Chemical Tools to Image the Activity of PAR-Cleaving Proteases.

Protease-activated receptors (PARs) comprise a family of four G protein-coupled receptors (GPCRs) that have broad functions in health and disease. Unlike most GPCRs, PARs are uniquely activated by proteolytic cleavage of their extracellular N termini. To fully understand PAR activation and function in vivo, it is critical to also study the proteases that activate them. As proteases are heavily regulated at the post-translational level, measures of total protease abundance have limited utility. Measures of protease activity are instead required to inform their function. This review will introduce several classes of chemical probes that have been developed to measure the activation of PAR-cleaving proteases. Their strengths, weaknesses, and applications will be discussed, especially as applied to image protease activity at the whole organism, tissue, and cellular level.

Development of a decision aid to address racial disparities in utilization of knee replacement surgery.

OBJECTIVE: Previous studies suggest that poorer knowledge and expectations about surgical outcomes may be responsible for low rates of total knee replacement (TKR) among African American males. The goal of this study was to pilot test the scope, acceptability, and efficacy of an educational videotape and tailored TKR decision aid designed to reduce disparities in TKR knowledge and expectations. METHODS: African American and Caucasian male veteran volunteers ages 55-85 years with moderate to severe knee osteoarthritis (OA) were recruited. During group meetings, patients viewed a video about knee OA treatments and were provided a personalized arthritis report that presented predicted patient outcomes should they decide to undergo TKR. Patients completed baseline and postintervention questionnaires that included an adapted Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) instrument to measure post-TKR expectations (0-100 scale with higher scores reflecting poorer outcomes). RESULTS: A total of 102 patients (54 African American, 48 Caucasian) completed the baseline survey and 64 patients attended the intervention. There were no significant differences by race between patients completing and those dropping out of the study. At baseline (n = 102), African American patients expressed lower expectations about post-TKR outcomes than did Caucasian patients for both pain (WOMAC score 41 versus 34; P = 0.18) and physical function expectations (WOMAC score 38 versus 30; P = 0.13). Among African Americans who underwent the intervention, expected pain and physical function improved to 31 (P = 0.04 versus baseline) and 30 (P = 0.09 versus baseline), respectively. Caucasian patients' expectations changed little. CONCLUSION: Disparities in baseline knowledge and expectations about TKR may be improved with the combined educational video and tailored decision aid.