Moringa oleifera Improves Skeletal Muscle Metabolism and Running Performance in Mice

Background: Recent estimates suggest that 7% of Americans use plant-derived nutritional supplements to treat a variety of complications and/or to improve athletic performance and skeletal muscle health. Unfortunately, these supplements are largely unregulated and understudied. For example, Moringa oleifera (M. oleifera) is a subtropical plant and is routinely used to treat inflammation, diabetes, obesity, cancer and HIV. However, the mechanism of action of M. oleifera has not been fully elucidated, thus the purpose of this study is to evaluate the role of M. oleifera as a novel ergogenic aid to improve exercise performance by driving peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-dependent signaling pathways implicated in mitochondrial biogenesis and oxidative metabolism in skeletal muscle tissue. Methods: Adult male C57BL/6 mice were treated with 1.0 g of M. oleifera (N = 20) per day or vehicle control (N = 20) for a total of 5 weeks. Following 3 weeks of supplementation, half of each group (RUN) was given access to running wheels every night for 2 weeks (Remaining half = SED), distances ran were recorded daily. After treatment protocols were complete, the gastrocnemius muscles were excised and assayed for known markers of mitochondrial biogenesis, angiogenesis, endurance capacity, and capillary density using immunohistochemistry and RT-PCR. Results: Our results showed a significant increase in average distance run in the M. oleifera + SED and M. oleifera + RUN groups. This physiological trend was consistent with the molecular profile of key metabolic markers, i.e., there was an increase in levels of PGC-1α, PPARγ, SDHB, SUCLG1, VEGF, PGAM-2, PGK1, and MYLPF in the M. oleifera treated groups compared to vehicle + SED. Moreover, M. oleifera also increased CSA and decreased markers of protein degradation. Conclusions: This data suggests that M. oleifera has the potential to be an ergogenic aid via enhancing energy metabolism in adult skeletal muscle by increasing the expression of key metabolic markers, including those involved in glycolysis, oxidative phosphorylation, mitochondrial biogenesis and angiogenesis

Brain activation during dual-task processing is associated with cardiorespiratory fitness and performance in older adults

Citation: Wong, C. N., Chaddock-Heyman, L., Voss, M. W., Burzynska, A. Z., Basak, C., Erickson, K. I., . . . Kramer, A. F. (2015). Brain activation during dual-task processing is associated with cardiorespiratory fitness and performance in older adults. Frontiers in Aging Neuroscience, 7, 10. doi:10.3389/fnagi.2015.00154Higher cardiorespiratory fitness is associated with better cognitive performance and enhanced brain activation. Yet, the extent to which cardiorespiratory fitness-related brain activation is associated with better cognitive performance is not well understood. In this cross-sectional study, we examined whether the association between cardiorespiratory fitness and executive function was mediated by greater prefrontal cortex activation in healthy older adults. Brain activation was measured during dual-task performance with functional magnetic resonance imaging in a sample of 128 healthy older adults (59-80 years). Higher cardiorespiratory fitness was associated with greater activation during dual-task processing in several brain areas including the anterior cingulate and supplementary motor cortex (ACC/SMA), thalamus and basal ganglia, right motor/somatosensory cortex and middle frontal gyrus, and left somatosensory cortex, controlling for age, sex, education, and gray matter volume. Of these regions, greater ACC/SMA activation mediated the association between cardiorespiratory fitness and dual-task performance. We provide novel evidence that cardiorespiratory fitness may support cognitive performance by facilitating brain activation in a core region critical for executive function

Diagnosis, Prognosis, Management, Treatment, Research and Advances in Canine Dilated Cardiomyopathy

Dilated cardiomyopathy involves enlargement of the ventricular chamber and systolic dysfunction. The reduction in quality of life and increased levels of congestive heart failure, combined with the high diagnosis rate within the canine population, highlights the need for research into this disorder. This chapter looks at prevention, diagnosis, prognosis, and treatment of dilated cardiomyopathy. It details the disease pathology and physiology through to present clinical practices and studies to support prevention and treatment. This chapter also looks at the research being undertaken to further understand cardiomyopathies in dogs and develop new interventions. This ranges from fatty acids profiles to genetics and even personalized medicine and comparisons with human cardiomyopathy

