Red Cross/Red Crescent Mine Action Involvement in the Middle East

The Middle East is an area significantly impacted by landmines, and there is a great need for the spread of mine awareness in mine-affected countries. The Red Cross and Red Crescent are hard at work in the region, attempting to raise mine awareness among the citizens of these nations

The International Committee of the Red Cross Mine/UXO Awareness Programs

Many current mine awareness strategies continue to use a “presentation approach,” in which the community remains passive and simply receives information. For organizations using such an approach, mine awareness amounts to a simple public information campaign isolated from other kinds of mine action and humanitarian activities. With the aim of addressing the threat of mines and UXO more effectively, the ICRC has adopted another approach. First, the ICRC gathers relevant information on local needs, which can be used to devise an appropriate mine/UXO awareness strategy. Next, the ICRC involves mine-contaminated communities in the mine awareness process. The ICRC also cooperates closely with other organizations in responding to community needs

Geographic Distribution and Mortality Risk Factors during the Cholera Outbreak in a Rural Region of Haiti, 2010-2011

In 2010 and 2011, Haiti was heavily affected by a large cholera outbreak that spread throughout the country. Although national health structure-based cholera surveillance was rapidly initiated, a substantial number of community cases might have been missed, particularly in remote areas. We conducted a community-based survey in a large rural, mountainous area across four districts of the Nord department including areas with good versus poor accessibility by road, and rapid versus delayed response to the outbreak to document the true cholera burden and assess geographic distribution and risk factors for cholera mortality

Model-Based Therapeutic Drug Monitoring of Infliximab Using a Single Serum Trough Concentration

International audienc

Infliximab Efficacy May Be Linked to Full TNF-α Blockade in Peripheral Compartment—A Double Central-Peripheral Target-Mediated Drug Disposition (TMDD) Model

Infliximab is an anti-TNF-α monoclonal antibody approved in chronic inflammatory bowel diseases (IBD). This study aimed at providing an in-depth description of infliximab target-mediated pharmacokinetics in 133 IBD patients treated with 5 mg/kg infliximab at weeks 0, 2, 14, and 22. A two-compartment model with double target-mediated drug disposition (TMDD) in both central and peripheral compartments was developed, using a rich database of 26 ankylosing spondylitis patients as a reference for linear elimination kinetics. Population approach and quasi-steady-state (QSS) approximation were used. Concentration-time data were satisfactorily described using the double-TMDD model. Target-mediated parameters of central and peripheral compartments were respectively baseline TNF concentrations (RC0 = 3.3 nM and RP0 = 0.46 nM), steady-stated dissociation rates (KCSS = 15.4 nM and KPSS = 0.49 nM), and first-order elimination rates of complexes (kCint = 0.17 day−1 and kPint = 0.0079 day−1). This model showed slower turnover of targets and infliximab-TNF complex elimination rate in peripheral compartment than in central compartment. This study allowed a better understanding of the multi-scale target-mediated pharmacokinetics of infliximab. This model could be useful to improve model-based therapeutic drug monitoring of infliximab in IBD patients

Use and storage of pesticides at home in France (the Pesti'home survey 2014)

Les données sont disponibles sur data.gouv.fr (cf. la section "voir aussi")International audienceSome epidemiological studies have raised health concerns following the chronic exposure of pregnant women and children to pesticides in the domestic environment. In France very little is known about potential exposure to pesticides at home. An observational study called Pesti'home was carried out in continental France between July and November 2014. The residential use of pesticides was investigated and an inventory of pesticides and active ingredients used and stored at home was drawn up. Plant protection products, biocides, and human and animal external pest control products were listed during face-to-face interviews.A random sample of households including at least one adult (18–79 years old) was selected following a two-stage stratified random sampling method using the national census database. Within each household, an adult was appointed to answer survey questions. Data related to the interviewee's sociodemographic and housing characteristics, the reported use of pesticides at home, and a visual inventory of all stored pesticides were collected. Overall, 1507 households participated. The participation rate was between 36% and 57% according to the definition chosen.Over the previous 12 months, 75% of households declared that they had used at least one pesticide. Households who used and stored at least one product most frequently used an insecticide (84%). The active ingredients most frequently used by these households as insecticides were pyrethroids, namely tetramethrin and permethrin.The Pesti'home survey collected detailed data on the residential use of pesticides for risk assessment at national and European levels

Étude Pesti’home - Enquête nationale sur les utilisations domestiques de pesticides - Départements et régions d’outre-mer (DROM) Guadeloupe - Martinique - La Réunion: Rapport d’étude scientifique

