Descending Aortic Distensibility and Cardiovascular Outcomes: A Cardiac Magnetic Resonance Imaging Study.

Background: Aortic distensibility (AD) is an important determinant of cardiovascular (CV) morbidity and mortality. There is scant data on the association between AD measured within the descending thoracic aorta and CV outcomes.

Objective: We evaluated the association of AD at the descending thoracic aorta (AD ) with the primary outcome of all-cause mortality, myocardial infarction (MI), stroke or coronary revascularization in patients referred for a cardiovascular magnetic resonance (CMR) study.

Characteristics of Cumulative Annual Radiation Exposure in Young Intensive Care Unit Survivors.

Objectives: Patients admitted to the intensive care unit (ICU) are at high risk for hazardous medical radiation exposure. However, the cumulative annual radiation exposure in ICU survivors remains unknown.

Methods: This was a single-center retrospective study of all critically ill adult patients admitted to the 64-bed adult medical ICU at a quaternary medical center.

OUTpatient intravenous LASix Trial in reducing hospitalization for acute decompensated heart failure (OUTLAST).

Background: Hospitalization for acute decompensated heart failure (ADHF) remains a major source of morbidity and mortality. The current study aimed to investigate the feasibility, safety, and efficacy of outpatient furosemide intravenous (IV) infusion following hospitalization for ADHF.

Methods: In a single center, prospective, randomized, double-blind study, 100 patients were randomized to receive standard of care (Group 1), IV placebo infusion (Group 2), or IV furosemide infusion (Group 3) over 3h, biweekly for a one-month period following ADHF hospitalization.

Divergent Nodes of Non-autonomous UPR Signaling through Serotonergic and Dopaminergic Neurons.

In multicellular organisms, neurons integrate a diverse array of external cues to affect downstream changes in organismal health. Specifically, activation of the endoplasmic reticulum (ER) unfolded protein response (UPR) in neurons increases lifespan by preventing age-onset loss of ER proteostasis and driving lipid depletion in a cell non-autonomous manner. The mechanism of this communication is dependent on the release of small clear vesicles from neurons.

Identification of novel human neutrophil elastase inhibitors from dietary phytochemicals using and studies.

Human neutrophil elastase (HNE) has been well studied as a therapeutic target for inflammatory diseases for several decades. A variety of small-molecule HNE inhibitors have been well known, and their mode of binding at the active site of the enzyme has been determined, but none of them reached clinical trials except sivelestat. In this study, we intended to identify potent dietary phytochemicals that can target the active site of HNE by employing computational methods and inhibition assay.

Anti-inflammatory effects of troxerutin are mediated through elastase inhibition.

Context: Obesity is a chronic low-grade inflammatory state associated with immune cell infiltration into the adipose tissue (AT). We hypothesize that the anti-obesity and anti-inflammatory effects of troxerutin (TX) are mediated through inhibition of elastase.

Objective: To determine the inhibitory effect of TX on elastase and in tumor necrosis factor alpha (TNFα) induced 3T3-L1 adipocytes and the molecular interaction of TX with human neutrophil elastase (HNE).

Evaluation of Serum miRNA-24, miRNA-29a and miRNA-502-3p Expression in PCOS Subjects: Correlation with Biochemical Parameters Related to PCOS and Insulin Resistance.

MicroRNAs (miRNAs) are small, endogenous, non-coding, single stranded RNAs which play a role in the regulation of gene expression and function. Therefore, the analysis of differentially expressed miRNAs are of great importance in disease diagnosis. This study is focussed on the differential expression of miRNAs in serum of PCOS subjects compared to control and their correlation with metabolic and endocrine parameters.

UPR promotes lipophagy independent of chaperones to extend life span.

Longevity is dictated by a combination of environmental and genetic factors. One of the key mechanisms to regulate life-span extension is the induction of protein chaperones for protein homeostasis. Ectopic activation of the unfolded protein response of the endoplasmic reticulum (UPR) specifically in neurons is sufficient to enhance organismal stress resistance and extend life span.

Oxidative stress, antioxidant status and lipid profile in pulmonary tuberculosis patients before and after anti-tubercular therapy.

Background: Pulmonary tuberculosis (PTB) is a highly infectious dreadful disease caused by mycobacterium tuberculosis (MTB). Numerous studies reported free radicals activity, antioxidant status and lipid profile in PTB patients, but previous studies have lacunae in comparing the biochemical variables between before and after anti-tubercular therapy (ATT) supplementation to PTB patients. Hence, the present study was carried out to investigate oxidative stress markers, antioxidant status, lipid profile, liver function markers, and glycoprotein components in pulmonary tuberculosis patients (PTB) patients before and after 60 days of ATT.

Supplementation of scopoletin improves insulin sensitivity by attenuating the derangements of insulin signaling through AMPK.

