Diabetic nephropathy (DN) is the main contributor to the incidence of end-stage renal disease and kidney failure. This research aims to explore the curative effect of leucine in the DN rat model.

40 male rats were sorted into four equal groups. Group I acted as the control group. Group II was given leucine (1.35g/kg orally, once daily) for 8 weeks. Group III administered a single intraperitoneal injection of Streptozotocin (STZ) (45 mg/kg, i.p.). Group IV was administered leucine following the diagnosis of diabetes for a duration of 8 weeks. In this study, samples were obtained from blood and renal tissue for biochemical assessments, evaluation of redox state, real-time polymerase chain reaction (RT-PCR) analysis of L-type amino acid transporter 1 (LAT1) and suppressor of Mothers against Decapentaplegic (SMAD3) genes, as well as histological examination.

Leucine supplementation to diabetic rats markedly reduced alterations in markers of kidney function. Furthermore, a reduction in redox markers and inflammatory cytokines was observed in tissues isolated from the leucine-treated diabetic group compared with diabetic rats. Additionally, the expression of the SMAD3 gene, mTOR, and c-JNK protein in renal tissue was significantly reduced in the leucine-diabetic group compared with the diseased group. Conversely, LAT1 tissue expression was upregulated in the leucine-diabetic group.

The administration of leucine inhibited renal damage by reducing activation of the profibrotic transforming growth factor beta-1 TGF-β/Smad3 signalling pathway.

The introduction of Competency-Based Medical Education (CBME) in India emphasizes outcome-oriented training and provides a framework for implementing integrated teaching strategies. Traditional discipline-based medical education often limits the ability of learners to integrate knowledge across domains required to manage such complex comorbidities. Evidence suggests that integrated teaching approaches improve knowledge acquisition, clinical reasoning, and learner engagement. The coexistence of tuberculosis (TB) and diabetes mellitus (DM) represents a significant and evolving public health challenge, particularly in high-burden countries such as India. Diabetes increases the risk of developing active TB and is associated with adverse treatment outcomes, including delayed sputum conversion, treatment failure, relapse, and increased mortality. This bidirectional interaction necessitates an integrated approach to both clinical management and medical education for TB and DM. This review synthesizes existing literature on the epidemiological and clinical interplay between TB and DM, along with educational frameworks supporting integration. This review of literature additionally presents a curriculum innovation comprising structured aligned integrated teaching (AIT) modules that integrate TB and DM across the MBBS curriculum using both horizontal and vertical integration strategies. The proposed framework may serve as a practical model for institutions implementing CBME. Adoption of structured integrated modules may enhance undergraduate medical training and better prepare future physicians for managing TB-DM comorbidity in high-burden settings.

Coronary artery disease (CAD) remains a leading cause of cardiovascular morbidity and mortality worldwide. Although traditional risk factors-including dyslipidemia, hypertension, diabetes mellitus, obesity, and smoking-account for a substantial proportion of CAD risk, they do not fully explain interindividual differences in disease onset, progression, or severity. Apolipoprotein E (ApoE) is a multifunctional protein involved in lipoprotein metabolism, inflammatory regulation, oxidative balance, endothelial function, and tissue repair. The APOE gene harbors three major alleles-ε2, ε3, and ε4-generating six common genotypes. Among these, the ε3/ε4 genotype has been associated in several studies with an unfavorable lipid profile and increased susceptibility to CAD and premature CAD.

This narrative review synthesizes current evidence on the association between the APOE ε3/ε4 genotype and CAD, with emphasis on lipid-mediated and non-lipid biological mechanisms, interactions with conventional cardiovascular risk factors, and potential implications for personalized cardiovascular prevention. Throughout the review, evidence obtained directly in ε3/ε4 carriers is distinguished from evidence extrapolated from ε4-carrier, ε4/ε4, or overall APOE-polymorphism analyses.

A narrative literature search was conducted in PubMed, Embase, Scopus, and Web of Science from database inception to August 2026, using the terms "Apolipoprotein E," "APOE ε3/ε4," "APOE polymorphism," "coronary artery disease," "premature coronary artery disease," "lipid metabolism," "atherosclerosis," and "cardiovascular genetics." English-language original articles, narrative reviews, and meta-analyses relevant to the APOE ε3/ε4 genotype and cardiovascular disease were included. Retrieved studies were classified by genotype contrast and by level of evidence (human observational, human interventional, or experimental).

