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/)

Adoption des articles 3 à 5 sur les crimes contre la sûreté extérieure de l'Etat du décret sur le Code pénal, lors de la séance du 6 juin 1791

Dauchy Luc Jacques Edouard, Le Peletier de Saint-Fargeau Louis-Michel. Adoption des articles 3 à 5 sur les crimes contre la sûreté extérieure de l'Etat du décret sur le Code pénal, lors de la séance du 6 juin 1791. In: Archives Parlementaires de 1787 à 1860 - Première série (1787-1799) Tome XXVII - Du 6 juin au 5 juillet 1791. Paris : Librairie Administrative P. Dupont, 1887. p. 13

Suite de la discussion du projet de Code pénal, lors de la séance du 16 juin 1791

Dauchy Luc Jacques Edouard, Le Peletier de Saint-Fargeau Louis-Michel. Suite de la discussion du projet de Code pénal, lors de la séance du 16 juin 1791. In: Archives Parlementaires de 1787 à 1860 - Première série (1787-1799) Tome XXVII - Du 6 juin au 5 juillet 1791. Paris : Librairie Administrative P. Dupont, 1887. pp. 275-276

Suite de la discussion du projet de Code pénal, lors de la séance du 16 juin 1791

Dauchy Luc Jacques Edouard, Le Peletier de Saint-Fargeau Louis-Michel. Suite de la discussion du projet de Code pénal, lors de la séance du 16 juin 1791. In: Archives Parlementaires de 1787 à 1860 - Première série (1787-1799) Tome XXVII - Du 6 juin au 5 juillet 1791. Paris : Librairie Administrative P. Dupont, 1887. pp. 275-276

Adoption des articles 3 à 5 sur les crimes contre la sûreté extérieure de l'Etat du décret sur le Code pénal, lors de la séance du 6 juin 1791

Dauchy Luc Jacques Edouard, Le Peletier de Saint-Fargeau Louis-Michel. Adoption des articles 3 à 5 sur les crimes contre la sûreté extérieure de l'Etat du décret sur le Code pénal, lors de la séance du 6 juin 1791. In: Archives Parlementaires de 1787 à 1860 - Première série (1787-1799) Tome XXVII - Du 6 juin au 5 juillet 1791. Paris : Librairie Administrative P. Dupont, 1887. p. 13

Viral infection impacts transposable element transcript amounts in Drosophila

International audienceTransposable elements (TEs) are genomic parasites that are found in all genomes, some of which display sequence similarity to certain viruses. In insects, TEs are controlled by the Piwi-interacting small interfering RNA (piRNA) pathway in gonads, while the small interfering RNA (siRNA) pathway is dedicated to TE somatic control and defense against viruses. So far, these two small interfering RNA pathways are considered to involve distinct molecular effectors and are described as independent. Using Sindbis virus (SINV) in Drosophila, here we show that viral infections affect TE transcript amounts via modulations of the piRNA and siRNA repertoires, with the clearest effects in somatic tissues. These results suggest that viral acute or chronic infections may impact TE activity and, thus, the tempo of genetic diversification. In addition, these results deserve further evolutionary considerations regarding potential benefits to the host, the virus, or the TEs

Projet de décret concernant les relations diplomatiques, lors de la séance du 21 juin 1791

Dauchy Luc Jacques Edouard, Regnaud de Saint-Jean d'Angély Michel Louis Etienne. Projet de décret concernant les relations diplomatiques, lors de la séance du 21 juin 1791. In: Archives Parlementaires de 1787 à 1860 - Première série (1787-1799) Tome XXVII - Du 6 juin au 5 juillet 1791. Paris : Librairie Administrative P. Dupont, 1887. pp. 384-385

Projet de décret concernant les relations diplomatiques, lors de la séance du 21 juin 1791

Dauchy Luc Jacques Edouard, Regnaud de Saint-Jean d'Angély Michel Louis Etienne. Projet de décret concernant les relations diplomatiques, lors de la séance du 21 juin 1791. In: Archives Parlementaires de 1787 à 1860 - Première série (1787-1799) Tome XXVII - Du 6 juin au 5 juillet 1791. Paris : Librairie Administrative P. Dupont, 1887. pp. 384-385

Neurexin-1β Binding to Neuroligin-1 Triggers the Preferential Recruitment of PSD-95 versus Gephyrin through Tyrosine Phosphorylation of Neuroligin-1

Adhesion between neurexin-1β (Nrx1β) and neuroligin-1 (Nlg1) induces early recruitment of the postsynaptic density protein 95 (PSD-95) scaffold; however, the associated signaling mechanisms are unknown. To dissociate the effects of ligand binding and receptor multimerization, we compared conditions in which Nlg1 in neurons was bound to Nrx1β or nonactivating HA antibodies. Time-lapse imaging, fluorescence recovery after photobleaching, and single-particle tracking demonstrated that in addition to aggregating Nlg1, Nrx1β binding stimulates the interaction between Nlg1 and PSD-95. Phosphotyrosine immunoblots and pull-down of gephyrin by Nlg1 peptides in vitro showed that Nlg1 can be phosphorylated at a unique tyrosine (Y782), preventing gephyrin binding. Expression of Nlg1 point mutants in neurons indicated that Y782 phosphorylation controls the preferential binding of Nlg1 to PSD-95 versus gephyrin, and accordingly the formation of inhibitory and excitatory synapses. We propose that ligand-induced changes in the Nlg1 phosphotyrosine level control the balance between excitatory and inhibitory scaffold assembly during synapse formation and stabilization

Second heart field cardiac progenitor cells in the early mouse embryo.

International audienceAt the end of the first week of mouse gestation, cardiomyocyte differentiation initiates in the cardiac crescent to give rise to the linear heart tube. The heart tube subsequently elongates by addition of cardiac progenitor cells from adjacent pharyngeal mesoderm to the growing arterial and venous poles. These progenitor cells, termed the second heart field, originate in splanchnic mesoderm medial to cells of the cardiac crescent and are patterned into anterior and posterior domains adjacent to the arterial and venous poles of the heart, respectively. Perturbation of second heart field cell deployment results in a spectrum of congenital heart anomalies including conotruncal and atrial septal defects seen in human patients. Here, we briefly review current knowledge of how the properties of second heart field cells are controlled by a network of transcriptional regulators and intercellular signaling pathways. Focus will be on 1) the regulation of cardiac progenitor cell proliferation in pharyngeal mesoderm, 2) the control of progressive progenitor cell differentiation and 3) the patterning of cardiac progenitor cells in the dorsal pericardial wall. Coordination of these three processes in the early embryo drives progressive heart tube elongation during cardiac morphogenesis. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction