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Sarco(endo)plasmic reticulum calcium ([Ca.sup.2+]) ATPase (SERCA) transports [Ca.sup.2+] in muscle. Impaired SERCA activity may contribute to diabetic myopathy. Sirtuin (SIRT) 3 regulates muscle metabolism and function; however, it is unknown if SIRT3 regulates muscle SERCA activity or acetylation. We determined if SIRT3 overexpression enhances SERCA activity in mouse gastrocnemius muscle and if SIRT3 overexpression preserves gastrocnemius SERCA activity in a model of type 2 diabetes, induced by high fat - high sucrose (HFHS) feeding. We also determined if the acetylation status of SERCA proteins in mouse gastrocnemius is altered by SIRT3 overexpression or HFHS feeding. Wild-type (WT) and SIRT3 transgenic ([SIRT3.sub.TG]) mice, overexpressing SIRT3 in skeletal muscle, were fed a standard or HFHS diet for 4 months. [SIRT3.sub.TG] and WT mice developed obesity and glucose intolerance after 4 months of HFHS feeding. SERCA [V.sub.max] was higher in gastrocnemius of [SIRT3.sub.TG] mice compared with WT mice. HFHS-fed mice had lower SERCA1a protein levels and lower SERCA [V.sub.max] in their gastrocnemius than control-fed mice. The decrease in SERCA [V.sub.max] in gastrocnemius muscle due to HFHS feeding was attenuated by SIRT3 overexpression in HFHS-fed [SIRT3.sub.TG] mice. SERCA1a and SERCA2a acetylation in mouse gastrocnemius was not altered by genotype or diet. These findings suggest SIRT3 overexpression improves SERCA function in mouse skeletal muscle. Key words: SERCA, sirtuins, acetylation, calcium handling, diabetes, muscle. La calcium ([Ca.sup.2+]) ATPase du reticulum sarco(endo)plasmique (ou SERCA pour << Sarco(endo)plasmic reticulum Calcium ATPase >>) effectue le transport des ions [Ca.sup.2+] dans le muscle. Les perturbations de l'activite de la SERCA pourraient contribuer a la myopathie diabetique. La sirtuine (SIRT) 3 participe a la regulation du metabolisme et du fonctionnement des muscles. Toutefois, on ne sait pas si la SIRT3 participe a l'activite ou a l'acetylation de la SERCA musculaire. Nous avons cherche a etablir que la surexpression de la SIRT3 favorise l'activite de la SERCA dans le muscle gastrocnemien de souris et que la surexpression de la SIRT3 permet de preserver l'activite de la SERCA du muscle gastrocnemien dans un modele de diabete de type 2 engendre par l'administration d'un regime alimentaire a teneur elevee en matieres grasses et en saccharose (HFHS). Nous avons aussi cherche a etablir que le statut d'acetylation de la SERCA en proteines dans le muscle gastrocnemien de souris est altere par la surexpression de la SIRT3 ou le regime alimentaire de type HFHS. Pendant 4 mois, nous avons administre un regime alimentaire de type standard ou HFHS chez des souris de type sauvage (WT) et transgeniques ([SIRT3.sub.TG]), surexprimant la SIRT3 dans le muscle squelettique. Les souris [SIRT3.sub.TG] et WT ont presente de l'obesite et de l'intolerance au glucose apres l'administration d'un regime de type HFHS pendant 4 mois. Le [V.sub.max] de la SERCA etait plus eleve dans le muscle gastrocnemien des souris [SIRT3.sub.TG] que des souris WT. Les souris HFHS presentaient un taux de SERCA1a en proteines et un [V.sub.max] de la SERCA dans le muscle gastrocnemien moins eleves que les souris temoins. La diminution du [V.sub.max] de la SERCA entraoenee dans le muscle gastrocnemien par le regime alimentaire de type HFHS s'attenuait avec la surexpression de la SIRT3 chez les souris [SIRT3.sub.TG] auxquelles etait administre un regime alimentaire de type HFHS. Le genotype ou le regime alimentaire n'entraoenaient pas d'alteration de l'acetylation de la SERCA1a et de la SERCA2a dans le muscle gastrocnemien de souris. Ces resultats laissent entendre que la surexpression de la SIRT3 permettrait d'ameliorer le fonctionnement de la SERCA dans le muscle squelettique de souris. [Traduit par la Redaction] Mots-cles : SERCA, sirtuines, acetylation, manipulation du calcium, diabete, muscle., Introduction Type 2 diabetes (T2D) is a complex metabolic syndrome, partly characterized by disordered glucose transport and disrupted insulin signaling (Javeed and Matveyenko 2018). A poor diet is one of [...]

