Area-level and individual correlates of active transportation among adults in Germany: A population-based multilevel study

This study aimed at estimating the prevalence in adults of complying with the aerobic physical activity (PA) recommendation through transportation-related walking and cycling. Furthermore, potential determinants of transportation-related PA recommendation compliance were investigated. 10,872 men and 13,144 women aged 18 years or older participated in the cross-sectional 'German Health Update 2014/15 - EHIS' in Germany. Transportation-related walking and cycling were assessed using the European Health Interview Survey-Physical Activity Questionnaire. Three outcome indicators were constructed: walking, cycling, and total active transportation (>= 600 metabolic equivalent, MET-min/week). Associations were analyzed using multilevel regression analysis. Forty-two percent of men and 39% of women achieved >= 600 MET-min/week with total active transportation. The corresponding percentages for walking were 27% and 28% and for cycling 17% and 13%, respectively. Higher population density, older age, lower income, higher work-related and leisure-time PA, not being obese, and better self-perceived health were positively associated with transportation-related walking and cycling and total active transportation among both men and women. The promotion of walking and cycling among inactive people has great potential to increase PA in the general adult population and to comply with PA recommendations. Several correlates of active transportation were identified which should be considered when planning public health policies and interventions

Nuclear receptors in vascular biology

Nuclear receptors sense a wide range of steroids and hormones (estrogens, progesterone, androgens, glucocorticoid, and mineralocorticoid), vitamins (A and D), lipid metabolites, carbohydrates, and xenobiotics. In response to these diverse but critically important mediators, nuclear receptors regulate the homeostatic control of lipids, carbohydrate, cholesterol, and xenobiotic drug metabolism, inflammation, cell differentiation and development, including vascular development. The nuclear receptor family is one of the most important groups of signaling molecules in the body and as such represent some of the most important established and emerging clinical and therapeutic targets. This review will highlight some of the recent trends in nuclear receptor biology related to vascular biology

What Do Men Want from a Health Screening Mobile App? A Qualitative Study.

There is a lack of mobile app which aims to improve health screening uptake developed for men. As part of the study to develop an effective mobile app to increase health screening uptake in men, we conducted a needs assessment to find out what do men want from a health screening mobile app. In-depth interviews and focus group discussions were conducted with 31 men from a banking institution in Kuala Lumpur. The participants were purposely sampled according to their job position, age, ethnicity and screening status. The recruitment was stopped once data saturation was achieved. The audio-recorded interviews were transcribed verbatim and analyzed using thematic approach. Three themes emerged from the analysis and they were: content, feature and dissemination. In terms of the content, men wanted the app to provide information regarding health screening and functions that can assess their health; which must be personalized to them and are trustable. The app must have user-friendly features in terms of information delivery, ease of use, attention allocation and social connectivity. For dissemination, men proposed that advertisements, recommendations by health professionals, providing incentive and integrating the app as into existing systems may help to increase the dissemination of the app. This study identified important factors that need to be considered when developing a mobile app to improve health screening uptake. Future studies on mobile app development should elicit users' preference and need in terms of its content, features and dissemination strategies to improve the acceptability and the chance of successful implementation

Pregnane X receptor regulates drug metabolism and transport in the vasculature and protects from oxidative stress

Aims Circulating endogenous, dietary and foreign chemicals can contribute to vascular dysfunction. The mechanism by which the vasculature protects itself from these chemicals is unknown. This study investigates whether the pregnane X receptor (PXR), the major transcriptional regulator of hepatic drug metabolism and transport that responds to such xenobiotics, mediates vascular protection by co-ordinating a defence gene program in the vasculature.Methods and Results PXR was detected in primary human and rat aortic endothelial and smooth muscle cells and blood vessels including human and rat aorta. Metabolic PXR target genes cytochrome P450 3A, 2B, 2C and glutathione-S-transferase mRNA and activity were induced by PXR ligands in rodent and human vascular cells and absent in the aortas from PXR null mice stimulated in vivo or in rat aortic smooth muscle cells expressing dominant negative PXR. Activation of aortic PXR by classical agonists had several protective effects; increased xenobiotic metabolism demonstrated by bio-activation of the pro-drug clopidogrel, which reduced adenosine diphosphate-induced platelet aggregation; increased expression of multidrug resistance protein 1, mediating chemical efflux from the vasculature; and protection from reactive oxygen species-mediated cell death.Conclusions PXR co-ordinately up-regulates drug metabolism, transport and anti-oxidant genes to protect the vasculature from endogenous and exogenous insults, thus representing a novel gatekeeper for vascular defence

Federated Learning for Breast Density Classification: A Real-World Implementation

Building robust deep learning-based models requires large quantities of diverse training data. In this study, we investigate the use of federated learning (FL) to build medical imaging classification models in a real-world collaborative setting. Seven clinical institutions from across the world joined this FL effort to train a model for breast density classification based on Breast Imaging, Reporting & Data System (BI-RADS). We show that despite substantial differences among the datasets from all sites (mammography system, class distribution, and data set size) and without centralizing data, we can successfully train AI models in federation. The results show that models trained using FL perform 6.3% on average better than their counterparts trained on an institute's local data alone. Furthermore, we show a 45.8% relative improvement in the models' generalizability when evaluated on the other participating sites' testing data.Comment: Accepted at the 1st MICCAI Workshop on "Distributed And Collaborative Learning"; add citation to Fig. 1 & 2 and update Fig.

Towards Customary Legal Empowerment

Rule of Law and Development: Formation, Implementation and Improvement of Law and Governance in Developing Countrie

P2 receptors are involved in the mediation of motivation-related behavior

The importance of purinergic signaling in the intact mesolimbic–mesocortical circuit of the brain of freely moving rats is reviewed. In the rat, an endogenous ADP/ATPergic tone reinforces the release of dopamine from the axon terminals in the nucleus accumbens as well as from the somatodendritic region of these neurons in the ventral tegmental area, as well as the release of glutamate, probably via P2Y1 receptor stimulation. Similar mechanisms may regulate the release of glutamate in both areas of the brain. Dopamine and glutamate determine in concert the activity of the accumbal GABAergic, medium-size spiny neurons thought to act as an interface between the limbic cortex and the extrapyramidal motor system. These neurons project to the pallidal and mesencephalic areas, thereby mediating the behavioral reaction of the animal in response to a motivation-related stimulus. There is evidence that extracellular ADP/ATP promotes goal-directed behavior, e.g., intention and feeding, via dopamine, probably via P2Y1 receptor stimulation. Accumbal P2 receptor-mediated glutamatergic mechanisms seem to counteract the dopaminergic effects on behavior. Furthermore, adaptive changes of motivation-related behavior, e.g., by chronic succession of starvation and feeding or by repeated amphetamine administration, are accompanied by changes in the expression of the P2Y1 receptor, thought to modulate the sensitivity of the animal to respond to certain stimuli

Generational Association Studies of Dopaminergic Genes in Reward Deficiency Syndrome (RDS) Subjects: Selecting Appropriate Phenotypes for Reward Dependence Behaviors

Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS). RDS results from a dysfunction in the “brain reward cascade,” a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic). Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function. We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]). Methodology: We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms). Data related to RDS behaviors were collected on these subjects plus 13 deceased family members. Results: Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015) more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32) and 47.8% of Family B subjects (11 of 23). No significant differences were found between the experimental and control positive rates for the other variants. Conclusions: Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific “reward” phenotype may be a paradigm shift in future association and linkage studies involving dopaminergic polymorphisms and other neurotransmitter gene candidates