Molecular targets of alcohol action: translational research for pharmacotherapy development and screening.

Alcohol abuse and dependence are multifaceted disorders with neurobiological, psychological, and environmental components. Research on other complex neuropsychiatric diseases suggests that genetically influenced intermediate characteristics affect the risk for heavy alcohol consumption and its consequences. Diverse therapeutic interventions can be developed through identification of reliable biomarkers for this disorder and new pharmacological targets for its treatment. Advances in the fields of genomics and proteomics offer a number of possible targets for the development of new therapeutic approaches. This brain-focused review highlights studies identifying neurobiological systems associated with these targets and possible pharmacotherapies, summarizing evidence from clinically relevant animal and human studies, as well as sketching improvements and challenges facing the fields of proteomics and genomics. Concluding thoughts on using results from these profiling technologies for medication development are also presented

Pymac: Quelle stratégie adopter pour une TPE (très petite entreprise ) digitale ?

Pymac est une agence web installée à Aix-en-Provence depuis 1998. L’arrivée des « systèmes de gestion de contenus » a bouleversé les acteurs traditionnels du marché. En effet, en proposant des modèles de sites avec un univers graphique et des cases préétablies, ces programmes informatiques ont facilité l’émergence de nouveaux entrants avec un coût moins élevé. Pymac s’est alors orientée vers la maintenance de sites afin de diversifier son offre et tirer parti de ses connaissances techniques.Pymac est ainsi reconnue pour sa technicité. Pourtant, tant le fondateur que la directrice actuelle ne sont pas informaticiens. Le fondateur vient de la distribution et sa fille, directrice actuelle, a également fait une formation en commerce. Ils se sont, certes, entourés d’informaticiens très compétents, mais la force de Pymac est sûrement de construire des sites comme des magasins en cherchant à susciter l’envie de rester aux utilisateurs. Ceci permet de mettre en évidence l’importance de la réflexion stratégique, marketing et commerciale

Copeptin assays in children for the differential diagnosis of polyuria‐polydipsia syndrome and reference levels in hospitalized children

International audienc

Congenital Central Hypothyroidism Caused by a Novel IGSF1 Variant Identified in a French Family

International audienceIntroduction: Congenital central hypothyroidism (CCH) is a rare disorder that can be caused by X-linked mutations in the immunoglobulin superfamily member 1 (IGSF1) gene. Here, we describe four familial cases with a variable presentation due to a novel IGSF1 pathogenic variant. Case Presentation: In the index case, an investigation at birth of a suspected brain-lung-thyroid syndrome surprisingly revealed a central hypothyroidism. Next-generation sequencing uncovered a novel IGSF1 pathogenic variant: a hemizygous single base duplication (G) resulting in a premature stop codon (NM_001555.4: c.2485dup, p.Ala829Glyfs*15). Further family investigations revealed missed neonatal CCH for the older brother who presented with prolonged jaundice (thyroid stimulating hormone 3.06 mUI/L, FT4 9.4 pmol/L, FT3 4.2 pmol/L). It also led to the diagnosis of CCH at 11 months of age for the younger brother, whose thyroid function was considered normal at birth. Neuropsychological evaluations showed no cognitive impairment for the eldest two brothers, but a slightly reduced processing-speed index compared with the other parameters for the oldest. Furthermore, a maternal uncle was diagnosed with biochemical CCH at 34 years of age, despite having few symptoms, and a complete workup revealed prolactin deficiency and macroorchidism. Discussion: This report of a rare case of neonatal CCH caused by IGSF1 deficiency highlights the importance of recognizing the neonatal signs of hypothyroidism to diagnose CCH as early as possible. Our results also show the importance of performing family genetic screening if a pathogenic variant is identified, to properly monitor carriers as CCH may develop over time. We suggest that these families should be followed up in the long term to better understand the natural history of this syndrome and evaluate the need for hormone substitution

RAPID DIFFERENTIAL DIAGNOSIS OF POLYURIA-POLYDIPSIA SYNDROME IN CHILDREN: THE COPEPTIN APPROACH. A CASE REPORT

International audienc

RAPID DIFFERENTIAL DIAGNOSIS OF POLYURIA-POLYDIPSIA SYNDROME IN CHILDREN: THE COPEPTIN APPROACH. A CASE REPORT

International audienc

Double diffusion encoding and applications for biomedical imaging

Diffusion Magnetic Resonance Imaging (dMRI) is one of the most important contemporary non-invasive modalities for probing tissue structure at the microscopic scale. The majority of dMRI techniques employ standard single diffusion encoding (SDE) measurements, covering different sequence parameter ranges depending on the complexity of the method. Although many signal representations and biophysical models have been proposed for SDE data, they are intrinsically limited by a lack of specificity. Advanced dMRI methods have been proposed to provide additional microstructural information beyond what can be inferred from SDE. These enhanced contrasts can play important roles in characterizing biological tissues, for instance upon diseases (e.g. neurodegenerative, cancer, stroke), aging, learning, and development. In this review we focus on double diffusion encoding (DDE), which stands out among other advanced acquisitions for its versatility, ability to probe more specific diffusion correlations, and feasibility for preclinical and clinical applications. Various DDE methodologies have been employed to probe compartment sizes (Section 3), decouple the effects of microscopic diffusion anisotropy from orientation dispersion (Section 4), probe displacement correlations, study exchange, or suppress fast diffusing compartments (Section 6). DDE measurements can also be used to improve the robustness of biophysical models (Section 5) and study intra-cellular diffusion via magnetic resonance spectroscopy of metabolites (Section 7). This review discusses all these topics as well as important practical aspects related to the implementation and contrast in preclinical and clinical settings (Section 9) and aims to provide the readers a guide for deciding on the right DDE acquisition for their specific application