GENETICS OF LARGE PIGMENT EPITHELIAL DETACHMENTS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: We hypothesized that severe forms of neovascular age-related macular degeneration (AMD) such as large pigment epithelial detachments poorly responding to anti-vascular endothelial growth factor therapy might present a distinct genotype compared with overall series of neovascular AMD. METHODS: This is a multicenter genetic association study. Sixty-eight patients presenting pigment epithelial detachments resistant to ranibizumab (issued from ARI2 study, register number NCT02157077 on clinicaltrials.gov) were compared with two series of patients derived from previously published clinical studies, presenting neovascular AMD (NAT2 study n = 300 and PHRC study n = 1,127), and with healthy controls (n = 441). The phenotype of neovascular AMD groups was based on visual acuity measurement, fundus examination, spectral-domain optical coherence tomography, and angiographic data. All samples were genotyped for three single-nucleotide polymorphisms: CFH (rs1061170), ARMS2 (rs10490924), and C3 (rs2230199). Significant difference in allele frequency between participants with neovascular AMD and control was the main outcome measurement. RESULTS: The GG genotype of the C3 rs2230199 was significantly more frequent in the ARI2 group (55.9%) than the PHRC group (6.0%, P < 0.0001; odds ratio = 24.0 [95% confidence interval 10.4-55.0]) and the NAT2 group (5.1%, P < 0.0001; odds ratio = 16.1 [95% confidence interval 5.0-51.9]). The repartition of patients carrying a T allele of the ARMS2 (rs10490924) or patients carrying a C allele of the CFH (rs1061170) was similar in the ARI2 group when compared with the NAT2 and PHRC groups. CONCLUSION: In our series, the genotype GG of C3 rs2230199 was more significantly associated with the phenotype of large vascularized pigment epithelial detachment poorly responding to anti-vascular endothelial growth factor therapy than in global AMD series.

Anemia management in non-menopausal women in a primary care setting: a prospective evaluation of clinical practice.

BACKGROUND: The study aimed to analyze anemia management in non-pregnant, and non-menopausal women aged from 18 to 50 years old, in a French primary care setting. METHODS: An observational descriptive prospective study was conducted between November 2018 and February 2019. Inclusion criteria were as followed: anemia diagnosed in women aged from 18 to 50, not pregnant and not menopausal. Quantitative and qualitative data were anonymized and collected through an electronic survey. Investigating general practitioners completed the questionnaire for each newly diagnosed woman. Mean values and medians were calculated for the quantitative data. Answers to the open questions were encoded manually and proportions of the different modalities have been calculated. RESULTS: Altogether, 43 women with anemia were ascertained. Moderate microcytic anemia, due to an iron deficiency in a context of menorrhagia, was the most observed anemia profile. The mean value of hemoglobin was 10.5 ± 1 g/dl. Among these women: 32 (74%) presented an iron deficiency, 17 (53%) had inappropriate intakes, and 9 (28%) reported menorrhagia. For 17 (40%) women, unnecessary or inappropriate exams were prescribed. The investigations did not allow to establish a differential diagnosis for 12 women (28%). Even for similar clinical situations, anemia management was variable. Among the women who presented iron deficiency, 15 (47%) were informed about an iron-rich diet and received a daily iron supplementation of ferrous sulfate between 80 mg and 160 mg. CONCLUSIONS: Our study highlights that, in the absence of specific national guidelines for anemia management in non-pregnant, non-menopausal women in primary care settings, French GPs undergo various clinical management strategies leading to a heterogeneous, sometimes inappropriate follow-up. Women with iron deficiency were prescribed higher daily iron supplementation than recommended, according to new evidence, suggesting a maximal daily dose of 50 mg of elementary iron in a context of Hepcidin up-regulation in the case of an iron overload. Additional longitudinal studies with a bigger sample size and randomized controlled trials are needed to confirm our results and to elaborate national guidelines.

Compared characteristics of current vs. past smokers at the time of diagnosis of a first-time lung or head and neck cancer: a cross-sectional study.

