Multiscale simulation approaches to modeling drug-protein binding.

Simulations can provide detailed insight into the molecular processes involved in drug action, such as protein-ligand binding, and can therefore be a valuable tool for drug design and development. Processes with a large range of length and timescales may be involved, and understanding these different scales typically requires different types of simulation methodology. Ideally, simulations should be able to connect across scales, to analyze and predict how changes at one scale can influence another.

Salt-inducible kinase 1 maintains HDAC7 stability to promote pathologic cardiac remodeling.

Salt-inducible kinases (SIKs) are key regulators of cellular metabolism and growth, but their role in cardiomyocyte plasticity and heart failure pathogenesis remains unknown. Here, we showed that loss of SIK1 kinase activity protected against adverse cardiac remodeling and heart failure pathogenesis in rodent models and cardiomyocytes derived from human induced pluripotent stem cells. We found that SIK1 phosphorylated and stabilized histone deacetylase 7 (HDAC7) protein during cardiac stress, an event that is required for pathologic cardiomyocyte remodeling.

Validation of Dipole Density Mapping During Atrial Fibrillation and Sinus Rhythm in Human Left Atrium.

Objectives: This study sought to validate the accuracy of noncontact electrograms against contact electrograms in the left atrium during sinus rhythm (SR) and atrial fibrillation (AF).

Background: Noncontact mapping offers the opportunity to assess global cardiac activation in the chamber of interest. A novel noncontact mapping system, which records intracardiac voltage to derive cellular charge sources (dipole density), allows real-time mapping of AF to guide ablation.

Genotypic characterization of 'inferred' rifampin mutations in GenoType MTBDRplus assay and its association with phenotypic susceptibility testing of Mycobacterium tuberculosis.

In GenoType MTBDRplus assay [line probe assay (LPA)], when Mycobacterium tuberculosis (M. tuberculosis) sample DNA fails to hybridize to at least 1 rpoB wild-type probe and any mutation probe, it is inferred as rifampin (RIF)-resistant. In this study, we sought to identify such 'inferred' mutations in M.

Focal source and trigger mapping in atrial fibrillation: Randomized controlled trial evaluating a novel adjunctive ablation strategy.

Background: Intraoperative mapping has demonstrated focal activations during human atrial fibrillation (AF). These putative AF sources can manifest sustained periodic bipolar and unipolar QS electrograms (EGMs). We have automated the detection of these EGM features using our validated Focal Source and Trigger (FaST) computational algorithm.

Effective deoxygenation for the production of liquid biofuels via microwave assisted co-pyrolysis of agro residues and waste plastics combined with catalytic upgradation.

Rice straw and sugarcane bagasse were co-pyrolyzed with polypropylene and polystyrene using microwaves, and the pyrolysis vapors were catalytically upgraded using HZSM-5 catalyst. The product yields, composition and properties of bio-oil from pyrolysis of individual feedstocks and equal composition mixtures before and after catalytic upgradation were thoroughly investigated. The pyrolysis oil yields from polypropylene (82 wt%) and polystyrene (98 wt%) were high compared to that from rice straw (26 wt%) and bagasse (29 wt%).

Use and impact of an online community for hospital patients.

Objective: Although patient-peer support technologies have demonstrated effectiveness in a variety of health contexts-including diabetes, weight loss, and cancer-less is known about how hospitalized patients can benefit from this support. We investigated the nature of peer support in the hospital and the impact this support had on patients' hospital stays.

Materials And Methods: We created a technology, resembling an online health community, in which patients could exchange advice about their hospitalization.

Living with the Unknown: A Qualitative Study of Parental Experience of Prognostic Uncertainty in the Neonatal Intensive Care Unit.

Objective: This study aims to characterize the experience of prognostic uncertainty for neonatal intensive care unit (NICU) parents.

Study Design: We conducted a qualitative interview study of current and former NICU parents regarding their experience with prognostic uncertainty in the NICU. Interviews were transcribed and analyzed using a grounded theory methodology.

Re-emergence of Chikungunya virus infection in Eastern India.

Chikungunya fever is a major public health issue in India. Re-emergence of chikungunya virus (CHIKV) in West Bengal was detected after 32 years in 2006. After 2010, this infection was in apparent decline, but in 2016 a massive outbreak affected the country.

Pulsed glucocorticoids enhance dystrophic muscle performance through epigenetic-metabolic reprogramming.

In humans, chronic glucocorticoid use is associated with side effects like muscle wasting, obesity, and metabolic syndrome. Intermittent steroid dosing has been proposed in Duchenne Muscular Dystrophy patients to mitigate the side effects seen with daily steroid intake. We evaluated biomarkers from Duchenne Muscular Dystrophy patients, finding that, compared with chronic daily steroid use, weekend steroid use was associated with reduced serum insulin, free fatty acids, and branched chain amino acids, as well as reduction in fat mass despite having similar BMIs.

Brown fat activity determined by infrared thermography and thermogenesis measurement using whole body calorimetry (BRIGHT Study).

To assess BAT activity in humans at a population level, infrared thermography (IRT) represents a safe, readily repeatable and affordable alternative to 18F-FDG-PET. Building upon a previously proposed method by our laboratory, we further refined the image computational algorithm to quantify BAT activation in the cervical-supraclavicular (C-SCV) region of healthy young men under thermo-neutral and cold exposure conditions. Additionally, we validated the whole-body calorimeter (WBC) in reliably measuring cold-induced thermogenesis.

The Evolving Neural Tissue Engineering Landscape of India.

The healthcare sector in India is witnessing unprecedented advancement. Tissue engineering has become an integral part of healthcare and medicine, particularly where treatments involve functional restoration of any injured or deceased part of the body. Not falling behind much with the progressing medical and healthcare sector of India, tissue engineering is also gaining momentum in the country.

