Complexity of the microglial activation pathways that drive innate host responses during lethal alphavirus encephalitis in mice

Microglia express multiple TLRs (Toll-like receptors) and provide important host defence against viruses that invade the CNS (central nervous system). Although prior studies show these cells become activated during experimental alphavirus encephalitis in mice to generate cytokines and chemokines that influence virus replication, tissue inflammation and neuronal survival, the specific PRRs (pattern recognition receptors) and signalling intermediates controlling microglial activation in this setting remain unknown. To investigate these questions directly in vivo, mice ablated of specific TLR signalling molecules were challenged with NSV (neuroadapted Sindbis virus) and CNS viral titres, inflammatory responses and clinical outcomes followed over time. To approach this problem specifically in microglia, the effects of NSV on primary cells derived from the brains of wild-type and mutant animals were characterized in vitro. From the standpoint of the virus, microglial activation required viral uncoating and an intact viral genome; inactivated virus particles did not elicit measurable microglial responses. At the level of the target cell, NSV triggered multiple PRRs in microglia to produce a broad range of inflammatory mediators via non-overlapping signalling pathways. In vivo, disease survival was surprisingly independent of TLR-driven responses, but still required production of type-I IFN (interferon) to control CNS virus replication. Interestingly, the ER (endoplasmic reticulum) protein UNC93b1 facilitated host survival independent of its known effects on endosomal TLR signalling. Taken together, these data show that alphaviruses activate microglia via multiple PRRs, highlighting the complexity of the signalling networks by which CNS host responses are elicited by these infections

Ultrasound-assessed perirenal fat is related to increased ophthalmic artery resistance index in HIV-1 patients

<p>Abstract</p> <p>Background</p> <p>The introduction of highly active antiretroviral therapy (HAART) has dramatically changed the prognosis of human immunodeficiency virus (HIV) infection, with a significant decline in morbidity and mortality.</p> <p>Changes in body fat distribution are a common finding in individuals with HIV infection being treated with antiretrovirals, and this condition (collectively termed lipodystrophy syndrome) is associated with depletion of subcutaneous fat, increased triglycerides and insulin resistance. Obesity, particularly visceral obesity, is associated with increased risk of cardiovascular disease. Therefore, estimating visceral fat distribution is important in identifying subjects at high risk for cardiovascular disease.</p> <p>The aim of our study was to evaluate whether perirenal fat thickness (PRFT), a parameter of central obesity, is related to ophthalmic artery resistance index (OARI), an index of occlusive carotid artery disease in HIV-1 infected patients.</p> <p>Methods</p> <p>We enrolled 88 consecutive HIV-1-infected patients receiving highly active antiretroviral therapy for more than 12 months, in a prospective cohort study. Echographically measured PRFT and OARI, as well as serum metabolic parameters, were evaluated. PRFT and OARI were measured by 3.75 MHz convex and 7.5 MHz linear probe, respectively.</p> <p>Results</p> <p>The means of PRFT and OARI in HIV-1-infected patients with visceral obesity was considerably higher than in patients without it (p < 0.0001 and p < 0.001, respectively). Using the average OARI as the dependent variable, total serum cholesterol level, HDL, triglycerides, glycemia, sex, blood pressure, age and PRFT were independent factors associated with OARI. A PRFT of 6.1 mm was the most discriminatory value for predicting an OARI > 0.74 (sensitivity 78.9%, specificity 82.8%).</p> <p>Conclusions</p> <p>Our data indicate that ultrasound assessment of PRFT may have potential as a marker of increased endothelial damage with specific involvement of the ocular vascular region in HIV-1-infected patients.</p

Les services environnementaux fournis par l’agriculture et leurs modes de gouvernance : un cadre d’analyse économique

National audienceThis paper proposes to analyze the environmental services provided by farmers in order to clarify the diversity of transactions within the same field. We distinguish two main categories of services: “Service internalization” corresponding to the internalization of an externality by seeking to modify the joint product, and "Service Delivery” corresponding to a contract to provide the service. We then cross this characterization with the modes of governance (sectorial vs. territorial) of the environmental services. This analysis allows us, first, to have a better understanding of the dynamics of environmental service supply, and second, to highlight the poor integration of environmental issues in agriculture. The categories generated are illustrated from several empirical studies carried out between 2002 and 2010 in the framework of three research programs.Cet article propose de caractériser les services environnementaux fournis par les agriculteurs dans le but de clarifier la diversité des transactions qui relèvent d’une même dénomination. Deux catégories principales de services avec quelques déclinaisons ressortent : le « service d’internalisation » visant à internaliser une externalité en cherchant à modifier le produit joint ; le « service prestation » correspondant à un contrat de prestation de service. Nous croisons alors cette caractérisation avec les modes de gouvernance (sectorielle vs territoriale) dans lesquels les services environnementaux s’inscrivent, croisement qui permet, d’une part, de comprendre les dynamiques d’offre de services environnementaux, et d’autre part, de remarquer la faible intégration des problèmes environnementaux dans le secteur agricole. Les catégories produites sont illustrées à partir de plusieurs investigations empiriques réalisées entre 2002 et 2010 dans trois programmes de recherche