En mars 2008, dans le cadre de son premier plan d’action (2006-2008), l’Observatoire des résidus de pesticides (ORP) a confié à un groupe d’experts pluridisciplinaire la réalisation d’un état des lieux des connaissances disponibles quant à l’exposition, l’imprégnation et les déterminants de l’exposition de la population générale aux pesticides. Ces travaux ont abouti, en octobre 2010, à la publication du rapport « Exposition de la population générale aux résidus de pesticides en France » (Anses, 2010). Dans le cadre de ces travaux, le terme « pesticides » englobe à la fois les substances et les produits phytopharmaceutiques (protection des plantes), certaines substances et produits biocides (élimination des nuisibles à domicile ou sur le lieu de travail), ainsi que certains antiparasitaires à usage humain et vétérinaire. Dans un premier temps, un inventaire des données existantes permettant de caractériser les utilisations de pesticides et d’identifier les substances actives présentes dans les différents milieux a été réalisé. L'exposition chronique de la population générale aux pesticides se caractérise par des expositions à faibles doses, répétées dans le temps. Selon l'Organisation mondiale de la santé (OMS), l'alimentation est la principale source d'exposition aux pesticides. Toutefois, la population générale est également exposée à d'autres sources d'exposition qui ne doivent pas être négligées. Ainsi, la contamination de l'air extérieur et intérieur, des sols ou des poussières intérieures, l'utilisation de pesticides dans les jardins, dans les habitations ou sur les animaux domestiques constituent également des sources potentielles d'exposition. Diverses équipes, de disciplines différentes, s’intéressent à ces différentes sources d'exposition et leur part dans l'exposition globale reste encore à déterminer. Toutefois, les données produites sont très hétérogènes (contextes d’étude et objectifs très divers, populations et/ou zones géographiques d’étude particulières) et ne sont pas suffisantes pour caractériser complètement les expositions de la population générale aux pesticides.À l’issue de ses travaux en 2010, le groupe d’experts pluridisciplinaire d’étude a recommandé notamment la réalisation d’une enquête nationale sur les utilisations domestiques de pesticides (biocides, produits de jardinage, traitement des plantes d’intérieur et antiparasitaires à usage humain et vétérinaire). Cette recommandation émane du constat d’un manque de données représentatives pour l’ensemble de la population française sur les produits utilisés, sur la fréquence et les modalités d’utilisation de ces produits avec pour conséquence une difficulté à évaluer l’exposition de la population générale aux pesticides à usages domestiques.Par ailleurs, l’expertise collective Inserm « Pesticides, effets sur la santé » (Inserm, 2013) a conclu à une présomption de lien entre l’exposition domestique de la femme enceinte à des pesticides organophosphorés et le neurodéveloppement de l’enfant. Au vu de ces résultats, le collectif d’experts réuni par l’Inserm a recommandé également de documenter les niveaux et les sources d’exposition de la population générale aux pesticides dans les différents environnements de vie, notamment par le biais d’enquêtes sur les pratiques d’utilisation de ces produits et/ou la réalisation de mesures. Une méta-analyse publiée en 2018 a depuis montré une association positive entre l’exposition aux pesticides domestiques et le cancer de l’enfant (Van Maele-Fabry, 2018).Dans ce contexte, des débats ont lieu sur la mise en place de dispositifs encadrant les ventes de pesticides, en particulier de biocides afin d’améliorer l’information des consommateurs, que ce soit via l’étiquetage, l’information en magasin voire le passage obligatoire par le conseil d’un vendeur (« mise sous clefs »).Pour répondre à ces questions et recommandations et dans le cadre de sa mission d’amélioration des connaissances sur l’exposition globale de la population aux pesticides (Action 6 du Plan national santé-environnement 2 - PNSE 2), l’ORP a proposé la mise en œuvre d’une enquête nationale représentative visant à décrire les utilisations domestiques de pesticides en population générale. Le projet d’étude a été présenté le 26 juin 2012 au Comité de suivi de l’ORP composé des tutelles (ministères chargés de la santé, de l’agriculture, de la consommation, de l’écologie et du travail) dont il a reçu l’avis favorable.L’enquête Pesti’home a été conduite sur la période de juillet 2014 à mars 2015 en France métropolitaine, en Guadeloupe, en Martinique et à La Réunion.Le présent rapport fait état des résultats de l’enquête réalisée dans les DROM de février à juillet 2015

In-cell intrabody selection from a diverse human library identifies C12orf4 protein as a new player in rodent mast cell degranulation.

The high specificity of antibodies for their antigen allows a fine discrimination of target conformations and post-translational modifications, making antibodies the first choice tool to interrogate the proteome. We describe here an approach based on a large-scale intracellular expression and selection of antibody fragments in eukaryotic cells, so-called intrabodies, and the subsequent identification of their natural target within living cell. Starting from a phenotypic trait, this integrated system allows the identification of new therapeutic targets together with their companion inhibitory intrabody. We applied this system in a model of allergy and inflammation. We first cloned a large and highly diverse intrabody library both in a plasmid and a retroviral eukaryotic expression vector. After transfection in the RBL-2H3 rat basophilic leukemia cell line, we performed seven rounds of selection to isolate cells displaying a defect in FcεRI-induced degranulation. We used high throughput sequencing to identify intrabody sequences enriched during the course of selection. Only one intrabody was common to both plasmid and retroviral selections, and was used to capture and identify its target from cell extracts. Mass spectrometry analysis identified protein RGD1311164 (C12orf4), with no previously described function. Our data demonstrate that RGD1311164 is a cytoplasmic protein implicated in the early signaling events following FcεRI-induced cell activation. This work illustrates the strength of the intrabody-based in-cell selection, which allowed the identification of a new player in mast cell activation together with its specific inhibitor intrabody

The Impairment of MAGMAS Function in Human Is Responsible for a Severe Skeletal Dysplasia

International audienceImpairment of the tightly regulated ossification process leads to a wide range of skeletal dysplasias and deciphering their molecular bases has contributed to the understanding of this complex process. Here, we report a homozygous mutation in the mitochondria-associated granulocyte macrophage colony stimulating factor-signaling gene (MAGMAS) in a novel and severe spondylodysplastic dysplasia. MAGMAS, also referred to as PAM16 (presequence translocase-associated motor 16), is a mitochondria-associated protein involved in preprotein translocation into the matrix. We show that MAGMAS is specifically expressed in trabecular bone and cartilage at early developmental stages and that the mutation leads to an instability of the protein. We further demonstrate that the mutation described here confers to yeast strains a temperature-sensitive phenotype, impairs the import of mitochondrial matrix pre-proteins and induces cell death. The finding of deleterious MAGMAS mutations in an early lethal skeletal dysplasia supports a key role for this mitochondrial protein in the ossification process