BACKGROUND: Active smoking at the time of diagnosis of a first head & neck (H&N) or lung cancer is associated with a worse cancer outcome and increased mortality. However, the compared characteristics of active vs. former smokers at cancer diagnosis are poorly known. METHODS: In 371 subjects with a first H&N or lung cancer, we assessed: 1) socio-demographic features; 2) lifelong types of smoking; 3) alcohol use disorder identification test (AUDIT); 4) cannabis abuse screening test (CAST); and 5) Mini International Neuropsychiatric Interview (MINI). Using a multivariable regression model, we compared the profile of current smokers and past smokers. RESULTS: Current smokers more frequently exhibited H&N cancer (OR 3.91; 95% CI [2.00-6.51]; p <  0.0001) and ever smoking of hand-rolled cigarettes (OR 2.2; 95% CI [1.25-3.88]; p = 0.007). Among subjects with lung cancer (n = 177), current smoking was primarily associated with ever smoking of hand-rolled cigarettes (OR 2.88; 95% CI [1.32-6.30]; p = 0.008) and negatively associated with age (OR 0.92; 95% CI [0.89-0.96]; p <  0.001). Among subjects with H&N cancer (n = 163), current smokers exhibited a significantly greater AUDIT score (OR = 1.08; 95% CI [1.01-1.16]; p = 0.03). CONCLUSION: At the time of diagnosis of the first lung or H&N cancer, current smoking is highly associated with previous type of smoking and alcohol drinking patterns. TRIAL REGISTRATION: NCT01647425 ; Registration date: July 23, 2012.

Karyotype diversity suggests that Laonastes aenigmamus (Laotian rock rat) (Rodentia, Diatomyidae) is a multi-specific genus.

Laonastes aenigmamus (Khanyou) is a recently described rodent species living in geographically separated limestone formations of the Khammuan Province in Lao PDR. Chromosomes of 21 specimens of L. aenigmamus were studied using chromosome banding as well as fluorescent in situ hybridization (FISH) techniques using human painting, telomere repeats, and 28S rDNA probes. Four different karyotypes were established. Study with human chromosome paints and FISH revealed that four large chromosomes were formed by multiple common tandem fusions, with persistence of some interstitial telomeres. The rearrangements separating the different karyotypes (I to IV) were also reconstructed. Various combinations of Robertsonian translocations or tandem fusions involving the same chromosomes differentiate these karyotypes. These rearrangements create a strong gametic barrier, which isolates specimens with karyotype II from the others. C-banding and FISH with telomere repeats also exhibit large and systematized differences between karyotype II and others. These data indicate an ancient reproductive separation and suggest that Laonastes is not a mono-specific genus.

Diversity and distribution of alpha satellite DNA in the genome of an Old World monkey: Cercopithecus solatus.

BACKGROUND: Alpha satellite is the major repeated DNA element of primate centromeres. Evolution of these tandemly repeated sequences has led to the existence of numerous families of monomers exhibiting specific organizational patterns. The limited amount of information available in non-human primates is a restriction to the understanding of the evolutionary dynamics of alpha satellite DNA. RESULTS: We carried out the targeted high-throughput sequencing of alpha satellite monomers and dimers from the Cercopithecus solatus genome, an Old World monkey from the Cercopithecini tribe. Computational approaches were used to infer the existence of sequence families and to study how these families are organized with respect to each other. While previous studies had suggested that alpha satellites in Old World monkeys were poorly diversified, our analysis provides evidence for the existence of at least four distinct families of sequences within the studied species and of higher order organizational patterns. Fluorescence in situ hybridization using oligonucleotide probes that are able to target each family in a specific way showed that the different families had distinct distributions on chromosomes and were not homogeneously distributed between chromosomes. CONCLUSIONS: Our new approach provides an unprecedented and comprehensive view of the diversity and organization of alpha satellites in a species outside the hominoid group. We consider these data with respect to previously known alpha satellite families and to potential mechanisms for satellite DNA evolution. Applying this approach to other species will open new perspectives regarding the integration of satellite DNA into comparative genomic and cytogenetic studies.

Improvement of the initial management of sarcomas after the dissemination of evidence-based guidelines depends on the primary sarcoma location: a population-based study.

BACKGROUND: Improvement of the initial management of sarcomas after the dissemination of evidence-based guidelines depends on the primary sarcoma location: a population-based study. To improve the initial management of adult sarcomas, a regional expert team in Northern France performed two actions: dissemination of evidence-based guidelines (EBG) for the management of soft tissue/visceral sarcoma and yearly educational symposia. The aim of this study was to measure the impact of the dissemination of EBG on the key-indicators of adult sarcoma management. METHODS: We conducted a before-after population-based study (before: 2005 with 63 cases, after: 2008-2009 with 86 cases) in the Lille area (Northern France urban/sub-urban area with 800,000 inhabitants). The following were the key-indicators of adult sarcoma management: pre-therapeutic biopsy, appropriate tumour and chest imaging, expert interdisciplinary discussion, expert interdisciplinary discussion before the first treatment and in operated cases, the rate of R0 resection. RESULTS: There was no statistically significant difference in patient and tumour characteristics for the two time periods in terms of gender, prior cancer, primary location, histological subtype, grade, size, metastasis and lymph node involvement. There was no statistically significant improvement in primary tumour imaging (83 versus 87%), chest imaging (67 vs 71%), pre-therapeutic biopsy (57 vs 58%). There was an improvement in expert multidisciplinary discussion (37 vs 45%) or discussion before the first treatment (26 vs 44%) but no statistically significant. However, when soft tissue and bone sarcomas were analysed separately, we observed statistically significant improvements in expert multidisciplinary discussion (50 vs 74%, p = 0.02) and R0 resection rate (58 vs 91%, p = 0.002). In contrast, in cases of visceral sarcoma, there was no improvement in expert multidisciplinary discussion (10 vs 16%, p = 0.7) or in R0 resection (88 vs 81%, p = 0.7). CONCLUSIONS: The dissemination of EBG was associated with a limited improvement in sarcoma management when measured in this before-after population-based study, and this improvement was dependent on the primary location of the tumour. Efforts to implement these guidelines by all surgical teams that could treat sarcoma, including visceral sarcoma, need to be made.

Treatment of sleep apnoea syndrome decreases cognitive decline in patients with Alzheimer's disease.

BACKGROUND: It is essential to detect and then treat factors that aggravate Alzheimer's disease (AD). Here, we sought to determine whether or not continuous positive airway pressure (CPAP) therapy for sleep apnoea syndrome (SAS) slows the rate of cognitive decline in mild-to-moderate AD patients. METHODS: Between January 2003 and June 2011, we included consecutive, mild-to-moderate AD patients (a Mini Mental State Examination (MMSE) score at inclusion ≥15) with severe SAS as determined by video-polysomnography (an apnoea-hypopnoea index ≥30). In this single-blind, proof-of-concept trial, we analysed the mean decline in the annual MMSE score (the main outcome measure) according to whether or not the patients had received CPAP therapy. The decline was computed for each patient and for the first 3 years of follow-up. RESULTS: Of the 23 included patients, 14 underwent CPAP treatment. The CPAP and non-CPAP groups did not differ significantly in terms of their demographic characteristics or MMSE score at baseline. The median annual MMSE decline was significantly slower in the CPAP group (-0.7 (-1.7; +0.8)) than in the non-CPAP group (-2.2 (-3.3; -1.9); p=0.013). CONCLUSIONS: In this pilot study, CPAP treatment of severe SAS in mild-to-moderate AD patients was associated with significantly slower cognitive decline over a three-year follow-up period. Our results emphasise the importance of detecting and treating SAS in this population.

Influence of chronic ethanol consumption on the neurological severity in patients with acute cerebral ischemia.

BACKGROUND AND PURPOSE: We tested the hypothesis that excessive chronic ethanol consumption is associated with more severe ischemic strokes. METHODS: We recruited patients with supratentorial cerebral ischemia within 48 hours of symptom onset. We defined heavy drinkers by a weekly consumption of ethanol of ≥300 g and severe strokes by a National Institutes of Health Stroke Scale score≥6. RESULTS: Of 436 patients, 60 were heavy drinkers. Being a heavy drinker was independently associated with baseline National Institutes of Health Stroke Scale scores≥6 (odds ratio, 2.35; 95% confidence interval, 1.12-5.26; P=0.023) at the logistic regression analysis. This result was not modified with the propensity analysis. CONCLUSION: An excessive chronic ethanol consumption is associated with higher baseline stroke severity.

Association between caffeine intake and age at onset in Huntington's disease.

Habitual consumption of caffeine, a non-selective adenosine receptor (AR) antagonist, has been suggested to be beneficial in Parkinson's and Alzheimer's diseases. Experimental evidence support that ARs play a role in Huntington's disease (HD) raising the hypothesis that caffeine may be a life-style modifier in HD. To determine a possible relationship between caffeine consumption and age at onset (AAO) in HD, we retrospectively assessed caffeine consumption in 80 HD patients using a dietary survey and determined relationship with AAO. Following adjustment for gender, smoking status and CAG repeat length, caffeine consumption greater than 190mg/day was significantly associated with an earlier AAO. These data support an association between habitual caffeine intake and AAO in HD patients, but further studies are warranted to understand the link between these variables.

Genetic association study of mitochondrial polymorphisms in neovascular age-related macular degeneration.

PURPOSE: Age-related macular degeneration (AMD) is a multifactorial disease involving genetic and environmental factors. Most of the genetic factors identified so far involve the nuclear genome. Recently, two studies in North America and Australia reported an association between advanced AMD and the mitochondrial T2 haplogroup. Our purpose was to assess this association in a large French population. METHODS: This case control study included 1,224 patients with neovascular AMD and 559 controls with normal fundus. Mitochondrial DNA polymorphisms at and around nucleotides 4917, 11,812, and 14,233 were determined using PCR amplification and direct sequencing of mitochondrial DNA. RESULTS: No association was found between the mitochondrial T2 haplogroup and neovascular AMD in the French population: 94/1,152 patients with neovascular AMD had the T2 haplogroup (8.2%) versus 34/482 controls (7.1%; odds ratio=0.9 [0.5-1.5], p=0.66). CONCLUSIONS: An association between AMD and the T2 haplogroup, previously described in North American and Australian populations, was not confirmed in a large French population.

Genetic and environmental factors associated with reticular pseudodrusen in age-related macular degeneration.

PURPOSE: To analyze the genetic and environmental factors associated with reticular pseudodrusen (RPD) in age-related macular degeneration (AMD). METHODS: In a large population, AMD patients (n = 519) with and without RPD were assessed with a standardized examination including infrared images and spectral domain optical coherence tomography scans. Three groups were defined: Group 1: AMD patients with RPD (n = 105); Group 2: AMD patients without RPD (n = 414); and Group 3: controls with no AMD and no RPD (n = 430). Four genes associated with AMD (CFH, ARMS2/HTRA1, C3, apolipoprotein E) and environmental factors were assessed between the 3 groups. RESULTS: None of the environmental factors studied were more significantly associated to either Group 1 or Group 2. The odds ratios and 95% confidence intervals for individuals homozygous for the CFH risk allele were 4.0 (2.1-7.7) ([95% confidence interval: 2.1-7.7]; P < 0.0004) in Group 1 and 4.3 ([2.6-7.1]; P < 0.0004) in Group 2, compared with Group 3. The odds ratios for individuals homozygous for the ARMS2 risk allele for Groups 1 and 2 compared with Group 3 were 16.3 ([7.6-35.4]; P < 0.0004) and 11.9 ([6.3-22.3]; P < 0.0004), respectively. None of the genotypes studied were more significantly associated to Group 1 than Group 2. CONCLUSION: Genotypes known to be associated with AMD were similarly observed in patients with and without RPD.

Aldosterone, mortality, and acute ischaemic events in coronary artery disease patients outside the setting of acute myocardial infarction or heart failure.

