Three Common Variants of LEP, NPY1R and GPR54 Show No Association with Age at Menarche

International audienc

The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis

Acknowledgments This work was supported by European Union ALLFUN (FP7/2007 2013, HEALTH-2010-260338) (Fungi in the setting of inflammation, allergy and autoimmune diseases: Translating basic science into clinical practices ‘‘ALLFUN’’) to D.C.I., F.C., C.F., M.G.N., and N.A.R.G. M.G.N and J.Q. were supported by a Vici grant of The Netherlands Organization of Scientific Research (to M.G.N.). M.G.N. was supported by an ERC Consolidator Grant (nr. 310372). N.A.R.G. was also supported by the Wellcome Trust (086827, 075470, 097377, & 101873).Peer reviewedPublisher PD

Clinical Impact of Antifungal Susceptibility, Biofilm Formation and Mannoside Expression of Candida Yeasts on the Outcome of Invasive Candidiasis in ICU: An Ancillary Study on the Prospective AmarCAND2 Cohort

Background: The link between Candida phenotypical characteristics and invasive candidiasis (IC) prognosis is still partially unknown.Methods:Candida strains isolated during the AmarCAND2 study were centrally analyzed for species identification, antifungal susceptibility, biofilm formation, and expression of surface and glycoconjugate mannosides. Correlation between these phenotypical features and patient outcome was sought using a multivariable Cox survival model.Results:Candida albicans was predominant (65.4%, n = 285), with a mortality rate significantly lower than that in patients with non-albicans strains [HR 0.67 (0.46–1.00), p = 0.048]. The rate of fluconazole-resistant strains was low (C. albicans and Candida glabrata: 3.5 and 6.2%, respectively) as well as caspofungin-resistant ones (1 and 3.1%, respectively). Early biofilm formation was less frequent among C. albicans (45.4%) than among non-albicans (81.2%). While the strains of C. albicans showed variable levels of surface mannosides expression, strains isolated from candidemia exhibited a high expression of β-man, which was correlated with an increased mortality (p = 0.02).Conclusion:Candida albicans IC were associated with lower mortality, and with strains that exhibited less frequently early biofilm formation than non-albicans strains. A high expression of β-man was associated with increased IC mortality. Further studies are warranted to confirm this data and to evaluate other virulence factors in yeasts

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

un modèle d’étude du vieillissement

Le vieillissement est un processus physiologique complexe qui accompagne l’avancée en âge de tout organisme vivant. L’utilisation d’organismes modèles considérés comme simples a été fondamentale pour la compréhension des mécanismes impliqués dans ce processus. Caenorhabditis elegans, nématode utilisé initialement pour établir les bases génétiques et moléculaires du développement, est devenu un des modèles d’étude du vieillissement. L’utilisation de cet invertébré a permis de détecter un lien direct entre l’activation de voies de signalisation cellulaire et la longévité. Si C. elegans ne permet pas d’analyser le processus complet du vieillissement humain, il reste un modèle de choix pour étudier des mécanismes et phénotypes particuliers du vieillissement

Glycannes pariétaux de levures et anticorps spécifiques

La paroi des levures est une structure complexe dont la variabilité régit les relations avec l’environnement. Les glycannes en sont des composés majeurs. Les anticorps expérimentaux ont permis de caractériser l’expression et le rôle biologique des séquences oligosaccharidiques les constituant et dont on a construit des analogues de synthèse. Ces outils ont été utilisés pour étudier la réponse humorale humaine lors des candidoses invasives déterminées par C. albicans et de la maladie de Crohn au cours de laquelle des anticorps anti-S. cerevisiae sont présents. Il a été démontré que les biomarqueurs de la maladie de Crohn étaient générés lors d’une candidose invasive, établissant un lien qui n’avait jamais été suspecté entre C. albicans et maladie de Crohn. Nous décrivons cette démarche et ses perspectives liées à l’utilisation de la technologie multiplex pour une meilleure compréhension et une meilleure prise en charge des candidoses invasives et de la maladie de Crohn

International Research Project on Job Retention and Return to Work Strategies for Disabled Workers: France

[Excerpt] The International Research Project on Job Retention and Return to Work Strategies for Disabled Workers is an initiative of the International Labour Organisation (ILO) and the Global Applied Research and Information Network on Employment and Training (GLADNET). It reflects ILO and GLADNET joint aims of establishing a base for cross-national research and strengthening links between research analysis and policy reform in the field of employment of disabled people. The Project is a response to a combination of developments which highlight the need for more effective policies and practices in support of workers whose prospects of remaining in employment are jeopardised by work injury, illness or disability. Persons with disabilities are increasingly claiming rights to stay in work as well as to access employment. Pressures on state budgets, the rising costs of compensation claims and disability benefits, and changes in the structure of the labour market are strengthening policies in favour of job retention and return to work. Enterprises are developing their own strategies to minimise the costs of disability and to retain valued employees. Overall, the balance of responsibility is shifting from the state to the enterprise. Policies and practices to prevent disabled workers from leaving work unnecessarily, and to facilitate rapid return to employment if job loss cannot be prevented, are recent developments in many countries. The cross-national exchange of information on initiatives and their effects is limited. The first aim of this Project has been to gather information about what has been attempted, by whom, for what purposes, in which contexts and to what effects. The second, more ambitious, aim, is to examine the interaction between the various policies and practices, identify dysfunctions, and work towards more coherent and cost-effective strategies for job retention and return to work which might be applied in different national systems. The ultimate objective is to identify strategies which can be put into effect in the workplace.International_Research_Project_France_Report.pdf: 13 downloads, before Oct. 1, 2020