Changes in physical activity in older adult patients with postoperative hip fractures in convalescent rehabilitation wards during rehabilitation time and during daily activities in the ward: a prospective cohort study.

As the older adult population increases, the number of patients with hip fractures is expected to increase. Hip fractures are a major factor in bedridden patients and decreased activities of daily living. Older adults may have multiple comorbidities, and improving their physical function under comprehensive care is better to meet their needs. Convalescent rehabilitation wards provide comprehensive care and aim to improve the activities of daily living and physical activity in older adults. This study aimed to identify the time of day, including rehabilitation, when physical activities improve in inpatients with subacute postoperative hip fracture, among the many comorbidities of older adults, in comprehensive care, including rehabilitation. This prospective cohort study was conducted in a comprehensive care setting in a subacute rehabilitation ward in a Japanese hospital. Older adult inpatients with a musculoskeletal disease in a subacute rehabilitation ward were divided into the postoperative hip fracture and non-hip fracture patients to examine age, frailty, activities of daily living, and longitudinal physical activity data from objective measures at admission and discharge. Physical activity increased in older adult inpatients with postoperative hip fractures not only during personalized rehabilitation time ( P  < 0.001) but also during free activity in the ward ( P  < 0.001), despite their tendency to be older, frailer, and lower activities of daily living. In conclusion, postoperative hip fracture inpatients may improve their fitness after receiving comprehensive care.

Structure-activity relationship of novel DAPK inhibitors identified by structure-based virtual screening.

Death-associated protein kinase (DAPK) is a serine/threonine protein kinase implicated in diverse programmed cell death pathways. DAPK is a promising target protein for the treatment of ischemic diseases. We identified novel potent and selective DAPK inhibitors efficiently by structure-based virtual screening, then further developed the hit compounds. In this paper, we describe the development of the hit compounds and the structure-activity relationship studies of the DAPK inhibitors in detail, including calculation of the solvated interaction energy (SIE), and verification of selectivity using a kinase panel.

Identification of death-associated protein kinases inhibitors using structure-based virtual screening.

Death-associated protein kinases (DAPKs) function in the early stages of eukaryotic programmed cell death. DAPKs are now emerging as targets for drug discovery in novel therapeutic approaches for ischemic diseases in the brain, heart, kidney, and other organs. Using a structure-based virtual screening approach, we discovered potent and selective DAPKs inhibitors. 6 was found to be the most potent inhibitor with enzyme selectivity (IC(50) = 69 nM for DAPK1).