Éditeur(s) : HAL CCSD WB Saunders
Résumé : International audience
OBJECTIVE: We hypothesized that, in Human Immunodeficiency Virus and Hepatitis C Virus (HIV/HCV) co-infected patients who did not respond to peg-interferon and ribavirin, a maintenance therapy with peg-interferon could induce fibrosis regression. METHODS: This was a randomized study with two parallel groups. HIV/HCV co-infected patients received peg-interferon α-2a at 180 μg/week or remained on observation for 96 weeks. The primary endpoint was the percentage of patients who experienced a decrease of at least one point in their Metavir fibrosis score between initial and final liver biopsies. Secondary endpoints included plasma fibrosis markers at week 96, occurrence of HCV-related complications, and survival. RESULTS: A total of 52 patients were randomized (peg-interferon: 25; control: 27) including 18 with cirrhosis. The median (interquartile range) age was 44 (40-46) years, and 69% were male. A total of 64% had ALT levels >1.5 normal values, and the CD4 cell count was 391 (296-537) cells/mm(3); 67% of patients had HIV RNA <200 copies/mL at entry. The main endpoint was assessed in 41 patients. Response rates were 3/20 (15%) and 4/21 (19%) in the peg-interferon and control groups, respectively (p = 0.99). There was no significant difference between peg-interferon and control groups on plasma fibrosis markers at the final visit. Severe liver-related complications were observed in 2 and 5 patients in peg-interferon and control groups, respectively. Three deaths were observed, all in the control group. CONCLUSIONS: A maintenance therapy with peg-interferon α-2a over 96 weeks in HIV/HCV co-infected patients, who were non-responders to HCV treatment, did not change liver fibrosis. ClinicalTrials.gov Identifier: NCT00122616.
ISSN: 0163-4453

hal-00875067
https://hal.archives-ouvertes.fr/hal-00875067
DOI : 10.1016/j.jinf.2013.05.007
PUBMED : 23800784

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 Wiley
Résumé : International audience
BACKGROUND: This study examines gene-environment interaction between the MTHFR C667T polymorphism and folic acid in the etiology of orofacial clefts (OFC). We used a pooled-analytical approach on four studies that used similar methods. METHODS: We used logistic regression to analyze the pooled sample of 1149 isolated cases and 1161 controls. Fetal and maternal MTHFR C677T genotypes, and maternal periconceptional exposure to smoking, alcohol, vitamin containing folic acid and folic acid supplements were contrasted between the cleft types [non-syndromic clefts lip or without cleft palate (CL(P)) and non-syndromic cleft palate (CP)] and control groups. RESULTS: There was a reduced risk of CL(P) with maternal folic acid use (p = 0.008; OR = 0.70, 95% CI: 0.65-0.94) and with supplements containing folic acid (p = 0.028, OR = 0.80, 95% CI: 0.65-0.94). Maternal smoking increased the risk of both CL(P) (p < 10 e-3; OR = 1.62, 95% CI: 1.35-1.95) and CP (p = 0.028; OR = 1.38, 95% CI: 1.04-1.83). No significant risk was observed with either maternal or fetal MTHFR C677T genotypes. CONCLUSION: This individual participant data (IPD) meta-analysis affords greater statistical power and can help alleviate the problems associated with aggregate-level data-sharing. The result of this IPD meta-analysis is consistent with previous reports suggesting that folic acid and smoking influence OFC outcomes.
ISSN: 1542-0752

hal-00875899
https://hal.archives-ouvertes.fr/hal-00875899
DOI : 10.1002/bdra.23133
PUBMED : 23670871

