Wabishki Bizhiko Skaanj: a learning pathway to foster better Indigenous cultural competence in Canadian health research.

OBJECTIVE: In Canada, Indigenous people experience racism across diverse settings, including within the health sector. This has negatively impacted both the quality of care that Indigenous people receive as well as how research related to Indigenous populations is conducted. Therefore, an Indigenous-led council at a kidney research network, in partnership with other key stakeholders, sought to create a learning pathway that aims to distill the racism that Indigenous people face, and build cultural competence, within the health sector. PARTICIPANTS: The learning pathway was designed for researchers, health care providers, patient partners and administrators. SETTING: Various components of the pathway are established trainings in healthcare and research settings at provincial and national levels. Provincially, some components are implemented in British Columbia, Alberta, Saskatchewan, Manitoba and Ontario. INTERVENTION: The pathway, called Wabishki Bizhiko Skaanj (meaning "White Horse" in Anishinaabemowin), involves six key steps: a culturally tailored blanket exercise that walks participants through the history of local Indigenous Nations/peoples; a more detailed online training program (San'yas); a series of webinars on Indigenous research ethics and protocols; an educational booklet about engaging Knowledge Keepers in research, as well as sharing details about their traditional knowledge and culture; two certification programs about Indigenous ownership of data; and a "book club," wherein the conversation of racism-and the goal for finding solutions-is continually discussed. OUTCOMES: Wabishki Bizhiko Skaanj is working to build cultural competence in the Canadian health sector. IMPLICATIONS: This learning pathway has the potential to address racial disparities across the country and improve health outcomes for Indigenous peoples.

RéSUMé: OBJECTIF: Au Canada, les autochtones font face au racisme dans divers milieux, y compris dans le secteur de la santé. Cela a eu une incidence négative sur la qualité des soins que reçoivent les peuples autochtones, ainsi que sur la façon dont la recherche sur les populations autochtones est menée. Par conséquent, un conseil dirigé par des Autochtones dans un réseau de recherche sur les reins, en partenariat avec d'autres parties prenantes, a cherché à créer une voie d'apprentissage visant à réduire le racisme auquel les peuples autochtones sont confrontés et à renforcer les compétences culturelles au sein du secteur de la santé. PARTICIPANTS: La voie d'apprentissage a été conçue pour les chercheurs, les fournisseurs de soins de santé, les patients partenaires et les administrateurs. CADRE: Cette voie d'apprentissage est composée de formations établies dans le milieu de la santé et de la recherche au niveau provincial et national. À l'échelle provinciale, il y a des programmes ayant lieu en Colombie-Britannique, en Alberta, en Ontario, en Saskatchewan et au Manitoba. INTERVENTION: La voie d'apprentissage, appelée Wabishki Bizhiko Skaanj (qui signifie « cheval blanc ¼ en Anishinaabemowin), comporte six étapes clés : un exercice culturel sur mesure qui guide les participants à travers l'histoire des nations/peuples autochtones locaux à l'aide de diverses couvertures culturelles; un programme de formation en ligne détaillé (San'yas); une série de webinaires sur l'éthique et les protocoles autochtones en matière de recherche; un livret pédagogique sur l'engagement des gardiens de la connaissance en recherche ainsi que le partage d'informations sur leur connaissance et leur culture traditionnelle; deux programmes de certification sur la propriété autochtone des données; et un « club de lecture ¼ dans lequel nous ne cessons de discuter du racisme tout en cherchant des solutions. RéSULTATS: Wabishki Bizhiko Skaanj s'efforce de renforcer les compétences culturelles dans le secteur de la santé au Canada. IMPLICATIONS: Cette voie d'apprentissage a le potentiel de s'attaquer aux disparités raciales à l'échelle nationale et d'améliorer les résultats en matière de santé pour les peuples autochtones.

Proposed trial: safety and efficacy of resveratrol for the treatment of non-alcoholic fatty liver disease (NAFLD) and associated insulin resistance in adolescents who are overweight or obese adolescents - rationale and protocol.

Non-alcoholic fatty liver (NAFL) disease (NAFLD) affects 30% of overweight adolescents and increases the risk of type 2 diabetes mellitus (T2D). Resveratrol is a naturally occurring compound with potential to reverse NAFL and its associated insulin resistance in adults. The use of resveratrol to reduce risk for T2D through its effect on NAFL has not been examined to date in youth. This paper provides a literature review and protocol for a 30 day proof of principle trial of resveratrol in a population of adolescents at risk for T2D. This randomized double-blind controlled trial is designed with the primary objective of evaluating a twice daily supplementation of 75 mg of resveratrol for safety and tolerability in overweight and obese adolescent subjects (13 to <18 years of age) with NAFL. Secondary objectives are to determine the effect size of the intervention on hepatic steatosis and whole body insulin sensitivity. Adolescents in the intervention arm (n = 10) will receive oral supplementation of resveratrol 75 mg twice daily (with breakfast and dinner) for a total daily dose of 150 mg for the duration of 30 days. The comparison group (n = 10) will receive a placebo twice daily for 30 days. Both cases and controls will receive a standardized lifestyle intervention program. Subjects in both groups will be followed for an additional 30 days post intervention for total study duration of approximately 60 days. Primary outcome measures include a primary side effect profile determined by participant interview, a side effect profile determined by serum biochemistry and vital signs. Secondary outcome measures include an oral glucose tolerance test, liver and cardiac fat content measured by magnetic resonance spectroscopy, anthropometric measures of overweight/obesity, inflammatory markers, and cardiac function and morphology measured with ultrasonography. Additional outcome measures include serum concentrations of resveratrol, compliance to protocol, physical activity, and nutritional assessment. This study will determine the safety and tolerability of resveratrol in an overweight adolescent population and inform the design of a larger randomized controlled trial.

