University of Swabi

Background: Tightness of the plantar fascia and calf muscles causes foot pain, altered gait, and reduced work efficiency. Salespersons, due to prolonged standing, repetitive lifting, and limited breaks, are at high risk. Despite global evidence linking these factors to foot disorders, local data from retail workers in Khyber Pakhtunkhwa remain limited. Objective: To determine the prevalence of plantar fascia and gastrocnemius tightness among salespersons in Swat and to identify associated demographic, lifestyle, and occupational factors. Methodology: A cross-sectional analytical study was conducted among 377 salespersons selected through convenience sampling from retail stores and shopping centers in Swat. Data were collected using a structured questionnaire and clinical assessment. The Windlass test evaluated plantar fascia tightness, while the Silfverskiöld test assessed gastrocnemius tightness. Demographic characteristics, body mass index, physical activity, smoking status, footwear type, and occupational factors were recorded. Associations were analyzed using the Chi-square test with a significance level of p<0.05. The study followed STROBE guidelines. Results: The mean age was 26.75±6.19 years, and the mean body mass index was 23.21±4.41. Males constituted 66% of participants. Plantar fascia tightness was found in 52.5%, and gastrocnemius tightness in 72.9% of participants. BMI showed significant associations with gastrocnemius (p=0.001) and plantar fascia tightness (p=0.025). Gender was significantly associated with plantar fascia tightness (p<0.001), with males more affected. Footwear type, physical activity level, and employment duration were significantly associated (p=0.001), while workplace type and daily working hours were not. Conclusion: Plantar fascia and calf muscle tightness are common among Swat salespersons, linked to body mass index, footwear, and lifestyle. Ergonomics, proper footwear, weight management, and stretching are recommended to prevent musculoskeletal issues.

Typhoid fever is a potentially fatal systemic infection caused by Salmonella typhi (S. typhi), a Gram-negative, rod-shaped, facultative anaerobe. This study aimed to characterize the efflux pump genes, molecular mutations, and antibiotic susceptibility patterns in clinical isolates. A total of 2950 blood samples were collected from suspected typhoid patients. Of these, 380 (12.88%) bacterial isolates were recovered, of which 236 (62.10%) were Gram-negative. S. typhi was detected in 95 isolates (25% of all bacterial isolates), corresponding to an overall prevalence of 3.22%. Identification was performed using API 20-E strips and partial 16S rRNA gene sequencing. Resistance profiling classified the isolates into multidrug-resistant (MDR, 13.68%) and extensively drug-resistant (XDR, 86.31%) categories. High resistance was observed to ampicillin (98.94%) and chloramphenicol (93.68%), whereas no resistance was detected to azithromycin or meropenem. Minimum inhibitory concentration (MIC) testing using E-Strips showed the highest MIC values for trimethoprimsulfamethoxazole (MIC50: 0.125 μg/ml, MIC90: 0.50 μg/ml) and the lowest for ciprofloxacin (MIC₅₀: 0.008 μg/ml, MIC₉₀: 0.023 μg/ml). Among the efflux pump genes, mdtB (32.63%) was the most prevalent, followed by mdtC (30.52%) and mdtA (29.47%). Multiple mutations were identified and evaluated using the I-Mutant 2.0 server. Protein structures were modeled using trRosetta and Discovery Studio. Phylogenetic analysis using MEGA-11 revealed evolutionary relationships with other Salmonella enterica serovars. A serious public health issue that increases mortality and morbidity rates worldwide is antibiotic resistance. Among the mechanisms underlying antibiotic resistance in bacteria are degradation of antibiotics and/or modification of enzymes, changing drug targets to alter the affinity of antibiotics, altering bacterial surfaces by changing the expression of external membrane proteins, and active bacterial efflux of drugs. The drug's binding affinity can be changed by mutations in efflux pump genes that change the shape of the substrate- binding pocket. These structural alterations may improve the pump's capacity to identify and eliminate antibiotics, reducing intracellular drug levels and increasing resistance to several drugs. This study highlights the alarming rise of multidrug resistance in S. typhi isolates and identifies key genetic mutations that may influence efflux pump function, potentially contributing to enhanced antibiotic resistance.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder linked with oxidative imbalance, cholinergic dysfunction and neuroinflammation, necessitates developing new multitarget natural compounds with potential disease-modifying action. Piperitone was evaluated using in-silico, in-vitro and in-vivo methods. In-silico study identified the pharmacokinetic parameters (PK) and the interaction stability of piperitone with acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase. In-vivo assessment of spatial memory in scopolamine-induced rat model was identified by behavioral assays with donepezil as a reference standard. In-vitro assays identified activity of cholinesterases, oxidative stress markers, levels of antioxidants and neuroinflammatory substrates, quantified with Reverse Transcription Polymerase Chain Reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Piperitone demonstrated favorable PK properties & docking scores comparable to Donepezil, Tacrine & QUD. Molecular dynamics simulations (MDS) confirmed stable associations with catalytic residues of cholinesterases and beta-secretase. Dose dependent reduction was recorded in cholinesterases, improvement in behavioral outcomes, and supplemented defenses of antioxidants including Glutathione (Reduced Form (GSH), Glutathione S-Transferase (GST), Catalase (CAT), Superoxide Dismutase (SOD), and diminished Lipid Peroxidation (LPO), Nitric Oxide (NO), Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-1β, IL-18, Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), NOD-like Receptor Family Pyrin Domain Containing 3 (NLRP3) and amyloid-β production, while improving Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Piperitone showed significant neuroprotective and cognitive enhancement benefits by modulating cholinergic signaling, oxidative stress, and neuroinflammation. These multitarget actions advocate piperitone as a prospective lead candidate for the development of disease modifying treatments for AD.

