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Background The objective of this study was to assess regional and ethnic differences in an unselected patient population treated with polymer-free sirolimus-eluting stents (PF-SES) in Asia and Europe. Methods Two all-comers observational studies based on the same protocol (ClinicalTrials.gov Identifiers: NCT02629575 and NCT02905214) were combined for data analysis to assure sufficient statistical power. The primary endpoint was the accumulated target lesion revascularization (TLR) rate at 9-12 months. Results Of the total population of 7243 patients, 44.0% (3186) were recruited in the Mediterranean region and 32.0% (2317) in central Europe. The most prominent Asian region was South Korea (17.6%, 1274) followed by Malaysia (5.7%, 413). Major cardiovascular risk factors varied significantly across regions. The overall rates for accumulated TLR and MACE were low with 2.2% (140/6374) and 4.4% (279/6374), respectively. In ACS patients, there were no differences in terms of MACE, TLR, MI and accumulated mortality between the investigated regions. Moreover, dual antiplatelet therapy (DAPT) regimens were substantially longer in Asian countries even in patients with stable coronary artery disease as compared to those in Europe. Conclusions PF-SES angioplasty is associated with low clinical event rates in all regions. Further reductions in clinical event rates seem to be associated with longer DAPT regimens.

International audience; OBJECTIVES:To assess the association between amyotrophic lateral sclerosis (ALS) and previous traumatic events, age of trauma, and site of injury.METHODS:A population-based case-control study was performed in five European countries (Italy, Ireland, France, United Kingdom, Serbia). Newly diagnosed ALS patients and matched controls were interviewed to collect relevant demographic factors and exposures. Key clinical features at diagnosis were collected in ALS patients. Trauma was any accidental event causing an injury. Injuries were dated and classified according to cause, severity, type, site, and complications. All exposures were censored five years before symptoms onset. Risks were computed as odds ratios (OR) with 95% confidence intervals (CI) using univariate and multivariate conditional logistic regression models.RESULTS:Five hundred and seventy-five ALS patients and 1150 controls were interviewed. Disabling traumatic events predominated in the cases (OR 1.54 (95% CI 1.24-1.92)) and maintained significance after adjustment, with a significant gradient. A history of 2 + head injuries was associated with an almost three-fold increased risk of ALS. The risk was almost two-fold when trauma occurred at age 35-54 years. Site of injury was uneventful.CONCLUSIONS:Traumatic events leading to functional disability or confined to the head are risk factors for ALS. Traumatic events experienced at age 35-54 years carry the highest risk.

Summary Purpose Epilepsy is a major clinical and social issue in Africa. This study was conducted to estimate the prevalence, incidence, mortality, and therapeutic outcome in rural Djidja in Benin. Methods This was a two-phase study with a cross-sectional phase and 18 months of follow-up. In the first phase, information was obtained using door-to-door surveys, reports from key informants, and medical sources. People were interviewed using a validated screening questionnaire for epilepsy in tropical regions. The diagnosis of epilepsy was confirmed by a neurologist. We used a capture–recapture method to estimate the number of people with epilepsy (PWE). PWE were followed every month for 18 months after the cross-sectional survey. We asked the health services, the general population, and village leaders in the study area to identify suspected cases of epilepsy occurring during the follow-up. New cases were updated every month after confirmation. Antiepileptic drugs were prescribed to PWE. Key Findings We surveyed 11,668 subjects (male-to-female ratio 0.9) and identified 123 PWE, yielding a prevalence of 10.5 per 1,000 (95% confidence interval (CI) 8.8–12.6/1,000). Combining the three sources, we found 148 PWE and a prevalence of 12.7 per 1,000 (95% CI 10.7–14.9/1,000). After application of the capture–recapture method, the prevalence was estimated to be as high as 38.4 per 1,000 (95% CI 34.9–41.9/1,000). The cumulative incidence was 104.2 per 100,000 and the mean annual incidence was 69.4 per 100,000. The mean annual mortality was 20.8 per 1,000. After treatment, 45% of PWE had total seizure remission and 35% had a decrease in the number of seizures. Significance This study shows that door-to-door survey findings could be improved by using information from other sources. The follow-up suggests that epilepsy could be controlled. Continuous drug delivery and regular follow-up are key.

