Surreptitious Administration of Disulfiram Along with Its Implantation Leading toDisulfiram-associated Encephalopathy: A Case Report.

Disulfiram is a US FDA-approved medication for the management of alcohol use disorder. However, compliance with disulfiram has been the Achilles' heel of its efficacy. Implantation and surreptitious administration of disulfiram are two methods occasionally used to ensure disulfiram compliance.

Understanding Indian Doctors' Attitudes Toward Alcohol Pharmacotherapy and Prescription: A Mediational Analysis.

Background: Alcohol use disorder (AUD) causes significant morbidity and mortality. Prescription of AUD pharmacotherapies remains low. Attitudes toward AUD pharmacotherapies influence their prescription rates.

A Survey of Medication Diffusion and Attitudes Among Indian Clinicians Toward Pharmacotherapies for Alcohol Use Disorder.

Introduction: Alcohol use disorder (AUD) is a significant cause of morbidity and mortality globally. However, uptake of AUD pharmacotherapies among clinicians has remained low. There exists a research gap regarding clinician attitudes and the diffusion of AUD pharmacotherapies among Indian clinicians.

Identification of novel brain penetrant GSK-3β inhibitors toward Alzheimer's disease therapy by virtual screening, molecular docking, dynamic simulation, and MMPBSA analysis.

One of the significant therapeutic targets for Alzheimer's disease (AD) is Glycogen Synthase Kinase-3β (GSK-3β). Inhibition of GSK-3β can prevent hyperphosphorylation of tau, and thus prevent formation and accumulation of neurofibrillary tangles and neuropil threads that block intracellular transport, trigger unfolded protein response, and increase oxidative stress, cumulatively leading to neurodegeneration. In this study, we have performed structure-based virtual screening of two small-molecule libraries from ChemDiv CNS databases using AutoDock Vina to identify hit molecules based on their binding affinities compared to that of an established GSK-3β inhibitor, indirubin-3'-monoxime (IMO).

Perceived Learning and Feedback of Students Following the Competency-based Clinical Rotation in Psychiatry: A Retrospective Review From Tertiary-care Teaching Institute in Central India.

Background: Competency-based medical education (CBME) offers avenues for effective psychiatry teaching to medical students. However, data concerning the feasibility, effectiveness, and students' perspectives on CBME-based clinical rotation, including psychiatry, needs to be explored in India. Therefore, this research aims to evaluate the student's learning effectiveness and feedback on the CBME-informed psychiatry posting.

Korsakoff Psychosis following involuntary treatment for alcohol use disorder.

Substance Use Disorders (SUDs) are a major cause of global mortality and morbidity. In India, Alcohol Use Disorder is among the most prevalent of these [1]. Inadequate knowledge about the illness and its treatment, lack of resources, and regressive government policies (criminalisation of drug use itself and lack of prioritisation for SUD treatment) are among the reasons for the large gap between the need for facilities and their availability [2].

Madhuca longifolia plant mediated green synthesis of cupric oxide nanoparticles: A promising environmentally sustainable material for waste water treatment and efficient antibacterial agent.

In current years, the development of efficient green methods for synthesis of metal oxide nanomaterials has attracted a great attention to the researchers since the plant-mediated synthesis is a cost-effective and a good alternative to chemical and physical methods. An efficient and eco-friendly route has been developed for the green synthesis of CuO nanoparticles (NPs) by Madhuca longifolia plant extract which acts as a non-toxic reducing agent. X-ray diffraction studies reveal the good crystallinity of the synthesized NPs and FTIR spectra confirm the synthesis of these NPs.

The scavenger receptor MARCO modulates TLR-induced responses in dendritic cells.

The scavenger receptor MARCO mediates macrophage recognition and clearance of pathogens and their polyanionic ligands. However, recent studies demonstrate MARCO expression and function in dendritic cells, suggesting MARCO might serve to bridge innate and adaptive immunity. To gain additional insight into the role of MARCO in dendritic cell activation and function, we profiled transcriptomes of mouse splenic dendritic cells obtained from MARCO deficient mice and their wild type counterparts under resting and activating conditions.

Design, synthesis and biological activity of multifunctional α,β-unsaturated carbonyl scaffolds for Alzheimer's disease.

A series of compounds containing an α,β-unsaturated carbonyl moiety, such as chalcones and coumarins were designed, synthesized and tested in a variety of assays to assess their potential as anti-Alzheimer's disease (AD) agents. The investigations included the inhibition of cholinesterases (AChE, BuChE), the inhibition of amyloid beta (Aβ) self-assembly and the disassembly of preformed Aβ oligomers. Several compounds showed excellent potential as multifunctional compounds for AD.

Diaryl hydrazones as multifunctional inhibitors of amyloid self-assembly.

The design and application of an effective, new class of multifunctional small molecule inhibitors of amyloid self-assembly are described. Several compounds based on the diaryl hydrazone scaffold were designed. Forty-four substituted derivatives of this core structure were synthesized using a variety of benzaldehydes and phenylhydrazines and characterized.

TRIF mediates Toll-like receptor 2-dependent inflammatory responses to Borrelia burgdorferi.

TRIF is an adaptor molecule important in transducing signals from intracellularly signaling Toll-like receptor 3 (TLR3) and TLR4. Recently, TLR2 was found to signal from intracellular compartments. Using a synthetic ligand for TLR2/1 heterodimers, as well as Borrelia burgdorferi, which is a strong activator of TLR2/1, we found that TLR2 signaling can utilize TRIF.

Environmental exposures, epigenetics and cardiovascular disease.

Purpose Of Review: Epigenetic modifications are heritable alterations of the genome, which can govern gene expression without altering the DNA sequence. The purpose of this review is to render an overview of the possible mechanisms of epigenetic regulation of gene expression in response to environmental pollutants leading to cardiovascular diseases (CVD).