Minimal requirements for developmentally regulated cardiac long intergenic non-coding RNAs.

Long intergenic non-coding RNAs (lincRNAs) have been implicated in gene regulation, but their requirement for development needs empirical interrogation. We computationally identified nine murine lincRNAs that have developmentally regulated transcriptional and epigenomic profiles specific to early heart differentiation. Six of the nine lincRNAs had expression patterns supporting a potential function in heart development, including a transcript downstream of the cardiac transcription factor , which we named (-associated lincRNA), and We genetically ablated these six lincRNAs in mouse, which suggested genomic regulatory roles for four of the cohort.

Temperature-dependent mucosal permeation kinetics of stigmasterol microspheres: In vivo mice model antioral candidiasis study.

Evaluation of mucosal permeation of stigmasterol from the glutaraldehyde cross linked chitosan microspheres at increasing experimental temperatures was performed. The activation energy of permeation, partition, and diffusion were estimated to understand the permeation kinetic with respect to the temperature. The formulation depicting least activation energy possessed the increased permeation thresholds of drug at the site of application.

Theranostic Application of a Novel G-Quadruplex-Forming DNA Aptamer Targeting Malate Synthase of Mycobacterium tuberculosis.

The successful management of tuberculosis (TB) requires efficient diagnosis and treatment. Further, the increasing prevalence of drug-resistant TB highlights the urgent need to develop novel inhibitors against both drug-susceptible and drug-resistant forms of disease. Malate synthase (MS), an enzyme of the glyoxylate pathway, plays a vital role in mycobacterial persistence, and therefore it is considered as an attractive target for novel anti-TB drug development.

Periodontal inflammation recruits distant metastatic breast cancer cells by increasing myeloid-derived suppressor cells.

Periodontal diseases can lead to chronic inflammation affecting the integrity of the tooth supporting tissues. Recently, a striking association has been made between periodontal diseases and primary cancers in the absence of a mechanistic understanding. Here we address the effect of periodontal inflammation (PI) on tumor progression, metastasis, and possible underlining mechanisms.

Characterization of phenazine-1-carboxylic acid by Klebsiella sp. NP-C49 from the coral environment in Gulf of Kutch, India.

Coral-associated microbes from Marine National Park (MNP), Gulf of Kutch (GoK), Gujarat, India, were screened for siderophore production. Maximum siderophore-producing isolate NP-C49 and its compound were identified and characterized. The isolate was identified as Klebsiella sp.

Differential in vitro degradation and protein adhesion behaviour of spark plasma sintering fabricated magnesium-based temporary orthopaedic implant in serum and simulated body fluid.

The interaction of proteins with implantable metallic surfaces has a great influence on the bioactivity and biodegradation of orthopaedic implants. Initial osseointegration is known to be critical for the long term success of orthopaedic implants. The surface properties of the implant and electrochemical milieu of the surrounding solution such as electrostatic, hydrophobic, and hydrogen bonding interactions significantly modulate protein adsorption by implants.

Surface Modified Metallic Orthopedic Implant for Sustained Drug Release and Osteocompatibility.

Designing implants with good antibacterial activity and simultaneously providing a platform for osteoblast adhesion is a challenge for researchers. All metallic implants, currently in use, are biocompatible but bioinert. This may lead to a weak interface with the bone and cause asceptic loosening.

Epigenetic changes in fibroblasts drive cancer metabolism and differentiation.

Genomic changes that drive cancer initiation and progression contribute to the co-evolution of the adjacent stroma. The nature of the stromal reprogramming involves differential DNA methylation patterns and levels that change in response to the tumor and systemic therapeutic intervention. Epigenetic reprogramming in carcinoma-associated fibroblasts are robust biomarkers for cancer progression and have a transcriptional impact that support cancer epithelial progression in a paracrine manner.

Informatics opportunities to involve patients in hospital safety: a conceptual model.

Objective: Inpatients could play an important role in identifying, preventing, and reporting problems in the quality and safety of their care. To support them effectively in that role, informatics solutions must align with their experiences. Thus, we set out to understand how inpatients experience undesirable events (UEs) and to surface opportunities for those informatics solutions.

Postprandial Glycemic and Insulinemic Effects of the Addition of Aqueous Extracts of Dried Corn Silk, Cumin Seed Powder or Tamarind Pulp, in Two Forms, Consumed with High Glycemic Index Rice.

Several plant-based traditional ingredients in Asia are anecdotally used for preventing and/or treating type 2 diabetes. We investigated three such widely consumed ingredients, namely corn silk (CS), cumin (CU), and tamarind (TA). The aim of the study was to determine the effects of aqueous extracts of these ingredients consumed either as a drink (D) with high-glycemic-index rice or added to the same amount of rice during cooking (R) on postprandial glycemia (PPG), insulinemia (PPI), and blood pressure (BP), over a 3 h measurement period.

Bioengineered smart trilayer skin tissue substitute for efficient deep wound healing.

Skin substitutes for deep wound healing require meticulous designing and fabrication to ensure proper structural and functional regeneration of the tissue. Range of physical and mechanical properties conducive for regeneration of different layers of skin is a prerequisite of an ideal scaffold. However, single or bilayer substitutes, lacking this feature, fail to heal full thickness wound.

Comparative study on the efficacy of the UHMWPE surface modification by chemical etching and electrostatic spraying method for drug release by orthopedic implants.

Failure of fixation between bone and implant surface due to bacterial infection, is one of the key challenges in total hip arthroplasty. It might lead to poor implant stability and complex revision surgery. Surface modification of an acetabular cup liner for sustained drug delivery is an effective approach to reduce the biofilms associated infection.