Éditeur(s) : HAL CCSD
Résumé : International audience
Despite the recent interest in psychiatric illness in prison, the psychopathology of the Remire-Montjoly prison population remains largely unknown. Subject to significant population movements, French Guiana and its prison houses a very mixed population in which recent history has left a strong mark (earthquake in Haïti, civil war in Suriname, violence related to gold mining population and drug trafficking). These negative life events appear as potential vectors of psychological trauma. Additionally, strong links have been established in the literature between post-traumatic stress disorder (PTSD) and many other psychiatric disorders, including suicidal behavior and addictions. Under these conditions, we felt it essential to focus on the identification of PTSD in this sensitive population.Through adapted reception interviews, we tried to identify the PTSD, to describe by means of socio-demographic factors the studied population and to detect psychiatric comorbidities. The screening tool was the M.I.N.I. 5.0, which identifies 17 psychiatric disorders including the PTSD, based on the DSM IV definition. The target population was the prison incomers, agreeing to participate in the study, aged more than 18 years old and imprisoned between 18 January 2013 and 31 December 2013. To this date, 549 inmates were included in the study.The main result of this study was a prevalence of PTSD of 17% for incomers in detention. We found that the PTSD+ population is more likely to be female (15% against 7% p = 0.0246), which is consistent with the literature data. The M.I.N.I. 5.0 showed a higher prevalence of psychiatric disorders in the PTSD+ group. This association was confirmed in several types of pathology like mood disorders including: major depressive episode and manic or hypomanic episode, suicidal risk, some anxiety disorders including: panic disorder, obsessive-compulsive disorder and generalized anxiety disorder. Strong association was found for current major depressive episode, current manic or hypomanic episode and suicidal risk (p < 0.005).The prevalence of PTSD is very high in this study, about 24 times higher than in a general population survey using the same screening tool.A large number of comorbidities have been identified, which corresponds to those described in the literature. The specific issues of psychiatry in prison lead us to examine more specifically the significance of the results about suicide risk. A comprehensive suicide risk (sum of medium and high risk screened by the M.I.N.I.) was found in significantly more PTSD+ inmates (17% versus 7%, p = 0.005). This study supports the need for routine screening of PTSD among incomers in detention. This disease is both worrying and common in this population but the real issues are the comorbidities. Suicidal potential is among the most important issues in detention. Its evaluation should be completed by an early recognition of a PTSD.
Soumis à des mouvements de population importants, la Guyane Française et son centre pénitentiaire abritentune population métissée chez qui l’histoire récente a laissé une empreinte forte (tremblement de terre en Haïti,guerre civile au Suriname, violence liée à l’orpaillage et au trafic de stupéfiants). Ces événements de vienégatifs apparaissent comme autant de vecteurs potentiels de psychotraumatismes. Dans ces conditions, il nous a paru essentiel de mettre l’accent sur le repérage du TSPT (Trouble de Stress Post-traumatique) dans cette population sensible. A l'aide d’entretiens d’accueil dédiés nous nous sommes proposé de repérer les TSPT, de décrire sur un plan sociodémographique la population étudiée et de rechercher les comorbidités psychiatriques. Le résultat principal de cette étude était une prévalence du TSPT de 17% chez les arrivants en détention. Le MINI 5.0 a montré une prévalence plus élevée des pathologies psychiatriques dans le groupe présentant un TSPT avec un lien très fort (p<0.005) pour l’épisode dépressif majeur actuel, l’épisode (hypo)maniaque actuel et le risque suicidaire. Cette étude appuie la nécessité d’avoir un dépistage systématique du TSPT chez les arrivants en détention. Cette pathologie est à la fois fréquente dans cette population et invalidante mais ce sont ses comorbidités, dont le potentiel suicidaire, qui font tout l’enjeu d’un repérage précoce.
ISSN: 0383-6320

inserm-01421075
http://www.hal.inserm.fr/inserm-01421075
http://www.hal.inserm.fr/inserm-01421075/document
http://www.hal.inserm.fr/inserm-01421075/file/2016%2C%20Arnal%20-%20Post-Traumatic%20Stress%20Disorder%20among%20Incomers%20in%20Remire-Montjoly%20Prison%2C%20French%20Guiana.pdf
PUBMED : 27570960

