Sema7A is crucial for resolution of severe inflammation

Endogenous mediators regulating acute inflammatory responses in both the induction and resolution phases of inflammatory processes are pivotal in host defense and tissue homeostasis. Recent studies have identified neuronal guidance proteins characterized in axonal development that display immunomodulatory functions. Here, we identify the neuroimmune guidance cue Semaphorin 7A (Sema7A), which appears to link macrophage (M Phi) metabolic remodeling to inflammation resolution. Sema7A orchestrated M Phi chemotaxis and chemokinesis, activated M Phi differentiation and polarization toward the proresolving M2 phenotype, and promoted leukocyte clearance. Peritoneal M Phi(sema7A-/-) displayed metabolic reprogramming, characterized by reductions in fatty acid oxidation and oxidative phosphorylation, increases in glycolysis and the pentose phosphate pathway, and truncation of the tricarboxylic acid cycle, which resulted in increased levels of the intermediates succinate and fumarate. The low accumulation of citrate in M Phi(sema7A-/-) correlated with the decreased synthesis of prostaglandins, leading to a reduced impact on lipid-mediator class switching and the generation of specialized pro resolving lipid mediators. Signaling network analysis indicated that Sema7A induced the metabolic reprogramming of M Phi by activating the mTOR-and AKT2-signaling pathways. Administration of Sema7A(SL4cd) orchestrated the resolution response to tissue homeostasis by shortening the resolution interval, promoting tissue protection in murine peritonitis, and enhancing survival in polymicrobial sepsis.Proteomic

Radiation-induced oscillatory magnetoresistance as a sensitive probe of the zero-field spin splitting in high mobility GaAs/AlGaAs devices

We suggest an approach for characterizing the zero-field spin splitting of high mobility two-dimensional electron systems, when beats are not readily observable in the Shubnikov-de Haas effect. The zero-field spin splitting and the effective magnetic field seen in the reference frame of the electron is evaluated from a quantitative study of beats observed in radiation-induced magnetoresistance oscillations.Comment: 4 pages, 4 color figure

Implementing evidence-based recommended practices for the management of patients with mild traumatic brain injuries in Australian emergency care departments: study protocol for a cluster randomised controlled trial

Background: Mild head injuries commonly present to emergency departments. The challenges facing clinicians in emergency departments include identifying which patients have traumatic brain injury, and which patients can safely be sent home. Traumatic brain injuries may exist with subtle symptoms or signs, but can still lead to adverse outcomes. Despite the existence of several high quality clinical practice guidelines, internationally and in Australia, research shows inconsistent implementation of these recommendations. The aim of this trial is to test the effectiveness of a targeted, theory- and evidence-informed implementation intervention to increase the uptake of three key clinical recommendations regarding the emergency department management of adult patients (18 years of age or older) who present following mild head injuries (concussion), compared with passive dissemination of these recommendations. The primary objective is to establish whether the intervention is effective in increasing the percentage of patients for which appropriate post-traumatic amnesia screening is performed. Methods/design: The design of this study is a cluster randomised trial. We aim to include 34 Australian 24-hour emergency departments, which will be randomised to an intervention or control group. Control group departments will receive a copy of the most recent Australian evidence-based clinical practice guideline on the acute management of patients with mild head injuries. The intervention group will receive an implementation intervention based on an analysis of influencing factors, which include local stakeholder meetings, identification of nursing and medical opinion leaders in each site, a train-the-trainer day and standardised education and interactive workshops delivered by the opinion leaders during a 3 month period of time. Clinical practice outcomes will be collected retrospectively from medical records by independent chart auditors over the 2 month period following intervention delivery (patient level outcomes). In consenting hospitals, eligible patients will be recruited for a follow-up telephone interview conducted by trained researchers. A cost-effectiveness analysis and process evaluation using mixed-methods will be conducted. Sample size calculations are based on including 30 patients on average per department. Outcome assessors will be blinded to group allocation

Does high-dose metformin cause lactic acidosis in type 2 diabetic patients after CABG surgery? A double blind randomized clinical trial

Metformin is a dimethyl biguanide oral anti-hyperglycemic agent. Lactic acidosis due to metformin is a fatal metabolic condition that limits its use in patients in poor clinical condition, consequently reducing the number of patients who benefit from this medication. In a double blind randomized clinical trial, we investigated 200 type 2 diabetic patients after coronary artery bypass surgery in the open heart ICU of the Mazandaran Heart Center, and randomly assigned them to equal intervention and control groups. The intervention group received regular insulin infusion along with 2 metformin 500 mg tablets every twelve hours, while the control group received only intravenous insulin with 2 placebo tablets every twelve hours. Lactate level, pH, base excess, blood glucose and serum creatinine were measured over five 12 h periods, with data averaged for each period. The primary outcome in this study was high lactate levels. Comparison between the 2 groups was made by independent Student’s t-test. To compare changes in multiple measures in each group and analysis of group interaction, a repeated measurement ANOVA test was used

Strength of the 18F(p, α)15O resonance at Ec.m. = 330 keV

The astrophysical rate of the 18F(p,α)15O reaction at nova temperatures is critical to understanding production of the radioisotope 18F, which may be used to constrain nova models via observations with the coming generation of satellite-based γ-ray telescopes. As such, a measurement is made of the strength of this resonance using a radioactive 18F beam at the HRIBF. As a result, it is indicated that the 18F(p,α)15O reaction rate is lower than previous estimates by a factor of ∼2

The role of lubricant feeding conditions on the performance improvement and friction reduction of journal bearings