The cardiac rehabilitation quality indicators (CRQIs) developed by the Canadian Cardiovascular Society provide a means to standardize program assessment and identify sex-related inequities. No formal evaluation of the CRQIs has been conducted in Manitoba. An environmental scan for the CRQIs was performed using data in the electronic medical record at two cardiac rehabilitation (CR) sites in Winnipeg for 2016–2019 referrals. Of the 8116 referrals, 7758 (5491 males and 2267 females) had geographical access and were eligible for CR. The Manitoba Centre for Health Policy Data Quality Framework informed the data quality assessment. Thirteen CRQIs were available; four were considered high quality; nine demonstrated moderate to significant missing data. In addition to missing values, potential misclassification of risk (CR-4) and physiologically implausible and invalid dates were assessed and identified (CR-13 and CR-17). Each site had a physician medical director (CR-31) and a documented emergency response strategy (CR-32). Only high-quality data were evaluated for sex-related differences using chi-square and median tests. Women had lower enrollment (CR-3), and more women enrolled after the median of 41 days (CR-2b). Engagement with CR partners, including frontline staff, and utilizing strategies to assess and limit physiologically implausible values and dates will enhance data capture and quality. [ABSTRACT FROM AUTHOR]

Context: Patients and caregivers possess experiential knowledge of living with a health condition and/or accessing the healthcare system. This value-added knowledge complements the scientific and clinical insights gained from primary care researchers' and clinicians' perspectives. While emerging evidence demonstrates that patients and caregivers are valuable research team members, uncertainty about the practicalities of how to engage, and the associated impacts of engagement, are documented barriers to their research engagement. Objective: To describe activities used to engage patients and caregivers as co-researchers, and the perceived impacts of their engagement across the research cycle. Study Design and Analysis: A national cross-sectional online survey conducted in partnership with patients. Descriptive statistics and thematic analysis of data addressed the research objective. Setting: Pan-Canadian. Population Studied: Patients, caregivers, and researchers involved in a Canadian Institute of Health Research project funded through one of 13 Strategy for Patient-Oriented Research (SPOR) funding calls. Intervention/Instrument: We developed a survey that included modified items drawing from Patient-Centered Outcomes Research Institute's WE-ENACT tool and newly created items measuring SPOR Patient Engagement Framework elements. Survey items also assessed sociodemographic characteristics and characteristics of participants' SPOR-funded projects. Outcome Measures: Types of engagement activities and perceived impacts of engagement activities across the research cycle. Results: Survey responses were collected from 66/551 contacted researchers and 20/28 patients and caregivers. Seven activities were used to engage patients and caregivers across the research cycle: (a) sharing experiences/giving advice, (b) identifying the research focus/methods, (c) developing/revising aspects of the project, (d) conducting research activities, (e) study participation, (f) presenting on behalf of the project, and (g) other grant development or knowledge translation activities. Impacts of engagement resided within six categories and related to knowledge, outputs, or direction taken. Conclusions: Our study provides primary care researchers with practical evidence for engaging patients and caregivers in research. Findings are also important for primary care physicians, as they are often the first point of contact for patients and caregivers interested in engaging in research., Presenters Anna Chudyk, PhD, BHSc, MSc, Annette Schultz, PhD, RN, Nicola McCleary, Roger Stoddard, Todd Duhamel, [...]

Context: Patient engagement in research refers to the meaningful and active involvement of patients and caregivers as co-researchers (patient partners). The interdisciplinary nature of patient engagement in primary care research inherently influences team dynamics. A shared understanding and respect for all team members' (including patient partners') backgrounds, motivations, and expectations is imperative to partnership. Objective: To explore the motivations and meanings that patient partners attach to their role. Study Design and Analysis: A qualitative study was co-designed and led with a patient partner, using semi-structured interviews. Analysis captured the voices of patient partners through a thematic analysis process. Setting: Pan-Canadian. Population Studied: Patient partners involved in a Canadian Institute of Health Research project funded through one of 13 Strategy for Patient-Oriented Research funding calls. Intervention/Instrument: Semi-structured interviews were co-conducted virtually by a patient partner (RS) and academic researcher (AMC) and lasted 60-90 minutes. Open-ended interview questions were co-developed to address the research objective. Outcome Measures: Participants': (a) reason(s) for becoming, and perceptions of the (b) definition, (c) purpose and/or value, and (d) roles and/or responsibilities of patient partners. Results: Twelve (out of 15) individuals agreed to participate; 10 are women. Participants shared that although knowledge of living with a health condition and/or accessing health services provided the lived experience required to be a patient partner, they had other personal drivers motivating their decision and hopes for being co-researchers. Motivations included: altruism, professional background, personal history, and desire for personal growth. While definitions of 'patient partner' varied, there was agreement that advancing our shared understanding of both the word 'patient' and the word 'partner', along with the underlying purpose(s), role(s) and responsibilities of patient partners is imperative. Conclusions: Our findings advance insights into patient partners, which are relevant to primary care researchers and physicians. Researchers will benefit from taking the time to enhance their understanding of patient partners' hopes and motivations for partnering in research. An appreciation for what patient partners feel they have to offer and ultimately hope to accomplish nurtures positive team dynamics., Presenters Anna Chudyk, PhD, BHSc, MSc, Roger Stoddard, Nicola McCleary, Annette Schultz, PhD, RN, Todd Duhamel, [...]

