Features and frequency of use of electronic health records in primary care across 20 countries: a cross-sectional study.

Objectives: Variation exists in the capabilities of electronic healthcare records (EHRs) systems and the frequency of their use by primary care physicians (PCPs) from different settings. We aimed to examine the factors associated with everyday EHRs use by PCPs, characterise the EHRs features available to PCPs, and to identify the impact of practice settings on feature availability.

Study Design: Cross-sectional study.

General practitioners' perceptions of using virtual primary care during the COVID-19 pandemic: An international cross-sectional survey study.

With the onset of COVID-19, general practitioners (GPs) and patients worldwide swiftly transitioned from face-to-face to digital remote consultations. There is a need to evaluate how this global shift has impacted patient care, healthcare providers, patient and carer experience, and health systems. We explored GPs' perspectives on the main benefits and challenges of using digital virtual care.

Evaluating the Impact of COVID-19 on the Adoption of Virtual Care in General Practice in 20 Countries (inSIGHT): Protocol and Rationale Study.

Background: In recent decades, virtual care has emerged as a promising option to support primary care delivery. However, despite the potential, adoption rates remained low. With the outbreak of COVID-19, it has suddenly been pushed to the forefront of care delivery.

A novel mutant 10Ala/Arg together with mutant 144Ser/Arg of hepatitis B virus X protein involved in hepatitis B virus-related hepatocarcinogenesis in HepG2 cell lines.

Hepatitis B virus (HBV) infection-related hepatocellular carcinoma (HCC) represents a major health problem worldwide. HBV X (HBx) protein is the most common open reading frame that may undergo mutations, resulting in the development of HCC. This study aimed to determine specific HBx mutations that differentiate the central- and para-tumor tissues, and identify their association with HCC development.

Pooled Nucleic Acid Testing to Detect Antiretroviral Treatment Failure in HIV-Infected Patients in Mozambique.

Background: In resource-limited settings, viral load monitoring of HIV-infected patients receiving antiretroviral therapy (ART) is not readily available because of high costs. Here, we compared the accuracy and costs of quantitative and qualitative pooled methods with standard viral load testing.

Methods: Blood was collected prospectively from 461 patients receiving first-line ART in Mozambique who had not been evaluated previously with viral load testing.

Genetic attributes of blood-derived subtype-C HIV-1 tat and env in India and neurocognitive function.

Genetic elements in HIV-1 subtype B tat and env are associated with neurotoxicity yet less is known about other subtypes. HIV-1 subtype C tat and env sequences were analyzed to determine viral genetic elements associated with neurocognitive impairment in a large Indian cohort. Population-based sequences of HIV-1 tat (exon 1) and env (C2-V3 coding region) were generated from blood plasma of HIV-infected patients in Pune, India.

A synthetic bivalent ligand of CXCR4 inhibits HIV infection.

G-protein-coupled receptors (GPCRs) are cell membrane protein receptors that transduce signals across the cell membrane and are important targets for therapeutic interventions. As members of the GPCR superfamily, chemokine receptors such as CXCR4 play critical roles in normal physiology as well as the pathology of many human diseases including cancer, inflammation, autoimmune diseases, and human immunodeficiency virus (HIV) infection. Here we report the discovery and study of a novel peptide ligand of CXCR4 using d-amino acids and bivalent ligand approach.

The relatedness of HIV epidemics in the United States-Mexico border region.

Phylogeography can improve the understanding of local and worldwide HIV epidemics, including the migration of subepidemics across national borders. We analyzed HIV-1 sequences sampled from Mexico and San Diego, California to determine the relatedness of these epidemics. We sampled the HIV epidemics in (1) Mexico by downloading all publicly available HIV-1 pol sequences from antiretroviral-naive individuals in GenBank (n = 100) and generating similar sequences from cohorts of injection drug users and female sex workers in Tijuana, Mexico (n = 27) and (2) in San Diego, California by pol sequencing well-characterized primary (n = 395) and chronic (n = 267) HIV infection cohorts.

Discovery of 1-[3-(4-bromo-2-methyl-2h-pyrazol-3-yl)-4-methoxyphenyl]-3-(2,4-difluorophenyl)urea (nelotanserin) and related 5-hydroxytryptamine2A inverse agonists for the treatment of insomnia.

