Accurate masses and radii of normal stars: modern results and applications

This paper presents and discusses a critical compilation of accurate, fundamental determinations of stellar masses and radii. We have identified 95 detached binary systems containing 190 stars (94 eclipsing systems, and alpha Centauri) that satisfy our criterion that the mass and radius of both stars be known to 3% or better. To these we add interstellar reddening, effective temperature, metal abundance, rotational velocity and apsidal motion determinations when available, and we compute a number of other physical parameters, notably luminosity and distance. We discuss the use of this information for testing models of stellar evolution. The amount and quality of the data also allow us to analyse the tidal evolution of the systems in considerable depth, testing prescriptions of rotational synchronisation and orbital circularisation in greater detail than possible before. The new data also enable us to derive empirical calibrations of M and R for single (post-) main-sequence stars above 0.6 M(Sun). Simple, polynomial functions of T(eff), log g and [Fe/H] yield M and R with errors of 6% and 3%, respectively. Excellent agreement is found with independent determinations for host stars of transiting extrasolar planets, and good agreement with determinations of M and R from stellar models as constrained by trigonometric parallaxes and spectroscopic values of T(eff) and [Fe/H]. Finally, we list a set of 23 interferometric binaries with masses known to better than 3%, but without fundamental radius determinations (except alpha Aur). We discuss the prospects for improving these and other stellar parameters in the near future.Comment: 56 pages including figures and tables. To appear in The Astronomy and Astrophysics Review. Ascii versions of the tables will appear in the online version of the articl

Botulinum Neurotoxin Devoid of Receptor Binding Domain Translocates Active Protease

Clostridium botulinum neurotoxin (BoNT) causes flaccid paralysis by disabling synaptic exocytosis. Intoxication requires the tri-modular protein to undergo conformational changes in response to pH and redox gradients across endosomes, leading to the formation of a protein-conducting channel. The ∼50 kDa light chain (LC) protease is translocated into the cytosol by the ∼100 kDa heavy chain (HC), which consists of two modules: the N-terminal translocation domain (TD) and the C-terminal Receptor Binding Domain (RBD). Here we exploited the BoNT modular design to identify the minimal requirements for channel activity and LC translocation in neurons. Using the combined detection of substrate proteolysis and single-channel currents, we showed that a di-modular protein consisting only of LC and TD was sufficient to translocate active protease into the cytosol of target cells. The RBD is dispensable for cell entry, channel activity, or LC translocation; however, it determined a pH threshold for channel formation. These findings indicate that, in addition to its individual functions, each module acts as a chaperone for the others, working in concert to achieve productive intoxication

An unusual cause of granulomatous disease

BACKGROUND: Chronic granulomatous disease (CGD) is an inherited disorder of phagocytic cells caused by an inability to generate active microbicidal oxygen species required kill certain types of fungi and bacteria. This leads to recurrent life-threatening bacterial and fungal infections with tissue granuloma formation. CASE PRESENTATION: We describe a case of X-linked Chronic granulomatous disease (CGD) diagnosed in an 18-year-old male. He initially presented with granulomatous disease mimicking sarcoidosis and was treated with corticosteroids. He subsequently developed Burkholderia cepacia complex pneumonia and further investigation confirmed a diagnosis of CGD. CONCLUSION: Milder phenotypes of CGD are now being recognised. CGD should be considered in patients of any age with granulomatous diseases, especially if there is a history of recurrent or atypical infection

Influence of Age on Upper Arm Cuff Blood Pressure Measurement

Blood pressure (BP) is a leading global risk factor. Increasing age is related to changes in cardiovascular physiology that could influence cuff BP measurement, but this has never been examined systematically and was the aim of this study. Cuff BP was compared with invasive aortic BP across decades of age (from 40 to 89 years) using individual-level data from 31 studies (1674 patients undergoing coronary angiography) and 22 different cuff BP devices (19 oscillometric, 1 automated auscultation, 2 mercury sphygmomanometry) from the Invasive Blood Pressure Consortium. Subjects were aged 64±11 years, and 32% female. Cuff systolic BP overestimated invasive aortic systolic BP in those aged 40 to 49 years, but with each older decade of age, there was a progressive shift toward increasing underestimation of aortic systolic BP (P<0.0001). Conversely, cuff diastolic BP overestimated invasive aortic diastolic BP, and this progressively increased with increasing age (P<0.0001). Thus, there was a progressive increase in cuff pulse pressure underestimation of invasive aortic PP with increasing decades of age (P<0.0001). These age-related trends were observed across all categories of BP control. We conclude that cuff BP as an estimate of aortic BP was substantially influenced by increasing age, thus potentially exposing older people to greater chance for misdiagnosis of the true risk related to BP

Prevalence of Helicobacter pylori infection and associated factors among adults in Southern Brazil: a population-based cross-sectional study