The heart is capable of responding to stressful situations by increasing muscle mass, which is broadly defined as cardiac hypertrophy. This phenomenon minimizes ventricular wall stress for the heart undergoing a greater than normal workload. At initial stages, cardiac hypertrophy is associated with normal or enhanced cardiac function and is considered to be adaptive or physiological; however, at later stages, if the stimulus is not removed, it is associated with contractile dysfunction and is termed as pathological cardiac hypertrophy. It is during physiological cardiac hypertrophy where the function of subcellular organelles, including the sarcolemma, sarcoplasmic reticulum, mitochondria, and myofibrils, may be upregulated, while pathological cardiac hypertrophy is associated with downregulation of these subcellular activities. The transition of physiological cardiac hypertrophy to pathological cardiac hypertrophy may be due to the reduction in blood supply to hypertrophied myocardium as a consequence of reduced capillary density. Oxidative stress, inflammatory processes, [Ca.sup.2+]-handling abnormalities, and apoptosis in cardiomyocytes are suggested to play a critical role in the depression of contractile function during the development of pathological hypertrophy. Key words: cardiac hypertrophy, cardiac remodeling, pathological cardiac hypertrophy, physiological cardiac hypertrophy, adaptive cardiac hypertrophy, cardiac contractile function. Le coeur est capable de reagir a des situations de stress par une augmentation de sa masse musculaire, que l'on caracterise plus largement comme etant de l'hypertrophie cardiaque. Ce phenomene permet de reduire au minimum la tension de la paroi ventriculaire dans un coeur soumis a une charge de travail plus elevee que normalement. Aux premiers stades, l'hypertrophie cardiaque est associee avec une fonction cardiaque normale ou amelioree et est consideree comme etant adaptative ou physiologique; toutefois, a des stades plus tardifs, si le stimulus n'est pas ecarte, elle est associee avec un dysfonctionnement contractile et alors nommee hypertrophie cardiaque pathologique. C'est pendant l'hypertrophie cardiaque physiologique que le fonctionnement des organites sous-cellulaires, y compris le sarcolemme, le reticulum sarcoplasmique, les mitochondries et les myofibrilles peut etre regule a la hausse, tandis que l'hypertrophie cardiaque pathologique est associee avec une regulation a la baisse de ces activites sous-cellulaires. La transition de l'hypertrophie cardiaque physiologique vers l'hypertrophie cardiaque pathologique pourrait etre le fait d'une diminution de l'apport sanguin au myocarde hypertrophie comme consequence de la diminution de la densite des capillaires. On laisse entendre que le stress oxydatif, les processus inflammatoires, les anomalies de la gestion des ions [Ca.sup.2+] dans les cardiomyocytes ainsi que l'apoptose joueraient des roles critiques dans la depression de la fonction contractile au cours du developpement de l'hypertrophie pathologique. [Traduit par la Redaction] Mots-cles : hypertrophie cardiaque, remodelage cardiaque, hypertrophie cardiaque pathologique, hypertrophie cardiaque physiologique, hypertrophie cardiaque adaptative, fonction cardiaque contractile., Introduction The heart adapts to a sustained increase in blood pressure, or a sustained increase in blood volume, by increasing cardiac muscle mass and this growth in myocardium is broadly [...]

