Brugada syndrome in Japan and Europe: a genome-wide association study reveals shared genetic architecture and new risk loci.

Background And Aims: Brugada syndrome (BrS) is an inherited arrhythmia with a higher disease prevalence and more lethal arrhythmic events in Asians than in Europeans. Genome-wide association studies (GWAS) have revealed its polygenic architecture mainly in European populations. The aim of this study was to identify novel BrS-associated loci and to compare allelic effects across ancestries.

Generation of human induced pluripotent stem cell lines from four unrelated healthy control donors carrying European genetic background.

Four human induced pluripotent stem cell (hiPSC) lines have been generated from healthy control European donors, and validated. This resource represents a useful tool for stem cell-based research, as references for developmental studies and disease modeling linked to any type of human tissue and organ, in an ethnical-, sex- and age-matched context. They providea reliable in-vitro model for single cell- and tissue-based investigations, and are also a valuable tool for genome editing-based studies.

Genetic Association Analyses Highlight , , and As 3 New Susceptibility Genes Underlying Calcific Aortic Valve Stenosis.

Background: Calcific aortic valve stenosis (CAVS) is a frequent and life-threatening cardiovascular disease for which there is currently no medical treatment available. To date, only 2 genes, and , have been identified as causal for CAVS. We aimed to identify additional susceptibility genes for CAVS.

RRAD mutation causes electrical and cytoskeletal defects in cardiomyocytes derived from a familial case of Brugada syndrome.

Aims: The Brugada syndrome (BrS) is an inherited cardiac disorder predisposing to ventricular arrhythmias. Despite considerable efforts, its genetic basis and cellular mechanisms remain largely unknown. The objective of this study was to identify a new susceptibility gene for BrS through familial investigation.

Rare Coding Variants in ANGPTL6 Are Associated with Familial Forms of Intracranial Aneurysm.

Intracranial aneurysms (IAs) are acquired cerebrovascular abnormalities characterized by localized dilation and wall thinning in intracranial arteries, possibly leading to subarachnoid hemorrhage and severe outcome in case of rupture. Here, we identified one rare nonsense variant (c.1378A>T) in the last exon of ANGPTL6 (Angiopoietin-Like 6)-which encodes a circulating pro-angiogenic factor mainly secreted from the liver-shared by the four tested affected members of a large pedigree with multiple IA-affected case subjects.

Dysfunction of the Voltage-Gated K+ Channel β2 Subunit in a Familial Case of Brugada Syndrome.

Background: The Brugada syndrome is an inherited cardiac arrhythmia associated with high risk of sudden death. Although 20% of patients with Brugada syndrome carry mutations in SCN5A, the molecular mechanisms underlying this condition are still largely unknown.

Methods And Results: We combined whole-exome sequencing and linkage analysis to identify the genetic variant likely causing Brugada syndrome in a pedigree for which SCN5A mutations had been excluded.

Genetic association analyses highlight biological pathways underlying mitral valve prolapse.

Nonsyndromic mitral valve prolapse (MVP) is a common degenerative cardiac valvulopathy of unknown etiology that predisposes to mitral regurgitation, heart failure and sudden death. Previous family and pathophysiological studies suggest a complex pattern of inheritance. We performed a meta-analysis of 2 genome-wide association studies in 1,412 MVP cases and 2,439 controls.

Testing the burden of rare variation in arrhythmia-susceptibility genes provides new insights into molecular diagnosis for Brugada syndrome.

The Brugada syndrome (BrS) is a rare heritable cardiac arrhythmia disorder associated with ventricular fibrillation and sudden cardiac death. Mutations in the SCN5A gene have been causally related to BrS in 20-30% of cases. Twenty other genes have been described as involved in BrS, but their overall contribution to disease prevalence is still unclear.

Impact of photocatalysis on fungal cells: depiction of cellular and molecular effects on Saccharomyces cerevisiae.

We have investigated the antimicrobial effects of photocatalysis on the yeast model Saccharomyces cerevisiae. To accurately study the antimicrobial mechanisms of the photocatalytic process, we focused our investigations on two questions: the entry of the nanoparticles in treated cells and the fate of the intracellular environment. Transmission electronic microscopy did not reveal any entry of nanoparticles within the cells, even for long exposure times, despite degradation of the cell wall space and deconstruction of cellular compartments.

Fine-scale human genetic structure in Western France.

The difficulties arising from association analysis with rare variants underline the importance of suitable reference population cohorts, which integrate detailed spatial information. We analyzed a sample of 1684 individuals from Western France, who were genotyped at genome-wide level, from two cohorts D.E.

Aged TiO2-based nanocomposite used in sunscreens produces singlet oxygen under long-wave UV and sensitizes Escherichia coli to cadmium.

TiO2-based nanocomposite (NC) are widely used as invisible UV protectant in cosmetics. These nanomaterials (NMs) end in the environment as altered materials. We have investigated the properties of T-Lite SF, a TiO2-NC used as sunscreen, after weathering in water and under light.

Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death.

