Study Protocol: Randomised Controlled Trial Assessing the Efficacy of Strategies Involving Self-Sampling in Cervical Cancer Screening

Objectives: The cervical cancer screening coverage remains moderate (60%) in France. The aim of the study is to evaluate the efficacy of two experimental invitation strategies (offer of urine or vaginal self-sampling kits) to reach under-screened populations and compare them with the current invitation strategy in rural departments (low medical density and low participation rate) in France.Methods: The study is a randomised controlled trial with three arms: a control arm (conventional invitation letter) and two experimental arms (mailing of a urine or vaginal self-sampling kit). The target population includes women aged 30–65 years, who had no screening test recorded since more than 4 years and who did not respond to an invitation letter within 12 months before. The primary outcome measure is the participation rate in each arm. A team of psychologists will also investigate attitudes and experiences by semi-structured/focus-group interviews with voluntary CapU4 participants and with health professionals.Result and conclusion: CapU4 will identify effective strategies to reach women not responding to current screening invitations and will generate information about acceptance of self-sampling among women and health professionals

Role of hepatitis B virus precore/core proteins and impact of precore/core region variability in liver pathogenesis : clinical approach and basic research

L’infection chronique par le virus de l’hépatite B (VHB) demeure un problème de santé publique majeur. Au stade chronique de l’infection, des complications peuvent survenir comme la fibrose hépatique qui peut évoluer vers une cirrhose ou un carcinome hépato cellulaire. Le mécanisme physiopathologique de la fibrose hépatique est complexe mais l'activation puis la prolifération des cellules hépatiques stellaires (CHS) joue un rôle primordial dans la fibrogenèse. L'implication du VHB, de ses protéines virales spécifiques ou de sa variabilité génétique dans la fibrose reste à préciser. Nos travaux de recherche ont permis de poursuivre l’étude du rôle de la variabilité des régions promoteur basal du core (PBC) / précore (PC) / core dans la fibrose hépatique. En parallèle, nous avons développé des outils moléculaires et cellulaires afin de reproduire in vitro un modèle de fibrose. Pour cela, nous avons fait le choix de la co-culture des HepaRG (hépatocytes) et des LX-2 (CHS). En alliant une approche clinique et fondamentale, ce travail a permis (i) de montrer un impact des mutants PBC/PC dans les mécanismes biologiques impliquant le TGF-β1 et le PDGF-BB ; (ii) d’instaurer la transduction des cellules HepaRG au laboratoire, utile pour la production de protéines d’intérêt du VHB au sein de ces cellules et le développement du modèle ; (iii) d’initier le développement d’un modèle in vitro d’étude de la fibrose lors de l’infection par le VHB. En perspective, le développement de ce modèle permettra d’étudier le rôle différencié ou combiné des protéines HBc et HBe du VHB dans la fibrose, et de mieux comprendre l’impact des mutants PBC/PC dans la fibrose hépatique.Chronic hepatitis B virus (HBV) infection remains a major public health problem. At the stage of chronic HBV infection, complications can occur such as liver fibrosis which can progress to cirrhosis or hepatocellular carcinoma. The pathophysiological mechanism of liver fibrosis is complex but the activation and proliferation of hepatic stellate cells (HSC) play a major role in fibrogenesis. The role of HBV, its viral proteins or its genomic variability in fibrosis remains to be clarified. We focused the study on investigating the role of the variability of the basal core promoter (BCP) / precore / core regions in liver fibrosis. In parallel, we have developed molecular and cellular tools to reproduce an in vitro model of liver fibrosis. For this purpose, we have chosen to culture two cell types: HepaRG (hepatocytes-like) and LX-2 (HSC-like). By combining a clinical and fundamental approachs, this work allowed (i) to show an impact of BCP/PC mutants in the biological mechanisms involving TGF-β1 and PDGF BB; (ii) to establish the transduction of HepaRG cells in the laboratory, useful for the production of HBV proteins within these cells and the development of the model; (iii) to initiate the development of an in vitro model for the study of liver fibrosis during HBV infection. In perspective, the development of this model will allow to study the differentiated or combined role of HBc and HBe proteins of HBV in fibrosis, and to better understand the impact of BCP/PC mutants in liver fibrosis

Spécificité du travail du pédopsychiatre dans la prise en charge des troubles oppositionnels du jeune enfant

RENNES1-BU Santé (352382103) / SudocSudocFranceF

A Pleiotropic Role of the Hepatitis B Virus Core Protein in Hepatocarcinogenesis

International audienceChronic hepatitis B virus (HBV) infection is one of the most common factors associated with hepatocellular carcinoma (HCC), which is the sixth most prevalent cancer among all cancers worldwide. However, the pathogenesis of HBV-mediated hepatocarcinogenesis is unclear. Evidence currently available suggests that the HBV core protein (HBc) plays a potential role in the development of HCC, such as the HBV X protein. The core protein, which is the structural component of the viral nucleocapsid, contributes to almost every stage of the HBV life cycle and occupies diverse roles in HBV replication and pathogenesis. Recent studies have shown that HBc was able to disrupt various pathways involved in liver carcinogenesis: the signaling pathways implicated in migration and proliferation of hepatoma cells, apoptosis pathways, and cell metabolic pathways inducing the development of HCC; and the immune system, through the expression and production of proinflammatory cytokines. In addition, HBc can modulate normal functions of hepatocytes through disrupting human host gene expression by binding to promoter regions. This HBV protein also promotes HCC metastasis through epigenetic alterations, such as micro-RNA. This review focuses on the molecular pathogenesis of the HBc protein in HBV-induced HCC

Les occupations laténiennes du Mesnil-Aubry « Le Bois Bouchard IV » (Val-d’Oise)

National audienc

Practical approach to method verification in plasma and validation in cerebrospinal fluid under accreditation using a flexible scope in molecular virology: setting up the HIV, HBV and HCV Aptima™ Quant Dx assays

International audienceAbstract Background Our laboratory obtained the ISO 15189 accreditation for the plasmatic HIV-1, HBV and HCV viral load (VL) using the m2000 RealTi m e™ system, which was recently changed for the platform Panther ® . Here, we discuss a strategy for performing method validation/verification very quickly. Methods We performed the mandatory (repeatability, internal quality assessment [IQA], measurement uncertainty [MU]) and optional technical verifications for CE/IVD assays using the flexible scope range A. We also performed the mandatory assays for the validation of HIV-1 VL in the cerebrospinal fluid (CSF) using the flexible scope range B. The change was checked by following up on the turnaround time (TAT). Results The coefficient of variation (CV%) for repeatability and IQA complied with the limit of 0.25 log. The MU results ranged from 0.04 to 0.25 log copies or IU/mL. The comparisons of methods showed excellent correlations (R 2 = 0.96 for the three parameters) but a delayed centrifugation on HCV VL showed variations of up to 2 log IU/mL. An excellent linearity for HIV-1 in the CSF was obtained from 1.5 to 5 log copies/mL with R 2 = 0.99. The TAT increased (84%–98%) in routine usage. Conclusions The three Aptima assays are well suited for routine laboratory use and can be integrated within less than 2 weeks in accordance with flexible scope range A. Our data allows us to confidently perform HIV-1 VL in CSF following flexible scope range B. Finally, we provide an organizational guide for flexible scope management in molecular virology within a short time frame