Leveraging HIV self-testing to achieve the UNAIDS 2025 targets in the South and Southeast Asia region.

Introduction: The South and Southeast Asia region has the second-highest number of people living with HIV globally. Despite progress in reducing HIV incidence and AIDS-related deaths, the region still has a long way to go in achieving the Joint United Nations Programme on HIV and AIDS (UNAIDS) 95-95-95 HIV testing, treatment and viral suppression targets. HIV self-testing (HIVST) is recommended by the World Health Organization as an additional approach to HIV testing.

A Cross-Sectional Assessment of HIV Self-Testing Preferences and Uptake Among Key Populations in Phnom Penh, Cambodia.

Background: HIV self-testing (HIVST) is recommended by the World Health Organization, but implementation remains limited. This cross-sectional study evaluated HIVST uptake among female entertainment workers (EWs), men who have sex with men (MSM), and transgender women in Phnom Penh, Cambodia, to inform national implementation.

Methods: Between December 2018 and September 2019, individuals reached through community outreach or via online advertising were offered HIVST or referrals to facility-based testing.

How Home Delivery of Antiretroviral Drugs Ensured Uninterrupted HIV Treatment During COVID-19: Experiences From Indonesia, Laos, Nepal, and Nigeria.

Introduction: Faced with the coronavirus disease (COVID-19) pandemic, governments worldwide instituted lockdowns to curtail virus spread. Health facility closures and travel restrictions disrupted access to antiretroviral (ARV) therapy for people living with HIV. This report describes how HIV programs in Indonesia, Laos, Nepal, and Nigeria supported treatment continuation by introducing home delivery of ARVs.

Uptake of oral fluid-based HIV self-testing among men who have sex with men and transgender women in Thailand.

Background: Suboptimal uptake of HIV testing remains a primary bottleneck to HIV prevention and treatment for men who have sex with men (MSM) and transgender women (TGW) in Thailand. The World Health Organization has recommended HIV self-testing (HIVST) as an additional strategic HIV service. However, HIVST has not been fully endorsed and implemented in many countries in Southeast Asia.

Go Where the Virus Is: An HIV Micro-epidemic Control Approach to Stop HIV Transmission.

Essentially all HIV transmission is from people living with HIV who are not virally suppressed. An HIV micro-epidemic control approach that differentiates treatment support and prevention services for people living with HIV and their network members according to viral burden could optimize the impact of epidemic control efforts.

Oligodendrocytes that survive acute coronavirus infection induce prolonged inflammatory responses in the CNS.

Neurotropic strains of mouse hepatitis virus (MHV), a coronavirus, cause acute and chronic demyelinating encephalomyelitis with similarities to the human disease multiple sclerosis. Here, using a lineage-tracking system, we show that some cells, primarily oligodendrocytes (OLs) and oligodendrocyte precursor cells (OPCs), survive the acute MHV infection, are associated with regions of demyelination, and persist in the central nervous system (CNS) for at least 150 d. These surviving OLs express major histocompatibility complex (MHC) class I and other genes associated with an inflammatory response.

Fast-tracking the end of HIV in the Asia Pacific region: domestic funding of key population-led and civil society organisations.

Ending AIDS in Asia Pacific by 2030 requires countries to give higher priority to financing community-based and key population-led service delivery. Mechanisms must be developed for civil society organisations to deliver health and HIV/AIDS services for key populations, especially men who have sex with men, and transgender people, within national health policy frameworks. Current investments in the HIV response in the Asia Pacific region reflect inadequate HIV financing for key populations, particularly for civil society and key population-led organisations that are optimally positioned to advance HIV epidemic control.

Getting to the First 90: Incentivized Peer Mobilizers Promote HIV Testing Services to Men Who Have Sex With Men Using Social Media in Mumbai, India.

Recent studies of Indian men who have sex with men (MSM) have shown widespread use of social media for seeking sex partners. We piloted a peer mobilization approach to explore the feasibility of engaging previously unreached MSM online to link them to HIV testing services (HTS). MSM were encouraged to seek HTS through messages posted on a popular dating website.

Characteristics and HIV epidemiologic profiles of men who have sex with men and transgender women in key population-led test and treat cohorts in Thailand.

