Objectives: This cross-sectional study examines the selfreported empathy levels of undergraduate students in five different health sciences disciplines before and after one year of training at the St Augustine Campus, University of the West Indies. Methods: Students enrolled into the schools of dentistry, pharmacy, medicine, veterinary medicine and nursing self administered the Jefferson Scale of Empathy on entering their first year of training (n=355). Mean empathy scores were then compared between and among groups to scores on retesting at the end (n=366) of their first year using independent t-tests and one way between groups using ANOVA with planned comparisons. Results: Female students and students older than 27 years were found to be more empathic than male students and those less than 21 years respectively. The highest mean empathy scores on entry to university were noted in nursing and dental students. On repeat testing mean empathy scores declined in all 5 groups, with the declines among medical, nursing and dental students achieving statistical significance. Conclusions: This study shows that the decline in self reported empathy scores starts during the first year of training. Whilst this decline may be partly due to a 'settling in' phenomenon with a change from idealism to realism, students may also be displaying an adaptive response to new responsibilities and an increasing workload. With the current trend of blurred professional boundaries for healthcare providers, empathy is an important skill to be developed by all disciplines. Health educators now need to consider addressing those factors that may check its further decline.
Regulation of tissue-type plasminogen activator (tPA) depends on fibrin binding and fibrin structure. tPA structure/ function relationships were investigated in fibrin formed by high or low thrombin concentrations to produce a fine mesh and small pores, or thick fibers and coarse structure, respectively. Kinetics studies were performed to investigate plasminogen activation and fibrinolysis in the 2 types of fibrin, using wild-type tPA (F-G-K1-K2-P, F and K2 binding), K1K1-tPA (F-G-K1-K1-P, F binding), and delF-tPA (G-K1-K2-P, K2 binding). There was a trend of enzyme potency of tPA > K1K1-tPA > delF-tPA, highlighting the importance of the finger domain in regulating activity, but the differences were less apparent in fine fibrin. Fine fibrin was a better surface for plasminogen activation but more resistant to lysis. Scanning electron and confocal microscopy using orange fluorescent fibrin with green fluorescent protein-labeled tPA variants showed that tPA was strongly associated with agglomerates in coarse but not in fine fibrin. In later lytic stages, delF-tPA-green fluorescent protein diffused more rapidly through fibrin in contrast to full-length tPA, highlighting the importance of finger domainagglomerate interactions. Thus, the regulation of fibrinolysis depends on the starting nature of fibrin fibers and complex dynamic interaction between tPA and fibrin structures that vary over time. (Blood. 2011;117(2):661-668)
IntroductionFibrin may be viewed as a substrate according to 2 distinct definitions of the word: (1) a surface or layer supporting biologic activity and (2) a substance acted on by an enzyme. The mechanism of tissue-type plasminogen activator (tPA) stimulation by fibrin is by "colocalization" of tPA and plasminogen on fibrin, which acts as a substrate (definition 1) or template; and the plasmin generated in this way is the enzyme that digests fibrin substrate (definition 2). Fibrinolysis encompasses both processes, which are distinct but overlapping. The role of fibrin structure in regulating the whole process of fibrinolysis is not completely understood, and there is disagreement over published results. For example, fibrin fiber diameter can be manipulated by thrombin, such that higher thrombin concentrations produce a fine network of thin fibers, whereas fibrin polymerization at lower thrombin concentration results in more lateral aggregation and produces clots composed of thicker fibers, as reviewed. 1 It has been observed from gross changes in turbidity of fibrin clots undergoing lysis 2,3 that clots made of thicker fibers appear to lyse more rapidly than clots made from fine fibers. However, this simple relationship has been questioned because clots made of thicker fibers are more turbid and lysis may appear to be faster when followed optically if turbidity is not normalized to correct for different starting values. 1 Furthermore, it has been noted from more detailed microscopic studies that thinner fibers are more susceptible to lysis than thick fibers, yet this relationship is not reflecte...
Objectives:This study explored the empathy profile of students across five years of medical training. In addition the study examined whether the Jefferson Scale for Physician Empathy correlated with a measure of cognitive empathy, the Reading the Mind in the Eyes Test and a measure of affective empathy, the Toronto Empathy Questionnaire.Methods:The study was a comparative cross-sectional design at one Caribbean medical school. Students were contacted in class, participation was voluntary and empathy was assessed using all three instruments Descriptive statistics were calculated and differences between groups evaluated using non-parametric tests.Results:Overall 669 students participated (response rate, 67%). There was a significant correlation between the Jefferson Scale of Physician Empathy and the Toronto Empathy Questionnaire (P = 0.48), both scales indicating a decline in medical student empathy scores over time. There was, however, little correlation between scores from the Reading the Mind in the Eyes Test and the Jefferson Scale of Physician Empathy. Female students demonstrated significantly higher scores on all three measures.Conclusions:Medical students’ lower empathy scores during their final years of training appear to be due to a change in the affective component of empathy. These findings may reflect an adaptive neurobiological response to the stressors associated with encountering new clinical situations. Attention should be paid not only to providing empathy training for students but also to teaching strategies for improved cognitive processing capacity when they are encountering new and challenging circumstances.
Summary. Background: Binding of tissue-type plasminogen (Pgn) activator (t-PA) and Pgn to fibrin regulates plasmin generation, but there is no consistent, quantitative understanding of the individual contribution of t-PA finger and kringle 2 domains to the regulation of fibrinolysis. Kringle domains bind to lysines in fibrin, and this interaction can be studied by competition with lysine analogs and removal of C-terminal lysines by carboxypeptidase B (CPB). Methods: Highthroughput, precise clot lysis assays incorporating the lysine analog tranexamic acid (TA) or CPB and genetically engineered variants of t-PA were performed. In particular, wild-type (WT) t-PA (F-G-K1-K2-P) and a domain-switched variant K1K1t-PA (F-G-K1-K1-P) that lacks kringle 2 but retains normal t-PA structure were compared to probe the importance of fibrin lysine binding by t-PA kringle 2. Results: WT t-PA showed higher rates of fibrinolysis than K1K1t-PA, but the inhibitory effects of TA or CPB were very similar for WT t-PA and the variant t-PA (< 10% difference). Urokinase plasminogen activator (u-PA)-catalyzed fibrinolysis was also inhibited by TA, even though Pgn activation could be stimulated. Fibrin treated with factor XIIIa (FXIIIa) generates crosslinked degradation products, but these did not affect the results obtained with WT t-PA and K1K1t-PA. Conclusions: t-PA kringle 2 has a minor role in the initial interaction of t-PA and fibrin, but stimulation of fibrinolysis by C-terminal lysines (or inhibition by carboxypeptidases or TA) operates through Pgn and plasmin binding, not through t-PA. This is also true when fibrin is crosslinked by treatment with FXIIIa.
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