Novel functional hepatitis C virus glycoprotein isolates identified using an optimised viral pseudotype entry assay

Retrovirus pseudotypes are a highly tractable model used to study the entry pathways of enveloped viruses. This model has been extensively applied to the study of the hepatitis C virus (HCV) entry pathway, pre-clinical screening of antiviral antibodies and for assessing the phenotype of patient-derived viruses using HCV pseudoparticles (HCVpp) possessing the HCV E1 and E2 glycoproteins. However, not all patient-isolated clones produce particles that are infectious in this model. This study investigated factors that might limit phenotyping of patient-isolated HCV glycoproteins. Genetically related HCV glycoproteins from individual patient quasispecies were discovered to behave very differently in this entry model. Empirical optimisation of the ratio of packaging construct and glycoprotein-encoding plasmid was required for successful HCVpp genesis for different clones. The selection of retroviral packaging construct also influenced the function of HCV pseudoparticles. Some glycoprotein constructs tolerated a wide range of assay parameters, while others were much more sensitive to alterations. Furthermore, glycoproteins previously characterised as unable to mediate entry were found to be functional. These findings were validated using chimeric cell-cultured HCV bearing these glycoproteins. Using the same empirical approach we demonstrated that generation of infectious ebolavirus pseudoviruses (EBOVpv) were also sensitive to the amount, and ratio, of plasmids used, and that protocols for optimal production of these pseudoviruses is dependent on the exact virus glycoprotein construct. These findings demonstrate that it is crucial for studies utilising pseudoviruses to conduct empirical optimisation of pseudotype production for each specific glycoprotein sequence to achieve optimal titres and facilitate accurate phenotyping

Les défis éthiques et managériaux de l'IA dans le secteur de la santé : une revue systématique de littérature

International audienceAre recent developments in Artificial Intelligence (AI) the solution to the crises facing the health sector? Experiments at the initiative of public authorities, large technological companies and healthcare organizations have experienced dazzling progress in recent years, as hopes are so high. The research objective of this paper is to achieve a systematic literature review on the AI technologies in the healthcare sector. The results reveal ethical and managerial challenges that arise from the perception of actors confronted with AI. These issues are included in a conceptual framework that provides a better understanding of the influence of actors' perceptions on the success of AI in health. Finally, this research allows to identify futures research avenues, a sign that this theme is richly promising for Information Systems research.Les développements récents de l'Intelligence Artificielle (IA) sont-ils la solution aux crises que traversent le secteur de la santé ? Les expérimentations à l'initiative des pouvoirs publics, des grandes sociétés technologiques et des organisations de soin connaissent ces dernières années une progression fulgurante tant les espoirs sont immenses. Cette étude a pour objectif de réaliser une revue de littérature sur les technologies de l'IA dans le secteur de la santé. Les résultats font apparaître des défis éthiques et managériaux qui naissent de la perception des acteurs confrontés à l'IA. Ces défis sont repris dans un cadre conceptuel qui permet de mieux appréhender l'influence des perceptions des acteurs sur la réussite de l'IA en santé. Enfin, ces travaux ont permis de dégager plusieurs pistes de recherche, signe que ce thème est riche et prometteur pour la recherche en management des systèmes d'information

Épidémiologie des états septiques sévères et des états de choc septique dans la région Languedoc-Roussillon en 2006

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Le taux de publications dans les revues scientifiques des thèses d'exercice de Médecine Générale soutenues à Marseille entre 2008 et 2013 et impact factor des travaux publiés

Thèse en BinômeIntroduction: The end of the general medical studies is marked by the defense of an exercise thesis. This thesis is made more and more in a format "thesis article" more adapted to a possible publication in a scientific journal.Our work aims on the one hand to determine the evolution of the rate of publication on the platforms PUBMED and/or GOOGLE SCHOLAR of the thesis of General medicine exercises supported at the Faculty of Medicine of Aix-Marseille between the first January 2008 and 31 December 2013. And on the other hand the impact factor of theses published.Method: This is a retrospective study that covers all the thesis supported between 2008 and 2013 that we have listed in relation to the University library.We searched for the identity of the PhD student and/or thesis Director first on PubMed and then on GOOGLE SCHOLAR if the thesis was not found on PubMed.Results: 645 theses were supported between 2008 and 2013, 68 were published on PUBMED and GOOGLE SCHOLAR, an average publication rate of 10.54%. The minimum publication rate was 7.08% in 2010 and the maximum of 14.17% in 2012. The average impact factor in the study period was 2.321.Discussion/Conclusion: The rate of publication of general medicine theses during this period increases but still remains low compared to other specialties. There are opportunities to overcome this lack: to encourage interns to publish (training in scientific research), to promote English as a language of publication, or to speed up certain administrative formalities necessary for research For interns. Between 2008 and 2013 the IF doubled. This means that there is an improvement in the quality of theses published.Introduction : la fin des études de médecine générale est marquée par la soutenance d’une thèse d’exercice. Cette thèse se fait de plus en plus sous un format « thèse article » plus adapté à une éventuelle publication dans une revue scientifique.Notre travail a pour objectif d’une part la détermination de l’évolution du taux de publication sur les plateformes PUBMED et/ou GOOGLE SCHOLAR des thèses d’exercices de médecine générale soutenues à la faculté de médecine d’Aix-Marseille entre le premier Janvier 2008 et le 31 Décembre 2013. Et d’autre part l’impact factor des thèses publiées.Méthode : il s’agit d’une étude rétrospective qui porte sur l’ensemble des thèses soutenues entre 2008 et 2013 que nous avons répertorié en relation avec la bibliothèque universitaire. Nous avons recherché l’identité du thésard et/ou du directeur de thèse premièrement sur PUBMED puis sur GOOGLE SCHOLAR si la thèse n’était pas retrouvée sur PUBMED.Résultats : 645 thèses ont été soutenues entre 2008 et 2013, 68 ont été publiées sur PUBMED et GOOGLE SCHOLAR, soit un taux de publication moyen de 10,54 %. Le taux de publication minimum été de 7,08 % en 2010 et le maximum de 14,17 % en 2012.Le facteur d’impact moyen dans la période étudiée était de 2,321.Discussion/conclusion : Le taux de publication des thèses de médecine générale durant cette période augmente mais reste encore faible comparé à d’autres spécialités. Il existe des perspectives pour pallier ce manque : inciter les internes à la publication (formation à la recherche scientifique), favoriser l’anglais comme langue de publication, ou accélérer certaines formalités administratives nécessaires à la recherche pour les internes. Entre 2008 et 2013 l’IF a doublé. Cela signifie qu’il y a une amélioration de la qualité des thèses publiées

The antiviral role of zinc and metallothioneins in hepatitis C infection

Metallothioneins (MTs) are small, cysteine-rich proteins characterized by a high affinity for monovalent and divalent cations, such as copper and zinc. Of the four known MT isoforms, only, members of the MT 1 and 2 subfamilies are widely expressed, acting as metal chaperones whose primary role is to mediate intracellular zinc homoeostasis. Metallothioneins are potently induced by heavy metals and other sources of oxidative stress where they facilitate metal binding and detoxification as well as free radical scavenging. Metallothionein expression is well documented in the context of viral infection; however, it remains uncertain whether MTs possess specific antiviral roles or whether induction is merely a consequence of cellular stress. To better understand the role of MTs following hepatitis C virus (HCV) infection, we examined MT expression and localization in vitro and in vivo and used a siRNA knockdown approach to ascertain their antiviral efficacy. We confirmed HCV-driven MT induction in vitro and demonstrated MT accumulation in the nucleus of HCV-infected hepatocytes by immunofluorescence. Using a pan-MT siRNA to knock down all members of the MT1 and MT2 subfamilies, we demonstrate that they are mildly antiviral against the JFH1 strain of HCV in vitro (~1.4 fold increase in viral RNA, P < .05). Furthermore, the antiviral effect of zinc treatment against HCV in vitro was mediated through MT induction (P < .05). Our data suggest a potential benefit of using zinc as a low-cost adjunct to current HCV antiviral therapies and suggest that zinc may facilitate the antiviral role of MTs against other viruses