Men who have sex with men (MSM) and Transgender Women (TGW) in Thailand contribute to more than half of all new HIV infections annually. This cross-sectional study describes epidemiologic profiles of these key populations (KP) in Key Population-led Test and Treat study. Baseline data were collected using self-administered questionnaires and HIV/STI testing from MSM and TGW aged ≥18 years enrolled in a cohort study in six community sites in Thailand between October 2015 and February 2016.

Importance of Risk Perception: Predictors of PrEP Acceptance Among Thai MSM and TG Women at a Community-Based Health Service.

Background: HIV prevalence among Thai men who have sex with men (MSM) and transgender women (TG) are 9.15% and 11.8%, respectively, compared with 1.

Evidence for intraventricular secretion of angiotensinogen and angiotensin by the subfornical organ using transgenic mice.

Direct intracerebroventricular injection of angiotensin II (ANG II) causes increases in blood pressure and salt and water intake, presumably mimicking an effect mediated by an endogenous mechanism. The subfornical organ (SFO) is a potential source of cerebrospinal fluid (CSF), ANG I, and ANG II, and thus we hypothesized that the SFO has a secretory function. Endogenous levels of angiotensinogen (AGT) and renin are very low in the brain.

Obesity-induced hepatic steatosis is mediated by endoplasmic reticulum stress in the subfornical organ of the brain.

Nonalcoholic fatty liver disease (NAFLD), characterized by an excess accumulation of hepatic triglycerides, is a growing health epidemic. While ER stress in the liver has been implicated in the development of NAFLD, the role of brain ER stress - which is emerging as a key contributor to a number of chronic diseases including obesity - in NAFLD remains unclear. These studies reveal that chemical induction of ER stress in the brain caused hepatomegaly and hepatic steatosis in mice.

Nervous System Expression of PPARγ and Mutant PPARγ Has Profound Effects on Metabolic Regulation and Brain Development.

Peroxisome proliferator activated receptor (PPARγ) is a nuclear receptor transcription factor that regulates adipogenesis and energy homeostasis. Recent studies suggest PPARγ may mediate some of its metabolic effects through actions in the brain. We used a Cre-recombinase-dependent (using Nestin) conditionally activatable transgene expressing either wild-type (WT) or dominant-negative (P467L) PPARγ to examine mechanisms by which PPARγ in the nervous system controls energy balance.

Selective Deletion of the Brain-Specific Isoform of Renin Causes Neurogenic Hypertension.

The renin-angiotensin system (RAS) in the brain is a critical determinant of blood pressure, but the mechanisms regulating RAS activity in the brain remain unclear. Expression of brain renin (renin-b) occurs from an alternative promoter-first exon. The predicted translation product is a nonsecreted enzymatically active renin whose function is unknown.

FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver.

The liver is an important integrator of nutrient metabolism, yet no liver-derived factors regulating nutrient preference or carbohydrate appetite have been identified. Here we show that the liver regulates carbohydrate intake through production of the hepatokine fibroblast growth factor 21 (FGF21), which markedly suppresses consumption of simple sugars, but not complex carbohydrates, proteins, or lipids. Genetic loss of FGF21 in mice increases sucrose consumption, whereas acute administration or overexpression of FGF21 suppresses the intake of both sugar and non-caloric sweeteners.

The Vulnerable Ventral Tegmental Area in Parkinson's Disease.

Introduction: The involvement of dopaminergic neurons in the ventral tegmental area (VTA) in Parkinson's disease (PD) has not been universally recognized by neuroscientists and neurologists. Here, we conduct a review of previous research documenting dopaminergic neuronal loss in both the substantia nigra pars compacta (SNpc) and VTA and add three new post-mortem PD cases to the literature.

Methods: PD and control brains were sectioned, stained for tyrosine hydroxylase, and cells in the SNpc and VTA were counted.

Nampt/PBEF/visfatin serum levels: a new biomarker for retinal blood vessel occlusions.