BACKGROUND: Helicobacter pylori (Hp) infection is associated with several upper gastrointestinal disorders. Local data on the epidemiology of the infection are scarce in Brazil. The purpose of this study is to measure the prevalence rate and to explore the associated factors among the adult population living in Pelotas, a southern Brazilin city. METHODS: This was a population-based cross-sectional study. Through a multi-stage sampling method all individuals 20 years and over living at the selected households at the urban area of the city were interviewed regarding past and current socio-economic indicators; demographic characteristics; nutritional and behavioural habits; and history of upper gastrointestinal symptoms.Hp infection was ascertained through the (13)C-UBT. Due to the high prevalence, data were analysed through robust Poisson regression. All analyses took into account the family clustering of the data. RESULTS: Among 563 eligible individuals, 363 agreed to perform the (13)C-UBT (refusal rate of 35.5%). Refusals were associated with female sex, consumption of mate drinking, and presence of upper gastrointestinal symptoms. The prevalence rate of H. pylori infection was 63.4% (95%CI 59.3%–69.3%). In crude analyses, prevalence was associated with increasing age, non-white skin colour, lower current family income, lower education level, higher size of the family, low socio-economic conditions in childhood, higher number of siblings and attendance to day-care centres in childhood, and presence of dyspeptic symptoms. In adjusted analysis the level of education of the father was inversely associated with the infection, whereas number of siblings and attendance to day-care centre in childhood were directly associated with it. Non-white skin colour remained significantly associated with increased prevalence even after allowing for past and current socio-economic characteristics, age and sex. Compared to non-symptomatic individuals, those reporting dyspeptic symptoms presented a higher prevalence of the infection even after allowing for current and past socio-economic conditions, ethnicity, age, and sex. CONCLUSION: Hp infection is as common among adults in southern Brazil as it is in other developing countries. Socio-economic conditions in childhood besides ethnicity and presence of dyspeptic symptoms were the factors significantly associated with the infection

Excessive Food Intake, Obesity and Inflammation Process in Zucker fa/fa Rat Pancreatic Islets

Inappropriate food intake-related obesity and more importantly, visceral adiposity, are major risk factors for the onset of type 2 diabetes. Evidence is emerging that nutriment-induced β-cell dysfunction could be related to indirect induction of a state of low grade inflammation. Our aim was to study whether hyperphagia associated obesity could promote an inflammatory response in pancreatic islets leading to ß-cell dysfunction. In the hyperphagic obese insulin resistant male Zucker rat, we measured the level of circulating pro-inflammatory cytokines and estimated their production as well as the expression of their receptors in pancreatic tissue and β-cells. Our main findings concern intra-islet pro-inflammatory cytokines from fa/fa rats: IL-1β, IL-6 and TNFα expressions were increased; IL-1R1 was also over-expressed with a cellular redistribution also observed for IL-6R. To get insight into the mechanisms involved in phenotypic alterations, abArrays were used to determine the expression profile of proteins implicated in different membrane receptors signaling, apoptosis and cell cycle pathways. Despite JNK overexpression, cell viability was unaffected probably because of decreases in cleaved caspase3 as well as in SMAC/DIABLO and APP, involved in the induction and amplification of apoptosis. Concerning β-cell proliferation, decreases in important cell cycle regulators (Cyclin D1, p35) and increased expression of SMAD4 probably contribute to counteract and restrain hyperplasia in fa/fa rat islets. Finally and probably as a result of IL-1β and IL-1R1 increased expressions with sub-cellular redistribution of the receptor, islets from fa/fa rats were found more sensitive to both stimulating and inhibitory concentrations of the cytokine; this confers some physiopathological relevance to a possible autocrine regulation of β-cell function by IL-1β. These results support the hypothesis that pancreatic islets from prediabetic fa/fa rats undergo an inflammatory process. That the latter could contribute to β-cell hyperactivity/proliferation and possibly lead to progressive β-cell failure in these animals, deserves further investigations

HemaMax™, a Recombinant Human Interleukin-12, Is a Potent Mitigator of Acute Radiation Injury in Mice and Non-Human Primates

HemaMax, a recombinant human interleukin-12 (IL-12), is under development to address an unmet medical need for effective treatments against acute radiation syndrome due to radiological terrorism or accident when administered at least 24 hours after radiation exposure. This study investigated pharmacokinetics, pharmacodynamics, and efficacy of m-HemaMax (recombinant murine IL-12), and HemaMax to increase survival after total body irradiation (TBI) in mice and rhesus monkeys, respectively, with no supportive care. In mice, m-HemaMax at an optimal 20 ng/mouse dose significantly increased percent survival and survival time when administered 24 hours after TBI between 8–9 Gy (p<0.05 Pearson's chi-square test). This survival benefit was accompanied by increases in plasma interferon-γ (IFN-γ) and erythropoietin levels, recovery of femoral bone hematopoiesis characterized with the presence of IL-12 receptor β2 subunit–expressing myeloid progenitors, megakaryocytes, and osteoblasts. Mitigation of jejunal radiation damage was also examined. At allometrically equivalent doses, HemaMax showed similar pharmacokinetics in rhesus monkeys compared to m-HemaMax in mice, but more robustly increased plasma IFN-γ levels. HemaMax also increased plasma erythropoietin, IL-15, IL-18, and neopterin levels. At non-human primate doses pharmacologically equivalent to murine doses, HemaMax (100 ng/Kg and 250 ng/Kg) administered at 24 hours after TBI (6.7 Gy/LD50/30) significantly increased percent survival of HemaMax groups compared to vehicle (p<0.05 Pearson's chi-square test). This survival benefit was accompanied by a significantly higher leukocyte (neutrophils and lymphocytes), thrombocyte, and reticulocyte counts during nadir (days 12–14) and significantly less weight loss at day 12 compared to vehicle. These findings indicate successful interspecies dose conversion and provide proof of concept that HemaMax increases survival in irradiated rhesus monkeys by promoting hematopoiesis and recovery of immune functions and possibly gastrointestinal functions, likely through a network of interactions involving dendritic cells, osteoblasts, and soluble factors such as IL-12, IFN-γ, and cytoprotectant erythropoietin