Décrire ses jeux de données dans les règles du FAIR : accompagner les chercheurs à l'utilisation des métadonnées

Cette fiche pratique à destination des établissements et organismes d'enseignement supérieur et de recherche pour objectif de faciliter l'accompagnement des chercheurs dans leur travail de documentation des données de la recherche. Elle est également à retrouver dans un format dynamique (grâce à l'outil Genially). Pour télécharger les sketchnotes de la fiche individuellement, rendez-vous ici : https://gtso.couperin.org/gtdonnees/facilitation-graphique

Gene therapy for aromatic L-amino acid decarboxylase deficiency: Requirements for safe application and knowledge-generating follow-up

The autosomal recessive defect of aromatic L-amino acid decarboxylase (AADC) leads to a severe neurological disorder with manifestation in infancy due to a pronounced, combined deficiency of dopamine, serotonin and catecholamines. The success of conventional drug treatment is very limited, especially in patients with a severe phenotype. The development of an intracerebral AAV2-based gene delivery targeting the putamen or substantia nigra started more than 10 years ago. Recently, the putaminally-delivered construct, Eladocagene exuparvovec has been approved by the European Medicines Agency and by the British Medicines and Healthcare products Regulatory Agency. This now available gene therapy provides for the first time also for AADC deficiency (AADCD) a causal therapy, leading this disorder into a new therapeutic era. By using a standardized Delphi approach members of the International Working Group on Neurotransmitter related Disorders (iNTD) developed structural requirements and recommendations for the preparation, management and follow-up of AADC deficiency patients who undergo gene therapy. This statement underlines the necessity of a framework for a quality-assured application of AADCD gene therapy including Eladocagene exuparvovec. Treatment requires prehospital, inpatient and posthospital care by a multidisciplinary team in a specialized and qualified therapy center. Due to lack of data on long-term outcomes and the comparative efficacy of alternative stereotactic procedures and brain target sites, a structured follow-up plan and systematic documentation of outcomes in a suitable, industry-independent registry study are necessary

Monter un service d'accompagnement aux données

Cette illustration a été réalisée dans le cadre de la fiche pratique Comment monter un service d’accompagnement aux données ? du GTSO Données de Couperin. Une offre complète ne peut être constituée en quelques mois. Il est recommandé, dans un premier temps, de mettre en place des services essentiels. Vous pourrez ainsi créer des liens avec des équipes de recherche et avoir des retours sur les actions mises en œuvre

Early origins of metabolic and overall health in young adults: An outcome-wide analysis in a general cohort population

International audienceIntroductionLong-term consequences of impaired fetal growth are well documented for cardiometabolic outcomes. We propose an outcome-wide analysis of the association between birth weight (BW) and long-term health in a large contemporary adult cohort.MethodsThe study included 73,315 participants under 60 years with a reliable BW from the French nationwide Constances cohort. Low and high BW (LBW/HBW) were defined as BW90th of sex-specific percentiles. Associations between BW and outcomes were analyzed with a sex-stratified modified Poisson regression adjusted for the participant's age, maternal health history, geographical origins, and parents' occupation.ResultsMean BW (10th -90th percentile) was 3390 g (2800-4000) for men and 3247g (2680-3820) for women. In men, LBW was associated with (RR [CI95]): fasting glucose impairment (1.33 [1.16;1.52]); hypertriglyceridemia (1.27 [1.17;1.37]); high blood pressure (HBP) (1.15 [1.07;1.24]); non-alcoholic fatty liver disease NAFLD (1.13 [1.02;1.24]); high LDL-cholesterol (1.12 [1.05;1.21]); anxiety (1.12 [1.01;1.24]) and depression (1.09 [1.00;1.18]). HBW was associated with obesity (1.21 [1.08;1.35]). In women, LBW was associated with fasting glucose impairment (1.31 [1.12;1.54]); HBP (1.27 [1.16;1.4]); hypertriglyceridemia (1.20 [1.05;1.36]); anxiety (1.10 [1.03;1.17]); and asthma (1.09 [1;1.19}). HBW was associated with obesity (1.24 [1.13;1.36]) and NAFLD (1.20 [1.06;1.37). LBW and HBW were associated with a lesser likelihood of tertiary education attainment in both sexes. Participants’ education level was a significant partial mediator of the association between LBW and outcomes.ConclusionExtreme BW is associated with long-term health. It should be considered in the personalized prevention of cardiometabolic, respiratory, and mental health conditions in adulthood, especially in socio-economically disadvantaged populations

The effectiveness of interventions during the first 1,000 days to improve energy balance‐related behaviors or prevent overweight/obesity in children from socio‐economically disadvantaged families of high‐income countries: a systematic review

