A Novel Extracytoplasmic Function (ECF) Sigma Factor Regulates Virulence in Pseudomonas aeruginosa

Next to the two-component and quorum sensing systems, cell-surface signaling (CSS) has been recently identified as an important regulatory system in Pseudomonas aeruginosa. CSS systems sense signals from outside the cell and transmit them into the cytoplasm. They generally consist of a TonB-dependent outer membrane receptor, a sigma factor regulator (or anti-sigma factor) in the cytoplasmic membrane, and an extracytoplasmic function (ECF) sigma factor. Upon perception of the extracellular signal by the receptor the ECF sigma factor is activated and promotes the transcription of a specific set of gene(s). Although most P. aeruginosa CSS systems are involved in the regulation of iron uptake, we have identified a novel system involved in the regulation of virulence. This CSS system, which has been designated PUMA3, has a number of unusual characteristics. The most obvious difference is the receptor component which is considerably smaller than that of other CSS outer membrane receptors and lacks a β-barrel domain. Homology modeling of PA0674 shows that this receptor is predicted to be a bilobal protein, with an N-terminal domain that resembles the N-terminal periplasmic signaling domain of CSS receptors, and a C-terminal domain that resembles the periplasmic C-terminal domains of the TolA/TonB proteins. Furthermore, the sigma factor regulator both inhibits the function of the ECF sigma factor and is required for its activity. By microarray analysis we show that PUMA3 regulates the expression of a number of genes encoding potential virulence factors, including a two-partner secretion (TPS) system. Using zebrafish (Danio rerio) embryos as a host we have demonstrated that the P. aeruginosa PUMA3-induced strain is more virulent than the wild-type. PUMA3 represents the first CSS system dedicated to the transcriptional activation of virulence functions in a human pathogen

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Promotion de la santé : sortir de la rhétorique 30 ans après ? Editorial

National audienc

Time derivative equations for mode I fatigue crack growth in metals

Predicting fatigue crack growth in metals remains a difficult task since the available models based on the Paris law are cycle-derivative equations (da/dN), while service loads are often far from being cyclic. This imposes a cycle-reconstruction of the load sequence, which significantly modifies the load history in the signal. The main objective of this paper is therefore to propose a set of time-defivative equations for fatigue crack growth in order to avoid any cycle reconstruction. The model is based on the thermodynamics of dissipative processes. Its main originality lies in the introduction of a supplementary state variable for the crack, which allows describing continuously the state of the crack throughout any complex load sequence. The state of the crack is considered to be fully characterized at the global scale by its length a, its plastic blunting p, and its elastic opening. In the equations, special attention is paid to the elastic energy stored inside the crack tip plastic zone, since, in practice, residual stresses at the crack tip are known to considerably influence fatigue crack growth. The model consists finally in two laws: a crack propagation law, which is a relationship between dp/dt and da/dt and which observes the inequality stemming from the inequality of Clausius Duhem, and an elastic-plastic constitutive behaviour for the cracked structure, which provides dp/dt versus load and which stems from the energy balance equation. The model was implemented and tested. It successfully reproduces the main features of fatigue crack growth as reported in the literature, such as the Paris law, the stress ratio effect, and the overload retardation effec

Les programmes de promotion de la santé en France : un état des lieux

National audienceLa promotion de la santé se distingue du champ général de la santé publique en ce qu’elle met en avant un agenda de justice sociale et s’inscrit dans un travail d’action sur les déterminants sociaux de la santé. A l’instar d’autres pays industrialisés, la France, à travers l’évolution des pratiques et de la recherche en santé publique, a fait écho, ces dernières années, au programme d’actions formulé dans la Charte d’Ottawa (OMS, 1986). Toutefois, l’approche en France est comparativement moins développée que chez ses voisins européens. Nous proposons ici un état des lieux des programmes en promotion de la santé en France et de leur inscription dans les axes de la Charte.Méthode : Nous avons recensé les articles publiés de 2000 à 2010 dans trois revues de santé publique : Santé de l’Homme, Santé Publique et la Revue d’Epidémiologie et de Santé Publique. Les articles retenus devaient comporter dans le titre ou le résumé l’expression « promotion de la santé ». Seuls ceux rapportant les résultats de programmes visant la population française ont été retenus. Les articles ont ensuite été analysés à la lumière des cinq leviers d’action de la Charte d’Ottawa.Résultats : Notre analyse démontre que les programmes ciblent plutôt l’acquisition d’aptitudes individuelles ou le renforcement de l’action communautaire, concernent souvent le milieu scolaire et demeurent majoritairement centrés sur des stratégies d’éducation à la santé. Le transfert d’expérience sur des programmes évalués demeure peu développé dans la littérature française.Discussion : Alors que 25 ans se sont écoulés depuis l’adoption de la Charte d’Ottawa, peu d’études s’inscrivent dans l’action sur les déterminants sociaux et environnementaux de la santé des populations. Pourtant, des projets existent sur l’ensemble du Territoire (ex. ville-santé OMS) ce qui suggère le besoin d’encourager l’évaluation et la diffusion des innovations locales

Reorienting a health promotion system to better address the social determinants of health: an intervention research in the Pays de Redon-Bretagne Sud,

International audienc

Implementing the SDOH agenda in local health systems: lessons from Pays de Redon-Bretagne Sud, France

International audienc

Empowering local stakeholders to tackle health inequalities: an interventional research project in Pays de Redon-Bretagne Sud, France

International audienc

Reorienting a health promotion system to better address the social determinants of health: An interventional research in Pays de Redon-Bretagne Sud, France

International audienc