Éditeur(s) : HAL CCSD American Physical Society (APS)
Résumé : International audience
Diffusion in natural and engineered media is quantified in terms of stochastic models for the heterogeneity-induced fluctuations of particle motion. However, fundamental properties such as ergodicity and self-averaging and their dependence on the disorder distribution are often not known. Here, we investigate these questions for diffusion in quenched disordered media characterized by spatially varying retardation properties, which account for particle retention due to physical or chemical interactions with the medium. We link self-averaging and ergodicity to the disorder sampling efficiency Rn, which quantifies the number of disorder realizations a noise ensemble may sample in a single disorder realization. Diffusion for disorder scenarios characterized by a finite mean transition time is ergodic and self-averaging for any dimension. The strength of the sample to sample fluctuations decreases with increasing spatial dimension. For an infinite mean transition time, particle motion is weakly ergodicity breaking in any dimension because single particles cannot sample the heterogeneity spectrum in finite time. However, even though the noise ensemble is not representative of the single-particle time statistics, subdiffusive motion in q≥2 dimensions is self-averaging, which means that the noise ensemble in a single realization samples a representative part of the heterogeneity spectrum.
ISSN: 2470-0053

hal-01622668
https://hal.archives-ouvertes.fr/hal-01622668
https://hal.archives-ouvertes.fr/hal-01622668v2/document
https://hal.archives-ouvertes.fr/hal-01622668/file/russian2017.pdf
DOI : 10.1103/PhysRevE.96.022156

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Two genome-wide association studies (GWASs) recently highlighted the HLA-DRA and HLA-DRB5 genes as associated with Parkinson disease (PD). However, because HLA-DRA displays a low level of polymorphisms and HLA-DRB5 is only present in approximately 20% of the population, these findings are difficult to interpret. Our aims were: (1) to replicate and investigate in greater detail the association between PD and the HLA-DR region; (2) to identify PD-associated HLA alleles; and (3) to perform a meta-analysis of our top finding. As part of 2 French population-based case-control studies of PD including highly ethnically homogeneous participants, we investigated the association between PD and 51 Single-nucleotide polymorphisms (SNPs) in the HLA-DR region. HLA-DRB1 alleles were imputed using the HLA(*) IMP software. HLA typing was performed in a subsample of the participants. We performed a meta-analysis of our top finding based on 4 GWAS data sets. Among 499 cases and 1123 controls, after correction for multiple testing, we found an association with rs660895 (OR/minor allele, 0.70; 95% CI, 0.57-0.87) within the HLA-DRB1 gene, which encodes the most polymorphic HLA-DR chain (DRβ). A meta-analysis (7996 cases, 36455 controls) confirmed this association (OR, 0.86; 95% CI, 0.82-0.91; P < .0001). SNP-based imputation of HLA alleles showed an inverse association between PD and the HLA-DRB1(*) 04 allele. We replicated an association between PD and the HLA-DR region and provided further insight into the loci and alleles involved. The highly polymorphic HLA-DRB1 locus contains rs660895, which represents a more legitimate candidate than previous ones. Our finding is in agreement with the hypothesis of an immune component in PD pathophysiology. © 2012 Movement Disorder Society.
ISSN: 0885-3185

inserm-00721562
http://www.hal.inserm.fr/inserm-00721562
http://www.hal.inserm.fr/inserm-00721562/document
http://www.hal.inserm.fr/inserm-00721562/file/Table1.pdf
http://www.hal.inserm.fr/inserm-00721562/file/Table2.pdf

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
The objective of this study is to assess the association of clinical manifestations of systemic sclerosis (SSc) with the absolute count of circulating blood monocyte subpopulations according to their membrane expression of CD16. Forty-eight consecutive patients fulfilling the 2013 ACR/EULAR classification criteria for SSc were included in this cross-sectional study. CD16+ monocyte absolute count was defined by flow cytometry and confronted to the clinical characteristics of SSc patients. Twenty-three healthy donors (HD) were randomly selected for comparison. SSc patients had an increased number of total circulating blood monocytes compared to HD (p < 0.001). The CD16- subpopulation absolute count was increased in SSc patients compared to HD (p < 0.001) but was similar in limited SSc (lSSc) and diffuse SSc (dSSc). On the contrary, the CD16+ population absolute count was increased in dSSc compared to both HD and lSSc patients (dSSc 0.071 Giga/L (+/- 0.034) vs HD 0.039 Giga/L (+/- 0.030), p < 0.01, and dSSc 0.071 Giga/L (+/- 0.034) vs lSSc 0.048 Giga/L (+/- 0.024), p < 0.05). The CD16+ monocyte subpopulation absolute count was significantly correlated with the severity of skin fibrosis evaluated by the modified Rodnan skin score (p < 0.001). The CD16+ monocyte subpopulation was also associated with pulmonary fibrosis (p < 0.05), with the severity of the restrictive ventilatory defect evaluated by total lung capacity (p < 0.05) and with the pulmonary function impairment reflected by diffusing capacity of the lungs for carbon monoxyde measures (p < 0.01). These results suggest that CD16+ monocytes are associated with the main fibrotic manifestations of SSc and their role in the pathogenesis of fibrosis in this autoimmune disorder should therefore be further considered.
ISSN: 0770-3198

hal-01560150
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560150
DOI : 10.1007/s10067-017-3597-6
PUBMED : 28293753

