Small critical RNAs in the scrapie agent

Unconventional infectious agents cause transmissible spongiform encephalopathy (TSE) diseases including scrapie and bovine spongiform encephalopathy (BSE) in animals and Creutzfeldt-Jakob disease in humans. The protein only hypothesis claims that the TSE agent is composed solely of the protein called prion (PrP^sc^)^1^. This protein is the misfolded form of a host-encoded cellular protein, PrP^c^ exerting presumably a vital role at the synapse^2^. Even though now widely accepted, the prion concept fails to provide in certain circumstances^3-6^, a satisfying interpretation of the infectious phenomenon. Using the 263K scrapie-hamster model, we conducted a transmission study to search for a putative prion-associated factor indispensable for infectivity. Here we show that innocuous recombinant prion protein (recPrP) was capable, in a reproducible manner, of transmitting scrapie disease when the protein was [beta]–sheet converted in a solution containing PrP^sc^-derived RNA material. Analysis of the PrP-RNA mixture revealed the association of recPrP with two prominent populations of small RNA molecules having an average length of about ~27 and ~55 nucleotides. We conclude that the nature of the TSE agent seems to be composed of a nucleoprotein molecular complex, in which informative RNA molecules of small sizes are associated with the misfolded prion protein (PrP^sc^)

Infecção por VIH entre imigrantes na Guiana Francesa: alto risco durante os primeiros anos após a chegada

Introduction. Over 75% of HIV patients in French Guiana are foreigners most of whom are actually infected locally. Objectives. We aimed to estimate the distribution of infections in time after arrival using a retrospective cohort. Methods. CD4 erosion modelling allowed to estimate the date of infection which was compared to the date of arrival in French Guiana in the subset of foreign patients that were estimated to have acquired HIV locally. Results. Among patients estimated to have been infected in French Guiana and having arrived after 1999, over half had been infected within 4 years and that a quarter of patients had acquired HIV within the 2 first years after arrival (median 3.9 years IQR=2.1-7.8 years). Conclusions. The added value of the present results is to show the rapid infection dynamics after arrival and emphasize the necessity of increasingly proactive combined prevention in recently arrived immigrants.Introdução. Mais de 75% dos pacientes com HIV na Guiana Francesa são estrangeiros, a maioria dos quais estão realmente infectados localmente. Objetivos. O nosso objetivo era estimar a distribuição das infecções no tempo após a chegada, utilizando uma coorte retrospectiva. Métodos. A modelagem da erosão CD4 permitiu estimar a data da infecção que foi comparada à data de chegada na Guiana Francesa no subconjunto de pacientes estrangeiros que foram estimados como tendo adquirido o HIV localmente.Resultados. Entre os pacientes estimados como tendo sido infectados na Guiana Francesa e tendo chegado após 1999, mais da metade tinha sido infectada dentro de 4 anos e que um quarto dos pacientes tinha adquirido o HIV dentro dos 2 primeiros anos após a chegada (mediana de 3,9 anos IQR=2,1-7,8 anos). Conclusões. O valor agregado dos resultados atuais é mostrar a rápida dinâmica da infecção após a chegada e enfatizar a necessidade de uma prevenção combinada cada vez mais proativa nos imigrantes recém-chegados

Respective roles of social deprivation, health literacy, and clinical factors for COVID-19: a case-control study in hospitalized patients

IntroductionTo investigate the association between social deprivation and COVID-19 among hospitalized patients in an underprivileged department of the greater Paris area.MethodsIndividuals hospitalized for COVID-19 between March 1st and October 31, 2020, were included, matched on age and sex, and compared with patients hospitalized for any other reason with negative RT-PCR for SARS-CoV-2, through a case-control study. Clinical, socio-demographic characteristics, health literacy, and social deprivation, assessed by the EPICES score, were collected. Factors associated with COVID-19 in hospitalized patients were assessed using univariate and multivariate logistic regression models.Results69 cases and 180 controls were included. Participants were mostly men (N = 148: 59.4%) aged 65 or older (N = 109: 44.1%). Median EPICES score was 43.2 (IQR 29.4–62.9). EPICES score > 30.17 (precariousness threshold) was not significantly associated with COVID-19 in hospitalized patients (adjusted odds ratio (aOR) = 0.46; 95% Confidence Interval (CI) [0.21–1.01]). Advanced age, higher BMI, professional activity, home area of less than 25 m2 per person, and low health literacy, were significantly associated with COVID-19 in hospitalized patients.DiscussionThis study highlights probable risk factors for specific exposition in disadvantaged area: maintenance of professional activity, smaller home area, and low health literacy