Preliminary analysis of immune activation in early onset type 2 diabetes.

INTRODUCTION: First Nations and other Aboriginal children are disproportionately affected by cardiometabolic diseases, including type 2 diabetes (T2D). In T2D, the disruption of insulin signalling can be driven by pro-inflammatory immunity. Pro-inflammatory responses can be fueled by toll-like receptors (TLR) on immune cells such as peripheral blood mononuclear cells (PBMC, a white blood cell population). TLR4 can bind to lipids from bacteria and food sources activating PBMC to produce cytokines tumour necrosis factor (TNF)-α and interleukin (IL)-1ß. These cytokines can interfere with insulin signalling. Here, we seek to understand how TLR4 activation may be involved in early onset T2D. We hypothesized that immune cells from youth with T2D (n = 8) would be more reactive upon TLR4 stimulation relative to cells from age and body mass index (BMI)-matched controls without T2D (n = 8). METHODS: Serum samples were assayed for adipokines (adiponectin and leptin), as well as cytokines. Freshly isolated PBMC were examined for immune reactivity upon culture with TLR4 ligands bacterial lipopolysaccharide (LPS, 2 and 0.2 ng/ml) and the fatty acid palmitate (200 µM). Culture supernatants were evaluated for the amount of TNF-α and IL-1ß produced by PBMC. RESULTS: Youth with T2D displayed lower median serum adiponectin levels compared to controls (395 vs. 904 ng/ml, p < 0.05). PBMC isolated from youth with and without T2D produced similar levels of TNF-α and IL-1ß after exposure to the higher LPS concentration. However, at the low LPS dose the T2D cohort exhibited enhanced IL-1ß synthesis relative to the control cohort. Additionally, exposure to palmitate resulted in greater IL-1ß synthesis in PBMCs isolated from youth with T2D versus controls (p < 0.05). These differences in cytokine production corresponded to greater monocyte activation in the T2D cohort. CONCLUSION: These preliminary results suggest that cellular immune responses are exaggerated in T2D, particularly with respect to IL-1ß activity. These studies aim to improve the understanding of the biology behind early onset T2D and its vascular complications that burden First Nations people.

Prolonged strenuous exercise alters the cardiovascular response to dobutamine stimulation in male athletes.

Prolonged strenuous exercise has been associated with transient impairment in left ventricular (LV) systolic and diastolic function that has been termed 'cardiac fatigue'. It has been postulated that cardiac beta-adrenoreceptor desensitization may play a central role; however, data are limited. Accordingly, we assessed the cardiovascular response to progressive dobutamine stimulation after prolonged strenuous exercise (2 km swim, 90 km bike, 21 km run). Nine experienced male athletes were studied: PRE (2-3 days before), POST (after) and REC (1-2 days later). The cardiovascular response to progressive continuous dobutamine stimulation (0, 5, 20, and 40 microg kg(-1) min(-1)) was assessed, including heart rate (HR), systolic blood pressure (SBP), LV cavity areas (two-dimensional echocardiography) and contractility (end-systolic elastance, SBP/end-systolic cavity area (ESCA)). POST there was limited evidence of myocardial necrosis (measured by troponin I), while catecholamines were elevated. HR was higher POST (mean +/-s.d.; PRE, 58 +/- 9; POST, 79 +/- 9; REC, 57 +/- 7 beats min(-1); P < 0.05), while SBP was lower (PRE, 127 +/- 15; POST, 116 +/- 9; REC, 121 +/- 12 mmHg; P < 0.05). A blunted HR, SBP and LV contractility (SBP/ESCA; PRE 29 +/- 6 versus POST 20 +/- 6 mmHg cm(-2); P < 0.05) response to dobutamine was demonstrated POST, with values returning towards baseline in REC. Following prolonged strenuous exercise, the chronotropic and inotropic response to dobutamine stimulation is blunted. This study supports the hypothesis that beta-receptor downregulation and/or desensitization may play a major role in prolonged-strenuous-exercise-mediated cardiac fatigue.

Late potentials in female triathletes before and after prolonged strenuous exercise.

The objectives of this study were to evaluate the prevalence of late potentials (LP) in female triathletes before and after prolonged strenuous exercise (PSE), and to determine whether LP are related to greater left ventricular (LV) dimensions and/or mass. Thirteen female triathletes were examined immediately before (Pre), one hour after (Post), and 24 to 48 hours after PSE (Recovery) using signal-averaged electrocardiography (SAECG). Late potentials were evaluated by two or more standard SAECG anomalies. Left ventricular dimensions and mass were measured Pre using two-dimensional echocardiography. Results revealed that no significant differences existed between Pre, Post, and Recovery in the SAECG parameters. Four athletes displayed LP during Pre. The incidence of LP during did not increase Post. There were no significant relationships between LV dimensions or mass and SAECG parameters. In conclusion, a small portion of female triathletes display LP before and after PSE, which are not worsened by PSE nor related to increased LV dimensions and/or mass.