PURPOSE: The p38 mitogen-activated protein kinase (MAPKs) play a crucial role in the production of pro-inflammatory cytokines and over-expression of it increase cytokines which promote cancer. Among four isoforms, p38α has been well studied in head and neck squamous cell carcinoma (HNSCC) and other cancers as a therapeutic target. p38δ has recently emerged as a potential disease-specific drug target. Elevated serum p38α level in HNSCC was reported earlier from our lab. This study aims to estimate the levels of p38 MAPK-isoforms in the serum of HNSCC and design peptide inhibitor targeting the same. MATERIALS AND METHODS: Levels of p38 MAPK isoforms in the serum of HNSCC and healthy controls were quantified by surface plasmon resonance technology. The peptide inhibitor for p38 MAPK was designed by molecular modeling using Grid-based Ligand Docking with Energetics tools and compared with known specific inhibitors. RESULTS: We have observed highly elevated levels of all four isoforms of p38 MAPK in serum of HNSCC patients compared to the control group. Further, serum p38α, p38β, and p38δ levels were down regulated after therapy in follow-up patients, while p38γ showed no response to the therapy. Present study screened designed peptide WFYH as a specific inhibitor against p38δ. The specific inhibitor of p38δ was found to have no effect on p38α due to great structural difference at ATP binding pocket. CONCLUSION: In this study, first time estimated the levels of p38 MAPK isoforms in the serum of HNSCC. It can be concluded that p38 MAPK isoforms can be a diagnostic and prognostic marker for HNSCC and p38δ as a therapeutic target.
Adenosine Triphosphate ; Carcinoma, Squamous Cell* ; Cytokines ; Epithelial Cells* ; Follow-Up Studies ; Head* ; Humans ; Models, Molecular ; Neck* ; p38 Mitogen-Activated Protein Kinases ; Protein Isoforms* ; Protein Kinases ; Surface Plasmon Resonance

Objective: Due to its comprehensive, reliable, and valid format, the objective structured clinical examination (OSCE) is the gold standard for assessing the clinical competency of medical students. In the present study, we evaluated the importance of the OSCE as a learning tool for postgraduate (PG) residents assessing their junior undergraduate students. We further aimed to analyze quality improvement during the pre-coronavirus disease (COVID) and COVID periods. Methods: This quality-improvement interventional study was conducted at the Department of Obstetrics and Gynecology. The PG residents were trained to conduct the OSCE. A formal feedback form was distributed to 22 participants, and their responses were analyzed using a five-point Likert scale. Fishbone analysis was performed, and the ‘plan-do-study-act’ (PDSA) cycle was implemented to improve the OSCE. Results: Most of the residents (95%) believed that this examination system was extremely fair and covered a wide range of clinical skills and knowledge. Further, 4.5% believed it was more labor- and resource intensive and time-consuming. Eighteen (81.8%) residents stated that they had learned all three domains: communication skills, time management skills, and a stepwise approach to clinical scenarios. The PDSA cycle was run eight times, resulting in a dramatic improvement (from 30% to 70%) in the knowledge and clinical skills of PGs and the standard of OSCE. Conclusion The OSCE can be used as a learning tool for young assessors who are receptive to novel tools. The involvement of PGs in the OSCE improved their communication skills and helped overcome human resource limitations while manning various OSCE stations.