Covichem: A biochemical severity risk score of COVID-19 upon hospital admission

Clinical and laboratory predictors of COVID-19 severity are now well described and combined to propose mortality or severity scores. However, they all necessitate saturable equipment such as scanners, or procedures difficult to implement such as blood gas measures. To provide an easy and fast COVID-19 severity risk score upon hospital admission, and keeping in mind the above limits, we sought for a scoring system needing limited invasive data such as a simple blood test and co-morbidity assessment by anamnesis. A retrospective study of 303 patients (203 from Bordeaux University hospital and an external independent cohort of 100 patients from Paris Pitié-Salpêtrière hospital) collected clinical and biochemical parameters at admission. Using stepwise model selection by Akaike Information Criterion (AIC), we built the severity score Covichem. Among 26 tested variables, 7: obesity, cardiovascular conditions, plasma sodium, albumin, ferritin, LDH and CK were the independent predictors of severity used in Covichem (accuracy 0.87, AUROC 0.91). Accuracy was 0.92 in the external validation cohort (89% sensitivity and 95% specificity). Covichem score could be useful as a rapid, costless and easy to implement severity assessment tool during acute COVID-19 pandemic waves

Genetic landscape of a large cohort of Primary Ovarian Insufficiency : New genes and pathways and implications for personalized medicine

Background Primary Ovarian Insufficiency (POI), a public health problem, affects 1-3.7% of women under 40 yield-ing infertility and a shorter lifespan. Most causes are unknown. Recently, genetic causes were identified, mostly in single families. We studied an unprecedented large cohort of POI to unravel its molecular pathophysiology.Methods 375 patients with 70 families were studied using targeted (88 genes) or whole exome sequencing with pathogenic/likely-pathogenic variant selection. Mitomycin-induced chromosome breakages were studied in patients' lymphocytes if necessary. Findings A high-yield of 29.3% supports a clinical genetic diagnosis of POI. In addition, we found strong evidence of pathogenicity for nine genes not previously related to a Mendelian phenotype or POI: ELAVL2, NLRP11, CENPE, SPATA33, CCDC150, CCDC185, including DNA repair genes: C17orf53(HROB), HELQ, SWI5 yielding high chromo-somal fragility. We confirmed the causal role of BRCA2, FANCM, BNC1, ERCC6, MSH4, BMPR1A, BMPR1B, BMPR2, ESR2, CAV1, SPIDR, RCBTB1 and ATG7 previously reported in isolated patients/families. In 8.5% of cases, POI is the only symptom of a multi-organ genetic disease. New pathways were identified: NF-kB, post-translational regulation, and mitophagy (mitochondrial autophagy), providing future therapeutic targets. Three new genes have been shown to affect the age of natural menopause supporting a genetic link.Interpretation We have developed high-performance genetic diagnostic of POI, dissecting the molecular pathogene-sis of POI and enabling personalized medicine to i) prevent/cure comorbidities for tumour/cancer susceptibility genes that could affect life-expectancy (37.4% of cases), or for genetically-revealed syndromic POI (8.5% of cases), ii) predict residual ovarian reserve (60.5% of cases). Genetic diagnosis could help to identify patients who may benefit from the promising in vitro activation-IVA technique in the near future, greatly improving its success in treating infertility.Funding Universite? Paris Saclay, Agence Nationale de Biome?decine.Copyright (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe

L'addiction, ses risques et sa prise en charge

L'addiction est un réel problème de santé publique de part sa complexité et la difficulté de son traitement, et du fait de tous les risques associés qu'elle engendre. Sa prise en charge est difficile, longue et compliquée, orchestrée par des rechutes et des retours au point de départ. Chaque avancée, même si petite qu'elle soit est une réussite. Le pharmacien d'officine a un rôle majeur à jouer dans la prise en charge de ces pathologies. Il est en première ligne. C'est un acteur incontournable et privilégié pour la prévention et la réduction des dommages. Une prise de conscience de ce rôle du pharmacien est encore à développer. Ce rôle de conseil devra être l'exception qui, à l'avenir va différencier le pharmacien d'officine indépendant, d'éventuels autres centres de délivrance. Il est impératif de développer une réelle information du public et de mieux former les professionnels afin de vaincre les réticences encore constatées.TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Etat des lieux de la prise en charge contraceptive par les médecins généralistes en Ille-et-Vilaine

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Les antibiotiques dans la rhinopharyngite de l'enfant (un exemple de la négociation en médecine générale)

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Modélisation et analyse temporelle par réseaux de Pétri et logique linéaire

