Use of Wearable Activity-Monitoring Technologies to Promote Physical Activity in Cancer Survivors: Challenges and Opportunities for Improved Cancer Care

The aim of this review was to explore the acceptability, opportunities, and challenges associated with wearable activity-monitoring technology to increase physical activity (PA) behavior in cancer survivors. A search of Medline, Embase, CINAHL, and SportDiscus was conducted from 1 January 2011 through 3 October 2022. The search was limited to English language, and peer-reviewed original research. Studies were included if they reported the use of an activity monitor in adults (+18 years) with a history of cancer with the intent to motivate PA behavior. Our search identified 1832 published articles, of which 28 met inclusion/exclusion criteria. Eighteen of these studies included post-treatment cancer survivors, eight were on active cancer treatment, and two were long-term cancer survivor studies. ActiGraph accelerometers were the primary technology used to monitor PA behaviors, with Fitbit as the most commonly utilized self-monitoring wearable technology. Overall, wearable activity monitors were found to be an acceptable and useful tool in improving self-awareness, motivating behavioral change, and increasing PA levels. Self-monitoring wearable activity devices have a positive impact on short-term PA behaviors in cancer survivors, but the increase in PA gradually attenuated through the maintenance phase. Further study is needed to evaluate and increase the sustainability of the use of wearable technologies to support PA in cancer survivors

Substituting bouts of sedentary behavior with physical activity: adopting positive lifestyle choices in people with a history of cancer

Purpose: To determine in people with a history of cancer, whether substituting sitting time with other daily activities (i.e., sleeping, walking, moderate and vigorous physical activity) was associated with changes in waist circumference (WC), an important surrogate marker of cardiometabolic risk. Methods: Cross-sectional analyses from the Atlantic Partnership for Tomorrow’s Health (Atlantic PATH) cohort was conducted using isotemporal substitution models to explore the associations of substituting sedentary time, physical activity behavior (International Physical Activity Questionnaire), or sleep (Pittsburgh Sleep Quality Index) with changes in WC. Analyses were conducted using sex-specific WC classifications. Results: In 3,684 people with a history of cancer [mean age (SD) 58.2 (7.3) years; BMI 28.9 (5.2) kgm−2; 71% female], reallocating 10min of sleep or sedentary time for 10min of walking was associated with lower WC in women (p < 0.01). In men, PA intensity appeared to be more strongly associated with a reduced WC. Replacing 10min of sedentary time with 10min of moderate or vigorous PA and replacing 10min of sleep with moderate PA were associated with a significantly reduced WC (p < 0.001). The largest effect was when 10min of moderate PA was replaced with vigorous PA, a reduction in WC (p < 0.01) was evident. Conclusion: For people with a history of cancer, adopting small but positive changes in lifestyle behaviors could help reduce WC and potentially offset negative health-related outcomes associated with higher WC. Further research is required to examine whether such an intervention may be acceptable and manageable among this population

Fruit and vegetable intake and body adiposity among populations in Eastern Canada: The Atlantic Partnership for Tomorrow's Health Study

Objectives The prevalence of obesity among populations in the Atlantic provinces is the highest in Canada. Some studies suggest that adequate fruit and vegetable consumption may help body weight management. We assessed the associations between fruit and vegetable intake with body adiposity among individuals who participated in the baseline survey of the Atlantic Partnership for Tomorrow’s Health (Atlantic PATH) cohort study.Methods We carried out a cross-sectional analysis among 26 340 individuals (7979 men and 18 361 women) aged 35–69 years who were recruited in the baseline survey of the Atlantic PATH study. Data on fruit and vegetable intake, sociodemographic and behavioural factors, chronic disease, anthropometric measurements and body composition were included in the analysis.Results In the multivariable regression analyses, 1 SD increment of total fruit and vegetable intake was inversely associated with body mass index (−0.12 kg/m2; 95% CI −0.19 to –0.05), waist circumference (−0.40 cm; 95% CI −0.58 to –0.23), percentage fat mass (−0.30%; 95% CI −0.44 to –0.17) and fat mass index (−0.14 kg/m2; 95% CI −0.19 to –0.08). Fruit intake, but not vegetable intake, was consistently inversely associated with anthropometric indices, fat mass, obesity and abdominal obesity.Conclusions Fruit and vegetable consumption was inversely associated with body adiposity among the participant population in Atlantic Canada. This association was primarily attributable to fruit intake. Longitudinal studies and randomised trials are warranted to confirm these observations and investigate the underlying mechanisms

Adiposity Measures and Plasma Adipokines in Females with Rheumatoid and Osteoarthritis