Most conventional hydrodynamic journal bearing performance tools can not suitably assess the effect of lubricant feeding conditions on bearing performance, even though these conditions are known to affect important performance parameters such as eccentricity and powerloss. A thermohydrodynamic analysis suitable to deal with realistic feeding conditions has been proposed. Special attention was given to the treatment of phenomena taking place within grooves and their vicinity,as well as to the ruptured film region. The effec to flubricant feeding pressure and temperature, groove length ratio,width ratio and number (single/twin) on bearing performance has been analyzed for a broad range of conditions.It was found that a careful tuning of the feeding conditions may indeed improve bearing performance.FCT - POCTI/EME/39202/200

Durability of concrete structures in marine atmosphere zones – The use of chloride deposition rate on the wet candle as an environmental indicator

Durability of concrete structures under marine environments has been studied for a long time. This work was focused on marine atmosphere zone and studied the deposition of chlorides on wet candle devices and its relation with chlorides accumulated into concrete. Concrete specimens with three different mixtures were exposed at places located at four different distances from the sea. Periodically, chloride profiles were obtained and analysed taking into account environmental data. Results of numerical extrapolations show that chloride deposition rate on the wet candle can be used as an environmental indicator, helping to preview the expectancy of service life of concrete structures or suggesting minimum concrete cover thicknesses for a required service life. Regarding the studied region, service life decreases between 30% and 60% were observed when changing chloride deposition from 120 mg/m2 day to 500 mg/m2 day, which shows that chloride deposition plays an important role as an environmental indicator on service-life analysis of concrete structures in marine atmosphere zone

Amygdala responses to emotional faces in twins discordant or concordant for the risk for anxiety and depression.

Background: Functional brain imaging studies have shown deviant amygdala responses to emotional stimuli in subjects suffering from anxiety and depressive disorder, but both hyperactivity and hypoactivity compared to healthy controls have been reported. To account for these discrepant findings, we hypothesize that genetic and environmental risk factors differently impact on amygdala functioning. Methods: To test this hypothesis, we assessed amygdala responses to an emotional faces paradigm during functional magnetic resonance imaging in monozygotic twin pairs discordant for the risk of anxiety and depression (n = 10 pairs) and in monozygotic twin pairs concordant for high (n = 7 pairs) or low (n = 15 pairs) risk for anxiety and depression. Results: Main effects (all faces vs. baseline) revealed robust bilateral amygdala activity across groups. In discordant twins, increased amygdala responses were found for negatively valenced stimuli (angry/anxious faces) in high-risk twins compared to their low-risk co-twins. In contrast, concordant high-risk pairs revealed blunted amygdala reactivity to both positive and negative faces compared with concordant low-risk pairs. Post-hoc analyses showed that these findings were independent of 5-HTTLPR genotype. Conclusions: Our findings indicate amygdala hyperactivity in subjects who are at high risk for anxiety and depression through environmental factors and amygdala hypoactivity in those at risk mainly through genetic factors. We suggest that this result reflects a difference in baseline amygdala activation in these groups. Future imaging studies on anxiety and depression should aim to avoid admixture of subjects who are at genetic risk with those at risk due to environmental factors. © 2008 Elsevier Inc. All rights reserved

Acute respiratory failure and the kinetics of neutrophil recovery in pediatric hematopoietic cell transplantation: a multicenter study

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.In this multicenter study, we investigated the kinetics of neutrophil recovery in relation to acuity and survival among 125 children undergoing allogeneic hematopoietic cell transplantation (allo-HCT) who required invasive mechanical ventilation (IMV). Recovery of neutrophils, whether prior to or after initiation of IMV, was associated with a significantly decreased risk of death relative to never achieving neutrophil recovery. A transient increase in acuity (by oxygenation index and vasopressor requirements) occurred among a subset of the patients who achieved neutrophil recovery after initiation of IMV; 61.5% of these patients survived to discharge from the intensive care unit (ICU). Improved survival among patients who subsequently achieved neutrophil recovery on IMV was not limited to those with peri-engraftment respiratory distress syndrome. The presence of a respiratory pathogen did not affect the risk of death while on IMV but was associated with an increased length of IMV (p < 0.01). Among patients undergoing HCT who develop respiratory failure and require advanced therapeutic support, neutrophil recovery at time of IMV and/or presence of a respiratory pathogen should not be used as determining factors when counseling families about survival

Discovery of high-confidence human protein-coding genes and exons by whole-genome PhyloCSF helps elucidate 118 GWAS loci.

The most widely appreciated role of DNA is to encode protein, yet the exact portion of the human genome that is translated remains to be ascertained. We previously developed PhyloCSF, a widely used tool to identify evolutionary signatures of protein-coding regions using multispecies genome alignments. Here, we present the first whole-genome PhyloCSF prediction tracks for human, mouse, chicken, fly, worm, and mosquito. We develop a workflow that uses machine learning to predict novel conserved protein-coding regions and efficiently guide their manual curation. We analyze more than 1000 high-scoring human PhyloCSF regions and confidently add 144 conserved protein-coding genes to the GENCODE gene set, as well as additional coding regions within 236 previously annotated protein-coding genes, and 169 pseudogenes, most of them disabled after primates diverged. The majority of these represent new discoveries, including 70 previously undetected protein-coding genes. The novel coding genes are additionally supported by single-nucleotide variant evidence indicative of continued purifying selection in the human lineage, coding-exon splicing evidence from new GENCODE transcripts using next-generation transcriptomic data sets, and mass spectrometry evidence of translation for several new genes. Our discoveries required simultaneous comparative annotation of other vertebrate genomes, which we show is essential to remove spurious ORFs and to distinguish coding from pseudogene regions. Our new coding regions help elucidate disease-associated regions by revealing that 118 GWAS variants previously thought to be noncoding are in fact protein altering. Altogether, our PhyloCSF data sets and algorithms will help researchers seeking to interpret these genomes, while our new annotations present exciting loci for further experimental characterization