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International audience; Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4).Methods: Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School.Results: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers.Conclusion: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.

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

In our current multicultural society, the general practitioner is confronted with patients from various geographical origins. The main objective of the study was to describe patients’ expectations concerning the access of the psycho-social field during a consultation according to their cultural origin. A quantitative study was carried out with 200 patients in 2015 in two municipal health care centers in the Ile-de-France region. The expectations of native patients and those belonging to another cultural group were compared by the Chi-square test then by multivariate analysis. Concerning the topics that were already addressed in consultation and those which were desired to be addressed, there was not a statistically significant difference after multivariate analysis between the two groups. Emotional and family life was more often considered as a legitimate subject to broach with the general practitioner by native patients than patients coming from another cultural group [OR=2,79 IC=1,16-7,08]. Sexuality and emotional and family life were more often considered as sensitive subjects by the patients belonging to another cultural group than the native patients with respectively [OR=3,13 IC=1,39-7,34] and [OR=6,02 IC=2,35-168]. The psycho-social field is not much broached during a consultation of general practice and particularly during intercultural consultations while patients, of all origins, would like to broach these subjects. To overcome this discrepancy, doctors should not only focus on the reason for consultation but also be interested in patients’ lifestyle, living hygiene and mental health whatever their cultural origin is.; Dans notre société multiculturelle actuelle, le médecin généraliste est confronté à des patients d’origines géographiques diverses. L’objectif principal de l’étude était de décrire les attentes des patients concernant l’abord du domaine psycho-social lors d’une consultation en fonction de leur origine culturelle. Une étude quantitative a été menée auprès de 200 patients en 2015 dans deux centres municipaux de santé en Ile-de-France. Les attentes des patients natifs et celles appartenant à un autre groupe culturel étaient comparées par test du chi2 puis par analyse multivariée. Concernant les sujets déjà abordés en consultation et ceux souhaités être abordés, il n’y avait pas de différence statistiquement significative après analyse multivariée entre les deux groupes. La vie affective et familiale était plus souvent considérée comme un sujet légitime d’aborder avec le médecin généraliste par les patients natifs que par les patients venant d’un autre groupe culturel [OR=2,79 IC=1,16-7,08]. La sexualité et la vie affective et familiale étaient plus souvent considérées comme des sujets sensibles par les patients appartenant à un autre groupe culturel que par les patients natifs avec respectivement [OR=3,13 IC=1,39-7,34] et [OR=6,02 IC=2,35-168]. Le domaine psycho-social est peu abordé en consultation de médecine générale et surtout lors des consultations interculturelles alors que les patients, toutes origines confondues, souhaitent aborder ces sujets. Pour pallier cette inadéquation, les médecins devraient ne pas s’arrêter au motif de consultation et s’intéresser au mode de vie, à l’hygiène de vie et à la santé mentale des patients, quelle que soit leur origine culturelle.

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; PURPOSE: To describe seizure types and risk factors among elderly people with newly diagnosed epileptic seizures living on La Réunion, a French Island in the Southern Indian Ocean. METHODS: We describe an elderly population with newly diagnosed epileptic seizures using data from the EPIREUN study conducted between July 1, 2004 and June 30, 2005. The methodology is described in detail in the EPIREUN study report (Mignard et al., 2009). KEY FINDINGS: There were 153 single unprovoked seizures (84.1%); their incidence was 278.1 [95% confidence interval (CI) 237.4-325.9] per 100,000. The incidence of newly diagnosed epilepsy was 125.4 (95% CI, 99.1-158.8) per 100,000. Twenty-eight acute symptomatic seizures occurred (15.4%); the incidence was 50.9 (95% CI 35.1-73.7) per 100,000. The annual incidence of newly diagnosed epileptic seizure in the elderly was 330.8 (95% CI 286.1-382.6) per 100,000: 403.0 (95% CI 328.5-494.3) per 100,000 in men and 279.6 (95% CI, 227.4-343.8) per 100,000 in women. Sex had a significant (p = 0.014) effect on incidence: elderly men had a risk ratio of 1.44 compared to women of developing a newly diagnosed epileptic seizure. The etiology of single unprovoked seizure was as follows: stroke, 77 cases (50.3%); cryptogenic, 36 (23.5%); alcoholism, 10 (6.6%); a combination of several causes such as polypathology, 9 (5.9%); degenerative disease, 6 (4.0%); HIV infection, 2 (2.0%), and undetermined causes (2.7%). Most patients (170; 93.4%) were hospitalized, and 110 (60.8%) were treated. Among patients treated, 49 (44.5%) were given sodium valproate, 25 (22.7%) benzodiazepines, 12 (10.9%) phenytoin, 9 (8.2%) lamotrigine, 8 (7.3%) Trileptal, and 7 (6.4%) gabapentin. SIGNIFICANCE: Our findings show that the incidences of newly diagnosed epileptic seizures and newly diagnosed epilepsy were high in the elderly population of La Réunion. These incidences were significantly higher in men than in women. These results may be attributable to the high incidence of cerebrovascular diseases and comorbidities in this population.

