Empowering ASHA Workers with Technology: Enhancing Primary Healthcare in Rural Communities.

This study aims to explore how technology can play a transformative role in empowering Accredited Social Health Activists (ASHAs) to enhance primary healthcare services within rural communities. ASHAs play a crucial role in delivering healthcare to underserved populations, yet their effectiveness is often hampered by resource limitations and restricted access to healthcare information. To address these challenges, this research investigates the integration of technology, specifically mobile applications, into the daily responsibilities of ASHAs. The research delves into how technology impacts ASHA workers' capacity to gather and share health-related information, enhance healthcare decision-making, and facilitate prompt referrals. Employing a mixed-methods approach, including surveys, interviews, and field observations, the study aims to capture the experiences and viewpoints of ASHAs, healthcare providers, and community members. Initial findings indicate that the adoption of technology has resulted in increased healthcare delivery efficiency, improved healthcare data tracking, and heightened community engagement. ASHAs equipped with technology can deliver healthcare services that are more personalized and timely, thereby contributing to improved health outcomes in rural areas. This research highlights the substantial potential of technology in empowering frontline healthcare workers and enhancing access to high-quality healthcare services in rural communities. It underscores the significance of tailored technological solutions to augment the effectiveness of ASHAs and, consequently, the overall healthcare ecosystem in underserved regions

Usefulness of C-Reactive Protein as a Marker for Prediction of Future Coronary Events in the Asian Indian Population: Indian Atherosclerosis Research Study

Inflammation plays a pivotal role in all stages of atherosclerosis. Numerous inflammatory, lipid, and cytokines markers have been associated with coronary artery disease (CAD) risk but data directly comparing their predictive value are limited. Studies were carried to elucidate the role of high-sensitivity C-reactive protein (hsCRP), other inflammatory as well as lipid markers and their associations. Among 1021 subjects, comprising 774 CAD affected members from Indian Atherosclerosis Research Study (IARS), plasma hsCRP levels showed strong correlation with inflammatory markers, namely, IL6 (r = .373; P = <.0001), sPLA2 (r = .544; P = <.0001) as also with fibrinogen (r = .579; P = <.0001). Levels of hsCRP were higher among subjects affected by CAD who suffered a repeat coronary event as compared to those who remained event free and subjects in the top quartile of hsCRP (>3.58 mg/L) were found to have a fourfold higher risk. In conclusion, hsCRP appears to be an independent predictor of recurrent CAD events in Asian Indian population

A versatile palindromic amphipathic repeat coding sequence horizontally distributed among diverse bacterial and eucaryotic microbes

<p>Abstract</p> <p>Background</p> <p>Intragenic tandem repeats occur throughout all domains of life and impart functional and structural variability to diverse translation products. Repeat proteins confer distinctive surface phenotypes to many unicellular organisms, including those with minimal genomes such as the wall-less bacterial monoderms, <it>Mollicutes</it>. One such repeat pattern in this clade is distributed in a manner suggesting its exchange by horizontal gene transfer (HGT). Expanding genome sequence databases reveal the pattern in a widening range of bacteria, and recently among eucaryotic microbes. We examined the genomic flux and consequences of the motif by determining its distribution, predicted structural features and association with membrane-targeted proteins.</p> <p>Results</p> <p>Using a refined hidden Markov model, we document a 25-residue protein sequence motif tandemly arrayed in variable-number repeats in ORFs lacking assigned functions. It appears sporadically in unicellular microbes from disparate bacterial and eucaryotic clades, representing diverse lifestyles and ecological niches that include host parasitic, marine and extreme environments. Tracts of the repeats predict a malleable configuration of recurring domains, with conserved hydrophobic residues forming an amphipathic secondary structure in which hydrophilic residues endow extensive sequence variation. Many ORFs with these domains also have membrane-targeting sequences that predict assorted topologies; others may comprise reservoirs of sequence variants. We demonstrate expressed variants among surface lipoproteins that distinguish closely related animal pathogens belonging to a subgroup of the <it>Mollicutes</it>. DNA sequences encoding the tandem domains display dyad symmetry. Moreover, in some taxa the domains occur in ORFs selectively associated with mobile elements. These features, a punctate phylogenetic distribution, and different patterns of dispersal in genomes of related taxa, suggest that the repeat may be disseminated by HGT and intra-genomic shuffling.</p> <p>Conclusions</p> <p>We describe novel features of PARCELs (<b>P</b>alindromic <b>A</b>mphipathic <b>R</b>epeat <b>C</b>oding <b>EL</b>ements), a set of widely distributed repeat protein domains and coding sequences that were likely acquired through HGT by diverse unicellular microbes, further mobilized and diversified within genomes, and co-opted for expression in the membrane proteome of some taxa. Disseminated by multiple gene-centric vehicles, ORFs harboring these elements enhance accessory gene pools as part of the "mobilome" connecting genomes of various clades, in taxa sharing common niches.</p

Genetic studies on the APOA1-C3-A5 gene cluster in Asian Indians with premature coronary artery disease