BACKGROUND: Recent studies have demonstrated that aldosterone levels measured in patients with heart failure or acute myocardial infarction (MI) are associated with long-term mortality, but the association with aldosterone levels in patients with coronary artery disease (CAD) outside these specific settings remains unknown. In addition, no clear mechanism has been elucidated to explain these observations. The present study was designed to evaluate the relationship between the level of aldosterone and the risk of death and acute ischaemic events in CAD patients with a preserved left ventricular (LV) function and no acute MI. METHODS AND RESULTS: In 799 consecutive CAD patients referred for elective coronary angioplasty measurements were obtained before the procedure for: aldosterone (median = 25 pg/mL), brain natriuretic peptide (BNP) (median = 35 pg/mL), hsC-reactive protein (median = 4.17 mg/L), and left ventricular ejection fraction (mean = 58%). Patients with acute MI or coronary syndrome (ACS) who required urgent revascularization were not included in the study. The primary endpoint, cardiovascular death, occurred in 41 patients during a median follow-up period of 14.9 months. Secondary endpoints-total mortality, acute ischaemic events (acute MI or ischaemic stroke), and the composite of death and acute ischaemic events-were observed in 52, 54, and 94 patients, respectively. Plasma aldosterone was found to be related to BMI, hypertension and NYHA class, and inversely related to age, creatinine clearance, and use of beta-blockers. Multivariate Cox model analysis demonstrated that aldosterone was independently associated with cardiovascular mortality (P = 0.001), total mortality (P = 0.001), acute ischaemic events (P = 0.01), and the composite of death and acute ischaemic events (P = 0.004). Reclassification analysis, using integrated discrimination improvement (IDI) and net reclassification improvement (NRI), demonstrated incremental predictive value of aldosterone (P < 0.0001). CONCLUSION: Our results demonstrate that, in patients with CAD but without heart failure or acute MI, the level of aldosterone is strongly and independently associated with mortality and the occurrence of acute ischaemic events.

Modifying effect of arterial hypertension on amyotrophic lateral sclerosis.

Given the high oxygen consumption of motor neurons, we sought to assess the frequency and prognostic value of arterial hypertension (affecting brain's oxygen supply) in amyotrophic lateral sclerosis (ALS). We consecutively and prospectively included all ALS patients with regular medical follow-up and documented blood pressure measurements and monitored them until death. Vascular factors diagnosed prior to the onset of motor signs in ALS patients were compared with those in a stratified, age- and gender-matched case-control population. The severity of leukoaraiosis on magnetic resonance imaging (MRI) was blindly assessed. Post mortem examinations were performed when authorized. Compared with controls (n = 408), the 102 ALS patients were significantly more likely to display hypertension (41-57%) and current smoking (15-26%). The number of years of hypertension was associated with survival (HR = 1.04 (1.01-1.07)). In a multivariate analysis, leukoaraiosis severity (HR = 1.214 (1.096-1.344)), current smoking (HR = 1.766 (1.085-2.872)) and low vital capacity (HR = 2.422 (1.266-4.633)) remained independent predictors of survival. Post mortem examinations revealed a greater frequency of leukoaraiosis in ALS patients (p = 0.02). In conclusion, the effect of chronic hypertension on survival might be exerted through abnormal neural perfusion. The higher frequency of recent hypertension in ALS patients may be due to a compensatory increase in blood pressure in response to a lower oxygen supply.

Three-Dimensional Printing Model Enhances Craniofacial Trauma Teaching by Improving Morphologic and Biomechanical Understanding: A Randomized Controlled Study.