International audience; We present an Aboriginal Australian genomic sequence obtained from a 100-year-old lock of hair donated by an Aboriginal man from southern Western Australia in the early 20th century. We detect no evidence of European admixture and estimate contamination levels to be below 0.5%. We show that Aboriginal Australians are descendants of an early human dispersal into eastern Asia, possibly 62,000 to 75,000 years ago. This dispersal is separate from the one that gave rise to modern Asians 25,000 to 38,000 years ago. We also find evidence of gene flow between populations of the two dispersal waves prior to the divergence of Native Americans from modern Asian ancestors. Our findings support the hypothesis that present-day Aboriginal Australians descend from the earliest humans to occupy Australia, likely representing one of the oldest continuous populations outside Africa.

International audience; The aim of the present study is to document the evolution of the lactase persistence trait in Central Asia, a geographical area that is thought to have been a region of long-term pastoralism. Several ethnic groups co-exist in this area: Indo-Iranian speakers who are traditionally agriculturist (Tajik) and Turkic speakers who used to be nomadic herders (Kazakh, Karakalpak, Kyrgyz, Turkmen). It was recently demonstrated that horse milking practice existed in the Botai culture of Kazakhstan as early as 5,500 BP ( Outram et al. 2009 ). However, the frequency of the lactase persistence trait and its genetic basis in Central Asian populations remain largely unknown. We propose here the first genotype-phenotype study of lactase persistence in Central Asia based on 183 individuals, as well as the estimation of the time of expansion of the lactase-persistence associated polymorphism. Our results show a remarkable genetic-phenotypic correlation, with the causal polymorphism being the same than in Europe (-13.910C>T, rs4988235). The lactase persistence trait is at low frequency in these populations: between 25% and 32% in the Kazakh population (traditionally herders), according to phenotype used, and between 11% and 30% in the Tajiko-Uzbek population (agriculturalists). The difference in lactase persistence between populations, even if small, is significant when using individuals concordant for both excretion of breath hydrogen and the lactose tolerance blood glucose test phenotypes (P = 0.018, 25% for Kazakh vs. 11% for Tajiko-Uzbeks), and the difference in frequency of the -13.910*T allele is almost significant (P = 0.06, 30% for Kazakhs vs. 19% for Tajiko-Uzbeks). Using the surrounding haplotype, we estimate a date of expansion of the T allele around 6,000-12,000 yrs ago, which is consistent with archaeological records for the emergence of agropastoralism and pastoralism in Central Asia.

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; The Noir Marron communities are the direct descendants of African slaves brought to the Guianas during the four centuries (16th to 19th) of the Atlantic slave trade. Among them, three major ethnic groups have been studied: the Aluku, the Ndjuka and the Saramaka. Their history led them to share close relationships with Europeans and Amerindians, as largely documented in their cultural records. The study of Gm polymorphisms of immunoglobulins may help to estimate the amount of gene flow linked to these cultural exchanges. Surprisingly, very low levels of European contribution (2.6%) and Amerindian contribution (1.7%) are detected in the Noir Marron gene pool. On the other hand, an African contribution of 95.7% redraws their origin to West Africa (F(ST) < or = 0.15). This highly preserved African gene pool of the Noir Marron is unique in comparison to other African American populations of Latin America, who are notably more admixed.

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.

Udgivelsesdato: January In order to better define the effects of methylmercury (MeHg) exposure on neurodevelopment, qualitative error types observed in the responses of exposed children to the Stanford-Binet Copying Test were categorized and quantified using raw data from two studies of 395 Amazonian children aged 7-12 years (from Brazil and French Guiana). These outcomes were related to hair-mercury concentration as the biomarker of MeHg exposure (range = 0.5-63.8 μg/g). The combined analysis of data from two separate countries had two major goals: (1) to gain clues concerning the underlying neuropathological mechanisms of observed effects based on convergent evidence of MeHg-related qualitative outcomes in the two studies and (2) to explore possible cultural determinants of test response based on divergent outcomes in the two countries. Multiple linear and logistic regression analyses were performed with adjustment for confounders. In the combined data set, mercury exposure was negatively associated with scores on the drawing task: a score reduction of 1.2 (s.e., 0.3) points was observed in the children with a hair-mercury concentration above 10 μg/g compared to those with a hair level below 1 μg/g; this effect appeared to be stronger in the younger children. Risk of committing one or more errors of rotation, simplification or perseveration in the drawings increased with hair-mercury concentration in both cultural settings, providing convergent evidence of specific types of MeHg-related neurocognitive outcomes. However, relationships between mercury exposure and scores on the Block organization component of the test varied according to the study site, indicating that other factors must be considered in evaluating responses to the demands of this cognitive task.

