Genetic variation in the HLA region is associated with susceptibility to herpes zoster.

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine

Sister species diverge in modality-specific courtship signal form and function

Understanding the relative importance of different sources of selection (e.g., the environment, social/sexual selection) on the divergence or convergence of reproductive communication can shed light on the origin, maintenance, or even disappearance of species boundaries. Using a multistep approach, we tested the hypothesis that two presumed sister species of wolf spider with overlapping ranges and microhabitat use, yet differing degrees of sexual dimorphism, have diverged in their reliance on modality- specific courtship signaling. We predicted that male Schizocosa crassipalpata (no ornamentation) rely predominantly on diet-dependent vibratory signaling for mating success. In contrast, we predicted that male S. bilineata (black foreleg brushes) rely on diet-dependent visual signaling. We first tested and corroborated the sister-species relationship between S. crassipalpata and S. bilineata using phylogenomic scale data. Next, we tested for species-specific, diet-dependent vibratory and visual signaling by manipulating subadult diet and subsequently quantifying adult morphology and mature male courtship signals. As predicted, vibratory signal form was diet-dependent in S. crassipalpata, while visual ornamentation (brush area) was diet-dependent in S. bilineata. We then compared the species-specific reliance on vibratory and visual signaling by recording mating across artificially manipulated signaling environments (presence/absence of each modality in a 2 × 2 full factorial design). In accordance with our diet dependence results for S. crassipalpata, the presence of vibratory signaling was important for mating success. In contrast, the light and vibratory environment interacted to influence mating success in S. bilineata, with vibratory signaling being important only in the absence of light. We found no differences in overall activity patterns. Given that these species overlap in much of their range and microhabitat use, we suggest that competition for signaling space may have led to the divergence and differential use of sensory modalities between these sister species

First International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions).

The purpose of this study is to obtain a consensus for the therapy of B3 lesions. The first International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions) including atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), papillary lesions (PL), benign phyllodes tumors (PT), and radial scars (RS) took place in January 2016 in Zurich, Switzerland organized by the International Breast Ultrasound School and the Swiss Minimally Invasive Breast Biopsy group-a subgroup of the Swiss Society of Senology. Consensus recommendations for the management and follow-up surveillance of these B3 lesions were developed and areas of research priorities were identified. The consensus recommendation for FEA, LN, PL, and RS diagnosed on core needle biopsy or vacuum-assisted biopsy (VAB) is to therapeutically excise the lesion seen on imaging by VAB and no longer by open surgery, with follow-up surveillance imaging for 5 years. The consensus recommendation for ADH and PT is, with some exceptions, therapeutic first-line open surgical excision. Minimally invasive management of selected B3 lesions with therapeutic VAB is acceptable as an alternative to first-line surgical excision

Fabrication and characterization of dual function nanoscale pH-scanning ion conductance microscopy (SICM) probes for high resolution pH mapping

The easy fabrication and use of nanoscale dual function pH-scanning ion conductance microscopy (SICM) probes is reported. These probes incorporate an iridium oxide coated carbon electrode for pH measurement and an SICM barrel for distance control, enabling simultaneous pH and topography mapping. These pH-SICM probes were fabricated rapidly from laser pulled theta quartz pipets, with the pH electrode prepared by in situ carbon filling of one of the barrels by the pyrolytic decomposition of butane, followed by electrodeposition of a thin layer of hydrous iridium oxide. The other barrel was filled with an electrolyte solution and Ag/AgCl electrode as part of a conductance cell for SICM. The fabricated probes, with pH and SICM sensing elements typically on the 100 nm scale, were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and various electrochemical measurements. They showed a linear super-Nernstian pH response over a range of pH (pH 2–10). The capability of the pH-SICM probe was demonstrated by detecting both pH and topographical changes during the dissolution of a calcite microcrystal in aqueous solution. This system illustrates the quantitative nature of pH-SICM imaging, because the dissolution process changes the crystal height and interfacial pH (compared to bulk), and each is sensitive to the rate. Both measurements reveal similar dissolution rates, which are in agreement with previously reported literature values measured by classical bulk methods

Strategies for Surveillance of Pediatric Hemolytic Uremic Syndrome: Foodborne Diseases Active Surveillance Network (FoodNet), 2000–2007

Background. Postdiarrheal hemolytic uremic syndrome (HUS) is the most common cause of acute kidney failure among US children. The Foodborne Diseases Active Surveillance Network (FoodNet) conducts population-based surveillance of pediatric HUS to measure the incidence of disease and to validate surveillance trends in associated Shiga toxin–producing Escherichia coli (STEC) O157 infection

The influence of calcium and magnesium in drinking water and diet on cardiovascular risk factors in individuals living in hard and soft water areas with differences in cardiovascular mortality

