Nutrigenomic modification induced by anthocyanin-rich bilberry extract in the hippocampus of ApoE-/- mice

Dietary anthocyanins may slow cognitive decline, improve cognitive performance and exert neuroprotective effects against neurodegenerative disorders. However, the underlying mechanisms of their action are not fully understood. This study investigated the effects of 12-week anthocyanin-rich bilberry extract supplementation (0.02%) on global gene expression in the hippocampus of ApoE-/- mice to help the understanding of molecular mechanisms underlying anthocyanin neuroprotective effects. Gene expression analysis identified 1698 differently expressed genes, with 611 downregulated and 1087 upregulated genes. Bioinformatics revealed that these genes regulate different biological processes, including neurogenesis, inflammation, metabolism, cell to cell adhesion, cytoskeleton organization, and Alzheimer's and Parkinson's disease pathology. The bioinformatic analysis also proposed potential miRNAs and transcription factors that could be involved in the mediation of these nutrigenomic effects. Results from molecular docking also suggested that anthocyanins could bind to top transcription factors with, as potential consequence, an impact on their gene expression regulation. Taken together, integrated analysis revealed a multi-target mode of action of anthocyanin-rich bilberry extract in the hippocampus underlying their neuroprotective properties

Prevalence of HIV-1 drug resistance in treated patients with viral load >50 copies/mL in 2009: a French nationwide study

Background Surveillance of HIV-1 drug resistance in treated patients with plasma viral load (VL) >50 copies/mL. Methods The protease and reverse transcriptase (RT) genes were systematically sequenced in samples from 756 patients with VL >50 copies/mL in 2009. The genotyping results were interpreted for each antiretroviral drug (ARV) by using the ANRS algorithm v21. Weighted analyses were used to derive representative estimates of percentages of patients. Prevalence rates were compared with those obtained in 2004 among patients with VL >1000 copies/mL. Results Sequences were obtained for 506 patients. Sequencing was successful in 45%, 80% and 96% of samples with VL of 51-500, 501-1000 and >1000 copies/mL, respectively. Resistance or possible resistance to at least one ARV was observed in 59% of samples. Overall, 0.9% of samples contained viruses resistant to all drugs belonging to at least three drug classes. All resistance prevalence rates were significantly lower in 2009 than in 2004. Conclusion In France, where 86% of patients were receiving combination antiretroviral therapy in 2009, only 15.0% of patients had a VL >50 copies/mL, suggesting that only 8.9% of treated patients could potentially transmit resistant viruses. Only 0.08% of patients harboured viruses fully resistant to at least three antiretroviral drug classes. Further studies are needed to determine whether resistance continues to decline over tim

HIV-1-infected patients from the French National Observatory experiencing virological failure while receiving enfuvirtide

Objectives We studied gp41 mutations associated with failing enfuvirtide salvage therapy. Methods This multicentre study involved patients with HIV-1 plasma viral load (pVL) > 5000 copies/mL after at least 3 months of uninterrupted enfuvirtide therapy and with plasma samples available at inclusion (T0), at initial enfuvirtide failure (T1) and at last follow-up visit during continued failing enfuvirtide therapy (T2). The HR-1 and HR-2 domains of the gp41 gene were sequenced at T0, T1 and T2. Results Ninety-nine patients were enrolled. At baseline, the median pVL and CD4 cell count were 5.1 log copies/mL and 72 cells/mm3, respectively. Based on the ANRS Resistance Group algorithm, the proportion of patients harbouring viruses with enfuvirtide resistance mutations increased significantly between T0 and T1. In the HR-1 domain, the V38A/M, Q40H, N42T, N43D and L45M mutations wereselected (P < 0.02). In the HR-2 domain, no mutations were significantly selected during the follow-up. None of the mutations was associated with a CD4 cell count increment. Conclusions Mutations selected during failing enfuvirtide salvage therapy are mainly located in the HR-1 domain of the gp41 gene, between codons 38 and 45. No mutations were associated with an increase in the CD4 cell coun

RReportGenerator: automatic reports from routine statistical analysis using R.