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.

Background The interconversion of two important energy metabolites, 3-hydroxybutyrate and acetoacetate (the major ketone bodies), is catalyzed by D-3-hydroxybutyrate dehydrogenase (BDH1: EC 1.1.1.30), a NAD+-dependent enzyme. The eukaryotic enzyme is bound to the mitochondrial inner membrane and harbors a unique lecithin-dependent activity. Here, we report an advanced purification method of the mammalian BDH applied to the liver enzyme from jerboa (Jaculus orientalis), a hibernating rodent adapted to extreme diet and environmental conditions. Results Purifying BDH from jerboa liver overcomes its low specific activity in mitochondria for further biochemical characterization of the enzyme. This new procedure is based on the use of polyclonal antibodies raised against BDH from bacterial Pseudomonas aeruginosa. This study improves the procedure for purification of both soluble microbial and mammalian membrane-bound BDH. Even though the Jaculus orientalis genome has not yet been sequenced, for the first time a D-3-hydroxybutyrate dehydrogenase cDNA from jerboa was cloned and sequenced. Conclusion This study applies immunoaffinity chromatography to purify BDH, the membrane-bound and lipid-dependent enzyme, as a 31 kDa single polypeptide chain. In addition, bacterial BDH isolation was achieved in a two-step purification procedure, improving the knowledge of an enzyme involved in the lipid metabolism of a unique hibernating mammal. Sequence alignment revealed conserved putative amino acids for possible NAD+ interaction.

International audience; BACKGROUND: This paper discusses the ethical aspects of a large research program in virology, conducted since 1994 and which has evolved in parallel with the elaboration of bioethics laws in France. This research, which involved the collection of a considerable amount of epidemiological data in the field, focused on epidemiological determinants (mother to child transmission, genetic susceptibility/resistance) of the human oncogenic retrovirus human T cell lymphotropic virus type 1 (HTLV-1). Data were collected from a specific population (Noirs Marrons) living in remote areas in French Guiana (South America). This ethnic group of African descent is highly endemic for HTLV-1 and associated adult T cell leukemia/lymphoma. The population has lived for two centuries on either side of the Maroni river, which constitutes the frontier between French Guiana and Surinam. The low socioeconomic and education levels of a large part of this population are mainly explained by a recent housing/residence fixation on the French side of the Maroni river. It is also linked to significant immigration from Surinam due to the civil war, which lasted for five years in the late 1990s, in this country. Conducting epidemiological surveys in this peculiar context illustrates the limitations of the available current legal framework in France for such studies. Indeed, several important ethical issues arose concerning not only individual and population benefits, but also specificities of the given information and of the informed consent. Another question concerns individual information feed-back in such a context of persistent viral infection, with a very low disease incidence, in a population with a relatively low education level. The goal of this work was mainly to report several of the ethical issues encountered and to discuss possible ways of achieving better information deliver and consent procedures in such a context. Indeed, these procedures should include new ideas and regulations promoting a real partnership, in order to conduct long-term epidemiological studies in populations with a low education level.

International audience; BACKGROUND: This paper discusses the ethical aspects of a large research program in virology, conducted since 1994 and which has evolved in parallel with the elaboration of bioethics laws in France. This research, which involved the collection of a considerable amount of epidemiological data in the field, focused on epidemiological determinants (mother to child transmission, genetic susceptibility/resistance) of the human oncogenic retrovirus human T cell lymphotropic virus type 1 (HTLV-1). Data were collected from a specific population (Noirs Marrons) living in remote areas in French Guiana (South America). This ethnic group of African descent is highly endemic for HTLV-1 and associated adult T cell leukemia/lymphoma. The population has lived for two centuries on either side of the Maroni river, which constitutes the frontier between French Guiana and Surinam. The low socioeconomic and education levels of a large part of this population are mainly explained by a recent housing/residence fixation on the French side of the Maroni river. It is also linked to significant immigration from Surinam due to the civil war, which lasted for five years in the late 1990s, in this country. Conducting epidemiological surveys in this peculiar context illustrates the limitations of the available current legal framework in France for such studies. Indeed, several important ethical issues arose concerning not only individual and population benefits, but also specificities of the given information and of the informed consent. Another question concerns individual information feed-back in such a context of persistent viral infection, with a very low disease incidence, in a population with a relatively low education level. The goal of this work was mainly to report several of the ethical issues encountered and to discuss possible ways of achieving better information deliver and consent procedures in such a context. Indeed, these procedures should include new ideas and regulations promoting a real partnership, in order to conduct long-term epidemiological studies in populations with a low education level.

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.

