Organisation temporelle des figures d'attachement selon les milieux écologiques de l'enfant et le stade de développement. Construction d'une échelle de mesure

International audienceIl a été montré que le lien d'attachement résulte d'un comportement inné, générateur de sécurité affective, qui doit être distingué de la sollicitation alimentaire et dissocié des autres liens affectifs (Bowlby, 1951, 1969 ; Harlow, 1958, 1969 ; Heinroth, 1910; Spitz, 1962, 1968). L'attachement est défini, selon Ainsworth (1989), comme un lien durable, caractérisé par un besoin de maintenir la proximité, par la détresse de séparation, mais aussi comme une base secure et une valeur refuge. Ces caractéristiques sont différemment impliquées selon le stade de développement (Georges & Solomon, 1996). Enfin, l'attachement naît de la durée et de la régularité des interactions (Ainsworth, 1979). Il se crée et se nourrit de signaux : la figure est perçue comme disponible et réactive aux besoins sociaux et psychologiques exprimés. Selon Montagner (2004), l'organisation temporelle des interactions avec la figure et les rythmes biopsychologiques de chacun ne doivent pas être à contretemps des rythmes familiaux, sociaux et naturels. Il existe très peu d'études sur les figures d'attachement en dehors du caregiver. Identifiée par Montagner (2006) comme une personne sécurisante, la figure d'attachement peut également être secondaire si une relation durable s'est établie dans les niches écologiques de l'enfant. Bowlby (1969) affirmait que les figures d'attachement n'ont pas la même importance et qu'il existe un ordre de préférence clair. Il est donc nécessaire d'évaluer et de hiérarchiser afin de comprendre les variations intra-individuelles des préférences, l'organisation hiérarchique et leur évolution au cours du développement (Kobak, Rosenthal & Serwik, 2005 ; Kobak, Rosenthal, Zajac & Madsen, 2007). L'objectif poursuivi ici est de présenter une échelle de mesure en seize items interrogeant les quatre caractéristiques d'attachement. Cinq items ont été adaptés de Emotional Reliance Questionnaire (Ryan, La Guardia, Solky-Butzel, Chirkov, & Kim, 2005) et de Measure of attachment features (Kudek, 2008). Onze items ont été créés et évoquent des contextes familiers aux enfants dans lesquels leur système d'attachement est susceptible d'être activé. Pour chacune des huit figures adultes proposées, l'enfant est invité à évaluer à l'aide d'échelles visuelles analogiques (EVA) la durée, la prévisibilité et la périodicité du temps passé auprès d'elles. Dans le cadre de travaux en chronopsychologie, cette échelle permettra d'identifier et de hiérarchiser les figures d'attachement issues des trois niches écologiques - famille, école et loisirs (Le Floc'h, 2009) - selon les caractéristiques d'attachement et le stade de développement. Les résultats obtenus permettront d'apprécier les effets d'une rythmicité temporelle sûre et sécurisante sur les comportements et les rythmes endogènes

Enseignement de la microélectronique à Supélec : Une nouvelle pédagogie mise en place en 2012

National audienceLa rentrée 2012 a été le cadre d’une réforme de l’enseignement de l’électronique intégrée au seinde la majeure MNE (Micro et Nano Electronique) à Supélec. Les objectifs étaient de proposer une nouvelleforme d’enseignement pratique au moyen d’un projet long, de regrouper un ensemble de cours dans unensemble cohérent, de faire intervenir tous les enseignants de l’équipe auprès des élèves dès la rentrée, etsurtout de proposer un maximum de pratique aux élèves de manière à remotiver les élèves autour d’unediscipline qui n’est pas toujours très à la mode dans le monde numérique actuel. L’évaluation des élèves aaussi été repensée de manière à sortir les élèves d’un cadre scolaire et les mettre dans la peau d’unresponsable de projet au sein de l’industrie. L’introduction de points de passage formels avec remise derapports et présentation orale permet aux élèves de découvrir la réalité de leur métier de futur ingénieur. Leretour des élèves a montré que ce nouvel enseignement a été très apprécié de l’ensemble des élèves

