Éditeur(s) : HAL CCSD
Résumé : International audience
STUDY QUESTION: Do freezing and in vitro culture procedures enhance the expression of proteins involved in apoptotic or autophagic pathways in murine pre-pubertal testicular tissue? SUMMARY ANSWER: IVM strongly modified apoptosis- and autophagy-related relative protein levels in mice testicular tissue whereas the impact of cryopreservation procedures was minimal at the end of the culture. WHAT IS KNOWN ALREADY: In vitro spermatogenesis remains a challenging technical issue as it imposes to find a very close balance between survival and death of germ cell natural precursors (i.e. gonocytes and spermatogonia), which will eventually undergo a complete spermatogenesis close to in vivo conditions. The establishment of efficient culture conditions coupled with suitable cryopreservation procedures (e.g. controlled slow freezing [CSF] and solid surface vitrification [SSV]) of pre-pubertal testicular tissue is a crucial step in the fields of fertility preservation and restoration to improve the spermatic yield obtained in vitro. STUDY DESIGN, SIZE, DURATION: Here, we study cryopreservation procedures (i.e. CSF or SSV) and the impact of culture media compositions. A first set of 66 mouse pre-pubertal testes were directly cultured during 30, 36, 38 and 60 days (D) from 2.5 to 6.5-day-old CD-1 mice to evaluate the impact of time-aspect of culture and to endorse the reverse phase protein microarrays (RPPM) technique as an adapted experimental tool for the field of in vitro spermatogenesis. Ninety others fresh, slow-frozen and vitrified pre-pubertal testes were cultured during 30 days for the principal study to evaluate the impact of cryopreservation procedures before and after culture. Thirty-four testes dissected from 2.5, 6.5, 36.5, 40.5, 42.5 and 62.5 days postpartum (dpp) mice, corresponding to the time frames of spermatogenesis orchestrated in vitro, were used as in vivo controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: After in vitro culture, testicular tissue samples originated from 2.5 or 6.5-day-old CD-1 male mice were analyzed using RPPM. This targeted proteomic technique allowed us to assess the expression level of 29 apoptosis- and autophagy-related factors by normalizing blank-corrected signal values. In addition, morphological analyses (e.g. HES, PAS, TRA98 and CREM) and DNA fragmentation in intra-tubular cells (i.e. terminal deoxynucleotidyl transferase dUTP nick end labeling; TUNEL) were assessed for the distinct experimental conditions tested as well as for in vivo control mouse testes. MAIN RESULTS AND THE ROLE OF CHANCE: A validation of the RPPM procedure in the field of in vitro spermatogenesis was completed with assay and array robustness before a principal study concerning the evaluation of the impact of in vitro culture and cryopreservation procedures. The proportion of elongated spermatids and the total cell number per seminiferous tubule tended to be very different between the in vivo and in vitro conditions (P < 0.05), suggesting the presence of a beneficial regulation on the first spermatogenesis wave by intrinsic apoptosis (Caspase₉) and autophagy (Atg5) factors (P < 0.0003 and r2 = 0.74). Concerning the impact of culture media compositions, a basic medium (BM) composed of αMEM plus 10% KnockOut™ serum replacement and gentamicin supplemented with retinol (Rol) and vitamin E (Vit. E) was selected as the best culture medium for fresh 6.5 dpp tissue cultured during 30D with 27.7 ± 8.10% of seminiferous tubules containing elongated spermatids. Concerning the impact of cryopreservation procedures, SSV did not have any impact on the morphological parameters evaluated after culture in comparison to fresh tissue (FT) controls. The proportion of tubules with elongated spermatids on testicular explants cultured with BMRol+Vit. E was not different between SSV (6.6 ± 1.6%) and CSF (5.3 ± 1.9%); however, round spermatids were observed more frequently for SSV (19 ± 6.2%) than CSF (3.3 ± 1.9%, P = 0.0317). Even if the proportion of TUNEL-positive cells for BMRol+Vit. E was higher at D30 after SSV (4.12 ± 0.26%) than CSF (1.86 ± 0.12%, P = 0.0022) and FT (2.69 ± 0.33%, P = 0.0108), the DNA damages observed at the end of the culture (i.e. D30) were similar to respective 6.5 dpp controls. In addition, the relative protein level expression ratio of an apoptotic factor, the phosphorylated FADD on Fas, was reduced by 64-fold in vitrified testes cultured with BMRol+Vit. E. Furthermore, we found in this study that the StemPro®-34 SFM culture medium supplemented with growth factors (e.g. EGF, bFGF, GDNF and LIF) prevented the differentiation of spermatogonial stem cells in favor of a significant proliferation with a better architectural pattern than in vivo 6.5 dpp controls with an increase of seminiferous tubules area for FT (P = 0.0357) and CSF (P = 0.0317). LIMITATIONS REASONS FOR CAUTION: Despite our promising results, the evaluation of apoptotic- and autophagic-related proteins was studied for a limited amount of proteins and on global testicular tissue. WIDER IMPLICATIONS OF THE FINDINGS: The data presented herein will help to improve apoptotic and autophagic understanding during the first spermatogenic wave. Moreover, our findings illustrate for the first time that, using finely-tuned experimental conditions, a testicular in vitro culture combined with proteomic technologies may significantly facilitate the study of cryopreservation procedures and in vitro culture evaluations. This study may also contribute to improve work on testicular tissues from pre-pubertal and adolescent cancer survivors. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a Ph.D. grant from the Rouen Normandie Université and a financial support from 'la Ligue nationale contre le cancer' (both awarded to L.D.), funding from Institute for Research and Innovation in Biomedicine (IRIB), Agence de la Biomédecine, and co-supported by European Union and Région Normandie. Europe gets involved in Normandie with European Regional Development Fund (ERDF). The authors declare that there is no conflict of interest.
Molecular Human Reproduction

hal-01647081
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647081
DOI : 10.1093/molehr/gax054
PUBMED : 29040674

