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External validation of pittsburgh infant brain injury score in a French pediatric study
No full textInternational audienceBackground: Abusive Head Trauma (AHT) is a leading cause of morbidity and mortality in infants requiring rapid neuroimaging performance and prognostic rapid diagnosis. The Pittsburgh Infant Brain Injury Score (PIBIS) clinical prediction rule (CPR) was derived to identify infants most likely to present brain injury, whose diagnosis would benefit from head CT. Our study aimed to externally validate the PIBIS CPR in a pediatric French population.Methods: A retrospective study was conducted in a French pediatric emergency department between 2015 and 2017. We included all consecutive infants who underwent a neurological imaging. Medical data were collected, and PIBIS score was determined, both retrospectively.Results: We included 129 infants among which 33 cases (including 20 with a diagnosis of AHT). The sensitivity and specificity of the PIBIS CPR were 75.8 % (95 % CI 57.7-88.9) and 61.4 % (51.0-71.2) and negative and positive predictive values 88.1 % (77.8-94.7) and 40.3 % (33.0-48.2). Among the 20 infants with a diagnosis of AHT, 19 (95.0 %) were correctly identified by the PIBIS CPR.Conclusion: Our external validation study found a lower diagnostic value of the PIBIS CPR than in the original study. This argues for adding biomarkers to improve its performance, notably in the context of suspected AHT
Congenital Heart Diseases and Neurodevelopmental Disorders: New Insights Through the DOHaD Hypothesis
No full textInternational audienceCongenital heart disease (CHD) is the primary cause of birth defects, affecting 9 per 1,000 live births. Up to 50% of them will develop neurodevelopmental disorders, two-thirds of which being unexplained by postnatal risk factors. Recent advances suggest a triangular relationship between the placenta and the fetal heart and brain in CHD, consistent with the Developmental Origins of Health and Disease hypothesis, ie, the in utero programming of early and later-in-life non-communicable cardiometabolic and mental diseases. The current review provides comprehensive evidence of placental, cardiac, and cerebral tissues interactions, and details how placental dysregulation may affect vasculogenesis, angiogenesis and neural tube closure, hemodynamics, energy supply, endocrine function, and epigenetic regulation of the developing heart and brain. Future studies should include placental research, since identifying placental biomarkers would allow early identification of CHD infants at higher risk for neurodevelopmental disorders, leading to targeted preventive personalized interventions
FUSE-PhyloTree: Linking functions and sequence conservation modules of a protein family through phylogenomic analysis
No full textInternational audienceSummary - FUSE-PhyloTree is a phylogenomic analysis software for identifying local sequence conservation associated with the different functions of a multi-functional (e.g., paralogous or multi-domain) protein family. FUSE-PhyloTree introduces an original approach that combines advanced sequence analysis with phylogenetic methods. First, local sequence conservation modules within the family are identified using partial local multiple sequence alignment. Next, the evolution of the detected modules and known protein functions is inferred within the family's phylogenetic tree using three-level phylogenetic reconciliation and ancestral state reconstruction. As a result, FUSE-PhyloTree provides a gene tree annotated with both predicted sequence modules and ancestral gene functions, enabling the association of functions with specific sequence regions based on their co-emergence. Availability and implementation - FUSE-PhyloTree is provided as Docker and Singularity images including all the required software tools. Images, source code, test data, and documentation are available at https://github.com/OcMalde/fuse-phylotree and https://zenodo.org/records/15855068. Supplementary information - Supplementary data, providing an illustration of the application of FUSE-PhyloTree to the fibulin protein family, are available at Bioinformatics online
Pharmacotherapy for Autoimmune Pulmonary Alveolar Proteinosis
No full textInternational audiencePulmonary alveolar proteinosis is suspected when a “crazy paving” pattern is observed on a chest CT scan. This diagnosis is confirmed by the presence of eosinophilic extracellular material that shows positive staining with Periodic Acid Schiff on bronchoalveolar lavage samples. The autoimmune form of pulmonary alveolar proteinosis is confirmed by detecting anti-granulocyte-macrophage colony-stimulating factor antibodies in the patient’s serum. The historical first-line treatment for autoimmune pulmonary alveolar proteinosis is whole lung lavage, which should only be performed in expert centers. It remains the preferred treatment for patients experiencing respiratory failure, especially at the time of diagnosis. Inhaled granulocyte-macrophage colony-stimulating factor supplementation with molgramostim or sargramostim is now considered a first-line treatment in the international guidelines for autoimmune pulmonary alveolar proteinosis, following the positive results of recent randomized placebo-controlled studies. Rituximab and plasmapheresis can be prescribed as third- and fourth-line treatments, respectively. Lung transplantation may be considered for eligible patients experiencing terminal respiratory failure. A deeper understanding of the pathogenesis of autoimmune pulmonary alveolar proteinosis has opened up new therapeutic avenues, such as the use of PPARγ agonists or statins
