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 BioMed Central
Résumé : International audience
BACKGROUND: Environmental exposures, including dietary contaminants, may influence the developing immune system. This study assesses the association between maternal pre-parturition consumption of seafood and wheeze, eczema, and food allergy in preschool children. Fish and shellfish were studied separately as they differ according to their levels of omega-3 polyunsaturated fatty acids (which have anti-allergic properties) and their levels of contaminants. METHODS: The PELAGIE cohort included 3421 women recruited at the beginning of pregnancy. Maternal fish and shellfish intake was measured at inclusion by a food frequency questionnaire. Wheeze, eczema, and food allergy were evaluated by a questionnaire completed by the mother when the child was 2 years old (n = 1500). Examination of the associations between seafood intake and outcomes took major confounders into account. Complementary sensitivity analyses with multiple imputation enabled us to handle missing data, due mostly to attrition. RESULTS: Moderate maternal pre-parturition fish intake (1 to 4 times a month) was, at borderline significance, associated with a lower risk of wheeze (adjusted OR = 0.69 (0.45-1.05)) before age 2, compared with low intake (< once/month). This result was not, however, consistent: after multiple imputation, the adjusted OR was 0.86 (0.63-1.17). Shellfish intake at least once a month was associated with a higher risk of food allergy before age 2 (adjusted OR = 1.62 (1.11-2.37)) compared to low or no intake (< once/month). Multiple imputation confirmed this association (adjusted OR = 1.52 (1.05-2.21)). CONCLUSIONS: This study suggests that maternal pre-parturition shellfish consumption may increase the risk of food allergy. Further large-scale epidemiologic studies are needed to corroborate these results, identify the contaminants or components of shellfish responsible for the effects observed, determine the persistence of the associations seen at age 2, and investigate potential associations with health effects observable at later ages, such as allergic asthma.
ISSN: 1476-069X

Droits : info:eu-repo/semantics/OpenAccess
inserm-00926282
http://www.hal.inserm.fr/inserm-00926282
http://www.hal.inserm.fr/inserm-00926282/document
http://www.hal.inserm.fr/inserm-00926282/file/1476-069X-12-102.pdf
DOI : 10.1186/1476-069X-12-102

Éditeur(s) : Université des Antilles Études caribéennes
Résumé : L’objectif de cette étude est d’analyser les impacts et les limites d’une expérience de lutte contre la pauvreté par le tourisme au travers d’une étude de cas dans le village d’Anse-la-Raye, à Sainte-Lucie.Depuis son indépendance en 1979, Sainte-Lucie a tenté de diversifier la structure économique héritée de son passé colonial, en développant notamment des sources alternatives de recettes. Au début, il y a eu un certain succès avec l'industrie de confection et le tourisme qui ont émergé comme des activités viables en dehors de l'agriculture d'exportation.À la fin des années 1980, le pays avait même atteint un taux de croissance qui aurait été considéré comme raisonnable. Sainte-Lucie a d’ailleurs été l’île ayant connu la plus grande croissance économique des Etats du CARICOM. L’exportation de la banane a contribué pour beaucoup à ces résultats, et les nouveaux secteurs ont permis la création d’emplois ainsi que des revenus et des recettes d'exportation supplémentaires.Mais comme tous les Petits Etats Insulaires en Développement (PEID), Sainte-Lucie est caractérisée par sa vulnérabilité économique face aux catastrophes naturelles et crises extérieures. Ainsi, deux des secteurs principaux de son économie se sont affaiblis ces dernières années (l’agriculture et l’industrie), avec pour résultat principal une aggravation de la pauvreté à Sainte-Lucie malgré les bons résultats du secteur touristique devenu le pilier principal de l’économie de l’île.Dans ce contexte de faible croissance économique, le gouvernement et les partenaires sociaux se sont rassemblés pour identifier les politiques susceptibles d’accélérer la croissance économique de Sainte-Lucie. Ainsi, trois axes principaux ont été retenus : l’augmentation de la production locale, la réduction du crime et la réduction de la pauvreté. Dans ce dernier cadre, le gouvernement a lancé plusieurs stratégies de lutte contre la pauvreté notamment l’aide au développement d’activités touristiques.L’étude s’intéresse plus particulièrement au village d’Anse-la-Raye et à une expérience de tourisme pro-pauvre qui y a été développé en 2000 : l’Anse-la-Raye Seafood Friday, une sorte de festival qui permet aux visiteurs de déguster les produits de la mer tous les vendredis. Ce festival a-t-il eu réellement des répercussions sur la population pauvre de la communauté d’Anse-la-Raye ? Est-il viable? Quel est son devenir?
The objective of this study is to analyse the impacts and limitations of attempts to combat poverty using tourism through a case study in the village of Anse-la-Raye, in St. Lucia.Since its independence in 1979, St. Lucia has attempted to diversify the economic structure it inherited from its colonial past, in particular developing alternative sources of revenue. Initially there was some success with the clothing industry and tourism, which emerged as viable business activities outside of agricultural exports.At the end of the 1980s, the country had reached a growth which was considered reasonable. Of all the states of CARICOM, St. Lucia has moreover experienced the greatest economic growth. Banana exports have contributed significantly to these results, and new sectors have led to the creation of jobs and income to supplement export income.But like all Small Island Developing States (SIDS), St. Lucia is characterized by vulnerability to natural disasters and external economic shocks. Two major sectors of the economy have weakened in recent years (agriculture and industry), resulting in an increase in poverty in St. Lucia despite favourable outcomes in the tourism sector, which became the primary pillar of the island.In the context of low economic growth the government and social partners gathered together to identify policies and accelerate economic growth in St. Lucia. Three main themes were identified: Increasing local production; reducing crime and reducing poverty. In this context, the government launched several strategies to combat poverty including assistance for the development of tourism.The study focuses on the village of Anse-la-Raye and the experiences of pro-poor tourism that was developed in 2000: Anse-la-Raye Seafood Friday, a kind of festival that allows visitors to taste the seafood on Fridays. Has this festival really had an impact on the poor of the community of Anse-la-Raye? Is it viable? And what is its future?
Sainte-Lucie

