Problematic Internet Use Among Adolescent School Attendees: A School-based Study from Tamil Nadu, India.

Objective: To investigate the prevalence of problematic internet use (PIU) among adolescents and determine the associated factors contributing to PIU.

Methods: In April/May 2023, a cross-sectional study was conducted among adolescents studying in grades 9 to 12 in government and private non-residential schools in Western Tamil Nadu, India. Participants completed a semi-structured questionnaire assessing demographic characteristics, behavioral patterns, and internet usage.

Oxygen Scarcity and COVID-19: Lessons Learned During the May-June 2021 Peak, Karnataka, India.

Oxygen is a most essential medical gas. This report shows the observations during the second wave of oxygen management in Karnataka, India, where there was an unprecedented rise in COVID-19 cases during May-June 2021. The state was allocated 731 metric tons against the actual requirement 1200 (63%).

Protocol for establishing a model for integrated influenza surveillance in Tamil Nadu, India.

The potential for influenza viruses to cause public health emergencies is great. The World Health Organisation (WHO) in 2005 concluded that the world was unprepared to respond to an influenza pandemic. Available surveillance guidelines for pandemic influenza lack the specificity that would enable many countries to establish operational surveillance plans.

Clinical profile of patients infected with suspected SARS-CoV-2 Omicron variant of concern, Tamil Nadu, India, December 2021-January 2022.

Background & Objectives: COVID-19 cases have been rising rapidly in countries where the SARS-CoV-2 variant of concern (VOC), Omicron (B.1.1.

Kyasanur Forest Disease, is our surveillance system healthy to prevent a larger outbreak? A mixed-method study, Shivamogga, Karnataka, India: 2019.

Background: Kyasanur Forest disease (KFD) is a tick-borne zoonosis that is endemic in Karnataka. Against the backdrop of the recent geographical expansion of KFD, indicating the inadequacy of policy and surveillance systems, the present study was performed to evaluate the KFD surveillance system in Shivamogga.

Methods: US Centers for Disease Control and Prevention guidelines for surveillance system evaluation were followed.

Reversible, orally available ADP receptor (P2Y) antagonists Part I: Hit to lead process.

A hit to lead process to identify reversible, orally available ADP receptor (P2Y) antagonists lead compounds is described. High throughput screening afforded 1. Optimization of 1, using parallel synthesis methods, a methyl scan to identify promising regions for optimization, and exploratory SAR on these regions, provided 22 and 23.

Discovery of Highly Potent Liver X Receptor β Agonists.

Introducing a uniquely substituted phenyl sulfone into a series of biphenyl imidazole liver X receptor (LXR) agonists afforded a dramatic potency improvement for induction of ATP binding cassette transporters, ABCA1 and ABCG1, in human whole blood. The agonist series demonstrated robust LXRβ activity (>70%) with low partial LXRα agonist activity (<25%) in cell assays, providing a window between desired blood cell ABCG1 gene induction in cynomolgus monkeys and modest elevation of plasma triglycerides for agonist . The addition of polarity to the phenyl sulfone also reduced binding to the plasma protein, human α-1-acid glycoprotein.

Beneficial and Adverse Effects of an LXR Agonist on Human Lipid and Lipoprotein Metabolism and Circulating Neutrophils.

The development of LXR agonists for the treatment of coronary artery disease has been challenged by undesirable properties in animal models. Here we show the effects of an LXR agonist on lipid and lipoprotein metabolism and neutrophils in human subjects. BMS-852927, a novel LXRβ-selective compound, had favorable profiles in animal models with a wide therapeutic index in cynomolgus monkeys and mice.

Assessment of 'accredited social health activists'-a national community health volunteer scheme in Karnataka State, India.

About 700,000 Accredited Social Health Activists (ASHA) have been deployed as community health volunteers throughout India over the last few years. The objective of our study was to assess adherence to selection criteria in the recruitment of ASHA workers and to assess their performance against their job descriptions in Karnataka state, India. A cross-sectional survey, using a combination of quantitative and qualitative methods, was undertaken in 2012.

Pharmacological characterization of a novel liver X receptor agonist with partial LXRα activity and a favorable window in nonhuman primates.

Liver X Receptors (LXRs) α and β are nuclear hormone receptors that regulate multiple genes involved in reverse cholesterol transport (RCT) and are potential drug targets for atherosclerosis. However, full pan agonists also activate lipogenic genes, resulting in elevated plasma and hepatic lipids. We report the pharmacology of BMS-779788 [2-(2-(1-(2-chlorophenyl)-1-methylethyl)-1-(3'-(methylsulfonyl)-4-biphenylyl)-1H-imidazol-4-yl)-2-propanol], a potent partial LXR agonist with LXRβ selectivity, which has an improved therapeutic window in the cynomolgus monkey compared with a full pan agonist.

Liver X receptor (LXR) partial agonists: biaryl pyrazoles and imidazoles displaying a preference for LXRβ.

A series of biaryl pyrazole and imidazole Liver X Receptor (LXR) partial agonists has been synthesized displaying LXRβ selectivity. The LXRβ selective partial agonist 18 was identified with potent induction of ATP binding transporters ABCA1 and ABCG1 in human whole blood (EC50=1.2μM, 55% efficacy).

