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Background/Objectives:Higher visceral fat mass (VFM) is associated with an increased risk for developing cardio-metabolic diseases. The mechanisms by which an unhealthy diet pattern may influence visceral fat (VF) development has yet to be examined through cutting-edge multi-omic methods. Therefore, our objective was to examine the dietary influences on VFM and identify gut microbiome and metabolite profiles that link food intakes to VFM.Subjects/Methods:In 2218 twins with VFM, food intake and metabolomics data available we identified food intakes most strongly associated with VFM in 50% of the sample, then constructed and tested the ‘VFM diet score’ in the remainder of the sample. Using linear regression (adjusted for covariates, including body mass index and total fat mass), we investigated associations between the VFM diet score, the blood metabolomics profile and the fecal microbiome (n=889), and confirmed these associations with VFM. We replicated top findings in monozygotic (MZ) twins discordant (⩾1 s.d. apart) for VFM, matched for age, sex and the baseline genetic sequence.Results:Four metabolites were associated with the VFM diet score and VFM: hippurate, alpha-hydroxyisovalerate, bilirubin (Z,Z) and butyrylcarnitine. We replicated associations between VFM and the diet score (beta (s.e.): 0.281 (0.091); P=0.002), butyrylcarnitine (0.199 (0.087); P=0.023) and hippurate (−0.297 (0.095); P=0.002) in VFM-discordant MZ twins. We identified a single species, Eubacterium dolichum to be associated with the VFM diet score (0.042 (0.011), P=8.47 × 10-5), VFM (0.057 (0.019), P=2.73 × 10-3) and hippurate (−0.075 (0.032), P=0.021). Moreover, higher blood hippurate was associated with elevated adipose tissue expression neuroglobin, with roles in cellular oxygen homeostasis (0.016 (0.004), P=9.82x10-6).Conclusions:We linked a dietary VFM score and VFM to E. dolichum and four metabolites in the blood. In particular, the relationship between hippurate, a metabolite derived from microbial metabolism of dietary polyphenols, and reduced VFM, the microbiome and increased adipose tissue expression of neuroglobin provides potential mechanistic insight into the influence of diet on VFM.International Journal of Obesity advance online publication, 4 April 2017; doi:10.1038/ijo.2017.70.

Thème de l'année 2017:" De l'implantation à la parturition: Bases fondamentales et cliniques"; Evaluation de la perfusion placentaire en IRM : variation des mesures de T2* chez un modèle lapin d’hypoperfusion placentaire aiguë. 6. Colloque International du Groupe de la Francophonie Placentaire

The sharing of legacy preclinical safety data among pharmaceutical companies and its integration with other information sources offers unprecedented opportunities to improve the early assessment of drug safety. Here, we discuss the experience of the eTOX project, which was established through the Innovative Medicines Initiative to explore this possibility.

International audience; Acute exacerbations are the most frequent complications during progression of the COPD disease. Within a therapeutic educational program, performing written action plans has been shown to impact the management and the consequences of these acute exacerbations. A personalized written action plan is a document generated by both health professionals and patients and is divided into three parts: detailed description of current clinical signs, of exacerbation symptoms and how to self-manage an exacerbation onset. The action plan is recorded in written document that should be kept by the patient. It is part of a therapeutic education course that allows making a patient competent to manage his life with the disease and to take the adequate measures when necessary. Education not only concerns the patient but also the caregiver, both being sensitized to the benefits of the action plan and both feeling competent for its realization and its implementation. Routine training is necessary to sensitize health care providers to increase the use of personalized written action plans. This will help to redefine the role of the patient and the professional in promoting his self-management.; Les exacerbations sont les complications évolutives les plus fréquentes dans la BPCO. En matière d’éducation thérapeutique, la réalisation de plans d’action personnalisés écrits a montré un impact sur la gestion et le retentissement des exacerbations. État de l’art. — Le plan d’action personnalisé est un document, élaboré conjointement entre les soignants et chaque patient, qui comporte trois parties : description des signes actuels dela maladie, description des signes des exacerbations et conduite à tenir par le patient en cas d’apparition d’une exacerbation. Le plan d’action est consigné dans un document conservé par le patient. Il fait partie d’un programme d’éducation thérapeutique qui permet de rendre le patient compétent pour gérer sa vie avec sa maladie et prendre les mesures adéquates quand nécessaire. L’éducation ne concerne pas seulement le patient mais aussi le soignant, chacun devant être sensibilisé à l’intérêt du plan d’action et arriver à se sentir compétent dans sa réalisation et sa mise en oeuvre. Conclusion. — Une formation régulière est nécessaire pour sensibiliser les soignants et augmenter le nombre de plans d’action personnalisés écrits. Une telle formation permet de redéfinir le rôle du patient et du professionnel dans cette démarche.

