Dépistage des anomalies de l'examen psychomoteur de l'enfant entre 28 jours et 6 ans par le médecin généraliste

Le but de notre étude est d évaluer, en tenant compte de l expérience pédiatrique des médecins généralistes, la faisabilité de l évaluation des anomalies de l examen psychomoteur de l enfant en médecine générale. Les outils sur lesquels repose notre travail sont les propositions de recommandations professionnelles de la Haute Autorité de Santé (HAS) de 2005 et la dernière version établie en 2005 du carnet de santé, principal instrument utilisé par les médecins généralistes en pratique quotidienne.AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Évolution cognitive des enfants et adolescents polyhandicapés

à veni

Role of intestinal epithelial AMPK in the protective effect of metformin on dextran sodium sulfate‐induced colitis in mice

International audienceBackgroundDysfunctions in the intestinal barrier, associated with an altered paracellular pathway, are commonly observed in gastrointestinal disorders, such as inflammatory bowel disease (IBD). The AMP-activated protein kinase (AMPK), principally known as a cellular energy sensor, has also been shown to play a key role in the stabilization and assembly of tight junctions following injury. Here, we aimed to investigate the effect of metformin in strengthening intestinal barrier function by activating intestinal epithelial AMPK.MethodsA dextran sodium sulfate (DSS)-induced colitis model was used to assess disease progression in WT and intestinal epithelial cell-specific AMPK KO (IEC AMPK KO) mice in response to metformin treatment. Barrier integrity was analyzed by measuring paracellular permeability following dextran-4kDa gavage and, pro-inflammatory cytokines and tight junctions expression.ResultsThe deletion of intestinal epithelial AMPK delayed intestinal injury repair after DSS-induced colitis and was associated with a slower re-epithelization of the intestinal mucosa coupled to a reduction in tight junctions expression and a higher paracellular permeability, inflammation and histological defects. Metformin administration attenuated the severity of DSS-induced colitis with improvement in intestinal permeability and inflammation in control mice but only partially in IEC AMPK KO mice.ConclusionsTaken together these findings suggest that IEC AMPK contributes to intestinal healing and epithelial integrity after injury and may be effective as a therapeutic target to ameliorate dysfunctions of the intestinal barrier

Intestinal Epithelial AMPK Deficiency Causes Delayed Colonic Epithelial Repair in DSS-Induced Colitis

International audienceDysfunctions in the intestinal barrier, associated with an altered paracellular pathway, are commonly observed in inflammatory bowel disease (IBD). The AMP-activated protein kinase (AMPK), principally known as a cellular energy sensor, has also been shown to play a key role in the stabilization and assembly of tight junctions. Here, we aimed to investigate the contribution of intestinal epithelial AMPK to the initiation, progression and resolution of acute colitis. We also tested the hypothesis that protection mediated by metformin administration on intestinal epithelium damage required AMPK activation. A dextran sodium sulfate (DSS)-induced colitis model was used to assess disease progression in WT and intestinal epithelial cell (IEC)-specific AMPK KO mice. Barrier integrity was analyzed by measuring paracellular permeability following dextran-4kDa gavage and pro-inflammatory cytokines and tight junction protein expression. The deletion of intestinal epithelial AMPK delayed intestinal injury repair after DSS exposure and was associated with a slower re-epithelization of the intestinal mucosa coupled with severe ulceration and inflammation, and altered barrier function. Following intestinal injury, IEC AMPK KO mice displayed a lower goblet cell counts with concomitant decreased Muc2 gene expression, unveiling an impaired restitution of goblet cells and contribution to wound healing process. Metformin administration during the recovery phase attenuated the severity of DSS-induced colitis through improvement in intestinal repair capacity in both WT and IEC AMPK KO mice. Taken together, these findings demonstrate a critical role for IEC-expressed AMPK in regulating mucosal repair and epithelial regenerative capacity following acute colonic injury. Our studies further underscore the therapeutic potential of metformin to support repair of the injured intestinal epithelium, but this effect is conferred independently of intestinal epithelial AMPK

AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation

AMPK activation inhibits cardiac hypertrophy. Here the authors show that this occurs independently of previously proposed mechanisms and that AMPK controls the phosphorylation of the aminotransferase GFAT, thereby preventing cardiac hypertrophy through the reduction of protein O-GlcNAcylation

Human γδ T cell sensing of AMPK-dependent metabolic tumor reprogramming through TCR recognition of EphA2

International audienceHuman γδ T cells contribute to tissue homeostasis and participate in epithelial stress surveillance through mechanisms that are not well understood. Here, we identified ephrin type-A receptor 2 (EphA2) as a stress antigen recognized by a human Vγ9Vδ1 TCR. EphA2 is recognized coordinately by ephrin A to enable γδ TCR activation. We identified a putative TCR binding site on the ligand-binding domain of EphA2 that was distinct from the ephrin A binding site. Expression of EphA2 was up-regulated upon AMP-activated protein kinase (AMPK)-dependent metabolic reprogramming of cancer cells, and coexpression of EphA2 and active AMPK in tumors was associated with higher CD3 T cell infiltration in human colorectal cancer tissue. These results highlight the potential of the human γδ TCR to cooperate with a co-receptor to recognize non-MHC-encoded proteins as signals of cellular dysregulation, potentially allowing γδ T cells to sense metabolic energy changes associated with either viral infection or cancer

Le site de référence du Partenariat européen d’innovation pour un vieillissement actif et en bonne santé MACVIA-LR (contre les maladies chroniques pour un vieillissement en bonne santé en Languedoc-Roussillon)

International audienceLe site de référence du Partenariat européen d'innovation pour un vieillissement actif et en bonne santé MACVIA-LR (contre les maladies chroniques pour un vieillissement en bonne santé en Languedoc-Roussillon