The main objective of the study was to quantify serum levels of nicotinamide phosphoribosyltransferase (Nampt/pre-B-Cell colony-enhancing factor 1/visfatin) in subjects with a history of retinal vascular occlusions (RVOs), disease conditions characterized by pronounced ischemia, and metabolic energy deficits. A case-control study of 18 subjects with a history of RVO as well as six healthy volunteers is presented. Serum Nampt levels were quantified using a commercially available enzyme-linked immunosorbent assay kit.

Brain endoplasmic reticulum stress mechanistically distinguishes the saline-intake and hypertensive response to deoxycorticosterone acetate-salt.

Endoplasmic reticulum stress has become an important mechanism in hypertension. We examined the role of endoplasmic reticulum stress in mediating the increased saline-intake and hypertensive effects in response to deoxycorticosterone acetate (DOCA)-salt. Intracerebroventricular delivery of the endoplasmic reticulum stress-reducing chemical chaperone tauroursodeoxycholic acid did not affect the magnitude of hypertension, but markedly decreased saline-intake in response to DOCA-salt.

Activation of the renin-angiotensin system, specifically in the subfornical organ is sufficient to induce fluid intake.

Increased activity of the renin-angiotensin system within the brain elevates fluid intake, blood pressure, and resting metabolic rate. Renin and angiotensinogen are coexpressed within the same cells of the subfornical organ, and the production and action of ANG II through the ANG II type 1 receptor in the subfornical organ (SFO) are necessary for fluid intake due to increased activity of the brain renin-angiotensin system. We generated an inducible model of ANG II production by breeding transgenic mice expressing human renin in neurons controlled by the synapsin promoter with transgenic mice containing a Cre-recombinase-inducible human angiotensinogen construct.

'Getting to zero' in Asia and the Pacific through more strategic use of antiretrovirals for HIV prevention.

Encouraged by experimental trials demonstrating the efficacy of antiretrovirals (ARVs) in preventing HIV infection, countries across the Asia-Pacific region have committed to the achievement of ambitious targets tantamount to ending AIDS. The available data suggest that some countries still can make progress through targeted condom promotion and the expansion of harm-reduction interventions, but that none may realise its vision of 'zero new HIV infections' without more strategic use of ARVs as part of a combination of HIV prevention efforts targeting key populations. Low rates of HIV testing among men who have sex with men, people who inject drugs, sex workers and other key populations evidence low treatment coverage where treatment could have the greatest impact on curbing local epidemics.

Interference with peroxisome proliferator-activated receptor-γ in vascular smooth muscle causes baroreflex impairment and autonomic dysfunction.

S-P467L mice expressing dominant negative peroxisome proliferator-activated receptor-γ selectively in vascular smooth muscle exhibit impaired vasodilation, augmented vasoconstriction, hypertension, and tachycardia. We hypothesized that tachycardia in S-P467L mice is a result of baroreflex dysfunction. S-P467L mice displayed increased sympathetic traffic to the heart and decreased baroreflex gain and effectiveness.

Activity of protein kinase C-α within the subfornical organ is necessary for fluid intake in response to brain angiotensin.

Angiotensin-II production in the subfornical organ acting through angiotensin-II type-1 receptors is necessary for polydipsia, resulting from elevated renin-angiotensin system activity. Protein kinase C and mitogen-activated protein kinase pathways have been shown to mediate effects of angiotensin-II in the brain. We investigated mechanisms that mediate brain angiotensin-II-induced polydipsia.

Localization and behaviors in null mice suggest that ASIC1 and ASIC2 modulate responses to aversive stimuli.

Acid-sensing ion channels (ASICs) generate H(+) -gated Na(+) currents that contribute to neuronal function and animal behavior. Like ASIC1, ASIC2 subunits are expressed in the brain and multimerize with ASIC1 to influence acid-evoked currents and facilitate ASIC1 localization to dendritic spines. To better understand how ASIC2 contributes to brain function, we localized the protein and tested the behavioral consequences of ASIC2 gene disruption.

Dimensions of subcortical infarcts associated with first- to third-order branches of the basal ganglia arteries.

Background: It has been described that lacunar infarct is characterized by its smallish size (15-20 mm) in the axial plane. However, the size of the basal ganglia artery responsible for this type of infarct is uncertain. Detection of small arterial occlusion is not possible with current angiography, hindering correlation of arterial occlusion with subcortical infarct size.