Evaluation of the benefits and risks of introducing Ebola community care centers, Sierra Leone.

In some parts of western Africa, Ebola treatment centers (ETCs) have reached capacity. Unless capacity is rapidly scaled up, the chance to avoid a generalized Ebola epidemic will soon diminish. The World Health Organization and partners are considering additional Ebola patient care options, including community care centers (CCCs), small, lightly staffed units that could be used to isolate patients outside the home and get them into care sooner than otherwise possible. Using a transmission model, we evaluated the benefits and risks of introducing CCCs into Sierra Leone's Western Area, where most ETCs are at capacity. We found that use of CCCs could lead to a decline in cases, even if virus transmission occurs between CCC patients and the community. However, to prevent CCC amplification of the epidemic, the risk of Ebola virus-negative persons being exposed to virus within CCCs would have to be offset by a reduction in community transmission resulting from CCC use

Functional characterization of the novel sequence variant p.S304R in the hinge region of TSHR in a congenital hypothyroidism patients and analogy with other formerly known mutations of this gene portion

Context: Thyroid dysgenesis may be associated with loss-of-function mutations in the thyrotropin receptor (TSHR) gene. Objectives: The aim of this study was to characterize a novel TSHR gene variant found in one patient harboring congenital hypothyroidism (CH) from a cohort of patients with various types of thyroid defects. Materials and methods: This cross-sectional cohort study involved 118 patients with CH and their family members, including 45 with familial and 73 with sporadic diseases. The thyroid gland was normal in 23 patients, 25 patients had hypoplasia, 25 hemithyroid agenesis, 21 had athyreosis, and 21 had ectopy. Genomic DNA was extracted, and 10 exons of the TSHR gene were amplified and sequenced. Mutations in other candidate genes were investigated. Ortholog alignment was performed, and TSHR functional assays were evaluated. Results: We identified one previously unknown missense variation in the hinge region (HinR) of the TSHR gene (p.S304R) in one patient with thyroid hypoplasia. This variant is conserved in our ortholog alignment. However, the p.S304R TSHR variant presented a normal glycosylation pattern and signal transduction activity in functional analysis. Conclusion: We report the ocurrence of a novel nonsynonymous substitution in the HinR of the large N-terminal extracellular domain of the TSHR gene in a patient with thyroid hypoplasia. In contrast with four others in whom TSHR mutations of the hinge portion were previously identified, the p.S304R TSHR variation neither affected TSH binding nor cAMP pathway activation. This TSHR gene variant was documented in a CH patient, but the current data do not support its role in the clinical phenotype

Genetic landscape of a large cohort of Primary Ovarian Insufficiency : New genes and pathways and implications for personalized medicine

Background Primary Ovarian Insufficiency (POI), a public health problem, affects 1-3.7% of women under 40 yield-ing infertility and a shorter lifespan. Most causes are unknown. Recently, genetic causes were identified, mostly in single families. We studied an unprecedented large cohort of POI to unravel its molecular pathophysiology.Methods 375 patients with 70 families were studied using targeted (88 genes) or whole exome sequencing with pathogenic/likely-pathogenic variant selection. Mitomycin-induced chromosome breakages were studied in patients' lymphocytes if necessary. Findings A high-yield of 29.3% supports a clinical genetic diagnosis of POI. In addition, we found strong evidence of pathogenicity for nine genes not previously related to a Mendelian phenotype or POI: ELAVL2, NLRP11, CENPE, SPATA33, CCDC150, CCDC185, including DNA repair genes: C17orf53(HROB), HELQ, SWI5 yielding high chromo-somal fragility. We confirmed the causal role of BRCA2, FANCM, BNC1, ERCC6, MSH4, BMPR1A, BMPR1B, BMPR2, ESR2, CAV1, SPIDR, RCBTB1 and ATG7 previously reported in isolated patients/families. In 8.5% of cases, POI is the only symptom of a multi-organ genetic disease. New pathways were identified: NF-kB, post-translational regulation, and mitophagy (mitochondrial autophagy), providing future therapeutic targets. Three new genes have been shown to affect the age of natural menopause supporting a genetic link.Interpretation We have developed high-performance genetic diagnostic of POI, dissecting the molecular pathogene-sis of POI and enabling personalized medicine to i) prevent/cure comorbidities for tumour/cancer susceptibility genes that could affect life-expectancy (37.4% of cases), or for genetically-revealed syndromic POI (8.5% of cases), ii) predict residual ovarian reserve (60.5% of cases). Genetic diagnosis could help to identify patients who may benefit from the promising in vitro activation-IVA technique in the near future, greatly improving its success in treating infertility.Funding Universite? Paris Saclay, Agence Nationale de Biome?decine.Copyright (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe

Anomalies osseuses et croissance dans le syndrome de Turner

CAEN-BU Médecine pharmacie (141182102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Hyperplasie congénitale des surrénales, formes virilisantes pures et traitement par minéralocorticoïdes

NICE-BU Médecine Odontologie (060882102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Evaluation de la fonction thyroïdienne des nouveau-nés de mère traitée pendant la grossesse pour une thyroïdite d'Hashimoto

POITIERS-BU Médecine pharmacie (861942103) / SudocSudocFranceF

Application du séchage micro-ondes aux peintures acryliques en phase aqueuse

Les nombreuses contraintes et pressions environnementales ont conduit les grandes sociétés de vernis et peintures industrielles à développer de nouvelles formulations sans solvant, respectant ainsi les exigences vis-à-vis de l environnement et des normes en vigueur. Le remplacement des peintures solvants par des peintures en phases aqueuses a permis de réduire la quantité de solvants émise par cette industrie. Cependant, le temps de séchage important des peintures en phase aqueuses constitue un obstacle considérable en termes de productivité. Un moyen de réduire ce temps de séchage est d employer les micro-ondes pour sécher ces peintures. Pour les peintures aqueuses, il s avère que l idée du séchage micro-ondes est particulièrement intéressante. Cependant, les formulations actuelles des peintures aqueuses ne sont pas adaptées à ce mode de séchage. Il faut donc entièrement repenser leur formulation, en vue de les rendre plus réactive vis-à-vis de ce mode de séchage. Trois objectifs ont été réalisés dans cette étude. Dans un premier temps, il s agissait de déterminer les règles de formulations des peintures aqueuses pour les rendre plus performantes vis-à-vis du séchage micro-ondes. Ce travail a fait l objet d un plan d expériences, dans lequel ont été étudiés les composants majeurs rentrant dans la constitution des vernis et peintures aqueuses. Cette phase d optimisation nous a permis de déterminer les meilleures formulations de peintures aqueuses destinées à être séchées par micro-ondes. La deuxième partie de ce travail a consisté à analyser au niveau microscopique et macroscopique les films de peintures obtenus à partir des meilleures formulations issues du plan d expériences. Des différences structurales ont été observées au niveau microscopique, pouvant ainsi expliquer les différences examinées au niveau macroscopique. Enfin, la troisième et dernière partie de ce travail nous a amené à réaliser une étude théorique de modélisation moléculaire sur le transport de l eau dans diverses matrices polymères. Cette étude théorique a confirmé les résultats obtenus lors du plan d expérience, démontrant ainsi la capacité des peintures aqueuses à être séchées par micro-ondes.NICE-BU Sciences (060882101) / SudocSudocFranceF

Evaluation d'un cohorte d'enfants présentant une anomalie du gène SHOX suivis à l'hôpital Armand-Trousseau [de Paris]

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

Sunnybrook Facial Grading System: Intra-rater and Inter-rater Variabilities

International audienceObjectives: Evaluate intra-rater and inter-rater variabilities of the Sunnybrook Facial Grading System (SFGS) and explore potential factors of variability.Study design: Prospective test of hypothesis.Setting: University tertiary referral center.Participants/methods: Facial video recordings of 20 patients with variable degrees of peripheral facial palsy (PFP) were anonymized then presented to 31 independents raters in 2 trials. The raters were senior and junior professionals involved in the management of PFP: ENT specialists, physiotherapists, and speech therapists. The SFGS was used for grading paralysis.Main outcome measure: Intra-rater and inter-rater variabilities were estimated by intraclass correlation coefficient (ICC [95% confidence interval]) for the composite score and the three subscores of the SFGS. Factors of variability studied were: rater professions and rater experience (senior vs junior).Results: For the total population, the intra-rater ICC was 0.915[0.900-0.929] for the composite score considered to represent almost perfect repeatability. Repeatability was important for symmetry at rest (0.694[0.646-0.737]), almost perfect for voluntary movements (0.903[0.886-0.918]), and important to almost perfect for synkinesis (0.810[0.778-0.838]). The inter-rater ICC for the composite score was 0.847[0.755-0.923] indicating important to almost perfect agreement between all raters. Agreement between raters was important to almost perfect for voluntary movements (0.839[0.746-0.919]), but moderate to important for symmetry at rest (0.553[0.408-0.730]) and weak to important for synkinesis (0.476[0.333-0.666]). Some variability was found between raters groups; however, repeatability and agreement were good for all raters.Conclusions: The SFGS is a reproducible scale. It can be used with good reproducibility by both novices and experts, and by all professionals involved in the management of PFP