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND: African Americans with head and neck squamous cell carcinoma (HNSCC) have a lower survival rate than whites. This study investigated the functional importance of ancestry-informative single-nucleotide polymorphisms (SNPs) in HNSCC and also examined the effect of functionally important genetic elements on racial disparities in HNSCC survival. METHODS: Ancestry-informative SNPs, RNA sequencing, methylation, and copy number variation data for 316 oral cavity and laryngeal cancer patients were analyzed across 178 DNA repair genes. The results of expression quantitative trait locus (eQTL) analyses were also replicated with a Gene Expression Omnibus (GEO) data set. The effects of eQTLs on overall survival (OS) and disease-free survival (DFS) were evaluated. RESULTS: Five ancestry-related SNPs were identified as cis-eQTLs in the DNA polymerase beta (POLB) gene (false discovery rate [FDR]<0.01). The homozygous/heterozygous genotypes containing the African allele showed higher POLB expression than the homozygous white allele genotype (P<.001). A replication study using a GEO data set validated all 5 eQTLs and also showed a statistically significant difference in POLB expression based on genetic ancestry (P=.002). An association was observed between these eQTLs and OS (P<.037; FDR<0.0363) as well as DFS (P=.018 to.0629; FDR<0.079) for oral cavity and laryngeal cancer patients treated with platinum-based chemotherapy and/or radiotherapy. Genotypes containing the African allele were associated with poor OS/DFS in comparison with homozygous genotypes harboring the white allele. CONCLUSIONS: Analyses show that ancestry-related alleles could act as eQTLs in HNSCC and support the association of ancestry-related genetic factors with survival disparities in patients diagnosed with oral cavity and laryngeal cancer. (C) 2016 American Cancer Society.
ISSN: 0008-543X

hal-01519253
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01519253
DOI : 10.1002/cncr.30457
PUBMED : 27906459

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Are bisphenol A (BPA) and BPA analogs (BPA-A) safe for male human reproductive function? The endocrine function of human testes explants [assessed by measuring testosterone and insulin-like factor 3 (INSL3)] was impacted by exposure of the human adult testis explants to BPA/BPA-A. The few epidemiologic studies performed suggest that bisphenols have potential endocrine disruptive properties, but they did not identify clear and direct patterns of endocrine disruption. Adult human testis explants in culture were exposed to BPA and the analogs bisphenol F (BPF), bisphenol S (BPS), bisphenol E (BPE), bisphenol B (BPB) and bisphenol A diglycidyl ether (BADGE) at 10(-9)-10(-5) M for 24 or 48 h. Human adult testes were obtained from prostate cancer patients who had no hormone therapy, or from multiorgan donors. After ex vivo exposure to the investigated bisphenols, the measured outcomes were related to histopathology (gross morphology and germ cell viability determined by anti-caspase three immunohistochemistry), and the levels of testosterone, INSL3 and inhibin B were measured using immunoassays. The levels of mRNA encoding key enzymes of bisphenol biotransformation were investigated by quantitative PCR: UGT2B15 UDP (glucuronosyltransferase two family, polypeptide B15), GUSB (glucuronidase beta), SULT1A1 and 3 (sulfotransferase family 1 A member 1 and 3) and STS (steroid sulfatase). A significant dose-dependent inhibition was found between testosterone levels measured in the culture medium and concentrations of BPA (P = 0.00778 at 24 h and P = 0.0291 at 48 h), BPE (P = 0.039) and BPF (P = 0.00663). The observed BPA and BPA-A-induced inhibition of testosterone production varied according to duration of exposure and BPA/BPA-A concentrations. BPA (10(-9) M; P < 0.05), BPB (10(-9) M; P < 0.05), BPS (10(-9) and 10(-8) M; P < 0.05) and BADGE (10(-5) M; P < 0.05) increased Leydig cell INSL3 production. By contrast, BPE dose dependently inhibited INSL3 (P = 0.0372). Conversely, Sertoli cell function (inhibin B) and germ cell viability were not significantly affected by either bisphenols. N/A. Environmental compounds cannot be deliberately administered to men, justifying the use of an ex vivo approach. A relatively low number of testes samples were available for analysis (n = 3, except for testosterone secretion with n = 5). The active concentrations of BPA and BPA-A used in the study were higher than those found in human biological fluids. Under our experimental conditions, direct exposure to BPA or BPA-A can result in endocrine disturbance in the adult human testis.
ISSN: 0268-1161

hal-01578582
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578582
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578582/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578582/file/Parallel%20assessment%20of%20the%20effects%20of%20bisphenol%20A_accepted.pdf
DOI : 10.1093/humrep/dex093

