Alcohol and cardio-respiratory deaths in Chinese: a population-based case-control study of 32,462 older Hong Kong adults

Background: In observational studies moderate alcohol use reduces cardio-respiratory mortality. However observational studies may be biased by many factors including residual confounding by unmeasured differences between moderate alcohol users and other groups or by changes in alcohol use with ill-health and aging. We used two different analytic strategies in an under-studied population, i.e. southern Chinese, to provide an assessment of the specific impact of moderate alcohol use on mortality from ischemic heart disease (IHD) and chronic obstructive pulmonary diseases (COPD). Methods: In a population-based case-control study of all adult deaths in Hong Kong Chinese in 1998, we used adjusted logistic regression to compare alcohol use in decedents aged ≥ 60 years from IHD (2270) and COPD (1441) with 10,320 living and 9043 dead controls (all non-alcohol related deaths). We also examined whether the association of alcohol use with death from IHD or COPD varied with sex or smoking status. Results: Using living controls and adjusted for age, socio-economic status and lifestyle, occasional and moderate alcohol use were generally associated with lower mortality from IHD and COPD. However, using dead controls the protection of occasional and moderate alcohol use appeared to be limited to ever-smokers for IHD (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.46 to 0.73 for moderate compared to never-use in ever-smokers, but OR 1.07, 95% CI 0.76 to 1.50 in never-smokers), and possibly to men for COPD. High alcohol use was associated with lower IHD mortality and possibly with lower COPD mortality. Conclusion: High levels of alcohol use in an older Chinese population were associated with lower IHD mortality. Moderate alcohol use was less consistently protective against IHD mortality. Alcohol use was associated with lower COPD mortality particularly in men, either due to some yet to be clarified properties of alcohol or as the artefactual result of genetic selection into alcohol use in a Chinese population. Given the increasing use of alcohol in China with economic development, other designs and analytic strategies are needed to assess the impact of alcohol in this population, so that an evidence-based public health policy can be formulated.link_to_subscribed_fulltex

Association between Variations in Cell Cycle Genes and Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a devastating and progressive lung disease. Its aetiology is thought to involve damage to the epithelium and abnormal repair. Alveolar epithelial cells near areas of remodelling show an increased expression of proapoptotic molecules. Therefore, we investigated the role of genes involved in cell cycle control in IPF. Genotypes for five single nucleotide polymorphisms (SNPs) in the tumour protein 53 (TP53) gene and four SNPs in cyclin-dependent kinase inhibitor 1A (CDKN1A), the gene encoding p21, were determined in 77 IPF patients and 353 controls. In peripheral blood mononuclear cells (PBMC) from 16 healthy controls mRNA expression of TP53 and CDKN1A was determined

Heart healthy cities:Genetics loads the gun but the environment pulls the trigger

The world’s population is estimated to reach 10 billion by 2050 and 75% of this population will live in cities. Two-third of the European population already live in urban areas and this proportion continues to grow. Between 60% and 80% of the global energy use is consumed by urban areas, with 70% of the greenhouse gas emissions produced within urban areas. The World Health Organization states that city planning is now recognized as a critical part of a comprehensive solution to tackle adverse health outcomes. In the present review, we address non-communicable diseases with a focus on cardiovascular disease and the urbanization process in relation to environmental risk exposures including noise, air pollution, temperature, and outdoor light. The present review reports why heat islands develop in urban areas, and how greening of cities can improve public health, and address climate concerns, sustainability, and liveability. In addition, we discuss urban planning, transport interventions, and novel technologies to assess external environmental exposures, e.g. using digital technologies, to promote heart healthy cities in the future. Lastly, we highlight new paradigms of integrative thinking such as the exposome and planetary health, challenging the one-exposure-one-health-outcome association and expand our understanding of the totality of human environmental exposures

Recessive <i>HYDIN</i> mutations cause primary ciliary dyskinesia without randomization of left-right body asymmetry

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder characterized by defective cilia and flagella motility. Chronic destructive-airway disease is caused by abnormal respiratory-tract mucociliary clearance. Abnormal propulsion of sperm flagella contributes to male infertility. Genetic defects in most individuals affected by PCD cause randomization of left-right body asymmetry; approximately half show situs inversus or situs ambiguous. Almost 70 years after the hy3 mouse possessing Hydin mutations was described as a recessive hydrocephalus model, we report HYDIN mutations in PCD- affected persons without hydrocephalus. By homozygosity mapping, we identified a PCD-associated locus, chromosomal region 16q21- q23, which contains HYDIN. However, a nearly identical 360 kb paralogous segment (HYDIN2) in chromosomal region 1q21.1 complicated mutational analysis. In three affected German siblings linked to HYDIN, we identified homozygous c.3985G>T mutations that affect an evolutionary conserved splice acceptor site and that subsequently cause aberrantly spliced transcripts predicting premature protein termination in respiratory cells. Parallel whole-exome sequencing identified a homozygous nonsense HYDIN mutation, c.922A>T (p.Lys307( *)), in six individuals from three Faroe Island PCD-affected families that all carried an 8.8 Mb shared haplotype across HYDIN, indicating an ancestral founder mutation in this isolated population. We demonstrate by electron microscopy tomography that, consistent with the effects of loss-of-function mutations, HYDIN mutant respiratory cilia lack the C2b projection of the central pair (CP) apparatus; similar findings were reported in Hydin-deficient Chlamydomonas and mice. High-speed videomicroscopy demonstrated markedly reduced beating amplitudes of respiratory cilia and stiff sperm flagella. Like the hy3 mouse model, all nine PCD-affected persons had normal body composition because nodal cilia function is apparently not dependent on the function of the CP apparatus