Éditeur(s) : HAL CCSD Ferrata Storti Foundation
Résumé : International audience
Lionnet et al. recently reported a high prevalence of retinopathy (RET) and otologic disorders (OTD) in patients with sickle cell-hemoglobin C disease (SC), while a significant number of patients had renal diseases (mainly glomerulopathy; GLO) and osteonecrosis (OST). The pathophysiological processes of these complications in SC are not well defined, although blood hyperviscosity has been suspected, but never tested to the best of our knowledge, as responsible for several chronic complications in SC disease1,2. The aim of this study was to analyze the associations between hematological and hemorheological parameters and chronic complications in adult SC patients.
ISSN: 0390-6078

inserm-01081709
http://www.hal.inserm.fr/inserm-01081709
http://www.hal.inserm.fr/inserm-01081709/document
http://www.hal.inserm.fr/inserm-01081709/file/2014%2C%20Lemonne%20-%20Impaired%20blood%20rheology%20plays%20a%20role%20in%20the%20chronic%20disorders%20associated%20with%20sickle%20cell-hemoglobin%20C%20disease.pdf
PUBMED : 24633868

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
BACKGROUND: A prospective study of infectious encephalitis was conducted in France in 2007. In total, 253 patients were enrolled with a proven etiological diagnosis for 52%. The cohort of surviving patients with encephalitis was assessed for sequelae and impairment 3 years after enrollment. METHODS: Patients, their family, and general practitioners (GPs) were interviewed by phone to document persisting symptoms, return to work, and past and current leisure activities, with standardized questionnaires. The IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly) was completed with relatives. The global outcome was determined in all patients with the Glasgow outcome scale. RESULTS: In 2010, 20 patients (10%) were unavailable for follow-up, 2 (1%) were excluded, and 18 (9%) had died since hospital discharge. Data were available for 167 survivors and 9 patients whose death was related to the encephalitis. The outcome was favorable in 108 of 176 patients (61%) (71 with complete resolution), 31 (18%) were mildly impaired, 25 (14%) were severely impaired, and 3 (1%) were in a vegetative state. The most frequent symptoms were difficulty concentrating (42%), behavioral disorders (27%), speech disorders (20%), and memory loss (19%). Fifteen of 63 patients (24%) previously employed were still unable to resume work. Long-term outcome was significantly associated with comorbid conditions, age, level of education, and the causative agent of encephalitis. CONCLUSIONS: Most patients with encephalitis experienced a favorable outcome 3 years after hospital discharge. However, minor to severe disability persists in a high number of cases with consequences for everyday life. Physical and mental impairment should be evaluated in all patients with encephalitis, and neuropsychological rehabilitation implemented whenever needed.
ISSN: 1058-4838

hal-00875190
https://hal.archives-ouvertes.fr/hal-00875190
DOI : 10.1093/cid/cis226
PUBMED : 22460967

Éditeur(s) : HAL CCSD
Résumé : International audience
Background Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. Methods We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. Results We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. Conclusions We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. Trial registration numbers NCT01746121 and NCT02397824
Journal of Medical Genetics

hal-01272929
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01272929
DOI : 10.1136/jmedgenet-2015-103302
PUBMED : 26502894

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 BioMed Central
Résumé : International audience
AbstractBackgroundSuicide rates in prison are high and their risk factors are incompletely understood. The objective of the present study is to measure the risk of suicide and its predictors in the only prison of multicultural French Guiana.MethodsAll new prisoners arriving between September 2013 and December 2014 were included. The Mini International Neuropsychiatric Interview (MINI) was used and socio-demographic data was collected. In order to identify the predictors of suicide risk multivariate logistic regression was used.ResultsOf the 707 prisoners included 13.2% had a suicidal risk, 14.0% of whom had a high risk, 15.1% a moderate risk and 41.9% a low risk. Predictive factors were depression (OR 7.44, 95% CI: 3.50–15.87), dysthymia (OR 4.22, 95% CI: 1.34–13.36), panic disorder (OR 3.47, 95% CI: 1.33–8.99), general anxiety disorder (GAD) (OR 2.19, 95% CI: 1.13–4.22), men having been abused during childhood (OR 21.01, 95%, CI: 3.26–135.48), having been sentenced for sexual assault (OR 7.12, 95% CI: 1.98–25.99) and smoking (OR 2.93, 95%, CI 1.30–6.63).ConclusionThe suicide risk was lower than in mainland France, possibly reflecting the differences in the social stigma attached to incarceration because of migrant populations and the importance and trivialization of drug trafficking among detainees. However, there were no differences between nationalities. The results reemphasize the importance of promptly identifying and treating psychiatric disorders, which were the main suicide risk factors.
ISSN: 1471-244X