With the establishment of high-throughput (HT) screening methods there is an increasing need for automatic analysis methods. Here we present RReportGenerator, a user-friendly portal for automatic routine analysis using the statistical platform R and Bioconductor. RReportGenerator is designed to analyze data using predefined analysis scenarios via a graphical user interface (GUI). A report in pdf format combining text, figures and tables is automatically generated and results may be exported. To demonstrate suitable analysis tasks we provide direct web access to a collection of analysis scenarios for summarizing data from transfected cell arrays (TCA), segmentation of CGH data, and microarray quality control and normalization. AVAILABILITY: RReportGenerator, a user manual and a collection of analysis scenarios are available under a GNU public license on http://www-bio3d-igbmc.u-strasbg.fr/~wraf

Influence de l’exposition environnementale au bruit sur la survie à un an post-accident vasculaire cérébral

Le lien entre exposition au bruit et la survenue d’une maladie cardiovasculaire ou d’un accident vasculaire cérébral (AVC) a été mis en évidence à plusieurs reprises. Cependant, l’impact du bruit environnemental sur le pronostic post-AVC (après la survenue d’un AVC) reste à étudier. Notre objectif est d’étudier la relation entre l'exposition au bruit environnemental et le pronostic à un an des patients ayant subi un AVC de type ischémique. Le registre dijonnais des AVC dispose d’une base de données contenant les caractéristiques des patients habitant Dijon et ayant présenté un AVC et leur devenir (suivi à un an). Dans cette étude, seuls les premiers AVC, de type ischémique, suivis d’un retour au domicile, sur la période 2005-2009 ont été inclus. L’exposition au bruit environnemental en façade du bâtiment d’habitation a été évaluée à partir de l’adresse du patient selon cinq indicateurs : l’indice combiné jour – soir – nuit Lden et les niveaux sonores continus équivalents pondérés à calculer pour différentes périodes : jour, soir nuit, 24 heures. Des analyses de sensibilité stratifiées sur l'âge et le sexe ont été réalisées. Le critère de jugement principal était la mortalité à 1 an post-AVC. Parmi les 896 AVC recensés, l’analyse a porté sur 359 patients éligibles. Aucune association significative n'a été observée entre l'exposition au bruit et la survie à 1 an post-AVC. Cependant, un effet différentiel entre sexe, en particulier chez les femmes âgées de moins de 65 ans, n'a pas pu être exclu. La différence de survie post-AVC entre hommes et femmes reste incertaine et mériterait d'être étudiée de manière plus approfondie en mettant l'accent sur : un autre facteur environnemental (pollution de l'air), la mortalité à long terme et les patients présentant un pronostic fonctionnel précoce plus restreint

Prevalence of HIV-1 drug resistance in treated patients with viral load >50 copies/mL in 2009: a French nationwide study.

International audienc

Prevalence of HIV-1 drug resistance in treated patients with viral load >50 copies/mL in 2009: a French nationwide study.

International audienc

Weak Immunogenicity of SARS-CoV-2 Vaccine in Patients with Hematologic Malignancies

Abstract This study evaluated the safety and immunogenicity of BNT162b2 vaccine in patients with hematological malignancies. Antibodies blocking spike binding to immobilized ACE-2 (NAb) correlated with anti-Spike (S) IgG d42 titers (Spearman r\,=\,0.865, p \,<\,0.0001), and an anti-S IgG d42 level ≥q3100 UA/mL was predictive of NAb\,≥q\,30%, the positivity cutoff for NAb ( p \,<\,0.0001). Only 47% of the patients achieved an anti-S IgG d42 level ≥q3100 UA/mL after the two BNT162b2 inocula, compared to 87% of healthy controls. In multivariable analysis, male patients, use of B-cell targeting treatment within the last 12 months prior to vaccination, and CD19 + B-cell level <120/uL, were associated with a significantly decreased probability of achieving a protective anti-S IgG level after the second BNT162b2 inoculum. Finally, using the IFN-γ ELISPOT assay, we found a significant increase in T-cell response against the S protein, with 53% of patients having an anti-S IgG-positive ELISPOT after the second BNT162b2 inoculum. There was a correlation between the anti-S ELISPOT response and IgG d42 level (Spearman r\,=\,0.3026, p \,=\,0.012). These findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with hematological malignancies, but only around half of the patients can likely achieve effective immune protection against COVID-19