Reform of the first year of medical studies and diversification of student profiles in France: an unmet need?

Objectives: To determine whether the reform of the first year of medical studies implemented in September 2020 in France met its objective of diversifying the profiles of students admitted to second year at the faculty of medicine at the University of Tours.

Methods: Single-centered, retrospective study, covering students who passed the first year of medical studies between 2018 and 2022. Student profiles originating from three different entry gateways (PACES, PASS and L.

Delivery of Anticancer Drugs Using Microbubble-Assisted Ultrasound in a 3D Spheroid Model.

Tumor spheroids are promising three-dimensional (3D) tumor models for the evaluation of drug delivery methods. The design of noninvasive and targeted drug methods is required to improve the intratumoral bioavailability of chemotherapeutic drugs and reduce their adverse off-target effects. Among such methods, microbubble-assisted ultrasound (MB-assisted US) is an innovative modality for noninvasive targeted drug delivery.

The KxGxYR and DxE motifs in the C-tail of the Middle East respiratory syndrome coronavirus membrane protein are crucial for infectious virus assembly.

The coronavirus' (CoV) membrane (M) protein is the driving force during assembly, but this process remains poorly characterized. Previously, we described two motifs in the C-tail of the Middle East respiratory syndrome CoV (MERS-CoV) M protein involved in its endoplasmic reticulum (ER) exit (DxE) and trans-Golgi network (TGN) retention (KxGxYR). Here, their function in virus assembly was investigated by two different virus-like particle (VLP) assays and by mutating both motifs in an infectious MERS-CoV cDNA clone.

The double-membrane vesicle (DMV): a virus-induced organelle dedicated to the replication of SARS-CoV-2 and other positive-sense single-stranded RNA viruses.

Positive single-strand RNA (+ RNA) viruses can remodel host cell membranes to induce a replication organelle (RO) isolating the replication of their genome from innate immunity mechanisms. Some of these viruses, including severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), induce double-membrane vesicles (DMVs) for this purpose. Viral non-structural proteins are essential for DMV biogenesis, but they cannot form without an original membrane from a host cell organelle and a significant supply of lipids.

A morphometric analysis of hepatitis B subviral particles shows no correlation of filament proportion and length with clinical stage and genotype.

It was recently suggested that the composition of circulating hepatitis B subviral particles (SVPs) could be used to differentiate the various stages in chronic hepatitis B virus (HBV) infection, with significantly lower proportions of L and M proteins in inactive carriers than in individuals with chronic hepatitis. L protein is abundant in virions and filamentous SVPs but almost absent from spherical SVPs. We, therefore, performed a morphometric analysis of SVPs in these two groups of patients, by conducting a retrospective analysis on sera from 15 inactive carriers and 11 patients with chronic hepatitis infected with various HBV genotypes.

Crystalline podocytopathy and tubulopathy linked to kappa light chain deposits in a context of smoldering multiple myeloma.

A 42-year-old man with smoldering immunoglobulin G kappa multiple myeloma showed a heavy proteinuria composed of free light chain, prompting performance of a kidney biopsy. Electron microscopy revealed numerous rhomboid-shaped crystals labelled by the anti-kappa in immunogold, notably in the cytoplasm of podocytes, establishing the diagnosis of crystalline podocytopathy. This case illustrates a rare form of monoclonal gammopathy of renal significance, and highlights the key role of electron microscopy and immunogold to better elucidate the location and composition of crystals.

Secretory Vesicles Are the Principal Means of SARS-CoV-2 Egress.

The mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) egress, similar to those of other coronaviruses, remain poorly understood. The virus buds in intracellular compartments and is therefore thought to be released by the biosynthetic secretory pathway. However, several studies have recently challenged this hypothesis.

Clinical spectrum of MTOR-related hypomelanosis of Ito with neurodevelopmental abnormalities.

Purpose: Hypomelanosis of Ito (HI) is a skin marker of somatic mosaicism. Mosaic MTOR pathogenic variants have been reported in HI with brain overgrowth. We sought to delineate further the pigmentary skin phenotype and clinical spectrum of neurodevelopmental manifestations of MTOR-related HI.

Alternative splicing creates a pseudo-strictosidine β-d-glucosidase modulating alkaloid synthesis in Catharanthus roseus.

Deglycosylation is a key step in the activation of specialized metabolites involved in plant defense mechanisms. This reaction is notably catalyzed by β-glucosidases of the glycosyl hydrolase 1 (GH1) family such as strictosidine β-d-glucosidase (SGD) from Catharanthus roseus. SGD catalyzes the deglycosylation of strictosidine, forming a highly reactive aglycone involved in the synthesis of cytotoxic monoterpene indole alkaloids (MIAs) and in the crosslinking of aggressor proteins.