ApoE plays a central role in plasma lipoprotein transport and hepatic clearance of triglyceride-rich lipoprotein remnants. The ε4 isoform has been associated with higher LDL cholesterol, apolipoprotein B, and remnant-lipoprotein concentrations, which may partly explain its association with coronary atherosclerosis. Beyond lipid transport, ApoE modulates macrophage activity, inflammatory signaling, oxidative stress, endothelial function, apoptosis, angiogenesis, and tissue repair. These non-lipid pathways derive predominantly from in vitro and animal models and remain unvalidated in human ε3/ε4 carriers. Where adjusted, ε3/ε3-referenced estimates are available, the effect size is modest, with odds ratios of approximately 1.5 for unselected CAD and 1.5-2.2 for premature coronary phenotypes.

The APOE ε3/ε4 genotype may represent a genetic modifier of CAD risk, particularly when combined with traditional cardiovascular risk factors. Current evidence remains heterogeneous, and APOE genotyping should be regarded as a potential adjunctive marker and not a stand-alone risk prediction tool; this is distinct from its established diagnostic role in dysbetalipoproteinemia. Prospective studies integrating genetic, lipid, inflammatory, and imaging data are needed to clarify its incremental clinical value beyond LDL-C, apolipoprotein B, lipoprotein(a), and coronary artery calcium.

The gut microbiota is recognized as essential for maintaining immune homeostasis, and dysbiosis of the gut microbiota has been increasingly associated with the pathogenesis of various autoimmune diseases. Emerging evidence suggests that alterations in gut microbial composition may contribute to dysregulation of the immune system, thereby promoting inflammatory responses and autoimmunity. Despite growing interest in this field, a comprehensive bibliometric analysis integrating global research trends, influential publications, and key contributors, as well as clinical translation perspectives, remains lacking. This study aims to systematically evaluate the research landscape on the relationship between the gut microbiota and autoimmune diseases, thereby providing insights into research development, emerging hotspots, and future directions.

Global publications on gut microbiota and autoimmune diseases were systematically retrieved and extracted from the Web of Science Core Collection (WOSCC) database, covering the period from January 2000 to February 2025. The literature search and data extraction were conducted in February 2025, which was predefined as the cutoff date for data collection, thereby ensuring dataset reproducibility. Publications from 2025 were treated as partial-year data due to incomplete annual coverage and were excluded from longitudinal trend analyses to minimize temporal bias. In addition, a separate search of the PubMed database was conducted to identify clinical trials in this field. Bibliometric analyses and visualization were performed using VOSviewer, CiteSpace, and R version 4.4.0.

A total of 3,004 publications were retrieved from the Web of Science Core Collection and 85 clinical trials from PubMed, covering the period from 2000 to 2025. The overall number of publications has steadily increased over time. Citation analysis indicates that the United States and China are the leading countries in terms of publication output and citation frequency. Harvard Medical School was identified as the most productive institution, while New York University received the highest citation counts. Ochoa-Reparaz, J was the most prolific author, whereas citation frequency was highest for Atarashi, K, followed by Ochoa-Reparaz, J. Frontiers in Immunology published the highest number of articles in this field. Keyword and literature analyses identified mechanistic links between gut dysbiosis and autoimmune diseases, clinical relevance, and causal inference as major research themes. Integration of clinical trial evidence revealed that these basic research themes have progressively translated into disease-specific investigations, particularly in type 1 diabetes mellitus, multiple sclerosis, and rheumatoid arthritis. Probiotic supplementation, dietary modulation, and fecal microbiota transplantation represented emerging microbiota-targeted strategies, highlighting the transition of this field from mechanistic exploration toward clinical intervention.

While previous bibliometric studies have primarily relied on a single database, the present study integrates bibliometric data from the Web of Science Core Collection with supplementary clinical trial data retrieved from PubMed. This study provides valuable reference for identifying research foci and highlighting future research directions.

