Evaluation of moderate alcohol use and cognitive function among men using a mendelian randomization design in the guangzhou biobank cohort study

Observational studies usually show that moderate alcohol use is associated with better cognitive function. Such studies are vulnerable to residual confounding arising from systematic differences between moderate alcohol users and others. A Mendelian randomization study carried out in a suitable population, such as southern Chinese men, in which alcohol use is low to moderate and is influenced by genotype, offers an alternative and superior approach for clarifying the causal effect of moderate alcohol use on cognitive function. The authors used aldehyde dehydrogenase 2 (ALDH2) genotype (AA, GA, or GG) as an instrumental variable in 2-stage least squares analysis to obtain unbiased estimates of the relation of alcohol consumption (measured in alcohol units (10 g ethanol) per day) with cognitive function, assessed from delayed 10-word recall score (n = 4,707) and Mini-Mental State Examination (MMSE) score (n = 2,284), among men from the Guangzhou Biobank Cohort Study (2003-2008). ALHD2 genotype was strongly associated with alcohol consumption, with an F statistic of 71.0 in 2-stage least squares analysis. Alcohol consumption was not associated with delayed 10-word recall score (-0.03 words per alcohol unit, 95% confidence interval:-0.18, 0.13) or MMSE score (0.06 points per alcohol unit, 95% confidence interval:-0.22, 0.34). Moderate alcohol use is unlikely to be cognitively protective. © The Author 2012. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved.postprin

Moderate alcohol use and cardiovascular disease from mendelian randomization

Background Observational studies show moderate alcohol use negatively associated with ischemic heart disease (IHD) and cardiovascular disease (CVD). However, healthier attributes among moderate users compared to never users may confound the apparent association. A potentially less biased way to examine the association is Mendelian randomization, using alcohol metabolizing genes which influence alcohol use. Methods We used instrumental variable analysis with aldehyde dehydrogenase 2 (ALDH2) genotypes (AA/GA/GG) as instrumental variables for alcohol use to examine the association of alcohol use (10 g ethanol/day) with CVD risk factors (blood pressure, lipids and glucose) and morbidity (self-reported IHD and CVD) among men in the Guangzhou Biobank Cohort Study. Results ALDH2 genotypes were a credible instrument for alcohol use (F-statistic 74.6). Alcohol was positively associated with HDL-cholesterol (0.05 mmol/L per alcohol unit, 95% confidence interval (CI) 0.02 to 0.08) and diastolic blood pressure (1.15 mmHg, 95% CI 0.23 to 2.07) but not with systolic blood pressure (1.00 mmHg, 95% CI -0.74 to 2.74), LDL-cholesterol (0.03 mmol/L, 95% CI -0.03 to 0.08), log transformed triglycerides (0.03 mmol/L, 95% CI -0.01 to 0.08) or log transformed fasting glucose (0.01 mmol/L, 95% CI -0.006 to 0.03), self-reported CVD (odds ratio (OR) 0.98, 95% CI 0.76 to 1.27) or self-reported IHD (OR 1.10, 95% CI 0.83 to 1.45). Conclusion Low to moderate alcohol use among men had the expected effects on most CVD risk factors but not fasting glucose. Larger studies are needed to confirm the null associations with IHD, CVD and fasting glucose.published_or_final_versio

Chemical Vapor Deposition (CVD) of Manganese Self-Aligned Diffusion Barriers for Cu Interconnections in Microelectronics

Barriers to prevent diffusion of copper, oxygen and water vapor were formed by CVD using a manganese precursor vapor that reacts with silica surfaces. The manganese metal penetrates only a few nanometers into the silica to make conformal amorphous manganese silicate layers. This MnSixOy was found to be an excellent barrier to the diffusion of Cu, O2 and H2O vapor. The adhesion strength of Cu to the MnSixOy was found to be sufficiently strong to satisfy the semiconductor industry requirements for interconnections in future microelectronic devices. CVD Mn dissolves into copper surfaces and then diffuses to increase adhesion to SiCNO capping layers.Chemistry and Chemical Biolog

Genetically predicted testosterone and systemic inflammation in men: A separate-sample mendelian randomization analysis in older chinese men

Objectives Observationally, testosterone is negatively associated with systemic inflammation, but this association is open to both residual confounding and reverse causality. Large-scale randomized controlled trials (RCTs), assessing exogenous effects, are presently unavailable. We examined the association of endogenous testosterone with well-established systemic inflammatory markers (white blood cell, granulocyte, lymphocyte and high-sensitivity C-reactive protein (hsCRP)) using a separate-sample Mendelian randomization analysis to minimize reverse causality. Methods A genetic prediction rule for serum testosterone was developed in 289 young Chinese men with mean age of 21.0, using selected testosterone-related SNPs (rs10046, rs1008805 and rs1256031). Multivariable linear regression was used to examine the association of genetically predicted serum testosterone with inflammatory markers among 4,212 older Chinese men from the Guangzhou Biobank Cohort Study. Results Genetically predicted testosterone was unrelated to white blood cell count (-0.01 109/L per nmol/L testosterone, 95% confidence interval (CI) -0.05 to 0.04), granulocyte count (-0.02 109/L, 95% CI -0.06 to 0.02), lymphocyte count (0.005 109/L, 95% CI -0.01 to 0.02) and hsCRP (-0.05 mg/L, 95% CI -0.15 to 0.06). Conclusion Our findings did not corroborate any anti-inflammatory effects of testosterone or corresponding potentially protective effects of testosterone on chronic diseases resulting from reduced low-grade systemic inflammation.published_or_final_versio

