Background: Immune checkpoint inhibitors (ICI) usage has increased in recent years, along with it the associated adverse effects. Objective: To conduct an observational study on immune checkpoint usage and adverse drug reactions associated with its use in a tertiary care center from coastal South India. Methodology: 228 patients were enrolled in this ambispective study, patient’s data was collected from the year 2020‑2024. Patients were selected based on inclusion criteria. Results: While adverse effects such as pruritus, tachycardia, and thyroiditis occurred infrequently, their clinical significance necessitates careful monitoring. A statistically significant association (p = 0.022) between treatment response and adverse events indicated a potential relationship between therapeutic effectiveness and toxicity. The instance of myocarditis was found to be 0.4%. Conclusion: These findings emphasize the significance of accurate monitoring, management, which includes various fields, and individualized therapies to maximize the outcomes for patients and reduce potential risks associated with Immune Checkpoint inhibitors (ICI).
Outer membrane protein A (OmpA) is an essential part of the Gram-negative bacterial outer membrane, which is essential in the stability of the membrane, the development of biofilm, and resistance to antibiotics. This is a detailed computational analysis involving the use of molecular dynamics (MD) simulations with GROMACS to examine using simulations in a lipid bilayer the structural dynamics, stability, and functional implications of Escherichia coli OmpA. We studied the conformational dynamics, membrane integration patterns, networks of hydrogen bonding, and structural stability of OmpA in physiological conditions through 200 nanoseconds of all-atom MD dynamics. Root mean square deviation (RMSD) was analyzed and showed that, on average the protein remained stable in conformation after 50 ns with average values of 2.8 ± 0.4 A. Root Mean square fluctuation (RMSF) analysis helped locate regions of the protein that are highly flexible (residues 160-180) with fluctuation greater than 4.5 A and the transmembrane 2-barrel domain was rigid (RMSF < 1.5 A). Measurement of radius of gyration was a sign of compact protein structure (17.2 ± 0.3 A) during the simulation. Analysis of secondary structure indicated that 43 percent of the 3D structure was also maintained with few transitions of 3D structures to 43% 3D structure. The analysis of hydrogen bonds showed that there were an average of 185 hydrogen bonds and a standard deviation of 15 intramolecular hydrogen bonds that forms the structure. Calculation of solvent accessible surface area revealed that hydrophobic residues (62) were mostly exposed to the lipid environment with the hydrophilic residues (38) being exposed to the aqueous environment. Three main motion modes with 68% of the total structural variance were obtained by principal component analysis. Analysis of free energy landscape showed that there are two conformational basins which are stable with energy barriers of 4.2 kcal/mol. These results not only give molecular-level information on the correlation between OmpA structure-function relationships, but also provide potential antimicrobial drug targets against Gram-negative pathogens.
BACKGROUND Teratomas are rare congenital tumors arising from pluripotent germ cells and contain tissues derived from all three germ layers: ectoderm, mesoderm, and endoderm. Intracranial teratomas are uncommon, accounting for less than 0.5% of all central nervous system tumors, and typically occur in midline structures such as the pineal or suprasellar regions. Primary involvement of cranial bones with transosseous extension is exceptionally rare. These lesions may lead to progressive cranial deformity and local bone destruction. While isolated cases involving the petrosal bone have been reported, localization at the cranial vault is exceedingly uncommon. To our knowledge, this report describes the first case of a transosseous teratoma involving the frontal and parietal bones. CASE PRESENTATION A 39‑year‑old male presented with persistent headache and vertigo, associated with a subcutaneous swelling at the bregma that progressively enlarged following a hair transplant procedure. Imaging revealed an osteolytic transosseous lesion involving both the external and internal cortical tables, with intraspongious extension and multiple hair follicles embedded within the mass. The patient underwent complete surgical excision, including resection of the outer cortical bone to delineate tumor margins and achieve total removal clearly. Histopathological examination confirmed the diagnosis of a mature teratoma. The postoperative course was uneventful, and the patient was discharged on the third postoperative day without neurological deficits. DISCUSSION Transosseous teratomas of the cranial vault are extremely rare. Their pathogenesis is thought to involve aberrant migration of germ cells during embryogenesis, resulting in ectopic growth within bone. Differential diagnosis includes dermoid and epidermoid cysts, osteolytic skull tumors, and other germ cell neoplasms. Complete surgical excision remains the treatment of choice to prevent recurrence. Given the potential for malignant transformation, long‑term clinical and radiological follow‑up is recommended. CONCLUSION: This case underscores the importance of early diagnosis and complete surgical resection in the management of transosseous cranial teratomas. Further reports are needed to better define optimal management strategies for these rare lesions.
Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by periods of relapse and remission, in which gut microbiota imbalance plays a role in triggering and sustaining inflammation through pro‑inflammatory cytokines. Therapeutic approaches targeting the gut microbiota, such as probiotics and synbiotics, have the potential to regulate disease activity by restoring microbial balance and reducing systemic inflammation. Several randomized controlled trials (RCTs) have explored the effects of microbiota‑based interventions in autoimmune diseases; however, comprehensive meta‑analyses summarizing their efficacy remain limited. Objective: To explore the potential benefit of probiotics and synbiotics supplementation in improving SLE disease activity and inflammatory markers. Methods: RCTs relevant to the treatment of SLE with probiotics and synbiotics were systematically retrieved from Pubmed, EMbase, Cochrane, Sinomed in accordance with the PRISMA guideline. The meta‑analysis was performed using RevMan 5.4.1 software. A fixed‑effects model was applied, Cochrane Risk of Bias 2 (ROB 2.0) was used as a bias assessment tool. Results: Seven studies with a total 460 subjects were included in this meta‑analysis. Data consisting of SLEDAI‑2K, IL‑17 and IgG from studies RCTs. The pooled analysis demonstrated that probiotic or synbiotic supplementation significantly reduced disease activity of SLE as assessed by the SLEDAI‑2K score (MD = ‑2.33, 95% CI ‑2.49, ‑2.16; P < 0.00001; I² = 61%). Similarly, the pro‑inflammatory markers of IL‑17 (MD = ‑1.04, 95% CI ‑1.55, ‑0.52; P < 0.0001) and IgG (MD = ‑2.64, 95% CI ‑2.77, ‑2.51; P < 0.00001) revealed a significant reduction compared to control group. Conclusion: Gut microbiota‑based therapies, including synbiotics and probiotics supplementation, demonstrate the potential benefit to reduce systemic inflammation and improve SLE disease activity through modulating gut microbiota composition and function. While promising as an adjunctive treatment for SLE, further studies are required to investigate its mechanisms and therapeutic efficacy.
Background: Cigarette smoking is a major risk factor for cardiovascular disease. Oxidative stress plays a central role in endothelial dysfunction and atherosclerosis. β-hydroxybutyrate (β-OHB), a ketone body, has been proposed to exert antioxidant and vascular protective effects. This study aimed to evaluate the effects of β-OHB on aortic histopathology and von Willebrand Factor (vWF) levels in Wistar rats exposed to cigarette smoke. Methods: This experimental randomized controlled animal study included 25 male Wistar rats divided into five groups: negative control (K−), positive control (K+; cigarette smoke exposure), and three treatment groups receiving β-hydroxybutyrate-(R)-1,3-butanediol monoester (DeltaG®, TDeltaS Global Inc., Orlando, FL, USA) at doses of 1.5 g/kg/day (P1), 3 g/kg/day (P2), and 6 g/kg/ day (P3). Rats were exposed to 40 cigarettes/day for 28 days. Aortic tissues were collected after euthanasia on day 28 for histopathological analysis and vWF measurement using ELISA. Data were analyzed using ANOVA with Fisher’s LSD post-hoc test. Results: β-OHB significantly reduced aortic histopathological alterations compared to the smoke-exposed control group (degeneration p = 0.001, hyperemia p = 0.002, hemorrhage p = 0.001, necrosis p = 0.000). vWF levels differed significantly among groups (p = 0.034), indicating improved endothelial function. Conclusions: β-OHB attenuates cigarette smoke-induced aortic injury and improves endothelial function. These findings support its potential role as a cardiometabolic therapeutic strategy.