Associations of levetiracetam use with the safety and tolerability profile of chemoradiotherapy for patients with newly diagnosed glioblastoma

Background Levetiracetam (LEV) is one of the most frequently used antiepileptic drugs (AED) for brain tumor patients with seizures. We hypothesized that toxicity of LEV and temozolomide-based chemoradiotherapy may overlap. Methods Using a pooled cohort of patients with newly diagnosed glioblastoma included in clinical trials prior to chemoradiotherapy (CENTRIC, CORE, AVAglio) or prior to maintenance therapy (ACT-IV), we tested associations of hematologic toxicity, nausea or emesis, fatigue, and psychiatric adverse events during concomitant and maintenance treatment with the use of LEV alone or with other AED versus other AED alone or in combination versus no AED use at the start of chemoradiotherapy and of maintenance treatment. Results Of 1681 and 2020 patients who started concomitant chemoradiotherapy and maintenance temozolomide, respectively, 473 and 714 patients (28.1% and 35.3%) were treated with a LEV-containing regimen, 538 and 475 patients (32.0% and 23.5%) with other AED, and 670 and 831 patients (39.9% and 41.1%) had no AED. LEV was associated with higher risk of psychiatric adverse events during concomitant treatment in univariable and multivariable analyses (RR 1.86 and 1.88, P < .001) while there were no associations with hematologic toxicity, nausea or emesis, or fatigue. LEV was associated with reduced risk of nausea or emesis during maintenance treatment in multivariable analysis (HR = 0.80, P = .017) while there were no associations with hematologic toxicity, fatigue, or psychiatric adverse events. Conclusions LEV is not associated with reduced tolerability of chemoradiotherapy in patients with glioblastoma regarding hematologic toxicity and fatigue. Antiemetic properties of LEV may be beneficial during maintenance temozolomide

A quantitative model of cellular decision making in direct neuronal reprogramming

Funder: Fonds du Québec en Recherche, Santé (FRQS)Funder: Parkinson Quebec.Funder: Lund UniversityAbstract: The direct reprogramming of adult skin fibroblasts to neurons is thought to be controlled by a small set of interacting gene regulators. Here, we investigate how the interaction dynamics between these regulating factors coordinate cellular decision making in direct neuronal reprogramming. We put forward a quantitative model of the governing gene regulatory system, supported by measurements of mRNA expression. We found that nPTB needs to feed back into the direct neural conversion network most likely via PTB in order to accurately capture quantitative gene interaction dynamics and correctly predict the outcome of various overexpression and knockdown experiments. This was experimentally validated by nPTB knockdown leading to successful neural conversion. We also proposed a novel analytical technique to dissect system behaviour and reveal the influence of individual factors on resulting gene expression. Overall, we demonstrate that computational analysis is a powerful tool for understanding the mechanisms of direct (neuronal) reprogramming, paving the way for future models that can help improve cell conversion strategies

On the benefits of rubbing salt in the cut: self-healing of saloplastic PAA/PAH compact polyelectrolyte complexes.

The inherent room temperature mending and self-healing properties of saloplastic PAA/PAH CoPECs are studied. After ultracentrifugation of PAA/PAH polyelectrolyte complexes, tough, elastic materials are obtained that undergo self-healing facilitated by salt. At intermediate salt concentrations the CoPECs remain elastic enough to recover their original shape while the chains are mobile enough to repair the cut, thus leading to actual self-healing behavior.journal articleresearch support, non-u.s. gov'tresearch support, u.s. gov't, non-p.h.s.2014 Apr 232014 01 29importe

Recombinant myelin oligodendrocyte glycoprotein quality modifies evolution of experimental autoimmune encephalitis in macaques

