The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Nouveaux développements autour des potentialités de l'antenne BIE planaire

L'antenne BIE planaire est réalisée à partir de matériaux à bande interdite électromagnétique. Le filtrage spatial et fréquentiel des ondes obtenu avec ces matériaux périodiques permet de contrôler les directions privilégiées du rayonnement ainsi que la directivité de l'antenne. Les diverses potentialités qu'offre cette structure rayonnante ont permis de nombreux développements qui sont présentés dans ce mémoire. Il propose outre une technique de dimensionnement fiable, de nouvelles avancées comme le fonctionnement multifréquences et multifaisceaux. De plus, une excitation multisources associée à une technique de calcul simple a permis une augmentation significative du gain et de la bande de rayonnement. Cette antenne peu encombrante et fort gain convient à un panel d'applications variées. Les réalisations présentées confirment avec succès les différents fonctionnements proposésLIMOGES-BU Sciences (870852109) / SudocSudocFranceF

HPLC Analysis of Trans-Resveratrol in Human Plasma After Red Wine Consumption

International audienceTrans-resveratrol (t-RES), a phenolic compound produced by several plants and present in wine, has been reported to be a potential chemopreventive agent for cardiovascular, cancer and neurodegenerative pathologies. Thus, understanding the plasma level in vivo of trans-resveratrol is the prerequisite to evaluate its potential health impact. Bioavailability studies mainly in animals or in humans using the pure compound at very high doses were performed. The objective of this present study was to detected trans-resveratrol in human plasma from two subjects who consumed 600 mL of red wine over 40 min. Plasma analyses were performed by HPLC and obtained results indicated the absence of t- RES in subject plasma at any time with limit of detection of 5 ng/mL. In conclusion, this study suggests that t-RES from red wine is poorly bioavailable and even an important red wine consumption does not make it possible to obtain detectable plasma concentrations of t-RES

Le contrôle de l'identité à travers les âges

Garnier Ludovic, Lebas Fabien, Leger Claire, Lemoine Raphaëlle, Marcilly Matthieu, Mellal Fatiha, Paillat Xavier, Vercelonne Samuel, Verge Mélanie. Le contrôle de l'identité à travers les âges. In: Revue juridique de l'Ouest, 2012-3. pp. 343-362

Porphyrin-xylan-coated silica nanoparticles for anticancer photodynamic therapy

International audiencePorphyrins are widely used in anticancer photodynamic therapy (PDT). However, low physiological solubility and lack of selectivity towards cancer cells are the main limitations of their clinical use. Nanoparticles are being intensively explored as photosensitizer carriers for PDT to overcome these limitations. The aims of this work are to synthesize core-shell hybrid nanoparticles formed by a silica core and xylan carrying a 5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin (TPPOH) shell, and evaluate their anticancer activity. To afford drug-controlled incorporation and enhance blood circulation, TPPOH was covalently linked to xylan. Different xylans with degrees of substitution in TPPOH ranging from 0.034 to 1.11, were obtained and characterized. Then, the xylan-TPPOH conjugate (PX) was used to coat the silica nanoparticles (PX SNPs). The obtained nano-objects were characterized and their therapeutic potential for photodynamic therapy evaluated against colorectal cancer cell lines. in vitro analysis showed that PX SNPs were 40-fold and 10-fold more effective against HCT116 cells and HT-29 cells respectively compared to free TPPOH

Photodynamic Therapy Activity of New Porphyrin-Xylan-Coated Silica Nanoparticles in Human Colorectal Cancer

International audiencePhotodynamic therapy (PDT) using porphyrins has been approved for treatment of several solid tumors due to the generation of cytotoxic reactive oxygen species (ROS). However, low physiological solubility and lack of selectivity towards tumor sites are the main limitations of their clinical use. Nanoparticles are able to spontaneously accumulate in solid tumors through an enhanced permeability and retention (EPR) effect due to leaky vasculature, poor lymphatic drainage, and increased vessel permeability. Herein, we proved the added value of nanoparticle vectorization on anticancer efficacy and tumor-targeting by 5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin (TPPOH). Using 80 nm silica nanoparticles (SNPs) coated with xylan-TPPOH conjugate (TPPOH-X), we first showed very significant phototoxic effects of TPPOH-X SNPs mediated by post-PDT ROS generation and stronger cell uptake in human colorectal cancer cell lines compared to free TPPOH. Additionally, we demonstrated apoptotic cell death induced by TPPOH-X SNPs-PDT and the interest of autophagy inhibition to increase anticancer efficacy. Finally, we highlighted in vivo, without toxicity, elevated anticancer efficacy of TPPOH-X SNPs through improvement of tumor-targeting compared to a free TPPOH protocol. Our work demonstrated for the first time the strong anticancer efficacy of TPPOH in vitro and in vivo and the merit of SNPs vectorization

Prognostic Factors of Paraneoplastic Pemphigus.

International audienceOBJECTIVE To identify the prognostic factors of overall survival in a series of patients with paraneoplastic pemphigus (PNP). DESIGN Multicenter retrospective cohort study. SETTING Twenty-seven dermatology departments in France. PATIENTS A total of 53 patients (31 men and 22 women; median age, 59 years; age range, 30-88 years) were diagnosed as having PNP between 1992 and 2010. MAIN OUTCOME MEASURES Overall Kaplan-Meier survival rates were estimated, and features associated with survival were assessed using univariate (log-rank test) and multivariate (Cox regression) analyses. RESULTS The study included 53 patients with PNP. Thirty-six patients (68%) died during the study. The 1-, 3-, and 5-year overall survival rates were 49%, 41%, and 38%, respectively. The main causes of death were infections (n = 21) and evolution of neoplasia (n = 6). In univariate analysis, the main detrimental prognostic factors identified were erythema multiforme-like skin lesions (P = .05) and histologic keratinocyte necrosis (P = .03). None of the 5 patients with Castleman disease died during the study. After adjustment for age and sex in multivariate analysis, erythema multiforme-like skin lesions remained predictive of fatal outcome, with a 2-fold increase in death rate (hazard ratio [HR], 2.3; 95% CI, 1.05-5.03; P = .04). The prognosis of patients with PNP was even poorer when erythema multiforme-like skin lesions were associated with severe skin or mucosal involvement at presentation (HR of death, 3.0; 95% CI, 1.01-8.92; P = .049). CONCLUSION Patients with PNP with erythema multiforme-like skin lesions and histologic keratinocyte necrosis, especially when associated with extensive lesions at presentation, are likely to have a more severe and rapid fatal outcome and should be managed very carefully