Caractérisation du profil lymphocytaire B et de la réponse vaccinale des enfants exposés non infectés par le virus de l'immunodéficience humaine

En bas âge, les enfants exposés au VIH mais non infectés (ENI) ont des risques de morbidité et de mortalité plus élevés. Des perturbations dans le profil immunitaire ont été mises en évidence et associées, en outre, aux paramètres maternels relatifs à l’infection au VIH y compris l’exposition au VIH, aux agents antirétroviraux et au milieu placentaire pro-inflammatoire. Ici, nous avons caractérisé le compartiment cellulaire B et la réponse vaccinale antitétanique d’enfants ENI durant leur 1re année de vie. Les enfants ENI (n = 68) de la cohorte du CMIS ont été stratifiés selon le zénith de la charge virale (CV; ≤40 vs. >40 copies/ml plasma) et le nadir du compte de CD4 (<500 vs. ≥500 cellules/mm3) de la mère en grossesse. Les nouveau-nés ont reçu une prophylaxie (AZT/3TC) 12 h après la naissance et jusqu'à leur 4e ou 6e semaine d’âge. Les cellules mononucléées de sang ont été isolées à la naissance, à 6 et à 12 mois d’âge. Les sous-populations de cellules B (naïves; transitionnelles T1/T2; plasmablastes; mémoires classiques, activées et atypiques) ont été analysées par cytométrie en flux grâce à un marquage pour CD10, CD20, CD21, CD27 et l’IgM de surface. Les cellules B spécifiques au tétanos et la capacité de sécrétion d'IgG de la fraction mémoire ont été étudiées à l’aide d’oligomères fluorescents du fragment C du toxoïde tétanique (TTCF) et d’une détection immunoenzymatique des IgG par ELISpot. Les nourrissons nés de mères avec une CV détectable en grossesse avaient une proportion élevée de plasmablastes (p=0,0449) et diminuée de cellules B CD19+ (p=0,0174) à la naissance en plus d'une proportion accrue de cellules B mémoires classiques IgM+ à 12 mois (p=0,0367). Ceux dont les mères avaient une immunité lymphocytaire T CD4+ altérée en grossesse (<500 cellules/mm3) présentaient des fréquences augmentées de plasmablastes (p=0,0458) et de cellules B mémoires activées IgM+ (p=0,0071) à la naissance et à 6 mois de vie respectivement. Ces résultats suggèrent une maturation précoce du compartiment cellulaire B et une altération dans la commutation de classe chez les bambins nés de mères avec une CV détectable et/ou un compte de CD4 sous-optimal. Aucune différence majeure n'a été notée dans la réponse vaccinale antitétanique des enfants ENI. Dans l’ensemble, nos résultats indiquent que la gravité des paramètres maternels en terme de CV et de compte de CD4 n’a que peu d'impact sur l'ontogénie des cellules B chez les enfants ENI et leur capacité à répondre à une vaccination.In early life, HIV-exposed uninfected (HEU) children experience higher rates of morbidity and mortality. Studies revealed evidences of alterations in their immunological profile that are associated, in part, with maternal parameters related to HIV infection including in utero exposure to HIV, antiretroviral therapy (ART) and the pro-inflammatory placental environment. Here, we performed a longitudinal profiling of the B cell subsets and response to tetanus vaccine in HEU children during their 1st year of life. HEU children (n = 68) from the CMIS Cohort were stratified based on the zenith of the maternal viral load (VL; ≤40 vs. >40 copies/ml plasma) and the nadir of the maternal CD4 count (<500 vs. ≥500 cells/mm3) during pregnancy. Newborns received prophylactic ART (AZT/3TC) from 12h after birth until week 4 or 6. Blood mononuclear cells were isolated at birth, 6, and 12 months of age. CD19+ B cell subsets (naïve; transitional T1/T2; classical, activated and atypical memory; plasmablasts) were analysed by flow cytometry using CD10, CD20, CD21, CD27 and surface IgM markers. Tetanus-specific B cells and the IgG secreting activity of the memory fraction were studied using fluorescent tetanus toxoid C fragment (TTCF) oligomers and an ELISpot assay. HEU infants born to mothers with a detectable VL during pregnancy had increased proportions of plasmablasts (p=0,0449) and a lower frequency of CD19+ B cells (p=0,0174) at birth in addition to having an expanded percentage of IgM+ classical memory B cells at 12 months (p=0,0367). Infants whose mothers had an impaired CD4 immunity throughout pregnancy (<500 cells/mm3) presented with greater frequencies of plasmablasts (p=0,0458) and IgM+ activated memory B cells (p=0,0071) at birth and 6 months respectively. These results suggest an early maturation of the B cell compartment and an alteration of the class switching mechanism in infants born to mothers with either a detectable VL or a low CD4 count. No relevant difference was noted in the TTCF-specific B cell subsets and the ability of memory B cells to generated specific antibodies. Overall, the severity of the maternal parameters in terms of VL and CD4 count had little impact on the ontogeny of the B cells subsets and their capacity to respond to vaccination