Éditeur(s) : HAL CCSD
Résumé : National audience
INTRODUCTION: Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis and detecting PAH efficiently remains challenging. The DETECT study has offered in 2013 a composite screening tool for PAH. The objective of our study was to compare the indication of right heart catheterisation (RHC) as suggested by the DETECT algorithm with the decisions of a multidisciplinary team. METHODS: This prospective monocentric non-interventional study consecutively included systemic sclerosis patients when data required to apply DETECT algorithm were available. We evaluate the number of RHC as requested by this algorithm and confronted it with the indications of RHC suggested by a multidisciplinary group blinded for the result of DETECT algorithm. RESULTS: In total, 117 systemic sclerosis patients were included. When DETECT algorithm was applied to all patients, RHC was suggested by this algorithm for 70 patients, whereas only 15 indications were required by the multidisciplinary group; among those patients only 7 had PAH. When DETECT algorithm was applied only to the 42 patients with DLCO<60% and disease duration of more than 3 years, RHC was suggested for 31 patients whereas only 13 were indicated by the multidisciplinary group; among those patients only 7 had PAH. CONCLUSION: The DETECT algorithm is able to efficiently detect all PAH patients finally diagnosed by our multidisciplinary team. However, it increases by 3 the number of RHC that should be performed.
La Revue de Médecine Interne

hal-01579606
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579606
DOI : 10.1016/j.revmed.2017.04.005
PUBMED : 28545856

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: Dengue fever is the most important arboviral infection that affects humans, particularly in tropical and subtropical regions. Here, we provide the first comprehensive overview of the severity of dengue epidemics in French Guiana. METHODOLOGY/PRINCIPAL FINDINGS: We monitored hospitalized cases between 2008 and 2013. Detailed clinical features and biological parameters were collected on a daily basis from all cases. Among the 1,356 cases, 216 (16%) were classified according to the WHO 2009 classification as dengue without warning signs (WS), 926 (68%) were classified as dengue with WS and 214 (16%) were classified as severe dengue. The severity rates were similar between the three major epidemics that occurred during the study period, whereas the hospitalization rate was highest in 2013. Fluid accumulation, aspartate aminotransferase (ASAT) counts>193 IU/L and platelet counts<75,000 cells/mm3 were associated with dengue severity. CONCLUSIONS/SIGNIFICANCE: Our findings provide a recent epidemiological description of the severity of dengue epidemics in French Guiana. These results highlight the potential impacts and consequences of implementing the WHO 2009 classification on hospital activity. Future studies should include virological and immunological investigations of well-documented serum samples.
ISSN: 1932-6203

hal-01477201
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477201
DOI : 10.1371/journal.pone.0172267
PUBMED : 28196111

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND: Recent studies suggest that a Mediterranean dietary pattern during pregnancy may influence pregnancy outcomes. The aim of this study was to evaluate the effect of adherence to a Mediterranean diet (MD) during pregnancy on fetal growth restriction (FGR) and preterm delivery (PTD) in a French Caribbean island where the population is largely of African descent and presents dietary patterns similar to MD. METHODS: Using data from the TIMOUN Mother-Child Cohort Study conducted in Guadeloupe (French West Indies) between 2004 and 2007, we analysed data for 728 pregnant women who delivered liveborn singletons without any major congenital malformations. Degree of adherence to MD during pregnancy was evaluated with a semi-quantitative food frequency questionnaire based on nine dietary criteria. Multiple logistic regression models were used to analyse birth outcomes while taking potential confounders into account. RESULTS: Overall there was no association between MD adherence during pregnancy and the risk of PTD or FGR. However, pre-pregnancy body mass index was a strong effect modifier, and MD adherence was associated with a decreased risk of PTD specifically in overweight and obese women (adjusted odds ratio 0.7, 95% confidence interval 0.6, 0.9) (P heterogeneity <0.01). CONCLUSIONS: These results suggest that Caribbean diet during pregnancy may carry some benefits of MD and may contribute to reduce the risk of PTD in overweight and obese pregnant women.
ISSN: 0269-5022

hal-00988172
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00988172
DOI : 10.1111/ppe.12113
PUBMED : 24754337

