-automatic in vitro cumulative gas production with the objective of evaluating the combination of energy and protein supplementations in diets based on low quality roughage, Tifton hay (Cynodon dactylon L.), with 7.69% of crude protein; 70.34% of neutral detergent fiber and 57.98% of organic matter in vitro digestibility. It was evaluated two sources of rumen degradable protein (urea or isolated soybean protein); four levels of ground corn grain (0, 20, 40 and 60%) and four supplementary levels of rumen degradable protein (0; 2.8; 5.6 and 8.4%) in complete random design in a 2 × 4 × 4 factorial arrangement. The organic matter in vitro digestibility increased linearly in response to grain corn inclusion with a greater slope by using isolated soybean protein. The partitioning factor was higher with isolated soybean protein and it was detected a linear increase in response to increasing rumen degradable protein with 20% of grain corn. The maximum gas production of the fraction of fast (A) and slow (D) degradation increased linearly in response to the grain corn inclusion, with isolated soybean protein, and it quadratically increased with urea. The A degradation rate was increased with inclusion of up to 20% of grain corn and the degradation rate of D was higher with urea. The A lag-time increased linearly with the inclusion of grain corn and in the D lag-time it was observed a decrease with up to 20% of grain corn unchanged at high levels. The supplementation with up to 60% of grain corn was beneficial to digestibility of diets with low quality roughage. The association between energy and protein supplementation was positive in some studied parameters. Urea gave better responses at moderate levels of ground grain corn