Long-chain saturated fatty acids, especially palmitic acid (PA), contribute to cardiomyocyte lipotoxicity. This study tests the effects of PA on adult rat cardiomyocyte contractile function and proteins associated with calcium regulating cardiomyocyte contraction and relaxation. Adult rat cardiomyocytes were pretreated with resveratrol (Resv) and then treated with PA. For the reversal study, cardiomyocytes were incubated with PA prior to treatment with Resv. Cardiomyocyte contractility, ratio of rod- to round-shaped cardiomyocytes, and Hoechst staining were used to measure functional and morphological changes in cardiomyocytes. Protein expression of sarco-endoplasmic reticulum ATPase 2a (SERCA2a), native phospholamban (PLB) and phosphorylated PLB (pPLB ser16 and pPLB thr17), and troponin I (TnI) and phosphorylated TnI (pTnI) were measured. SERCA2a activity was also measured. Our results show that PA (200 [micro]M) decreased the rate of cardiomyocyte relaxation, reduced the number of rod-shaped cardiomyocytes, and increased the number of cells with condensed nuclei; pre-treating cardiomyocytes with Resv significantly prevented these changes. Post-treatment with Resv did not reverse morphological changes induced by PA. Protein expression levels of SERCA2a, PLB, pPLBs, TnI, and pTnI were unchanged by PA or Resv. SERCA2a activity assay showed that [V.sub.max] and Iono ratio were increased with PA and pre-treatment with Resv prevented this increase. In conclusion, our results show that Resv protect cardiomyocytes from contractile dysfunction induced by PA. Key words: resveratrol, saturated fatty acid, cardiomyocyte contractility, obesity. Les acides gras a chaine longue satures, particulierement l'acide palmitique (AP), contribuent a la lipotoxicite contre les cardiomyocytes. Cette etude porte sur les effets de l'AP sur la fonction contractile de cardiomyocytes de rats adultes et les proteines associees avec le calcium assurant la regulation de la contraction et de la relaxation des cardiomyocytes. Nous avons mis au prealable des cardiomyocytes de rats adultes en presence de resveratrol, puis administre de l'AP. Pour l'etude d'inversion, nous avons incube les cardiomyocytes avec de l'AP avant l'administration de resveratrol. Nous avons mesure des variations fonctionnelles et morphologiques dans les cardiomyocytes a l'aide de l'evaluation de la contractilite des cardiomyocytes, du ratio de cardiomyocytes en batonnets et arrondis, ainsi que de la coloration de Hoechst. Nous avons mesure l'expression en proteines de l'ATPase 2a du reticulum sarco-endoplasmique (SERCA2a), du phospholamban (PLB) natif et du PLB phosphoryle (pPLB ser16 et pPLB thr17), de la troponine I (TnI) et de la TnI phosphorylee (pTnI). Nous avons aussi mesure l'activite de la SERCA2a. Nos resultats montrent que l'AP (a 200 [micro]M) entrainait un abaissement de la vitesse de relaxation des cardiomyocytes, une diminution du nombre de cardiomyocytes en batonnets, ainsi qu'une augmentation du nombre de cellules dotees d'un noyau dense; mais l'administration prealable de resveratrol permettait de prevenir ces changements. L'administration ulterieure de resveratrol n'a pas permis d'inverser les changements morphologiques provoques par l'AP. Les taux d'expression en proteines de SERCA2a, de PLB, de pPLBs, de TnI et de pTnI demeuraient inchanges avec l'AP et le resveratrol. La mesure de l'activite de la SERCA2a a montre que l'AP entrainait une augmentation du [V.sub.max] et du ratio Iono, et que l'administration prealable de resveratrol permettait de prevenir cette augmentation. En conclusion, nos resultats montrent que le resveratrol permet de proteger les cardiomyocytes contre un dysfonctionnement contractile engendre par l'AP. [Traduit par la Redaction] Mots-cles: resveratrol, acide gras sature, contractilite des cardiomyocytes, obesite., Introduction Excessive body fat results in increased levels of circulating lipids that have been linked to cardiovascular pathologies. Dysregulation of fat storage in pathological conditions leads to elevated lipid levels [...]

Within the Canadian context, the physical activity levels of children and youth in the after school time period has become a source of public health concern. We argue that this concern is informed by broader public health crises, in particular the "global obesity epidemic" and the closely related "global pandemic of physical inactivity," and that these so-called "crises" operate as part of a discursive regime that serves to justify after school interventions aimed at increasing the physical activity practices of children and youth. Although the objectives of such interventions are seemingly well intentioned, we suggest that such interventions nonetheless harbor difficult to discern, but potentially pernicious consequences, for the communities in which they are implemented. We focus our attention on the place-specific effects of one Public Health Agency of Canada-funded after school physical activity intervention--After the School Bell Rings (ASBR)--that was implemented in the mostly Indigenous, northern community of Placid, Manitoba. Based on a critical analysis of the ASBR program itself, along with interviews and focus groups with children, parents and recreation providers (n = 10) from the community of Placid, we contend that the ASBR serves to govern Indigenous recreation at a distance. We argue that when implemented in the place-specific context of Placid, the ASBR functions as part of a broader governmental assemblage composed of loosely connected discourses, institutions, socio-structural conditions and individuals that, when assembled, ultimately serve to govern geographically and culturally distinct communities. We conclude by suggesting that the objectives of broad-based health interventions, such as the goal of increasing after school physical activity levels, should not be universally implemented across diverse locales, but need to account for the diverse, place-specific priorities and needs of the communities into which they are implemented.