Identification et notion de coûts d'organisation dans les services collectifs locaux Étude de cas : le service d'épandage agricole des boues d'épuration

Cet article analyse l'organisation et les coûts de la fourniture du service d'épandage agricole des boues résiduaires. Certains coûts supportés par les producteurs de boues ont été jusqu'ici négligés : coûts de réalisation des études préalables, coûts de rédaction des conventions d'épandage, coûts d'adaptation des plans d'épandage. À partir d'une enquête menée auprès de cinquante communes des départements du Puy-de-Dôme et de la Haute-Vienne, nous montrons que le niveau de ces coûts, qualifiés de coûts d'organisation, contribue à expliquer les choix des communes. Enfin, un certain nombre de leviers d'action publique sont identifiés tant à un niveau national que local. / This article analyzes the organization and the costs of the sewage sludge spreading service. Indeed, some costs bore by the sewage sludge mud producers were neglected up to now : assessment costs of spreading environmental impacts, planning and contracting costs (with farmers), miscoordination costs. From a survey carried out near 50 municipalities of the districts of Puy-de-Dome and Haute-Vienne, we show that the level of these organizational costs contributes to explain the choices of the municipalities. Lastly, we stress several policy instruments as well on a central as a local level

Capnocytophaga canimorsus sepsis presenting as an acute abdomen in an asplenic patient.

Item does not contain fulltextAcute abdominal symptoms are frequently caused by surgical intra-abdominal problems. However, the differential diagnosis also includes several internal diseases. Overwhelming infections may present with acute abdominal signs, particularly in the immunocompromised host. Asplenic patients are highly susceptible to infections with encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. Severe infections due to Capnocytophaga canimorsus (DF2), are also common in this group. C. canimorsus is a Gram-negative rod, present as a commensal organism in cat and dog saliva. We describe the atypical presentation of a fatal C. canimorsus-sepsis in a 46-year-old man, who underwent traumatic splenectomy two decades earlier

Les micro-institutions pour limiter les risques contractuels dans les contrats administrés : le cas des boues de station d'épuration

Notre article fait le point sur des développements récents de la littérature qui mettent l'accent sur l'articulation entre les deux volets du programme de recherche de la nouvelle économie institutionnelle : le volet institutionnel (North) et le volet organisationnel (Williamson). Nous reprenons à notre compte une intuition théorique développée par Ménard (2003) et arguant du rôle clé de la notion de « micro-institution » dans l'encadrement des transactions de services collectifs en général et de services environnementaux (eau, déchets) en particulier. L'idée défendue dans notre article est que les micro-institutions contribueraient à réduire les coûts (supportés à la fois par les agents régulés et le régulateur) des contrats administrés de services collectifs environnementaux. Nous proposons une application aux contrats de recyclage des déchets organiques (boues d'épuration) signés entre les communes françaises et les agriculteurs. L'originalité de notre travail repose également sur le protocole empirique mis en oeuvre et les indicateurs de coûts utilisés

Production de services environnementaux et économie néo-institutionnelle : un nouveau programme de recherche pour une équipe d`économistes

The article is about coordination problems when producing environmental services. Our paper is based on the example of sewage sludge management, from urban waste water treatment. The supply of this environmental service reveals a coordination problem that involves a transfer of property rights on sludge (when manuring on agricultural spaces). We propose an analytical framework using new institutional economics. The conclusion of the paper concerns empirical perspectives and methods (case studies, the collecting of data and econometric tests about determinants of the production of environmental services).L'article traite de problèmes de coordination lors de la production de services environnementaux. Notre papier est basé sur l'exemple de la gestion des boues d`épuration issues du traitement des eaux usées municipales. La fourniture de ce service environnemental révèle un problème de coordination qui implique un transfert de droits de propriété sur les boues (lors de l`épandage sur des espaces agricoles). Nous proposons un cadre d`analyse utilisant la nouvelle économie institutionnelle. La conclusion du papier concerne les perspectives empiriques et les méthodes (des études de cas, la collecte de données et des tests économétriques des déterminants de la production de services environnementaux)

Impact of water on the dielectric properties of papers in the radiofrequency domain

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