<p>Abstract</p> <p>Background</p> <p>The APOA1-C3-A5 gene cluster plays an important role in the regulation of lipids. Asian Indians have an increased tendency for abnormal lipid levels and high risk of Coronary Artery Disease (CAD). Therefore, the present study aimed to elucidate the relationship of four single nucleotide polymorphisms (SNPs) in the Apo11q cluster, namely the -75G>A, +83C>T SNPs in the APOA1 gene, the Sac1 SNP in the APOC3 gene and the S19W variant in the APOA5 gene to plasma lipids and CAD in 190 affected sibling pairs (ASPs) belonging to Asian Indian families with a strong CAD history.</p> <p>Methods & results</p> <p>Genotyping and lipid assays were carried out using standard protocols. Plasma lipids showed a strong heritability (h²48% – 70%; <it>P </it>< 0.0001). A subset of 77 ASPs with positive sign of Logarithm of Odds (LOD) score showed significant linkage to CAD trait by multi-point analysis (LOD score 7.42, <it>P </it>< 0.001) and to Sac1 (LOD score 4.49) and -75G>A (LOD score 2.77) SNPs by single-point analysis (<it>P </it>< 0.001). There was significant proportion of mean allele sharing (pi) for the Sac1 (pi 0.59), -75G>A (pi 0.56) and +83C>T (pi 0.52) (<it>P </it>< 0.001) SNPs, respectively. QTL analysis showed suggestive evidence of linkage of the Sac1 SNP to Total Cholesterol (TC), High Density Lipoprotein-cholesterol (HDL-C) and Apolipoprotein B (ApoB) with LOD scores of 1.42, 1.72 and 1.19, respectively (<it>P </it>< 0.01). The Sac1 and -75G>A SNPs along with hypertension showed maximized correlations with TC, TG and Apo B by association analysis.</p> <p>Conclusion</p> <p>The APOC3-Sac1 SNP is an important genetic variant that is associated with CAD through its interaction with plasma lipids and other standard risk factors among Asian Indians.</p

Epidemiology, baseline characteristics and risk of progression in the first South-Asian prospective longitudinal observational IgA nephropathy cohort

Introduction: Glomerular Research And Clinical Experiments-IgA Nephropathy in Indians (GRACE-IgANI) is the first prospective South Asian IgAN cohort with protocolized follow-up and extensive biosample collection. Here we report the baseline clinical, biochemical, and histopathologic characteristics of GRACE IgANI and calculate baseline risk of progression for the cohort. Methods: 201 incident adults with kidney biopsy-proven primary IgAN were recruited into GRACE-IgANI between March 2015 and September 2017. As of April 30, 2020, the cohort had completed a median followup of 30 months (interquartile range [IQR] 16-39). Results: The commonest clinical presentation in GRACE IgANI was hypertension, with or without proteinuria, and nephrotic-range proteinuria was present in 34%, despite Conclusions: The predicted risk of progression in this cohort was considerable. Over the next 5 years, we will dissect the pathogenic pathways that underlie this severe South Asian IgAN phenotype

Correlation between oestrogen receptor (ERα) and Ki-67 receptor expression in canine genital neoplasms by immunohistochemistry

The objective of the current study involved assessment of correlation between the expression of oestrogen receptor (ERα) and Ki-67 by immunohistochemistry, in the genital borne neoplasms in 12 postpubertal bitches between 2 to 12 years of age, presented at University Veterinary Hospitals, Kokkalai and Mannuthy. The age group of 5-8 years had the highest incidence of neoplasia (50.00 %) in comparison with other groups. Episiotomy was performed for extraluminal tumours while local excision performed in all intraluminal tumours except canine transmissible venereal tumour (CTVT). A chemotherapeutic regimen involving intravenous infusion of vincristine sulphate at 0.025 mg/kg was administered to bitches with CTVT and squamous cell carcinoma (SCC) until complete remission of the neoplasm. The tumours were histopathologically confirmed as myofibroma (n=6), CTVT (n= 3), leiomyoma (n = 1), SCC (n = 1) and fibroma (n = 1). Immunohistochemical staining of the neoplastic tissues was performed to evaluate ERα and Ki-67 expression status which could aid in estimating the malignancy potential and influence of ERα on the same. Spearman’s rank correlation between the immunohistochemical scores for the expression of ERα and Ki-67 in these tumours was highly significant (p<0.01). The correlation between ERα and Ki-67 had a significant negative correlation (p < 0.05). In conclusion, the study suggests that higher expression of Ki-67 of a neoplasm coupled with lower expression of ERα bears evidence to a malignant process

A comparative study of mutation screening of sarcomeric genes (MYBPC3, MYH7, TNNT2) using single gene approach versus targeted gene panel next generation sequencing in a cohort of HCM patients in Egypt