BACKGROUND: The role of water hardness as a risk factor for cardiovascular disease has been widely investigated and evaluated as regards regional differences in cardiovascular disease. This study was performed to evaluate the relation between calcium and magnesium in drinking water and diet and risk factors for cardiovascular disease in individuals living in hard and soft water areas with considerable differences in cardiovascular mortality. METHODS: A random sample of 207 individuals living in two municipalities characterised by differences in cardiovascular mortality and water hardness was invited for an examination including a questionnaire about health, social and living conditions and diet. Intake of magnesium and calcium was calculated from the diet questionnaire with special consideration to the use of local water. Household water samples were delivered by each individual and were analysed for magnesium and calcium. RESULTS: In the total sample, there were positive correlations between the calcium content in household water and systolic blood pressure (SBP) and negative correlations with s-cholesterol and s-LDL-cholesterol. No correlation was seen with magnesium content in household water to any of the risk factors. Calcium content in diet showed no correlation to cardiovascular risk factors. Magnesium in diet was positively correlated to diastolic blood pressure (DBP). In regression analyses controlled for age and sex 18.5% of the variation in SBP was explained by the variation in BMI, HbA1c and calcium content in water. Some 27.9% of the variation in s-cholesterol could be explained by the variation in s-triglycerides (TG), and calcium content in water. CONCLUSIONS: This study of individuals living in soft and hard water areas showed significant correlations between the content of calcium in water and major cardiovascular risk factors. This was not found for magnesium in water or calcium or magnesium in diet. Regression analyses indicated that calcium content in water could be a factor in the complexity of relationships and importance of cardiovascular risk factors. From these results it is not possible to conclude any definite causal relation and further research is needed

Endogenous sex hormones and prostate cancer: a quantitative review of prospective studies

This paper presents a quantitative review of the data from eight prospective epidemiological studies, comparing mean serum concentrations of sex hormones in men who subsequently developed prostate cancer with those in men who remained cancer free. The hormones reviewed have been postulated to be involved in the aetiology of prostate cancer: androgens and their metabolites testosterone (T), non-SHBG-bound testosterone (non-SHBG-bound T), di-hydrotestosterone (DHT), androstanediol glucuronide (A-diol-g), androstenedione (A-dione), dehydroepiandrosterone sulphate (DHEAS), sex hormone binding globulin (SHBG), the oestrogens, oestrone and oestradiol, luteinizing hormone (LH) and prolactin. The ratio of the mean hormone concentration in prostate cancer cases to that of controls (and its 95% confidence interval (CI)) was calculated for each study, and the results summarized by calculating the weighted average of the log ratios. No differences in the average concentrations of the hormones were found between prostate cancer cases and controls, with the possible exception of A-diol-g which exhibited a 5% higher mean serum concentration among cases relative to controls (ratio 1.05, 95% CI 1.00-1.11), based on 644 cases and 1048 controls. These data suggest that there are no large differences in circulating hormones between men who subsequently go on to develop prostate cancer and those who remain free of the disease. Further research is needed to substantiate the small difference found in A-diol-g concentrations between prostate cancer cases and controls

The Tuberculin Skin Test versus QuantiFERON TB Gold® in Predicting Tuberculosis Disease in an Adolescent Cohort Study in South Africa

Setting: This study was conducted in a high tuberculosis (TB) burden area in Worcester, South Africa, with a notified all TB incidence rate of 1,400/100,000. Main Objective: To compare the predictive value of a baseline tuberculin skin test (TST) with that of the QuantiFERON TB Gold (In-tube) assay (QFT) for subsequent microbiologically confirmed TB disease among adolescents. Methods: Adolescents aged 12-18 years were recruited from high schools in the study area. At baseline, blood was drawn for QFT and a TST administered. Participants were followed up for up to 3.8 years for incident TB disease (median 2.4 years). Results: After exclusions, 5244 (82.4%) of 6,363 adolescents enrolled, were analysed. The TB incidence rate was 0.60 cases per 100 person years (pyrs) (95% CI 0.43-0.82) for baseline TST positive (>= 5 mm) participants and 0.64 cases per 100 pyrs (95% CI 0.45-0.87) for baseline QFT positive participants. TB incidence rates were 0.22 per 100 pyrs (0.11-0.39) and 0.22 per 100 pyrs (0.12-0.38) among those with a negative baseline TST and QFT respectively. Sensitivity for incident TB disease was 76.9% for TST and 75.0% for QFT (p = 0.81). Positive predictive value was 1.4% for TST and 1.5% for QFT. Conclusion: Positive TST and QFT tests were moderately sensitive predictors of progression to microbiologically confirmed TB disease. There was no significant difference in the predictive ability of these tests for TB disease amongst adolescents in this high burden setting. Therefore, these findings do not support use of QFT in preference to TST to predict the risk of TB disease in this study populatio