Éditeur(s) : HAL CCSD American Academy of Neurology
Résumé : International audience
OBJECTIVE: We examined if the CNS Penetration-Effectiveness (CPE) score of antiretroviral drugs was associated with survival after a diagnosis of HIV-related encephalopathy, progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis, or cryptococcal meningitis. METHODS: Using data from the FHDH-ANRS CO4, we compared the survival of 9,932 HIV-infected patients diagnosed with a first neurologic AIDS-defining event in the pre-combination antiretroviral therapy (cART) (1992-1995), early cART (1996-1998), or late cART (1999-2004) periods. Follow-up was subdivided (CPE < 1.5 and CPE ≥ 1.5), and relative rates (RR) of death were estimated using multivariable Poisson regression models. RESULTS: In the pre-cART and early cART periods, regimens with CPE ≥ 1.5 were associated with lower mortality after HIV-related encephalopathy (RR 0.64; 95% confidence interval [CI] 0.47-0.86 and RR 0.45; 95% CI 0.35-0.58) and after PML (RR 0.79; 95% CI 0.55-1.12 and RR 0.45; 95% CI 0.31-0.65), compared to regimens with CPE < 1.5, while in the late cART period there was no association between the CPE score and the mortality. A higher CPE score was also associated with a lower mortality in all periods after cerebral toxoplasmosis (RR 0.68, 95% CI 0.56-0.84) or cryptococcal meningitis (RR 0.50, 95% CI 0.34-0.74). Whatever the neurologic event, these associations were not maintained after adjustment on updated plasma HIV-RNA (missing, <500, ≥500 copies/mL) with RR ranging from 0.82 (95% CI 0.36-1.91) to 1.02 (0.69-1.52). CONCLUSION: At the beginning of the cART era, the CPE score was of importance for survival after severe neurologic event, while in the late cART period, the additional effect of CPE score vanished with more powerful antiretroviral regimens associated with plasma viral load control.
ISSN: 0028-3878

hal-00875434
https://hal.archives-ouvertes.fr/hal-00875434
DOI : 10.1212/WNL.0b013e31820c3089
PUBMED : 21248274

Éditeur(s) : HAL CCSD
Résumé : International audience
Leishmania parasites induce an immunomodulation by subverting the host immune response towards a CD4(+) Th2 lymphocytic cell response that favors parasite persistence. Here, we report that after successful treatment of visceral leishmaniasis due to Leishmania infantum, an immune reconstitution syndrome revealing hip septic arthritis was associated with a switch from Th2 towards a Th1 cytokine profile, and a decrease in the level of immunomodulating factors, such as soluble HLA-G and indoleamine 2,3-dioxygenase (IDO) activity. We then measured IDO activity in a cohort of 39 patients and uninfected control subjects. Results showed significantly enhanced IDO activity in patients with visceral Leishmania infection, compared with uninfected control subjects (P < 0.001), but also compared with treated patients (P < 0.05). A decrease in IDO activity could constitute a relevant biomarker for the restoration of the immune response during visceral leishmaniasis.
Innate Immunity

inserm-00818884
http://www.hal.inserm.fr/inserm-00818884
DOI : 10.1177/1753425912473170
PUBMED : 23413147

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
PURPOSE: Two hundred and fifty-three patients were included in a study on the etiology of encephalitis, carried out in France in 2007. Tuberculosis was the second most frequently identified cause, after HSV and with the same number of cases as VZV. The authors report the specific features of patients presenting with tuberculosis encephalitis (TE). METHODS: TE patients were defined as patients presenting with encephalitis, with positive culture or PCR for Mycobacterium tuberculosis, or the association of clinical, biological, imaging, and epidemiological evidence (possible cases). Clinical, microbiological, and brain imaging data was analyzed and compared to that of other included patients. RESULTS: Twenty cases of TE were identified. The M/F sex-ratio was 1.5, the mean age 53 years. Four (20%) patients had a history of tuberculosis before the encephalitis. The median delay between the onset of general and neurological symptoms was significantly longer for tuberculosis cases than for others (10 days vs. 2; P<10(-10)). The median CSF protein level was significantly higher for tuberculosis cases (2.1 g/L vs. 0.8 g/L, P=0.002). CT scan and MRI were normal on admission for eight patients out of 17. Fourteen isolated strains of M. tuberculosis were susceptible to first-line anti-tuberculosis drugs and one was rifampicin-resistant. Six (33%) patients died during hospitalization and two were lost to follow-up. Ten out of 12 (78.6%) had persisting neurological symptoms on discharge. DISCUSSION: Despite non-multiresistant MT strains, the case fatality rate among TE patients was high in our series. Early brain imaging is poor contributive for the diagnosis of TE.
ISSN: 0399-077X

hal-00874835
https://hal.archives-ouvertes.fr/hal-00874835
DOI : 10.1016/j.medmal.2013.05.003
PUBMED : 23816146

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.
ISSN: 0001-6322

hal-00875723
https://hal.archives-ouvertes.fr/hal-00875723
DOI : 10.1007/s00401-013-1084-y
PUBMED : 23400299

