Reduced contraction strength with increased intracellular [Ca2+] in left ventricular trabeculae from failing rat hearts

Intracellular calcium ([Ca2+](i)) and isometric force were measured in left ventricular (LV) trabeculae from spontaneously hypertensive rats (SHR) with failing hearts and normotensive Wistar-Kyoto (WKY) controls. At a physiological stimulation frequency (5 Hz), and at 37 degrees C, the peak stress of SHR trabeculae was significantly (P <or = 0.05) reduced compared to WKY (8 +/- 1 mN mm(-2) (n = 8) vs. 21 +/- 5 mN mm(-2) (n = 8), respectively). No differences between strains in either the time-to-peak stress, or the time from peak to 50 % relaxation were detected. Measurements using fura-2 showed that in the SHR both the peak of the Ca2+ transient and the resting [Ca2+](i) were increased compared to WKY (peak: 0.69 +/- 0.08 vs. 0.51 +/- 0.08 microM(P <or = 0.1) and resting: 0.19 +/- 0.02 vs. 0.09 +/- 0.02 microM(P <or = 0.05), SHR vs. WKY, respectively). The decay of the Ca2+ transient was prolonged in SHR, with time constants of: 0.063 +/- 0.002 vs. 0.052 +/- 0.003 s (SHR vs. WKY, respectively). Similar results were obtained at 1 Hz stimulation, and for [Ca2+ ](o) between 0.5 and 5 mM. The decay of the caffeine-evoked Ca2+ transient was slower in SHR (9.8 +/- 0.7 s (n = 8) vs. 7.7 +/- 0.2 s (n = 8) in WKY), but this difference was removed by use of the SL Ca2+ -ATPase inhibitor carboxyeosin. Histological examination of transverse sections showed that the fractional content of perimysial collagen was increased in SHR compared to WKY (18.0 +/- 4.6 % (n = 10) vs. 2.9 +/- 0.9 % (n = 11) SHR vs. WKY, respectively). Our results show that differences in the amplitude and the time course of the Ca2+ transient between SHR and WKY do not explain the reduced contractile performance of SHR myocardium per se. Rather, we suggest that, in this animal model of heart failure, contractile function is compromised by increased collagen, and its three-dimensional organisation, and not by reduced availability of intracellular Ca2+

L'innovation en formation à l'enseignement : pistes de réflexion et d'action /

Réf. bibliogr.Webographie

Women with breast cancer’s perceptions of nurse-led telephone-based motivational interviewing consultations to enhance adherence to adjuvant endocrine therapy: a qualitative study

Background: Daily adjuvant endocrine therapy (AET) for 5 or 10 years is the standard of care for women diagnosed with non-metastatic hormone receptor-positive breast cancer. However, many women experience AET-related issues that may hamper quality of life and adherence. Here, we aimed to describe women's perceptions of motivational interviewing (MI)-guided consultations delivered by a trained nurse navigator over the telephone to enhance AET adherence. Methods: Eighteen women who were first prescribed AET for non-metastatic breast cancer in the last 5 years, who self-reported AET-related issues, and who participated in at least two MI-guided consultations over a year were interviewed about their perceptions of the intervention, using a semi-structured interview guide. Audio recordings were transcribed verbatim and analyzed using a thematic analysis approach. Results: Three main themes emerged from the data about women's perceptions on MI-guided consultations. These consultations were described as (1) a person-centred experience, (2) providing key information about AET, and (3) supportive of present and future AET experience, by contributing to AET side-effect management, motivation, adherence, calming negative emotions, improving well-being and self-esteem, and making women to feel empowered. Conclusions: Nurse-led telephone-based MI-guided consultations about AET were found to respond to participants' needs and to enhance participants' perceptions of being informed and being supported in experiencing various facets of AET. Telephone-based consultations for AET are perceived as a promising strategy in an increasing virtual care world

Telephone-based motivational interviewing consultations to enhance adherence to adjuvant endocrine therapy: A qualitative study on the experiences of women with non-metastatic breast cancer

Background/Purpose: Daily adjuvant endocrine therapy (AET) is prescribed to women for 5–10 years for hormone-sensitive breast cancer (60%–75% of breast cancer cases) to prevent recurrence and reduce mortality. However, a significant number of women experience AET-related issues that may affect quality of life and AET adherence. Few interventions to enhance AET adherence have been developed and tested, and the few studies available to date have generally produced inconclusive results. A telephone consultation program about AET using motivational interviewing (MI) principles was developed to be delivered by nurse navigators. This study aimed to describe women's experiences and perceived impact of this supportive program. Methods: 20 women who were first prescribed AET for nonmetastatic breast cancer in the last 5 years and who self-reported AET issues were provided with at least 2 individual, telephone-based MI consultations. Following the last MI consultation, we conducted a qualitative study. Participants were interviewed by a research team member about their experiences and perceptions using a semi-structured interview guide. Interviews were audio-taped, transcribed verbatim, and analyzed using thematic analysis. Results: Four key themes emerged from the analysis. The program was described by participants as: (1) a person-centered cancer care experience; (2) providing key information for self-management; (3) supportive regarding AET side effect management and adherence; and (4) contributing to a more optimistic perspective on AET. Overall, consultations via telephone were considered as convenient by most participants. Conclusions and Implications: Findings suggest that a telephone-based MI program can enhance side-effect management, motivation and adherence among women with non-metastatic breast cancer who have an AET. Ultimately, the program can better equip women to cope with AET in a less distressing and more optimistic manner. Future work would rely on quantitative approach to assess more broadly these findings

Higher angiotensin-converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease

Abstract Cognitive decline due to Alzheimer’s disease (AD) is frequent in the geriatric population, which has been disproportionately affected by the COVID-19 pandemic. In this study, we investigated the levels of angiotensin-converting enzyme 2 (ACE2), a regulator of the renin-angiotensin system and the main entry receptor of SARS-CoV-2 in host cells, in postmortem parietal cortex samples from two independent AD cohorts, totalling 142 persons. Higher concentrations of ACE2 protein (p < 0.01) and mRNA (p < 0.01) were found in individuals with a neuropathological diagnosis of AD compared to age-matched healthy control subjects. Brain levels of soluble ACE2 were inversely associated with cognitive scores (p = 0.02) and markers of pericytes (PDGFRβ, p = 0.02 and ANPEP, p = 0.007), but positively correlated with concentrations of soluble amyloid-β peptides (Aβ) (p = 0.01) and insoluble phospho-tau (S396/404, p = 0.002). However, no significant differences in ACE2 were observed in the 3xTg-AD mouse model of tau and Aβ neuropathology. Results from immunofluorescence and Western blots showed that ACE2 protein is predominantly localized in microvessels in the mouse brain whereas it is more frequently found in neurons in the human brain. The present data suggest that higher levels of soluble ACE2 in the human brain may contribute to AD, but their role in CNS infection by SARS-CoV-2 remains unclear