Droits : info:eu-repo/semantics/openAccess
urn:doi:10.4000/etudescaribeennes.6525
http://journals.openedition.org/etudescaribeennes/6525

Résumé : This synthesis, outcome from the reconstitution of chronological series of catches, replaces this economical activity in its human and climatic context, including society facts, wars and ships evolution
Cette synthèse, le résultat d'une reconstitution de séries chronologiques de pêches, remet cette activité économique dans son contexte humain et climatique, y compris l'évolution des faits de société, des guerres et des bateaux.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/1995/rapport-1446.pdf
http://archimer.ifremer.fr/doc/00000/1446/

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : International audience
The HIWATE (Health Impacts of long-term exposure to disinfection byproducts in drinking WATEr) project was a systematic analysis that combined the epidemiology on adverse pregnancy outcomes and other health effects with long-term exposure to low levels of drinking water disinfection byproducts (DBPs) in the European Union. The present study focused on the relationship of the occurrence and concentration of DBPs with in vitro mammalian cell toxicity. Eleven drinking water samples were collected from five European countries. Each sampling location corresponded with an epidemiological study for the HIWATE program. Over 90 DBPs were identified; the range in the number of DBPs and their levels reflected the diverse collection sites, different disinfection processes, and the different characteristics of the source waters. For each sampling site, chronic mammalian cell cytotoxicity correlated highly with the numbers of DBPs identified and the levels of DBP chemical classes. Although there was a clear difference in the genotoxic responses among the drinking waters, these data did not correlate as well with the chemical analyses. Thus, the agents responsible for the genomic DNA damage observed in the HIWATE samples may be due to unresolved associations of combinations of identified DBPs, unknown emerging DBPs that were not identified, or other toxic water contaminants. This study represents the first to integrate quantitative in vitro toxicological data with analytical chemistry and human epidemiologic outcomes for drinking water DBPs.
ISSN: 0013-936X

hal-00875923
https://hal.archives-ouvertes.fr/hal-00875923
DOI : 10.1021/es3024226
PUBMED : 22958121

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
To analyze the characteristics and outcome of infective endocarditis (IE) according to the time interval between IE first symptoms and diagnosis.
Among the IE cases of a French population-based epidemiological survey, patients having early-diagnosed IE (diagnosis of IE within 1 month of first symptoms) were compared with those having late-diagnosed IE (diagnosis of IE more than 1 month after first symptoms).
Among the 486 definite-IE, 124 (25%) had late-diagnosed IE whereas others had early-diagnosed IE. Early-diagnosed IE were independently associated with female gender (OR = 1.8; 95% CI [1.0-3.0]), prosthetic valve (OR= 2.6; 95% CI [1.4-5.0]) and staphylococci as causative pathogen (OR = 3.7; 95% CI [2.2-6.2]). Cardiac surgery theoretical indication rates were not different between early and late-diagnosed IE (56.3% vs 58.9%), whereas valve surgery performance was lower in early-diagnosed IE (41% vs 53%; p = .03). In-hospital mortality rates were higher in early-diagnosed IE than in late-diagnosed IE (25.1% vs 16.1%; p < .001).
The time interval between IE first symptoms and diagnosis is closely related to the IE clinical presentation, patient characteristics and causative microorganism. Better prognosis reported in late-diagnosed IE may be related to a higher rate of valvular surgery. KEY MESSAGES Infective endocarditis, which time interval between first symptoms and diagnosis was less than one month, were mainly due to Staphylococcus aureus in France. Staphylococcus aureus infective endocarditis were associated with septic shock, transient ischemic attack or stroke and higher mortality rates than infective endocarditis due to other bacteria or infective endocarditis, which time interval between first symptoms and diagnosis was more than one month. Infective endocarditis, which time interval between first symptoms and diagnosis was more than one month, were accounting for one quarter of all infective endocarditis in our study and were associated with vertebral osteomyelitis and a higher rate of cardiac surgery performed for hemodynamic indication than other infective endocarditis.
ISSN: 0785-3890