Approche systémique du fonctionnement d'un territoire agricole bocager

International audienceCet article présente une approche systémique du fonctionnement de territoires bocagers porteurs d'enjeux environnementaux. Après l'étude des dynamiques spatiotemporelles passées et actuelles des paysages, l'identification et la hiérarchisation des facteurs explicatifs des changements observés, cette approche met en évidence les échelles auxquelles ils se produisent et les différents acteurs qui interviennent dans l'évolution de ces paysages. Cette approche illustre la complexité des changements d'usage des sols dans des paysages très fragmentés en région agricole intensive. Elle constitue un préalable à la simulation de changements futurs et à l'élaboration de politiques de gestion durable

Le De aduerbio de Priscien

International audienceQuantitativement, l’essentiel du De aduerbio est consacré à deux classifications: la classification morphologique selon la finale, et la classification sémantique. Cela étant, ce qui précède ces deux ensembles définit un cadre d’analyse qui leur donne leur sens. La définition initiale de l’adverbe en dégage deux caractères : l’un formel, l’invariabilité, l’autre sémantico-fonctionnel, à savoir que sa signification se combine avec celle du verbe. L’ensemble du livre sur l’adverbe illustre ensuite de diverses façons les problèmes que pose la relation entre ces niveaux formel, sémantique et fonctionnel

Association of selenium, tocopherols, carotenoids, retinol, and 15-isoprostane F(2t) in serum or urine with prostate cancer risk: the multiethnic cohort.

We examine the association of antioxidants and 15-isoprostane F(2t) with risk of prostate cancer.We conducted a nested case-control study of serum antioxidant biomarkers (selenium, tocopherols, carotenoids, and retinol) and a urinary oxidation biomarker (15-isoprostane F(2t)) with risk of prostate cancer within the Multiethnic Cohort. Demographic, dietary, and other exposure information was collected by self-administered questionnaire in 1993-1996. We compared prediagnostic biomarker levels from 467 prostate cancer cases and 936 cancer free controls that were matched on several variables. Multivariate conditional logistic regression models were used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs).We observed that there was no overall association of serum concentrations of antioxidants and urinary concentrations of 15-isoprostane F(2t) with risk of prostate cancer or risk of advanced prostate cancer. However, we did observe an inverse association for serum selenium only among African-American men (p trend = 0.02); men in the third tertile of selenium concentrations had a 41% lower risk (95% CI: 0.38-0.93) of prostate cancer when compared to men in the first tertile.Overall, our study found no association of serum antioxidants or 15-isoprostane F(2t) with the risk of prostate cancer. The observed inverse association of selenium with prostate cancer in African-Americans needs to be validated in other studies

Le Lamentin – Chambord

Le projet de construction de logements au lieu-dit Chambord sur la commune du Lamentin a entraîné l’émission d’une prescription de fouille archéologique préventive. Cette prescription faisait suite à un diagnostic réalisé par Nicolas Biwer (Inrap) au premier trimestre 2015 sur un peu plus de 12 000 m2. Il avait permis de mettre en évidence de nombreux vestiges archéologiques maçonnés et fossoyés en lien avec une occupation d’époque coloniale de la fin de l’époque moderne et du début de la pér..