International audience; OBJECTIVES: To gain insight into early mechanisms of aortic widening, we examined associations between the diameter of the abdominal aorta (AD) and cardiovascular disease (CVD) risk factors and biomarkers, as well as measures of subclinical atherosclerosis, in a multi-ethnic population. DESIGN: Cross-sectional cohort. METHODS: A total of 1926 participants (mean age 62, 50% women) underwent chest and abdomen scanning by computed tomography, ultrasound of the carotid arteries, and CVD risk factor assessment. AD was measured 5 cm above and at the bifurcation. RESULTS: In a model containing traditional CVD risk factors, biomarkers and ethnicity, only age (standardized β = 0.97), male sex (β = 1.88), body surface area (standardized β = 0.92), current smoking (β = 0.42), D-dimer levels (β = 0.19) and hypertension (β = 0.53) were independently and significantly associated with increasing AD (in mm) at the bifurcation; use of cholesterol-lowering medications predicted smaller AD (β = -0.70) (P < 0.01 for all). These findings were similar for AD 5 cm above the bifurcation with one exception: compared to Caucasian-Americans, Americans of Chinese, African and Hispanic descent had significantly smaller AD 5 cm above the bifurcation (β's = -0.59, -0.49, and -0.52, respectively, all P < 0.01), whereas AD at the bifurcation did not differ by ethnicity. Physical activity, alcohol consumption, diabetes and levels of IL-6, CRP and homocysteine were not independently associated with AD. Higher aortic and coronary artery calcium burden, but not common carotid artery intima-media thickness, were independently, but modestly (β = 0.11 to 0.19), associated with larger AD. CONCLUSIONS: Incremental widening of the aortic diameter shared some, but not all, risk factors for occlusive vascular disease.

International audience; OBJECTIVE: Lower-extremity peripheral artery disease (LE-PAD), is strongly related to traditional risk factors (smoking, hypertension, dyslipidemia, diabetes). We hypothesized that the prevalence of LE-PAD in the absence of traditional CVD risk factors is not negligible, and that this condition would remain associated with subclinical atherosclerosis in other territories. METHODS: In the Multi-Ethnic Study of Atherosclerosis, we classified participants without any traditional risk factor according to their ankle-brachial index (ABI) into 3 groups: low (1.30) ABI. Coronary or carotid artery diseases were defined by the presence of any coronary artery calcification (CAC score>0) or carotid plaque, respectively. RESULTS: Among the 6814 participants, 1932 had no traditional risk factors. A low- and high ABI were found in 176 (9%) and 149 (7.8%) cases, respectively. Lower glomerular filtration rate (OR: 0.88/10 units, p=0.04) and higher Interleukin-6 levels (OR: 1.42/natural-log unit, p=0.02) were associated with low ABI. Past smoking (cessation>10 years) and pulse pressure had borderline association with low ABI. In adjusted models, low-ABI was significantly associated with CAC prevalence (OR: 1.22, p

International audience; Melatonin is involved in the regulation of circadian and seasonal rhythms and immune function. Prior research reported low melatonin levels in autism spectrum disorders (ASD). ASMT located in pseudo-autosomal region 1 encodes the last enzyme of the melatonin biosynthesis pathway. A previous study reported an association between ASD and single nucleotide polymorphisms (SNPs) rs4446909 and rs5989681 located in the promoter of ASMT. Furthermore, rare deleterious mutations were identified in a subset of patients. To investigate the association between ASMT and autism, we sequenced all ASMT exons and its neighboring region in 398 Chinese Han individuals with autism and 437 healthy controls. Although our study did not detect significant differences of genotypic distribution and allele frequencies of the common SNPs in ASMT between patients with autism and healthy controls, we identified new rare coding mutations of ASMT. Among these rare variants, 4 were exclusively detected in patients with autism including a stop mutation (p.R115W, p.V166I, p.V179G, and p.W257X). These four coding variants were observed in 6 of 398 (1.51%) patients with autism and none in 437 controls (Chi-Square test, Continuity Correction p = 0.032, two-sided). Functional prediction of impact of amino acid showed that p.R115W might affect protein function. These results indicate that ASMT might be a susceptibility gene for autism. Further studies in larger samples are needed to better understand the degree of variation in this gene as well as to understand the biochemical and clinical impacts of ASMT/melatonin deficiency.