BACKGROUND: Teaching about craniofacial traumas is challenging given the complexity of the craniofacial anatomy and the necessity for good spatial representation skills. To solve these problems, three-dimensional printing seems to be an appropriate educative material. In this study, the authors conducted a randomized controlled trial. The authors' main objective was to compare the performance of the undergraduate medical students in an examination based on the teaching support: three-dimensionally printed models versus two-dimensional pictures. METHODS: All participants were randomly assigned to one of two groups using a random number table: the three-dimensionally-printed support group (three-dimensional group) or the two-dimensionally-displayed support group (two-dimensional group). All participants completed a multiple-choice question evaluation questionnaire on facial traumatology (first, a zygomatic bone fracture; then, a double mandible fracture). Sex and potential confounding factors were evaluated. RESULTS: Four hundred thirty-two fifth-year undergraduate medical students were enrolled in this study. Two hundred six students were allocated to the three-dimensional group, and 226 were allocated to the two-dimensional group. The three-dimensionally printed model was considered to be a better teaching material compared with two-dimensional support. The global mean score was 2.36 in the three-dimensional group versus 1.99 in the two-dimensional group (p = 0.008). Regarding teaching of biomechanical aspects, three-dimensionally-printed models provide better understanding (p = 0.015). Participants in both groups exhibited similar previous student educational achievements and visuospatial skills. CONCLUSIONS: This prospective, randomized, controlled educational trial demonstrated that incorporation of three-dimensionally-printed models improves medical students' understanding. This trial reinforces previous studies highlighting academic benefits in using three-dimensionally-printed models mostly in the field of understanding complex structures.

No association between the T280M polymorphism of the CX3CR1 gene and exudative AMD.

Major genetic factors for age-related macular degeneration (AMD) have recently been identified as susceptibility risk factors. The CX3CR1 gene has been shown to be associated with AMD in some studies. Our purpose was to analyze the role of the T280M polymorphism of the CX3CR1 gene in a large French population, in a case-control study. 1093 patients with exudative AMD and 396 controls have been recruited and genotyped for the Y402H of CFH, rs10490924 of ARMS2 and T280M of the CX3CR1 gene. The distribution of the Y402H of CFH and of the rs10490924 of ARMS2 was significantly different between cases and controls (p < 0.0001). The distribution of the T280M genotypes was not significantly different in the AMD patients compared to controls (p = 0.99). The Odds Ratio compared to TT individuals was 1.0 (95% CI 0.8-1.3) for TM individuals and 1.0 (95% CI 0.5-2.1) for MM individuals. The M allele frequency was 0.157 in cases and 0.154 in controls (p = 0.87). Our study exclude an association between the T280M of the CX3CR1 gene and exudative AMD in a French population.

R102G polymorphism of the C3 gene associated with exudative age-related macular degeneration in a French population.

PURPOSE: Major genetic factors for age-related macular degeneration (AMD) have recently been identified as susceptibility risk factors, underlying the role of the complement pathway in AMD. Our purpose was to analyze the role of the R102G polymorphism of the complement component (C3) gene in a French population, in a case-control study. METHODS: A total of 1,080 patients with exudative AMD and 406 controls were recruited and genotyped for Y402H of complement factor H (CFH), rs10490924 of age-related maculopathy susceptibility 2 (ARMS2), and R102G of the C3 gene. RESULTS: The distribution of the R102G genotypes was significantly different in the AMD patients compared to controls (p=0.02). The Odds Ratio compared to C/C individuals was 1.4 (95% CI 1.1-1.8) for C/G individuals and 1.4 (95% CI 0.8-2.4) for G/G individuals. In a dominant model, the adjusted Odds Ratio for carriers of the G allele is 1.4 (95% CI 1.0-1.9; p=0.03). CONCLUSIONS: Our study shows C3 to be a moderate susceptibility gene for exudative AMD in the French population.

Metabolic syndrome and collateral vessel formation in patients with documented occluded coronary arteries: association with hyperglycaemia, insulin-resistance, adiponectin and plasminogen activator inhibitor-1.

