Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism

ANKRD17 is an ankyrin repeat-containing protein thought to play a role in cell cycle progression, whose ortholog in Drosophila functions in the Hippo pathway as a co-factor of Yorkie. Here, we delineate a neurodevelopmental disorder caused by de novo heterozygous ANKRD17 variants. The mutational spectrum of this cohort of 34 individuals from 32 families is highly suggestive of haploinsufficiency as the underlying mechanism of disease, with 21 truncating or essential splice site variants, 9 missense variants, 1 in-frame insertion-deletion, and 1 microdeletion (1.16 Mb). Consequently, our data indicate that loss of ANKRD17 is likely the main cause of phenotypes previously associated with large multi-gene chromosomal aberrations of the 4q13.3 region. Protein modeling suggests that most of the missense variants disrupt the stability of the ankyrin repeats through alteration of core structural residues. The major phenotypic characteristic of our cohort is a variable degree of developmental delay/intellectual disability, particularly affecting speech, while additional features include growth failure, feeding difficulties, non-specific MRI abnormalities, epilepsy and/or abnormal EEG, predisposition to recurrent infections (mostly bacterial), ophthalmological abnormalities, gait/balance disturbance, and joint hypermobility. Moreover, many individuals shared similar dysmorphic facial features. Analysis of single-cell RNA-seq data from the developing human telencephalon indicated ANKRD17 expression at multiple stages of neurogenesis, adding further evidence to the assertion that damaging ANKRD17 variants cause a neurodevelopmental disorder

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Performance de la mesure d'hémoglobine capillaire dans l'estimation de l'hémoglobinémie chez les patients de réanimation

POITIERS-BU Médecine pharmacie (861942103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Evolution du concept de mise en charge immédiate d'un implant unitaire situé au maxillaire antérieur

REIMS-BU Santé (514542104) / SudocSudocFranceF

Les chapes de Lepers sont elles toujours d'actualité en prothèse fixée ?

REIMS-BU Santé (514542104) / SudocSudocFranceF

Isolement géographique et état de santé maternel et néonatal dans un réseau de santé en périnatalité: étude en population générale Contexte

National audienceLa ruralité = facteur de vulnérabilité chez la femme enceinte • Offre hétérogène de l'offre de soins • Concentration des professionnels autour des métropoles • Réduction du nombre de plateaux techniques Risques de morbi-mortalité néonatales et maternelles plus élevés pour les femmes habitant à plus de 30 minutes d'une maternité

Le retour de la restitution (3): Géopolitiques du patrimoine, éthiques du transfert, économies du retour

Séance 3 : Que penser, que faire des objets rapatriés ? Modération : Odile COPPEY (Université de Limoges) et Anne DOQUET (IRD-Imaf) [00:00:00 à 03:54:07] Présentation par Odile COPPEY (Université de Limoges) [03:54:07 à 18:05:01] Brice Medard CHANHOUN (Migrantour Paris): « Visite d’adieu aux objets rapatriés » [18:05:01 à 32:18:20] Emmanuelle CADET (directrice d’Alter Natives) : « Jeunesses du Bénin, du Sénégal et des diasporas : comment partager l’histoire des objets ? » [32:18:20 à 45:18:04] Sara TASSI (Habiter, ULB) & Amandine YÉHOUÉTOMÈ (U. Paris 1): « Un Gou de Blanc ! Le Gou du Louvre au regard de ses initié.e.s Ainonvis » [45:18:04 à 01:00:42:02] Saskia COUSIN (Canthel, U. Paris Descartes) « Porto-Novo contre le retour, tout contre : le musée de l’amitié coloniale et la résistance des maquis » [01:00:42:02 à fin] DiscussionPrésentation du colloque : Repatriation strikes back. Sujet récurrent depuis une trentaine d’année, la question de la restitution des objets volés ou spoliés est de retour, dans un contexte politique a priori plus favorable. Si les préconisations du rapport Sarr-Savoy (2018) suscitent de vives confrontations au sein des mondes muséaux et marchands, cette journée d’études vise à dépayser le débat en donnant la parole aux acteurs, aux publics et aux pays concernés par le retour et l’accueil de ces objets. La restitution est-elle le fait du prince, ou l’aboutissement de décennies de réclamations successives? De quelle géopolitique est-elle le nom ? Quels sont les acteurs de cette histoire ? Quelles places donner aux diasporas longtemps ignorées par les musées européens ? Comment penser les transferts et les appropriations ici et là-bas ? Quels statuts ces objets sacrés et royaux devenus « fétiches de musées » vont-ils prendre lors de leur retour ? Quels seront leurs publics ? Comment considérer et expliquer les oppositions locales au retour ? Mêlant acteurs et chercheurs, organisée autour de questions vives et actuelles, mais aussi immémoriales, cette journée ambitionne de lancer le débat plutôt que de le clore. Programme Contacts : [email protected] / [email protected]