Background: NGS enables simultaneous sequencing of large numbers of associated genes in genetic heterogeneous disorders, in a more rapid and cost-effective manner than traditional technologies. However there have been limited direct comparisons between NGS and more established technologies to assess the sensitivity and false negative rates of this new approach. The scope of the present manuscript is to compare variants detected in MYBPC3, MYH7 and TNNT2 genes using the stepwise dHPLC/ Sanger versus targeted NGS.Methods: In this study, we have analysed a group of 150 samples of patients from the Bibliotheca Alexandrina-Aswan Heart Centre National HCM program. The genetic testing was simultaneously undertaken by high throughput denaturing high-performance liquid chromatography (dHPLC) followed by Sanger based sequencing and targeted next generation deep sequencing using panel of inherited cardiac genes (ICC). The panel included over 100 genes including the 3 sarcomeric genes. Analysis of the sequencing data of the 3 genes was undertaken in a double blinded strategy.Results: NGS analysis detected all pathogenic and likely pathogenic variants identified by dHPLC (50 in total, some samples had double hits). There was a 0% false negative rate for NGS based analysis. Nineteen variants were missed by dHPLC and detected by NGS, thus increasing the diagnostic yield in this co- analysed cohort from 22.0% (33/150) to 31.3% (47/150). Of interest to note that the mutation spectrum in this Egyptian HCM population revealed a high rate of homozygosity in MYBPC3 and MYH7 genes in comparison to other population studies (6/150, 4%). None of the homozygous samples were detected by dHPLC analysis.Conclusion: NGS provides a useful and rapid tool to allow panoramic screening of several genes simultaneously with a high sensitivity rate amongst genes of known etiologic role allowing high throughput analysis of HCM patients and relevant control series in a less characterised population

Reconstruction of a Bacterial Genome from DNA Cassettes

This basic research program comprised two major areas: (1) acquisition and analysis of marine microbial metagenomic data and development of genomic analysis tools for broad, external community use; (2) development of a minimal bacterial genome. Our Marine Metagenomic Diversity effort generated and analyzed shotgun sequencing data from microbial communities sampled from over 250 sites around the world. About 40% of the 26 Gbp of sequence data has been made publicly available to date with a complete release anticipated in six months. Our results and those mining the deposited data have revealed a vast diversity of genes coding for critical metabolic processes whose phylogenetic and geographic distributions will enable a deeper understanding of carbon and nutrient cycling, microbial ecology, and rapid rate evolutionary processes such as horizontal gene transfer by viruses and plasmids. A global assembly of the generated dataset resulted in a massive set (5Gbp) of genome fragments that provide context to the majority of the generated data that originated from uncultivated organisms. Our Synthetic Biology team has made significant progress towards the goal of synthesizing a minimal mycoplasma genome that will have all of the machinery for independent life. This project, once completed, will provide fundamentally new knowledge about requirements for microbial life and help to lay a basic research foundation for developing microbiological approaches to bioenergy

Next generation diagnostics in inherited arrhythmia syndromes : a comparison of two approaches.

Next-generation sequencing (NGS) provides an unprecedented opportunity to assess genetic variation underlying human disease. Here, we compared two NGS approaches for diagnostic sequencing in inherited arrhythmia syndromes. We compared PCR-based target enrichment and long-read sequencing (PCR-LR) with in-solution hybridization-based enrichment and short-read sequencing (Hyb-SR). The PCR-LR assay comprehensively assessed five long-QT genes routinely sequenced in diagnostic laboratories and "hot spots" in RYR2. The Hyb-SR assay targeted 49 genes, including those in the PCR-LR assay. The sensitivity for detection of control variants did not differ between approaches. In both assays, the major limitation was upstream target capture, particular in regions of extreme GC content. These initial experiences with NGS cardiovascular diagnostics achieved up to 89 % sensitivity at a fraction of current costs. In the next iteration of these assays we anticipate sensitivity above 97 % for all LQT genes. NGS assays will soon replace conventional sequencing for LQT diagnostics and molecular pathology

Next Generation Diagnostics in Inherited Arrhythmia Syndromes A Comparison of Two Approaches

Abstract Next-generation sequencing (NGS) provides an unprecedented opportunity to assess genetic variation underlying human disease. Here, we compared two NGS approaches for diagnostic sequencing in inherited arrhythmia syndromes. We compared PCR-based target enrichment and long-read sequencing (PCR-LR) with in-solution hybridization-based enrichment and short-read sequencing (Hyb-SR). The PCR-LR assay comprehensively assessed five long-QT genes routinely sequenced in diagnostic laboratories and &quot;hot spots&quot; in RYR2. The Hyb-SR assay targeted 49 genes, including those in the PCR-LR assay. The sensitivity for detection of control variants did not differ between approaches. In both assays, the major limitation was upstream target capture, particular in regions of extreme GC content. These initial experiences with NGS cardiovascular diagnostics achieved up to 89 % sensitivity at a fraction of current costs. In the next iteration of these assays we anticipate sensitivity above 97 % for all LQT genes. NGS assays will soon replace conventional sequencing for LQT diagnostics and molecular pathology