Fin 2018, la France connaît un soulèvement populaire sans précédent, motivé dans un premier temps par le refus de l’augmentation du prix des carburants automobiles. Pour se reconnaître, les individus ...concernés endossent un gilet de haute visibilité, le fameux « gilet jaune ». Rapidement, la mobilisation s’étend à la Belgique, principalement à Bruxelles et à la Wallonie. Ce mouvement, ou plutôt ces mouvements, en renouvelant les modalités de la mobilisation, rebattent les cartes de l’analyse. Leur caractère spontané, apartisan sans être apolitique, interroge les rapports qui se nouent entre Gilets jaunes et syndicats d’une part, entre Gilets jaunes et institutions d’autre part. Force est ainsi de constater qu’à des aspirations démocratiques de plus en plus affirmées répondent une répression policière et des sanctions judiciaires inégalées. La confrontation entre terrain belge et terrain français, les enquêtes et les observations sociologiques, les entretiens individuels ou collectifs, les portraits d’individus mobilisés et les photographies de terrain sont autant d’outils utilisés dans cet ouvrage pour tenter de redonner une parole longtemps confisquée aux principaux acteurs de cette mobilisation : les Gilets jaunes eux-mêmes.
Loin d'être sans leader, le mouvement des gilets jaunes est constamment traversé par des luttes de leadership. L'ethnographie d'un rond-point de mobilisation et des tensions qui traversent différents ...groupes lyonnais permettent de mieux comprendre l'inscription dans le temps de ce mouvement.
Impossible pour les personnes mobilisées dans le mouvement des Gilets jaunes (GJ) de faire abstraction de la présence policière. Médiatiquement, les « affrontements entre la police et les ...manifestants », selon la formule journalistique consacrée, représentent l’angle privilégié par de nombreux acteurs (journalistes, documentaristes, militants ou universitaires) pour relater la mobilisation. Ils donnent généralement à voir l’action des forces de l’ordre sous son visage le plus connu, essentiel...
Background: Preterm infants frequently present eating difficulties in early childhood. Determinants of these difficulties are not known.Objective: We assessed the influence of neonatal and maternal ...characteristics on eating behaviors at 2 y of age.Design: The following 2 cohorts were compared: 234 preterm children born <33 wk of gestational age from the POLYmorphisme génétique, Nutrition et Comportement Alimentaire cohort and 245 term children from the Observation des Préférences ALImentaires du Nourrisson et de l'Enfant cohort. Eating behaviors were assessed by using the validated Children's Eating Difficulties Questionnaire, which assesses the following 2 dimensions: a low drive to eat and narrow food repertoire. Each dimension was graded from 2 to 10 with more severe difficulties reflected by a higher score. Children in the upper quintile were classified as having eating disorders.Results: Compared with term children, preterm children had a worse drive-to-eat score (4.3 ± 1.6 compared with 3.6 ± 1.5, respectively; P = 0.001) and a marginally lower food-repertoire score (5.0 ± 1.5 compared with 4.8 ± 1.6, respectively; P = 0.05). In a multilevel logistic regression model, female sex adjusted OR (aOR): 1.76; 95% CI: 1.08, 2.88; P = 0.025 and birth weight less than −1 z score (aOR: 2.88; 95% CI: 1.47, 5.67; P = 0.002) but not gestational age were associated with a worse drive to eat. A maternal level of education beyond high school was associated with lower risk of a poor food-repertoire score (aOR: 0.54; 95% CI: 0.32, 0.90; P = 0.02).Conclusions: Preterm children have more eating difficulties than term children do, but after adjustment for maternal and neonatal characteristics, gestational age is not associated with impaired eating behaviors at the age of 2 y. Female sex, a low maternal level of education, and less than −1 SD intrauterine growth are associated with eating difficulties at 2 y of age. This trial was registered at clinicaltrials.gov as NCT 00663572.
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Targeting the IL17 pathway and more specifically the nuclear receptor RORγ is thought to be beneficial in multiple skin disorders. The Letter describes the discovery of ...phenoxyindazoles and thiophenoxy indazoles as potent RORγ inverse agonists. Optimization of the potency and efforts to mitigate the phototoxic liability of the series are presented. Finally, crystallization of the lead compound revealed that the series bound to an allosteric site of the nuclear receptor. Such compounds could be useful as tool compounds for understanding the impact of topical treatment on skin disease models.
Rationale
Intestinal permeability plays an important role in gut-brain axis communication. Recent studies indicate that intestinal permeability increases in neonate pups during maternal separation ...(MS).
Objectives
The present study aims to determine whether pharmacological inhibition of myosin light chain kinase (MLCK), which regulates tight junction contraction and controls intestinal permeability, in stressed neonates, protects against the long-term effects of MS.
Methods
Male Wistar rats were exposed to MS (3 h per day from post-natal day (PND)2 to PND14) or left undisturbed and received daily intraperitoneal injection of a MLCK inhibitor (ML-7, 5 mg/kg) or vehicle during the same period. At adulthood, emotional behaviors, corticosterone response to stress, and gut microbiota composition were analyzed.