We describe a case of breast metastasis originating from a small-cell neuroendocrine carcinoma (SCNEC) of the uterine cervix, an uncommon presentation that can be difficult to distinguish from a primary breast malignancy. We report a 29-year-old woman treated three years earlier for FIGO stage IB2 cervical SCNEC with chemotherapy, surgery, and radiotherapy, who presented with a 1.5-cm mass in the left breast. Imaging suggested a primary breast malignancy, but her oncologic history raised concern for metastasis. Core-needle biopsy showed a high-grade small-cell neoplasm expressing synaptophysin, chromogranin A, and CD56, with a high Ki-67 index (>80%); breast-lineage markers, including GATA3 and mammaglobin, were negative. Whole-body fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) showed an isolated hypermetabolic breast lesion without other disease. Nipple-sparing mastectomy with immediate reconstruction was performed, followed by platinum-etoposide chemotherapy; at 18 months, there was no evidence of recurrence. Breast metastasis from cervical SCNEC can mimic primary breast cancer; diagnosis relies on integrating clinical history, imaging, and immunohistochemistry. Selected patients with isolated disease may benefit from individualised multimodal therapy.

Posterior reversible encephalopathy syndrome (PRES) is a neurological disorder characterized by nonspecific acute neurological signs and symptoms combined with typical imaging findings. It usually has a favorable prognosis but can occasionally be complicated by severe and life-threatening manifestations. Malignant PRES is the most severe form of this condition, defined by coma, refractory intracranial hypertension, and radiological evidence of cerebral edema or hemorrhage associated with a mass effect. We report a case of a 53-year-old woman with high-risk myelodysplastic neoplasm with increased blasts-2 who underwent allogeneic hematopoietic stem cell transplantation. The post-allograft period was complicated by grade III acute graft-versus-host disease, which required intensified immunosuppression with high-dose prednisolone and therapeutic doses of cyclosporine. Eighty-three days after transplantation, the patient was admitted to the emergency department with acute neurological symptoms. Rapid development of coma and clinical signs of intracranial hypertension, refractory to osmotic therapy with mannitol and hypertonic saline, prompted an emergency decompressive craniectomy. Magnetic resonance imaging confirmed the diagnosis of malignant PRES. Withdrawal of cyclosporine, mycophenolate mofetil, and voriconazole, along with intensive supportive management in the neurocritical care unit, resulted in complete neurological recovery.

Definitive radiotherapy represents a cornerstone treatment for localized prostate cancer, offering curative potential comparable to surgery. However, biochemical failure remains a concern, signaling possible disease progression.

This study aimed to evaluate the frequency, timing, and predictors of biochemical failure in patients receiving definitive radiotherapy for localized prostate cancer at a military oncology center.

We conducted a retrospective cohort study of 91 patients with localized or locally advanced prostate cancer (cT1-T3, N0-1, M0) treated with definitive radiotherapy at the Military Cancer Center in Jordan between 2020 and 2025. Biochemical failure was defined using the Phoenix criteria (prostate-specific antigen (PSA) nadir + 2 ng/mL). Biochemical recurrence-free survival was estimated using Kaplan-Meier analysis, and independent predictors of biochemical failure were identified using Cox proportional hazards regression.

The median age was 70 years, and the median pre-treatment PSA was 18.0 ng/mL. According to National Comprehensive Cancer Network (NCCN) risk stratification, 62/91 (68.1%) had high/very high-risk disease, 25/91 (27.5%) had intermediate-risk disease, and 4/91 (4.4%) had low-risk disease. Over a median follow-up of 36 months, 22 patients (24.2%) experienced biochemical failure, with a median time to failure of 24 months. The two-year and five-year biochemical recurrence-free survival rates were 84.6% and 70.3%, respectively. Multivariable analysis identified pre-treatment PSA greater than 20 ng/mL (hazard ratio (HR): 2.8; 95% confidence interval (CI): 1.4-5.6; p = 0.004) and PSA nadir greater than 0.1 ng/mL (HR: 3.2; 95% CI: 1.6-6.4; p = 0.001) as the strongest independent predictors of biochemical failure. Patients with PSA nadir > 0.1 ng/mL had a 3.2-fold higher hazard of biochemical failure compared to those with PSA nadir ≤ 0.1 ng/mL.

Definitive radiotherapy provides favorable biochemical control in this military cohort, with outcomes comparable to international benchmarks. Pre-treatment PSA and post-treatment PSA nadir independently predict biochemical failure, supporting their role in risk stratification and individualized follow-up planning. However, these findings require prospective validation in larger, multicenter cohorts before individualized surveillance strategies can be widely implemented.