AIMS: The metabolic syndrome (MS) is associated with an increased cardiovascular risk. Patients with the MS have endothelial dysfunction, decreased circulating adiponectin, and a high expression of angiogenic inhibitors such as plasminogen activator inhibitor-1 (PAI-1). We hypothesized that such patients, in the event of a coronary occlusion, might exhibit a less developed collateral circulation. METHODS AND RESULTS: Three hundred and eighty-seven consecutive patients with at least one coronary occlusion of a major coronary vessel at diagnostic angiography were prospectively enrolled. Collateral development was graded with validated angiographic methods. The MS was defined according to the ATP-III definition. Fasting glucose, adiponectin, insulin concentrations, and PAI-1 were measured at the time of angiography. MS was associated with less developed collateral vessels (P = 0.005). In multivariable analysis adjusting for potential confounding factors including the duration of coronary occlusion (P = 0.0001), fasting glycaemia (P = 0.0007), low adiponectin concentration (P = 0.01), insulin-resistance (HOMA-IR; P = 0.01), high circulating PAI-1 concentration (P = 0.01), and hypertension (P = 0.008) were independently associated with poor coronary collateral vessel development. CONCLUSION: This study shows that in patients with coronary occlusion, collateral circulation is impaired in patients with the MS. This association is partly related to fasting glycaemia and to key parameters linked to insulin resistance.

Twenty-year trends in patient referrals throughout the creation and development of a regional memory clinic network.

INTRODUCTION: Memory clinics (MCs) are the main model for dementia diagnosis and care. Following the development of a MC network in Northern France, our objectives were to assess its impact on patient characteristics over 20 years. METHODS: The characteristics of new consultants were studied from 1997 to 2016. RESULTS: New consultants increased from 774 per year in 1997 to 26258 per year in 2016, as the number of MCs increased from 12 to 29. Over time, patients were progressively older and less educated, and more were living alone. A greater proportion of patients were referred by specialists. Referral delay and home-to-MC distance kept decreasing. The oldest patients were referred at a progressively less-severe stage. The proportion of young patients kept increasing in the tertiary referral center. DISCUSSIONS: The development of a region-wide MC network led to increased referral of vulnerable patients and differentiation of the tertiary referral center over time.

A possible role for the PPARG Pro12Ala polymorphism in preterm birth.

The links between preterm birth, low birth weight, and adult vascular/metabolic morbidity remain unclear. Genetic susceptibility of babies related to these three conditions might contribute to this long-term association. We tested whether the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma (PPARG) gene could play a role in birth weight and duration of gestation. We genotyped two independent cross-sectional studies from Northern Ireland (n = 382 and 620). In combined populations, the PPARG Ala12 allele was associated (P = 0.03) with lower birth weight, primarily caused by shorter gestational duration (P = 0.04). The frequency of Ala12 allele carriers was higher (P = 0.027) in the group of individuals born before term (35%, n = 60) than in the group of individuals born at term (22%, n = 942). The odds ratios (95% CI) of preterm birth for Ala12 allele carriers were 1.9 (1.1-3.4), P = 0.022, and 4.2 (1.9-9.7), P = 0.0006 (adjusted for sex, maternal age, and study), when considering 37 or 35 weeks of pregnancy as a threshold for preterm birth, respectively. Interestingly, the same allele was also associated with a moderate decreased risk of miscarriages in mothers. In conclusion, the PPARG Pro12Ala polymorphism might represent a genetic susceptibility factor for preterm birth and constitute a link between preterm birth and metabolic diseases later in life.

Haplotypes across ACE and the risk of Alzheimer's disease: the three-city study.

The purpose of this study was to examine the impact of two polymorphisms (rs4291A>T and rs4343G>A) in the ACE gene on the risk of Alzheimer's disease (AD), using a population-based cohort of 9294 subjects selected from the electoral rolls of three French cities (the Three-City Study). Two follow-up examinations took place 2 and 4 years after inclusion. Diagnosis of dementia was assessed at baseline and at each follow-up examination by neurologists independent of the 3C Study group. For the present analysis, subjects whose mother tongue was not French, those from abroad and those lost at follow-up were excluded, leaving a sample of 6791 subjects. 108 subjects were demented at baseline and 216 subjects, among which 141 had AD, developed a dementia during follow-up. The genotype distributions of the ACE SNPs rs4291 and rs4343 did not differ according to cognitive status. After adjustment for confounding variables, the risk of developing AD was similar whatever the genotype (rs4291 AT vs TT: OR=0.90, p=0.65; AA vs TT: OR=1.05, p= 0.84; rs4343 GA vs GG: OR=1.15, p= 0.48; AA vs GG: OR=1.25, p= 0.37). No global haplotype effect could be observed on the risk of AD.