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Understanding the factors underlying the spatio-temporal distribution of infectious diseases provides useful information regarding their prevention and control. Dengue fever spatio-temporal patterns result from complex interactions between the virus, the host, and the vector. These interactions can be influenced by environmental conditions. Our objectives were to analyse dengue fever spatial distribution over New Caledonia during epidemic years, to identify some of the main underlying factors, and to predict the spatial evolution of dengue fever under changing climatic conditions, at the 2100 horizon. We used principal component analysis and support vector machines to analyse and model the influence of climate and socio-economic variables on the mean spatial distribution of 24,272 dengue cases reported from 1995 to 2012 in thirty-three communes of New Caledonia. We then modelled and estimated the future evolution of dengue incidence rates using a regional downscaling of future climate projections. The spatial distribution of dengue fever cases is highly heterogeneous. The variables most associated with this observed heterogeneity are the mean temperature, the mean number of people per premise, and the mean percentage of unemployed people, a variable highly correlated with people's way of life. Rainfall does not seem to play an important role in the spatial distribution of dengue cases during epidemics. By the end of the 21st century, if temperature increases by approximately 3°C, mean incidence rates during epidemics could double. In New Caledonia, a subtropical insular environment, both temperature and socio-economic conditions are influencing the spatial spread of dengue fever. Extension of this study to other countries worldwide should improve the knowledge about climate influence on dengue burden and about the complex interplay between different factors. This study presents a methodology that can be used as a step by step guide to model dengue spatial heterogeneity in other countries.
ISSN: 1935-2727

Droits : http://creativecommons.org/licenses/by/
pasteur-01247037
https://hal-riip.archives-ouvertes.fr/pasteur-01247037
https://hal-riip.archives-ouvertes.fr/pasteur-01247037/document
https://hal-riip.archives-ouvertes.fr/pasteur-01247037/file/journal.pntd.0004211.pdf
DOI : 10.1371/journal.pntd.0004211

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Heterogeneous patterns of malaria transmission are thought to be driven by factors including host genetics, distance to mosquito breeding sites, housing construction, and socio-behavioural characteristics. Evaluation of local transmission epidemiology to characterize malaria risk is essential for planning malaria control and elimination programmes. The use of geographical information systems (GIS) techniques has been a major asset to this approach. To assess time and space distribution of malaria disease in Bandiagara, Mali, within a transmission season, data were used from an ongoing malaria incidence study that enrolled 300 participants aged under six years old ". Methods: Children's households were georeferenced using a handheld global position system. Clinical malaria was defined as a positive blood slide for Plasmodium falciparum asexual stages associated with at least one of the following signs: headache, body aches, fever, chills and weakness. Daily rainfall was measured at the local weather station. Landscape features of Bandiagara were obtained from satellite images and field survey. QGIS™ software was used to map malaria cases, affected and non-affected children, and the number of malaria episodes per child in each block of Bandiagara. Clusters of high or low risk were identified under SaTScan W software according to a Bernoulli model. Results: From June 2009 to May 2010, 296 clinical malaria cases were recorded. Though clearly temporally related to the rains, Plasmodium falciparum occurrence persisted late in the dry season. Two " hot spots " of malaria transmission also found, notably along the Yamé River, characterized by higher than expected numbers of malaria cases, and high numbers of clinical episodes per child. Conversely, the northeastern sector of the town had fewer cases despite its proximity to a large body of standing water which was mosquito habitat. Conclusion: These results confirm the existence of a marked spatial heterogeneity of malaria transmission in Bandiagara, providing support for implementation of targeted interventions. Background Malaria is one of the leading causes of morbidity and mortality in the world, with an estimated 3.3 billion people at risk of malaria [1]. The incidence of malaria worldwide is estimated to be 216 million cases per year, with 81% of these cases occurring in sub-Saharan Africa. Malaria kills approximately 655,000 people per year; 91% of deaths occur in sub-Saharan Africa [1], mostly in children under five years of age. In Mali, West Africa, malaria represents 36.5% of consultation motives in health center, it is a leading cause of morbidity and mortality children of less than five years of age and the first reason of anaemia in pregnant women [2]. Malaria transmission is seasonal. Malaria parasite transmission and clinical disease are characterized by important microgeographic variation, often between adjacent villages, households or families [3-8]. This local heterogeneity is driven by a variety of factors including human genetics [9,10], distance to potential breeding sites [11,12], housing construction
ISSN: 1475-2875

hal-01307672
https://hal-amu.archives-ouvertes.fr/hal-01307672
https://hal-amu.archives-ouvertes.fr/hal-01307672/document
https://hal-amu.archives-ouvertes.fr/hal-01307672/file/1475-2875-12-82.pdf
DOI : 10.1186/1476-072X-2-5