Workplace stress is a pervasive and escalating concern within healthcare environments, posing serious risks to the psychological well-being of healthcare professionals. Chronic exposure to high workloads, emotional demands, time pressure, and organizational constraints often results in elevated psychological distress, including anxiety, depression, and burnout. This study investigates the mediating role of coping styles in the relationship between workplace stress and psychological distress and examines gender as a moderating factor within this pathway. A cross-sectional survey design was employed, drawing data from 1,200 healthcare professionals, including physicians, nurses, and allied health staff, working in tertiary healthcare institutions. Validated instruments the Perceived Stress Scale, Brief COPE, and General Health Questionnaire were utilized to measure workplace stress, coping strategies, and psychological distress, respectively. Mediation and moderation analyses revealed that both adaptive and maladaptive coping styles significantly mediated the stress–distress relationship, while gender moderated the strength of these indirect effects. Female healthcare professionals reported higher stress levels and greater reliance on emotion-focused coping strategies compared to males. These findings highlight the importance of incorporating gender-sensitive coping interventions and stress management programs within healthcare organizations.

Auditory-driven analgesia through music exposure is emerging as a biologically measurable modulator of pain memory rather than a distraction-based coping tool alone. Latest 2025 neurochemical mapping shows that structured music stimuli activate mesolimbic dopamine release, reduce amygdalar pain-trace reconsolidation, and gate nucleus accumbens–periaqueductal gray pain-memory coupling. These effects reshape nociceptive recall strength without pharmacologic replacement, supporting early auditory therapy integration alongside standard analgesic frameworks.

Dear Editor, We read with great interest the recent approval of semaglutide by the U.S. Food and Drug Administration for reducing the risk of kidney disease progression and cardiovascular death in adults with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD)[1]. This milestone expands the therapeutic horizon of GLP-1 receptor agonists beyond glycemic control and weight management, representing a paradigm shift in nephrology and endocrinology. The pivotal FLOW trial demonstrated a 24% relative risk reduction in major kidney outcomes and a 5% reduction in cardiovascular mortality, underscoring the dual renal-cardiac benefit of semaglutide in this high-risk population[2]. Mechanistically, GLP-1 receptor agonism has been shown to attenuate hyperfiltration, reduce glomerular injury, and modulate inflammation and oxidative stress, all key contributors to CKD progression in T2DM[3]. Prior nephrology therapies predominantly targeted downstream pathways (e.g., RAAS inhibition, SGLT2 blockade) rather than upstream metabolic regulators; hence, semaglutide introduces a novel metabolic-renal axis approach. However, several critical questions remain. The FLOW trial’s median follow-up of approximately 3 years may not fully capture the long-term durability of renal protection or its impact on progression to end-stage kidney disease; real-world evidence and cost-effectiveness analyses will be essential for global adoption[4]. Furthermore, the incremental benefit of semaglutide when used alongside SGLT2 inhibitors and mineralocorticoid receptor antagonists is yet to be established. Notably, an updated meta-analysis by Wanner et al revealed that GLP-1 receptor agonists consistently reduce albuminuria and major adverse renal events across diverse CKD cohorts, supporting additive potential with established nephroprotective drugs[5]. From a safety standpoint, Johnsson et al demonstrated reassuring results regarding tolerability in patients with advanced CKD, showing no unexpected rise in pancreatitis or gastrointestinal adverse events, even with reduced renal clearance[6]. Nevertheless, continued pharmacovigilance is warranted to monitor rare adverse events in real-world populations and polypharmacy contexts. Finally, as Packer (2025) eloquently argues, semaglutide’s approval signals a broader paradigm shift; diabetic nephropathy management is moving from renal replacement strategies toward endocrine modulation and metabolic restoration[7]. This underscores the urgent need to integrate GLP-1 receptor agonists into future nephrology and endocrinology guidelines, complemented by clinician education and equitable drug access. In conclusion, semaglutide’s kidney-protective indication represents a seminal advance in CKD management. Translating this breakthrough into routine practice through multidisciplinary collaboration, cost accessibility, and long-term surveillance will define the next era of metabolic-renal therapeutics. This manuscript complies with TITAN Guidelines, 2025, declaring no use of AI[8].

This study examines the China-India bilateral rivalry through multiple lenses: competitive dynamics, strategic interests, and geopolitical tensions. It analyzes Sino-Indian competition in the Indian Ocean and South China Sea, where India seeks to secure maritime interests amid China's expanding influence. China's ambitions in the Indian Ocean contrast with India's aspirations, sparking a contest for regional dominance. The research also explores India's strategic engagement in the South China Sea, China's assertive claims, and the impact of US involvement on Sino-Indian relations. Additionally, it addresses persistent boundary disputes and the Dalai Lama's role in shaping China-India affairs. By examining these dimensions, this research offers insights into the evolving rivalry's implications for regional stability and global geopolitics.