TLR9 activation dampens the early inflammatory response to paracoccidioides brasiliensis, Impacting host survival

Background: Paracoccidioides brasiliensis causes paracoccidioidomycosis, one of the most prevalent systemic mycosis in Latin America. Thus, understanding the characteristics of the protective immune response to P. brasiliensis is of interest, as it may reveal targets for disease control. The initiation of the immune response relies on the activation of pattern recognition receptors, among which are TLRs. Both TLR2 and TLR4 have been implicated in the recognition of P. brasiliensis and regulation of the immune response. However, the role of TLR9 during the infection by this fungus remains unclear.J.F. Menino was supported by a grant from Fundacao para a Ciencia e Tecnologia (FCT), Portugal (SFRH/BD/33446/2008). This work was supported by a grant from FCT (PTDC/BIA-MIC/108309/2008). M. Saraiva is a Ciencia 2007 fellow and M. Sturme is a Ciencia 2008 fellow. We would also like to thank FAPESP (Fundacao para Amparo a Pesquisa do Estado de Sao Paulo) and CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) for financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Moderate beer consumption does not change early or mature atherosclerosis in mice

BACKGROUND: Although the consumption of wine in particular has been associated with a lower risk of atherothrombotic cardiovascular disease, systematic reviews differ as to the relative protective effect of beer, wine and spirits. Two previous studies showed that red wine reduces fatty streak formation (early atherosclerosis) but not mature atherosclerosis in apolipoprotein (apo) E-deficient (apoE-/-) mice. AIM OF THE STUDY: To determine whether a moderate beer intake would affect early and mature atherosclerotic lesion formation using control C57BL/6 and apoE-/- mice, respectively, as models. METHODS: Control C57BL/6 and apoE-/- mice were randomized to receive either water, ethanol, mild beer, dark beer or ethanol-free beer. The level of beer was designed to approximate the alcohol intake currently believed to be beneficial in reducing human vascular risk. Control C57BL/6 mice were fed a Western diet for 24 weeks, and apoE-/- mice a chow diet for 12 weeks. At the end of the trial period, mice were euthanized and atherosclerotic lesions quantified. Plasma lipid concentrations were also measured. RESULTS: The amount of atherosclerosis and average number of lesions in the proximal aortic region did not differ among groups in control C57BL/6 mice (p = 0.32 and p = 0.29, respectively) and apoE-/- mice (p = 0.19 and p = 0.59, respectively). No consistent differences were observed in plasma lipid and lipoprotein concentrations among water, ethanol and beer groups. CONCLUSIONS: Moderate beer consumption does not change the development of early or mature atherosclerosis in mice. Our findings do not support the hypothesis of an anti-atherogenic effect of beer. Other potential protective actions of moderate beer consumption such as plaque stabilization, a reduction in plaque intrinsic thrombogenicity, or a reduction in the systemic propensity to thrombosis, remain to be studied

The evolutionary signal in metagenome phyletic profiles predicts many gene functions

Background. The function of many genes is still not known even in model organisms. An increasing availability of microbiome DNA sequencing data provides an opportunity to infer gene function in a systematic manner. Results. We evaluated if the evolutionary signal contained in metagenome phyletic profiles (MPP) is predictive of a broad array of gene functions. The MPPs are an encoding of environmental DNA sequencing data that consists of relative abundances of gene families across metagenomes. We find that such MPPs can accurately predict 826 Gene Ontology functional categories, while drawing on human gut microbiomes, ocean metagenomes, and DNA sequences from various other engineered and natural environments. Overall, in this task, the MPPs are highly accurate, and moreover they provide coverage for a set of Gene Ontology terms largely complementary to standard phylogenetic profiles, derived from fully sequenced genomes. We also find that metagenomes approximated from taxon relative abundance obtained via 16S rRNA gene sequencing may provide surprisingly useful predictive models. Crucially, the MPPs derived from different types of environments can infer distinct, non-overlapping sets of gene functions and therefore complement each other. Consistently, simulations on > 5000 metagenomes indicate that the amount of data is not in itself critical for maximizing predictive accuracy, while the diversity of sampled environments appears to be the critical factor for obtaining robust models. Conclusions. In past work, metagenomics has provided invaluable insight into ecology of various habitats, into diversity of microbial life and also into human health and disease mechanisms. We propose that environmental DNA sequencing additionally constitutes a useful tool to predict biological roles of genes, yielding inferences out of reach for existing comparative genomics approaches

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Recent developments in genetics and medically assisted reproduction : from research to clinical applications

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.Peer reviewe

Large-scale unit commitment under uncertainty: an updated literature survey

The Unit Commitment problem in energy management aims at finding the optimal production schedule of a set of generation units, while meeting various system-wide constraints. It has always been a large-scale, non-convex, difficult problem, especially in view of the fact that, due to operational requirements, it has to be solved in an unreasonably small time for its size. Recently, growing renewable energy shares have strongly increased the level of uncertainty in the system, making the (ideal) Unit Commitment model a large-scale, non-convex and uncertain (stochastic, robust, chance-constrained) program. We provide a survey of the literature on methods for the Uncertain Unit Commitment problem, in all its variants. We start with a review of the main contributions on solution methods for the deterministic versions of the problem, focussing on those based on mathematical programming techniques that are more relevant for the uncertain versions of the problem. We then present and categorize the approaches to the latter, while providing entry points to the relevant literature on optimization under uncertainty. This is an updated version of the paper "Large-scale Unit Commitment under uncertainty: a literature survey" that appeared in 4OR 13(2), 115--171 (2015); this version has over 170 more citations, most of which appeared in the last three years, proving how fast the literature on uncertain Unit Commitment evolves, and therefore the interest in this subject

