The dopamine D1 receptor positive allosteric modulator, DETQ, improves cognition and social interaction in aged mice and enhances cortical and hippocampal acetylcholine efflux.

Dopamine (DA) D1 and D2 receptors (Rs) are critical for cognitive functioning. D1 positive allosteric modulators (D1PAMs) activate D1Rs without desensitization or an inverted U-shaped dose response curve. DETQ, [2-(2,6-dichlorophenyl)-1-((1S,3R)-3-(hydroxymethyl)-5-(2-hydroxypropan-2-yl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one] is highly selective for the human D1Rs as shown in humanized D1R knock-in (hD1Ki) mice.

NU-1223, a simplified analog of alstonine, with 5-HTR agonist-like activity, rescues memory deficit and positive and negative symptoms in subchronic phencyclidine mouse model of schizophrenia.

The serotonin (5-HT) receptor(R) is a widely distributed G-protein-coupled receptor, expressed abundantly in the central nervous system. Alstonine is a natural product that has significant properties of atypical antipsychotic drugs (AAPDs), in part attributed to 5-HTR agonism. Based on alstonine, we developed NU-1223, a simplified β carboline analog of alstonine, which shows efficacies comparable to alstonine and to other 5-HTR agonists, Ro-60-0175 and lorcaserin.

Repeated administration of rapastinel produces exceptionally prolonged rescue of memory deficits in phencyclidine-treated mice.

Rapastinel, a positive N-methyl-D-aspartate receptor (NMDAR) modulator with rapid-acting antidepressant properties, rescues memory deficits in rodents. We have previously reported that a single intravenous dose of rapastinel, significantly, but only transiently, prevented and rescued deficits in the novel object recognition (NOR) test, a measure of episodic memory, produced by acute or subchronic administration of the NMDAR antagonists, phencyclidine (PCP) and ketamine. Here, we tested the ability of single and multiple subcutaneous doses per day of rapastinel to restore NOR and operant reversal learning (ORL) deficits in subchronic PCP-treated mice.

Single-View Echocardiography by Nonexpert Practitioners to Detect Rheumatic Heart Disease: A Prospective Study of Diagnostic Accuracy.

Background: Echocardiographic screening can detect asymptomatic cases of rheumatic heart disease (RHD), facilitating access to treatment. Barriers to implementation of echocardiographic screening include the requirement for expensive equipment and expert practitioners. We aimed to evaluate the diagnostic accuracy of an abbreviated echocardiographic screening protocol (single parasternal-long-axis view with a sweep of the heart) performed by briefly trained, nonexpert practitioners using handheld ultrasound devices.

Hyperendemic rheumatic heart disease in a remote Australian town identified by echocardiographic screening.

Objectives: Using echocardiographic screening, to estimate the prevalence of rheumatic heart disease (RHD) in a remote Northern Territory town.

Design: Prospective, cross-sectional echocardiographic screening study; results compared with data from the NT rheumatic heart disease register.

Setting, Participants: People aged 5-20 years living in Maningrida, West Arnhem Land (population, 2610, including 2366 Indigenous Australians), March 2018 and November 2018.

Human Papillomavirus Vaccine Uptake, Knowledge, and Acceptance for Youth: A Systematic Review of Appalachia.

Though vaccine uptake and public support have risen since the release of the first HPV vaccines, the United States has far lower initiation and completion rates for the HPV vaccine series in comparison to other vaccines indicated for youth. Disparities are even greater in the Appalachian regions. Understanding factors contributing to these discrepancies is vital to improving vaccine rates in Appalachia.