Éditeur(s) : HAL CCSD
Résumé : Pregnancy is a sensitive and critical period for the development of the child and the health of adults-to-be. The biological and physiological adaptation of the body dealing physical and psychosocial stressors during this period may exert its effects in adulthood (and possibly over several generations). This delayed toxicity presupposes intrinsically the need to study the effects of exposure to environmental risk factors during fetal life using a holistic approach involving risk factors at both the micro (individual characteristics) and the macro level (physical and psycho-social context). Given the heterogeneity of the Breton territory in which this work was conducted, we explored whether the impact of social inequalities and the physical environment (air pollution) on birth outcomes (fetal growth and the risk of prematurity) could be modified according to an urban or rural place of residence. This work was based on data collected as part of the Breton mother-child cohort PELAGIE, which had included 3421 pregnant women between 2002- 2006. The anthropometric parameters and gestational age at birth were measured by medical personnel at delivery. We defined urban and rural areas according to the definition of “urban units” from the National Census Bureau (INSEE). The annual concentrations of air pollution (nitrogen dioxide (NO2)) were estimated using a land-use regression modeled at a 100 m scale and developed as part of an European project. Finally, neighbourhood deprivation was estimated using a composite index developed at census blocks level and whose use was legitimated over both urban and rural areas. Neighbourhood deprivation was associated with an increased risk of infants with fetal growth restriction, only for women living in rural areas. We also observed an increased risk of preterm birth associated with NO2 concentrations > 16.4 μg.m-3, only among women residing in urban areas. The associations between air pollution and fetal growth, although sex-specific, did not seem on the other hand, to vary significantly according to the urban-rural spectrum. This work confirms the need to explore the influence of both social and environmental inequalities on intrauterine development, and to assess the role of place-based factors, such as the urban-rural context, in shaping these inequalities.
La grossesse est une période sensible et déterminante pour le développement de l’enfant et l’état de santé à l’âge adulte. L'adaptation biologique et physiologique de l'organisme face à des « stresseurs » physiques et psychosociaux au cours de cette période peut ainsi exercer ses effets à l'âge adulte (et possiblement sur plusieurs générations). Cette toxicité différée suppose intrinsèquement la nécessité d’étudier les conséquences des expositions environnementales au cours de la vie foetale et ce suivant une approche holistique intégrant autant les facteurs de risque à des niveaux micro (caractéristiques individuelles) et macro (expositions physiques externes et contexte psycho-social). Etant donné l’hétérogénéité du territoire breton dans lequel s’inscrit ce travail de thèse, nous avons cherché à explorer l’impact des inégalités sociales et de l’environnement physique (pollution atmosphérique) sur l’issue de la grossesse (croissance foetale et risque de prématurité) indépendamment chez des femmes enceintes résidant dans des zones urbaines et rurales. Ce travail s’est appuyé sur les données issues de la cohorte bretonne mère-enfant PELAGIE, qui a inclus 3421 femmes enceintes entre 2002- 2006. Les paramètres anthropométriques et l’âge gestationnel à la naissance ont été renseignés à l’accouchement par le personnel médical. Le contexte urbain et rural breton a été caractérisé à partir de la définition des unités urbaines de l’INSEE. Les concentrations annuelles de pollution atmosphérique (dioxyde d’azote (NO2)) ont été modélisées à une échelle de 100 m à partir d’un modèle de "land-use regression" développé à l’échelle européenne. Enfin, le niveau socio-économique des IRIS a été estimé à l’aide d’un indice de désavantage social - construit à partir des données du recensement de l’INSEE et dont la validité et l’adaptabilité à des territoires à la fois urbains et ruraux a été examinée au préalable. Nos résultats suggèrent une influence délétère d’un contexte de vie socioéconomique défavorable sur la croissance intra-utérine, spécifiquement chez les femmes résidant en milieu rural. Nous avons également observé une augmentation du risque de prématurité associée à des niveaux > 16.4 μg.m-3 de NO2 dans l’air, à l’inverse, uniquement chez les femmes résidant dans des zones urbaines. Les associations entre l’exposition à la pollution atmosphérique et les marqueurs de la croissance intra-utérine, bien que sexe-spécifiques, ne semblent en revanche pas varier sensiblement suivant le gradient urbain-rural. Ce travail confirme la nécessité d’évaluer l’influence des inégalités sociales et environnementales sur le développement intra-utérin et de considérer l’importance et le rôle du contexte de vie, notamment urbain-rural, dans la formation de ces inégalités.
https://tel.archives-ouvertes.fr/tel-01308518

NNT : 2015REN1B010
tel-01308518
https://tel.archives-ouvertes.fr/tel-01308518
https://tel.archives-ouvertes.fr/tel-01308518/document
https://tel.archives-ouvertes.fr/tel-01308518/file/BERTIN_M--lanie.pdf

Éditeur(s) : HAL CCSD Society for the Study of Reproduction
Résumé : International audience
Spermmotility notably depends on the structural integrity of the flagellum and the regulation ofmicrotubule dynamics. Although researchers have started to use " omics" techniques to characterize the human sperm's molecular landscape, the constituents responsible for the assembly, organization, and dynamics of the flagellum microtubule have yet to be fully defined. In this study, we defined a core set of 116 gene products associated with the human sperm microtubulome (including products potentially involved in abnormal ciliary phenotypes and male infertility disorders). To this end, we designed and applied an integrated genomics workflow and combined relevant proteomics, transcriptomics, and interactomics datasets to reconstruct a dynamic interactome map. By further integrating phenotypic information, we defined a disease-interaction network; this enabled us to highlight a number of novel factors potentially associated with altered sperm motility and male fertility. Lastly, we experimentally validated the expression pattern of two candidate genes (CUL3 and DCDC2C) that had never previously been associated with male germline differentiation. Our analysis suggested that CUL3 and DCDC2C's products have important roles in the sperm flagellum. Taken as a whole, our results demonstrate that an integrated genomics strategy can highlight relevant molecular factors in specific sperm components. This approach could be easily extended by including other " omics" data (from asthenozoospermic men, for example) and identifying other critical proteins from the human sperm microtubulome. Summary Sentence Although researchers have started to use "omics" techniques to characterize the human sperm's molecular landscape, the constituents responsible for the assembly, organization, and dynamics of the flagellum microtubule have yet to be fully defined.
ISSN: 0006-3363

hal-01515563
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01515563
DOI : 10.1095/biolreprod.116.143479
PUBMED : 28395323