International audience; CONTEXT: Sex steroids play a central role in breast cancer development. OBJECTIVE: This study aimed to relate polymorphic variants in 36 candidate genes in the sex steroid pathway to serum concentrations of sex steroid hormones and SHBG. DESIGN: Data on 700 genetic polymorphisms were combined with existing hormone assays and data on breast cancer incidence, within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nurses' Health Study (NHS) cohorts; significant findings were reanalyzed in the Multiethnic Cohort (MEC). SETTING AND PARTICIPANTS: We analyzed data from a pooled sample of 3852 pre- and postmenopausal Caucasian women from EPIC and NHS and 454 postmenopausal women from MEC. MAIN OUTCOME MEASURES: Outcome measures were SHBG, testosterone, dehydroepiandrosterone (DHEAS), androstenedione, estrone (E1), and estradiol (E2) as well as breast cancer risk. RESULTS: Globally significant associations were found among pre- and postmenopausal women combined between levels of SHBG and the SHBG gene and between DHEAS and the FSHR and AKR1C3 genes. Among postmenopausal women, serum E1 and E2 were significantly associated with the genes CYP19 and FSHR, and E1 was associated with ESR1. None of the variants related to serum hormone levels showed any significant association with breast cancer risk. CONCLUSIONS: We confirmed associations between serum levels of SHBG and the SHBG gene and of E1 and E2 and the CYP19 and ESR1 genes. Novel associations were observed between FSHR and DHEAS, E1, and E2 and between AKR1C3 and DHEAS.

The BRCA1 mutation c.5266dupC was originally described as a founder mutation in the Ashkenazi Jewish (AJ) population. However, this mutation is also present at appreciable frequency in several European countries, which raises intriguing questions about the origins of the mutation. We genotyped 245 carrier families from 14 different population groups (Russian, Latvian, Ukrainian, Czech, Slovak, Polish, Danish, Dutch, French, German, Italian, Greek, Brazilian and AJ) for seven microsatellite markers and confirmed that all mutation carriers share a common haplotype from a single founder individual. Using a maximum likelihood method that allows for both recombination and mutational events of marker loci, we estimated that the mutation arose some 1800 years ago in either Scandinavia or what is now northern Russia and subsequently spread to the various populations we genotyped during the following centuries, including the AJ population. Age estimates and the molecular evolution profile of the most common linked haplotype in the carrier populations studied further suggest that c.5266dupC likely entered the AJ gene pool in Poland approximately 400-500 years ago. Our results illustrate that (1) BRCA1 c.5266dupC originated from a single common ancestor and was a common European mutation long before becoming an AJ founder mutation and (2) the mutation is likely present in many additional European countries where genetic screening of BRCA1 may not yet be common practice.European Journal of Human Genetics advance online publication, 1 December 2010; doi:10.1038/ejhg.2010.203.

Background: Data on dementia from low- and middle-income countries are still necessary to quantify the burden of this condition. This multicenter cross-sectional study aimed at estimating the prevalence of dementia in 2 large cities of Central Africa. Methods: General population door-to-door surveys were conducted in the districts of Bangui (Republic of Central Africa) and Brazzaville (Congo) in elderly aged ≧65 years. The subjects were screened with the Community Screening Interview for Dementia and the Five-Words Test. Diagnosis of dementia was made according to the DSM-IV criteria and to the clinical criteria proposed by the NINCDS-ADRDA for Alzheimer’s disease. Results: We enrolled 496 subjects in Bangui and 520 in Brazzaville. The prevalence of dementia was estimated at 8.1% (95% CI = 5.8–10.8) in Bangui and 6.7% (95% CI = 4.7–9.2) in Brazzaville. Conclusion: The prevalence of dementia in urban areas of Central Africa is close to those observed in high-income countries.

