Genetic risk converges on regulatory networks mediating early type 2 diabetes.

Type 2 diabetes mellitus (T2D), a major cause of worldwide morbidity and mortality, is characterized by dysfunction of insulin-producing pancreatic islet β cells. T2D genome-wide association studies (GWAS) have identified hundreds of signals in non-coding and β cell regulatory genomic regions, but deciphering their biological mechanisms remains challenging. Here, to identify early disease-driving events, we performed traditional and multiplexed pancreatic tissue imaging, sorted-islet cell transcriptomics and islet functional analysis of early-stage T2D and control donors.

Pharmacoeconomic Analysis of Fixed-Dose Combinations of Proton Pump Inhibitors Available in India.

Introduction The global proton pump inhibitors (PPIs) market was valued at US$ 2.9 billion in 2020 and is expected to exhibit a compound aggregated growth rate of 4.30% during the forecast period (2020-2027), as they are regularly prescribed for many gastrointestinal disorders, and the treatment usually lasts for a longer period.

Adverse drug reactions reporting: Five years analysis from a teaching hospital.

Background: Adverse drug reactions (ADRs) are important cause of morbidity and mortality. Despite its known importance, rate and quality (completeness score) of ADR reporting is not satisfactory. The objective of this study was to analyze pattern and completeness score of ADRs during past five-years.

Renal Function in Hypertensive Patients Receiving Cilnidipine and L-Type Calcium Channel Blockers: A Meta-Analysis of Randomized Controlled and Retrospective Studies.

Nearly 65%-95% of chronic kidney disease (CKD) patients have hypertension. Calcium-channel blockers are the first-line drugs for the treatment of hypertension, including hypertension with diabetes. This study aims to estimate the effect of an L-type calcium channel blocker (CCB), cilnidipine, on the renal function of hypertensive patients.

A cost comparison of atrial fibrillation monitoring strategies after embolic stroke of undetermined source.

Background: Detection of atrial fibrillation (AF) in patients with embolic stroke of undetermined source (ESUS) is challenging due to its paroxysmal nature. We sought to assess AF detection with an insertable cardiac monitor (ICM) and to perform cost analysis for various AF monitoring strategies post-ESUS We applied this cost analysis modeling to recently published Stroke AF and Per Diem trials.

Methods: Retrospective chart review was performed in consecutive hospitalized patients with ESUS who had ICM placed prior to discharge.

Protocol for accelerated skeletal muscle regeneration and hypertrophic muscle formation in mice.

The skeletal muscle system is the major organ associated with movement of the body. Myogenesis and regeneration induced post-injury contribute to muscle formation and maintenance. Here, we provide detailed protocol for the accelerated repair of injured skeletal muscles and generation of hypertrophic muscle fibers.

Assessment of Oral Health-related Quality of Life in Patients Suffering from Systemic Diseases.

Aim: To assess the oral health-related quality of life (OHRQoL) among children suffering from congestive heart failure and bronchial asthma in Lucknow city.

Materials And Method: Methodology: Patients aged 6-12 years were assessed using Child Perception Questionnaire (CPQ). DMFT was assessed in same patients to measure their caries experience.

Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits.

Skeletal muscle accounts for the largest proportion of human body mass, on average, and is a key tissue in complex diseases and mobility. It is composed of several different cell and muscle fiber types. Here, we optimize single-nucleus ATAC-seq (snATAC-seq) to map skeletal muscle cell-specific chromatin accessibility landscapes in frozen human and rat samples, and single-nucleus RNA-seq (snRNA-seq) to map cell-specific transcriptomes in human.

p32 promotes melanoma progression and metastasis by targeting EMT markers, Akt/PKB pathway, and tumor microenvironment.

Melanoma originates from melanin-producing cells called melanocytes. Melanoma poses a great risk because of its rapid ability to spread and invade new organs. Cellular metastasis involves alteration in the gene expression profile and their transformation from epithelial to mesenchymal state.

Delays in thrombolysis during COVID-19 are associated with worse neurological outcomes: the Society of Vascular and Interventional Neurology Multicenter Collaboration.

Introduction: We have demonstrated in a multicenter cohort that the COVID-19 pandemic has led to a delay in intravenous thrombolysis (IVT) among stroke patients. Whether this delay contributes to meaningful short-term outcome differences in these patients warranted further exploration.

Methods: We conducted a nested observational cohort study of adult acute ischemic stroke patients receiving IVT from 9 comprehensive stroke centers across 7 U.

Genetic effects on liver chromatin accessibility identify disease regulatory variants.

Identifying the molecular mechanisms by which genome-wide association study (GWAS) loci influence traits remains challenging. Chromatin accessibility quantitative trait loci (caQTLs) help identify GWAS loci that may alter GWAS traits by modulating chromatin structure, but caQTLs have been identified in a limited set of human tissues. Here we mapped caQTLs in human liver tissue in 20 liver samples and identified 3,123 caQTLs.

Atx regulates skeletal muscle regeneration via LPAR1 and promotes hypertrophy.