Relationship of personality dimensions and aggression in romantic relationship among youth.

Background: Aggression in romantic relationships is a continuing factor for breakups, physical assault, kidnapping, rape and even murder. It is also associated with adjustment difficulties including peer rejection, depression and maladaptive personality features. The present study aims to explore the personality correlates of aggression in romantic relationship.

Discovery and characterization of an inhibitor of glucosylceramide synthase.

Targeting glycosphingolipid synthesis has emerged as a novel approach for treating metabolic diseases. 32 (EXEL-0346) represents a new class of glucosylceramide synthase (GCS) inhibitors. This report details the elaboration of hit 8 with the goal of achieving and maintaining maximum GCS inhibition in vivo.

Discovery of a new class of glucosylceramide synthase inhibitors.

A novel series of potent inhibitors of glucosylceramide synthase are described. The optimization of biochemical and cellular potency as well as ADME properties led to compound 23c. Broad tissue distribution was obtained following oral administration to mice.

Test Anxiety Scale: reliability among Ethiopian students.

Sarason's Test Anxiety Scale, translated into an Ethiopian language, was administered to 391 students in Grade 8 and to 422 students in preparatory school (Grades 11 and 12). In the first sample, 32 items loaded above the 0.3 criterion of acceptable item-remainder correlations and Cronbach alpha of .

Death anxiety among Ethiopian undergraduate students.

Measurement of Death Anxiety among 151 Ethiopian undergraduate students using Templer's scale and Thorson and Powell's scale revealed that the sample has slightly higher than average death anxiety. The results also indicate that in this largely Orthodox Christian sample, students were afraid of the pain in death and less afraid of what happens to their body after death. As some items in each scale did not work well, the Cronbach alphas were low, .

Discovery of XL335 (WAY-362450), a highly potent, selective, and orally active agonist of the farnesoid X receptor (FXR).

Azepino[4,5-b]indoles have been identified as potent agonists of the farnesoid X receptor (FXR). In vitro and in vivo optimization has led to the discovery of 6m (XL335, WAY-362450) as a potent, selective, and orally bioavailable FXR agonist (EC(50) = 4 nM, Eff = 149%). Oral administration of 6m to LDLR(-/-) mice results in lowering of cholesterol and triglycerides.

1-(1,3-Benzodioxol-5-ylmethyl)-3-[4-(1H-imidazol-1-yl)phenoxy]-piperidine analogs as potent and selective inhibitors of nitric oxide formation.

A new series of 1-(1,3-benzodioxol-5-ylmethyl)-3-[4-(1H-Imidazol-1-yl)phenoxy]-piperidine analogs were designed and identified as potent and selective inhibitors of NO formation based both on the crystal structure of a murine iNOS Delta114 monomer domain/ inhibitor complex and inhibition of the NO formation in human A172 cell assays. Compound 12S showed high potency and high iNOS selectivity versus nNOS and eNOS.

3-Mercaptopropionic acids as efficacious inhibitors of activated thrombin activatable fibrinolysis inhibitor (TAFIa).

A novel series of cyclic potent, selective, small molecule, thiol-based inhibitors of activated thrombin activatable fibrinolysis inhibitor (TAFIa) and the crystal structures of TAFIa inhibitors bound to porcine pancreatic carboxypeptidase B are described. Three series of cyclic arginine and lysine mimetic inhibitors vary significantly in their selectivity against other human basic carboxypeptidases, carboxypeptidase N and carboxypeptidase B. (-)2a displays TAFIa IC50 = 3 nM and 600-fold selectivity against CPN.

Attitude towards euthanasia in relation to death anxiety among a sample of 343 nurses in India.

Scores on Attitude towards Euthanasia were correlated with scores on Death Anxiety among 343 female nurses in India using Templer's Death Anxiety Scale and the authors' 24-item attitude scale. No significant correlation was found between the two sets of scores (r = -.09) or a nonlinear score on relation.

Crystal structures of potent thiol-based inhibitors bound to carboxypeptidase B.

This paper presents the crystal structure of porcine pancreatic carboxypeptidase B (pp-CpB) in complex with a variety of thiol-based inhibitors that were developed as antagonists of activated thrombin-activatable fibrinolysis inhibitor (TAFIa). Recent studies have indicated that a selective inhibitor of TAFIa could enhance the efficacy of existing thrombolytic agents for the treatment of acute myocardial infarction, one of the most prevalent forms of heart attacks. Unfortunately, activated TAFIa rapidly degrades in solution and cannot be used for crystallographic studies.

Solid-phase synthesis of naphthylamidines as factor VIIa/tissue factor inhibitors.

Reductive amination followed by acylation of polymer-linked formyl aryl amidines generate combinatorial libraries of aryl amidines 8-13. Potent small molecule naphthylamidine inhibitors 12 (Ki<100 nM) of FVIIa/TF have been discovered and their activity against other serine proteases in the coagulation cascade is reported.

Identification of a selective inverse agonist for the orphan nuclear receptor estrogen-related receptor alpha.

The estrogen-related receptor alpha (ERRalpha) is an orphan receptor belonging to the nuclear receptor superfamily. The physiological role of ERRalpha has yet to be established primarily because of lack of a natural ligand. Herein, we describe the discovery of the first potent and selective inverse agonist of ERRalpha.