Brugada syndrome is a rare cardiac arrhythmia disorder, causally related to SCN5A mutations in around 20% of cases. Through a genome-wide association study of 312 individuals with Brugada syndrome and 1,115 controls, we detected 2 significant association signals at the SCN10A locus (rs10428132) and near the HEY2 gene (rs9388451). Independent replication confirmed both signals (meta-analyses: rs10428132, P = 1.

Temporal trends in Inuit, First Nations and non-Aboriginal birth outcomes in rural and northern Quebec.

Objectives: The objective was to assess trends in Inuit, First Nations and non-Aboriginal birth outcomes in the rural and northern regions of Quebec.

Study Design And Methods: In a birth cohort-based study of all births to residents of rural and northern Quebec from 1991 through 2000 (n = 177,193), we analyzed birth outcomes and infant mortality for births classified by maternal mother tongue (Inuit, First Nations or non-Aboriginal) and by community type (predominantly First Nations, Inuit or non-Aboriginal).

Results: From 1991-1995 to 1996-2000, there was a trend of increasing rates of preterm birth for all 6 study groups.

Bactericidal efficiency and mode of action: a comparative study of photochemistry and photocatalysis.

In order to compare the disinfection potential of photocatalysis and photochemistry, the effects of these two processes on bacteria in water were investigated under exposure to UV-A and UV-C. The well-known bacterial model Escherichia coli (E. coli) was used as the experimental organism.

Diabetes in pregnancy may differentially affect neonatal outcomes for twins and singletons.

Aim: We tested the hypothesis that diabetes in pregnancy may differentially affect neonatal outcomes in twin vs. singleton pregnancies.

Methods: In a retrospective cohort analysis of twins (n = 422 068) and singletons (n = 14 298 367) born in the USA from 1998 to 2001, we evaluated the adjusted odds ratios of adverse neonatal outcomes comparing diabetic vs.

Association of macrosomia with perinatal and postneonatal mortality among First Nations people in Quebec.

Background: High prevalence of infant macrosomia (up to 36%, the highest in the world) has been reported in some First Nations communities in the Canadian province of Quebec and the eastern area of the province of Ontario. We aimed to assess whether infant macrosomia was associated with elevated risks of perinatal and postneonatal mortality among First Nations people in Quebec.

Methods: We calculated risk ratios (RRs) of perinatal and postneonatal mortality by birthweight for gestational age, comparing births to First Nations women (n = 5193) versus women whose mother tongue is French (n = 653 424, the majority reference group) in Quebec 1991-2000.

Birth outcomes and infant mortality among First Nations Inuit, and non-Indigenous women by northern versus southern residence, Quebec.

Background: In circumpolar countries such as Canada, northern regions represent a unique geographical entity climatically, socioeconomically and environmentally. There is a lack of comparative data on birth outcomes among Indigenous and non-Indigenous subpopulations within northern regions and compared with southern regions.

Methods: A cohort study of all births by maternal mother tongue to residents of northern (2616 First Nations (North American Indians), 2388 Inuit and 5006 non-Indigenous) and southern (2563 First Nations, 810,643 non-Indigenous) Quebec, 1991-2000.

Birth outcomes and infant mortality by the degree of rural isolation among first nations and non-first nations in Manitoba, Canada.

Context: It is unknown whether rural isolation may affect birth outcomes and infant mortality differentially for Indigenous versus non-Indigenous populations. We assessed birth outcomes and infant mortality by the degree of rural isolation among First Nations (North American Indians) and non-First Nations populations in Manitoba, Canada, a setting with universal health insurance.

Methods: A geocoding-based birth cohort study of 25,143 First Nations and 125,729 non-First Nations live births to Manitoban residents, 1991-2000.

Birth outcomes in the Inuit-inhabited areas of Canada.

Background: Information on health disparities between Aboriginal and non-Aboriginal populations is essential for developing public health programs aimed at reducing such disparities. The lack of data on disparities in birth outcomes between Inuit and non-Inuit populations in Canada prompted us to compare birth outcomes in Inuit-inhabited areas with those in the rest of the country and in other rural and northern areas of Canada.

Methods: We conducted a cohort study of all births in Canada during 1990-2000 using linked vital data.

Optimal birth weight percentile cut-offs in defining small- or large-for-gestational-age.

Aims: It remains questionable what birth weight for gestational age percentile cut-offs should be used in defining clinically important poor or excessive foetal growth. We aimed to evaluate the optimal birth weight percentile cut-offs for defining small- or large-for-gestational-age (SGA or LGA).

Methods: In a birth cohort-based analysis of 17 979 120 non-malformation singleton live births, U.

North-South Gradients in Adverse Birth Outcomes for First Nations and Others in Manitoba, Canada.

OBJECTIVE: to determine the relationship of north-south place of residence to adverse birth outcomes among First Nations and non-First Nations in Manitoba, Canada, a setting with universal health insurance. STUDY DESIGN: Live birth records (n=151,472) for the province of Manitoba, Canada 1991-2000 were analyzed, including 25,743 First Nations and 125,729 non-First Nations infants. North-south and rural-urban residence was determined for each birth through geocoding.