Central nervous system (CNS) tumours are one of the most important entities in neurosurgery. The recent changes in the framework of the World Health Organization (WHO) classification of tumours reshape the diagnostic paradigm from morphological assessment to molecular characterization. This has elevated the standards of diagnostic precision, as well as in tailoring targeted regimes for CNS tumour management. The problem, however, lies in its limited applicability in low- and middle-income countries (LMICs) as opposed to high-income countries (HICs), where greater diagnostic precision is more likely to translate into improved patient outcomes through access to appropriate targeted therapies. Collectively, these challenges have led to the emergence of the concept of "therapeutic reciprocity." This principle emphasizes that improvements in diagnostic precision do not necessarily translate into equitable access to targeted therapies, particularly in LMICs. Consequently, without a realistic prospect of improving treatment availability, patient outcomes, or follow-up care, these out-of-pocket and non-actionable tests raise ethical and clinical-value concerns in LMIC settings. However, diagnostic precision upholds its own independent value for prognostication, avoidance of unnecessary toxicities, medication selection, surgical planning, and eligibility for clinical trials. LMICs play a huge role in collecting genomic datasets through sample donations and collaborations, yet remain underprivileged in therapeutic innovations reaching their population. Therefore, this editorial highlights these concerns while proposing strategies to bridge the gap in diagnostic precision and therapeutic innovations between LMICs and HICs.

Pediatric primary spinal cord tumors are rare, accounting for approximately 6% of central nervous system neoplasms. Most published data come from high-income countries (HICs) with access to early diagnosis, intraoperative monitoring, and specialized neuro-oncology units. In low- and middle-income countries (LMICs), diagnostic and therapeutic resources are limited. This report summarizes the first cohort of pediatric cases from Pakistan, highlighting surgical outcomes and systemic challenges in a resource-constrained setting.

We conducted a retrospective cohort study of patients ≤18 years who underwent surgery for primary pediatric spinal tumors at a tertiary hospital in Karachi (2008-2025). Demographics, presentation, tumor location and compartment, histopathology, extent of resection, postoperative complications, adjuvant therapy status, mortality, recurrence/progression, and follow-up outcomes were extracted from records.

Nineteen children were included (11 female; median age, 12 years). Lower-limb weakness (n = 11) and back pain (n = 7/15 with available data) were the most common presentations, with a median diagnostic delay of 90 days. Tumors were most often lumbar (n = 6), cervical (n = 5), or thoracic (n = 5). Among 13 patients with documented compartment data, 7 tumors were intramedullary, 4 were extramedullary/intradural or paramedullary, and 2 were intradural without further compartment specification. Ependymoma (n = 5) and astrocytoma (n = 4) predominated. Gross total resection (GTR) was documented in 10 patients and maximal safe/subtotal resection (MSR/STR) in 7. Postoperative complications were documented in 2/16 patients with available data. At the last follow-up, 5/12 patients with neurological follow-up improved, 5 remained stable, and 2 worsened. Mortality was documented in 5/17 patients with survival status available patient had recurrence after GTR, and 1 had progression after MSR/STR.

Surgical management of pediatric primary spinal tumors in an LMIC tertiary center was feasible, with limited documented perioperative morbidity after data correction. However, small sample size, missing event-level data, and a short median follow-up of 4 months limit interpretation of recurrence, progression-free status, and mortality. Earlier diagnosis, standardized surveillance, multidisciplinary review, rehabilitation, infection prevention, and improved access to adjuvant therapy may help strengthen care pathways in resource-constrained settings.

Glomus tumors are benign neoplasms typically found in the fingers and usually present with localized pain, swelling, and cold sensitivity. Extradigital glomus tumors are rare, and their diagnosis is often delayed due to atypical location and lack of cold sensitivity. In this article, we report a unique case of an extradigital glomangioma, a subset of glomus tumors, masquerading as more common ulnar-sided wrist pathology, such as a triangular fibrocartilage complex tear or extensor carpi ulnaris tendinitis. The patient presented with a two-year history of gradually worsening ulnar-sided wrist pain with no history of trauma. Examination revealed localized tenderness on the ulnar wrist without a palpable mass. X-rays were normal, and the pain was unresponsive to nonsteroidal anti-inflammatory medication and cortisone injection. Magnetic resonance imaging revealed a subcentimeter mass in the subcutaneous fat on the ulnar side of the wrist. The lesion was bright on T2-weighted and IV gadolinium-enhanced sequences. Excisional biopsy allowed the pathological diagnosis of benign glomangioma to be established. The patient reported immediate, complete resolution of pain postoperatively. This case underscores the importance of advanced imaging, clinical vigilance, and surgical excision for this rare tumor.