Insomnia affects a growing portion of the adult population in the U.S. Most current therapeutic approaches to insomnia primarily address sleep onset latency.

Lorcaserin, a novel selective human 5-hydroxytryptamine2C agonist: in vitro and in vivo pharmacological characterization.

5-Hydroxytryptamine (5-HT)(2C) receptor agonists hold promise for the treatment of obesity. In this study, we describe the in vitro and in vivo characteristics of lorcaserin [(1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3 benzazepine], a selective, high affinity 5-HT(2C) full agonist. Lorcaserin bound to human and rat 5-HT(2C) receptors with high affinity (K(i) = 15 +/- 1 nM, 29 +/- 7 nM, respectively), and it was a full agonist for the human 5-HT(2C) receptor in a functional inositol phosphate accumulation assay, with 18- and 104-fold selectivity over 5-HT(2A) and 5-HT(2B) receptors, respectively.

Discovery and structure-activity relationship of (1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine (Lorcaserin), a selective serotonin 5-HT2C receptor agonist for the treatment of obesity.

The synthesis and SAR of a novel 3-benzazepine series of 5-HT2C agonists is described. Compound 7d (lorcaserin, APD356) was identified as one of the more potent and selective compounds in vitro (pEC50 values in functional assays measuring [(3)H]phosphoinositol turnover: 5-HT2C = 8.1; 5-HT2A = 6.

Characteristics of recently HIV-infected men who use the Internet to find male sex partners and sexual practices with those partners.

Objective: To examine (1) characteristics of recently HIV-infected men who have sex with men (MSM) who find sex partners through the Internet and (2) differences in characteristics of and sexual behaviors practiced with Internet partners as compared to other partner types.

Methods: From May 2002 to 2005, a computer-assisted self-interview was administered to 194 recently HIV-infected MSM in southern California. MSM who used the Internet to find sex partners were compared with those who did not report Internet use, and partners found from the Internet were compared with those who were found from other venues using chi analyses, t tests, logistic regression, and generalized estimating equations.

Synthesis and SAR of novel di- and trisubstituted 1,4-dihydroquinoxaline-2,3-diones related to licostinel (Acea 1021) as NMDA/glycine site antagonists.

A series of novel di- and trisubstituted 1,4-dihydroquinoxaline-2,3-diones (QXs) related to licostinel (Acea 1021) was synthesized and evaluated as antagonists for the glycine site of the N-methyl-D-asparate (NMDA) receptor. The in vitro potency of these antagonists was determined by displacement of the glycine site radioligand [(3)H]-5,7-dichlorokynurenic acid ([(3)H]DCKA) in rat brain cortical membranes. Structure-activity relationship studies indicate that a cyano group is a good replacement for the nitro group in the 5-position of licostinel while 5-carboxy, 5-ester, 5-ketone and 5-amide derivatives showed reduced potency.

Synthesis and SAR of 5-, 6-, 7- and 8-aza analogues of 3-aryl-4-hydroxyquinolin-2(1H)-one as NMDA/glycine site antagonists.

A series of 5-, 6-, 7- and 8-aza analogues of 3-aryl-4-hydroxyquinolin-2(1H)-one was synthesized and assayed as NMDA/glycine receptor antagonists. The in vitro potency of these antagonists was determined by displacement of the glycine site radioligand [(3)H]5,7-dicholorokynurenic acid ([(3)H]DCKA) in rat brain cortical membranes. Selected compounds were also tested for functional antagonism using electrophysiological assays in Xenopus oocytes expressing cloned NMDA receptor (NR) 1A/2C subunits.

Subtype-selective N-methyl-D-aspartate receptor antagonists: synthesis and biological evaluation of 1-(heteroarylalkynyl)-4-benzylpiperidines.

4-[4-(4-Benzylpiperidin-1-yl)but-1-ynyl]phenol (8) and 4-[3-(4-benzylpiperidin-1-yl)prop-1-ynyl]phenol (9) are potent NR1A/2B receptor antagonists (IC(50) values 0.17 and 0.10 microM, respectively).