L'objectif de cette thèse est de contribuer à l'élaboration de méthodes d'aide à la conception de systèmes coopératifs en prenant en compte les contraintes temporelles de manière quantitative. L'approche développée est fondée sur les réseaux de Petri, la logique linéaire et les graphes de contraintes temporelles. C'est une approche orientée " événements " et non orientée " états " comme c'est souvent le cas dans les approches fondées sur les réseaux de Petri. Elle est décomposée en deux étapes : une étape d'analyse " qualitative " et une étape d'analyse " quantitative ". La première consiste à obtenir les relations de causalité entre les événements appartenant à un scénario donné. L'équivalence entre un arbre de preuve en logique linéaire et le processus fini obtenu par dépliage d'un réseau de Petri à partir du même marquage initial montre que ces relations sont des relations de précédence. L'introduction de la notion de séquent caractéristique permet de mettre en œuvre une approche compositionnelle des processus à partir des règles du calcul des séquents. La deuxième étape consiste à passer du graphe décrivant les relations de précédence à un graphe de contraintes temporelles exprimant de façon linéaire l'ensemble des contraintes temporelles quantitatives que doivent vérifier les dates des franchissements des transitions dans un scénario. Il devient ainsi possible d'exploiter tous les résultats des techniques classiques d'analyse et de propagation de contraintes. Cette démarche est complètement cohérente avec les réseaux de Petri p-temporels mais difficilement compatible avec les t-temporels car ils engendrent des ensembles de contraintes qui sont plus complexes. Nous avons illustré cette démarche par un problème simple d'ordonnancement de documents multimédias. Nous avons par la suite montré comment, pour les réseaux de Petri t-temporels, nous pouvions calculer les dates de franchissements et les durées de séjour des jetons dans les places en restant sous une forme symbolique dans le cadre de la sémantique faible.The aim of this thesis is to contribute to the elaboration of design assistance methods of cooperative systems while taking into account temporal constraints in a quantitative way. The developed approach is based on Petri nets, linear logic and temporal constraints networks. This is an "event" oriented approach and not a "state" oriented one as it is often the case in the approaches based on Petri nets. It is split in two steps: a step of "qualitative" analysis and a step of "quantitative" one. The first consists in obtaining the causality relations between the events belonging to a given scenario. The equivalence between a proof tree in linear logic and the finite process obtained by the unfolding of a Petri net from the same initial marking shows that these relations are precedence relations. The introduction of the concept of characteristic sequent makes it possible to implement a compositional approach of the processes from the rules of the linear logic sequent calculus. The second step consists in changing the graph describing the precedence relations into a temporal constraints graph expressing in a linear way the set of the quantitative temporal constraints which have to be verified by the dates of the firing transitions in a scenario. Thus, it become possible to exploit all the results of traditional techniques of analysis and constraints propagation. This step is completely consistent with p-time Petri nets but not easily compatible with the t-timed ones because they generate sets of constraints which are more complex. This approach is illustrated by a simple scheduling problem of multimedia documents. We showed thereafter how, for the t-timed Petri nets, we could process the firing dates and the sojourn durations of the tokens in the places of a net while remaining in a symbolic form within the framework of the weak semanticsINIST-CNRS (INIST), under shelf-number: RP 17272 / SudocSudocFranceF

Molecular characterization of Lma-p54, a new epicuticular surface protein in the cockroach Leucophaea maderae (Dictyoptera, oxyhaloinae)

0965-1748 (Print) Journal Article Research Support, Non-U.S. Gov'tThe epicuticular surface protein Lma-p54 is imbedded in the "cuticular waxes" which cover the abdominal surface of the adult Leucophaea maderae. Natural Lma-p54 was purified and the complete cDNA sequence was determined by RT-PCR using primers based on Edman degradation fragments. Northern blot and in situ hybridization analyses showed that Lma-p54 was expressed in the adult abdominal epidermis and in the chemical sense organs of both sexes. Sequence alignment indicates that Lma-p54 is closely related to aspartic proteases (EC 3.4.23). However, there are critical amino acid substitutions at the level of the active site and, since no proteolytic activity was detected in the abdominal secretion, the protein is likely inactive. As an inactive aspartic protease, Lma-p54 is related to pregnancy-associated glycoproteins (PAGs) which still present a peptide-binding ability. According to recent experiments using whole tergal protein secretions, a role in intraspecific contact recognition was proposed for this surface protein

Selection of reference genes for quantitative gene expression normalization in flax (<it>Linum usitatissimum </it>L.)

<p>Abstract</p> <p>Background</p> <p>Quantitative real-time PCR (qRT-PCR) is currently the most accurate method for detecting differential gene expression. Such an approach depends on the identification of uniformly expressed 'housekeeping genes' (HKGs). Extensive transcriptomic data mining and experimental validation in different model plants have shown that the reliability of these endogenous controls can be influenced by the plant species, growth conditions and organs/tissues examined. It is therefore important to identify the best reference genes to use in each biological system before using qRT-PCR to investigate differential gene expression. In this paper we evaluate different candidate HKGs for developmental transcriptomic studies in the economically-important flax fiber- and oil-crop (<it>Linum usitatissimum </it>L).</p> <p>Results</p> <p>Specific primers were designed in order to quantify the expression levels of 20 different potential housekeeping genes in flax roots, internal- and external-stem tissues, leaves and flowers at different developmental stages. After calculations of PCR efficiencies, 13 HKGs were retained and their expression stabilities evaluated by the computer algorithms geNorm and NormFinder. According to geNorm, 2 Transcriptional Elongation Factors (TEFs) and 1 Ubiquitin gene are necessary for normalizing gene expression when all studied samples are considered. However, only 2 TEFs are required for normalizing expression in stem tissues. In contrast, NormFinder identified glyceraldehyde-3-phosphate dehydrogenase (GADPH) as the most stably expressed gene when all samples were grouped together, as well as when samples were classed into different sub-groups.</p> <p>qRT-PCR was then used to investigate the relative expression levels of two splice variants of the flax <it>LuMYB1 </it>gene (homologue of <it>AtMYB59</it>). <it>LuMYB1-1 </it>and <it>LuMYB1-2 </it>were highly expressed in the internal stem tissues as compared to outer stem tissues and other samples. This result was confirmed with both geNorm-designated- and NormFinder-designated-reference genes.</p> <p>Conclusions</p> <p>The use of 2 different statistical algorithms results in the identification of different combinations of flax HKGs for expression data normalization. Despite such differences, the use of geNorm-designated- and NormFinder-designated-reference genes enabled us to accurately compare the expression levels of a flax MYB gene in different organs and tissues. Our identification and validation of suitable flax HKGs will facilitate future developmental transcriptomic studies in this economically-important plant.</p