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
A nested case-control association study was designed to investigate the influence of maternal and fetal copy number variants (CNVs) on reproductive outcomes. Genotypes of ten CNVs encompassing GST and CYP genes were assessed. Significant associations were only found for child CNV genotypes. In particular, the child GSTM1 insertion allele was associated with prematurity protection (odds ratio, 95% CI: 0.67, 0.51-0.89; P < 0.01), whereas the child GSTT2B insertion allele was associated with an increased risk of being small for gestational age (odds ratio, 95% CI: 1.33, 1.07-1.67; P = 0.01). The study highlights the role of the fetal genome in prenatal development and also the need to analyse CNVs in a systematic manner.
ISSN: 1470-0328

hal-00875955
https://hal.archives-ouvertes.fr/hal-00875955
DOI : 10.1111/j.1471-0528.2012.03400.x
PUBMED : 22676722

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Few studies have considered using environmental amenities to explain social health inequalities.Nevertheless, Green spaces that promote good health may have an effect on socioeconomic health inequalities. In developed countries, there is considerable evidence that green spaces have a beneficial effect on the health of urban populations and recent studies suggest they can have a positive effect on pregnancy outcomes. To investigate the relationship between green spaces and the spatial distribution of infant mortality taking account neighborhood deprivation levels. METHODS: The study took place in Lyon metropolitan area, France. All infant deaths that occurred between 2000 and 2009 were geocoded at census block level. Each census block was assigned greenness and socioeconomic deprivation levels. The spatial--scan statistic was used to identify high risk cluster of infant mortality according to these neighborhood characteristics. RESULTS: The spatial distribution of infant mortality was not random with a high risk cluster in the south east of the Lyon metropolitan area (p<0.003). This cluster disappeared (p=0.12) after adjustment for greenness level and socioeconomic deprivation, suggesting that these factors explain part of the spatial distribution of infant mortality. These results are discussed using a conceptual framework with 3 hypothetical pathways by which green spaces may have a beneficial effect on adverse pregnancy outcomes: (i) a psychological pathway, (ii) a physiological disruption process and (iii) an environmental pathway. CONCLUSIONS: These results add some evidence to the hypothesis that there is a relationship between access to green spaces and pregnancy outcomes but further research is required to confirm this.
ISSN: 1471-2393

inserm-00878362
http://www.hal.inserm.fr/inserm-00878362
http://www.hal.inserm.fr/inserm-00878362/document
http://www.hal.inserm.fr/inserm-00878362/file/1471-2393-13-191.pdf
DOI : 10.1186/1471-2393-13-191

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
BACKGROUND: People in developed countries are widely exposed to low levels of organochlorine pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). Seafood is a major contributor to PCB exposure. Toxicity of those various pollutants to reproductive and endocrine functions raises questions about possible effects on fertility. We explored whether serum levels of these pollutants and seafood consumption were associated with the fertility of couples enrolled in a French birth cohort (PELAGIE). METHODS: Time-to-pregnancy was investigated in 3,421 pregnant women by asking how many months they had taken to conceive. Levels of 14 organochlorine pesticides, 12 PCBs, and 10 PBDE compounds were measured in cord blood serum from a random subcohort (n = 394). Mercury concentrations measured in maternal hair were considered as a potential coexposure. Fecundability odds ratios (ORs) were estimated from multivariate discrete-time Cox proportional hazard models. RESULTS: Shellfish consumption was associated with longer time-to-pregnancy (fecundability OR ≥twice/week vs. 0.410 µg/L vs. <0.266 µg/L, fecundability OR = 0.46 [0.32-0.66]). In multiple sensitivity analyses, reduced fecundability was most consistently associated with shellfish consumption, p,p'-DDE, total PCBs, PCB153, and PCB187. Models that simultaneously included multiple coexposure factors led to similar conclusions. CONCLUSIONS: Our findings were robust in sensitivity analyses, including analysis restricted to primiparous women. These results suggest that PCBs, p,p'-DDE, and other shellfish contaminants may impair human fertility.
ISSN: 1044-3983

inserm-00826533
http://www.hal.inserm.fr/inserm-00826533
DOI : 10.1097/EDE.0b013e31827f53ec
PUBMED : 23348067