7 pages; International audience; Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson's disease (PD) and in sporadic cases; the G2019S mutation is the single most frequent. Intriguingly, the frequency of this mutation in PD patients varies greatly among ethnic groups and geographic origins: it is present at

International audience; BACKGROUND: Obesity is related to asthma, but factors influencing this relation have not been clearly defined. OBJECTIVE: This study was designed to assess the role of eating behaviors and weight concerns in the association between obesity and asthma. DESIGN: A population-based sample of 11,710 adolescents, recruited from 186 secondary schools of 8 educational districts in France, completed a self-administered standardized questionnaire including DSM IV (Diagnostic and Statistical Manual of Mental Disorders) questions on eating disorders. RESULTS: Obesity (body mass index >/=95th percentile according to age and sex) was associated with asthma in girls (odds ratio: 1.48; 95% CI: 1.05, 2.08) but not in boys (odds ratio: 1.07; 95% CI: 0.75, 1.54). Both obese and asthmatic adolescents were more likely to have abnormal eating behaviors and weight concerns (P < 0.05). In an adjusted polytomous logistic model with 4 categories based on the presence and/or the absence of asthma and obesity as the dependent variable, the odds ratio for weight concerns increased from a minimum value for asthmatic nonobese adolescents (odds ratio: 6.3; P < 0.001) with nonasthmatic, nonobese adolescents as the reference group. Similar patterns were observed for overweight. CONCLUSIONS: Our data suggest that, besides well-known factors such as genetic background, direct mechanical effects, and reduced physical activity, abnormal eating behaviors and weight concerns might intervene in the relation between obesity and asthma. Psychosocial dimension has to be considered to disentangle the complex relation between obesity and asthma in adolescence in view of prevention.

International audience; A search for human T lymphotropic virus (HTLV) types 1 and 2 and related viruses was performed by serological and molecular means on samples obtained from 421 adult villagers from the southern Cameroon forest areas. One individual (a 56-year-old Baka Pygmy hunter) was found to be HTLV-3 infected; however, there was a low proviral load in blood cells. Complete sequence analysis of this virus (HTLV-3Lobak18) indicated a close relationship to human HTLV-3Pyl43 and simian STLV-3CTO604 strains. Plasma samples from Lobak18, the HTLV-3 infected individual, exhibited a peculiar "HTLV-2-like" pattern on Western blot analysis and were serologically untypeable by line immunoassay. These results were different from those for the 2 previously reported HTLV-3 strains, raising questions about serological confirmation of infection with such retroviruses.