Intracardiac electrophysiology to characterize susceptibility to ventricular arrhythmias in murine models

Introduction: Sudden cardiac death (SCD) and ventricular fibrillation are rare but severe complications of many cardiovascular diseases and represent a major health issue worldwide. Although the primary causes are often acute or chronic coronary diseases, genetic conditions, such as inherited channelopathies or non-ischemic cardiomyopathies are leading causes of SCD among the young. However, relevant experimental models to study the underlying mechanisms of arrhythmias and develop new therapies are still needed. The number of genetically engineered mouse models with cardiac phenotype is growing, making electrophysiological studies in mice essential tools to study arrhythmogenicity and arrhythmia mechanisms and to test novel treatments. Recently, intracardiac catheterization via the jugular vein was described to induce and record ventricular arrhythmias in living anesthetized mice. Several strategies have been reported, developed in healthy wild-type animals and based on aggressive right ventricular stimulation.Methods: Here, we report a protocol based on programmed electrical stimulation (PES) performed in clinical practice in patients with cardiac rhythm disorders, adapted to two transgenic mice models of arrhythmia - Brugada syndrome and cardiolaminopathy.Results: We show that this progressive protocol, based on a limited number of right ventricular extrastimuli, enables to reveal different rhythmic phenotypes between control and diseased mice. In this study, we provide detailed information on PES in mice, including catheter positioning, stimulation protocols, intracardiac and surface ECG interpretation and we reveal a higher susceptibility of two mouse lines to experience triggered ventricular arrhythmias, when compared to control mice.Discussion: Overall, this technique allows to characterize arrhythmias and provides results in phenotyping 2 arrhythmogenic-disease murine models

Factors influencing ability to access to health care among sub-Saharan African migrants living in France : a comparison according to their HIV and HBV status

Les immigrés originaires d’Afrique subsaharienne (ASS) sont souvent exposés à des périodes de précarité et sont également une des populations les plus touchées par les infections par le VIH et le VHB. L’objectif de cette thèse était d’étudier leur accès aux soins en fonction de leur statut vis-à-vis du VIH ou le VHB. L’enquête ANRS-Parcours a été réalisée auprès de 2468 immigrés d’ASS vivant en Ile-de-France. Elle a utilisé une grille biographique analysée à l’aide de modèles de régression logistique à temps discret. L’enquête Baromètre santé 2010 a interrogé 27 653 personnes vivant en France dont 9% d’immigrés. Les immigrés subsahariens accèdent à une couverture maladie l’année de leur arrivée en France, mais un sur dix n’en disposait toujours pas trois ans après l’arrivée (plus souvent en l'absence de droit au séjour). Ils renoncent plus souvent aux soins pour raisons financières que la population majoritaire. Ce constat est aggravé par des refus de prise en charge des bénéficiaires de la CMU-C ou l’AME et des participants vivant avec le VIH. L’entrée en soins a lieu la même année que celle du diagnostic. La probabilité d’avoir fait une demande de titre de séjour pour raison de santé était plus élevée parmi les participants vivant avec le VIH. Les difficultés que peuvent rencontrer les immigrés dans la prise en charge de leurs maladies dépendent de leur situation sociale qui peut varier selon les étapes de la vie. Dans des vies marquées par une migration, ces situations sociales diffèrent selon les raisons et les conditions d’arrivée en France, selon le statut du séjour en France (avoir ou pas un titre de séjour, le droit de travailler…) et la façon dont celui-ci évolue.Immigrants from sub-Saharan Africa (SSA) are often exposed to periods of precariousness after arriving in France and are also one of the most affected populations by HIV and HBV infections. The aim of this thesis was to study the access to care of SSA immigrants according to their HIV or HBV status. The ANRS-Parcours survey was conducted among 2,468 SSA immigrants living in Paris area and the Baromètre santé 2010 among 27,653 people living in France. The Parcours survey used a biographical grid to collect indicators year after year analysed with a discrete-time logistic regression method. Sub-Saharan immigrants have access to health insurance coverage the year they arrived in France, but one in ten still did not have one three years after their arrival (more often in the absence of a permit of residence). They are more exposed to unmet health care needs than the rest of the population in France. This finding is aggravated by refusals to provide healthcare for participants covered by the specific health insurance for precarious or undocumented migrants and people living with HIV. The linkage to care takes place the year of the diagnosis. The likelihood of applying for a medical residence permit was higher among participants living with HIV. Social situations, which can change over time, affect the ability of immigrants to access health care. In the context of immigration, these social situations differ according to the reasons and conditions of arrival in France, depending on the status of the stay in France (having or not a residence permit, the right to work ...) and the way in which it evolves