Scopoletin (SPL), a phenolic coumarin, is reported to regulate glucose metabolism. This study is initiated to substantiate the action of SPL on the regulation of insulin signaling in insulin resistant RIN5f cells and high fat, high fructose diet (HFFD)-fed rat model. Adult male Sprague Dawley rats were fed HFFD for 45 days to induce type 2 diabetes and then treated or untreated with SPL for the next 45 days.

Radiation Exposure in the Medical ICU: Predictors and Characteristics.

Background: Patients admitted to the medical ICU (MICU) are often subjected to multiple radiologic studies. We hypothesized that some endure radiation dose exposure (cumulative effective dose [CED]) in excess of annual US federal occupational health standard limits (CED ≥ 50 mSv) and 5-year cumulative limit (CED ≥ 100 mSv). We also evaluated the correlation of CED with Acute Physiology and Chronic Health Evaluation (APACHE) III score and other clinical variables.

Prevalence of dry eye disease and its association with dyslipidemia.

Background: Dry eye disease (DED) is a common ocular surface disease significantly affecting the quality of life of patients. The aim of our study is to focus on the prevalence of DED and to determine the relationship between dyslipidemia and DED.

Methods: The study was performed with the age group of 25-70 years, who attended the ophthalmology outpatient department at Sri Lakshmi Narayana Institute of Medical Sciences with complaints of dry eye.

Apigenin attenuates hippocampal oxidative events, inflammation and pathological alterations in rats fed high fat, fructose diet.

High calorie diet promotes oxidative stress and chronic low grade inflammation that predispose to brain dysfunction and neurodegeneration. Hippocampus region of the brain has been shown to be particularly sensitive to high calorie diet. We hypothesize that apigenin (API), a flavonoid could attenuate hippocampal derangements induced by high fat-high fructose diet (HFFD).

Processing body and stress granule assembly occur by independent and differentially regulated pathways in Saccharomyces cerevisiae.

A variety of ribonucleoprotein (RNP) granules form in eukaryotic cells to regulate the translation, decay, and localization of the encapsulated messenger RNA (mRNAs). The work here examined the assembly and function of two highly conserved RNP structures, the processing body (P body) and the stress granule, in the yeast Saccharomyces cerevisiae. These granules are induced by similar stress conditions and contain translationally repressed mRNAs and a partially overlapping set of protein constituents.

The cAMP-dependent protein kinase signaling pathway is a key regulator of P body foci formation.

In response to stress, eukaryotic cells accumulate mRNAs and proteins at discrete sites, or foci, in the cytoplasm. However, the mechanisms regulating foci formation, and the biological function of the larger ribonucleoprotein (RNP) assemblies, remain poorly understood. Here, we show that the cAMP-dependent protein kinase (PKA) in Saccharomyces cerevisiae is a key regulator of the assembly of processing bodies (P bodies), an RNP complex implicated in mRNA processing and translation.

Antagonistic interactions between the cAMP-dependent protein kinase and Tor signaling pathways modulate cell growth in Saccharomyces cerevisiae.

Eukaryotic cells integrate information from multiple sources to respond appropriately to changes in the environment. Here, we examined the relationship between two signaling pathways in Saccharomyces cerevisiae that are essential for the coordination of cell growth with nutrient availability. These pathways involve the cAMP-dependent protein kinase (PKA) and Tor proteins, respectively.

The Tor and cAMP-dependent protein kinase signaling pathways coordinately control autophagy in Saccharomyces cerevisiae.

Macroautophagy (hereafter autophagy) is a conserved membrane trafficking pathway responsible for the turnover of cytosolic protein and organelles during periods of nutrient deprivation. This pathway is also linked to a number of processes important for human health, including tumor suppression, innate immunity and the clearance of protein aggregates. As a result, there is tremendous interest in autophagy as a potential point of therapeutic intervention in a variety of pathological states.

The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy.

Macroautophagy (or autophagy) is a conserved degradative pathway that has been implicated in a number of biological processes, including organismal aging, innate immunity, and the progression of human cancers. This pathway was initially identified as a cellular response to nutrient deprivation and is essential for cell survival during these periods of starvation. Autophagy is highly regulated and is under the control of a number of signaling pathways, including the Tor pathway, that coordinate cell growth with nutrient availability.

Distal recognition sites in substrates are required for efficient phosphorylation by the cAMP-dependent protein kinase.

Protein kinases are important mediators of signal transduction in eukaryotic cells, and identifying the substrates of these enzymes is essential for a complete understanding of most signaling networks. In this report, novel substrate-binding variants of the cAMP-dependent protein kinase (PKA) were used to identify substrate domains required for efficient phosphorylation in vivo. Most wild-type protein kinases, including PKA, interact only transiently with their substrates.