Coupling Complete Blood Count and Steroidomics to Track Low Doses Administration of Recombinant Growth Hormone: An Anti-Doping Perspective

Growth Hormone (GH) under its human recombinant homologue (rhGH), may be abused by athletes to take advantage of its well-known anabolic and lipolytic properties; hence it is prohibited in sports by the World Anti-Doping Agency. Due to the rapid turnover of rhGH, anti-doping screening tests have turned to monitor two endocrine biomarkers (IGF-I and P-III-NP), but unfortunately, they show population-wise variability, limiting the identification rate of rhGH users. Previous studies have evidenced the numerous effects of GH on human physiology, especially in hematopoiesis and steroidogenesis. In this work, aiming to discover novel physiological rhGH biomarkers, we analyzed the complete blood count and the steroidomics profile of healthy, physically active, young males treated either with EPO + rhGH or EPO + placebo. The time-trends of these two physiological routes have been analyzed through geometric trajectory analysis (GTA) and OPLS-DA. Individuals supplemented with micro-doses of rhGH exhibited different leukopoietic and steroidal profiles compared to the control population, suggesting a role of the rhGH in both pathways. In the article, hypotheses on the observed differences are discussed according to the most recent literature and compared to results in animal models. The use of leukopoietic and steroidal biomarkers together with endocrine biomarkers (IGF-1 and P-III-NP) allows to correctly classify over 98% of samples with no false positives, miss-classifying only one single sample (false negative) over a total of 56; a promising result, if compared to the current rhGH detection strategies

TWEAK Appears as a Modulator of Endometrial IL-18 Related Cytotoxic Activity of Uterine Natural Killers

BACKGROUND: TWEAK (Tumor necrosis factor like WEAK inducer of apoptosis) is highly expressed by different immune cells and triggers multiple cellular responses, including control of angiogenesis. Our objective was to investigate its role in the human endometrium during the implantation window, using an ex-vivo endometrial microhistoculture model. Indeed, previous results suggested that basic TWEAK expression influences the IL-18 related uNK recruitment and local cytotoxicity. METHODOLOGY/PRINCIPAL FINDINGS: Endometrial biopsies were performed 7 to 9 days after the ovulation surge of women in monitored natural cycles. Biopsies were cut in micro-pieces and cultured on collagen sponge with appropriate medium. Morphology, functionality and cell death were analysed at different time of the culture. We used this ex vivo model to study mRNA expressions of NKp46 (a uNK cytotoxic receptor) and TGF-beta1 (protein which regulates uNK cytokine production) after adjunction of excess of recombinant IL-18 and either recombinant TWEAK or its antibody. NKp46 protein expression was also detailed by immunohistochemistry in selected patients with high basic mRNA level of IL-18 and either low or high mRNA level of TWEAK. The NKp46 immunostaining was stronger in patients with an IL-18 over-expression and a low TWEAK expression, when compared with patients with both IL-18 and TWEAK high expressions. We did not observe any difference for TWEAK expression when recombinant protein IL-18 or its antibody was added, or conversely, for IL-18 expression when TWEAK or its antibody was added in the culture medium. In a pro-inflammatory environment (obtained by an excess of IL-18), inhibition of TWEAK was able to increase significantly NKp46 and TGF-beta1 mRNA expressions. CONCLUSIONS/SIGNIFICANCE: TWEAK doesn't act on IL-18 expression but seems to control IL-18 related cytotoxicity on uNK cells when IL-18 is over-expressed. Thus, TWEAK appears as a crucial physiological modulator to prevent endometrial uNK cytotoxicity in human

Phospholipid Profiles of Oleaginous Pressed Cakes Using NMR and Gas Chromatography

Camelina, flaxseed, hemp, sesame, and walnut cakes were analyzed for their phospholipid (PL) content and composition using P-31 and H-1 nuclear magnetic resonance and gas chromatography. The data evidenced variations between the sources in terms of (1) total lipid content and PL concentration, camelina cake being the richest source of PLs, (2) PL composition, phosphatidylcholine being the most abundant phospholipid in sesame and hemp cakes, whereas phosphatidylinositol represented about 25% of the total PLs in most cakes, and (3) fatty acid composition of the PLs, camelina cake being the richest source of omega 3 polyunsaturated fatty acids. These data may be useful to diversify the PL sources available and to provide PL fractions with specific nutritional or functional properties