Barrières et facteurs favorisant l'accès aux soins des immigrés originaires d'Afrique subsaharienne en France. Une comparaison en fonction de leur statut vis-à-vis du VIH et du VHB

Immigrants from sub-Saharan Africa (SSA) are often exposed to periods of precariousness after arriving in France and are also one of the most affected populations by HIV and HBV infections. The aim of this thesis was to study the access to care of SSA immigrants according to their HIV or HBV status. The ANRS-Parcours survey was conducted among 2,468 SSA immigrants living in Paris area and the Baromètre santé 2010 among 27,653 people living in France. The Parcours survey used a biographical grid to collect indicators year after year analysed with a discrete-time logistic regression method. Sub-Saharan immigrants have access to health insurance coverage the year they arrived in France, but one in ten still did not have one three years after their arrival (more often in the absence of a permit of residence). They are more exposed to unmet health care needs than the rest of the population in France. This finding is aggravated by refusals to provide healthcare for participants covered by the specific health insurance for precarious or undocumented migrants and people living with HIV. The linkage to care takes place the year of the diagnosis. The likelihood of applying for a medical residence permit was higher among participants living with HIV. Social situations, which can change over time, affect the ability of immigrants to access health care. In the context of immigration, these social situations differ according to the reasons and conditions of arrival in France, depending on the status of the stay in France (having or not a residence permit, the right to work ...) and the way in which it evolves.Les immigrés originaires d’Afrique subsaharienne (ASS) sont souvent exposés à des périodes de précarité et sont également une des populations les plus touchées par les infections par le VIH et le VHB. L’objectif de cette thèse était d’étudier leur accès aux soins en fonction de leur statut vis-à-vis du VIH ou le VHB. L’enquête ANRS-Parcours a été réalisée auprès de 2468 immigrés d’ASS vivant en Ile-de-France. Elle a utilisé une grille biographique analysée à l’aide de modèles de régression logistique à temps discret. L’enquête Baromètre santé 2010 a interrogé 27 653 personnes vivant en France dont 9% d’immigrés. Les immigrés subsahariens accèdent à une couverture maladie l’année de leur arrivée en France, mais un sur dix n’en disposait toujours pas trois ans après l’arrivée (plus souvent en l'absence de droit au séjour). Ils renoncent plus souvent aux soins pour raisons financières que la population majoritaire. Ce constat est aggravé par des refus de prise en charge des bénéficiaires de la CMU-C ou l’AME et des participants vivant avec le VIH. L’entrée en soins a lieu la même année que celle du diagnostic. La probabilité d’avoir fait une demande de titre de séjour pour raison de santé était plus élevée parmi les participants vivant avec le VIH. Les difficultés que peuvent rencontrer les immigrés dans la prise en charge de leurs maladies dépendent de leur situation sociale qui peut varier selon les étapes de la vie. Dans des vies marquées par une migration, ces situations sociales diffèrent selon les raisons et les conditions d’arrivée en France, selon le statut du séjour en France (avoir ou pas un titre de séjour, le droit de travailler…) et la façon dont celui-ci évolue

Rerum Burgundionum chronicon : in quo etiam rerum Gallicarum tempora accurate demonstrantur: permulta autem pro utriusque Historiae, necnon etiam Germanicae notitia, dubia confirmantur, obscura illustrantur, & ab aliis aut non animadversa, aut non comperta enucleantur: non pauca vero quorum memoria penitus interciderat, ex probatissimorum autorum libris nunquam antea editis & veteribus monimentis exhibentur

Ex bibliotheca historica Nicolai Vignierij Barrensis ad Sequana

Théâtre de l'Antéchrist : auquel est respondu au Cardinal Bellarmin, au Sieur de Remond, à Pererius, Ribera, Viegas, Sanderus & autres qui par leurs escrits condamnent la doctrine des églises réformés sur se subjet

par Nicolas Vignie