Éditeur(s) : HAL CCSD
Résumé : International audience
Background: The aim of this study was to identify the predictive factors of HIV disclosure to the sex partner in HIV pregnant women in Cayenne (French Guiana). Methods: A case control study was conducted including all deliveries in Cayenne from 2003 to 2010. For each case, a standardized questionnaire including epidemiological, clinical, and biological data was administered. Thirty-four women in the first group and 95 in the control group were included in the study. Results: The logistic regression showed that the variables that independently predicted HIV disclosure to the sex partner were the existence of a profession (OR=5.62, IC95% =1.3-24.26, p=0.021), disclosure to the doctor (OR=12.65, IC95% =2.87-55.8, p<0.001), the negative representations of HIV (OR=5.99, IC95% =1.17-30.69, p=0.032). The partner's HIV status was also linked to the outcome (OR=0.01, IC95% =0.001-0.07, p<0.001). Conclusion: These predictive factors should be considered in positive prevention programs and prevention of mother to child transmission.
Epidemiol

inserm-00915113
http://www.hal.inserm.fr/inserm-00915113
http://www.hal.inserm.fr/inserm-00915113/document
http://www.hal.inserm.fr/inserm-00915113/file/2012_Elenga_-_Predictive_Factorssur HIV_Status_Disclosure_to_Sex_Partner_in_Pregnant_women_in_cayenne_french_guiana.pdf
DOI : 10.4172/2161-1165.1000116

Éditeur(s) : HAL CCSD
Résumé : Semi-volatile organic compounds (SVOCs) are widely present in indoor environments and are suspected to be repro- or neurotoxic but little is known on the health impact on SVOC mixtures. The objective of this work is to derive cumulative toxicity indicators for SVOCs detected in French dwellings in carrying forward a cumulative health risk assessment. SVOCs were grouped according to their repro- and neurotoxic common modes of action (i.e. decrease in serum testosterone concentrations, decrease in neuronal viability). Benchmark doses (BMDs) were then estimated by modeling dose-response relationships from scientific literature (Hill models, PROAST, RIVM). Comparable BMDs were estimated only for 6 of the 19 reprotoxic SVOCs which are responsible to 10 or 50% decrease in testosterone in adult male rats orally exposed. Estimated relative potency factors (RPFs) from BMDs are similar according to the response level (from 1600 for the B(a)P to 0.1 for the BBP), excepted for bisphenol A moving from 7E+6 to 180. For in vitro neuronal death, BMDs were estimated for 13 neurotoxic SVOCs using data from different cell lines and species. BMDs equivalent to a 10% of response range from 0.07 (PCB-153) to 95 µM (diazinon). The originality of this work is the grouping of compounds from different chemical families which we are really exposed to. BMDs estimation from published data was possible but many methodological limitations lead us to put forward recommendations especially on the standardization of experimental protocols and the availability of results in adapted format for dose-response relationship modeling.
Les composés organiques semi volatils (COSV) sont largement présents dans les environnements intérieurs et sont suspectés d’être repro- ou neurotoxiques, mais peu de données sont disponibles quant à leur toxicité en mélanges. L’objectif de cette thèse est de proposer des indicateurs de toxicité cumulés pour les COSV détectés dans les logements français, dans un cadre d’évaluation des risques sanitaires cumulés. Les COSV ont été regroupés en fonction de leurs modes d’action communs, en lien avec les effets reprotoxiques (diminution de la concentration de testostérone sérique) et neurotoxiques (diminution de la viabilité neuronale). Des benchmark doses (BMD) ont ensuite été estimées par modélisation (modèle de Hill, PROAST, RIVM) des relations dose-réponse de la littérature décrivant la réponse d’intérêt. Des BMD comparables ont pu être estimées seulement pour 6 des 19 COSV reprotoxiques induisant une diminution de testostérone de 10 ou 50 % chez le rat adulte exposé par voie orale. Les facteurs de toxicité relatifs (RPF) estimés à partir des BMD sont sensiblement les mêmes en fonction du niveau de réponse (de 1600 pour le B(a)P à 0,1 pour le BBP), excepté pour le biphénol A qui passe de 7E+6 à 180. Considérant la mort neuronale in vitro, des BMD ont pu être estimées pour 13 COSV neurotoxiques, à partir de données provenant de différentes lignées et espèces. Les BMD équivalent à un niveau de réponse de 10 % s’échelonnent de 0,07 (PCB-153) à 95 µM (diazinon). L’originalité de ce travail repose sur le regroupement de composés de familles chimiques différentes qui constituent des contaminations réelles de notre environnement. Si l’estimation des quelques BMD a été possible à partir des données de la littérature, de nombreuses limites méthodologiques conduisent à émettre des recommandations en particulier sur la standardisation des protocoles expérimentaux et la disponibilité des résultats sous une forme adaptée à la modélisation de la relation dose-réponse.
https://tel.archives-ouvertes.fr/tel-01308535