Mast Cells Are Not Essential for Pubertal Mammary Gland Branching
No full textInternational audienceMast cells are long‐lived, tissue‐resident immune cells of the myeloid lineage with cardinal functions in allergy and atopic disease. They are now increasingly recognized also for protective roles, for example against infections and venoms. Other functions originally assigned to mast cells in development and physiology, however, have been refuted, and for yet others, the true contribution of mast cells remains uncertain. Mast cells have been implicated in promoting ductal branching in the pubertal mammary gland, the organ that produces and secretes milk in mammals, but these findings are based on mouse models that are not mast cell‐specific. In this study, we therefore re‐addressed the impact of mast cells on mammary gland branching using several complementary genetic models, including a newly generated transgenic mouse line (Ms4a2lsl‐hDTR). We report that neither constitutive deficiency of mast cells, nor their conditional ablation induced at puberty affects mammary gland branching. Our results thus dispute that mast cells promote this process in mice, at least in a unique and non‐redundant manner. This study adds to a growing body of work clarifying the biological roles of mast cells and further expands the toolbox available to the field of mast cell research
Will we miss specific IgA detection for the diagnosis of congenital toxoplasmosis? A French retrospective monocenter study on 483 infants
No full textInternational audienceTo estimate the performance of anti-Toxoplasma IgA assay for the diagnosis of congenital toxoplasmosis, a retrospective monocenter study was conducted comparing serological results obtained in the framework of routine diagnosis workup. All infants born to mothers infected with Toxoplasma gondii during pregnancy from 2010 to 2023 with at least 6 months of serological follow-up were included. Four hundred and eighty-three cases (1,171 sera) were included, of which 56 infants (11.6%) were infected. Twenty out of 60 infants (33.3%) with positive IgA were not infected. The sensitivity to detect IgA antibodies in infected neonates was 71.4%. The specificity was 97.3%. The mean time to detect IgA was 7.7 ± 13.0 days in infected neonates. Anti-Toxoplasma IgA was the earliest positive serological test in only two cases (5.0%) but turned negative at 1 month in the absence of specific treatment, suggesting non-specific detection. IgA was associated with anti-Toxoplasma IgM, neosynthetized IgG or IgM on comparative Western blotting (WB), or both IgM and neosynthetized IgG or IgM on WB, in 12 cases (30.0%), 2 cases (5.0%), and 19 cases (47.5%), respectively. Sixteen infants with no IgA after birth were diagnosed via neosynthetized IgG or IgM on comparative WB and/or IgM (n = 10), or via PCR on amniotic fluid (n = 5), or persistent IgG (n = 1). Our study suggests that anti-Toxoplasma IgA is not a critical serological parameter for the diagnosis of congenital toxoplasmosis, and the recent withdrawal of commercialized reference anti-Toxoplasma IgA assays should not affect patient care.IMPORTANCEThis study will help clinical microbiologists estimate the impact of the withdrawal of anti-Toxoplasma IgA reference assays for the diagnosis of congenital toxoplasmosis and will contribute to actualize the recommendations for laboratory diagnosis
Computerized predictive approaches of genotoxicity and mutagenesis in 3D Hepoid of normal and transformed human hepatocytes
No full textInternational audienceThe low specificity of standard in vitro genotoxicity tests in mammalian cells continues to necessitate animal experimentation, raising ethical concerns that conflict with the principles of the 3Rs (Replacement, Reduction, and Refinement). This underscores the urgent need for reliable alternative in vitro assays. Given the liver's critical role in xenobiotic detoxification and bioactivation, we developed an advanced 3D in vitro model of human hepatocytes that supports the proliferation and long-term differentiation of primary human hepatocytes and HepaRG cells. Using a range of methodologies, including the γH2AX assay, the comet assay, the micronucleus test, and transcriptomic analysis, we investigated DNA damage induced by well-known genotoxic carcinogens such as methylmethane