Annulate lamellae and intracellular pathogens.

Annulate lamellae (AL) have been observed many times over the years on electron micrographs of rapidly dividing cells, but little is known about these unusual organelles consisting of stacked sheets of endoplasmic reticulum-derived membranes with nuclear pore complexes (NPCs). Evidence is growing for a role of AL in viral infection. AL have been observed early in the life cycles of the hepatitis C virus (HCV) and, more recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), suggesting a specific induction of mechanisms potentially useful to these pathogens.

Ultrastructural modifications induced by SARS-CoV-2 in Vero cells: a kinetic analysis of viral factory formation, viral particle morphogenesis and virion release.

Many studies on SARS-CoV-2 have been performed over short-time scale, but few have focused on the ultrastructural characteristics of infected cells. We used TEM to perform kinetic analysis of the ultrastructure of SARS-CoV-2-infected cells. Early infection events were characterized by the presence of clusters of single-membrane vesicles and stacks of membrane containing nuclear pores called annulate lamellae (AL).

Hepatitis B Virus Entry into Cells.

Hepatitis B virus (HBV), an enveloped partially double-stranded DNA virus, is a widespread human pathogen responsible for more than 250 million chronic infections worldwide. Current therapeutic strategies cannot eradicate HBV due to the persistence of the viral genome in a special DNA structure (covalently closed circular DNA, cccDNA). The identification of sodium taurocholate co-transporting polypeptide (NTCP) as an entry receptor for both HBV and its satellite virus hepatitis delta virus (HDV) has led to great advances in our understanding of the life cycle of HBV, including the early steps of infection in particular.

Clinicopathologic features of infection-related glomerulonephritis with IgA deposits: a French Nationwide study.

Background: Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA.

Hepatitis B virus entry into HepG2-NTCP cells requires clathrin-mediated endocytosis.

Hepatitis B virus (HBV) is a leading cause of cirrhosis and hepatocellular carcinoma worldwide, with 250 million individuals chronically infected. Many stages of the HBV infectious cycle have been elucidated, but the mechanisms of HBV entry remain poorly understood. The identification of the sodium taurocholate cotransporting polypeptide (NTCP) as an HBV receptor and the establishment of NTCP-overexpressing hepatoma cell lines susceptible to HBV infection opens up new possibilities for investigating these mechanisms.

BK Polyomavirus Hijacks Extracellular Vesicles for Transmission.

Most people are asymptomatic carriers of the BK polyomavirus (BKPyV), but the mechanisms of persistence and immune evasion remain poorly understood. Furthermore, BKPyV is responsible for nephropathies in kidney transplant recipients. Unfortunately, the sole therapeutic option is to modulate immunosuppression, which increases the risk of transplant rejection.

Histogenesis of Merkel Cell Carcinoma: A Comprehensive Review.

Merkel cell carcinoma (MCC) is a primary neuroendocrine carcinoma of the skin. This neoplasia features aggressive behavior, resulting in a 5-year overall survival rate of 40%. In 2008, Feng et al.

The Centriolar Adjunct⁻Appearance and Disassembly in Spermiogenesis and the Potential Impact on Fertility.

During spermiogenesis, the proximal centriole forms a special microtubular structure: the centriolar adjunct. This structure appears at the spermatid stage, which is characterized by a condensed chromatin nucleus. We showed that the centriolar adjunct disappears completely in mature porcine spermatozoa.

Virus detection by transmission electron microscopy: Still useful for diagnosis and a plus for biosafety.

Transmission electron microscopy (TEM) is the only imaging technique allowing the direct visualization of viruses, due to its nanometer-scale resolution. Between the 1960s and 1990s, TEM contributed to the discovery of many types of viruses and served as a diagnostic tool for identifying viruses directly in biological samples, either in suspension or in sections of tissues or mammalian cells grown in vitro in contact with clinical samples. The diagnosis of viral infections improved considerably during the 1990s, with the advent of highly sensitive techniques, such as enzyme-linked immunosorbent assay (ELISA) and PCR, rendering TEM obsolete for this purpose.

The Hepatitis C Virus-Induced Membranous Web in Liver Tissue.

Host cell membrane rearrangements induced by the hepatitis C virus (HCV) have been exclusively studied in vitro These studies have shown that HCV induces double-membrane vesicles (DMVs), which probably serve to separate replication sites from the cytoplasmic sensors of the innate immune response. We report for the first time the observation of HCV-induced membrane rearrangements in liver biopsy specimens from patients chronically infected with HCV. Unlike observations performed in vitro, the membranous web detected in liver tissue seems essentially made of clusters of single-membrane vesicles derived from the endoplasmic reticulum and close to lipid droplets.