NNT : 2015REN1B019
tel-01308535
https://tel.archives-ouvertes.fr/tel-01308535
https://tel.archives-ouvertes.fr/tel-01308535/document
https://tel.archives-ouvertes.fr/tel-01308535/file/Kevin_Fournier-.pdf

Éditeur(s) : HAL CCSD
Résumé : International audience
An efficient management of natural hazards cannot be only a hazard assessment and the location of population in danger. It is necessary to take into account an estimation of the human vulnerability, communications, local infrastructure (individual and collective). Research work engaged in Ecuador on the Cotopaxi volcanic region and more recent projects illustrate this taking into account human factors and contribute to a hazard global approach.
La gestión completa de los riesgos naturales debe tener en cuenta la evaluación de probabilidades, la localización de la población, pero también el conjunto de factores humanos de vulnerabilidad. Las investigaciones llevadas a cabo en Ecuador, en la región del volcán Cotopaxi, constituyen un buen ejemplo.
Une gestion efficace des risques naturels ne peut se satisfaire de la seule évaluation des aléas et de la localisation des populations menacées. Elle doit également s'appuyer sur l'appréciation des facteurs humains de vulnérabilité, que ce soit sur le plan individuel ou collectif. Les travaux de recherche engagés en Equateur dans les régions exposées au volcan Cotopaxi el d'autres projets plus récents vont dans cette voie et concourent à une approche globale des risques. Leur caractère opérationnel ne peut que contribuer â la mitigation des effets des catastrophes naturelles.
Pangea

hal-01168555
https://hal.archives-ouvertes.fr/hal-01168555
https://hal.archives-ouvertes.fr/hal-01168555/document
https://hal.archives-ouvertes.fr/hal-01168555/file/D%27Ercole%201993%20Pangea%20Gestion%20risques%20r%C3%A9alit%C3%A9s%20sociales.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Monocytes/macrophages (MΦ), considered as plastic cells, can differentiate into either a pro-inflammatory (M1) subtype, also known as a classically activated subtype, or an anti-inflammatory alternatively activated subtype (M2) according to their microenvironment. Phenotypic markers of mouse polarized MΦ have been extensively studied, whereas their human counterparts remain less characterized. The main goal of this study was therefore to carefully characterize phenotypic and genomic markers of primary human MΦ generated from M-CSF-treated blood monocytes and polarized towards M1 or M2 subtype upon the action of lipopolysaccharide and interferon-γ (for M1) or interleukin (IL)-4 (for M2). Membrane expression of the markers CD80 and CD200R was found to be specific of human M1 and M2 polarized MΦ, respectively, whereas, by contrast, mannose receptor (CD206) expression did not discriminate between M1 and M2. mRNA expression analysis further identified six markers of M1 polarization (IL-12p35, CXCL10, CXCL11, CCL5, CCR7 and IDO1), five markers of M2 polarization (TGF-β, CCL14, CCL22, SR-B1 and PPARγ) and transcription factors involved in MΦ polarization. Ability of human M-CSF-generated MΦ to polarize toward M1 or M2 subtype was also associated with enhanced secretion of TNFα, IL-1β, IL-12p40, CXCL10 and IL-10 (for M1) or CCL22 (for M2). Moreover, the comparison of the expression of M1 markers in M-CSF- and GM-CSF-MΦ polarized towards M1 subtype has revealed similarities. In conclusion, we demonstrated that human M-CSF MΦ can polarize toward a M1 type after IFNγ/LPS stimulation. Moreover, the M1 and M2 markers of human polarized MΦ identified in the present study may be useful to better identify human MΦ subtypes, particularly at the tissue level, in order to better understand their respective roles in the development of pathologies.
ISSN: 0008-8749

inserm-00823273
http://www.hal.inserm.fr/inserm-00823273
DOI : 10.1016/j.cellimm.2013.01.010
PUBMED : 23454681

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
UNLABELLED: ABSTRACT: BACKGROUND: Malaria is a major health issue in French Guiana. Amerindian communities remain the most affected. A previous study in Camopi highlighted the predominant role of environmental factors in the occurrence of malaria. However, all parameters involved in the transmission were not clearly identified. A new survey was conducted in order to clarify the risk factors for the presence of malaria cases in Camopi. METHODS: An open cohort of children under seven years of age was set up on the basis of biologically confirmed malaria cases for the period 2001-2009. Epidemiological and observational environmental data were collected using two structured questionnaires. Data were analysed with a multiple failures multivariate Cox model. The influence of climate and the river level on malaria incidence was evaluated by time-series analysis. Relationships between Anopheles darlingi human biting rates and malaria incidence rates were estimated using Spearman's rank correlation. RESULTS: The global annual incidence over the nine-year period was 238 per 1,000 for Plasmodium falciparum, 514 per 1,000 for Plasmodium visa and 21 per 1,000 for mixed infections. The multivariate survival analysis associated higher malaria incidence with living on the Camopi riverside vs. the Oyapock riverside, far from the centre of the Camopi hamlet, in a home with numerous occupants and going to sleep late. On the contrary, living in a house cleared of all vegetation within 50 m and at high distance of the forest were associated with a lower risk. Meteorological and hydrological characteristics appeared to be correlated with malaria incidence with different lags. Anopheles darlingi human biting rate was also positively correlated to incident malaria in children one month later. CONCLUSIONS: Malaria incidence in children remains high in young children despite the appearance of immunity in children around three years of age. The closeness environment but also the meteorological parameters play an important role in malaria transmission among children under seven years of age in Camopi.
ISSN: 1475-2875

inserm-00633771
http://www.hal.inserm.fr/inserm-00633771
http://www.hal.inserm.fr/inserm-00633771/document
http://www.hal.inserm.fr/inserm-00633771/file/1475-2875-10-246.pdf
DOI : 10.1186/1475-2875-10-246

