Prenatal and postnatal exposure to persistent organic pollutants and Infant growth: A pooled analysis of seven european birth cohorts

Background: Infant exposure to persistent organic pollutants (POPs) may contribute to obesity. However, many studies so far have been small, focused on transplacental exposure, used an inappropriate measure to assess postnatal exposure through breastfeeding if any, or did not discern between prenatal and postnatal effects. Objectives: We investigated prenatal and postnatal exposure to POPs and infant growth (a predictor of obesity). Methods: We pooled data from seven European birth cohorts with biomarker concentrations of polychlorinated biphenyl 153 (PCB-153) (n = 2,487), and p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) (n = 1,864), estimating prenatal and postnatal POPs exposure using a validated pharmacokinetic model. Growth was change in weight-for-age z-score between birth and 24 months. Per compound, multilevel models were fitted with either POPs total exposure from conception to 24 months or prenatal or postnatal exposure. Results: We found a significant increase in growth associated with p,p´-DDE, seemingly due to prenatal exposure (per interquartile increase in exposure, adjusted β = 0.12; 95% CI: 0.03, 0.22). Due to heterogeneity across cohorts, this estimate cannot be considered precise, but does indicate that an association with infant growth is present on average. In contrast, a significant decrease in growth was associated with postnatal PCB-153 exposure (β = –0.10; 95% CI: –0.19, –0.01). Conclusion: To our knowledge, this is the largest study to date of POPs exposure and infant growth, and it contains state-of-the-art exposure modeling. Prenatal p,p´-DDE was associated with increased infant growth, and postnatal PCB-153 with decreased growth at European exposure levels

Effect of Lactobacillus rhamnosus CGMCC1.3724 supplementation on weight loss and maintenance in obese men and women

The present study investigated the impact of a Lactobacillus rhamnosus CGMCC1.3724 (LPR) supplementation on weight loss and maintenance in obese men and women over 24 weeks. In a double-blind, placebo-controlled, randomised trial, each subject consumed two capsules per d of either a placebo or a LPR formulation (1·6×108 colony-forming units of LPR/capsule with oligofructose and inulin). Each group was submitted to moderate energy restriction for the first 12 weeks followed by 12 weeks of weight maintenance. Body weight and composition were measured at baseline, at week 12 and at week 24. The intention-to-treat analysis showed that after the first 12 weeks and after 24 weeks, mean weight loss was not significantly different between the LPR and placebo groups when all the subjects were considered. However, a significant treatment×sex interaction was observed. The mean weight loss in women in the LPR group was significantly higher than that in women in the placebo group (P=0·02) after the first 12 weeks, whereas it was similar in men in the two groups (P=0·53). Women in the LPR group continued to lose body weight and fat mass during the weight-maintenance period, whereas opposite changes were observed in the placebo group. Changes in body weight and fat mass during the weight-maintenance period were similar in men in both the groups. LPR-induced weight loss in women was associated not only with significant reductions in fat mass and circulating leptin concentrations but also with the relative abundance of bacteria of the Lachnospiraceae family in faeces. The present study shows that the Lactobacillus rhamnosus CGMCC1.3724 formulation helps obese women to achieve sustainable weight los

Fifteen years of research on oral–facial–digital syndromes: from 1 to 16 causal genes

Oral–facial–digital syndromes (OFDS) gather rare genetic disorders characterised by facial, oral and digital abnormalities associated with a wide range of additional features (polycystic kidney disease, cerebral malformations and several others) to delineate a growing list of OFDS subtypes. The most frequent, OFD type I, is caused by a heterozygous mutation in the OFD1 gene encoding a centrosomal protein. The wide clinical heterogeneity of OFDS suggests the involvement of other ciliary genes. For 15 years, we have aimed to identify the molecular bases of OFDS. This effort has been greatly helped by the recent development of whole-exome sequencing (WES). Here, we present all our published and unpublished results for WES in 24 cases with OFDS. We identified causal variants in five new genes (C2CD3, TMEM107, INTU, KIAA0753 and IFT57) and related the clinical spectrum of four genes in other ciliopathies (C5orf42, TMEM138, TMEM231 and WDPCP) to OFDS. Mutations were also detected in two genes previously implicated in OFDS. Functional studies revealed the involvement of centriole elongation, transition zone and intraflagellar transport defects in OFDS, thus characterising three ciliary protein modules: the complex KIAA0753-FOPNL-OFD1, a regulator of centriole elongation; the Meckel-Gruber syndrome module, a major component of the transition zone; and the CPLANE complex necessary for IFT-A assembly. OFDS now appear to be a distinct subgroup of ciliopathies with wide heterogeneity, which makes the initial classification obsolete. A clinical classification restricted to the three frequent/well-delineated subtypes could be proposed, and for patients who do not fit one of these three main subtypes, a further classification could be based on the genotype