Accessibilité de la remédiation cognitive en Île-de-France, en psychiatrie adulte et infanto-juvénile, et dispositifs de réhabilitation

R É S U M É La remé diation cognitive (RC) vise à ré duire des dé ficits cognitifs et fournir des straté gies palliatives en vue d'une ré insertion de patients avec handicap psychique. Elle s'inscrit dans un parcours de soin personnalisé et né cessite une é valuation et une prise en charge multidisciplinaires, incluant é ventuellement d'autres thé rapies psychosociales. Cette é tude, ré alisé e en 2016, a pour ambition d'é tablir un é tat des lieux de l'accessibilité et de la pratique de la RC en le-de-France, pour promouvoir un accè s large en systé matisant l'inté gration de la RC dans un parcours global et cohé rent. Si la RC est proposé e par prè s de 58 % des structures ayant ré pondu à l'enquête, sa mise en oeuvre gagnerait à être amé lioré e : elle s'inscrit à 58 % dans un projet de ré habilitation pré cis et l'é valuation multidisciplinaire avant/aprè s est ré alisé e à 51 % en psychiatrie adulte et 20 % en psychiatrie infanto-juvé nile (PIJ), peut-être du fait d'un manque de personnel qualifié (neuropsychologues). Les programmes utilisé s en PIJ sont peu spé cifiques. La capacité d'accueil, encore faible, devrait être majoré e par des programmes de groupe. Malgré un manque de connaissance à combler, il ressort un inté rêt important pour la RC avec une volonté exprimé e par douze structures à se former. Les autres thé rapies psychosociales, bien que mieux connues, gagneraient à être plus souvent proposé es et labellisé es par l'ARS. Nos ré sultats confirment une rareté de l'offre de soin en psychiatrie dans le 77, le 91 et 93. Quatre unité s de ré habilitation dans le 77 et trois dans le 91 sont en formation. Trois structures dans le 77 et deux dans le 91 souhaitent se former. Les soutenir est d'autant plus important que la bonne pratique de la RC a un effet direct sur les bé né fices en termes de coû ts socié taux. Depuis, dans toute l'IDF, huit structures ont dé posé un projet de plateforme de RC et Ré habilitation. C 2018 Elsevier Masson SAS. Tous droits ré servé s. A B S T R A C T Cognitive remediation (CR) aims to decrease cognitive deficits and provide palliative strategies for reintegration of patients with psychic disability. It is part of a personalized care program and requires multidisciplinary assessment and management, including eventually other psychosocial therapies. This study, carried out in 2016, aims to establish an inventory of accessibility and practice of the CR in le-de-France, to promote broad access and systematize the integration of CR in a global and coherent course. The CR is proposed by nearly 58 % of the structures that answered the survey, but its implementation could be improved: it stands for 58 % in a specific project and the multidisciplinary evaluation before/ after is carried out at 51 % in Adult Psychiatry and 20 % in Child and Teen Psychiatry (CTP), perhaps due to a lack of qualified staff (neuropsychologists). The programs used in CTP are nonspecific. The accommodation capacity should be increased by group programs. Despite a lack of knowledge to fill

Evaluation du risque sanitaire lié aux expositions environnementales des populations à l'ammoniac atmosphérique en zone rurale

International audienceUne étude des lichens dans les Côtes d'Armor a fait état d'une adaptation de la flore lichénique à la présence de composés azotés (ammoniac) dans l'atmosphère. L'ammoniac étant connu comme étant un gaz irritant, ces travaux ont, dans la région étudiée, suscité des interrogations sur un éventuel impact des émissions d'ammoniac sur la santé des populations vivant en zone d'élevage intensif. C'est dans ce contexte qu'a été fixé l'objectif d'évaluer le risque lié aux teneurs atmosphériques en ammoniac pour les personnes non exposées professionnellement. L'identification du potentiel dangereux de la substance et la détermination de la probabilité de survenue du danger ont été réalisées au moyen d'une étude bibliographique. Cette étude a montré que les niveaux d'exposition mesurés et modélisés restent inférieurs aux valeurs recommandées pour la protection de la santé et il est possible, en considérant l'existence d'un seuil, de conclure que l'ammoniac atmosphérique ne devrait pas provoquer de phénomènes irritatifs pour les populations

Phases précoces du parasitisme tellurique : dynamique microbienne et chimique des sols et communication via l'exsudation racinaire : Réponses bactériennes aux exsudats racinaires

National audienc