Opioid activity profiles indicate similarities between the nociceptin/orphanin FQ and opioid receptors.

Nociceptin (orphanin FQ) is the recently discovered peptide agonist for the orphan receptor opioid receptor-like 1 (ORL1). Despite the high sequence homology between ORL1 and the opioid receptors, most opioids lack affinity for the nociceptin receptor. The affinity and functional profile of opioids possessing activity at the nociceptin receptor was determined using [3H]nociceptin and nociceptin-stimulated [35S]GTPgammaS binding.

4-Hydroxy-1-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzyl)piperidine: a novel, potent, and selective NR1/2B NMDA receptor antagonist.

A structure-based search and screen of our compound library identified N-(2-phenoxyethyl)-4-benzylpiperidine (8) as a novel N-methyl-D-aspartate (NMDA) receptor antagonist that has high selectivity for the NR1/2B subunit combination (IC(50) = 0.63 microM). We report on the optimization of this lead compound in terms of potency, side effect liability, and in vivo activity.

5-(N-oxyaza)-7-substituted-1,4-dihydroquinoxaline-2,3-diones: novel, systemically active and broad spectrum antagonists for NMDA/glycine, AMPA, and kainate receptors.

A group of 5-aza-7-substituted-1,4-dihydroquinoxaline-2,3-diones (QXs) and the corresponding 5-(N-oxyaza)-7-substituted QXs were prepared and evaluated as antagonists of ionotropic glutamate receptors. The in vitro potency of these QXs was determined by inhibition of [3H]-5,7-dichlorokynurenic acid ([3H]DCKA) binding to N-methyl-D-aspartate (NMDA)/glycine receptors, [3H]-(S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([3H]AMPA) binding to AMPA receptors, and [3H]kainate ([3H]KA) binding to KA receptors in rat brain membranes. 5-(N-Oxyaza)-QXs 12a-e all have low micromolar or submicromolar potency for NMDA/glycine receptors and low micromolar potencies for AMPA and KA receptors.

Effects of thiocyanate and AMPA receptor ligands on (S)-5-fluorowillardiine, (S)-AMPA and (R,S)-AMPA binding.

AMPA receptors can be labeled using the agonist radioligands [3H](R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H](R,S)-AMPA), [3H](S)-AMPA or [3H](S)-5-fluorowillardiine. In the presence of KSCN, [3H](R,S)-AMPA and [3H](S)-AMPA bind to a single population of sites in rat brain membranes, whereas [3H](S)-5-fluorowillardiine binds with two affinity components. KSCN increased the affinity of the low affinity [3H](S)-5-fluorowillardiine component > 4-fold and increased the density of both components 1.

Structure-activity relationships of alkyl- and alkoxy-substituted 1,4-dihydroquinoxaline-2,3-diones: potent and systemically active antagonists for the glycine site of the NMDA receptor.

We report on a series of alkyl- and alkoxy-substituted 1,4-dihydroquinoxaline-2,3-diones (QXs), prepared as a continuation of our structure-activity relationship (SAR) study of QXs as antagonists for the glycine site of the N-methyl-D-aspartate (NMDA) receptor. The in vitro potency of these antagonists was determined by displacement of the glycine site radioligand [3H]-5,7-dichlorokynurenic acid ([3H]DCKA) in rat brain cortical membranes. In general, methyl is a good replacement for chloro or bromo in the 6-position, and alkoxy-substituted QXs have lower potencies than alkyl- or halogen-substituted QXs.

Analogs of 3-hydroxy-1H-1-benzazepine-2,5-dione: structure-activity relationship at N-methyl-D-aspartate receptor glycine sites.

A series of aromatic and azepine ring-modified analogs of 3-hydroxy-1H-1-benzazepine-2,5-dione (HBAD) were synthesized and evaluated as antagonists at NMDA receptor glycine sites. Aromatic ring-modified HBADs were generally prepared via a Schmidt reaction with substituted 2-methoxynaphthalene-1,4-diones followed by demethylation. Electrophilic aromatic substitution of benzazepine 3-methyl ethers gave 7-substituted analogs.