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International audience; AimMetabolic sources switch from carbohydrates in utero, to fatty acids after birth and then a mix once adults. O‐GlcNAcylation (O‐GlcNAc) is a post‐translational modification considered as a nutrient sensor. The purpose of this work was to assess changes in protein O‐GlcNAc levels, regulatory enzymes and metabolites during the first periods of life and decipher the impact of O‐GlcNAcylation on cardiac proteins.MethodsHeart, brain and liver were harvested from rats before and after birth (D‐1 and D0), in suckling animals (D12), after weaning with a standard (D28) or a low‐carbohydrate diet (D28F), and adults (D84). O‐GlcNAc levels and regulatory enzymes were evaluated by western blots. Mass spectrometry (MS) approaches were performed to quantify levels of metabolites regulating O‐GlcNAc and identify putative cardiac O‐GlcNAcylated proteins.ResultsProtein O‐GlcNAc levels decrease drastically and progressively from D‐1 to D84 (13‐fold, P < .05) in the heart, whereas the changes were opposite in liver and brain. O‐GlcNAc levels were unaffected by weaning diet in any tissues. Changes in expression of enzymes and levels of metabolites regulating O‐GlcNAc were tissue‐dependent. MS analyses identified changes in putative cardiac O‐GlcNAcylated proteins, namely those involved in the stress response and energy metabolism, such as ACAT1, which is only O‐GlcNAcylated at D0.ConclusionOur results demonstrate that protein O‐GlcNAc levels are not linked to dietary intake and regulated in a time and tissue‐specific manner during postnatal development. We have identified by untargeted MS putative proteins with a particular O‐GlcNAc signature across the development process suggesting specific role of these proteins.

Best strategies for the management of severe paediatric traumatic brain injury (TBI) are not clearly established with wide variations among professional practices. This study's main objective was to assess the adequacy between professional practices and paediatric TBI guidelines 2019. A survey was conducted among French-speaking pediatric intensive care clinicians from April 1st to June 30th, 2019. The survey was conducted as a progressive clinical case with 70 questions based on guidelines 2012. The questions related to the assessment and management of TBI during the acute and intensive care phase. Seventy-eight surveys were included. The adherence to guidelines 2019 was good, with 11 items out of 15 obtaining an adherence rate of more than 60%. There was strong agreement among clinicians on the intracranial pressure (> 80%) and cerebral perfusion pressure (> 70%) thresholds used according to age. Strong adherence to recent guidelines was achieved: seizure prophylaxis with levitracetam (n=21/33, 64%) and capnia threshold (n=52, 67%). On the other hand, the natremia and glycemia thresholds and the role of transcranial doppler were not consistent. Assessment of brain tissue oxygenation (n=12, 16%) and autoregulation (n=35; 45%) was not a common practice. Overall, practices for the management of TBI appear to be standardised. Variations persist in areas where there is a lack of literature and guidelines in paediatrics, so clinicians seem to refer to adult guidelines.; Les stratégies optimales de prise en charge du traumatisme crânien grave pédiatrique (TCG) ne sont pas clairement établies et il existe de grandes variations de pratiques entre professionnels. L'objectif de ce travail était d’évaluer l’adéquation des pratiques professionnelles aux recommandations pédiatriques de prise en charge du TCG 2019. Une enquête de pratique a été adressée aux médecins seniors exerçant dans un service de réanimation pédiatrique francophone du 1er 1 avril au 30 juin 2019. L’enquête consistait en un cas clinique évolutif de 70 questions élaboré à partir des recommandations 2012. Elles portaient sur la prise en charge des TCGs lors de la phase aigüe et réanimatoire. Soixante-dix-huit questionnaires ont été inclus. L’adhésion des praticiens aux recommandations 2019 était bonne avec 11 items sur 15 obtenant une adhésion de plus de 60%. Les praticiens étaient en accord fort sur les valeurs cibles de pression intracrânienne (> 80%) et pression de perfusion cérébrale (> 70%) en fonction de l’âge. Une adhésion forte à certaines recommandations récentes était obtenue : prophylaxie anti-convulsivante par lévitéracétam (n=21/33, 64%) et le seuil de capnie (n=52, 67%). Les seuils de natrémie, de glycémie et le rôle du doppler transcrânien restaient controversés. L’évaluation de la pression en O2 du tissu cérébral (n=12, 16%) et de l’autorégulation (n=35 ; 45%) n’était pas une pratique courante. Dans l’ensemble, les pratiques de prise en charge du TCG pédiatrique semblent uniformisées. Les variations persistent concernant les domaines dont la littérature fait défaut en pédiatrie, les praticiens semblent alors s’appuyer sur les recommandations adultes.

Rationale: O-GlcNAc, a post-translational modification closely linked to cell metabolism, has been suggested to play an important role in development. The suckling to weaning transition is associated with important change in metabolism but its impact on O-GlcNAc has never been explored. Objective: To evaluate O-GlcNAc level from birth to adulthood in different organs.Methods: Blood and tissue samples (heart, liver, kidney, lung, hind limb and brain) were harvested between 8 and 10 am at J0 (newbn), J12, J28 (before / after weaning) and J84 (adulthood) wistar rats to evaluate O-GlcNAc, GFAT (the rate limiting enzyme of hexosamine biosynthesis pathway), OGA (O-GlcNAcase) and OGT (O-GlcNAc transferase) levels.Results: O-GlcNAc level decreased progressively from J0 to J84 in the heart (5 fold) along with GFAT (50 fold) and OGT (10 fold) while the OGA main isoform is absent at J0. In the liver, O-GlcNAc levels were similar between J0 and J84 but OGT and GFAT decreased (2 and 3 fold respectively). O-GlcNAc proteomic study revealed different targets of interest.Conclusion: O-GlcNAc level decreases with ageing in the heart but not in the liver. Our results pinpoint to major and tissue-specific modulation in the expression and activity of the enzymes involved in the regulation of O-GlcNAcylation levels during post-natal development.