hal-01509563
https://hal.archives-ouvertes.fr/hal-01509563
PUBMED : 27607562

Éditeur(s) : HAL CCSD
Résumé : International audience
We assessed whether maternal employment during pregnancy - overall and in selected occupational sectors - is associated with birth weight, small for gestational age (SGA), term low birth weight (LBW), length of gestation, and preterm delivery in a population-based birth cohort design. We used data from >200 000 mother-child pairs enrolled in 13 European birth cohorts and compared employed versus non-employed women. Among employees, we defined groups of occupations representing the main sectors of employment for women where potential reproductive hazards are considered to be present. The comparison group comprised all other employed women not included in the occupational sector being assessed. We performed meta-analyses of cohort-specific estimates and explored heterogeneity. Employees had a lower risk of preterm delivery than non-employees [adjusted odds ratio (OR adj) 0.86, 95% confidence interval (95% CI) 0.81-0.91]. Working in most of the occupational sectors studied was not associated with adverse birth outcomes. Being employed as a nurse was associated with lower risk SGA infants (OR adj0.91, 95% CI 0.84-0.99) whereas food industry workers had an increased risk of preterm delivery (OR adj1.50, 95% CI 1.12-2.02). There was little evidence for heterogeneity between cohorts. This study suggests that, overall, employment during pregnancy is associated with a reduction in the risk of preterm birth and that work in certain occupations may affect pregnancy outcomes. This exploratory study provides an important platform on which to base further prospective studies focused on the potential consequences of maternal occupational exposures during pregnancy on child development.
Scandinavian journal of work, environment & health

Droits : info:eu-repo/semantics/OpenAccess
hal-01151621
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01151621
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01151621/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01151621/file/Maternal%20occupation%20during%20pregnancy_supplementary%20material.pdf
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01151621/file/Maternal%20occupation%20during%20pregnancy_accepted.pdf

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: The aryl hydrocarbon receptor (AhR) has gradually emerged as a regulator of inflammation in the lung and other tissues. AhR may interact with the p65-subunit of the nuclear factor (NF)-κB transcription factors, but reported outcomes of AhR/NF-κB-interactions are conflicting. Some studies suggest that AhR possess pro-inflammatory activities while others suggest that AhR may be anti-inflammatory. The present study explored the impact of AhR and its binding partner AhR nuclear translocator (Arnt) on p65-activation and two differentially regulated chemokines, CXCL8 (IL-8) and CCL5 (RANTES), in human bronchial epithelial cells (BEAS-2B). RESULTS: Cells were exposed to CXCL8- and CCL5-inducing chemicals, 1-nitropyrene (1-NP) and 1-aminopyrene (1-AP) respectively, or the synthetic double-stranded RNA analogue, polyinosinic-polycytidylic acid (Poly I:C) which induced both chemokines. Only CXCL8, and not CCL5, appeared to be p65-dependent. Yet, constitutively active unligated AhR suppressed both CXCL8 and CCL5, as shown by siRNA knock-down and the AhR antagonist α-naphthoflavone. Moreover, AhR suppressed activation of p65 by TNF-α and Poly I:C as assessed by luciferase-assay and p65-phosphorylation at serine 536, without affecting basal p65-activity. In contrast, Arnt suppressed only CXCL8, but did not prevent the p65-activation directly. However, Arnt suppressed expression of the NF-κB-subunit RelB which is under transcriptional regulation by p65. Furthermore, AhR-ligands alone at high concentrations induced a moderate CXCL8-response, without affecting CCL5, but suppressed both CXCL8 and CCL5-responses by Poly I:C. CONCLUSION: AhR and Arnt may differentially and independently regulate chemokine-responses induced by both inhaled pollutants and pulmonary infections. Constitutively active, unligated AhR suppressed the activation of p65, while Arnt may possibly interfere with the action of activated p65. Moreover, ligand-activated AhR suppressed CXCL8 and CCL5 responses by other agents, but AhR ligands alone induced CXCL8 responses when given at sufficiently high concentrations, thus underscoring the duality of AhR in regulation of inflammation. We propose that AhR-signaling may be a weak activator of p65-signaling that suppresses p65-activity induced by strong activators of NF-κB, but that its anti-inflammatory properties also are due to interference with additional pathways.
Cell communication and signaling: CCS

hal-01063555
https://hal.archives-ouvertes.fr/hal-01063555
DOI : 10.1186/s12964-014-0048-8

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Background: Influenza is an important cause of serious illness and death, particularly in elderly and high-risk groups. Objectives Aim of this study was to identify factors associated with poor outcomes among adults hospitalized in France for laboratory-confirmed seasonal influenza. Study design Patients hospitalized for influenza were identified in a prospective, multicenter study carried out in French hospitals during three consecutive influenza seasons (2012–2015). Influenza virus infection was confirmed by reverse transcription polymerase chain reaction. Sociodemographic and clinical variables were compared according to the virus type and subtype. Risk factors for complications, intensive care unit (ICU) admission and death were analyzed by backward stepwise logistic regression. Results The study population consisted of 566 patients, of whom 56% were older than 65 years and 82% had underlying chronic illnesses. Type A influenza viruses infected 422 patients (75%), including subtype H3N2 in 239 patients (57%). The prior vaccine coverage rate was 38%. Complications occurred in 255 patients (45%), consisting mainly of pneumonia (n = 143, 30%) and respiratory failure (n = 116, 20%). Eighty-three patients (15%) were admitted to an ICU, and the in-hospital mortality rate was 4% (n = 21). Sixty-six patients (12%) received oseltamivir. Age over 65 years was the only identified risk factor for complications. Risk factors for ICU admission were an absence of vaccination, no oseltamivir administration before admission, pre-existing chronic respiratory disease, and current smoking. Age over 65 years and ICU admission were risk factors for death. Conclusions Older individuals and patients with underlying conditions are most at risk of influenza complications. Vaccination and early oseltamivir administration, both of which are recommended for these patients, appear to reduce ICU admissions
ISSN: 1386-6532