National audience

International audience; The islands of the West Mediterranean have played a central role in numerous archaeological, historical and anthropological studies due to their active participation in the history of main Mediterranean civilisations. However, genetic data failed to fit in both their degree of internal differentiation and relationships. A set of 18 Alu markers and three short tandem repeats (STRs) closely linked to the CD4, F13B and DM Alu have been analysed in seven samples from Majorca, Corsica, Sardinia and Sicily to explore some of these issues. Our samples show a high genetic heterogeneity inside and among islands for the Alu data. Global differentiation among islands (F(ST) 2.2%) is slightly higher than that described for Europeans and North Africans. Both the estimated divergence times among samples and the high population heterogeneity revealed by Alu data are compatible with population differences since the first islands' settlement in the Paleolithic period. However, the high within-population diversities and the remarkable homogeneity observed in both STR and Alu/STR haplotype variation indicated that, at least since Neolithic times, gene flow has been acting in west Mediterranean. Genetic drift in west-coast Sardinia and gene flow in west Sicily have contributed to their general differentiation, whereas Corsica, Majorca and east Sicily seem to reflect more recent historical relationships from continental south Europe.

We read with interest the paper by Mak et al. (1) on asthma in a Hong Kong Chinese population. They reported a protective effect of the catalase (CAT)–262 T allele in non­smoking asthma patients. This result is of importance, as it suggests for the first time a potential role of the CAT–262 polymorphism in the etiology of asthma. At variance with previous publications was the lack of association of erythrocyte catalase activity with the CAT–262 polymorphism within controls and cases. In a cohort of 196 coal miners, we observed lower erythrocyte catalase activities in miners heterozygous and in those homozygous for the CAT–262 T allele, heterozygotes having an intermediate activity (2). Although the difference was not statistically significant, a 28 percent decrease in catalase activity was observed in the non-smoker T carrier controls by Mak et al. (1), similar to the 31 and 33 percent of decrease reported by us (2), and by Ahn et al. (3) in 18 women from a population-based case-control study respectively. As Mak et al. (1) observed a decrease in catalase activity related to CAT–262 polymorphism in non-smokers only, we stratified on smoking status in our coal miner cohort. We found again a significant decrease in catalase activity with the CAT–262 T allele in current and in ex- or non-smokers (see figure), as we found previously in miners with current high and low exposure to coal dust (2), which demonstrates the consistency of the association. The lack of significance of the association in the study by Mak et al. (1) may be due to a low statistical power as 28 subjects were heterozygous and only one was homozygous for the CAT–262 T allele out of the 308 Chinese controls. Figure Catalase activity according to smoking status and to CAT–262 genotype It is interesting to note that Mak et al (1) observed a protective effect of the CAT–262 T allele in non-smoking asthma patients only. Regardless of the disease, an oxidant-rich environment has been found to increase risk only in subjects with the low-activity catalase CAT–262 T allele (4). Factors previously found to be protective, such as an antioxidant-rich dietary environment or a low level of circulating proinflammatory cytokines, seemed to be beneficial only in subjects with the high catalase activity CC genotype (5). Similar to the oxidant-rich environment in our occupational study, asthma may generate reactive oxygen species, and catalase activity significantly increases in asthma patients compared to controls (1). As catalase is involved in the first response to oxidative stimuli, the increase in its activity may be interpreted as a compensatory response to the changes in the oxidant/antioxidant imbalance occuring in asthmatics. In the study of Mak et al. (1), the level of the oxidant state related to asthma may partly mask the a priori deleterious effect of the CAT–262 T allele. Further, the CAT–262 T allele frequency in this Chinese population (1) was five times lower than that observed in Caucasians (mean 26 percent [20–56] from 7 studies), and was similar to the frequency observed in 40 African Americans (6 percent) by Zhou et al. (6). The differences in reported CAT–262 T allele frequency between studies indicates significant variation between populations, and could also partly explain the a priori deleterious effect of the CAT–262 T allele, as patterns of linkage disequilibrium across populations were different. In summary, these results highlight the complexity of the potential role of the CAT–262 polymorphism in the etiology of oxidant-related diseases.

International audience; There are many birthweight reference curves in the literature. This study reviews birthweight curves that are commonly used in France as well as references that provide birthweight by sex. The 19 curves selected for review were published between 1971 and 2001 using samples of between 300 to 3 million newborns in Europe, Australia and North America. Our objective was to summarize their main characteristics and to provide guidelines for analysis by explaining which factors are responsible for differences between curves, and discussing the methods used to construct them. The characteristics of the population must be taken into account and study samples must be recent and representative. The sample size must be sufficient to ensure stable estimates for premature infants. It is preferable to use different curves for boys and girls because sex is a key determinant of birth weight. The choice of appropriate birth weight reference remains difficult in some countries, in France particularly, and the use of individual customised birth weight curves provides an interesting alternative.

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 (