Pakistan Institute of Medical Sciences

Vaccinia virus (VACV) is a member of the Poxviridae family and served as the vaccine strain used to eradicate smallpox. As a large double-stranded DNA virus, VACV exhibits a broad host range and remains a model organism for studying viral evolution and gene expression. Codon usage bias (CUB) is a fundamental feature of genome evolution that reflects the interplay between mutational pressure and natural selection. In this study, we systematically analyzed codon usage patterns in 107 strains of Vaccinia virus (VACV) to uncover the driving forces behind its genomic evolution and host adaptation. Our findings revealed a strong A/T bias across all codon positions, particularly at the third codon position (AT3 = 66.59

Fluoride is a naturally occurring compound widely present in soil, water, rocks and is essential to maintain the physiological function and structure of bones and teeth. However, chronic exposure to elevated fluoride levels has been linked to adverse neurological effects. Despite its widespread environmental presence, the molecular mechanisms underlying fluoride-induced neurotoxicity remain incompletely understood. This study aimed to elucidate the effects of fluoride on oxidative stress, endoplasmic reticulum (ER) stress, apoptosis, and associated histopathological alterations in brain tissue. Forty Sprague–Dawley rats were randomly assigned to four groups (n = 10 per group; 5 male + 5 female) and administered sodium fluoride (NaF) in drinking water at concentrations of < 0.5 ppm (control), 50 ppm, 150 ppm, and 300 ppm for 90 consecutive days. The expression of antioxidant genes (SOD1 and GCLC), ER stress, and apoptosis-related genes (XBP1, GRP78, BCL-2, and BAX) was quantified using real-time quantitative PCR (RT-qPCR), and histopathological analysis of the brain tissues was performed. Fluoride exposure caused a dose-dependent downregulation of antioxidant and ER stress–related genes and concurrent upregulation of the pro-apoptotic genes. Histopathological analysis revealed structural damage in hippocampus and cerebral cortex, including neuronal shrinkage, vacuolization, and apoptotic features. These findings indicate that prolonged NaF exposure impairs antioxidant defenses, induces ER stress, and activates apoptotic pathways, thereby contributing to neuronal damage. This study provides mechanistic insights into fluoride-induced neurotoxicity and highlights the need for further research on potential therapeutic strategies targeting oxidative and ER stress pathways.

Background Long-acting injectable antiretroviral therapy (LAI-ART) is an emerging alternative to daily oral ART, offering the potential to improve adherence, reduce dosing frequency, and alleviate treatment fatigue among people with HIV. There is limited evidence on its real-world acceptability, feasibility, and implementation challenges in low- and middle-income countries, such as Pakistan, where structural barriers and health system limitations may influence uptake. Objective This study explores the perspectives on the feasibility and acceptability of LAI-ART among people currently receiving oral ART in Pakistan. Methods A qualitative study was conducted from November 2024 to January 2025, involving in-depth interviews from people in the ART center in Islamabad and community-based organizations, and one focus group discussion (FGD) with participants who are actively engaged in community-based peer advocacy across Pakistan. The data were analyzed using conventional thematic analysis with inductive coding. Results We conducted interviews with 37 participants, with one-to-one discussions with 31 people with HIV and 6 participants in FGD. Participants perceived LAI-ART as beneficial due to the elimination of pill burden, improved adherence, fewer side effects, lesser logistical demands, and greater privacy. However, injection-related adverse events, longer clinic waiting times, and limited availability were key barriers to its implementation. Those unwilling to adopt LAI-ART cited trust in oral ART, the convenience of multi-month refills, concerns of reduced adherence, work-related constraints. Conclusion LAI-ART is acceptable to people with HIV in Pakistan, offering adherence and privacy benefits. However, successful implementation depends on addressing concerns around safety, supply, and access through responsive, stigma-free, and people-centered care models.

Pain is the leading cause of disability worldwide, yet no harmonised self-reported reference framework exists to characterise how its burden is distributed across the lifespan and world regions. Here, we harmonised individual-level self-reported pain data from 6,075,021 participants across 894 population-based data sources in 118 countries to establish global reference trajectories of pain. We implemented these trajectories in an open-access benchmarking platform for positioning external datasets against global pain norms. Pain prevalence ranged from 2.5% for facial pain to 45.0% for back pain, was consistently higher in women across all eleven anatomical sites (risk ratio range 1.09 to 1.83), and increased most steeply before age 55 years. Contrary to existing estimates that generally project higher prevalence of pain conditions in higher Human Development Index (HDI) regions, we found that individuals in the lowest HDI countries experienced nearly twice the late-life prevalence of any bodily pain compared with those in the highest (risk difference 31.8 percentage points [95% CI 30.1–33.6]). Globally, 18.3% of pain burden across anatomical sites was attributable to three modifiable risk factors (smoking, obesity, and low income) but this varied from 12.6% in sub-Saharan Africa to 27.1% in eastern Europe, indicating that the drivers of pain in lower-HDI settings remain poorly characterised.