Results
ML-7 restored gut barrier function in MS rats specifically during the neonatal period. Remarkably, ML-7 prevented MS-induced sexual reward–seeking impairment and reversed the alteration of corticosterone response to stress at adulthood. The effects of ML-7 were accompanied by the normalization of the abundance of members of Lachnospiraceae, Clostridiales,
Desulfovibrio
, Bacteroidales,
Enterorhabdus
, and
Bifidobacterium
in the feces of MS rats at adulthood.
Conclusions
Altogether, our work suggests that improvement of intestinal barrier defects during development may alleviate some of the long-term effects of early-life stress and provides new insight on brain–gut axis communication in a context of stress.
Compound 4a CD4 IL-17 IC50 = 17 nM.
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Progress in the identification of suitable RORγ inverse agonists as clinical candidates has been hampered by the high lipophilicity that seems ...required for high potency on this nuclear receptor. In this context, we decided to focus on the replacement of the hydroxymethyl group found on known modulators to determine if more polarity could be tolerated in this position. SAR of the replacement of this moiety is presented in this article leading to the identification of sulfoximine derivatives as potent modulators with pharmacological activity in the in vivo mouse Imiquimod psoriasis model.
With possible implications in multiple autoimmune diseases, the retinoic acid receptor‐related orphan receptor RORγ has become a sought‐after target in the pharmaceutical industry. Herein are ...described the efforts to identify a potent RORγ inverse agonist compatible with topical application for the treatment of skin diseases. These efforts culminated in the discovery of N‐(2,4‐dimethylphenyl)‐N‐isobutyl‐2‐oxo‐1‐(tetrahydro‐2H‐pyran‐4‐yl)methyl‐2,3‐dihydro‐1H‐benzodimidazole‐5‐sulfonamide (CD12681), a potent inverse agonist with in vivo activity in an IL‐23‐induced mouse skin inflammation model.
You′re gonna hear me ROR! The pressure is on to find RORγ modulators, which show promise in the treatment of autoimmune diseases, specifically psoriasis. The optimization of heterobicyclic sulfonamides is presented here with a focus on minimizing lipophilicity. These efforts culminated in the identification of CD12681, a potent RORγ inverse agonist compatible with topical application and efficacy in vivo.
Preterm infants frequently present eating difficulties in early childhood. Determinants of these difficulties are not known.
We assessed the influence of neonatal and maternal characteristics on ...eating behaviors at 2 y of age.
The following 2 cohorts were compared: 234 preterm children born <33 wk of gestational age from the POLYmorphisme génétique, Nutrition et Comportement Alimentaire cohort and 245 term children from the Observation des Préférences ALImentaires du Nourrisson et de l’Enfant cohort. Eating behaviors were assessed by using the validated Children’s Eating Difficulties Questionnaire, which assesses the following 2 dimensions: a low drive to eat and narrow food repertoire. Each dimension was graded from 2 to 10 with more severe difficulties reflected by a higher score. Children in the upper quintile were classified as having eating disorders.
Compared with term children, preterm children had a worse drive-to-eat score (4.3 ± 1.6 compared with 3.6 ± 1.5, respectively; P = 0.001) and a marginally lower food-repertoire score (5.0 ± 1.5 compared with 4.8 ± 1.6, respectively; P = 0.05). In a multilevel logistic regression model, female sex adjusted OR (aOR): 1.76; 95% CI: 1.08, 2.88; P = 0.025 and birth weight less than -1 z score (aOR: 2.88; 95% CI: 1.47, 5.67; P = 0.002) but not gestational age were associated with a worse drive to eat. A maternal level of education beyond high school was associated with lower risk of a poor food-repertoire score (aOR: 0.54; 95% CI: 0.32, 0.90; P = 0.02).
Preterm children have more eating difficulties than term children do, but after adjustment for maternal and neonatal characteristics, gestational age is not associated with impaired eating behaviors at the age of 2 y. Female sex, a low maternal level of education, and less than -1 SD intrauterine growth are associated with eating difficulties at 2 y of age. This trial was registered at clinicaltrials.gov as NCT 00663572.
Children born preterm are more likely than full-term infants to develop eating difficulties that can affect their growth. Although this behavior is certainly influenced by their fetal and postnatal ...history, a large individual variability exists that results from a complex interaction between genetic and environmental factors. We performed an original pilot study to identify common genetic variants associated with eating difficulties at 2 years of age in the POLYNUCA cohort of preterm infants.
Eating behavior was assessed using a parental questionnaire in a cohort of 234 very preterm infants (including 38 pairs of twins). Eighty-two common single nucleotide polymorphisms (SNPs) were selected in a total of 40 candidate genes involved in the regulation of energy homeostasis and food intake.
Eating behavior was strongly correlated in monozygotic (r = 0.92, p = 0.001) but not dizygotic twins (r = 0.27, p = 0.14), suggesting a strong heritability of this trait. One SNP (rs11671975) in the insulin receptor (INSR) gene was significantly associated with eating behavior. This effect was maintained after adjustment for birth weight Z score and maternal education level, two factors that are associated with eating difficulties at 2 years of age.
The INSR gene is potentially associated with eating difficulties in preterm infants.
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