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Plasmodium vivax malaria is an important public health issue in the Amazon region, and it accounts for approximately 84 % of cases of the disease. Migration across the border between Brazil and French Guiana contributes to the maintenance of the disease. The aim of this study was to evaluate the therapeutic and parasitological responses of patients with P. vivax malaria treated with chloroquine and primaquine in the socio-environmental context of cross-border interactions between Brazil and French Guiana. The factors controlled were diagnostic agreement, adherence, adjustment of primaquine doses for patient weight, and quality of the drugs used. A prospective study was conducted in 2011 with 103 individuals aged 10-60 years with a positive diagnosis of P. vivax treated with chloroquine (10 mg base/kg on the first day, followed by 7.5 mg/kg on the second and third days) and primaquine for 7 days, who were followed for 28 days. The primaquine doses were adjusted for the patients' weight. A number of factors were determined: epidemiological characteristics, origin of patients, signs and symptoms, initial parasitaemia and parasitaemia clearance time, blood concentrations of chloroquine and primaquine, quality of anti-malarial drugs and diagnostic agreement. Ninety-five patients were followed for 28 days. There was a 100 % agreement in microscopic diagnosis between field laboratory and reference centre. The adhesion to the treatment was 100 %. Of these patients, 32.6 % received a weight-adjusted dose of primaquine. The chloroquine and primaquine tablets were consistent with the optimal quality limits for human consumption. The investigated patients achieved optimal blood exposure to anti-malarial drugs. The parasitological and therapeutic response was adequate in 99.0 % of cases. In the municipality of Oiapoque, the therapeutic regime used for the treatment of P. vivax malaria using chloroquine combined with primaquine remains effective, when external factors are controlled, such as the quality of anti-malarial drugs, the adhesion to the treatment prescribed, the correct diagnostic and the adjustment of primaquine dose for patient body weight.
ISSN: 1475-2875

Droits : http://creativecommons.org/licenses/by/
pasteur-01229355
https://hal-pasteur.archives-ouvertes.fr/pasteur-01229355
https://hal-pasteur.archives-ouvertes.fr/pasteur-01229355/document
https://hal-pasteur.archives-ouvertes.fr/pasteur-01229355/file/s12936-015-0925-7.pdf
PUBMEDCENTRAL : PMC4600333

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The hypothalamic-pituitary-adrenal (HPA) axis response to chronic stress is far from straight forward, particularly with regards to animal welfare. There are reports of no effect as well as both decreases and increases in cortisol after chronic stressors. Therefore, the first aim of the present study was to determine how measures of compromised welfare, such as chronic pain and haematological anomalies, related to cortisol levels in domestic horses (Equus caballus). Domestic horses are an informative model to investigate the impact of chronic stress (due to environment, pain, work, housing conditions…) on the HPA axis. The second aim was to determine whether levels of fecal cortisol metabolites (FCM) may be used as an indicator of welfare measures. The present study used fifty-nine horses (44 geldings and 15 mares), from three riding centres in Brittany, France. The primary findings show that horses whose welfare was clearly compromised (as indicated by an unusual ears backward position, presence of vertebral problems or haematological anomalies, e.g. anaemia) also had lower levels of both FCM and plasma cortisol. This work extends our previous findings showing that withdrawn postures, indicators of depressive-like behavior in horses, are associated with lower plasma cortisol levels. We also found that evening plasma cortisol levels positively correlated with FCM levels in horses. Future research aims to determine the extent to which factors of influence on welfare, such as living conditions (e.g. single stalls versus group housing in pasture or paddocks), early life factors, and human interaction, act as mediators of cortisol levels in horses.
ISSN: 1932-6203

hal-01588159
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01588159
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01588159/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01588159/file/Pawluski_et_al_-_PLOSONE-2017.pdf
DOI : 10.1371/journal.pone.0182257

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Purpose The objective of this article was to estimate the social cost of respiratory cancer cases attributable to occupational risk factors in France in 2010. Methods According to the attributable fraction method and based on available epidemiological data from the lit- erature, we estimated the number of respiratory cancer cases due to each identified risk factor. We used the cost- of-illness method with a prevalence-based approach. We took into account the direct and indirect costs. We estimated the cost of production losses due to morbidity (absenteeism and presenteeism) and mortality costs (years of production losses) in the market and nonmarket spheres. Results The social cost of lung, larynx, sinonasal and mesothelioma cancer caused by exposure to asbestos, chromium, diesel engine exhaust, paint, crystalline silica, wood and leather dust in France in 2010 were estimated at between 917 and 2,181 million euros. Between 795 and 2,011 million euros (87-92 %) of total costs were due to lung cancer alone. Asbestos was by far the risk factor representing the greatest cost to French society in 2010 at between 531 and 1,538 million euros (58-71 %), ahead of diesel engine exhaust, representing an estimated social cost of between 233 and 336 million euros, and crystalline silica (119-229 million euros). Indirect costs represented about 66 % of total costs. Conclusion Our assessment shows the magnitude of the economic impact of occupational respiratory cancers. It allows comparisons between countries and provides valu- able information for policy-makers responsible for defining public health priorities.
ISSN: 1618-7598

halshs-00922838
https://halshs.archives-ouvertes.fr/halshs-00922838
DOI : 10.1007/s10198-013-0528-6
PUBMED : 23974964