hal-01302409
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01302409
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01302409/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01302409/file/Factors%20associated%20with%20poor%20outcomes.pdf
DOI : 10.1016/j.jcv.2016.04.005

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
ABSTRACT: In the past decade, there has been an increasing number of studies on co-infections between worms and malaria. However, this increased interest has yielded results that have been at times conflicting and made it difficult to clearly grasp the outcome of this interaction. Despite the heterogeneity of study designs, reviewing the growing body of research may be synthesized into some broad trends: Ascaris emerges mostly as protective for malaria and its severe manifestations, whereas hookworm seems to increase malaria incidence. As efforts are made to de-worm populations in malaria endemic areas, there is still no clear picture of the impact these programmes have in terms of quantitative and qualitative changes in malaria.
ISSN: 1475-2875

inserm-00632065
http://www.hal.inserm.fr/inserm-00632065
http://www.hal.inserm.fr/inserm-00632065/document
http://www.hal.inserm.fr/inserm-00632065/file/1475-2875-10-259.pdf
DOI : 10.1186/1475-2875-10-259

Éditeur(s) : Université de la Rochelle
Résumé : In order to better understand the functioning of the Brouage intertidal mudflat (Marennes- Oléron Basin, France), its carbon-based trophic web has been modelled and analyzed. The foodweb building is based on the 4 step method of Inverse Analysis: 1) conceive an a priori model as the graph of compartments (nodes) between which exist fluxes of material (vertices). These vertices are the unknowns for the problem; 2) gather all the existing knowledge about the ecosystem and translate it into linear equations and inequalities involving the fluxes; 3) complete this set of data by common knowledge on the behaviour of the compartments and translate it into inequalities, 4) solve the obtained linear system under the parsimony principle to find a unique solution vector. The food-web analysis is based on. The first purpose of this work was a methodological one: inverse analysis method has been adapted to consider the seasonal and spatial variability of the temperate ecosystem: two seasons have been coupled in the computation and the area has been divided into three geographical zones along a cross-shore gradient. Hence, two types of physical exchanges are involved: the benthicpelagic ones and the advection ones. Statistical results can also be obtained by coupling Monte Carlo methods to Inverse Analysis. To study the obtained networks, new indices based on Markov Chains take delay into account in describing integrative transfers of material between compartments. This lets emerge the systems' properties that are not obvious at first sight and emphasizes the role of peculiar components. The second purpose was to apply such methods to the Brouage mudflat ecosystem in order to better understand its functioning. As the knowledge and methods evolve, various food webs were computed and analyzed with the help such indices and existing ones. Sensitivity analyses allow to point at the most crucial lacks of knowledge, which can orientate future field research. New data would improve the quality of the model in two ways: one the one hand, they would validate or invalidate the outcomes and on the other hand, they would give useful information to better constrain some of the black boxes and most uncertain fluxes, especially the advection and vertical flows. The main results of the study show a strongly seasonal system in which benthic and pelagic components are linked with intensity. The system is driven by its high local benthic primary production, but also depends on imports from the basin. Each of the 3 geographic zones has a peculiar functioning. The central zone corresponds to the classical description of European intertidal mudflats: very productive, it can feed the other regions. It is a production zone. The upper part is less productive but is fed by the middle one via the water column and can be exploited by shorebirds. It is a degradation zone (material is transformed for less qualitative). The lower part strongly depends on the basin imports for its functioning, as the cultivated bivalves act as a pump for pelagic material of which a great part is deposited under the cultivation structures (oyster racks or mussels "bouchots"). It is a transformation zone.
Un double objectif (méthodologique et appliqué) a été visé par une modélisation du réseau trophique de la vasière de Brouage (Bassin de Marennes Oléron, France) à l'aide de l'analyse inverse, et son étude à l'aide de l'analyse des réseaux. L'Analyse Inverse permet en effet de reconstruire l'ensemble du réseau à partir de données éparses, le problème du manque de données étant récurrent en Ecologie. Au plan méthodologique, l'analyse inverse a été adaptée à la prise en compte des caractères saisonnier et spatialement hétérogène d'un écosystème tempéré de zone intertidale : deux saisons ont ainsi été couplées et la vasière a été considérée le long d'un transect perpendiculaire au rivage et divisé en trois zones spatiales. Deux types de flux physiques interviennent donc : les flux verticaux de dépôt et remise en suspension, et les flux d'advection via la colonne d'eau. Des pistes d'amélioration et de nouvelles méthodes sont proposées. Un résultat sous forme statistique peut être obtenu en couplant l'utilisation de méthodes de Monte Carlo à l'analyse inverse pour la construction des réseaux trophiques. Les moyens d'étude des modèles ont été enrichis par la mise au point d'indices issus de la construction de chaînes de Markov et prenant en compte le caractère temporel des transferts de matière entre compartiments. Enfin, la transformation mathématique du modèle statique pour une étude dynamique de la stabilité de l'équilibre décrit est abordée. Plusieurs modèles ont été construits au cours de l'évolution des méthodes et de l'acquisition de connaissances sur le site. Des méthodes d'analyses existantes et d'autres mises au point dans le cadre de cet ouvrage ont été appliquées aux réseaux obtenus afin de faire émerger les propriétés du fonctionnement de la vasière et de souligner le rôle de certains compartiments. Des analyses de sensibilité permettent d'évaluer la robustesse des résultats et d'orienter les recherches futures en mettant en évidence les manques les plus cruciaux. Des données supplémentaires, notamment concernant les foraminifères benthiques, le zooplancton ou les mouvements verticaux du microphytobenthos permettront de fournir de meilleures contraintes et de valider (ou non) les résultats obtenus. Les principaux résultats montrent un système au fort caractère saisonnier dont les compartiments benthiques et pélagiques sont très liés. La production primaire benthique locale est un moteur important, mais qui ne suffirait pas à suppléer l'indispensable importation de matériel détritique. Le découpage de la vasière en trois zones fait apparaître les particularités de chacune. La zone centrale correspond à la description classique des « vasières intertidales européennes » : très productive, elle peut alimenter les autres régions. C'est une zone de production et d'exportation. La partie supérieure est moins productive et reçoit de la matière de la zone de milieu d'estran via la colonne d'eau. Sa production secondaire peut alors être exploitée par les limicoles, nombreux en hiver. C'est une zone de dégradation et d'exportation. Le bas d'estran dépend fortement des importations extérieures, « pompées » par les bivalves cultivés qui sont ainsi directement responsables d'une forte sédimentation sous les structures mytilicoles et ostréicoles. C'est une zone de transformation.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/2005/these-2260.pdf
http://archimer.ifremer.fr/doc/00000/2260/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Recent research has linked early life exposure to selective serotonin reuptake inhibitor medications (SSRIs) to modifications of social behaviors in children. Serotonin is a key regulator of neurodevelopment, social behaviors and mental health, and with the growing use of SSRIs to treat maternal affective disorders during the perinatal period, questions have been raised about the benefits and risks of perinatal SSRI exposure on the developing child. This review will highlight how perinatal SSRIs affect maternal care and neurodevelopmental outcomes related to social affiliative behaviors in offspring; such as play behaviors, social interactions, reproductive behaviors, and maternal care of the next generation. We will also review how early life exposure to SSRIs can alter related neurobiology, and the epigenome. Both clinical research and findings from animal models will be discussed. Understanding the impact of perinatal SSRIs on neurobehavioral outcomes will improve the health and well-being of subsequent generations.
ISSN: 0149-7634