National audience; The placental dysfunction, which seems to be caused by a defect of trophoblastic invasion and impaired uterine vascular remodeling since the first trimester, is responsible in a non-exclusive way for the chronic placental hypoxia, resulting secondarily in the intra-uterine growth restriction (IUGR) and/or pre-eclampsia (PE). The quality of utero-placental vasculature is essential for a proper fetal development and a successful progress of pregnancy. However, the in vivo assessment of placental vascularization with non-invasive methods is complicated by the small size of placental terminal vessel and its complex architecture. Moreover, imaging with contrast agent is not recommended to pregnant women. Until recently, the fetal and maternal vascularization could only be evaluated through pulse Doppler of uterine arteries during pregnancy, which has little clinical value for utero-placental vascularization defects assessment. Recently, a non-invasive study, without use of contrast agent for vasculature evaluation of an organ of interest has become possible by the development of 3D Doppler angiography technique. The objective of this review was to make an inventory of its current and future applications for utero-placental vasculature quantification. The main findings of the literature on the assessment of utero-placental vascularization in physiological situation and major placental vascular dysfunction pathologies such as PE and IUGR were widely discussed.; La dysfonction placentaire, qui semble être causée par un défaut d’invasion trophoblastique et un défaut de remodelage vasculaire utérin dès le premier trimestre, est responsable de manière non exclusive d’une hypoxie placentaire chronique qui aboutit secondairement au retard de croissance intra-utérin (RCIU) et/ou pré-éclampsie (PE). La qualité de la vascularisation utéroplacentaire est primordiale au bon développement fœtal et au déroulement satisfaisant de la grossesse. Cependant, l’évaluation de la vascularisation placentaire in vivo avec des méthodes non invasives est compliqué par la petite taille des vaisseaux terminaux placentaires et son architecture très complexe. Par ailleurs, le produit de contraste de l’imagerie n’est pas recommandé aux femmes enceintes. Jusque récemment, la vascularisation maternelle et fœtale ne pouvait être étudiée en cours de grossesse que par Doppler pulsé de l’artère utérine, qui n’a qu’une faible valeur clinique pour l’étude de défauts de vascularisation utéroplacentaire. Dernièrement, l’étude non invasive et sans produit de contraste de la vascularisation d’un organe d’intérêt a été rendue possible par l’essor de la technique d’angiographie Doppler 3D. L’objectif de cette revue était de réaliser un état des lieux des applications actuelles et futures pour la quantification de la vascularisation utéroplacentaire. Nous rapportons et discutons les principaux résultats de la littérature sur l’évaluation de la vascularisation utéroplacentaire en cas de grossesses physiologiques et de dysfonctions vasculaires placentaires telles que la PE et le RCIU.

In opdracht van het Astmafonds worden in dit rapport beschikbare gegevens in kaart gebracht over de gezondheidsgerelateerde kwaliteit van leven van personen met astma en COPD vergeleken met die van andere groepen. Hiertoe is enerzijds een literatuurstudie uitgevoerd waarvoor studies zijn geselecteerd waarin de kwaliteit van leven van personen met astma of COPD wordt vergeleken met die van de algemene bevolking of van personen met een andere (chronische) ziekte. Anderzijds zijn nieuwe analyses uitgevoerd op basis van twee epidemiologische studies. Gezondheidsgerelateerde kwaliteit van leven is een begrip met meerdere dimensies. Zowel de gezondheidstoestand als de gevolgen daarvan voor het functioneren en de waardering daarvoor zijn van belang. Het literatuur onderzoek en de analyses toonden aan dat zowel het fysieke, emotionele als sociale functioneren wordt be6nvloed door astma. Personen met COPD bleken lager te scoren op maten voor kwaliteit van leven dan personen met astma. Personen met astma of COPD gaven de laagste score aan hoe zij hun algemene gezondheid ervoeren in vergelijking met personen met een andere chronische ziekte. Veel gegevens over de gezondheidsgerelateerde kwaliteit van leven van personen met astma en COPD in Nederland in vergelijking met andere groepen bleken beschikbaar. Andere gegevens zijn niet gepubliceerd maar lijken wel aanwezig. Zo is er nog weinig bekend over verschillen tussen mannen en vrouwen. Ook verschillen tussen leeftijdsgroepen, mensen met een verschillende sociaal-economische achtergrond of uit verschillende regio's binnen de groep personen met astma of COPD zijn niet direct beschikbaar. Deze gegevens zijn wel via secundaire analyses te verkrijgen. Enkele gegevens blijken in de huidige studies niet aanwezig. Dat betreft de kwaliteit van leven van kinderen met astma in de leeftijd van 0-6 jaar en 14-20 jaar. Ook over de subjectieve beleving van het functioneren en specifieke activiteiten of situaties waarin men beperkingen ervaart is nog weinig bekend.