Exercise enhances cardiac sarcoplasmic reticulum [Ca.sup.2+]-ATPase 2a (SERCA2a) function through unknown mechanisms. The present study tested the hypothesis that the positive effects of exercise on SERCA2a expression and function in the left ventricle is dependent on adenosine-monophosphate-activated protein kinase (AMPK) [[alpha].sub.2] function. [AMPK[alpha].sub.2] kinase-dead (KD) transgenic mice, which overexpress inactivated [AMPK[alpha].sub.2] subunit, and wild-type C57Bl/6 (WT) mice were randomized into sedentary groups or groups with access to running wheels. After 5 months, exercised KD mice exhibited shortened deceleration time compared with sedentary KD mice. In left ventricular tissue, the ratio of phosphorylated [AMPK[alpha].sup.Thr72]:total AMPK[alpha] was 65% lower (P < 0.05) in KD mice compared with WT mice. The left ventricle of KD mice had 37% lower levels of SERCA2a compared with WT mice. Although exercise increased SERCA2a protein levels in WT mice by 53%, this response of exercise was abolished in exercised KD mice. Exercise training reduced total phospholamban protein content by 23% in both the WT and KD mice but remained 20% higher overall in KD mice. Collectively, these data suggest that AMPK[alpha] influences SERCA2a and phospholamban protein content in the sedentary and exercised heart, and that exercise-induced changes in SERCA2a protein are dependent on AMPK[alpha] function. Key words: AMPK, SERCA, exercise training, phospholamban, [Ca.sup.2+] handling, left ventricle, diastolic function. L'exercice physique permet d'ameliorer le fonctionnement de la pompe [Ca.sup.2+]-ATPase 2a du reticulum sarcoplasmique (SERCA2a) par l'intermediaire de modes d'action inconnus. La presente etude tentait de verifier l'hypothese selon laquelle les effets positifs de l'exercice physique sur l'expression de la SERCA2a et la fonction ventriculaire gauche dependent du fonctionnement de la proteine kinase [[alpha].sub.2] activee par l'AMP ([AMPK[alpha].sub.2]). Nous avons reparti aleatoirement des souris transgeniques KD (pour<>), qui surexpriment la sous-unite [AMPK[alpha].sub.2] inactivee, ainsi que des souris C57Bl/6 de type sauvage (WT) dans des groupes sedentaires ou avec acces a des roues porteuses. Apres 5 mois, les souris entrainees presentaient une diminution du temps de deceleration par rapport aux souris KD sedentaires. Dans le tissu ventriculaire gauche, le ratio entre les taux d'[AMPK[alpha].sup.Thr172] phosphorylee et d'AMPK[alpha] totale etait 65 % plus bas chez les souris KD que chez les souris WT (P < 0,05). Le ventricule gauche des souris KD presentait des taux de SERCA2a 37 % plus bas que les souris WT. Meme si l'exercice physique entrainait une augmentation des taux de SERCA2a en proteines de 53 % chez les souris WT, cette reaction etait abolie chez les souris KD entrainees. L'exercice physique entrainait une diminution des taux de phospholamban en proteines total de 23 % chez les souris WT comme chez les souris KD, mais ils demeuraient 20 % plus eleves pour l'ensemble des souris KD. Collectivement, ces resultats laissent entendre que l'AMPK[alpha] influencerait les taux de SERCA2 et de phospholamban en proteines dans les creurs sedentaires ou entraines, et que les variations engendrees par l'exercice physique quant aux taux de SERCA2a en proteines dependent du fonctionnement de l'AMPK[alpha]. [Traduit par la Redaction] Mots-cles: AMPK, SERCA, entrainement physique, phospholamban, gestion du [Ca.sup.2+], ventricule gauche, fonction diastolique., Introduction Physical activity is an important factor for the prevention of heart disease and also an important component of rehabilitation for patients with established cardiovascular disease (Perez-Terzic 2012). Even so, [...]