hal-01619303
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01619303
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01619303/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01619303/file/Perinatal%20selective%20serotonin%20reuptake%20inhibitor%20medication_revised.pdf
DOI : 10.1016/j.neubiorev.2017.04.023

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Low-level exposure to polychlorinated biphenyl-153 (PCB-153) and dichlorodiphenyldichloroethylene (p-p'-DDE) can impair fetal growth; however, the exposure-response relationship and effect modifiers of such association are not well established. This study is an extension of an earlier European meta-analysis. Our aim was to explore exposure-response relationship between PCB-153 and p-p'-DDE and birth outcomes; to evaluate whether any no exposure-effect level and susceptible subgroups exist; and to assess the role of maternal gestational weight gain (GWG). We used a pooled dataset of 9377 mother-child pairs enrolled in 14 study populations from 11 European birth cohorts. General additive models were used to evaluate the shape of the relationships between organochlorine compounds and birth outcomes. We observed an inverse linear exposure-response relationship between prenatal exposure to PCB-153 and birth weight [decline of 194g (95% CI -314, -74) per 1μg/L increase in PCB-153]. We showed effects on birth weight over the entire exposure range, including at low levels. This reduction seems to be stronger among children of mothers who were non-Caucasian or had smoked during pregnancy. The most susceptible subgroup was girls whose mothers smoked during pregnancy. After adjusting for absolute GWG or estimated fat mass, a reduction in birth weight was still observed. This study suggests that the association between low-level exposure to PCB-153 and birth weight exists and follows an inverse linear exposure-response relationship with effects even at low levels, and that maternal smoking and ethnicity modify this association.
ISSN: 0160-4120

hal-01118572
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118572
PUBMED : 25314142
DOI : 10.1016/j.envint.2014.09.013