Early results of treatment for congenital clubfoot using the Ponseti method

The purpose of this study was to evaluate the early results of the Ponseti method in reducing extensive corrective surgery rates for congenital idiopathic clubfoot in patients treated in Children’s Orthopaedic Clinic and Rehabilitation Department Medical University of Lublin between the years 2007–2011. Thirty-five patients with 47 idiopathic clubfeet were followed prospectively while being managed with the Ponseti method. Clubfoot severity was graded with use of the Dimeglio system. The initial correction was achieved, and early results were measured by using Pirani scoring method

Change in bias in self-reported body mass index in Australia between 1995 and 2008 and the evaluation of correction equations

<p>Abstract</p> <p>Background</p> <p>Many studies have documented the bias in body mass index (BMI) determined from self-reported data on height and weight, but few have examined the change in bias over time.</p> <p>Methods</p> <p>Using data from large, nationally-representative population health surveys, we examined change in bias in height and weight reporting among Australian adults between 1995 and 2008. Our study dataset included 9,635 men and women in 1995 and 9,141 in 2007-2008. We investigated the determinants of the bias and derived correction equations using 2007-2008 data, which can be applied when only self-reported anthropometric data are available.</p> <p>Results</p> <p>In 1995, self-reported BMI (derived from height and weight) was 1.2 units (men) and 1.4 units (women) lower than measured BMI. In 2007-2008, there was still underreporting, but the amount had declined to 0.6 units (men) and 0.7 units (women) below measured BMI. The major determinants of reporting error in 2007-2008 were age, sex, measured BMI, and education of the respondent. Correction equations for height and weight derived from 2007-2008 data and applied to self-reported data were able to adjust for the bias and were accurate across all age and sex strata.</p> <p>Conclusions</p> <p>The diminishing reporting bias in BMI in Australia means that correction equations derived from 2007-2008 data may not be transferable to earlier self-reported data. Second, predictions of future overweight and obesity in Australia based on trends in self-reported information are likely to be inaccurate, as the change in reporting bias will affect the apparent increase in self-reported obesity prevalence.</p

Ultrastructural changes of the intracellular surfactant pool in a rat model of lung transplantation-related events

<p>Abstract</p> <p>Background</p> <p>Ischemia/reperfusion (I/R) injury, involved in primary graft dysfunction following lung transplantation, leads to inactivation of intra-alveolar surfactant which facilitates injury of the blood-air barrier. The alveolar epithelial type II cells (AE2 cells) synthesize, store and secrete surfactant; thus, an intracellular surfactant pool stored in lamellar bodies (Lb) can be distinguished from the intra-alveolar surfactant pool. The aim of this study was to investigate ultrastructural alterations of the intracellular surfactant pool in a model, mimicking transplantation-related procedures including flush perfusion, cold ischemia and reperfusion combined with mechanical ventilation.</p> <p>Methods</p> <p>Using design-based stereology at the light and electron microscopic level, number, surface area and mean volume of AE2 cells as well as number, size and total volume of Lb were determined in a group subjected to transplantation-related procedures including both I/R injury and mechanical ventilation (I/R group) and a control group.</p> <p>Results</p> <p>After I/R injury, the mean number of Lb per AE2 cell was significantly reduced compared to the control group, accompanied by a significant increase in the luminal surface area per AE2 cell in the I/R group. This increase in the luminal surface area correlated with the decrease in surface area of Lb per AE2. The number-weighted mean volume of Lb in the I/R group showed a tendency to increase.</p> <p>Conclusion</p> <p>We suggest that in this animal model the reduction of the number of Lb per AE2 cell is most likely due to stimulated exocytosis of Lb into the alveolar space. The loss of Lb is partly compensated by an increased size of Lb thus maintaining total volume of Lb per AE2 cell and lung. This mechanism counteracts at least in part the inactivation of the intra-alveolar surfactant.</p

Height outcomes in Korean children with idiopathic short stature receiving growth hormone treatment

OBJECTIVES: Growth hormone (GH) therapy's capacity to increase height velocity and height at the end of the study in children with idiopathic short stature (ISS) is controversial. We aimed to investigate the height standard deviation score (SDS) and height velocity of patients with ISS in Korea who received GH treatment. METHODS: We retrospectively reviewed and performed linear mixed model and survival analyses on data from 12 tertiary hospitals in Korea, including subjects diagnosed with ISS from January 2009 to September 2019, treated with GH therapy for more than 6 months, and who were at a pre-pubertal state at the time of diagnosis. RESULTS: We included 578 children (330 boys and 248 girls). The mean daily dose of GH in this study was 0.051 mg/kg, which was lower than the approved dose in Korea of 0.062 - 0.067 mg/kg. Height SDS was higher in patients who started treatment before the age of 6 years. The probability of reaching the target SDS (-1 SDS) from the beginning of treatment to 2-3 years after its start was higher in children starting treatment before the age of 6 years. The hazard ratio to reach the target SDS (-1 SDS) when using automatic pen or electronic devices was 1.727 times higher than that when using the needle and syringe device. CONCLUSION: ISS patients should start GH treatment at an early age, and even lower-than-recommended drug doses may be effective. The selection of automatic pen or electronic device can have a positive effect on reaching the target height SDS