The authors describe quantitatively and qualitatively different forms of experimental autoimmune encephalitis (EAE) in cynomolgus macaques. They found that bacterial contaminants within recombinant human myelin oligodendrocyte glycoprotein seemed to aggravate disease evolution. They provide anatomopathological features of fulminant and progressive forms of EAE, allowing them to distinguish specific factors influencing the evolution of this model of autoimmune demyelinating disease. Experimental autoimmune encephalitis (EAE) is a well-recognized model for the study of human acquired demyelinating diseases (ADD), a group of inflammatory disorders of the central nervous system (CNS) characterized by inflammation, myelin loss, and neurological impairment of variable severity. In rodents, EAE is typically induced by active immunization with a combination of myelin-derived antigen and a strong adjuvant as complete Freund's adjuvant (CFA), containing components of the mycobacterial wall, while myelin antigen alone or associated with other bacterial components, as lipopolysaccharides (LPS), often fails to induce EAE. In contrast to this, EAE can be efficiently induced in non-human primates by immunization with the recombinant human myelin oligodendrocyte glycoprotein (rhMOG), produced in Escherichia coli (E. coli), purified and formulated with incomplete Freund's adjuvant (IFA), which lacks bacterial elements. Here, we provide evidence indicating how trace amounts of bacterial contaminants within rhMOG may influence the course and severity of EAE in the cynomolgus macaque immunized with rhMOG/IFA. The residual amount of E. coli contaminants, as detected with mass spectrometry within rhMOG protein stocks, were found to significantly modulate the severity of clinical, radiological, and histologic hallmarks of EAE in macaques. Indeed, animals receiving the purest rhMOG showed milder disease severity, increased numbers of remissions, and reduced brain damage. Histologically, these animals presented a wider diversity of lesion types, including changes in normal-appearing white matter and prephagocytic lesions. Non-human primates EAE model with milder histologic lesions reflect more accurately ADD and permits to study of the pathogenesis of disease initiation and progression

Association Between Toll‐Like Receptor 4 ( TLR4 ) and Triggering Receptor Expressed on Myeloid Cells 2 ( TREM2 ) Genetic Variants and Clinical Progression of Huntington's Disease

Background: Although Huntington's disease (HD) is caused by a single dominant gene, it is clear that there are genetic modifiers that may influence the age of onset and disease progression. Objectives: We sought to investigate whether new inflammation‐related genetic variants may contribute to the onset and progression of HD. Methods: We first used postmortem brain material from patients at different stages of HD to look at the protein expression of toll‐like receptor 4 (TLR4) and triggering receptor expressed on myeloid cells 2 (TREM2). We then genotyped the TREM2 R47H gene variant and 3 TLR4 single nucleotide polymorphisms in a large cohort of HD patients from the European Huntington's Disease Network REGISTRY. Results: We found an increase in the number of cells expressing TREM2 and TLR4 in postmortem brain samples from patients dying with HD. We also found that the TREM2 R47H gene variant was associated with changes in cognitive decline in the large cohort of HD patients, whereas 2 of 3 TLR4 single nucleotide polymorphisms assessed were associated with changes in motor progression in this same group. Conclusions: These findings identify TREM2 and TLR4 as potential genetic modifiers for HD and suggest that inflammation influences disease progression in this condition. © 2019 International Parkinson and Movement Disorder Societ

Human pre-valvular endocardial cells derived from pluripotent stem cells recapitulate cardiac pathophysiological valvulogenesis

