Association between fetal DES-exposure and psychiatric disorders in adolescence/adulthood: evidence from a French cohort of 1002 prenatally exposed children

International audienceIn utero diethylstilbestrol (DES) exposure has been demonstrated to be associated with somatic abnormalities in adult men and women. Conversely, the data are contradictory regarding the association with psychological or psychiatric disorders during adolescence and adulthood. This work was designed to determine whether prenatal exposure to DES affects brain development and whether it is associated with psychiatric disorders in male and female adolescents and young adults. HHORAGES Association, a national patient support group, has assembled a cohort of 1280 women who took DES during pregnancy. We obtained questionnaire responses from 529 families, corresponding to 1182 children divided into three groups: Group 1 (n = 180): firstborn children without DES treatment, Group 2 (n = 740): exposed children, and Group 3 (n = 262): children born after a previous pregnancy treated by DES. No psychiatric disorders were reported in Group 1. In Group 2, the incidence of disorders was drastically elevated (83.8%), and in Group 3, the incidence was still elevated (6.1%) compared with the general population. This work demonstrates that prenatal exposure to DES is associated with a high risk of psychiatric disorders in adolescence and adulthood

Project management case analysis in technology companies

Este artículo tiene como objetivo identificar y analizar tres empresas tecnológicas como Google, Globant y Zemoga, a través del reconocimiento de unas variables comunes de la metodología de Gestión de Proyectos evidenciadas en cada empresa. Entre las variables a destacar están: la innovación, la metodología de gestión de proyectos, la estructura organizacional, el trabajo en equipo, la complejidad y la cultura organizacional. Este análisis de las variables muestra como el ambiente de trabajo y los incentivos a la innovación dentro de la organización, pueden generar una relación simbiótica entre los empleados y la empresa lo que aumenta las probabilidades de tener éxito en la ejecución de proyectos.This article attempts to identify and analyze success technological companies like Google, Globant and Zemoga by recognizing some common variables of the Project Management model of each one. The variables to stand out are: innovation, methodology for project management, organizational structure, teamwork, complexity and organizational culture. This analysis recognizes common strengths in project management and highlight what elements can lead to successful management in technology companies

Fulvestrant treatment of precocious puberty in girls with McCune-Albright syndrome

BACKGROUND: McCune-Albright Syndrome (MAS) is usually characterized by the triad of precocious puberty (PP), fibrous dysplasia, and café au lait spots. Previous treatments investigated for PP have included aromatase inhibitors and the estrogen receptor modulator, tamoxifen. Although some agents have been partially effective, the optimal pharmacologic treatment of PP in girls with MAS has not been identified. The objective of this study was to evaluate the safety and efficacy of fulvestrant (Faslodex(TM)), a pure estrogen receptor antagonist, in girls with progressive precocious puberty (PP) associated with McCune-Albright Syndrome (MAS). METHODS: In this prospective international multicenter trial, thirty girls ≤ 10 years old with MAS and progressive PP received fulvestrant 4 mg/kg via monthly intramuscular injections for 12 months. Changes in vaginal bleeding, rates of bone age advancement, growth velocity, Tanner staging, predicted adult heights, and uterine and ovarian volumes were measured. RESULTS: Median vaginal bleeding days decreased from 12.0 days per year to 1.0 day per year, with a median change in frequency of -3.6 days, (95% confidence interval (CI) -10.10, 0.00; p = 0.0146). Of patients with baseline bleeding, 74% experienced a ≥50% reduction in bleeding, and 35% experienced complete cessation during the study period (95% CI 51.6%, 89.8%; 16.4%, 57.3%, respectively). Average rates of bone age advancement (ΔBA/ΔCA) decreased from 1.99 pre-treatment to 1.06 on treatment (mean change -0.93, 95% CI -1.43, -0.43; p = 0.0007). No significant changes in uterine volumes or other endpoints or serious adverse events occurred. CONCLUSIONS: Fulvestrant was well tolerated and moderately effective in decreasing vaginal bleeding and rates of skeletal maturation in girls with MAS. Longer-term studies aimed at further defining potential benefits and risks of this novel therapeutic approach in girls with MAS are needed. TRIAL REGISTRATION: NCT0027891

Immunological and Metabolomic Impacts of Administration of Cry1Ab Protein and MON 810 Maize in Mouse