inserm-01517176
http://www.hal.inserm.fr/inserm-01517176
http://www.hal.inserm.fr/inserm-01517176/document
http://www.hal.inserm.fr/inserm-01517176/file/12888_2017_Article_1320.pdf
DOI : 10.1186/s12888-017-1320-4

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 Elsevier
Résumé : International audience
BACKGROUND: Thrombophilias are common disorders that increase the risk of pregnancy-associated venous thromboembolism and pregnancy loss and can also increase the risk of placenta-mediated pregnancy complications (severe pre-eclampsia, small-for-gestational-age infants, and placental abruption). We postulated that antepartum dalteparin would reduce these complications in pregnant women with thrombophilia. METHODS: In this open-label randomised trial undertaken in 36 tertiary care centres in five countries, we enrolled consenting pregnant women with thrombophilia at increased risk of venous thromboembolism or with previous placenta-mediated pregnancy complications. Eligible participants were randomly allocated in a 1:1 ratio to either antepartum prophylactic dose dalteparin (5000 international units once daily up to 20 weeks' gestation, and twice daily thereafter until at least 37 weeks' gestation) or to no antepartum dalteparin (control group). Randomisation was done by a web-based randomisation system, and was stratified by country and gestational age at randomisation day with a permuted block design (block sizes 4 and 8). At randomisation, site pharmacists (or delegates) received a randomisation number and treatment allocation (by fax and/or e-mail) from the central web randomisation system and then dispensed study drug to the local coordinator. Patients and study personnel were not masked to treatment assignment, but the outcome adjudicators were masked. The primary composite outcome was independently adjudicated severe or early-onset pre-eclampsia, small-for-gestational-age infant (birthweight <10th percentile), pregnancy loss, or venous thromboembolism. We did intention-to-treat and on-treatment analyses. This trial is registered with ClinicalTrials.gov, number NCT00967382, and with Current Controlled Trials, number ISRCTN87441504. FINDINGS: Between Feb 28, 2000, and Sept 14, 2012, 292 women consented to participate and were randomly assigned to the two groups. Three women were excluded after randomisation because of ineligibility (two in the antepartum dalteparin group and one in the control group), leaving 146 women assigned to antepartum dalteparin and 143 assigned to no antepartum dalteparin. Some patients crossed over to the other group during treatment, and therefore for on-treatment and safety analysis there were 143 patients in the dalteparin group and 141 in the no dalteparin group. Dalteparin did not reduce the incidence of the primary composite outcome in both intention-to-treat analysis (dalteparin 25/146 [17.1%; 95% CI 11.4-24.2%] vs no dalteparin 27/143 [18.9%; 95% CI 12.8-26.3%]; risk difference -1.8% [95% CI -10.6% to 7.1%)) and on-treatment analysis (dalteparin 28/143 [19.6%] vs no dalteparin 24/141 [17.0%]; risk difference +2.6% [95% CI -6.4 to 11.6%]). In safety analysis, the occurrence of major bleeding did not differ between the two groups. However, minor bleeding was more common in the dalteparin group (28/143 [19.6%]) than in the no dalteparin group (13/141 [9.2%]; risk difference 10.4%, 95% CI 2.3-18.4; p=0.01). INTERPRETATION: Antepartum prophylactic dalteparin does not reduce the occurrence of venous thromboembolism, pregnancy loss, or placenta-mediated pregnancy complications in pregnant women with thrombophilia at high risk of these complications and is associated with an increased risk of minor bleeding. FUNDING: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and Pharmacia and UpJohn.
ISSN: 0923-7577

hal-01258557
http://hal.univ-brest.fr/hal-01258557
DOI : 10.1016/S0140-6736(14)60793-5
PUBMED : 25066248

