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.

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.

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.

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.

The Targeted Sequencing of Alpha Satellite DNA in Cercopithecus pogonias Provides New Insight Into the Diversity and Dynamics of Centromeric Repeats in Old World Monkeys.

Alpha satellite is the major repeated DNA element of primate centromeres. Specific evolutionary mechanisms have led to a great diversity of sequence families with peculiar genomic organization and distribution, which have till now been studied mostly in great apes. Using high throughput sequencing of alpha satellite monomers obtained by enzymatic digestion followed by computational and cytogenetic analysis, we compare here the diversity and genomic distribution of alpha satellite DNA in two related Old World monkey species, Cercopithecus pogonias and Cercopithecus solatus, which are known to have diverged about 7 Ma. Two main families of monomers, called C1 and C2, are found in both species. A detailed analysis of our data sets revealed the existence of numerous subfamilies within the centromeric C1 family. Although the most abundant subfamily is conserved between both species, our fluorescence in situ hybridization (FISH) experiments clearly show that some subfamilies are specific for each species and that their distribution is restricted to a subset of chromosomes, thereby pointing to the existence of recurrent amplification/homogenization events. The pericentromeric C2 family is very abundant on the short arm of all acrocentric chromosomes in both species, pointing to specific mechanisms that lead to this distribution. Results obtained using two different restriction enzymes are fully consistent with a predominant monomeric organization of alpha satellite DNA that coexists with higher order organization patterns in the C. pogonias genome. Our study suggests a high dynamics of alpha satellite DNA in Cercopithecini, with recurrent apparition of new sequence variants and interchromosomal sequence transfer.

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.

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.

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.

National Esophageal Atresia Register.

National Esophageal Atresia was created in 2008 by the National Reference Center for Esophageal Congenital Abnormalities created in 2006. Primary goal was estimation of live birth prevalence in France. A national network of surgeons and pediatricians was initiated and entire teams dealing with esophageal atresia accepted to participate in an exhaustive national register. A questionnaire was validated by a national committee and data were centralized in our center. Scientific exploitation showed that such database is useful for health authorities as for medical professionals. Live birth prevalence in France is at 1.9/10,000 births. Prenatal diagnosis is more common but its effect on prevalence is not yet fully understood. Associated congenital abnormalities are frequent and major malformations with termination of pregnancy can influence prevalence.

CFH Y402H and ARMS2 A69S Polymorphisms and Oral Supplementation with Docosahexaenoic Acid in Neovascular Age-Related Macular Degeneration Patients: The NAT2 Study.

PURPOSE: Genetic susceptibility could be modified by environmental factors and may also influence differential responses to treatments for age-related macular degeneration (AMD). We investigated whether genotype could influence response to docosahexaenoic acid (DHA)-supplementation in the occurrence of choroidal new vessels (CNV). METHODS: The Nutritional AMD Treatment 2 (NAT2) study was a randomized, placebo-controlled, double-blind, parallel, comparative study, including 250 patients aged 55 to 85 years with early lesions of age-related maculopathy, visual acuity better than 0.4 Logarithm of Minimum Angle of Resolution units in the study eye and neovascular AMD in the fellow eye. Patients were randomized at baseline to receive either 3 daily fish-oil capsules, each containing 280 mg DHA, 90 mg EPA and 2 mg Vitamin E, or placebo. RESULTS: Patients carrying the risk allele (C) for CFH Y402H had no statistically significant increased risk for developing CNV in the study eye (Hazard Ratio (HR)=0.97; 95% Confidence Interval (CI): 0.54-1.76 for heterozygous and HR=1.29; 95%CI: 0.69-2.40 for homozygous). Patients carrying the risk allele (T) for ARMS2 A69S had no statistically significant increased risk for developing CNV in the study eye (HR=1.68; 95%CI: 0.91-3.12) for heterozygous and HR=1.78; 95%CI: 0.90-3.52 for homozygous). A significant interaction was observed between CFH Y402H and DHA-supplementation (p=0.01). We showed a protective effect of DHA-supplementation among homozygous non-risk patients. Among these patients, occurrence of CNV was 38.2% in placebo group versus 16.7% in DHA group (p=0.008). CONCLUSIONS: These results suggest that a genetic predisposition to AMD conferred by the CFH Y402H variant limits the benefit provided by DHA supplementation. TRIAL REGISTRATION: ISRCTN registry 98246501.

Use of emergency departments by known epileptic patients: An underestimated problem?

BACKGROUND AND PURPOSE: Seizure is a frequent reason of admission in emergency department (ED) but little is known about the proportion and the characteristics of known epileptic patients (KEPs) who used emergency services. METHODS: Over a 12-month period, we prospectively recruited adults admitted for seizure to a tertiary hospital ED. For KEPs, clinical epilepsy features and characteristics of the admission were collected. RESULTS: Of the 60,578 ED admissions, 990 were related to seizure; 580 of these admissions concerned 448 different KEPs (257 males; median age: 44); 339 were residents in the health district. Epilepsy was structural/metabolic in 268 (59.8%) patients, genetic in 44 (9.8%) and unknown/undetermined in 136 (30.3%); 218 (48.7%) patients were under a single antiepileptic drug and 135 (30.1%) were followed by an epileptologist. Of the 580 KEP admissions, 440 (75.8%) concerned patients who had called the emergency medical assistance number, 252 (43.4%) with a discharge diagnosis of usual seizure and 43 (7.4%) of a status epilepticus. Half the KEPs were discharged without hospitalization. We estimated that 9.0% of KEPs residing in the district had used the ED during the period. CONCLUSION: Proportion of KEPs using ED is high. Most of the admissions concerned usual seizures suggesting that staff training and educational programmes for patients and for their relatives need to be improved. The organization of the prehospital and of the emergency medical services should also be adjusted to this specific need. Further research should be conducted to optimize the seizure care pathway for KEPs.

