Reduced CSF turnover and decreased ventricular Aβ42 levels are related

International audienceBACKGROUND: The appearance of Aβ42 peptide deposits is admitted to be a key event in the pathogenesis of Alzheimer's disease, although amyloid deposits also occur in aged non-demented subjects. Aβ42 is a degradation product of the amyloid protein precursor (APP). It can be catabolized by several enzymes, reabsorbed by capillaries or cleared into cerebrospinal fluid (CSF). The possible involvement of a decrease in CSF turnover in A4β2 deposit formation is up to now poorly known. We therefore investigated a possible relationship between a reduced CSF turnover and the CSF levels of the A4β2 peptide.To this aim, CSF of 31 patients with decreased CSF turnover were studied. These patients presented chronic hydrocephalus communicating or obstructive, which required surgery (ventriculostomy or ventriculo-peritoneal shunt). Nine subjects had idiopathic normal pressure hydrocephalus (iNPH), and the other 22 chronic hydrocephalus from other origins (oCH).The Aβ42 peptide concentration was measured by an ELISA test in 31 ventricular CSF samples and in 5 lumbar CSF samples from patients with communicating hydrocephalus. RESULTS: The 5 patients with lumbar CSF analysis had similar levels of lumbar and ventricular Aβ42. A significant reduction in Aβ42 ventricular levels was observed in 24 / 31 patients with hydrocephalus. The values were lower than 300 pg/ml in 5 out of 9 subjects with iNPH, and in 15 out of 22 subjects with oCH. CONCLUSION: The decrease of CSF Aβ42 seems to occur independently of the surgical hydrocephalus aetiology. This suggests that a CSF reduced turnover may play an important role in the decrease of CSF Aβ42 concentration

Early B-cell Factor gene association with multiple sclerosis in the Spanish population

BACKGROUND: The etiology of multiple sclerosis (MS) is at present not fully elucidated, although it is considered to result from the interaction of environmental and genetic susceptibility factors. In this work we aimed at testing the Early B-cell Factor (EBF1) gene as a functional and positional candidate risk factor for this neurological disease. Axonal damage is a hallmark for multiple sclerosis clinical disability and EBF plays an evolutionarily conserved role in the expression of proteins essential for axonal pathfinding. Failure of B-cell differentiation was found in EBF-deficient mice and involvement of B-lymphocytes in MS has been suggested from their presence in cerebrospinal fluid and lesions of patients. METHODS: The role of the EBF1 gene in multiple sclerosis susceptibility was analyzed by performing a case-control study with 356 multiple sclerosis patients and 540 ethnically matched controls comparing the EBF1 polymorphism rs1368297 and the microsatellite D5S2038. RESULTS: Significant association of an EBF1-intronic polymorphism (rs1368297, A vs. T: p = 0.02; OR = 1.26 and AA vs. [TA+TT]: p = 0.02; OR = 1.39) was discovered. This association was even stronger after stratification for the well-established risk factor of multiple sclerosis in the Major Histocompatibility Complex, DRB1*1501 (AA vs. [TA+TT]: p = 0.005; OR = 1.78). A trend for association in the case-control study of another EBF1 marker, the allele 5 of the very informative microsatellite D5S2038, was corroborated by Transmission Disequilibrium Test of 53 trios (p = 0.03). CONCLUSION: Our data support EBF1 gene association with MS pathogenesis in the Spanish white population. Two genetic markers within the EBF1 gene have been found associated with this neurological disease, indicative either of their causative role or that of some other polymorphism in linkage disequilibrium with them

Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques

A systematic review of the effectiveness of taxes on nonalcoholic beverages and high-in-fat foods as a means to prevent obesity trends

Nikolaos Maniadakis,1 Vasiliki Kapaki,1,2 Louiza Damianidi,3Georgia Kourlaba4 1Department of Health Services Organization and Management, National School of Public Health, Athens, 2University of Peloponnese, Peloponnese, 3Department of Allergy, Second Pediatric Clinic, National and Kapodistrian University of Athens School of Medicine, Athens, 4The Stavros Niarchos Foundation – Collaborative Center for Clinical Epidemiology and Outcomes Research (CLEO), First and Second Departments of Pediatrics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece Background: As part of the efforts to curb obesity, a new focus seems to be put on taxing foods that are perceived as being associated with obesity (eg, sugar-sweetened beverages and foods high in fat, sugar, and salt content) as a policy instrument to promote healthier diets.Objective: To assess the possible effects of such taxation policies by identifying and analyzing all studies which investigate the impact of price increases on consumption, caloric intake, or weight outcomes.Methods: Electronic data bases were searched with appropriate terms and their combinations. Thereafter, abstracts were reviewed and studies were selected based on predefined criteria. The characteristics of the selected studies and the results were extracted in a special form and consequently were reviewed and synthesized.Results: Price increase may lead to a reduction in consumption of the targeted products, but the subsequent effect on caloric intake may be much smaller. Only a limited number of the identified studies reported weight outcomes, most of which are either insignificant or very small in magnitude to make any improvement in public health.Conclusion: The effectiveness of a taxation policy to curb obesity is doubtful and available evidence in most studies is not very straightforward due to the multiple complexities in consumer behavior and the underling substitution effects. There is need to investigate in-depth the potential underlying mechanisms and the relationship between price-increase policies, obesity, and public health outcomes. Keywords: price, fat tax, sugar-sweetened beverages, calorie(s), elasticity, weight, body mass inde

A systematic review of the effectiveness of taxes on nonalcoholic beverages and high-in-fat foods as a means to prevent obesity trends

Background: As part of the efforts to curb obesity, a new focus seems to be put on taxing foods that are perceived as being associated with obesity (eg, sugar-sweetened beverages and foods high in fat, sugar, and salt content) as a policy instrument to promote healthier diets. Objective: To assess the possible effects of such taxation policies by identifying and analyzing all studies which investigate the impact of price increases on consumption, caloric intake, or weight outcomes. Methods: Electronic data bases were searched with appropriate terms and their combinations. Thereafter, abstracts were reviewed and studies were selected based on predefined criteria. The characteristics of the selected studies and the results were extracted in a special form and consequently were reviewed and synthesized. Results: Price increase may lead to a reduction in consumption of the targeted products, but the subsequent effect on caloric intake may be much smaller. Only a limited number of the identified studies reported weight outcomes, most of which are either insignificant or very small in magnitude to make any improvement in public health. Conclusion: The effectiveness of a taxation policy to curb obesity is doubtful and available evidence in most studies is not very straightforward due to the multiple complexities in consumer behavior and the underling substitution effects. There is need to investigate in-depth the potential underlying mechanisms and the relationship between price-increase policies, obesity, and public health outcomes. © 2013 Maniadakis et al