Socio-demographic, behavioural and cognitive correlates of work-related sitting time in German men and women

Background: Sitting time is ubiquitous for most adults in developed countries and is most prevalent in three domains: in the workplace, during transport and during leisure time. The correlates of prolonged sitting time in workplace settings are not well understood. Therefore, the aim of this study was to examine the gender-specific associations between the socio-demographic, behavioural and cognitive correlates of work-related sitting time. Methods: A cross-sectional sample of working German adults (n = 1515; 747 men; 43.5 ± 11.0 years) completed questionnaires regarding domain-specific sitting times and physical activity (PA) and answered statements concerning beliefs about sitting. To identify gender-specific correlates of work-related sitting time, we used a series of linear regressions. Results The overall median was 2 hours of work-related sitting time/day. Regression analyses showed for men (β = -.43) and for women (β = -.32) that work-related PA was negatively associated with work-related sitting time, but leisure-related PA was not a significant correlate. For women only, transport-related PA (β = -.07) was a negative correlate of work-related sitting time, suggesting increased sitting times during work with decreased PA in transport. Education and income levels were positively associated, and in women only, age (β = -.14) had a negative correlation with work-related sitting time. For both genders, TV-related sitting time was negatively associated with work-related sitting time. The only association with cognitive correlates was found in men for the belief ‘Sitting for long periods does not matter to me’ (β = .10) expressing a more positive attitude towards sitting with increasing sitting durations. Conclusions: The present findings show that in particular, higher educated men and women as well as young women are high-risk groups to target for reducing prolonged work-related sitting time. In addition, our findings propose considering increasing transport-related PA, especially in women, as well as promoting recreation-related PA in conjunction with efforts to reduce long work-related sitting times

A framework for parameter estimation and model selection from experimental data in systems biology using approximate Bayesian computation.

As modeling becomes a more widespread practice in the life sciences and biomedical sciences, researchers need reliable tools to calibrate models against ever more complex and detailed data. Here we present an approximate Bayesian computation (ABC) framework and software environment, ABC-SysBio, which is a Python package that runs on Linux and Mac OS X systems and that enables parameter estimation and model selection in the Bayesian formalism by using sequential Monte Carlo (SMC) approaches. We outline the underlying rationale, discuss the computational and practical issues and provide detailed guidance as to how the important tasks of parameter inference and model selection can be performed in practice. Unlike other available packages, ABC-SysBio is highly suited for investigating, in particular, the challenging problem of fitting stochastic models to data. In order to demonstrate the use of ABC-SysBio, in this protocol we postulate the existence of an imaginary reaction network composed of seven interrelated biological reactions (involving a specific mRNA, the protein it encodes and a post-translationally modified version of the protein), a network that is defined by two files containing 'observed' data that we provide as supplementary information. In the first part of the PROCEDURE, ABC-SysBio is used to infer the parameters of this system, whereas in the second part we use ABC-SysBio's relevant functionality to discriminate between two different reaction network models, one of them being the 'true' one. Although computationally expensive, the additional insights gained in the Bayesian formalism more than make up for this cost, especially in complex problems

Methods to Quantify Nanomaterial Association with, and Distribution across, the Blood-Brain Barrier in Vivo

The role and functional anatomy of the blood-brain barrier (BBB) is summarized to enable the investigator to appropriately address evaluation of nanomaterial interaction with, and distribution across, it into brain tissue (parenchyma). Transport mechanisms across the BBB are presented, in relation to nanomaterial physicochemical properties. Measures and test substances to assess BBB integrity/disruption/permeation are introduced, along with how they are used to interpret the results obtained with the presented methods. Experimental pitfalls and misinterpretation of results of studies of brain nanomaterial uptake are briefly summarized, that can be avoided with the methods presented in this chapter. Two methods are presented. The in situ brain perfusion technique is used to determine rate and extent of nanomaterial distribution into the brain. The capillary depletion method separates brain parenchymal tissue from the endothelial cells that contribute to the BBB. It is used to verify nanomaterial brain tissue entry. These methods are best used together, the latter refining the results obtained with the former. Details of the materials and equipment needed to conduct these methods, and description of the procedures and data interpretation, are provided

Plastidial Starch Phosphorylase in Sweet Potato Roots Is Proteolytically Modified by Protein-Protein Interaction with the 20S Proteasome

Post-translational regulation plays an important role in cellular metabolism. Earlier studies showed that the activity of plastidial starch phosphorylase (Pho1) may be regulated by proteolytic modification. During the purification of Pho1 from sweet potato roots, we observed an unknown high molecular weight complex (HX) showing Pho1 activity. The two-dimensional gel electrophoresis, mass spectrometry, and reverse immunoprecipitation analyses showed that HX is composed of Pho1 and the 20S proteasome. Incubating sweet potato roots at 45°C triggers a stepwise degradation of Pho1; however, the degradation process can be partially inhibited by specific proteasome inhibitor MG132. The proteolytically modified Pho1 displays a lower binding affinity toward glucose 1-phosphate and a reduced starch-synthesizing activity. This study suggests that the 20S proteasome interacts with Pho1 and is involved in the regulation of the catalytic activity of Pho1 in sweet potato roots under heat stress conditions