Éditeur(s) : HAL CCSD
Résumé : International audience
Up-to-date estimates of the health outcomes of preterm children are needed for assessing perinatal care, informing parents, making decisions about care, and providing evidence for clinical guidelines. To determine survival and neonatal morbidity of infants born from 22 through 34 completed weeks' gestation in France in 2011 and compare these outcomes with a comparable cohort in 1997. The EPIPAGE-2 study is a national, prospective, population-based cohort study conducted in all maternity and neonatal units in France in 2011. A total of 2205 births (stillbirths and live births) and terminations of pregnancy at 22 through 26 weeks' gestation, 3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort data were collected from January 1 through December 31, 1997, and from March 28 through December 31, 2011. Analyses for 1997 were run for the entire year and then separately for April to December; the rates for survival and morbidities did not differ. Data are therefore presented for the whole year in 1997 and the 8-month and 6-month periods in 2011. Survival to discharge and survival without any of the following adverse outcomes: grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or necrotizing enterocolitis (stages 2-3). A total of 0.7% of infants born before 24 weeks' gestation survived to discharge: 31.2% of those born at 24 weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27 through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks, 30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at 32 through 34 weeks. Compared with 1997, the proportion of infants surviving without severe morbidity in 2011 increased by 14.4% (P < .001) at 25 through 29 weeks and 6% (P < .001) at 30 through 31 weeks but did not change appreciably for those born at less than 25 weeks. The rates of antenatal corticosteroid use, induced preterm deliveries, cesarean deliveries, and surfactant use increased significantly in all gestational-age groups, except at 22 through 23 weeks. The substantial improvement in survival in France for newborns born at 25 through 31 weeks' gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard.
ISSN: 2168-6211

hal-01258705
http://hal.univ-brest.fr/hal-01258705
PUBMED : 25621457
DOI : 10.1001/jamapediatrics.2014.3351

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
Anti-Aspergillus IgG antibodies are important biomarkers for the diagnosis of chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). We compared the performance of a new commercial EIA (Bordier Affinity Products) with those of the Bio-Rad and VirionSerion EIAs. This assay is novel in the association of two recombinant antigens with somatic and metabolic antigens of A. fumigatus. In a prospective multicentre study, 436 serum samples from 147 patients diagnosed with CPA (136 sera/104 patients) or ABPA (94 sera/43 patients) and from 205 controls (206 sera) were tested. We obtained sensitivities of 97%, 91.7%, and 86.1%, and specificities of 90.3%, 91.3%, and 81.5% for the Bordier, Bio-Rad and VirionSerion tests, respectively. The Bordier kit was more sensitive than the Bio-Rad kit (p < 0.01), which was itself more sensitive than the VirionSerion kit (p=0.04). The Bordier and Bio-Rad kits had similar specificities (p=0.8), both higher than that of the VirionSerion kit (p=0.02). The areas under the ROC curves confirmed the superiority of the Bordier kit over the Bio-Rad and the VirionSerion kits (0.977, 0.951 and 0.897, respectively; p < 0.01 for each comparison). In a subset analysis of 279 sera tested with the Bordier and Bio-Rad kits and an in-house immunoprecipitin assay (IPD), the Bordier kit had the highest sensitivity (97.7%), but the IPD tended to be more specific (71.2 and 84.7%, respectively; p=0.10).The use of recombinant, somatic and metabolic antigens in a single EIA improved the balance between sensitivity and specificity, resulting in an assay highly suitable for use in the diagnosis of chronic and allergic aspergillosis.
ISSN: 0095-1137

hal-01282328
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282328
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282328/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282328/file/Prospective%20evaluation%20of%20a%20new%20Aspergillus.pdf
DOI : 10.1128/JCM.03261-15

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND:Dengue fever is the most important arboviral infection that affects humans, particularly in tropical and subtropical regions. Here, we provide the first comprehensive overview of the severity of dengue epidemics in French Guiana.METHODOLOGY/PRINCIPAL FINDINGS:We monitored hospitalized cases between 2008 and 2013. Detailed clinical features and biological parameters were collected on a daily basis from all cases. Among the 1,356 cases, 216 (16%) were classified according to the WHO 2009 classification as dengue without warning signs (WS), 926 (68%) were classified as dengue with WS and 214 (16%) were classified as severe dengue. The severity rates were similar between the three major epidemics that occurred during the study period, whereas the hospitalization rate was highest in 2013. Fluid accumulation, aspartate aminotransferase (ASAT) counts>193 IU/L and platelet counts<75,000 cells/mm3 were associated with dengue severity.CONCLUSIONS/SIGNIFICANCE:Our findings provide a recent epidemiological description of the severity of dengue epidemics in French Guiana. These results highlight the potential impacts and consequences of implementing the WHO 2009 classification on hospital activity. Future studies should include virological and immunological investigations of well-documented serum samples
ISSN: 1932-6203

