Karachi Medical and Dental College

N-acetyl-L-leucine (NALL), a stereospecific derivative of the essential amino acid L-leucine, has attracted increasing attention as a candidate therapy for neurological disorders. Preclinical and clinical studies suggest both symptomatic and neuroprotective effects. This review summarizes evidence on the mechanisms of action, preclinical findings, and clinical outcomes of NALL, and discusses its therapeutic prospects in neurological health and disease. A structured literature search of PubMed, Scopus, and Google Scholar was conducted to identify preclinical and clinical studies evaluating N-acetyl-L-leucine (NALL) in neurological disorders. Preclinical studies demonstrated that NALL enhances mitochondrial bioenergetics, reduces oxidative stress, restores lysosomal and autophagic function, and modulates neuroinflammation. In rodent models, NALL improved motor coordination, neuronal survival, and recovery following traumatic brain injury. Clinical trials in Niemann-Pick disease type C and GM2 gangliosidoses showed improvements in motor function, quality of life, and disease progression, with sustained benefit during extension phases. Preliminary evidence also suggests possible roles in multiple sclerosis, ataxia telangiectasia, Parkinson’s disease, and multiple sulfatase deficiency. NALL was consistently well tolerated with a favorable safety profile. NALL shows multimodal mechanisms and promising translational potential for both rare and common neurological disorders. While early evidence is encouraging, larger randomized trials are required to confirm efficacy, define optimal dosing, and determine its place in neurological therapeutics.

Foot-and-mouth disease (FMD) is one of the most contagious viral infections affecting livestock, including cattle, water buffalo, pigs, sheep, goats, and African buffalo. Caused by the foot-and-mouth disease virus (FMDV), it continues to impose a significant economic burden, with annual losses estimated at up to 21 billion U.S. dollars. This review examines the worldwide epidemiology and control of FMD through a One Health approach, emphasizing the interconnectedness of animal, human, and environmental health. Vaccination remains the most effective strategy for preventing and controlling FMD in both endemic and non-endemic regions, particularly when vaccines are well-matched to circulating strains. However, silent circulation of FMDV, where animals carry and shed the virus without showing clinical signs, presents a critical challenge to eradication efforts. Mucosal immunity emerges as a key component of protection, serving as the first line of defense at the virus’s point of entry and playing a vital role in blocking transmission. Equally important is the establishment of robust and systematic surveillance systems capable of detecting asymptomatic FMDV infections, which are essential for identifying hidden reservoirs and preventing undetected spread. Effectively combating FMD requires coordinated efforts that go beyond vaccine development alone. Success depends on integrated surveillance networks, strict quarantine and movement restriction policies, reliable diagnostic infrastructure, and the implementation of One Health frameworks that bring together veterinary services, agricultural authorities, and public health sectors. Together, these strategies bridge the gap between disease control and ultimate eradication.

Vascular disorders of the intestine (VDI) and ischemic heart disease (IHD) are linked by shared atherosclerotic risk factors including diabetes, hypertension, and smoking. Their coexistence poses a significant threat to population health, with associated high morbidity and mortality. While advances in care have improved outcomes, evolving trends and disparities remain under-investigated at the national level. This study assessed national mortality trends and demographic disparities in deaths attributed to vascular disorders of the intestine and ischemic heart disease among all age groups in the United States from 1999 to 2023. We used the CDC WONDER Multiple Cause of Death database (1999–2023) and identified deaths in which ICD-10 code K55 (vascular disorders of the intestine) and ICD-10 codes I20–I25 (ischemic heart disease) were concurrently listed on the same death certificate. Age-adjusted mortality rates were calculated and stratified by sex, race/ethnicity, and U.S. census regions. Joinpoint regression analysis was applied to evaluate temporal trends and compute annual percent change with 95

Granzyme B (GzmB), beyond its established role in corneal and conjunctival disease, is increasingly recognized in the retinal and choroidal distribution of several pathologies. GzmB targets tight-junction proteins (e.g., ZO-1, JAM-A) and extracellular proteins such as fibronectin and laminin within the retinal pigment epithelium (RPE) and Bruch’s membrane, thereby disrupting the outer blood–retinal barrier and contributing to the pathogenesis of age-related macular degeneration (AMD) and Macular neovascularization (MNV). This mini review highlights recent mechanistic insights into how GzmB drives extracellular matrix breakdown, inflammation, and angiogenesis; summarizes experimental and clinical evidence supporting its role in AMD; and discusses emerging therapeutic approaches, limitations, and translational potential for targeted therapy. Extracellular Granzyme B (GzmB) contributes to age-related degradation of retinal extracellular matrix and tight-junction proteins, weakening the outer blood–retinal barrier and facilitating early AMD pathology. Preclinical inhibition of GzmB reduces matrix proteolysis, inflammation, and tissue injury, highlighting its relevance as a modifiable driver of age-associated ocular degeneration. New data clarify how GzmB-driven ECM cleavage products shape angiogenic and fibrotic signaling, providing measurable endpoints that can guide therapeutic optimization and early-phase clinical testing. GzmB is identified as an active driver of AMD progression by degrading anti-angiogenic proteins (e.g., TSP-1) and generating pro-angiogenic ECM fragments, thereby promoting Macular neovascularization and subretinal fibrosis. Emerging selective small-molecule and cyclic-peptide GzmB inhibitors with ocular-targeted delivery systems represent a novel therapeutic class designed to limit extracellular proteolysis while avoiding systemic immune suppression.

The overuse of antibiotics without medical prescription is a major public health concern, leading to bacterial resistance that causes severe infections and increases global mortality. This study aimed to determine the prevalence and identify the main risk factors of antibiotic self-medication among patients admitted to the emergency department. This cross-sectional, descriptive, and analytical study was conducted over a five-month period (July to November 2024) among patients aged 18 years and older admitted to the emergency department. We collected sociodemographic data, data on self-medication practices, and data on access to care. Multivariable logistic regression was applied to identify independent factors associated with antibiotic self-medication. The prevalence of antibiotic self-medication among participants was 77.7