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Rheumatoid arthritis (RA) is a debilitating autoimmune disorder with an inflammatory condition targeting the joints that affects millions of patients worldwide. Several unmet needs still need to be addressed despite recent improvements in the management of RA. Although current RA therapies can diminish inflammation and alleviate symptoms, many patients remain unresponsive or experience flare-ups of their ailment. The present study aims to address these unmet needs through in silico research, with a focus on the identification of novel, potentially active molecules. Therefore, a molecular docking analysis has been conducted using AutoDockTools 1.5.7 on Janus kinase (JAK) inhibitors that are either approved for RA or in advanced phases of research. The binding affinities of these small molecules against JAK1, JAK2, and JAK3, which are target proteins implicated in the pathophysiology of RA, have been assessed. Subsequent to identifying the ligands with the highest affinity for these target proteins, a ligand-based virtual screening was performed utilizing SwissSimilarity, starting with the chemical structures of the previously identified small molecules. ZINC252492504 had the highest binding affinity (−9.0 kcal/mol) for JAK1, followed by ZINC72147089 (−8.6 kcal/mol) for JAK2, and ZINC72135158 (−8.6 kcal/mol) for JAK3. Using SwissADME, an in silico pharmacokinetic evaluation showed that oral administration of the three small molecules may be feasible. Based on the preliminary results of the present study, additional extensive research is required for the most promising candidates to be conducted so their efficacy and safety profiles can be thoroughly characterized, and they can become medium- and long-term pharmacotherapeutic solutions for the treatment of RA. [ABSTRACT FROM AUTHOR]

In the field of orthopedic surgery, cemented total knee arthroplasty (TKA) is considered to be one of the gold standards. However, there are categories of patients (i.e., obese and morbidly obese patients, younger than 65 years old) among whom cemented TKA has however a high failure rate. Moreover, the frequency of using uncemented TKA is increasing due to the potential benefits of long-term biological fixation, being an innovative field that addresses a new generation orthopedic surgical treatment which is more suitable for young patients who have good bone quality (good to very good, in terms of density). The survival rates and functional results of the latest generation of cementless TKAs may be similar to functional results and survival rates of cemented prosthesis. In conclusion, this review-type article can be considered a powerful database, extremely informative, dense, and focused on the topic mentioned above, in the interest of all medical professionals and all interested individuals. [ABSTRACT FROM AUTHOR]