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.

Telomere regulation during ageing and tumorigenesis of the grey mouse lemur.

Telomere erosion leading to replicative senescence has been well documented in human and anthropoid primates, and provides a clue against tumorigenesis. In contrast, other mammals, such as laboratory mice, with short lifespan and low body weight mass have different telomere biology without replicative senescence. We analyzed telomere biology in the grey mouse lemur, a small prosimian model with a relative long lifespan currently used in ageing research. We report an average telomere length by telomere restriction fragment (TRF) among the longest reported so far for a primate species (25-30 kb), but without detectable overall telomere shortening with ageing on blood samples. However, we demonstrate using universal STELA (Single Telomere Length Amplification) the existence of short telomeres, the increase of which, while correlating with ageing might be related to another mechanism than replicative senescence. We also found a low stringency of telomerase restriction in tissues and an ease to immortalize fibroblasts in vitro upon spontaneous telomerase activation. Finally, we describe the first grey mouse lemur cancer cell line showing a dramatic telomere shortening and high telomerase activity associated with polyploidy. Our overall results suggest that telomere biology in grey mouse lemur is an exception among primates, with at best a physiologically limited replicative telomere ageing and closest to that observed in small rodents.

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.

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.

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.

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.

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.

Plasma amyloid-ß levels and prognosis in incident dementia cases of the 3-City Study.

Studies of plasma amyloid-ß (Aß) levels as potential biomarkers for incident Alzheimer's disease (AD) have yielded contradictory results. We explored the associations between plasma Aß(40), Aß(42), and truncated Aß levels, and prognosis of dementia in participants of the prospective 3-City Study. 120 aged individuals diagnosed with 2-year incident dementia were followed up for seven years. The associations between Aß plasma levels and baseline cognitive score, cognitive decline, and death were examined. A higher level of baseline plasma Aß was associated with worse cognitive status two years prior to incident dementia diagnosis. In incident AD patients, the association was only significant for Aß(40) and Aß(n-42). In the fast cognitive decliners group, especially in AD cases, a higher level of 5 pg/ml of baseline Aß(42), Aß(n-42), Aß(n-42)/Aß(n-40), and Aß(42)/Aß(40) ratios were associated with a lower risk of fast cognitive decline based on the Isaacs Set Test score. There was no association between peptide levels and mortality in demented subjects. When assayed at prodromal stage, plasma Aß levels may be potentially useful markers of fast cognitive decline in individuals who subsequently become demented.

Single nucleotide polymorphism in the cholesterol-24S-hydroxylase (CYP46A1) gene and its association with CFH and LOC387715 gene polymorphisms in age-related macular degeneration.

PURPOSE: We investigated the association of single nucleotide polymorphism (SNP) in the cholesterol-24S-hydroxylase (CYP46A1) gene, according to CFH and LOC387715 SNPs, with age-related macular degeneration (AMD). METHODS: We enrolled 1388 AMD patients with neovascular AMD or geographic atrophy and 487 unrelated control subjects. SNPs were genotyped in the CYP46A1 (rs754203), LOC387715 (rs10490924), and CFH (rs1061170) genes. Plasma 24S-hydroxycholesterol, the metabolic product of CYP46A1, was quantified by gas chromatography-mass spectrometry using an authentic deuterated internal standard in subgroups of patients and controls. The χ(2) test was used to compare categoric allelic and genotype distributions between cases and controls. The odds ratio (OR) with a 95% confidence interval (95% CI) was calculated for AMD risk, and adjusted for age and gender. Significance levels were set at P < 0.05. RESULTS: The rs754203 SNP in the CYP46A1 gene was not associated with AMD (crude OR = 1.2, 95% CI = 0.9-1.4, P = 0.2). The crude OR for risk of AMD was 2.9 (95% CI = 2.4-3.4, P < 0.0001) according to the number of rs10490924 T alleles in the LOC387715 gene, and 2.0 (95% CI = 1.7-2.3, P < 0.0001) according to the number of rs1061170 C alleles in the CFH gene. After adjustment for age and gender, an OR of 2.2 (95% CI = 1.1-4.1, P = 0.04) was obtained for AMD cases with the C allele in the CYP46A1 gene, and carrying no risk alleles in the CFH and LOC387715 genes. CONCLUSIONS: The rs754203 C allele in the CYP46A1 gene may confer a higher risk for exudative AMD in patients who carry no risk alleles in the CFH and LOC387715 genes. Additional studies with larger sample sizes are needed in AMD subjects at no risk in CFH and LOC387715.