sulfonate (MMS), mitomycin C (MMC), colchicine, vinblastine, 1,2-dimethylhydrazine (DMH), and aflatoxin B1 (AFB1), as well as non-genotoxic carcinogens, including di-2-ethylhexyl phthalate (DEHP) and methylcarbamate. Our data demonstrate the reliability of the 3D human hepatocyte Hepoid model in replicating in vivo results. We effectively discriminated between genotoxic and non-genotoxic carcinogenic molecules using complementary methods analyzed with advanced computational approaches. We further studied the in vitro genotoxic potential of four main Heterocyclic Aromatic Amines (HAAs) including 2-amino-9H-pyrido[2,3-b]indole (AαC), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2- amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which are food-borne and environmental contaminants suspected to contribute to hepatocellular carcinoma. Our results validate the Hepoid model as a reliable in vitro system for assessing the genotoxic and mutagenic risks of chemicals and confirm the ability of HAAs to induce DNA damage in a highly differentiated human liver model
Adverse reactions of liquorice consumed in the diet: a 10-year retrospective study of poison centres in France
No full textInternational audienceIntroduction: We aimed to describe the symptoms, patient demographics, and trends over time of adverse effects related to liquorice consumed in the diet reported to French poison centres.Methods: We performed a retrospective study of data from French poison centres of cases of adverse effects of liquorice consumed in the diet, with a high causality score, between 2012 and 2021 (10 years).Results: Sixty-four cases were included. The annual number of cases ranged from three to nine, with no significant variation over the study period. Liquorice-induced reactions were very rare (0.008% of all cases with symptoms reported to French poison centres). The products consumed were non-alcoholic beverages (non-alcoholic pastis, liquorice-based Antésite®, and liquorice syrup), alcoholic beverages of the pastis type (10.9%), confectionery containing liquorice (12.5%), confectionery made with liquorice extract only (9.4%), herbal teas (12.5%) and food supplements (4.7%). Consumption was commonly chronic (67.2%) and non-compliant (70.3%). Chronic users presented with symptoms suggestive of pseudohyperaldosteronism, the severity of which seemed to correlate with the amount of glycyrrhizin ingested. Severity was high in 43.8% of cases. When the outcome was known (56.3%), it was favourable in almost all cases (94.4%), often after inpatient care, particularly in an intensive care unit. One patient had sequelae due to a stroke, and one fatality was reported. Severe cases were observed with all types of products, except liquorice syrup and food supplements, and more frequently with beverages (pastis with or without alcohol, and Antésite®).Discussion: Due to significant variability in response to glycyrrhizin, some patients presented signs and symptoms suggestive of pseudohyperaldosteronism such as hypokalaemia, salt and water retention, and hypertension despite consuming the product as directed.Conclusions: Liquorice-induced effects were rarely reported to French poison centres, but their severity was high. Most patients were adults with chronic and non-compliant consumption, especially of soft drinks, with a clinical presentation suggestive of pseudohyperaldosteronism
La folie du pouvoir : Hérodote et l’invention d’un motif historiographique
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Agrégation anglais 2026 - Mark Twain. Adventures of Huckleberry Finn et le film de Wes Anderson, Moonrise Kingdom.
No full textInternational audienceCet ouvrage a été conçu pour préparer les candidats à la quatrième question du volet littéraire des épreuves écrites de la session 2026 de l’agrégation externe d’anglais. Celle-ci porte à la fois sur le roman de Mark Twain, Adventures of Huckleberry Finn (1884) et sur le film de Wes Anderson, Moonrise Kingdom (2012).La forme « hybride » littérature-cinéma se compose de deux œuvres différentes, et non d’une œuvre littéraire associée à son adaptation cinématographique, comme il en va habituellement de cette épreuve. Le défi interdisciplinaire, certes stimulant, prend cette année une tournure particulière. Outre les caractéristiques propres à chaque médium, nous avons cette fois-ci affaire à deux œuvres dont la « personnalité » artistique est bien établie, créées par deux auteurs dont le style est tout aussi distinct et marquant. La préparation au concours devra donc tenir compte de l’originalité de chaque œuvre tout en permettant un « dialogue » fructueux entre elles. C’est pourquoi les essais réunis dans cet ouvrage mettent en lumière la singularité de chaque œuvre, saisie dans sa dimension générique, contextuelle ou stylistique, en même temps que d’autres proposent des lectures croisées qui facilitent l’identification de nombreuses passerelles entre deux créations a priori exclusives l’une à l’autre, mais reliées de plusieurs manières