inserm-01481447
http://www.hal.inserm.fr/inserm-01481447
http://www.hal.inserm.fr/inserm-01481447/document
http://www.hal.inserm.fr/inserm-01481447/file/2017%2C%20Flamand%20-%20Epidemiological%20assessment%20of%20the%20severity%20of%20dengue%20epidemics%20in%20French%20Guiana.pdf
DOI : 10.1371/journal.pone.0172267.t003

Éditeur(s) : HAL CCSD
Résumé : International audience
A prospective study on randomized patients was conducted to determine how morphokinetic parameters are altered in embryos grown in sequential versus global culture media. Eleven morphokinetic parameters of 160 single embryos transferred were analyzed by time lapse imaging involving two University-affiliated in vitro fertilization (IVF) centers. We found that the fading of the two pronuclei occurred earlier in global (22.56±2.15 hpi) versus sequential media (23.63±2.71 hpi; p=0.0297). Likewise, the first cleavage started earlier at 24.52±2.33 hpi vs 25.76±2.95 hpi (p=0.0158). Also, the first cytokinesis was shorter in global medium, lasting 18±10.2 minutes in global versus 36±37.8 minutes in sequential culture medium (p <0.0001). We also observed a significant shortening in the duration of the 2-cell stage in sequential medium: 10.64 h±2.75 versus 11.66 h±1.11 in global medium (p=0.0225) which suggested a faster progression of the embryos through their first mitotic cell cycle. In conclusion, morphokinetic analysis of human embryos by Time lapse imaging reveals significant differences in five kinetic variables according to culture medium. Our study highlights the need to adapt morphokinetic analysis accordingly to the type of media used to best support human early embryo development.
Annales de Biologie Clinique

hal-01579406
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579406
DOI : 10.1684/abc.2017.1259
PUBMED : 28751285

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
ABSTRACT: BACKGROUND: Climate change poses unprecedented challenges, ranging from global and local policy challenges to personal and social action. Heat-related deaths are largely preventable, but interventions for the most vulnerable populations need improvement. Therefore, the prior identification of high risk areas at the community level is required to better inform planning and prevention. We aimed to demonstrate a simple and flexible conceptual framework relying upon satellite thermal data and other digital data with the goal of easily reproducing this framework in a variety of urban configurations. RESULTS: The study area encompasses Rennes, a medium-sized French city. A Landsat ETM + image (60 m resolution) acquired during a localized heatwave (June 2001) was used to estimate land surface temperature (LST) and derive a hazard index. A land-use regression model was performed to predict the LST. Vulnerability was assessed through census data describing four dimensions (socio-economic status, extreme age, population density and building obsolescence). Then, hazard and vulnerability indices were combined to deliver a heatwave health risk index. The LST patterns were quite heterogeneous, reflecting the land cover mosaic inside the city boundary, with hotspots of elevated temperature mainly observed in the city center. A spatial error regression model was highly predictive of the spatial variation in the LST (R2 = 0.87) and was parsimonious. Three land cover descriptors (NDVI, vegetation and water fractions) were negatively linked with the LST. A sensitivity analysis (based on an image acquired on July 2000) yielded similar results. Southern areas exhibited the most vulnerability, although some pockets of higher vulnerability were observed northeast and west of the city. The heatwave health risk map showed evidence of infra-city spatial clustering, with the highest risks observed in a north--south central band. Another sensitivity analysis gave a very high correlation between 2000 and 2001 risk indices (r = 0.98, p < 10-12). CONCLUSIONS: Building on previous work, we developed a reproducible method that can provide guidance for local planners in developing more efficient climate impact adaptations. We recommend, however, using the health risk index together with hazard and vulnerability indices to implement tailored programs because exposure to heat and vulnerability do not require the same prevention strategies.
ISSN: 1476-072X

inserm-00762303
http://www.hal.inserm.fr/inserm-00762303
http://www.hal.inserm.fr/inserm-00762303/document
http://www.hal.inserm.fr/inserm-00762303/file/1476-072X-11-38.pdf
DOI : 10.1186/1476-072X-11-38