Éditeur(s) : HAL CCSD American Society of Tropical Medicine and Hygiene
Résumé : International audience
In disease-endemic areas, histoplasmosis is the main differential diagnosis for tuberculosis among human immunodeficiency virus (HIV)-infected patients. However, no study has compared the two diseases. Thus, the objective of this study was to compare tuberculosis and histoplasmosis in HIV-infected patients. A population of 205 HIV-infected patients (99 with tuberculosis and 106 with histoplasmosis) hospitalized in Cayenne, French Guiana during January 1, 1997-December 31, 2008 were selected retrospectively from the French Hospital Database on HIV. Multivariate analysis showed that tuberculosis was associated with cough (adjusted odds ratio [AOR] = 0.20, 95% confidence interval [CI] = 0.05-0.73) and a C-reactive protein level > 70 mg/L (AOR = 0.98, 95% CI = 0.97-0.99). Variables associated with disseminated histoplasmosis were a γ-glutamyl transferase level > 72 IU/L (AOR = 4.99, 95% CI = 1.31-18.99), origin from French Guiana (AOR = 5.20, 95% CI = 1.30-20.73), disseminated localization (AOR = 6.40, 95% CI = 1.44-28.45), a concomitant opportunistic infection (AOR = 6.71, 95% CI = 1.50-29.96), a neutrophil count < 2,750 cells/mm(3) (AOR = 10.54, 95% CI = 2.83-39.24), a CD4 cell count < 60 cells/mm(3) (AOR = 11.62, 95% CI = 2.30-58.63), and a platelet count < 150,000/mm(3) (AOR = 19.20, 95% CI = 3.35-110.14). Tuberculosis and histoplasmosis have similarities, but some factors show a greater association with one of these diseases. Thus, adapted therapeutic choices can be made by using simple clinical and paraclinical criteria.
ISSN: 0002-9637

inserm-01065027
http://www.hal.inserm.fr/inserm-01065027
http://www.hal.inserm.fr/inserm-01065027/document
http://www.hal.inserm.fr/inserm-01065027/file/2014_Adenis_-_Tuberculosis_and_Histoplasmosis_among_HIV.pdf
DOI : 10.4269/ajtmh.13-0084

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The non-classical human leukocyte antigen-G, HLA-G, plays an important role in inducing tolerance, through its immunosuppressive effects on all types of immune cells. Immune tolerance is a key issue in the liver, both in liver homeostasis and in the response to liver injury or cancer. It would therefore appear likely that HLA-G plays an important role in liver diseases. Indeed, this molecule was recently shown to be produced by mast cells in the livers of patients infected with hepatitis C virus (HCV). Furthermore, the number of HLA-G-positive mast cells was significantly associated with fibrosis progression. The generation of immune tolerance is a role common to both HLA-G, as a molecule, and the liver, as an organ. This review provides a summary of the evidence implicating HLA-G in liver diseases. In the normal liver, HLA-G transcripts can be detected, but there is no HLA-G protein. However, HLA-G protein is detectable in the liver tissues and/or plasma of patients suffering from hepatocellular carcinoma, hepatitis B or C, or visceral leishmaniasis and in liver transplant recipients. The cells responsible for producing HLA-G differ between diseases. HLA-G expression is probably induced by microenvironmental factors, such as cytokines. The expression of HLA-G receptors, such as ILT2, ILT4, and KIRD2L4, on liver cells has yet to be investigated, but these receptors have been detected on all types of immune cells, and such cells are present in liver. The tolerogenic properties of HLA-G explain its deleterious effects in cancers and its beneficial effects in transplantation. Given the key role of HLA-G in immune tolerance, new therapeutic agents targeting HLA-G could be tested for the treatment of these diseases in the future.
ISSN: 0168-8278

hal-01134468
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134468
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134468/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134468/file/Biology%20of%20the%20immunomodulatory%20molecule%20HLA-G.pdf
DOI : 10.1016/j.jhep.2015.03.007

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
BACKGROUND: Chronic HCV infection is associated with the development of hepatic fibrosis. The direct role of HCV in the fibrogenic process is unknown. Specifically, whether HCV is able to infect hepatic stellate cells (HSCs) is debated. OBJECTIVE: To assess whether human HSCs are susceptible to HCV infection. DESIGN: We combined a set of original HCV models, including the infectious genotype 2a JFH1 model (HCVcc), retroviral pseudoparticles expressing the folded HCV genotype 1b envelope glycoproteins (HCVpp) and a subgenomic genotype 1b HCV replicon, and two relevant cellular models, primary human HSCs from different patients and the LX-2 cell line, to assess whether HCV can infect/replicate in HSCs. RESULTS: In contrast with the hepatocyte cell line Huh-7, neither infectious HCVcc nor HCVpp infected primary human HSCs or LX-2 cells. The cellular expression of host cellular factors required for HCV entry was high in Huh-7 cells but low in HSCs and LX-2 cells, with the exception of CD81. Finally, replication of a genotype 2a full-length RNA genome and a genotype 1b subgenomic replicon was impaired in primary human HSCs and LX-2 cells, which expressed low levels of cellular factors known to play a key role in the HCV life-cycle, suggesting that human HSCs are not permissive for HCV replication. CONCLUSIONS: Human HSCs are refractory to HCV infection. Both HCV entry and replication are deficient in these cells, regardless of the HCV genotype and origin of the cells. Thus, HCV infection of HSCs does not play a role in liver fibrosis. These results do not rule out a direct role of HCV infection of hepatocytes in the fibrogenic process.
ISSN: 0017-5749

hal-01063909
https://hal.archives-ouvertes.fr/hal-01063909
DOI : 10.1136/gutjnl-2013-305634
PUBMED : 25063678