Recent Findings: An era of cataloging epigenetic marks of the various diseased states has recently commenced, including those within the genes responsible for atherosclerosis, ischemia, hypertension and heart failure.

MARCO regulates early inflammatory responses against influenza: a useful macrophage function with adverse outcome.

Lung macrophages use the scavenger receptor MARCO to bind and ingest bacteria, particulate matter, and post cellular debris. We investigated the role of MARCO in influenza A virus (IAV) pneumonia. In contrast to higher susceptibility to bacterial infection, MARCO(-/-) mice had lower morbidity and mortality from influenza pneumonia than wild-type (WT) mice.

Anti-inflammatory effects of thiazolidinediones in human airway smooth muscle cells.

Airway smooth muscle (ASM) cells have been reported to contribute to the inflammation of asthma. Because the thiazolidinediones (TZDs) exert anti-inflammatory effects, we examined the effects of troglitazone and rosiglitazone on the release of inflammatory moieties from cultured human ASM cells. Troglitazone dose-dependently reduced the IL-1β-induced release of IL-6 and vascular endothelial growth factor, the TNF-α-induced release of eotaxin and regulated on activation, normal T expressed and secreted (RANTES), and the IL-4-induced release of eotaxin.

Left-sided cardiac valvulitis in tristetraprolin-deficient mice: the role of tumor necrosis factor alpha.

Inflammation may play a role in the etiology of both degenerative and rheumatic cardiac valve diseases. We report here that mice deficient in tristetraprolin (TTP), a protein with known anti-inflammatory functions, develop severe left-sided cardiac valvulitis. TTP is an mRNA binding protein that inhibits inflammation by destabilizing the mRNA encoding tumor necrosis factor alpha (TNF).

Production and characterization of ZFP36L1 antiserum against recombinant protein from Escherichia coli.

Tristetraprolin/zinc finger protein 36 (TTP/ZFP36) family proteins are anti-inflammatory. They bind and destabilize some AU-rich element-containing mRNAs such as tumor necrosis factor mRNA. In this study, recombinant ZFP36L1/TIS11B (a TTP homologue) was overexpressed in E.

An unusual pro-inflammatory role of interleukin-10 induced by arabinosylated lipoarabinomannan in murine peritoneal macrophages.

Various species of Mycobacteria produce a major cell wall-associated lipoglycan, called Lipoarabinomannan (LAM), which is involved in the virulence of Mycobacterial species. In this study, we tried to establish the role of the increased IL-10 secretion under Arabinosylated-LAM (Ara-LAM) treatment, the LAM that induces apoptosis in host macrophages or PBMC. We have studied the survival and apoptotic factors by western blotting, and estimated nitrite generation by Griess reaction, quantified iNOS mRNA by semi-quantitative RT-PCR, and ultimately the fate of the cells were studied by Flow Cytometric Analysis of AnnexinV-FITC binding.

Attempts to delineate the relative contributions of changes in hydrophobicity and packing to changes in stability of ribonuclease S mutants.

While the hydrophobic driving force is thought to be a major contributor to protein stability, it is difficult to experimentally dissect out its contribution to the overall free energy of folding. We have made large to small substitutions of buried hydrophobic residues at positions 8 and 13 in the peptide/protein complex, RNase-S, and have characterized the structures by X-ray crystallography. The thermodynamics of association of these mutant S peptides with S protein was measured in the presence of different concentrations of methanol and ethanol.

Zfp36l3, a rodent X chromosome gene encoding a placenta-specific member of the Tristetraprolin family of CCCH tandem zinc finger proteins.

Members of the tristetraprolin (TTP) family of CCCH tandem zinc finger (TZF) proteins can bind directly to AU-rich elements (ARE) in mRNA, causing deadenylation and destabilization of the transcripts to which they bind. We describe here a novel fourth mammalian member of the TTP protein family, designated ZFP36L3, which could also bind directly to ARE-containing RNAs and could promote the deadenylation and degradation of ARE-containing target RNAs. Zfp36l3 transcript expression was detected only in placenta and extraembryonic tissues in the mouse.

Chorioallantoic fusion defects and embryonic lethality resulting from disruption of Zfp36L1, a gene encoding a CCCH tandem zinc finger protein of the Tristetraprolin family.

The mouse gene Zfp36L1 encodes zinc finger protein 36-like 1 (Zfp36L1), a member of the tristetraprolin (TTP) family of tandem CCCH finger proteins. TTP can bind to AU-rich elements within the 3'-untranslated regions of the mRNAs encoding tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), leading to accelerated mRNA degradation. TTP knockout mice exhibit an inflammatory phenotype that is largely due to increased TNF secretion.

Leishmania donovani suppresses activated protein 1 and NF-kappaB activation in host macrophages via ceramide generation: involvement of extracellular signal-regulated kinase.

In vitro infection of murine peritoneal macrophages with the protozoan Leishmania donovani has been found to alter the signaling parameters of the host. The present study indicates that the enhancement of intracellular ceramide level in macrophages after infection is a major event relating to macrophage dysfunction. We have previously demonstrated that increased ceramide synthesis in host macrophages was involved in the dephosphorylation of extracellular signal-regulated kinase (ERK).

Chemokine-induced leishmanicidal activity in murine macrophages via the generation of nitric oxide.

This study explored the role of the proinflammatory chemokines macrophage inflammatory protein (MIP)-1alpha and macrophage chemoattractant protein (MCP)-1 for development of antileishmanial activity. There was substantial inhibition in nitrite generation in Leishmania donovani-infected macrophages. A marked elevation of nitrite generation and induction of inducible nitric oxide (NO) synthase (iNOS) mRNA was found in chemokine-primed parasite-infected macrophages.