Specific versus Non-Specific Immune Responses in an Invertebrate Species Evidenced by a Comparative de novo Sequencing Study

Our present understanding of the functioning and evolutionary history of invertebrate innate immunity derives mostly from studies on a few model species belonging to ecdysozoa. In particular, the characterization of signaling pathways dedicated to specific responses towards fungi and Gram-positive or Gram-negative bacteria in Drosophila melanogaster challenged our original view of a non-specific immunity in invertebrates. However, much remains to be elucidated from lophotrochozoan species. To investigate the global specificity of the immune response in the fresh-water snail Biomphalaria glabrata, we used massive Illumina sequencing of 5′-end cDNAs to compare expression profiles after challenge by Gram-positive or Gram-negative bacteria or after a yeast challenge. 5′-end cDNA sequencing of the libraries yielded over 12 millions high quality reads. To link these short reads to expressed genes, we prepared a reference transcriptomic database through automatic assembly and annotation of the 758,510 redundant sequences (ESTs, mRNAs) of B. glabrata available in public databases. Computational analysis of Illumina reads followed by multivariate analyses allowed identification of 1685 candidate transcripts differentially expressed after an immune challenge, with a two fold ratio between transcripts showing a challenge-specific expression versus a lower or non-specific differential expression. Differential expression has been validated using quantitative PCR for a subset of randomly selected candidates. Predicted functions of annotated candidates (approx. 700 unisequences) belonged to a large extend to similar functional categories or protein types. This work significantly expands upon previous gene discovery and expression studies on B. glabrata and suggests that responses to various pathogens may involve similar immune processes or signaling pathways but different genes belonging to multigenic families. These results raise the question of the importance of gene duplication and acquisition of paralog functional diversity in the evolution of specific invertebrate immune responses

Performances of domiciliary ventilators compared by using a parametric procedure

WOS:000379882100001International audienceBackground: Noninvasive mechanical ventilation is sufficiently widely used to motivate bench studies for evaluating and comparing performances of the domiciliary ventilators. In most (if not in all) of the previous studies, ventilators were tested in a single (or a very few) conditions, chosen to avoid asynchrony events. Such a practice does not reflect how the ventilator is able to answer the demand from a large cohort of patients with their inherent inter-patient variability. We thus developed a new procedure according which each ventilator was tested with more than 1200 "simulated" patients. Methods: Three lung mechanics (obstructive, restrictive and normal) were simulated using a mechanical lung (ASL 5000) driven by a realistic muscular pressure. 420 different dynamics for each of these three lung mechanics were considered by varying the breathing frequency and the mouth occlusion pressure. For each of the nine ventilators tested, five different parameter settings were investigated. The results are synthesized in colored maps where each color represents the ventilator (in) ability to synchronize with a given muscular pressure dynamics. A synchronizability e is then computed for each map. Results: The lung model, the breathing frequency and the mouth occlusion pressure strongly affect the synchronizability of ventilators. The Vivo 50 (Breas) and the SomnoVENT autoST (Weinmann) are well synchronized with the restrictive model ((epsilon) over bar = 86 and 78 %, respectively), whereas the Elisee 150 (ResMed), the BiPAP A40 and the Trilogy 100 (Philips Respironics) better fit with an obstructive lung mechanics ((epsilon) over bar = 87, 86 and 86 %, respectively). Triggering and pressurization performances of the nine ventilators present heterogeneities due to their different settings and operating strategies. Conclusion: Performances of domiciliary ventilators strongly depend not only on the breathing dynamics but also on the ventilator strategy. One given ventilator may be more adequate than another one for a given patient

Causes of early mortality after liver transplantation: A twenty-years single centre experience

Objective. - To define the causes of mortality of patients who died within the first three months after a liver transplantation. Type of study. - Retrospective, observational, and single centre study. Patients and methods. - Between March 1989 and July 2010, all patients who died within three months after a liver transplantation were included. Demographic characteristics, preoperative and peroperative data, donor characteristics, postoperative complications and causes of mortality were collected. Results. - Among the 788 performed liver transplantations, 76 patients died in intensive care unit (11%). The main indications of liver transplantation were alcoholic cirrhosis (30%), hepatitis C (28%), hepatocarcinoma (15%), primitive or secondary biliary cirrhosis (10%). Fifty percent of the patients were categorized as Child C. The main causes of death were non-function or dysfunction with retransplantation contra-indication graft (18%), sepsis (18%), neurological complications (12%), hemorrhagic shock (13%), (9%), multiorgan failures (5%), cardiac complications (6%). Conclusion. In this study, the main causes of mortality were infectious, neurological and hemorrhagic. These results emphasize the necessity for better control of sepsis, haemorrhage and immunosupressors. (C) 2011 Elsevier Masson SAS. All rights reserved

Antifungal therapy for patients with proven or suspected Candida peritonitis: Amarcand2, a prospective cohort study in French intensive care units

International audienceOBJECTIVE:The clinical characteristics and prognosis of patients treated for Candida peritonitis (CP) were compared according to the type of systemic antifungal therapy (SAT), empiric (EAF) or targeted (TAF) therapies, and the final diagnosis of infection.METHODS:Patients in intensive care units (ICU) treated for CP were selected among the AmarCAND2 cohort, to compare patients receiving EAF for unconfirmed suspicion of CP (EAF/nonCP), to those with suspected secondarily confirmed CP (EAF/CP), or with primarily proven CP receiving TAF.RESULTS:In all, 279 patients were evaluated (43.4% EAF/nonCP, 29.7% EAF/CP and 25.8% TAF patients). At SAT initiation, the severity of illness was similar among EAF/nonCP and EAF/CP patients, lower among TAF patients (median Simplified Acute Physiology Score II (SAPS II) 49 and 51 versus 35, respectively; p 0.001). Candida albicans was involved in 67%, Candida glabrata in 15.6%. All strains were susceptible to echinocandin; 84% to fluconazole. Echinocandin was administered to 51.2% EAF/nonCP, 49% EAF/CP and 40% TAF patients. At day 28, 72%, 76% and 75% of EAF/nonCP, EAF/CP and TAF patients, respectively, were alive. An increased mortality was observed in patients with a Sequential Organ Failure Assessment (SOFA) score <7 if SAT was delayed by ≥6 days (p 0.04). Healthcare-associated CP (OR 3.82, 95% CI 1.52-9.64, p 0.004), SOFA ≥8 at ICU admission (OR 2.61, 95% CI 1.08-6.34; p 0.03), and SAPS II ≥45 at SAT initiation (OR 5.08, 95% CI 1.04-12.67; p 0.001) impacted the 28-day mortality.CONCLUSIONS:In summary, only 56.6% of ICU patients receiving SAT had CP. Most strains were susceptible to SAT. A similar 28-day mortality rate was observed among groups; the late administration of SAT significantly worsened the prognosis of patients with less severe CP