Impact of Metabolically Healthy Obesity on Cardiovascular Outcomes in Older Adults with HFpEF: Insights from a Nationwide Sample.

Clinical outcomes among older adults hospitalized with heart failure with preserved ejection fraction (HFpEF) in the setting of metabolically healthy obesity (MHO) remain insufficiently explored. This study aimed to evaluate whether MHO status is associated with different rates of major adverse cardiac and cerebrovascular events (MACCEs) during HFpEF-related hospitalizations compared to patients without MHO. Data from the 2019 National Inpatient Sample (NIS) database was analyzed using relevant ICD-10 codes to identify HFpEF admissions in older adults.

In-hospital outcomes in COVID-19 patients with non-alcoholic fatty liver disease by severity of obesity: Insights from national inpatient sample 2020.

Background: Non-alcoholic fatty liver disease (NAFLD) increases the risk of cardiovascular diseases independently of other risk factors. However, data on its effect on cardiovascular outcomes in coronavirus disease 2019 (COVID-19) hospitalizations with varied obesity levels is scarce. Clinical management and patient care depend on understanding COVID-19 admission results in NAFLD patients with varying obesity levels.

Role of Colchicine in Cardiovascular Disorders.

Inflammation has played a pivotal role in atherosclerosis and other cardiovascular disorders, prompting the exploration of anti-inflammatory therapies to improve cardiovascular outcomes. Colchicine, a well-established agent in conditions such as gout and familial Mediterranean fever, has emerged as a promising novel anti-inflammatory agent in the realm of cardiovascular diseases. Its ability to target both traditional risk factors and residual inflammatory risk marks a significant advancement in cardiovascular prevention strategies, indicating a new era in cardiovascular care.

Should I stay or should I go? The cerebral bases of street-crossing decision.

An observer willing to cross a street must first estimate if the approaching cars offer enough time to safely complete the task. The brain areas supporting this perception, known as Time-To-Contact (TTC) perception, have been mainly studied through noninvasive correlational approaches. We carried out an experiment in which patients were tested during an awake brain surgery electrostimulation mapping to examine the causal implication of various brain areas in the street-crossing decision process.

How mechanisms of stem cell polarity shape the human cerebral cortex.

Apical-basal progenitor cell polarity establishes key features of the radial and laminar architecture of the developing human cortex. The unique diversity of cortical stem cell populations and an expansion of progenitor population size in the human cortex have been mirrored by an increase in the complexity of cellular processes that regulate stem cell morphology and behaviour, including their polarity. The study of human cells in primary tissue samples and human stem cell-derived model systems (such as cortical organoids) has provided insight into these processes, revealing that protein complexes regulate progenitor polarity by controlling cell membrane adherence within appropriate cortical niches and are themselves regulated by cytoskeletal proteins, signalling molecules and receptors, and cellular organelles.

A common Matrix metalloproteinase 8 promoter haplotype enhances the risk for hypertension via diminished interactions with nuclear factor kappa B.

Objectives: Matrix metalloproteinase 8 (MMP8) has a prominent role in collagen turnover in blood vessels and vascular remodeling. The contribution of regulatory single nucleotide polymorphisms in MMP8 to cardiovascular diseases is unclear. We aimed to delineate the influence of MMP8 promoter variations on hypertension.

A comparison of daytime and nighttime pedestrian road-crossing behavior using an immersive virtual environment.

Objective: Reduced visibility for both drivers and pedestrians is a key factor underlying the higher risk of vehicle-pedestrian collisions in dark conditions. This study investigated the extent to which pedestrians adjust for the higher risk of road crossing at night by comparing daytime and nighttime pedestrian road crossing using an immersive virtual environment.

Method: Participants physically crossed a single lane of continuous traffic in an immersive pedestrian simulator.

Functional Gly297Ser Variant of the Physiological Dysglycemic Peptide Pancreastatin Is a Novel Risk Factor for Cardiometabolic Disorders.

Pancreastatin (PST), a chromogranin A-derived potent physiological dysglycemic peptide, regulates glucose/insulin homeostasis. We have identified a nonsynonymous functional PST variant (p.Gly297Ser; rs9658664) that occurs in a large section of human populations.

Contra: Contrarian statistics for controlled variable selection.

The holdout randomization test (HRT) discovers a set of covariates most predictive of a response. Given the covariate distribution, HRTs can explicitly control the false discovery rate (FDR). However, if this distribution is unknown and must be estimated from data, HRTs can inflate the FDR.

How do pedestrians respond to adaptive headlamp systems in vehicles? A road-crossing study in an immersive virtual environment.

Three-fourths of pedestrian fatalities in the U.S. occur in the dark (National Center for Statistics and Analysis, 2020).

mTOR signaling regulates the morphology and migration of outer radial glia in developing human cortex.

Outer radial glial (oRG) cells are a population of neural stem cells prevalent in the developing human cortex that contribute to its cellular diversity and evolutionary expansion. The mammalian Target of Rapamycin (mTOR) signaling pathway is active in human oRG cells. Mutations in mTOR pathway genes are linked to a variety of neurodevelopmental disorders and malformations of cortical development.

Cortical Malformations: Lessons in Human Brain Development.

Creating a functional cerebral cortex requires a series of complex and well-coordinated developmental steps. These steps have evolved across species with the emergence of cortical gyrification and coincided with more complex behaviors. The presence of diverse progenitor cells, a protracted timeline for neuronal migration and maturation, and diverse neuronal types are developmental features that have emerged in the gyrated cortex.

A Common Tag Nucleotide Variant in Promoter Increases Risk for Hypertension via Enhanced Interactions With CREB (Cyclic AMP Response Element-Binding Protein) Transcription Factor.

