METHODS: A cross-sectional descriptive study was conducted among PLWHA attending an ART centre of a tertiary care hospital in Islamabad, Pakistan. HRQoL was assessed using a validated Urdu version of EuroQol 5 dimensions 3 level (EQ-5D-3L) and its Visual Analogue Scale (EQ-VAS).
RESULTS: Of the 602 patients included in the analyses, 59.5% (n = 358) reported no impairment in self-care, while 63.1% (n = 380) were extremely anxious/depressed. The overall mean EQ-5D utility score and visual analogue scale (EQ-VAS) score were 0.388 (SD: 0.41) and 66.20 (SD: 17.22), respectively. Multivariate linear regression analysis revealed that the factors significantly associated with HRQoL were: female gender; age > 50 years; having primary and secondary education; > 1 year since HIV diagnosis; HIV serostatus AIDS-converted; higher CD 4 T lymphocytes count; detectable viral load; and increased time to ART.
CONCLUSIONS: The current findings have shown that PLWHA in Pakistan adherent to ART had a good overall HRQoL, though with significantly higher depression. Some of the factors identified are amenable to institution-based interventions while mitigating depression to enhance the HRQoL of PLWHA in Pakistan. The HRQoL determined in this study could be useful for future economic evaluation studies for ART and in designing future interventions.
OBJECTIVES: The present study investigates the effect of a novel 5-HT3 receptor antagonist 3-methoxy-N-p-tolylquinoxalin-2-carboxamide (QCM-4) on several pathogenic markers of depression associated with obesity such as plasma insulin resistance, hippocampal cyclic adenosine monophosphate (cAMP), brain-derived neurotrophic factor (BDNF), serotonin (5-HT) concentrations, hippocampal neuronal damage, and p53 protein expression in high-fat-diet (HFD)-fed mice.
METHODS: Obesity was experimentally induced in mice by feeding with HFD for 14 weeks followed by administration of QCM-4 (1 and 2 mg/kg, p.o.)/standard escitalopram (ESC) (10 mg/kg, p.o.)/vehicle (10 ml/kg, p.o.) for 28 days. Behavioral assays such as sucrose preference test (SPT); forced swim test (FST); elevated plus maze (EPM); biochemical assays including oral glucose tolerance tests (OGTT), insulin, cAMP, BDNF, and 5-HT concentrations; and molecular assays mainly histology and immunohistochemistry (IHC) of p53 protein in the dentate gyrus (DG), CA1, and CA3 regions of hippocampus in HFD fed mice were performed.
RESULTS: Chronic treatment with QCM-4 in HFD-fed mice reversed the behavioral alterations in SPT, FST, and EPM. QCM-4 showed poor sensitivity for plasma glucose, improved insulin sensitivity, increased hippocampal cAMP, BDNF, and 5-HT concentrations. In the hippocampal DG, CA1, and CA3 regions, QCM-4 treatment improved the neuronal morphology in the histopathology and inhibited p53 protein expression in IHC assay in HFD-fed mice.
CONCLUSION: QCM-4 attenuated the depressive-like phenotype in HFD-fed mice by improving behavioral, biochemical, and molecular alterations through serotonergic neuromodulation.