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
Under physiological conditions, the liver sinusoidal endothelial cells (LSECs) mediate hepatic immune tolerance toward self or foreign antigens through constitutive expression of anti-inflammatory mediators. However, upon viral infection or Toll-like receptor 2 (TLR2) activation, LSECs can achieve proinflammatory functions, but their role in hepatic inflammation during acute viral hepatitis is unknown. Using the highly virulent mouse hepatitis virus type 3 (MHV3) and the attenuated variants 51.6-MHV3 and YAC-MHV3, exhibiting lower tropism for LSECs, we investigated in vivo and in vitro the consequence of LSEC infection on their proinflammatory profiles and the aggravation of acute hepatitis process. In vivo infection with virulent MHV3, in comparison to attenuated strains, resulted in fulminant hepatitis associated with higher hepatic viral load, tissue necrosis, and levels of inflammatory mediators and earlier recruitment of inflammatory cells. Such hepatic inflammatory disorders correlated with disturbed production of interleukin-10 (IL-10) and vascular factors by LSECs. We next showed in vitro that infection of LSECs by the virulent MHV3 strain altered their production of anti-inflammatory cytokines and promoted higher release of proinflammatory and procoagulant factors and earlier cell damage than infection by attenuated strains. This higher replication and proinflammatory activation in LSECs by the virulent MHV3 strain was associated with a specific activation of TLR2 signaling by the virus. We provide evidence that TLR2 activation of LSCEs by MHV3 is an aggravating factor of hepatic inflammation and correlates with the severity of hepatitis. Taken together, these results indicate that preservation of the immunotolerant properties of LSECs during acute viral hepatitis is imperative in order to limit hepatic inflammation and damage. IMPORTANCE Viral hepatitis B and C infections are serious health problems affecting over 350 million and 170 million people worldwide, respectively. It has been suggested that a balance between protection and liver damage mediated by the host's immune response during the acute phase of infection would be determinant in hepatitis outcome. Thus, it appears crucial to identify the factors that predispose in exacerbating liver inflammation to limit hepatocyte injury. Liver sinusoidal endothelial cells (LSECs) can express both anti- and proinflammatory functions, but their role in acute viral hepatitis has never been investigated. Using mouse hepatitis virus (MHV) infections as animal models of viral hepatitis, we report for the first time that in vitro and in vivo infection of LSECs by the pathogenic MHV3 serotype leads to a reversion of their intrinsic anti-inflammatory phenotype toward a proinflammatory profile as well to as disorders in vascular factors, correlating with the severity of hepatitis. These results highlight a new virus-promoted mechanism of exacerbation of liver inflammatory response during acute hepatitis.
ISSN: 0022-538X

hal-01390974
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390974
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390974/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390974/file/Mouse%20Hepatitis%20Virus%20Infection_accepted.pdf
DOI : 10.1128/JVI.01069-16

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
ObjectivesTo compare the efficacy, in current clinical practice, of ă first regimens containing abacavir with lamivudine (ABC/3TC) or ă tenofovir with emtricitabine (TDF/FTC) in patients with baseline viral ă load 100000 HIV-1 RNA copies/mL. ă MethodsUsing a prospective cohort, we selected all patients starting a ă first HIV regimen based either on ABC/3TC or on TDF/FTC. The propensity ă score (PS) method was used to limit the indication bias due to the ă observational nature of the data. Adjusting and weighting methods via PS ă were used to compare the effectiveness of a first regimen containing ă ABC/3TC or TDF/FTC. The primary outcome was treatment failure by month ă 12 (M12). ă ResultsOverall, 2781 patients started an antiretroviral (ARV) regimen ă with ABC/3TC or TDF/FTC each in combination with efavirenz, boosted ă atazanavir or boosted darunavir. Among the 2472 uncensored patients ă before M12, 962 (39%) had a baseline viral load 100000 copies/mL of ă whom 294 were in treatment failure at or before M12. Our analyses showed ă no difference between ABC/3TC and TDF/FTC in the risk of treatment ă failure at M12 in patients starting an ARV regimen with a high viral ă load (100000 copies/mL). ă ConclusionsUsing a large prospectively collected cohort of patients ă seeking care in France, we found no evidence that ABC/3TC based regimens ă led to more failures than TDF/FTC based ones in patients with high ă baseline viral loads.
ISSN: 1464-2662

hal-01482656
https://hal.archives-ouvertes.fr/hal-01482656
DOI : 10.1111/hiv.12306

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Maternal affective disorders are frequently treated with selective serotonin reuptake inhibitor medications (SSRIs); with up to 10% of women being prescribed these medications during pregnancy. Infant development depends on the early serotonergic environment, which is altered by perinatal SSRIs, raising concern about how these medications affect neural outcomes. While clinical and preclinical research suggests an impact of SSRIs on the developing brain, more research is needed to determine the effects on neuroplasticity, the serotonergic system, and the hypothalamic-pituitary-adrenal axis in neural regions mediating behavior. The current work investigated the effects of the SSRI, fluoxetine, on the serotonergic system in the prefrontal cortex (PFC) during pre-adolescence, and changes to synaptic markers and glucocorticoid receptor density in the cingulate cortex (medial PFC) of pre-adolescent and adult Sprague-Dawley male and female rats. To model aspects of Perinatal Depression and maternal anxiety, pre-gestational maternal stress was used resulting in male and female offspring from 4 groups: 1) control, 2) perinatal fluoxetine exposed, 3) pre-gestational maternal stress exposed, and 4) pre-gestational maternal stress + fluoxetine. Perinatal fluoxetine prevented the effects of maternal stress on 5-HT levels and 5-HT turnover ratio in the PFC of pre-adolescent offspring, particularly in females. However, pre-gestational stress reduced synaptophysin and PSD-95 densities in the cingulate cortex, effects that were more pronounced in males. Interestingly, perinatal fluoxetine exposure reduced GR density in adult males in this same brain area. Together, results show differential effects of perinatal SSRIs and pre-gestational maternal stress on neurodevelopment in the PFC of males and females.
ISSN: 0028-3908