Aldehyde dehydrogenase 2-a potential genetic risk factor for lung function among southern Chinese: Evidence from the Guangzhou Biobank Cohort Study

Purpose: In Asia, moderate alcohol users have better lung function. Never users have more inactive aldehyde dehydrogenase 2 (ALDH2) alleles (A) potentially generating confounding because inactive alleles may increase acetaldehyde exposure and reduce lung function. Methods: We examined the association of ALDH2 genotypes with percentage predicted lung function (forced expiratory volume in 1second; forced vital capacity) for age, sex, and height among 5641 older Chinese using multivariable linear regression. Results: ALDH2 genotypes were associated with alcohol use and height but not other attributes. Inactive alleles were inversely associated with lung function (percentage predicted forced expiratory volume in 1second-1.52%, 95% confidence interval [CI],-2.52% to-0.51% for one inactive allele and-2.05%, 95% CI,-3.85% to-0.26% for two inactive alleles compared with two active alleles; and for percentage predicted forced vital capacity-1.25%, 95% CI-2.15% to-0.35% and-1.65%, 95% CI,-3.25% to-0.04%). The association of moderate use with lung function was attenuated after adjusting for ALDH2, in addition to other potential confounders. Conclusions: Previous findings in Chinese may be confounded by ALDH2. High frequency of inactive ALDH2 alleles in East Asia may exacerbate the effect of environmental acetaldehyde exposure on lung function and potentially on chronic obstructive pulmonary disease. © 2014 Elsevier Inc.postprin

Distinct but overlapping roles of LRRTM1 and LRRTM2 in developing and mature hippocampal circuits

LRRTMs are postsynaptic cell adhesion proteins that have region-restricted expression in the brain. To determine their role in the molecular organization of synapses in vivo, we studied synapse development and plasticity in hippocampal neuronal circuits in mice lacking both Lrrtm1 and Lrrtm2. We found that LRRTM1 and LRRTM2 regulate the density and morphological integrity of excitatory synapses on CA1 pyramidal neurons in the developing brain but are not essential for these roles in the mature circuit. Further, they are required for long-term-potentiation in the CA3-CA1 pathway and the dentate gyrus, and for enduring fear memory in both the developing and mature brain. Our data show that LRRTM1 and LRRTM2 regulate synapse development and function in a cell-type and developmental-stage-specific manner, and thereby contribute to the fine-tuning of hippocampal circuit connectivity and plasticity

Enzymatic Ligation Creates Discrete Multi-Nanoparticle Building Blocks for Self-Assembly

Enzymatic ligation of discrete nanoparticle?DNA conjugates creates nanoparticle dimer and trimer structures in which the nanoparticles are linked by single-stranded DNA, rather than double-stranded DNA as in previous experiments. Ligation is verified by agarose gel and small-angle X-ray scattering. This capability is utilized in two ways: first to create a new class of multiparticle building blocks for nanoscale self-assembly; second to develop a system which can amplify a population of discrete nanoparticle assemblies

Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-gamma-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-gamma expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-gamma production, but also the protective function of iNKT cells in arthritis

Semantic contextualisation of social tag-based profiles and item recommendations

Proceedigns of 12th International Conference, EC-Web 2011, Toulouse, France, August 30 - September 1, 2011.The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-23014-1_9We present an approach that efficiently identifies the semantic meanings and contexts of social tags within a particular folksonomy, and exploits them to build contextualised tag-based user and item profiles. We apply our approach to a dataset obtained from Delicious social bookmarking system, and evaluate it through two experiments: a user study consisting of manual judgements of tag disambiguation and contextualisation cases, and an offline study measuring the performance of several tag-powered item recommendation algorithms by using contextualised profiles. The results obtained show that our approach is able to accurately determine the actual semantic meanings and contexts of tag annotations, and allow item recommenders to achieve better precision and recall on their predictions.This work was supported by the Spanish Ministry of Science and Innovation (TIN2008-06566-C04-02), and the Community of Madrid (CCG10- UAM/TIC-5877

How parents perceive and feel about participation in community activities: The comparison between parents of preschoolers with and without autism spectrum disorders

The present study compared how parents of preschoolers with and without Autism Spectrum Disorders (ASD) perceived and felt about participation in community activities. A questionnaire survey was conducted with 380 Hong Kong parents of preschoolers with ASD and 214 Hong Kong parents of preschoolers without ASD. The two groups were not different in their willingness and frequency of participation in community activities. However, the psychological processes underneath their willingness were very different. Among the parents of preschoolers with ASD, their willingness was associated with how they perceived the difficulty and importance of the participation and what emotions they experienced during the activities. This pattern of association was not evident among the parents of preschoolers without ASD. Copyright © The Author(s), 2010.published_or_final_versio