Blood pressure and cholesterol level checks as dynamic interrelated screening examinations

This study analysed the determinants of screening uptake for blood pressure and cholesterol level checks. Furthermore, it investigated the presence of possible spillover effects from one type of cardiovascular screening to another type of cardiovascular screening. A dynamic random effects bivariate panel probit model with initial conditions (Wooldridge-type estimator) was adopted for the estimation. The outcome variables were the participation in blood pressure and cholesterol level checks by individuals in a given year. The balanced panel sample of 21,138 observations was constructed from 1,626 individuals from the British Household Panel Survey (BHPS) between 1996 and 2008. The analysis showed the significance of past screening behaviour for both cardiovascular screening examinations. For both cardiovascular screening examinations state dependence exist. The study also shows a significant spillover effect of the cholesterol level check on the blood pressure check and vice versa. Also a poorer health status led to a higher uptake for both types of screening examinations. Changes in recommendations have to consider the fact that taking part in one type of cardiovascular screening examination can influence the decision to take part in the other type of cardiovascular screening examination

The role of the EP receptors for prostaglandin E2 in skin and skin cancer

One of the most common features of exposure of skin to ultraviolet (UV) light is the induction of inflammation, a contributor to tumorigenesis, which is characterized by the synthesis of cytokines, growth factors and arachidonic acid metabolites, including the prostaglandins (PGs). Studies on the role of the PGs in non-melanoma skin cancer (NMSC) have shown that the cyclooxygenase-2 (COX-2) isoform of the cyclooxygenases is responsible for the majority of the pathological effects of PGE2. In mouse skin models, COX-2 deficiency significantly protects against chemical carcinogen- or UV-induced NMSC while overexpression confers endogenous tumor promoting activity. Current studies are focused on identifying which of the G protein-coupled EP receptors mediate the tumor promotion/progression activities of PGE2 and the signaling pathways involved. As reviewed here, the EP1, EP2, and EP4 receptors, but not the EP3 receptor, contribute to NMSC development, albeit through different signaling pathways and with somewhat different outcomes. The signaling pathways activated by the specific EP receptors are context specific and likely depend on the level of PGE2 synthesis, the differential levels of expression of the different EP receptors, as well as the levels of expression of other interacting receptors. Understanding the role and mechanisms of action of the EP receptors potentially offers new targets for the prevention or therapy of NMSCs

Statistical and integrative system-level analysis of DNA methylation data

Epigenetics plays a key role in cellular development and function. Alterations to the epigenome are thought to capture and mediate the effects of genetic and environmental risk factors on complex disease. Currently, DNA methylation is the only epigenetic mark that can be measured reliably and genome-wide in large numbers of samples. This Review discusses some of the key statistical challenges and algorithms associated with drawing inferences from DNA methylation data, including cell-type heterogeneity, feature selection, reverse causation and system-level analyses that require integration with other data types such as gene expression, genotype, transcription factor binding and other epigenetic information

GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans

A saturated map of common genetic variants associated with human height

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes(1). Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel(2)) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants

Persistence of silver nanoparticles in the rat lung: Influence of dose, size, and chemical composition

Increasing silver nanoparticle (AgNP) use in sprays, consumer products and medical devices has raised concerns about potential health effects. While previous studies have investigated AgNPs, most were limited to a single particle size or surface coating. In this study, we investigated the effect of size, surface coating and dose on the persistence of silver in the lung following exposure to AgNP. Adult male rats were intratracheally instilled with four different AgNPs: 20 or 110nm in size and coated with either citrate or polyvinylpyrrolidone (PVP) at 0.5 or 1.0mg/kg doses. Silver retention was assessed in the lung at 1, 7 and 21 days post exposure. ICP-MS quantification demonstrated that citrate coated AgNPs persisted in the lung to 21 days with greater than 90% retention, while PVP coated AgNP had less than 30% retention. Localization of silver in lung tissue at one day post exposure demonstrated decreased silver in proximal airways exposed to 110nm particles compared with 20nm AgNPs. In terminal bronchioles one day post exposure, silver was localized to surface epithelium but was more prominent in the basement membrane at 7 days. Silver positive macrophages in bronchoalveolar lavage fluid decreased more quickly after exposure to particles coated with PVP. We conclude that PVP coated AgNPs had less retention in the lung tissue over time and larger particles were more rapidly cleared from large airways than smaller particles. The 20nm citrate particles the greatest effect; increasing lung macrophages even 21days after exposure and resulted in the greatest silver retention in lung tissue

Bacterial and yeast flora of root surface caries in elderly, ethnic Chinese

OBJECTIVES: Root caries is emerging as a significant problem in the middle aged and elderly. As little data is available on the microbiology of root caries in Chinese cohorts, we evaluated 30 such lesions in elderly, institutionalized, ethnic Chinese. METHODS: Samples of carious dentine were aseptically taken from root caries lesions of 18 subjects (five males and 13 females, mean age 79.67 ± 8.57). The cultivable bacteria, both aerobic and anaerobic, were isolated and identified using standard methods and commercial identification kits. The yeasts were isolated on Sabouraud's agar and identified using the API system. RESULTS: The main findings were: (1) of the total isolates, 91.09% were Gram-positive and 8.91% were Gram-negative microorganisms; (2) the proportions of cocci and rods were 36.68 and 63.31%, respectively; (3) the predominant groups of organisms isolated were Streptococcus spp., Lactobacillus spp., Staphylococcus spp. and Actinomyces spp. with isolation frequencies of 100, 90.00, 73.33 and 63.33%, respectively; (4) the isolation frequency of yeasts belonging to Candida spp. (63.33%) was notably high although the proportion of yeasts within each sample was low (0.01%). Candida dubliniensis, a newly identified yeast species particularly prevalent in HIV infection, comprised 14.29% of yeasts. CONCLUSIONS: This study provides baseline information on the microbiologic features of root caries in the elderly, ethnic Chinese. Whilst our data on the most predominant bacteria isolated in root caries concur with those from other regions of the world the isolation of C. dubliniensis from these lesions has not been documented before.link_to_subscribed_fulltex