International audienceThis narrative systematic review examined effectiveness of interventions during pregnancy and up to 2 years of age in improving energy balance-related behaviors or prevent overweight/obesity in children from families experiencing socioeconomic disadvantage. We identified 24 interventions, from 33 articles, since 1990. Overall, despite their heterogeneity and variability in internal and external validity, there was some evidence of beneficial impact of interventions on obesity risk (4/15), and associated behaviors, e.g.: breastfeeding (9/18), responsive feeding (11/16), diet (7/8), sedentary (1/3) and movement (4/7) behaviors, and sleep (1/2). The most effective interventions aimed at promoting breastfeeding commenced antenatally; this was similar for the prevention of obesity, provided the intervention continued for at least 2 years postnatally and was multibehavioral. Effective interventions were more likely to target first-time mothers and involve professional delivery agents, multidisciplinary teams and peer groups. Among ethnic/racial minorities, interventions delivered by lay agents had some impact on dietary behavior but not weight outcomes. Co-creation with stakeholders, including parents, and adherence to theoretical frameworks were additional ingredients for more pragmatic, inclusive, non-judgmental, and effective programs. The growing body of evidence on obesity prevention interventions targeting families experiencing socioeconomic disadvantage is promising for reducing early inequalities in obesity risk

Clinical and Electrophysiological Characterization of Essential Tremor in 18 Children and Adolescents

International audienceBackground: Essential tremor (ET) is considered the most frequent abnormal movement in the general population, with childhood onset in 5 to 30% of the patients.Methods: A multicenter, descriptive cross-sectional study enrolled patients ⩽18 years with a definite diagnosis of ET according to the International Parkinson and Movement Disorders Society criteria. Demographic data, clinical and electrophysiological characteristics of the tremor, neurological examination and impact on quality of life were collected.Results: 9 males and 9 females were included (mean age of 13.9 years). Tremor was characterized by : upper limb onset at a mean age of 6.5 years; at enrollment, upper limbs localization, and involvement of an additional body region in 28% of the patients; kinetic tremor in all of the patients combined with postural tremor in 17 and rest tremor in 3; tremor mean frequency of 7.6 Hz, mean burst duration of 82.7 ms; identification of mild myoclonic jerks on the polymyographic recordings in 7 patients; altered quality of life with worse emotional outcomes in girls and when a disease duration >5 years was suggested.Discussion: Childhood-onset ET is associated with delayed diagnosis and remarkable functional impact. Electromyographic identification of additional mild myoclonus is a new finding whose significance is discussed.Highlights: ET onset involved upper limbs and at inclusion, 28% of the patients exhibited involvement of an additional body region.ET impacted quality of life for all patients.Girls and patients affected for >5 years reported worse emotional outcomes.Mild myoclonic jerks were identified on 7/17 polymyographic recordings

Evaluating next-generation sequencing in neuromuscular diseases with neonatal respiratory distress

International audienc

Movement disorders in valine métabolism diseases caused by HIBCH and ECHS1 deficiencies

International audienceBackground and purpose: HIBCH and ECHS1 genes encode two enzymes implicated in the critical steps of valine catabolism, 3-hydroxyisobutyryl-coenzyme A (CoA) hydrolase (HIBCH) and short-chainenoyl-CoA hydratase (ECHS1), respectively. HIBCH deficiency (HIBCHD) and ECHS1 deficiency (ECHS1D) generate rare metabolic dysfunctions, often revealed by neurological symptoms. The aim of this study was to describe movement disorders spectrum in patients with pathogenic variants in ECHS1 and HIBC.Methods: We reviewed a series of 18 patients (HIBCHD: 5; ECHS1D: 13) as well as 105 patients from the literature. We analysed the detailed phenotype of HIBCHD (38 patients) and ECHS1D (85 patients), focusing on MDs.Results: The two diseases have a very similar neurological phenotype, with an early onset before 10 years of age for three clinical presentations: neonatal onset, Leigh-like syndrome (progressive onset or acute neurological decompensation), and isolated paroxysmal dyskinesia. Permanent or paroxysmal MDs were recorded in 61% of HIBCHD patients and 72% of ECHS1D patients. Patients had a variable combination of either isolated or combined MD, and dystonia was the main MD. These continuous MDs included dystonia, chorea, parkinsonism, athetosis, myoclonus, tremors, and abnormal eye movements. Patients with paroxysmal dyskinesia (HIBCHD: 4; ECHS1D: 9) usually had pure paroxysmal dystonia with normal clinical examination and no major impairment in psychomotor development. No correlation could be identified between clinical pattern (especially MD) and genetic pathogenic variants.Conclusions: Movement disorders, including abnormal ocular movements, are a hallmark of HIBCHD and ECHS1D. MDs are not uniform; dystonia is the most frequent, and various types of MD are combined in single patient