Design and In Vitro Validation of an Orthopaedic Drill Guide for Femoral Stem Revision in Total Hip Arthroplasty.

Objective: Cemented total hip arthroplasty (THA) demonstrates superior survival rates compared to uncemented procedures. Nevertheless, most younger patients opt for uncemented THA, as removing well-fixed bone cement in the femur during revisions is complex, particularly the distal cement plug. This removal procedure often increases the risk of femoral fracture or perforation, haemorrhage and weakening bone due to poor drill control and positioning.

Treating Parental Burnout: Impact and Particularities of a Mindfulness- and Compassion-Based Approach.

Mindfulness- and self-compassion-based programs have been shown to reduce parental stress, and levels of mindfulness and self-compassion have been shown to be negatively related to parental burnout (PB) factors. Based on these results, the present study aimed to test the efficacy of an 8-week mindfulness and compassion-based group approach (MCA) ( = 29) compared with the existing Parenting in Balance Program (PBP) ( = 25). Parents were blindly enrolled in one of the two conditions.

Optimisation of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors.

Rho kinase is an important target implicated in a variety of cardiovascular diseases. Herein, we report the optimisation of the fragment derived ATP-competitive ROCK inhibitors 1 and 2 into lead compound 14A. The initial goal of improving ROCK-I potency relative to 1, whilst maintaining a good PK profile, was achieved through removal of the aminoisoquinoline basic centre.

Fragment-based discovery of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors.

Fragment-based NMR screening of a small literature focused library led to identification of a historical thrombin/FactorXa building block, 17A, that was found to be a ROCK-I inhibitor. In the absence of an X-ray structure, fragment growth afforded 6-substituted isoquinolin-1-amine derivatives which were profiled in the primary ROCK-I IMAP assay. Compounds 23A and 23E were selected as fragment optimized hits for further profiling.