Association of Serum γ-Tocopherol Levels with Mortality: The Multiethnic Cohort Study

Background/Objectives—γ-Tocopherol has unique properties that protect against nitrogen oxide-mediated cellular damage. To elucidate the potential role of γ-tocopherol in the aging process, we examined the associations of serum γ-tocopherol levels with all-cause and cause-specific mortality. Subjects/Methods—Among participants in the biorepository subcohort of the Multiethnic Cohort Study, pre-cancer diagnostic serum γ-tocopherol levels were measured in a subset of 3904 men and 4461 women. Of these, 22.7% of men and 13.5% of women died during a mean follow- up time of 9.6±2.6 years. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) for mortality associated with γ-tocopherol were estimated by Cox proportional hazards regression. Results—Positive associations of serum γ-tocopherol with all-cause, cancer and cardiovascular disease mortality (CVD) (Ptrend\u3c0.05) were detected after adjusting for age, race-ethnicity and serum cholesterol levels. The respective HRs (95%CIs) for the highest versus the lowest sex- specific γ-tocopherol quartile were 1.43 (1.17–1.74), 1.79 (1.22–2.64), and 1.52 (1.10–2.11) for men and 1.58 (1.25–2.00), 1.59 (1.05–2.41), and 1.59 (1.07–2.37) for women. Associations remained significant for all-cause mortality among women after further adjusting for smoking variables and history of cancer, CVD, diabetes, and hypertension at cohort entry (highest vs. lowest γ-tocopherol quartile: HR=1.38; 95%CI=1.08–1.75; Ptrend= 0.005). Overall, associations with all-cause mortality were consistent across race/ethnicity and were significant in three of ten sex-specific racial/ethnic groups in the fully adjusted models with no interactions between ethnicity and γ-tocopherol. Conclusions—The positive association between γ-tocopherol and mortality suggests a potential physiological role for γ-tocopherol in response to pathological conditions

Clinical Chorioamnionitis and Neurodevelopment at 5 Years of Age in Children Born Preterm: The EPIPAGE-2 Cohort Study.

OBJECTIVE To assess the association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born preterm. STUDY DESIGN EPIPAGE 2 is a national, population-based cohort study of children born before 35 weeks of gestation in France in 2011. We included infants born alive between 24+0 and 34+6 weeks following preterm labor (PTL) or preterm premature rupture of membranes (PPROM). Clinical chorioamnionitis was defined as maternal fever before labor (>37.8°C) with at least two of the following criteria: maternal tachycardia, hyperleukocytosis, uterine contractions, purulent amniotic fluid, or fetal tachycardia. The primary outcome was a composite including cerebral palsy, coordination disorders, cognitive disorders, sensory disorders, or behavioral disorders. We also analyzed each of these disorders separately as secondary outcomes. We performed a multivariable analysis using logistic regression models. We accounted for the non-independence of twins and missing data by generalized estimating equation models and multiple imputations, respectively. RESULTS Among 2927 children alive at 5 years of age, 124 (3%) were born in a context of clinical chorioamnionitis. Overall, 8.2% and 9.6% of children exposed and unexposed respectively to clinical chorioamnionitis had moderate-to-severe neurodevelopmental disorders. After multiple imputations and multivariable analysis, clinical chorioamnionitis was not associated with the occurrence of moderate-to-severe neurodevelopmental disorders (adjusted odds ratio = 0.9, 95%CI: 0.5-1.8). CONCLUSION We did not find any association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born before 35 weeks of gestation after PTL or PPROM