hal-01647158
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647158
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647158/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647158/file/Gemmel%20-%20Perinatal%20fluoxetine%20prevents%20the%20effect.pdf
DOI : 10.1016/j.neuropharm.2017.10.009

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Background Experimental evidence suggests that developmental exposure to persistent organic pollutants (POP) and to some non persistent pesticides may disrupt metabolic regulation of glucose metabolism and insulin secretion, and thereby contribute to the current epidemic of obesity and metabolic disorders. Quasi-experimental situations of undernutrition in utero have provided some information. However, the evidence in humans concerning the role of the prenatal environment in these disorders is contradictory, and little is known about long-term outcomes, such as type 2 diabetes, of prenatal exposure. Objectives Our aim was to evaluate the effects of prenatal exposure to POP and organophosphate pesticides on fetal markers of glucose metabolism in a sample of newborns from the Pelagie mother–child cohort in Brittany (France). Methods Dialkylphosphate (DAP) metabolites of organophosphate pesticides were measured in maternal urine collected at the beginning of pregnancy. Cord blood was assayed for polychlorinated biphenyl congener 153 (PCB153), p,p′-dichlorodiphenyl dichloroethene (DDE) and other POP. Insulin and adiponectin were determined in cord blood serum (n=268). Results A decrease in adiponectin and insulin levels was observed with increasing levels of DDE, but only in girls and not boys. Adiponectin levels were not related to the concentrations of other POP or DAP metabolites. Decreasing insulin levels were observed with increasing PCB153 concentrations. Insulin levels increased with DAP urinary levels. Additional adjustment for BMI z-score at birth modified some of these relations. Conclusions Our observations bring support for a potential role of organophosphate pesticides and POP in alterations to glucose metabolism observable at birth
ISSN: 0013-9351

hal-01259218
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259218
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259218/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259218/file/Prenatal%20exposure%20to%20persistent%20organic%20pollutants%20and%20organophosphate%20pesticides%2C%20and%20markers%20of%20glucose%20metabolism%20at%20birth.pdf
DOI : 10.1016/j.envres.2016.01.005

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
STUDY QUESTION: Can protein biomarkers of the male genital tract be identified in human seminal plasma? SUMMARY ANSWER: We identified potential biomarkers for each of the organs participating in the secretions of the human seminal plasma. WHAT IS KNOWN ALREADY: The seminal plasma fulfills critical functions for fertility by providing spermatozoa with a protective milieu, promoting their final maturation and modulating the immune responsiveness of the female reproductive tract. It is also considered to be a promising source of biomarkers of male infertility and/or pathologies of the male genital tract. STUDY DESIGN, SIZE, DURATION: This study combines proteomic analyses of normal seminal plasma together with transcriptomic gene expression profiling of human healthy tissues. MATERIALS, SETTING, METHODS: Non-liquefied seminal plasma proteins from a healthy donor were prefractionated using two sequential Proteominer™ libraries. Eight subproteome fractions were collected, trypsin digested and subjected to three successive mass spectrometry analyses for peptide characterization. The list of identified proteins was compared with and merged with other available data sets of the human seminal plasma proteome. The expression of corresponding genes was then investigated using tissue transcriptome profiles to determine where, along the male reproductive tract, these proteins were produced. Finally, tissue specificity of a selected subset of biomarker candidates was validated on human tissues. MAIN RESULTS AND THE ROLE OF CHANCE: We first performed a proteomic analysis of the human seminal plasma and identified 699 proteins. By comparing our protein list with other previous proteomic data sets, we found that 2545 unique proteins have been described so far in the human seminal plasma. We then profiled their expression at the gene level and identified 83 testis, 42 epididymis, 7 seminal vesicle and 17 prostate candidate protein markers. For a subset of testis-specific candidates, i.e. TKTL1, LDHC and PGK2, we further validated their germ cell expression and demonstrated that such markers could distinguish between semen from fertile and infertile men. LIMITATIONS, REASONS FOR CAUTION: While some of the markers we identified are well-known tissue-specific products, further dedicated studies to validate the biomarker status of new candidates will be required. Additionally, whether or not the abundance of these proteins is indeed decreased in some specific pathological situations remains to be determined. WIDER IMPLICATIONS OF THE FINDINGS: Using an integrative genomics approach, we identified biomarker candidates for each of the organs participating in the seminal plasma production. In this study, we essentially focused on germ cell markers and their potential application for the diagnosis of male infertility. Other types of markers also deserve a focused attention given their potential predictive value for various reproductive disorders, notably for prostate cancers. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Proteomics Core Facility at Biogenouest and was funded by Conseil Régional de Bretagne, IBiSA and Agence de la Biomédecine grants. The authors declare that there exists a competing financial interest in this work that is related to a patent application on the use of identified germ cell-specific proteins in an antibody-based assay (Fertichip™) to predict the successful testicular biopsy outcomes in human non-obstructive azoospermia.
ISSN: 0268-1161

inserm-00814146
http://www.hal.inserm.fr/inserm-00814146
DOI : 10.1093/humrep/des360
PUBMED : 23024119

