Knee osteoarthritis (OA) is a degenerative joint disease involving progressive cartilage loss, subchondral bone remodelling, and inflammation. This systematic review and meta-analysis aimed to assess the efficacy and safety of metformin in reducing knee pain and adverse events among overweight and obese adults with symptomatic knee OA. We systematically searched PubMed, Scopus, and CENTRAL from inception to August 2025. Eligible randomised controlled trials (RCTs) compared oral metformin with placebo or standard care in adults with BMI ≥ 25 kg/m2 and symptomatic knee OA. Primary outcomes were pain reduction (standardised mean difference) and gastrointestinal (GI) adverse events (risk ratio). Risk of bias was assessed using the Cochrane ROB 2 tool, publication bias using the Doi plot and LFK index, and evidence certainty using the GRADE-pro approach. Seven studies (n = 1237) were included: six RCTs and one observational study. Meta-analysis included only RCTs. Metformin significantly reduced knee pain compared with controls (SMD: − 0.42; 95
Aphthous stomatitis frequently affects oral mucosa, though its exact cause remains uncertain. Given vitamin D’s role in immune regulation and mucosal integrity, it may contribute to ulcer development. To assess the relationship between serum vitamin D levels and the occurrence, classification, and anatomical distribution of aphthous ulcers. This case-control study involved 74 patients diagnosed with aphthous stomatitis and 74 age- and sex-matched healthy controls. Data collected included demographic details, serum 25-hydroxyvitamin D levels, ulcer classification, and site of involvement. Vitamin D status was categorized as deficient (< 20 ng/mL), insufficient (20–29 ng/mL), or sufficient (≥ 30 ng/mL). Statistical analysis was performed using the Chi-square test. Over half of the patients (54.1
Background: Accurate diagnosis of infectious diseases is essential for appropriate clinical management and effective antimicrobial stewardship. Conventional diagnostic modalities such as histopathology and microbiological culture have inherent limitations, while molecular techniques offer enhanced sensitivity but require careful interpretation. Integrating these approaches may improve diagnostic accuracy and therapeutic outcomes. Objective: To systematically evaluate the diagnostic concordance between histopathology and microbiological methods, assess the incremental value of molecular diagnostics, and determine the impact of multimodal diagnostic strategies on antimicrobial stewardship. Methods: A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines. Electronic databases including PubMed, Embase, Scopus, and Cochrane Library were searched up to January 2026. Studies reporting paired histopathological and microbiological findings in infectious diseases were included. Pooled sensitivity, specificity, and concordance were analyzed using a random-effects model. Heterogeneity was assessed using the I² statistic, and risk of bias was evaluated using the QUADAS-2 tool. Results: Fifty-two studies comprising 8,746 patients were included. Histopathology demonstrated high sensitivity for detecting tissue invasion (0.88; 95% CI: 0.83–0.92), while microbiological methods showed higher specificity (0.91; 95% CI: 0.87–0.94). Molecular diagnostics yielded the highest sensitivity (0.92; 95% CI: 0.88–0.95), particularly in culture-negative cases. Overall concordance between histopathology and microbiology was 74%, with substantial heterogeneity (I² = 68%). Multimodal diagnostic approaches improved pathogen detection and reduced inappropriate antimicrobial use by approximately 28%, facilitating earlier targeted therapy. Conclusion: Histopathology, microbiology, and molecular diagnostics are complementary modalities that collectively enhance diagnostic accuracy in infectious diseases. Their integration supports timely, evidence-based antimicrobial therapy and strengthens antimicrobial stewardship efforts. Adoption of standardized multimodal diagnostic algorithms is recommended to optimize patient outcomes and mitigate antimicrobial resistance.
Aims: There is increasing evidence that suggests that different subtypes of major depressive disorders, particularly treatment-resistant depression and anhedonia-predominant forms, have dysregulation in reward processing and chronic neuroimmune activation. Low-dose naltrexone (LDN), which is administered at low doses (1–5 mg/day), modifies both the signalling from the body’s endogenous system and the inflammatory pathways of microglia and thus can be used as a potential therapeutic for depression. This mechanistic systematic review aims to evaluate the dual mechanism of Low Dose Naltrexone in Treatment-Resistant Depression. This study aims to provide an analysis of the human clinical and biological effects of low dose naltrexone (LDN) in depression based upon a mechanistic convergence framework. Methods: Human studies examining the effects of LDN on outcomes such as mood, fatigue, pain, quality of life, inflammatory markers, or opioid-related variables, published in PubMed, EMBASE, Scopus, Web of Science, the Cochrane Library, or Google Scholar, wereidentified. The quality of randomized controlled trials was evaluated according to the Risk of Bias 2 tool, and the quality of non-randomized studies was evaluated according to the Risk Of Bias In Non-randomized Studies–Instrument (ROBINS-I). Results from studies of human subjects were synthesized narratively using a mechanism-based approach. Results: Improvements in quality of life, fatigue, and mood-related symptoms in disorders characterized by immune activation and central sensitization (e.g. fibromyalgia, multiple sclerosis) were observed across randomized trials, observational cohorts, and case reports after administration of LDN. Biomarkers of inflammation (pro-inflammatory cytokine levels) were lower in human studies after administration of LDN. Indirect indicators of enhancement of endogenous opioid function (e.g. improved pain tolerance, decreased consumption of analgesics and psychotropics) were also reported in human studies after administration of LDN. The mechanisms by which LDN exerts these beneficial effects occur in the same patient population and therefore suggest a biological convergence of immune suppression and opioid-mediated reward modulation. Conclusion: The results from the literature support a “Dual Mechanistic Model” where LDN suppresses inflammation by activated microglia and at the same time increases signalling of endogenous opioids, both of which have been implicated in the pathophysiology of depression and anhedonia. Thus there is a strong mechanistic basis for testing LDN as a treatment for patients who have failed to respond to current treatments for depression.
Tuberculosis (TB) remains a major public health challenge globally, particularly in low- and middle-income countries. Mental health disorders such as depression and anxiety are increasingly recognized as important comorbidities among TB patients, adversely affecting treatment adherence and outcomes. To estimate the proportion of depression and anxiety among tuberculosis patients attending a Tuberculosis Unit in Bangalore and to determine associated factors. A cross-sectional study was conducted among 66 adult TB patients at the Yeswanthpur TU, Bangalore. Depression and anxiety were assessed using PHQ-9 and GAD-7 scales. Data were analysed using descriptive statistics and Chi-square/Fisher’s exact test. The median age of study participants was 41 years (IQR: 29–43), and 71