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Implication of immune processes in bipolar disorder (BD) has recently gained increasing attention. Tolerogenic molecules, among which HLA-G plays a prominent role, mediate the modulation of such processes. The HLA-G locus is characterized by a high number of polymorphisms including a functionally relevant 14 base pair (bp) insertion/deletion (Ins/Del) allele affecting the HLA-G expression. Here, we analyzed the distribution of this polymorphism in 561 BD patients and 161 healthy and found that the HLA-G 14bp Ins/Ins genotype was significantly more prevalent in healthy controls than in patients (corrected p; pc=0.032) and that the prevalence of such protective genotype is lower among patients born during the winter season as compared to those born in other periods (pc=0.006). Possible mechanisms between low HLA G expression and resistance to infections as well as potential relationships between infections in early life and susceptibility to BD are discussed.
ISSN: 0198-8859

inserm-00864639
http://www.hal.inserm.fr/inserm-00864639
http://www.hal.inserm.fr/inserm-00864639/document
http://www.hal.inserm.fr/inserm-00864639/file/HLA-G_and_BD_manuscript_-1.pdf
DOI : 10.1016/j.humimm.2012.11.032

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
Regarding nerves as simple cables and electrical conduits is a gross error that does not allow us to understand the anomalies and disorders observed postoperatively. Instead, nerves should be seen as a living tissue of which physiological regulation is as complex as that of the blood-brain barrier. This review describes the basic structure and functions of this blood-nerve barrier and highlights the mechanisms of its breakdown and the resultant disorders. For clinical practice, it is important to note that the diffusion of molecules from the perineurium or from the blood is very limited, and so the blood-nerve barrier is a major pharmacologic barrier. Any stress upon neural physiological balance, particularly the terminal vascular blood supply, will induce the classic inflammatory cascade. Due to the complexity of the vascular system, nerve ischaemia will occur more quickly when the terminal blood supply is compromised. This blood supply can adapt in a variety of ways but when these possibilities of adaptation are exceeded, tissue ischaemia may be more extensive. Also, even after the initial injury has subsided, inflammation can cause a secondary insult. This could be particularly important in some patients with subclinical neuropathy.
ISSN: 0265-0215

hal-01477207
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477207
DOI : 10.1097/EJA.0000000000000590
PUBMED : 28146457

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
Objective The potential impact of environmental exposure to pyrethroid insecticides on child neurodevelopment has only just started to receive attention despite their widespread use. We investigated the associations between prenatal and childhood exposure to pyrethroid insecticides and behavioural skills in 6-year-olds. Methods The PELAGIE cohort enrolled 3421 pregnant women from Brittany, France between 2002 and 2006. 428 mothers were randomly selected for the study when their children turned 6, and 287 (67%) agreed to participate. Children's behaviour was assessed using the Strengths and Difficulties Questionnaire (SDQ). Three subscales (prosocial behaviour, internalising disorders and externalising disorders) were considered. Five pyrethroid metabolites were measured in maternal and child urine samples collected between 6 and 19 gestational weeks and at 6 years of age, respectively. Logistic regression and reverse-scale Cox regression models were used to estimate the associations between SDQ scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders. Results Increased prenatal cis-3-(2,2-dichlorovinyl)-2,2dimethylcyclopropane carboxylic acid (DCCA) concentrations were associated with internalising difficulties (Cox p value=0.05). For childhood 3phenoxybenzoic acid (PBA) concentrations, a positive association was observed with externalising difficulties (Cox p value=0.04) and high ORs were found for abnormal or borderline social behaviour (OR 2.93, 95% CI 1.27 to 6.78, and OR 1.91, 95% CI 0.80 to 4.57, for the intermediate and highest metabolite categories, respectively). High childhood trans-DCCA concentrations were associated with reduced externalising disorders (Cox p value=0.03). Conclusions The present study suggests that exposure to certain pyrethroids, at environmental levels, may negatively affect neurobehavioral development by 6 years of age.
ISSN: 1351-0711

hal-01519255
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01519255
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01519255/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01519255/file/Behavioural%20disorders%20in%206-year-old%20children_JFViel_HAL.pdf
DOI : 10.1136/oemed-2016-104035