We have investigated the immunological and metabolomic impacts of Cry1Ab administration to mice, either as a purified protein or as the Cry1Ab-expressing genetically modified (GM) MON810 maize. Humoral and cellular specific immune responses induced in BALB/cJ mice after intra-gastric (i.g.) or intra-peritoneal (i.p.) administration of purified Cry1Ab were analyzed and compared with those induced by proteins of various immunogenic and allergic potencies. Possible unintended effects of the genetic modification on the pattern of expression of maize natural allergens were studied using IgE-immunoblot and sera from maize-allergic patients. Mice were experimentally sensitized (i.g. or i.p. route) with protein extracts from GM or non-GM maize, and then anti-maize proteins and anti-Cry1Ab–induced immune responses were analyzed. In parallel, longitudinal metabolomic studies were performed on the urine of mice treated via the i.g. route. Weak immune responses were observed after i.g. administration of the different proteins. Using the i.p. route, a clear Th2 response was observed with the known allergenic proteins, whereas a mixed Th1/Th2 immune response was observed with immunogenic protein not known to be allergenic and with Cry1Ab. This then reflects protein immunogenicity in the BALB/c Th2-biased mouse strain rather than allergenicity. No difference in natural maize allergen profiles was evidenced between MON810 and its non-GM comparator. Immune responses against maize proteins were quantitatively equivalent in mice treated with MON810 vs the non-GM counterpart and no anti-Cry1Ab–specific immune response was detected in mice that received MON810. Metabolomic studies showed a slight “cultivar” effect, which represented less than 1% of the initial metabolic information. Our results confirm the immunogenicity of purified Cry1Ab without evidence of allergenic potential. Immunological and metabolomic studies revealed slight differences in mouse metabolic profiles after i.g. administration of MON810 vs its non-GM counterpart, but no significant unintended effect of the genetic modification on immune responses was seen

The ANTENATAL multicentre study to predict postnatal renal outcome in fetuses with posterior urethral valves: objectives and design

Abstract Background Posterior urethral valves (PUV) account for 17% of paediatric end-stage renal disease. A major issue in the management of PUV is prenatal prediction of postnatal renal function. Fetal ultrasound and fetal urine biochemistry are currently employed for this prediction, but clearly lack precision. We previously developed a fetal urine peptide signature that predicted in utero with high precision postnatal renal function in fetuses with PUV. We describe here the objectives and design of the prospective international multicentre ANTENATAL (multicentre validation of a fetal urine peptidome-based classifier to predict postnatal renal function in posterior urethral valves) study, set up to validate this fetal urine peptide signature. Methods Participants will be PUV pregnancies enrolled from 2017 to 2021 and followed up until 2023 in >30 European centres endorsed and supported by European reference networks for rare urological disorders (ERN eUROGEN) and rare kidney diseases (ERN ERKNet). The endpoint will be renal/patient survival at 2 years postnatally. Assuming α = 0.05, 1–β = 0.8 and a mean prevalence of severe renal outcome in PUV individuals of 0.35, 400 patients need to be enrolled to validate the previously reported sensitivity and specificity of the peptide signature. Results In this largest multicentre study of antenatally detected PUV, we anticipate bringing a novel tool to the clinic. Based on urinary peptides and potentially amended in the future with additional omics traits, this tool will be able to precisely quantify postnatal renal survival in PUV pregnancies. The main limitation of the employed approach is the need for specialized equipment. Conclusions Accurate risk assessment in the prenatal period should strongly improve the management of fetuses with PUV

Etude et modélisation des mécanismes de transfert de matière en ultrafiltration

Cette étude nous a permis de mieux comprendre et de modéliser le transfert de matière en ultrafiltration. Tout d'abord grâce à une étude expérimentale dans des conditions de complexité contrôlée, nous avons pu mettre en évidence les différentes résistances au transfert de matière et étudier l'influence des paramètres opératoires sur le "poids" relatif de chacune d'elles. Pour prédire les flux de perméat en fonction des conditions opératoires nous avons eu recours à la modélisation. Grâce à de nouveaux résultats expérimentaux, nous avons décrit, appliqué et analysé les modèles classiquement utilisés en ultrafiltration qui sont le modèle de gel, le modèle de la pression osmotique et celui des résistances en série. Les résultats expérimentaux montrent que les deux premiers modèles reposent sur des hypothèses erronées. Le modèle des résistances en série ne permet pas de prédire le flux de perméat malgré plusieurs modifications. Quoi qu'il en soit, pour utiliser ces modèles il faut connaître le coefficient de transfert de matière k qui peut en principe être estimé par les corrélations du nombre de Sherwood. Par une étude bibliographique, nous avons fait le point sur les corrélations classiques ainsi que sur les corrélations améliorées. A l'évidence, la difficulté dans l'estimation du coefficient de transfert de matière est due au couplage des phénomènes de transfert (diffusion-convection-accumulation de matière à la membrane) localisés au voisinage de la membrane. Nous avons donc développé un modèle à deux dimensions basé sur la résolution numérique des équations de diffusion-convection. Ce modèle permet de prédire le flux de perméat en fonction des différents paramètres comme la pression transmembranaire, la concentration de la solution, la vitesse de circulation du fluide et la longueur de la membrane. Nous avons testé ce nouveau modèle pour deux solutés et deux types de membranes et les flux calculés sont en très bon accord avec les valeurs expérimentales.AIX-MARSEILLE3-BU Sc.St Jérô (130552102) / SudocSudocFranceF

Intérêt des lignées cellulaires bioluminescentes pour l'analyse des effets estrogéniques, androgéniques et antiandrogéniques (implication en pathologie endocrinienne et/ou environnementale)

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUP (751062107) / SudocMONTPELLIER-BU Médecine (341722104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

L' Enfant et le cabinet dentaire (une approche comportementale)

MONTROUGE-BUFR Odontol.PARIS5 (920492101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF