51 research outputs found

    Rate-dependent Ca2+ signalling underlying the force-frequency response in rat ventricular myocytes: A coupled electromechanical modeling study

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    Rate-dependent effects on the Ca2+ sub-system in a rat ventricular myocyte are investigated. Here, we employ a deterministic mathematical model describing various Ca2+ signalling pathways under voltage clamp (VC) conditions, to better understand the important role of calmodulin (CaM) in modulating the key control variables Ca2+/calmodulin-dependent protein kinase-II (CaMKII), calcineurin (CaN), and cyclic adenosine monophosphate (cAMP) as they affect various intracellular targets. In particular, we study the frequency dependence of the peak force generated by the myofilaments, the force-frequency response (FFR). Our cell model incorporates frequency-dependent CaM-mediated spatially heterogenous interaction of CaMKII and CaN with their principal targets (dihydropyridine (DHPR) and ryanodine (RyR) receptors and the SERCA pump). It also accounts for the rate-dependent effects of phospholamban (PLB) on the SERCA pump; the rate-dependent role of cAMP in up-regulation of the L-type Ca2+ channel (ICa;L); and the enhancement in SERCA pump activity via phosphorylation of PLB.Our model reproduces positive peak FFR observed in rat ventricular myocytes during voltage-clamp studies both in the presence/absence of cAMP mediated -adrenergic stimulation. This study provides quantitative insight into the rate-dependence of Ca2+-induced Ca2+-release (CICR) by investigating the frequency-dependence of the trigger current (ICa;L) and RyR-release. It also highlights the relative role of the sodium-calcium exchanger (NCX) and the SERCA pump at higher frequencies, as well as the rate-dependence of sarcoplasmic reticulum (SR) Ca2+ content. A rigorous Ca2+ balance imposed on our investigation of these Ca2+ signalling pathways clarifies their individual roles. Here, we present a coupled electromechanical study emphasizing the rate-dependence of isometric force developed and also investigate the temperature-dependence of FFR. Our model provides mechanistic biophysically based explanations for the rate-dependence of CICR, generating useful and testable hypotheses. Although rat ventricular myocytes exhibit a positive peak FFR in the presence/absence of beta-adrenergic stimulation, they show a characteristic increase in the positive slope in FFR due to the presence of Norepinephrine or Isoproterenol. Our study identifies cAMP-mediated stimulation, and rate-dependent CaMKII-mediated up-regulation of ICa;L as the key mechanisms underlying the aforementioned positive FFR

    Archimedean actions on median pretrees

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    In this paper we consider group actions on generalized treelike structures (termed ‘pretrees’) defined simply in terms of betweenness relations. Using a result of Levitt, we show that if a countable group admits an archimedean action on a median pretree, then it admits an action by isometries on an [open face R]-tree. Thus the theory of isometric actions on [open face R]-trees may be extended to a more general setting where it merges naturally with the theory of right-orderable groups. This approach has application also to the study of convergence group actions on continua

    Using virtual reality to improve health care providers⇔ cultural self-efficacy and diabetes attitudes: pilot questionnaire study

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    Background: In southeastern Appalachian Ohio, the prevalence of diabetes is 19.9%, nearly double that of the national average of 10.5%. Here, people with diabetes are more likely to have a delayed diagnosis, limited access to health care, and lower health literacy. Despite the high rates of diabetes in the region, the availability of endocrinologists and certified diabetes care and education specialists is limited. Therefore, innovative strategies to address the growing diabetes care demands are needed. One approach is to train the primary care workforce in new and emerging therapies for type 2 diabetes to meet the increasing demands and complexity of diabetes care. Objective: The aim of this study was to assess the effectiveness of a virtual reality training program designed to improve cultural self-efficacy and diabetes attitudes. Methods: Health care providers and administrators were recruited from large health care systems, private practices, university-owned hospitals or clinics, Federally Qualified Health Centers, local health departments, and AmeriCorps. Providers and administrators participated in a 3-hour virtual reality training program consisting of 360-degree videos produced in a professional, cinematic manner; this technique is called virtual reality cinema (cine-VR). Questionnaires measuring cultural self-efficacy, diabetes attitudes, and presence in cine-VR were administered to providers and administrators before and after the program. Results: A total of 69 participants completed the study. The mean age of the sample was 42.2 years (SD 13.7), 86% (59/69) identified as female, 83% (57/69) identified as White, 86% (59/69) identified as providers, and 25% (17/69) identified as nurses. Following the training program, we observed positive improvements in all three of the cultural self-efficacy subscales: Cognitive (mean change –1.29; t65=–9.309; P\u3c.001), Practical (mean change –1.85; t65=–9.319; P\u3c.001), and Affective (mean change –0.75; t65=–7.067; P\u3c.001). We observed the largest magnitude of change with the subscale, with a Cohen d of 1.16 indicating a very large effect. In addition, we observed positive improvements in all five of the diabetes attitude subscales: Need for special training (mean change –0.21; t67=–6.154; P\u3c.001), Seriousness of type 2 diabetes (mean change –0.34; t67=–8.114; P\u3c.001), Value of tight glucose control (mean change –0.13; t67=–3.029; P=.001), Psychosocial impact of diabetes (mean change –0.33; t67=–6.610; P\u3c.001), and Attitude toward patient autonomy (mean change –0.17; t67=–3.889; P\u3c.001). We observed the largest magnitude of change with the Psychosocial impact of diabetes subscale, with a Cohen d of 0.87 indicating a large effect. We observed only one significant correlation between presence in cine-VR (ie, Interface Quality) and a positive change score (ie, Affective self-efficacy) (r=.285; P=.03). Conclusions: Our findings support the notion that cine-VR education is an innovative approach to improve cultural self-efficacy and diabetes attitudes among health care providers and administrators. The long-term impact of cine-VR education on cultural self-efficacy and diabetes attitudes needs to be determined
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