Activation of the CXC chemokine receptor 4 (CXCR4) in Cajal–Retzius cells by CXC chemokine ligand 12 (CXCL12) is important for controlling their excitability. CXCR4 is also a co-receptor for the glycoprotein 120 (gp120) of the envelope of the human immunodeficiency virus type 1 (HIV-1), and binding of gp120 to CXCR4 may produce pathological effects. In order to study CXCR4-dependent modulation of membrane excitability, we recorded in cell-attached configuration spontaneous action currents from hippocampal stratum lacunosum-moleculare Cajal–Retzius cells of the CXCR4-EGFP mouse. CXCL12 (50 nm) powerfully inhibited firing independently of synaptic transmission, suggesting that CXCR4 regulates an intrinsic conductance. This effect was prevented by conditioning slices with BAPTA-AM (200 μm), and by blockers of the BK calcium-dependent potassium channels (TEA (1 mm), paxilline (10 μm) and iberiotoxin (100 nm)). In contrast, exposure to gp120 (pico- to nanomolar range, alone or in combination with soluble cluster of differentiation 4 (CD4)), enhanced spontaneous firing frequency. This effect was prevented by the CXCR4 antagonist AMD3100 (1 μm) and was absent in EGFP-negative stratum lacunosum-moleculare interneurons. Increased excitability was prevented by treating slices with BAPTA-AM or bumetanide, suggesting that gp120 activates a mechanism that is both calcium- and chloride-dependent. In conclusion, our results demonstrate that CXCL12 and gp120 modulate the excitability of Cajal–Retzius cells in opposite directions. We propose that CXCL12 and gp120 either generate calcium responses of different strength or activate distinct pools of intracellular calcium, leading to agonist-specific responses, mediated by BK channels in the case of CXCL12, and by a chloride-dependent mechanism in the case of gp120.

12 páginas, 4 figuras, 3 tablas., Defining population structure and genetic diversity levels is of the utmost importance for developing efficient conservation strategies. Overfishing has caused mean annual catches of the European spiny lobster (Palinurus elephas) to decrease alarmingly along its distribution area. In this context, there is a need for comprehensive studies aiming to evaluate the genetic health of the exploited populations. The present study is based on a set of ten nuclear markers amplified in 331 individuals from ten different localities covering most of P. elephas distribution area. Samples from Atlantic and Mediterranean basins showed small but significant differences, indicating that P. elephas populations do not behave as a single panmictic unit but form two partially-overlapping groups. Despite intense overfishing, our dataset did not recover a recent bottleneck signal, and instead showed a large and stable historical effective size. This result could be accounted for by specific life-history traits (reproduction and longevity) and the limitations of molecular markers in covering recent timescales for nontemporal samples. The findings of the present study emphasize the need to integrate information on effective population sizes and life-history parameters when evaluating population connectivity levels from genetic data., This work was supported by a predoctoral fellowship awarded by the Autonomous Government of Catalonia to F.P. (2006FIC-00082). Research was funded by projects FBBVA-BIOCON 08-187/09, CGL2006-13423, and CTM2007-66635. The authors are part of the research group 2009SGR- 636, 2009SGR-655, and 2009SGR-1364 of the Generalitat de Catalunya. F.P. acknowledges EU-Synthesys grant (GB-TAF-4474).

Recent papers have promoted the view that model-based methods in general, and those based on Approximate Bayesian Computation (ABC) in particular, are flawed in a number of ways, and are therefore inappropriate for the analysis of phylogeographic data. These papers further argue that Nested Clade Phylogeographic Analysis (NCPA) offers the best approach in statistical phylogeography. In order to remove the confusion and misconceptions introduced by these papers, we justify and explain the reasoning behind model-based inference. We argue that ABC is a statistically valid approach, alongside other computational statistical techniques that have been successfully used to infer parameters and compare models in population genetics. We also examine the NCPA method and highlight numerous deficiencies, either when used with single or multiple loci. We further show that the ages of clades are carelessly used to infer ages of demographic events, that these ages are estimated under a simple model of panmixia and population stationarity but are then used under different and unspecified models to test hypotheses, a usage the invalidates these testing procedures. We conclude by encouraging researchers to study and use model-based inference in population genetics.

International audience

The survey of the available data on morbidity and mortality of asthma and Chronic Obstructive Pulmonary Disease (COPD) in the Netherlands presented here was carried out by order of the Netherlands Asthma Foudation. Objectives were to: 1) collect the available data on asthma and COPD in the Netherlands and identify gaps in these data and 2) describe the incidence and prevalence of asthma and COPD. The description, taking asthma and COPD separately, was to focus on the degrees of severity and on the specific subgroups in the general population, e.g. ethnic and socio-economic groups. The available data were seen to provide a reasonable picture of the morbidity caused by asthma and COPD in the Netherlands; this picture will be improved by more specific secondary analysis of the available data. Nevertheless, inherent to the overlapping of these two diseases is the failure to always being able to make a valid distinction between asthma and COPD. Data on degrees of severity may be obtained though registration if consensus can be reached on the definition of degrees of severity. The most noticeable gaps were in the lack of data for very young children, young adults and the elderly, and for the ethnic subgroups.