International audience; BACKGROUND: Initiation of antiretroviral therapy during primary human immunodeficiency virus (HIV)-1 infection may confer long-term benefit. METHODS: After initiation of zidovudine, lamivudine, abacavir, and amprenavir therapy in patients in the QUEST cohort, predictors of virological outcome, virological and immunological changes, and adverse events were evaluated over 48 weeks. RESULTS: One hundred forty-eight patients started antiretroviral therapy during primary HIV-1 infection with < or =3 bands on Western Blot (median plasma HIV-1 RNA load, 5.4 log copies/mL; median CD4 cell count, 517 cells/mm(3)). By week 48, 36% of patients had stopped treatment or were lost to follow-up. Among the 115 patients receiving follow-up care at week 48 (102 of whom were receiving antiretroviral therapy), the median viral load decrease was -5.4 log copies/mL (interquartile range [IQR], -6.4 to -3.9 log copies/mL), and the median increase in CD4 cell count was 147 cells/mm(3) (IQR, -1 to 283 cells/mm(3)); 84.2% of patients had a viral load < or =50 copies/mL, and 44.7% of patients had a viral load < or =3 copies/mL. The median cell-associated RNA level decreased from 3.4 log copies/million PBMCs (IQR, 2.9-4.1 log copies/million PBMCs) to 0.8 log copies/million PBMCs (IQR, 0.5-1.4 log copies/million PBMCs), and the median cell-associated DNA level decreased from 2.8 log copies/million PBMCs (IQR, 2.4-3.0 log copies/million PBMCs) to 1.6 log copies/million PBMCs (IQR, 1.2-1.9 log copies/million PBMCs); 33.3% of patients had an undetectable RNA level, and 9.5% of patients had an undetectable cell-associated DNA level. The median CD8(+)/CD38(++) T cell count decreased from 459 cells/mm(3) (IQR, 208-974 cells/mm(3)) to 33 cells/mm(3) (IQR, 19-75 cells/mm(3)). Baseline CD8(+)/CD38(++) T cell count and cell-associated DNA level were independent inverse predictors for reaching a viral load < or =3 copies/mL. Eighty-three patients experienced a serious adverse event (median duration of an adverse event, 15 days).Conclusions. Initiation of antiretroviral therapy during primary HIV-1 infection was associated with very significant antiretroviral activity and a decrease in immune activation. Lower baseline CD8(+)/CD38(++) T cell count and cell-associated DNA level were predictive of achieving a viral load < or =3 copies/mL.

Summary: Purpose: A case-control study to assess the relationship between epilepsy and toxocariasis was carried out in the Kiremba population, Burundi. Methods: People with epilepsy (PWE) were diagnosed according to the definition proposed by the International League Against Epilepsy (ILAE). Seizures were classified according to the classification proposed by ILAE in 1981. One control per case was selected matched by age (±5 years). Control subjects also lived in Kiremba, had neither neurological disorders nor kinship with the PWE. Cases and controls were assessed serologically for antibodies against Toxocara canis by an immunoblotting assay. Odds ratios (ORs) and 95% CI were determined using conditional regression analysis for matched case-control study. Results: One hundred ninety-one PWE (99 men and 92 women) and 191 age-matched controls (72 men and 112 women) were enrolled in the study. Of the 191 PWE, 113 presented partial seizures while 73 generalized seizures and five were unclassifiable. Antibodies anti T. canis were found in 114 PWE (59.7%) and in 97 controls (50.8%). Multivariate analysis (conditional logistic regression) showed a significant association between positivity for T canis and epilepsy with an adjusted OR of 2.13 (95% CI 1.18–3.83; p-value 0.01). Conclusions: We found a significant association between toxocariasis and epilepsy. In agreement with a previous study, our finding suggests that toxocariasis may increase the risk of developing epilepsy in endemic areas and could participate to the high burden of epilepsy in tropical areas.

To evaluate the reproductive outcome after ectopic pregnancy and to assess the contribution of risk factors to future fertility., Cumulative pregnancy rate.

International audience; Erythropoietic protoporphyria (EPP) is an inherited disorder of heme biosynthesis that results from a partial deficiency of ferrochelatase (FECH). Recently, we have shown that the inheritance of the common hypomorphic IVS3-48C allele trans to a deleterious mutation reduces FECH activity to below a critical threshold and accounts for the photosensitivity seen in patients. Rare cases of autosomal recessive inheritance have been reported. We studied a cohort of 173 white French EPP families and a group of 360 unrelated healthy subjects from four ethnic groups. The prevalences of the recessive and dominant autosomal forms of EPP are 4% (95% confidence interval 1-8) and 95% (95% confidence interval 91-99), respectively. In 97.9% of dominant cases, an IVS3-48C allele is co-inherited with the deleterious mutation. The frequency of the IVS3-48C allele differs widely in the Japanese (43%), southeast Asian (31%), white French (11%), North African (2.7%), and black West African (