Safe driving recommendations following lower extremity orthopedic surgery: a systematic review.

PURPOSE: We analyzed the published literature on return-to-driving (RTD) recommendations following lower extremity orthopedic surgery, including knee and hip arthroplasty and ankle and foot surgery. METHODS: We conducted a PubMed MEDLINE database search for the relevant literature spanning from 1988 to 2022. Data were extracted from the selected articles independently by six investigators, and the mean, standard deviation, and range of RTD recommendations for each surgical region and procedure were calculated. RESULTS: The 34 studies included in our review evaluated brake response time, reaction time, movement time, braking force, and other parameters. Average RTD recommendations in weeks were: hip surgeries, 4.1 (± 2.7); foot surgeries, 6.67 (± 0.94); Achilles surgeries, 6.67 (± 0.25); ankle surgeries, 4 (± 2); knee surgeries, 5.42 (± 0.77); and multiple lower extremity surgeries, 3.85 (± 0.15). CONCLUSION: Our findings can assist physicians in providing informed recommendations to patients, promoting safe driving practices, and optimizing postoperative recovery. LEVEL OF EVIDENCE: Therapeutic, Level III: Retrospective comparative study.

Discovery of small molecules targeting the tandem tudor domain of the epigenetic factor UHRF1 using fragment-based ligand discovery.

Despite the established roles of the epigenetic factor UHRF1 in oncogenesis, no UHRF1-targeting therapeutics have been reported to date. In this study, we use fragment-based ligand discovery to identify novel scaffolds for targeting the isolated UHRF1 tandem Tudor domain (TTD), which recognizes the heterochromatin-associated histone mark H3K9me3 and supports intramolecular contacts with other regions of UHRF1. Using both binding-based and function-based screens of a ~ 2300-fragment library in parallel, we identified 2,4-lutidine as a hit for follow-up NMR and X-ray crystallography studies. Unlike previous reported ligands, 2,4-lutidine binds to two binding pockets that are in close proximity on TTD and so has the potential to be evolved into more potent inhibitors using a fragment-linking strategy. Our study provides a useful starting point for developing potent chemical probes against UHRF1.