The objective of this study was to examine the relationship between adipokines and adiposity in individuals with rheumatoid and osteoarthritis in the Atlantic PATH cohort. Using a nested case-control analysis, participants in the Atlantic PATH cohort with rheumatoid or osteoarthritis were matched for measures of adiposity with participants without a history of arthritis. Both measured and self-reported data were used to examine disease status, adiposity, and lifestyle factors. Immunoassays were used to measure plasma markers. BMI was positively correlated with percentage body fat, fat mass index (FMI), and a change in BMI from 18 years of age in all 3 groups. There were no statistical differences between levels of plasma adipokines; adiponectin levels were 6.6, 7.9, and 8.2 μg/ml, leptin levels were 10.3, 13.7, and 11.5 ng/ml, and resistin levels were 10.0, 12.1, and 10.8 ng/ml in participants without arthritis, with rheumatoid arthritis, and with osteoarthritis, respectively. Those with higher levels of adiponectin were more likely to have osteoarthritis (but not rheumatoid arthritis). No association was found between arthritis types and leptin or resistin. This study demonstrates differences in measures of adiposity and adipokines in specific types of arthritis and highlights the need for more research targeting specific adipokines during arthritic disease progression

The relationship between anthropometric measures and cardiometabolic health in shift work: findings from the Atlantic PATH Cohort Study

PurposeTo evaluate the relationship between anthropometric measures and cardiometabolic health in shift workers compared to non-shift workers.MethodsA population health study was conducted with 4155 shift workers and 8258 non-shift workers from the Atlantic Partnership for Tomorrow’s Health (PATH) cohort. Linear and logistic regression models were used to assess the differences in anthropometric measures (body adiposity) and self-reported cardiometabolic disease outcomes (obesity, diabetes, and cardiovascular disease) between shift workers and non-shift workers.ResultsThere was a significant increased risk of cardiovascular disease, obesity, and diabetes among shift workers compared to matched controls despite higher levels of physical activity and lower levels of sedentary behaviour. Shift workers were 17% more likely to be obese (95% CI 7–27) and 27% more likely to have diabetes (95% CI 8–51). The strength of this association was demonstrated by also controlling for body mass index and fat mass index.ConclusionsShift work is associated with obesity, cardiovascular disease, and diabetes despite higher levels of physical activity and lower levels of sedentary behaviour. The association between shift work and cardiometabolic health was independent of body mass index for cardiovascular disease and diabetes, and independent of fat mass index for diabetes

Relationship between Adiponectin and apoB in individuals with diabetes in the Atlantic PATH Cohort

ContextThe increasing prevalence of obesity and diabetes greatly influences the risk for cardiovascular (CV) comorbidities and affects the quality of life of many people. However, the relationship among diabetes, obesity, and cardiovascular risk is complex and requires further investigation to understand the biological milieu connecting these conditions.ObjectiveThe aim of the current study was to explore the relationship between biological markers of adipose tissue function (adiponectin) and CV risk (apolipoprotein B) in body mass index (BMI)–matched participants with and without diabetes.DesignNested case-control study.SettingThe Atlantic Partnership for Tomorrow’s Health (PATH) cohort represents four Atlantic Canadian provinces: Newfoundland and Labrador, New Brunswick; Nova Scotia; and Prince Edward Island.ParticipantsThe study population (n = 480) was aged 35 to 69 years, 240 with diabetes and 240 without diabetes.Main Outcome MeasuresGroups with and without diabetes were matched for sex and BMI. Both measured and self-reported data were used to examine disease status, adiposity, and lifestyle factors. Immunoassays were used to measure plasma markers.ResultsIn these participants, plasma adiponectin levels were lower among those with diabetes than those without diabetes; these results were sex-specific, with a strong relationship seen in women. In contrast, in participants matched for sex and adiposity, plasma apoB levels were similar between participants with and those without diabetes.ConclusionMeasures of adiposity were higher in participants with diabetes. However, when matched for adiposity, the adipokine adiponectin exhibited a strong inverse association with diabetes

The use of plasma aldosterone and urinary sodium to potassium ratio as translatable quantitative biomarkers of mineralocorticoid receptor antagonism