MMP (matrix metalloproteinase)-7-a potent extracellular matrix degrading enzyme-is emerging as a new regulator of cardiovascular diseases. However, potential contributions of genetic variations to hypertension remain unknown. In this study, we probed for the association of a tag single-nucleotide polymorphism in the promoter (-181A/G; rs11568818) with hypertension in an urban South Indian population (n=1501).

Organotypic Explants of the Embryonic Rodent Hippocampus: An Accessible System for Transgenesis.

This protocol describes the technique of electroporation to target embryonic hippocampal progenitors in an organotypic slice preparation. This technique allows gene perturbation for examining developmental processes in the embryonic hippocampus while retaining the environment and connectivity of the cells. Gene perturbation can include Cre-mediated recombination, RNAi-mediated knockdown, gene overexpression, or a combination of any of these.

A haplotype variant of the human chromogranin A gene () promoter increases CHGA expression and the risk for cardiometabolic disorders.

The acidic glycoprotein chromogranin A (CHGA) is co-stored/co-secreted with catecholamines and crucial for secretory vesicle biogenesis in neuronal/neuroendocrine cells. CHGA is dysregulated in several cardiovascular diseases, but the underlying mechanisms are not well established. Here, we sought to identify common polymorphisms in the promoter and to explore the mechanistic basis of their plausible contribution to regulating CHGA protein levels in circulation.

Dynamic behaviour of human neuroepithelial cells in the developing forebrain.

To understand how diverse progenitor cells contribute to human neocortex development, we examined forebrain progenitor behaviour using timelapse imaging. Here we find that cell cycle dynamics of human neuroepithelial (NE) cells differ from radial glial (RG) cells in both primary tissue and in stem cell-derived organoids. NE cells undergoing proliferative, symmetric divisions retract their basal processes, and both daughter cells regrow a new process following cytokinesis.

Functional promoter polymorphisms direct the expression of cystathionine gamma-lyase gene in mouse models of essential hypertension.

Despite the well-known role of cystathionine γ-lyase (Cth) in cardiovascular pathophysiology, transcriptional regulation of Cth remains incompletely understood. Sequencing of the Cth promoter region in mouse models of genetic/essential hypertension (viz. Blood Pressure High [BPH], Blood Pressure Low [BPL] and Blood Pressure Normal [BPN] mice) identified several genetic variations.

Catestatin Gly364Ser Variant Alters Systemic Blood Pressure and the Risk for Hypertension in Human Populations via Endothelial Nitric Oxide Pathway.

Catestatin (CST), an endogenous antihypertensive/antiadrenergic peptide, is a novel regulator of cardiovascular physiology. Here, we report case-control studies in 2 geographically/ethnically distinct Indian populations (n≈4000) that showed association of the naturally-occurring human CST-Gly364Ser variant with increased risk for hypertension (age-adjusted odds ratios: 1.483; P=0.

Post-Transcriptional Regulation of Renalase Gene by miR-29 and miR-146 MicroRNAs: Implications for Cardiometabolic Disorders.

Renalase, a recently identified oxidoreductase, is emerging as a novel regulator of cardiovascular and metabolic disease states. The mechanism of regulation of renalase gene, especially at the post-transcriptional level, is completely unknown. We set out to investigate the possible role of microRNAs in regulation of renalase gene in this study.

Association of MMP7 -181A→G Promoter Polymorphism with Gastric Cancer Risk: INFLUENCE OF NICOTINE IN DIFFERENTIAL ALLELE-SPECIFIC TRANSCRIPTION VIA INCREASED PHOSPHORYLATION OF cAMP-RESPONSE ELEMENT-BINDING PROTEIN (CREB).

Elevated expression of matrix metalloproteinase7 (MMP7) has been demonstrated to play a pivotal role in cancer invasion. The -181A→G (rs11568818) polymorphism in the MMP7 promoter modulates gene expression and possibly affects cancer progression. Here, we evaluated the impact of -181A→G polymorphism on MMP7 promoter activity and its association with gastric cancer risk in eastern Indian case-control cohorts (n = 520).

Epigenomic footprints across 111 reference epigenomes reveal tissue-specific epigenetic regulation of lincRNAs.

Tissue-specific expression of lincRNAs suggests developmental and cell-type-specific functions, yet tissue specificity was established for only a small fraction of lincRNAs. Here, by analysing 111 reference epigenomes from the NIH Roadmap Epigenomics project, we determine tissue-specific epigenetic regulation for 3,753 (69% examined) lincRNAs, with 54% active in one of the 14 cell/tissue clusters and an additional 15% in two or three clusters. A larger fraction of lincRNA TSSs is marked in a tissue-specific manner by H3K4me1 than by H3K4me3.

Seizure evoked regulation of LIM-HD genes and co-factors in the postnatal and adult hippocampus.

The LIM-homeodomain (LIM-HD) family of transcription factors is well known for its functions during several developmental processes including cell fate specification, cell migration and axon guidance, and its members play fundamental roles in hippocampal development. The hippocampus is a structure that displays striking activity dependent plasticity.  We examined whether LIM-HD genes and their co-factors are regulated during kainic acid induced seizure in the adult rat hippocampus as well as in early postnatal rats, when the hippocampal circuitry is not fully developed.

Functional genetic variants of the catecholamine-release-inhibitory peptide catestatin in an Indian population: allele-specific effects on metabolic traits.

Catestatin (CST), a chromogranin A (CHGA)-derived peptide, is a potent inhibitor of catecholamine release from adrenal chromaffin cells and postganglionic sympathetic axons. We re-sequenced the CST region of CHGA in an Indian population (n = 1010) and detected two amino acid substitution variants: G364S and G367V. Synthesized CST variant peptides (viz.