Éditeur(s) : Edp Sciences S A
Résumé : Reared sea bass were submitted to six stressful situations: hyperoxia with or without hypercapnia, increased stocking density in an open flow or recirculating system, transfer to another tank and nodavirus injection. The potentially negative impact of these factors on the lives of sea bass was investigated by measuring 9 water parameters and 19 fish parameters including total serum protein (TSP). TSP has already been used to evaluate stress. The present study investigates data of previous and new experiments, concentrating on the potential use of TSP as a routine indicator to assess welfare in sea bass reared on fish farms. In the current experiment, oxygen and carbon dioxide were seen to affect levels of TSP, but alterations were too erratic to enable proper comparison, probably because they are normal components of the fish environment and become toxic only by dose increase. TSP decreased when stocking density increased. After transfer to another tank, TSP decreased to 14% for three weeks and then increased during the fourth week through compensative overproduction, before returning to normal levels after 2 months. The results confirmed that transfer is an important stress factor for fish, with cumulative effects for successive transfers. TSP alteration of nodavirus-injected fish depends on the type of symptoms, which can be divided into 3 groups: (i) dying fish, in which TSP increased sharply due to over-production of protein involved in non-specific defences and inflammation, then decreased dramatically before death; (ii) whirling fish, a group that included both fish that later died, in which TSP decreased, and fish that subsequently survived, in which TSP increased due to development of specific immunity; and (iii) asymptomatic fish, in which TPS was similar to control levels and which were probably insensitive to nodavirus and/or had developed defences. In this paper, different mechanisms of TSP alteration are proposed and the interest of TSP as a field parameter is discussed. TSP is a non-destructive parameter that is robust, easy to measure everywhere and cheap, representing a suitable way of monitoring the overall welfare of fish by its regular increase. It can be used only as a "warning" of poor rearing conditions, however, and further investigations would be needed to identify the specific stress or health disorder.
Aquatic Living Resources (0990-7440) (Edp Sciences S A), 2011-04 , Vol. 24 , N. 2 , P. 121-127

Droits : EDP Sciences, IFREMER, IRD 2011
http://archimer.ifremer.fr/doc/00043/15382/12740.pdf
DOI:10.1051/alr/2011130
http://archimer.ifremer.fr/doc/00043/15382/

Éditeur(s) : HAL CCSD
Résumé : International audience
How do we learn to communicate: how do we come to language or how does language come to us? Would it be a question of adaptation to the world by the act of speaking as suggested by J. Bernicot 1 (1992); would man benefit first and foremost from a genetic patrimony that enabled him to make use of language, as N. Chomsky (1985) points out by asking the existence of a competence related to generative mechanisms? J. Bruner (1996) proposes the idea of an education likely to "adapt a culture to the needs of its members and to adapt its members and their ways of learning to the needs of culture". 2. A / Motivations and objects An approach to mother-child relationships (master's thesis in developmental psychology 3, Miehakanda, 1998) has given me the opportunity to highlight the mediation of play in the structuring of relationships between the child with academic difficulties and his parents. The specific framework of this research-action was that of the educational and therapeutic care of children attending primary school (CE1-CLIS-CLAD) 4. These seven children (three girls / four boys) who were reported for various personality and behavioral disorders all had a lack of self-esteem and self-esteem affecting their relationships with those around them (peers, teachers ...).
Comment apprenons-nous à communiquer : comment venons-nous au langage ou comment le langage vient-il à nous ? Serait-ce une question d'adaptation au monde par l'action de parler comme le suggère J. Bernicot 1 (1992) ; l'homme bénéficierait-il prioritairement d'un patrimoine génétique le disposant à faire usage du langage, comme l'indique N. Chomsky (1985) en posant l'existence d'une compétence reliée à des mécanismes génératifs ? J. Bruner (1996) propose l'idée d'une éducation susceptible «d'adapter une culture aux besoins de ses membres et d'adapter ses membres et leurs manières d'apprendre aux besoins de la culture» 2. A/ Motivations et objets Une approche des relations mères-enfants (mémoire de maîtrise de psychologie du développement 3 ; Miehakanda, 1998) m'a donné l'occasion de mettre en évidence la médiation du jeu dans la structuration des rapports entre l'enfant rencontrant des difficultés scolaires et ses parents. Le cadre spécifique de cette recherche-action était celui des prises en charge éducatives et thérapeutiques d'enfants scolarisés à l'école primaire (CE1-CLIS-CLAD) 4. Ces sept enfants (trois filles / quatre garçons) qui étaient signalés pour diverses formes de troubles de la personnalité et du comportement éprouvaient tous un manque de confiance en soi et d'estime de soi affectant leurs rapports avec leur entourage (pairs ; enseignants…).
https://hal.univ-antilles.fr/tel-01658934

ISBN : Livre broché : ISBN-10: 3841633412 ISBN-13: 978-3841633415. 2015, pp 316
tel-01658934
https://hal.univ-antilles.fr/tel-01658934