Regulatory T-cell dysfunctions are associated with increase in tumor necrosis factor α in autoimmune hemolytic anemia and participate in Th17 polarization

Warm autoimmune hemolytic anemia (wAIHA) is a rare acquired autoimmune disease mediated by antibodies targeting red blood cells. The involvement of CD4 T-helper cells has been scarcely explored, with most findings extrapolated from animal models. Here, we performed quantification of both effector T lymphocytes (Teff) and regulatory T cells (Treg), associated with functional and transcriptomic analyses of Treg in human wAIHA. We observed a shift of Teff toward a Th17 polarization concordant with an increase in serum interleukin-17 concentration that correlates with red blood cell destruction parameters, namely lactate dehydrogenase and bilirubin levels. A decrease in circulating Treg, notably effector Treg, associated with a functional deficiency, as represented by their decrease capability to inhibit Teff proliferation, were also observed. Treg deficiency was associated with a reduced expression of Foxp3, the master transcription factor known to maintain the Treg phenotype stability and suppressive functions. Transcriptomic profiling of Treg revealed activation of the tumor necrosis facto (TNF)-α pathway, which was linked to increased serum TNF-α concentrations that were twice as high as in controls. Treg transcriptomic profiling also suggested that post-translational mechanisms possibly accounted for Foxp3 downregulation and Treg dysfunctions. Since TNF-α participates in the rupture of immune tolerance during wAIHA, its inhibition could be of interest. To this end, the effects of fostamatinib, a SYK inhibitor, were investigated in vitro, and we showed that besides the inhibition of erythrocyte phagocytosis by monocytes, fostamatinib is also able to dampen TNF-α production, thus appearing as a promising multitargeting therapy in wAIHA (clinicaltrials gov. Identifier: NCT02158195)

Influence de la fréquence temporelle sur la perception de la vitesse linéaire : étude génétique de la perception de la vitesse en éclairage intermittent

Summary Four groups of 24 children (ages 7, 9, 11 and 13) were required to adjust the speed of motion of a continuously illuminated comparison target so as to match that of an identical target illuminated by a flickering light (frequencies 3, 6, 9, 12 and 15 cps). An effect of speed enhancement was found for ail ages and for all five frequencies. Furthermore, this effect varies according to a U-shaped function with a decline between ages 7 and 9 and an increase between ages 9 and 13. These results seem to favour a physiological explanation of the phenomenon more than a eue explanation.Résumé Quatre groupes de 24 enfants âgés respectivement de 7, 9, 11 et 13 ans doivent ajuster la vitesse d'un mobile éclairé de façon continue par comparaison à un mobile éclairé de façon intermittente (fréquence 3, 6, 9, 12 et 15 cps). Les résultats révèlent un effet d'accentuation de la vitesse en éclairage intermittent à tous les âges et pour toutes les conditions de fréquence. En outre, l'effet évolue avec l'âge suivant une courbe en U (baisse entre 7 et 9 ans et remontée à 13 ans). Ces données sont en faveur d'une interprétation du phénomène en termes physiologiques par opposition à une interprétation en termes d'indices perceptifs.Delorme André, Chevrier Jacques. Influence de la fréquence temporelle sur la perception de la vitesse linéaire : étude génétique de la perception de la vitesse en éclairage intermittent. In: L'année psychologique. 1974 vol. 74, n°2. pp. 363-372

Towards standards for Pervasive Computing evaluation: using the multi-model and multi-agent paradigms for mobility

Abstract. Pervasive Computing is about interconnected computing resources embedded in our daily lives and providing contextual services to users. One key element of the equation is ”the human ” and more specifically his behavior that is influenced and influences the environment. This article shows a generic way, using multi-agent systems (MAS) and multi-model paradigms, to evaluate communication related technologies based on a closed-loop between users and the pervasive computing environment. Our goal is to provide a framework where technologies could be evaluated and ideally certified ”for a standard type of environment”. First we present our generic framework for mobility modeling in dynamic networks and describe the design. We will describe its implementation and the experiments we have conducted in order to show its validity. Finally we argue that our framework could change how dynamic networks and more generally how behavior dependent technology will be evaluated in the future, which could lead to new standards