Muscle differentiation is a multifaceted and tightly controlled process required for the formation of skeletal muscle fibers. Satellite cells are the direct cellular contributors to muscle repair in injuries or disorders. Here, we show that autotaxin (Atx) expression and activity is required for satellite cell differentiation.

Endovascular thrombectomy time metrics in the era of COVID-19: observations from the Society of Vascular and Interventional Neurology Multicenter Collaboration.

Background: Unprecedented workflow shifts during the coronavirus disease 2019 (COVID-19) pandemic have contributed to delays in acute care delivery, but whether it adversely affected endovascular thrombectomy metrics in acute large vessel occlusion (LVO) is unknown.

Methods: We performed a retrospective review of observational data from 14 comprehensive stroke centers in nine US states with acute LVO. EVT metrics were compared between March to July 2019 against March to July 2020 (primary analysis), and between state-specific pre-peak and peak COVID-19 months (secondary analysis), with multivariable adjustment.

Decline in mild stroke presentations and intravenous thrombolysis during the COVID-19 pandemic: The Society of Vascular and Interventional Neurology Multicenter Collaboration.

Background: To evaluate overall ischemic stroke volumes and rates, specific subtypes, and clinical presentation during the COVID-19 pandemic in a multicenter observational study from eight states across US.

Methods: We compared all ischemic strokes admitted between January 2019 and May 2020, grouped as; March-May 2020 (COVID-19 period) and March-May 2019 (seasonal pre-COVID-19 period). Primary outcome was stroke severity at admission measured by NIHSS stratified as mild (0-7), moderate [8-14], and severe (>14).

Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease.

Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits.

Lysophosphatidic acid-RAGE axis promotes lung and mammary oncogenesis via protein kinase B and regulating tumor microenvironment.

Background: Receptor for advanced glycation end products (RAGE) is a multi-ligand transmembrane receptor of the immunoglobulin superfamily. Lysophosphatidic acid (LPA) is a ligand for RAGE and is involved in physiological and pathophysiological conditions including cancer. However, RAGE-LPA axis is unexplored in lung and mammary cancer.

RAGE and its ligands: from pathogenesis to therapeutics.

Receptor for advanced glycation end products (RAGE) is an immunoglobulin-like receptor present on cell surface. RAGE binds to an array of structurally diverse ligands, acts as a pattern recognition receptor (PRR) and is expressed on cells of different origin performing different functions. RAGE ligation leads to the initiation of a cascade of signaling events and is implicated in diseases, such as inflammation, cancer, diabetes, vascular dysfunctions, retinopathy, and neurodegenerative diseases.

MYH9 suppresses melanoma tumorigenesis, metastasis and regulates tumor microenvironment.

Non-muscle myosin IIA heavy chain (MYH9) has been implicated in many physiological and pathological functions including cell adhesion, polarity, motility to cancer. However, its role in melanoma remains unexplored. The aim of our study was to evaluate the role of MYH9 in melanoma tumor development and metastasis and further to find out the potential underlying mechanisms.

Single-cell ATAC-Seq in human pancreatic islets and deep learning upscaling of rare cells reveals cell-specific type 2 diabetes regulatory signatures.

Objective: Type 2 diabetes (T2D) is a complex disease characterized by pancreatic islet dysfunction, insulin resistance, and disruption of blood glucose levels. Genome-wide association studies (GWAS) have identified > 400 independent signals that encode genetic predisposition. More than 90% of associated single-nucleotide polymorphisms (SNPs) localize to non-coding regions and are enriched in chromatin-defined islet enhancer elements, indicating a strong transcriptional regulatory component to disease susceptibility.

Sequenceserver: A Modern Graphical User Interface for Custom BLAST Databases.

Comparing newly obtained and previously known nucleotide and amino-acid sequences underpins modern biological research. BLAST is a well-established tool for such comparisons but is challenging to use on new data sets. We combined a user-centric design philosophy with sustainable software development approaches to create Sequenceserver, a tool for running BLAST and visually inspecting BLAST results for biological interpretation.

Hypoplastic left heart syndrome [HLHS]: treatment options in present era.

Hypoplastic left heart syndrome (HLHS) is the most severe form of congenital heart defect (CHD). The first successful intervention for it was undertaken by Norwood in 1983. Since then, there have been much development in the pre, intra, and postoperative treatment option in staged palliative surgical procedures.

Risk factors for recoarctation of aorta after Norwood procedure in patients with hypoplastic left heart syndrome.

Background: Recoarctation (reCoA) of the aorta is a common complication afer the Norwood procedure. Untreated, it can lead to failure of the systemic ventricle and death. The main goal of the study is to define risk factors of reCoA after the Norwood procedure in hypoplastic left heart syndrome (HLHS).

Initial experience with intracorporeal continuous ow LVAD in pediatric patients in Poland.

The Aim: The aim of the study is to present the initial experience with continuous flow left ventricle assist device (CF-LVAD) in pediatric patients with BSA below 1.5 m2.

Material And Methods: Between 2016 and 2017, CF-LVAD (the Heartware System) have been implanted in three pediatric patients in the Department of Pediatric Cardiac Surgery, Jagiellonian University, Krakow, Poland.