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
STUDY QUESTION: Is prenatal exposure to persistent organic pollutants (POPs) associated with variations of sex hormone levels in cord blood? SUMMARY ANSWER: Prenatal exposure to a number of POPs is associated with a disruption of hormone levels in cord blood, with sex specificities. WHAT IS KNOWN ALREADY: Epidemiological studies have reported disorders of reproductive health, in relation with POPs exposure during early life and the endocrine disruption properties of these chemicals have been suggested as possible mechanisms. STUDY DESIGN, SIZE, DURATION: A subset of 282 mother-child pairs was selected from the prospective population-based PELAGIE birth cohort (n = 3421, 2002-2006, Brittany, France). Pregnant women were recruited before 19 weeks of gestation and followed until delivery. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sex hormone levels including sex hormone-binding globulin (SHBG), estradiol (E2), total testosterone (T), free testosterone (fT = T/SHBG) and the aromatase index (AI = T/E2) were measured in 282 cord blood samples. Anti-Müllerian hormone (AMH) was measured in male newborns only. Pesticide concentrations of α-endosulfan, β-hexachlorocyclohexane (β-HCH), γ-HCH, dieldrin, pp'-dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), heptachlor epoxide (HCE), as well as PCBs (congeners 153, 187 and the sum of anti-estrogenic PCBs 118, 138, and 170) and decabrominated diphenyl ether (BDE209) were also measured in cord blood. Associations between sex hormones and POPs exposure were explored using multiple linear regressions adjusted for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: High PCB levels were associated with an increase of SHBG (P-trend extless 0.01) and AMH (P-trend extless 0.05) and a decrease of fT (P-trend extless 0.05) and AI (P-trend extless 0.01). High pesticide levels, particularly α-endosulfan and HCE, were associated with an increase of SHBG (P extless 0.05) and E2 (P extless 0.01) and a decrease of fT (P extless 0.05) and AI (P extless 0.01). Several of these associations were stronger, or specific, among male or female newborns. The associations were not altered in the sensitivity analyses. LIMITATIONS, REASONS FOR CAUTION: The study population was of relatively small sample size, and some compounds rarely detected in cord blood. The high level of correlation between POPs makes it difficult to identify the most contributing POPs. Hormone measurements were performed at birth (in cord blood) and may not adequately represent the infant endocrine system. Multiple statistical testing may have led to false-positive associations. WIDER IMPLICATIONS OF THE FINDINGS: Our results are in discordance with those reported in the only published study of the kind but in accordance with studies about prenatal exposure to other endocrine disruptors such as phthalates. These findings may help understanding the pathways involved in adverse reproductive outcomes associated with POPs exposure. STUDY FUNDING/COMPETING INTERESTS: The PELAGIE cohort is funded by Inserm, French Ministry of Health, French Ministry of Labor, InVS, ANR, ANSES, and French Ministry of Ecology. None of the authors has any competing interest to declare
ISSN: 0268-1161

hal-01220641
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01220641
DOI : 10.1093/humrep/dev260
PUBMED : 26493407

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
STUDY QUESTION: Is there evidence at the population level of associations between different male genital disorders, outside Scandinavian countries? SUMMARY ANSWER: At an international scale, there is evidence for a number of correlations between rates of four male reproductive disorders (hypospadias, cryptorchidism, testicular cancer and low sperm concentration). WHAT IS KNOWN ALREADY: Some associations between these outcomes have been shown in studies focusing on individuals and mainly in Nordic European countries. These associations, together with histological evidence of a dysgenesis pattern in testicular tissue specimens, have generated the concept of the existence of a 'testicular dysgenesis syndrome' originating in utero. STUDY DESIGN, SIZE, DURATION: This is a geographical correlation study using cancer, malformations rates and sperm quality data collected between the years 1998 and 2005. PARTICIPANTS/MATERIALS, SETTING, METHODS: Incidence rates of testicular cancer were extracted from International Agency for Research on Cancer registries and Globocan, while cryptorchidism and hypospadias prevalence rates were obtained from EUROCAT and International Clearinghouse for Birth Defects Surveillance and Research registries. Sperm concentration data were extracted from recent studies using standardized methodology. A total of 39 registries and 9 sperm studies were selected. Non-parametric Spearman correlation tests were used to test the association between these four disorders. Correlations were computed for all registries together, for registries with high-quality matching coverage only and by continents. Sensitivity analyses were also conducted using data from prospective clinical studies to take into account potential bias related mainly to ascertainment of malformation rates. MAIN RESULTS AND THE ROLE OF CHANCE: We found positive correlations between testicular cancer and hypospadias (r = 0.32, P = 0.05) and between hypospadias and cryptorchidism (r = 0.70, P = 0.008). Stronger correlations were observed when using registries with high-quality matching coverage. Among these registries, differences between Europe and the rest of the world appeared (the positive correlation between testicular cancer and cryptorchidism was stronger outside Europe, r = 0.83, P = 0.01 compared with 0.40, P = 0.60 for European registries). A negative correlation between testicular cancer and sperm concentration was observed (r = -0.88, P = 0.002). These correlations support our initial hypothesis but remain only suggestive due to the intrinsic limitations in the study design (i.e. geographical correlation study) and do not allow causal inference. LIMITATIONS, REASONS FOR CAUTION: Differences in the ascertainment of malformations rates (definition, length of follow-up) make the international comparison difficult. The small number of registries for some conditions (cryptorchidism) or of studies (for sperm quality) and the absence of information about major risk factors such as ethnicity and socioeconomic status in the registries are also limitations. WIDER IMPLICATIONS OF THE FINDINGS: Our findings are in agreement with results of studies focusing on individuals and suggest that shared risk factors are present in the populations studied.
ISSN: 0268-1161

inserm-00863412
http://www.hal.inserm.fr/inserm-00863412
DOI : 10.1093/humrep/det111
PUBMED : 23670171

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
INTRODUCTION: Light chain deposition disease is a rare clinical entity characterized by deposition of monoclonal immunoglobulin light chains in organs. The kidneys are almost always affected, while the lung manifestations that have been reported, including nodular or diffuse disease, especially cystic lesions, are unusual. CASE REPORT: We report the case of a 60-year-old man with a diffuse infiltrative lung disease characterized by numerous apical cysts. The diagnosis of light chain deposition cystic lung disease was obtained by surgical lung biopsy. Light chain deposits in the salivary glands were the only extrapulmonary manifestation. Despite 12 chemotherapy cycles, the patient's lung function and radiological appearances worsened. CONCLUSION: This is the fourth case describing a cystic lung disease due to light chain deposition in the literature. It highlights the need for comprehensive investigations so as not to miss this rare cause of cystic lung disease, which appears to be related to a primary pulmonary lymphoproliferative disorder. The only treatment that appears to be effective is lung transplantation.
ISSN: 0761-8425

hal-00873356
https://hal.archives-ouvertes.fr/hal-00873356
https://hal.archives-ouvertes.fr/hal-00873356/document
https://hal.archives-ouvertes.fr/hal-00873356/file/DA_pots_chaines_lA_gA_res_non_amyloides_version_finale.pdf
DOI : 10.1016/j.rmr.2013.02.003

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
This paper presents a synthesis of a multidisciplinary study carried out along the Nîmes Roman aqueduct, located in the southeast part of France. The study was motivated by archaeologists attempting to explain the partial destructions of only one aerial bridge of the aqueduct (Pont de la Lône). Given its close proximity to the Nîmes seismically active fault, a possible seismic origin for the destructions was invoked. Seismologists and structural engineers thus carried out a variety of field and numerical investigations to test the seismic hypothesis. Supporting field evidence was found first along the aerial bridge section of the aqueduct: broken stalactites, arch warping, cracks and destruction of the bridge just above a breast wall shortly after its construction. Secondly, the underground part of the canal was analysed: irregularity in the thickness of calcite deposits of the canal walls, presence of numerous cracks, horizontal shift of the otherwise linear structure of the canal and presence of calcite twins in the deposits, found only where the canal crosses the Nîmes fault system. Numerical modelling and experimental results show that (1) only the Pont de la Lône would have suffered serious damage under seismic solicitation (assuming an M6 earthquake at 10 km distance). The second aerial bridge, the three levels arches Pont du Gard, an historical monument still standing today, would have suffered less damage, due to its very different fundamental frequency of around 0.4 Hz, far from the amplified seismic near-field spectrum; (2) the numerical models also show that a fall of the canal wall would require a higher magnitude event (M > 6); (3) the presence of calcite twinning requires a differential static stress of 4 MPa or greater, which can only be achieved very close to the fault rupture of a M > 6 earthquake; (4) finally, local surface rupturing of such a fault would also corroborate the hypothesis that the observed offset of the canal may be partly seismically induced. Although other possible origins for each individual evidence may not be excluded, the observed spatiotemporal concentration of architectural/geological anomalies together with the numerical results allow us to support a possible co-seismic origin for these disorders, indirectly attesting to the potential seismic activity (M > 6) of the nearby Nîmes fault. Furthermore, following the conclusions of archaeological studies, the disorders occurred between 250 and 350 year AD, thus providing timing for this possible seismic event, an essential parameter in seismic hazard analysis. These results validate the archaeo-seismological approach as a tool that may help improve the knowledge of major infrequent earthquakes in areas of moderate seismic activity.
ISSN: 0921-030X

hal-00379064
https://hal.archives-ouvertes.fr/hal-00379064
DOI : 10.1007/s11069-008-9276-9