Genetically modified mice have advanced our understanding of valve development and disease. Yet, human pathophysiological valvulogenesis remains poorly understood. Here we report that, by combining single cell sequencing and in vivo approaches, a population of human pre-valvular endocardial cells (HPVCs) can be derived from pluripotent stem cells. HPVCs express gene patterns conforming to the E9.0 mouse atrio-ventricular canal (AVC) endocardium signature. HPVCs treated with BMP2, cultured on mouse AVC cushions, or transplanted into the AVC of embryonic mouse hearts, undergo endothelial-to-mesenchymal transition and express markers of valve interstitial cells of different valvular layers, demonstrating cell specificity. Extending this model to patient-specific induced pluripotent stem cells recapitulates features of mitral valve prolapse and identified dysregulation of the SHH pathway. Concurrently increased ECM secretion can be rescued by SHH inhibition, thus providing a putative therapeutic target. In summary, we report a human cell model of valvulogenesis that faithfully recapitulates valve disease in a dish.We thank the Leducq Fondation for supporting Tui Neri, and funding this research under the framework of the MITRAL network and for generously awarding us for the equipment of our cell imaging facility in the frame of their program “Equipement de Recherche et Plateformes Technologiques” (ERPT to M.P.), the Genopole at Evry and the Fondation de la recherche Medicale (grant DEQ20100318280) for supporting the laboratory of Michel Puceat. Part of this work in South Carolina University was conducted in a facility constructed with support from the National Institutes of Health, Grant Number C06 RR018823 from the Extramural Research Facilities Program of the National Center for Research Resources. Other funding sources: National Heart Lung and Blood Institute: RO1-HL33756 (R.R.M.), COBRE P20RR016434–07 (R.R.M., R.A. N.), P20RR016434–09S1 (R.R.M. and R.A.N.); American Heart Association: 11SDG5270006 (R.A.N.); National Science Foundation: EPS-0902795 (R.R.M. and R.A. N.); American Heart Association: 10SDG2630130 (A.C.Z.), NIH: P01HD032573 (A.C. Z.), NIH: U54 HL108460 (A.C.Z), NCATS: UL1TR000100 (A.C.Z.); EH was supported by a fellowship of the Ministere de la recherche et de l’éducation in France.TM-M was supported by a fellowship from the Fondation Foulon Delalande and the Leducq Foundation. P.v.V. was sponsored by a UC San Diego Cardiovascular Scholarship Award and a Postdoctoral Fellowship from the California Institute for Regenerative Medicine (CIRM) Interdisciplinary Stem Cell Training Program II. S.M.E. was funded by a grant from the National Heart, Lung, and Blood Institute (HL-117649). A.T. is supported by the National Heart, Lung, and Blood Institute (R01-HL134664).S

Antiretroviral penetration into the CNS and incidence of AIDS-defining neurologic conditions

Objective: The link between CNS penetration of antiretrovirals and AIDS-defining neurologic disorders remains largely unknown. Methods: HIV-infected, antiretroviral therapy-naive individuals in the HIV-CAUSAL Collaboration who started an antiretroviral regimen were classified according to the CNS Penetration Effectiveness (CPE) score of their initial regimen into low (,8), medium (8-9), or high (.9) CPE score. We estimated "intention-to-treat" hazard ratios of 4 neuroAIDS conditions for baseline regimens with high and medium CPE scores compared with regimens with a low score. We used inverse probability weighting to adjust for potential bias due to infrequent follow-up. Results: A total of 61,938 individuals were followed for a median (interquartile range) of 37 (18, 70) months. During follow-up, there were 235 cases of HIV dementia, 169 cases of toxoplasmosis, 128 cases of cryptococcal meningitis, and 141 cases of progressive multifocal leukoencephalopathy. The hazard ratio (95% confidence interval) for initiating a combined antiretroviral therapy regimen with a high vs low CPE score was 1.74 (1.15, 2.65) for HIV dementia, 0.90 (0.50, 1.62) for toxoplasmosis, 1.13 (0.61, 2.11) for cryptococcal meningitis, and 1.32 (0.71, 2.47) for progressive multifocal leukoencephalopathy. The respective hazard ratios (95% confidence intervals) for a medium vs low CPE score were 1.01 (0.73, 1.39), 0.80 (0.56, 1.15), 1.08 (0.73, 1.62), and 1.08 (0.73, 1.58). Conclusions: We estimated that initiation of a combined antiretroviral therapy regimen with a high CPE score increases the risk of HIV dementia, but not of other neuroAIDS conditions