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Children are exposed to toxic metals and metalloids via their diet and environment. Our objective was to assess the aggregate chronic exposure of children aged 3–6 years, living in France, to As, Cd, Cr, Cu, Mn, Pb, Sb, Sr, and V present in diet, tap water, air, soil and floor dust in the years 2007–2009. Dietary data came from the French Total Diet Study, while concentrations in residential tap water, soil and indoor floor dust came from the ‘Plomb-Habitat’ nationwide representative survey on children's lead exposure at home. Indoor air concentrations were assumed to be equal to outdoor air concentrations, which were retrieved from regulatory measurements networks. Human exposure factors were retrieved from literature. Data were combined with Monte Carlo simulations. Median exposures were 1.7, 0.3, 10.2, 34.1, 60.3, 0.7, 0.1, 44.3, 1.5 and 95th percentiles were 4.4, 0.5, 15.8, 61.3, 98.3, 2.5, 0.1, 111.1, 2.9 μg/kg bw/d for As, Cd, Cr, Cu, Mn, Pb, Sb, Sr, and V respectively. Dietary exposures dominate aggregate exposures, with the notable exception of Pb - for which soils and indoor floor dust ingestion contribute most at the 95th percentile. The strengths of this study are that it aggregates exposures that are often estimated separately, and uses a large amount of representative data. This assessment is limited to main diet and residential exposure, and does not take into account the relative bioavailability of compounds. These results could be used to help target prevention strategies.
ISSN: 0160-4120

inserm-01404061
http://www.hal.inserm.fr/inserm-01404061
http://www.hal.inserm.fr/inserm-01404061/document
http://www.hal.inserm.fr/inserm-01404061/file/rev1%20-%20MS%20Expo%20metals.pdf
DOI : 10.1016/j.envint.2016.10.009

Éditeur(s) : HAL CCSD Society for Personality Research
Résumé : International audience
The purpose of this study was to examine self-efficacy and self-esteem as predictors of claimed and behavioral self-handicapping, and to compare the relationship between behavioral and claimed self-handicaps and athletic performance. A total of 31 basketball players participated in the study. Claimed self-handicaps were significantly negatively correlated with self-esteem whereas behavioral self-handicapping was significantly negatively correlated with self-efficacy. Performance was negatively correlated with behavioral self-handicapping, but was not correlated with claimed self-handicapping. These findings reinforce the conceptual distinction between claimed and behavioral self-handicaps by demonstrating that the two strategies are indeed related to different factors and that they have different consequences for performance.
ISSN: 0301-2212

Droits : info:eu-repo/semantics/OpenAccess
hal-01343254
https://hal.univ-antilles.fr/hal-01343254
https://hal.univ-antilles.fr/hal-01343254/document
https://hal.univ-antilles.fr/hal-01343254/file/Social%20Behavior%20and%20Personality.%20HAL.pdf
DOI : 10.2224/sbp.2008.36.3.391

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Humans are exposed to a large number of contaminants, many of which may have similar health effects. This paper presents a framework for identifying pollutants to be included in a cumulative risk assessment approach. To account for the possibility of simultaneous exposure to chemicals with common toxic modes of action, the first step of the traditional risk assessment process, i.e. hazard identification, is structured in three sub-steps: (1a) Identification of pollutants people are exposed to, (1b) identification of effects and mechanisms of action of these pollutants, (1c) grouping of pollutants according to similarity of their mechanism of action and health effects. Based on this exposure-based grouping we can derive "multi-pollutant" toxicity reference values, in the "dose-response assessment" step. The approach proposed in this work is original in that it is based on real exposures instead of a limited number of pollutants from a unique chemical family, as traditionally performed. This framework is illustrated by the case study of semi-volatile organic compounds in French dwellings, providing insights into practical considerations regarding the accuracy of the available toxicological information. This case study illustrates the value of the exposure-based approach as opposed to the traditional cumulative framework, in which chemicals with similar health effects were not always included in the same chemical class.
ISSN: 0013-9351

hal-00982315
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00982315
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00982315/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00982315/file/An_exposure-based_framework_for_grouping_pollutants_accepted.pdf
DOI : 10.1016/j.envres.2014.01.007

Éditeur(s) : Pergamon-elsevier Science Ltd
Résumé : Consumption of marine organisms represents one of the main exposure sources of contaminants for human populations. To obtain a global view of the contamination in commercial fish in the NW Mediterranean Sea, we analysed four types of priority contaminants (PCBs, PBDEs, Hg and Cs-137) in the European hake, Merluccius merluccius, from the Gulf of Lions in relation with organism's trophic level (delta N-15). All contaminants presented a significant increase in concentration in hake muscle with trophic level. However, obvious differences between contaminants were evidenced. Biomagnification factors (BMF and FWMF) along the hake food web were higher for Hg and CB-153 than for BDE-47 and Cs-137, and increase in contaminant concentration with trophic level occurred at different rates depending on contaminants. Such differences of biomagnification patterns can be related to physico-chemical properties of the different contaminants. (C) 2012 Elsevier Ltd. All rights reserved.
Marine Pollution Bulletin (0025-326X) (Pergamon-elsevier Science Ltd), 2012-05 , Vol. 64 , N. 5 , P. 974-983

Droits : 2012 Elsevier Ltd. All rights reserved.
http://archimer.ifremer.fr/doc/00085/19583/17484.pdf
DOI:10.1016/j.marpolbul.2012.02.014
http://archimer.ifremer.fr/doc/00085/19583/