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Mixtures of polybrominated diphenyl ethers (PBDEs) are present in indoor environments. Studies of the developmental effects of exposure to these chemicals in large prospective mother-child cohorts are required, with data on prenatal exposure and long-term follow-up of the children. We aimed to investigate the relationship between prenatal and childhood exposure to PBDEs and neurodevelopment at the age of six years. We determined the levels of PBDEs and other neurotoxicants in cord blood and dust collected from the homes of children for 246 families included in the PELAGIE mother-child cohort in France. We assessed two cognitive domains of the six-year-old children using the Wechsler Intelligence Scale for Children-IV. Verbal comprehension scores were lower in children from homes with higher concentrations of BDE99 (βDetects < median_vs_NonDetects = −1.6; 95% CI: −6.1, 2.9; βDetects≥median_vs_NonDetects = −5.4; −9.9, −1.0; ptrend = 0.02) and of BDE209 (β2nd_vs₁st_tertile = −1.8; 95% CI: −6.1, 2.5; β3rd_vs₁st_tertile = −3.2; −7.5, 1.2; ptrend = 0.15) in dust, particularly for boys (ptrend = 0.02 and 0.04, respectively). Working memory scores seemed to be lower in children with higher BDE99 concentrations in dust (ptrend = 0.10). No association was observed with cord blood levels of BDE209. Our findings are in agreement with those of four previous studies suggesting adverse cognitive outcomes among children associated with early-life exposure to penta-BDE mixtures, and provide new evidence for the potential neurotoxicity of BDE209. Several countries are in the process of banning the use of PBDE mixtures as flame-retardants. However, these compounds are likely to remain present in the environment for a long time to come
ISSN: 0161-813X

hal-01286255
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01286255
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01286255/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01286255/file/Childhood%20exposure%20to%20polybrominated%20diphenyl-accepted.pdf
DOI : 10.1016/j.neuro.2016.03.002

Éditeur(s) : HAL CCSD American Medical Association (AMA)
Résumé : International audience
IMPORTANCE Although frequently used in treating intensive care unit (ICU) patients with sepsis, empirical antifungal therapy, initiated for suspected fungal infection, has not been shown to improve outcome. OBJECTIVE To determine whether empirical micafungin reduces invasive fungal infection (IFI)-free survival at day 28. DESIGN, SETTING, AND PARTICIPANTS Multicenter double-blind placebo-controlled study of 260 nonneutropenic, nontransplanted, critically ill patients with ICU-acquired sepsis, multiple Candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents, and enrolled between July 2012 and February 2015 in 19 French ICUs. INTERVENTIONS Empirical treatment with micafungin (100mg, once daily, for 14 days) (n = 131) vs placebo (n = 129). MAIN OUTCOMES AND MEASURES The primary end pointwas survival without proven IFI 28 days after randomization. Key secondary end points included new proven fungal infections, survival at day 28 and day 90, organ failure, serum (1-3)-beta-D-glucan level evolution, and incidence of ventilator-associated bacterial pneumonia. RESULTS Among 260 patients (mean age 63 years; 91 [35%] women), 251 (128, micafungin group; 123, placebo group) were included in the modified intent-to-treat analysis. Median values were 8 for Sequential Organ Failure Assessment (SOFA) score, 3 for number of Candida-colonized sites, and 99 pg/mL for level of (1-3)-beta-D-glucan. On day 28, there were 82 (68%) patients in the micafungin group vs 79 (60.2%) in the placebo group who were alive and IFI free (hazard ratio [HR], 1.35 [95% CI, 0.87-2.08]). Results were similar among patients with a (1-3)-beta-D-glucan level of greater than 80 pg/mL (n = 175; HR, 1.41 [95% CI, 0.85-2.33]). Day-28 IFI-free survival in patients with a high SOFA score (> 8) was not significantly different when compared between the micafungin vs placebo groups (HR, 1.69 [95% CI, 0.96-2.94]). Use of empirical micafungin decreased the rate of new invasive fungal infection in 4 of 128 patients (3%) in the micafungin group vs placebo (15/123 patients [12%]) (P =.008). CONCLUSIONS AND RELEVANCE Among nonneutropenic critically ill patients with ICU-acquired sepsis, Candida species colonization at multiple sites, and multiple organ failure, empirical treatment with micafungin, compared with placebo, did not increase fungal infection-free survival at day 28.
ISSN: 0098-7484

hal-01405822
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01405822
DOI : 10.1001/jama.2016.14655
PUBMED : 27706483