In vivo RNA interference analysis reveals an unexpected role for GNBP1 in the defense against Gram-positive bacterial infection in Drosophila adults

The Drosophila immune system discriminates between different classes of infectious microbes and responds with pathogen-specific defense reactions via the selective activation of the Toll and the immune deficiency (Imd) signaling pathways. The Toll pathway mediates most defenses against Gram-positive bacteria and fungi, whereas the Imd pathway is required to resist Gram-negative bacterial infection. Microbial recognition is achieved through peptidoglycan recognition proteins (PGRPs); Gram-positive bacteria activate the Toll pathway through a circulating PGRP (PGRP-SA), and Gram-negative bacteria activate the Imd pathway via PGRP-LC, a putative transmembrane receptor, and PGRP-LE. Gram-negative binding proteins (GNBPs) were originally identified in Bombyx mori for their capacity to bind various microbial compounds. Three GNBPs and two related proteins are encoded in the Drosophila genome, but their function is not known. Using inducible expression of GNBP1 double-stranded RNA, we now demonstrate that GNBP1 is required for Toll activation in response to Gram-positive bacterial infection; GNBP1 double-stranded RNA expression renders flies susceptible to Gram-positive bacterial infection and reduces the induction of the antifungal peptide encoding gene Drosomycin after infection by Gram-positive bacteria but not after fungal infection. This phenotype induced by GNBP1 inactivation is identical to a loss-of-function mutation in PGRP-SA, and our genetic studies suggest that GNBP1 acts upstream of the Toll ligand Spätzle. Altogether, our results demonstrate that the detection of Gram-positive bacteria in Drosophila requires two putative pattern recognition receptors, PGRP-SA and GNBP1

Impact of post-procedural glycemic variability on cardiovascular morbidity and mortality after transcatheter aortic valve implantation : a post hoc cohort analysis

International audienceBackground : Glycemic variability is associated with worse outcomes after cardiac surgery, but the prognosis value of early glycemic variability after transcatheter aortic valve implantation is not known. This study was therefore designed to analyze the prognosis significance of post-procedural glycemic variability within 30 days after transcatheter aortic valve implantation.Methods : A post hoc analysis of patients from our center included in the FRANCE and FRANCE-2 registries was conducted. Post-procedural glycemic variability was assessed by calculating the mean daily δ blood glucose during the first 2 days after transcatheter aortic valve implantation. Major complications within 30 days were death, stroke, myocardial infarction, acute heart failure, and life-threatening cardiac arrhythmias.Results : We analyzed 160 patients (age (median [interquartile] = 84 [80–88] years; diabetes mellitus (n) = 41 (26%) patients; logistic Euroscore = 20 [12–32]). The median value of mean daily δ blood glucose was 4.3 mmol l−1. The rate of major complications within 30 days after procedure among patients with the lowest quartile of glycemic variability was 12%, increasing from 12 to 26%, and 39% in the second, third, and fourth quartiles, respectively. In multivariate analysis, glycemic variability was independently associated with an increased risk of major complications within 30 days after the procedure (odds ratio [95% CI] = 1.83 [1.19–2.83]; p = 0.006).Conclusions : This study showed that post-procedural glycemic variability was associated with an increased risk of major complications within 30 days after transcatheter aortic valve implantation

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Anesthésie des patients porteurs de stimulateurs cardiaques en chirurgie non cardiaque (une étude prospective)

PARIS5-BU Méd.Cochin (751142101) / SudocPARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Introduction de l’APP et formation des enseignants à la fonction de tuteur : l’expérience de la Faculté de Médecine Xavier Bichat

But : Évaluer l’impact des programmes de formation, mis en place à la faculté de Médecine Xavier Bichat, sur l’évolution des compétences pédagogiques des enseignants exerçant une fonction de tuteur. Méthodes : Le programme se compose de trois ateliers, deux de formation pédagogique générale d’une journée et demie chacun, et d’un atelier de formation à la fonction de tuteur d’une durée de deux jours. Chaque tuteur devra avoir suivi les trois ateliers. Les compétences présumées acquises par les enseignants ont été évaluées à partir 1- d’un questionnaire rempli par les étudiants, évaluant les comportements de l’enseignant face à son nouveau rôle ; 2- d’une grille d’auto-évaluation, remplie par chaque enseignant, estimant lui-même ses comportements avant et après l’atelier de formation à la fonction de tuteur. Résultats : Les 7 tâches définies nécessaires pour enseigner comme tuteur d’APP sont significativement améliorées après l’atelier (p < 0,0001). Stimuler la motivation ou évaluer de façon formative les étudiants restent néanmoins des tâches difficiles. La cohérence des réponses des étudiants et des enseignants, montrée par les corrélations existant entre les deux séries de scores (auto-évaluation des enseignants vs évaluation des étudiants) confirme la validité de l’évaluation réalisée. Conclusion : Les enseignants ont acquis à la suite de ces cinq jours de formation des compétences spécifiques pour enseigner dans des groupes d’APP. Trois séries de mesure doivent, cependant, être développées : renforcement de certains contenus, développement d’outils d’évaluation continue et mise en place d’une formation continue

Facteurs associés à la survenue d'une péritonite à levures admise en réanimation

International audienc

Surgical antibiotic prophylaxis compliance in a university hospital.

International audienceTo assess surgical antibiotic prophylaxis (SAP) practices in a university hospital in order to identify risk factors associated with non-compliance. Retrospective monocentric study conducted over a 4-month period. Data were collected from the software used in the operating theatre. Practice non-compliance was evaluated in comparison with the 2010 version of the French national recommendations. We only took in account the interventions identified as priority surveillance interventions according to the surgical site infections national surveillance. The risk factors associated with SAP non-compliance were identified with a multivariate statistical analysis. We evaluated 1312 SAPs. Among the 1298 indicated SAPs, 44.4% were not compliant. The most frequent inappropriate criterion was the timing of injection (34.8% non-compliance), which was, in the majority of cases, too close to the time of incision. Other inappropriate criteria were identified: antibiotic choice for patients allergic to β-lactams (inappropriate among 45% of allergic patients), and antibiotic dosing for obese patients (96% of non-compliance). Obesity (OR=84.32), allergy to β-lactams (OR=17.11) and certain types of surgery (digestive, OR=4.56; gynaecological and obstetrical, OR=7.10; urological, OR=3.95) were independently associated with the non-compliance of SAP practices. Improvement measures that target the timing of injection, obese or allergic patients are necessary

Epidémiologie de la colonisation fongique en réanimation

International audienc