<p>Abstract</p> <p>Background</p> <p>Accumulating evidence supports the role of the mineralocorticoid receptor (MR) in the pathogenesis of diabetic nephropathy. These findings have generated renewed interest in novel MR antagonists with improved selectivity against other nuclear hormone receptors and a potentially reduced risk of hyperkalemia. Characterization of novel MR antagonists warrants establishing translatable biomarkers of activity at the MR receptor. We assessed the translatability of urinary sodium to potassium ratio (Na⁺/K⁺) and plasma aldosterone as biomarkers of MR antagonism using eplerenone (Inspra^®), a commercially available MR antagonist. Further we utilized these biomarkers to demonstrate antagonism of MR by PF-03882845, a novel compound.</p> <p>Methods</p> <p>The effect of eplerenone and PF-03882845 on urinary Na⁺/K⁺and plasma aldosterone were characterized in Sprague-Dawley rats and spontaneously hypertensive rats (SHR). Additionally, the effect of eplerenone on these biomarkers was determined in healthy volunteers. Drug exposure-response data were modeled to evaluate the translatability of these biomarkers from rats to humans.</p> <p>Results</p> <p>In Sprague-Dawley rats, eplerenone elicited a rapid effect on urinary Na⁺/K⁺yielding an EC₅₀that was within 5-fold of the functional <it>in vitro </it>IC₅₀. More importantly, the effect of eplerenone on urinary Na⁺/K⁺in healthy volunteers yielded an EC₅₀that was within 2-fold of the EC₅₀generated in Sprague-Dawley rats. Similarly, the potency of PF-03882845 in elevating urinary Na⁺/K⁺in Sprague-Dawley rats was within 3-fold of its <it>in vitro </it>functional potency. The effect of MR antagonism on urinary Na⁺/K⁺was not sustained chronically; thus we studied the effect of the compounds on plasma aldosterone following chronic dosing in SHR. Modeling of drug exposure-response data for both eplerenone and PF-03882845 yielded EC₅₀values that were within 2-fold of that estimated from modeling of drug exposure with changes in urinary sodium and potassium excretion. Importantly, similar unbound concentrations of eplerenone in humans and SHR rats yielded the same magnitude of elevations in aldosterone, indicating a good translatability from rat to human.</p> <p>Conclusions</p> <p>Urinary Na⁺/K⁺and plasma aldosterone appear to be translatable biomarkers of MR antagonism following administration of single or multiple doses of compound, respectively.</p> <p>Trial Registration</p> <p>For clinical study reference EE3-96-02-004, this study was completed in 1996 and falls out scope for disclosure requirements.</p> <p>Clinical study reference A6141115: <url>http://clinicaltrials.gov</url>, <url>http://NIHclinicaltrails.gov</url>; NCTID: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00990223">NCT00990223</a></p

Percutaneous Transendocardial Delivery of Self-complementary Adeno-associated Virus 6 Achieves Global Cardiac Gene Transfer in Canines

Achieving efficient cardiac gene transfer in a large animal model has proven to be technically challenging. Previous strategies have used cardiopulmonary bypass or dual catheterization with the aid of vasodilators to deliver vectors, such as adenovirus, adeno-associated virus (AAV), or plasmid DNA. Although single-stranded AAV (ssAAV) vectors have shown the greatest promise, they suffer from delayed expression, which might be circumvented using self-complementary vectors. We sought to optimize cardiac gene transfer using a percutaneous transendocardial injection catheter to deliver adeno-associated viral vectors to the canine myocardium. Four vectors were evaluated-ssAAV9, self-complementary AAV9 (scAAV9), scAAV8, scAAV6-so that comparison could be made between single-stranded and self-complementary vectors as well as among serotypes 9, 8, and 6. We demonstrate that scAAV is superior to ssAAV and that AAV 6 is superior to the other serotypes evaluated. Biodistribution studies revealed that vector genome copies were 15-4,000 times more abundant in the heart than in any other organ for scAAV6. Percutaneous transendocardial injection of scAAV6 is a safe, effective method to achieve efficient cardiac gene transfer

The membrane mucin MUC4 is elevated in breast tumor lymph node metastases relative to matched primary tumors and confers aggressive properties to breast cancer cells

Abstract Introduction Previous studies indicate that overexpression of the membrane-associated mucin MUC4 is potently anti-adhesive to cultured tumor cells, and suppresses cellular apoptotic response to a variety of insults. Such observations raise the possibility that MUC4 expression could contribute to tumor progression or metastasis, but the potential involvement of MUC4 in breast cancer has not been rigorously assessed. The present study aimed to investigate the expression of the membrane mucin MUC4 in normal breast tissue, primary breast tumors and lymph node metastases, and to evaluate the role of MUC4 in promoting the malignant properties of breast tumor cells. Methods MUC4 expression levels in patient-matched normal and tumor breast tissue was initially examined by immunoblotting lysates of fresh frozen tissue samples with a highly specific preparation of anti-MUC4 monoclonal antibody 1G8. Immunohistochemical analysis was then carried out using tissue microarrays encompassing patient-matched normal breast tissue and primary tumors, and patient-matched lymph node metastases and primary tumors. Finally, shRNA-mediated knockdown was employed to assess the contribution of MUC4 to the cellular growth and malignancy properties of JIMT-1 breast cancer cells. Results Immunoblotting and immunohistochemistry revealed that MUC4 levels are suppressed in the majority (58%, p &lt; 0.001) of primary tumors relative to patient-matched normal tissue. On the other hand, lymph node metastatic lesions from 37% (p &lt; 0.05) of patients expressed higher MUC4 protein levels than patient-matched primary tumors. MUC4-positive tumor emboli were often found in lymphovascular spaces of lymph node metastatic lesions. shRNA-mediated MUC4 knockdown compromised the migration, proliferation and anoikis resistance of JIMT-1 cells, strongly suggesting that MUC4 expression actively contributes to cellular properties associated with breast tumor metastasis. Conclusions Our observations suggest that after an initial loss of MUC4 levels during the transition of normal breast tissue to primary tumor, the re-establishment of elevated MUC4 levels confers an advantage to metastasizing breast tumor cells by promoting the acquisition of cellular properties associated with malignancy