Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Studies on Modified Atmosphere Packaging of Pearl Spot (Etroplussuratensis) With Special Emphasis to Biochemical and Microbiological Parameters

A modified atmosphere may be defined as a packaging or storage of a perishable product in an atmosphere other than that of air. A modified atmosphere (MA) applies to food packaged products changes continuously throughout the storage period. The pearl spot (Etroplus suratensis) is an important brackish water fish belonging to the family Cichlidae. The present work was carried out to see the effect of modified atmosphere packaging on the shelf life fresh pearl spot stored in ice to extent the shelf life. The objectives of the present study are to study the suitability of Thermoformed Trays for modified atmosphere packaging, to standardize the most suitable gas mixture for modified atmosphere packaging pearl spot based on sensory evaluation, to find out the effect of modified atmosphere packaging in comparison to air packaging, to study the biochemical, microbiological, sensory and textural characteristics during storage, to study the safety concern regarding the Clostridium botulinum during modified atmosphere packaging, to find out the most suitable chemical quality indices for modified atmosphere stored pearl spo

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Not AvailableQuality changes of vacuum packed Black Pomfret (Parastromateus niger) and Pearlspot (Etroplus suratensis) treated with sodium acetate and potassium sorbate, respectively, and subsequently stored in vacuum packs in ice during chill storage were evaluated by measuring the volatile base nitrogen values, K-values and sensory parameters. The effects of sodium acetate (2 % w / v) and potassium sorbate (2 % w / v) dip treatments on vacuum packed Black Pomfret and Pearlspot were also examined. Total volatile base nitrogen values were found to increase slowly with time, whereas the K-values were found to increase linearly with time in samples of both the species and exceeded the acceptability limit on the day of sensory rejection. The K-values, representing the ratio between the sum of inosine and hypoxanthine to the sum of all other ATP breakdown products, was found to be a more reliable method for estimation of the quality of fresh/preserved fish. Sodium acetate/potassium sorbate dip treated and vacuum packed Black Pomfret and Pearlspot exhibited lower K-values compared to untreated samples. Treated vacuum packed samples of Black Pomfret were found to be in good and acceptable condition up to 16 days whereas treated vacuum packed samples of pearlspot remained in good condition up to 15 days compared to vacuum packed and air packed samples which were acceptable only up to 10 and 8 days, respectively. The sensory characteristics correlated well with the K-values for both the species.Not Availabl

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Not AvailableThe effect of modified atmosphere packaging (MAP) at different gas concentration on chill stored pearl spot (Etroplus suratensis Bloch) was examined by means of nucleotide degradation and sensory evaluation. K value, a quality index for fish, the ratio of the sum of inosine and hypoxanthine to the sum of ATP and related catabolites expressed as a percentage, was determined until sensory rejection during storage up to 23 days at 0 - 20C. The C02 concentration did not affect the K values of pearl spot. K value increased linearly in samples stored under air and four different modified atmospheres. Identical K values were obtained for Pearl spot packed in either aerobic or carbon dioxide modified atmosphere. K values were independent of sensory spoilage and correlate only with the length of storage of pearl spot packed under MAP.Not Availabl

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Not AvailableThe necessity and the importance of value added products are growing rapidly during the last few decades, which helped to popularize modern technologies like extrusion. In the present study less utilized pink perch (Nemipterus japonicus) was blended with the corn starch to produce Spaghetti typed extruded product using single screw extruder. Standardization was done with increasing concentrations of fish mince. Physical properties like bulk density, linear expansion, colour etc., were found to be changed by the increase in the concentration of the fish muscle in the premix. It was found that premix with 10% fish mince had better. physical properties like colour, linear expansion, shearing force etc.Not Availabl

Abstracts of the International Conference on Recent Trends in Mathematics and Computer Science 2023

This book presents the abstracts of the selected contributions to the International Conference on Recent Trends in Mathematics and Computer Science 2023 (ICRTMCS-2023), held on 19-21 October 2023 by the Auxilium College of Arts and Science for Women, Regunathapuram, Tamil Nadu, India. ICRTMCS-2023 was a multidisciplinary conference organized with the objective of bringing together eminent academicians, research scholars, and students to exchange ideas, communicate, to discuss research findings and new advances on recent and emerging trends in the field of Mathematics and Computer Science. Moreover, the conference would also enable the participants to explore new fields and gain immense knowledge. Conference Title: International Conference on Recent Trends in Mathematics and Computer Science 2023Conference Acronym: ICRTMCS-2023Conference Date: 19-21 October 2023Conference Venue: Hybrid (Online and Auxilium College of Arts and Science for Women, Regunathapuram, India)Conference Organizer: Departments of Mathematics and Computer Science, Auxilium College of Arts and Science for Women, Regunathapuram, Tamil Nadu, Indi

Time-dependent analysis of extra length of stay and mortality due to ventilator-associated pneumonia in intensive-care units of ten limited-resources countries: findings of the International Nosocomial Infection Control Consortium (INICC)

Ventilator-associated pneumonias (VAPs) are a worldwide problem that significantly increases patient morbidity, mortality, and length of stay (LoS), and their effects should be estimated to account for the timing of infection. The purpose of the study was to estimate extra LoS and mortality in an intensive-care unit (ICU) due to a VAP in a cohort of 69 248 admissions followed for 283 069 days in ICUs from 10 countries. Data were arranged according to the multi-state format. Extra LoS and increased risk of death were estimated independently in each country, and their results were combined using a random-effects meta-analysis. VAP prolonged LoS by an average of 2.03 days (95% CI 1.52-2.54 days), and increased the risk of death by 14% (95% CI 2-27). The increased risk of death due to VAP was explained by confounding with patient morbidity

Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study

ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases).ResultsIn standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 × 10-4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 × 10-4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype.ConclusionsThis study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype

Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations

Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes. To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events. Methods: Summary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI-1]) and three major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi-trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85 × 10 obtained after applying Bonferroni correction for the number of multi-trait combinations performed (n = 27). Across the 27 multi-trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes. The discovery of four novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits