Thrombospondin-1-derived peptide RFYVVMWK improves the adhesive phenotype of CD34sup+/sup cells from atherosclerotic patients with type 2 diabetes

International audienceBackground: CD34(+) progenitor cells are growingly used for vascular repair. However, in diabetic individuals with cardiovascular diseases, these cells have dysfunctional engraftment capabilities, which compromise their use for autologous cell therapy. The thrombospondin-1-derived peptide RFYVVMWK has previously been reported to stimulate cell adhesiveness through CD47 and integrin activation pathways.Objectives: Our aim was to test whether RFYVVMWK preconditioning could modulate CD34(+) cells phenotype and enhance its pro-adhesive properties in diabetic patients.Patients/methods: Peripheral blood mononuclear CD34(+) cells isolated from 40 atherosclerotic patients with (T2D; n=20) or without (NonT2D; n=20) type 2 diabetes were pre-conditioned with 30µM of RFYVVMWK (or truncated peptide RFYVVM. CD34(+) cell adhesion was assessed on a vitronectin-collagen matrix and on a TNFα or IL-1β- stimulated HUVEC monolayers. Adhesion receptors, platelet/CD34(+) cell conjugates, and cell viability were analyzed by flow cytometry and confocal microscopy.Results: RFYVVMWK increased by 8 folds the adhesion of T2D CD34(+) cells to the vitronectin-collagen matrix (p Conclusions: Priming CD34(+) cells with RFYVVMWK may enhance their vascular engraftment during autologous pro-angiogenic cell therapy.

Previsibilite et prevision des pics de pollution en region parisienne

Available from INIST (FR), Document Supply Service, under shelf-number : RP 400 (2264) / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEAgence de l'Environnement et de la Maitrise de l'Energie (ADEME), 75 - Paris (France)FRFranc

Les fruits et légumes dans l'alimentation : enjeux et déterminants de la consommation

Le rapport de l'expertise scientifique collective Inra (novembre 2007) disponible sur le site de l'Institut, comprend les 1 330 références bibliographiques des publications scientifiques citées dans le rapport.National audienceL'objectif de cette expertise (commandée par le ministère de l'Agriculture et de la Pêche à l'Inra) est d'éclairer les pouvoirs publics sur les actions à mener pour répondre au double objectif de soutien économique aux filières de production et de protection de la santé publique. À partir des recherches et des publications scientifiques, les experts ont analysé les questions suivantes : les fondements scientifiques des recommandations nutritionnelles ; les caractéristiques nutritionnelles des fruits et légumes ; la variabilité de la consommation et ses déterminants socio-économiques ; l'impact de la promotion de la consommation ; les liens entre caractéristiques des produits et fonctionnement des filières

Associations between usual diet and gut microbiota composition: results from the Milieu Interieur cross-sectional study

Background: Diet is widely recognized as one of the main modifiable drivers of gut microbiota variability, and its influence on microbiota composition is an active area of investigation.Objective: The present work aimed to explore the associations between usual diet and gut microbiota composition in a large sample of healthy French adults.Methods: Gut microbiota composition was established through sequencing of the 16S rRNA gene in stool samples from 862 healthy French adults of the Milieu Interieur study. Usual dietary consumptions were determined through the administration of a food-frequency questionnaire. The associations between dietary variables and alpha- and beta-diversity indexes and relative taxa abundances were tested using Spearman correlations, permutational ANOVAs, and multivariate analyses with linear models, respectively.Results: Foods generally considered as healthy (raw fruits, fish) were positively associated with alpha-diversity, whereas food items for which a limited consumption is generally recommended (fried products, sodas or sugary drinks, fatty sweet products, processed meats, ready-cooked meals, and desserts) were negatively associated with alpha-diversity. Fruits, fried products, ready-cooked meals, and cheese contributed to shifts within microbiota composition (beta-diversity). Our results also highlighted a number of associations between various food group intakes and abundances of specific phyla, genera, and species. For instance, the consumption of cheese was negatively associated with Akkermansia muciniphila abundance.Conclusions: This large-scale population-based study supports that the usual consumption of certain food items is associated with several gut microbial features, and extends the mechanistic arguments linking Western diet to an altered microbiota composition. These results provide new insights into the understanding of complex diet-gut microbiota relations, and their implications for host health deserve further investigation because altered microbiota diversity was consistently linked to increased risk of several health outcomes. This trial was registered at clinicaltrials.gov as NCT01699893

New OFSEP recommendations for MRI assessment of multiple sclerosis patients: Special consideration for gadolinium deposition and frequent acquisitions

International audiencePurposeNew multiple sclerosis (MS) disease-modifying therapies (DMTs), which exert beneficial effects through prevention of relapse, limitation of disability progression, and improvement of patients’ quality of life, have recently emerged. Nonetheless, these DMTs are not without associated complications (severe adverse events like. progressive multifocal leukoencephalopathy). Patient follow-up requires regular clinical evaluations and close monitoring with magnetic resonance imaging (MRI). Detection of new T2 lesions and potential brain atrophy measurements contribute to the evaluation of treatment effectiveness. Current MRI protocols for MS recommend the acquisition of an annual gadolinium (Gd) enhanced MRI, resulting in administration of high volume of contrast agents over time and Gd accumulation in the brain.MethodsA consensus report was established by neuroradiologists and neurologists from the French Observatory of MS, which aimed at reducing the number of Gd injections required during MS patient follow-up.RecommendationsThe French Observatory of MS recommends the use of macrocyclic Gd enhancement at time of diagnosis, when a new DMT is introduced, at 6-month re-baseline, and when previous scans are unavailable for comparison. Gd administration can be performed as an option in case of relapse or suspicion of intercurrent disease such as progressive multifocal leukoencephalopathy. Other follow-up MRIs do not require contrast enhancement, provided current and previous MRI acquisitions follow the same standardized protocol including 3D FLAIR sequences

Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial

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Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia

International audienceImportance Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19).Objective To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia.Design, Setting, and Particpants This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes.Interventions Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants.Main Outcomes and Measures Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events.Results Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21).Conclusions and Relevance In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care unit, TCZ did not reduce WHO-CPS scores lower than 5 at day 4 but might have reduced the risk of NIV, MV, or death by day 14. No difference on day 28 mortality was found. Further studies are necessary for confirming these preliminary results.Trial Registration ClinicalTrials.gov Identifier: NCT0433180

Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial

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