Using oral bioaccessibility measurements to refine risk assessment of potentially toxic elements in topsoils across an urban area

Elevated concentrations of As, Cr, Cu, Ni, Pb, V and Zn in topsoils in Belfast, Northern Ireland have been found to exceed assessment criteria in the city and therefore may pose a risk to human health. Most generic assessment criteria (GAC) for potentially toxic elements (PTEs) in soils assume PTEs are 100% bioavailable to humans. Here we use in-vitro oral bioaccessibility testing using the Unified BARGE method (UBM) to measure what proportion of soil contamination dissolves in the digestive tract and therefore is available for absorption by the body. This study considers how PTE bioaccessibility in soils varies spatially across urban areas and refines human health risk assessment for these PTEs using site specific oral bioaccessibility results to present the first regional assessment of risk that incorporates bioaccessibility testing. A total of 103 urban soil samples were selected for UBM testing. Results showed low bioaccessible fraction (BAF) for the PTEs from geogenic sources: Cr (0.45–5.9%), Ni (1.1–46.3%) and V (2.2–23.9%). Higher BAF values were registered for PTEs from anthropogenic sources: As (8.0–86.9%), Cu (3.4–67.8%), Pb (9.1–106.2%) and Zn (2.4–77.5%). Graphs of bioaccessibility adjusted assessment criteria (BAAC) were derived for each urban land use type and PTE. These provide a visual representation of the significance of oral bioaccessibility when deriving BAAC and how this is affected by 1) dominant exposure pathways for each land use and 2) relative harm posed from exposure to PTEs via each pathway, allowing oral bioaccessibility research to be targeted to contaminants and pathways that most significantly impact risk assessment. Pb was the most widespread contaminant with 16.5% of sites exceeding the Pb GAC. Applying BAAC did not significantly change risk evaluation for these samples as many had Pb BAF>50%. In contrast, all samples that exceeded the As GAC were found to no longer exceed a minimal level of risk when oral bioaccessibility was considered. Oral bioaccessibility testing resulted in a 45% reduction in the number of sites identified as posing a potential risk to human health

Physical activity coaching for adults with mobility limitations: protocol for the ComeBACK pragmatic hybrid effectiveness-implementation type 1 randomised controlled trial

INTRODUCTION: Mobility limitation is common and often results from neurological and musculoskeletal health conditions, ageing and/or physical inactivity. In consultation with consumers, clinicians and policymakers, we have developed two affordable and scalable intervention packages designed to enhance physical activity for adults with self-reported mobility limitations. Both are based on behaviour change theories and involve tailored advice from physiotherapists. METHODS AND ANALYSIS: This pragmatic hybrid effectiveness-implementation type 1 randomised control trial (n=600) will be undertaken among adults with self-reported mobility limitations. It aims to estimate the effects on physical activity of: (1) an enhanced 6-month intervention package (one face-to-face physiotherapy assessment, tailored physical activity plan, physical activity phone coaching from a physiotherapist, informational/motivational resources and activity monitors) compared with a less intensive 6-month intervention package (single session of tailored phone advice from a physiotherapist, tailored physical activity plan, unidirectional text messages, informational/motivational resources); (2) the enhanced intervention package compared with no intervention (6-month waiting list control group); and (3) the less intensive intervention package compared with no intervention (waiting list control group). The primary outcome will be average steps per day, measured with the StepWatch Activity Monitor over a 1-week period, 6 months after randomisation. Secondary outcomes include other physical activity measures, measures of health and functioning, individualised mobility goal attainment, mental well-being, quality of life, rate of falls, health utilisation and intervention evaluation. The hybrid effectiveness-implementation design (type 1) will be used to enable the collection of secondary implementation outcomes at the same time as the primary effectiveness outcome. An economic analysis will estimate the cost-effectiveness and cost-utility of the interventions compared with no intervention and to each other. ETHICS AND DISSEMINATION: Ethical approval has been obtained by Sydney Local Health District, Royal Prince Alfred Zone. Dissemination will be via publications, conferences, newsletters, talks and meetings with health managers. TRIAL REGISTRATION NUMBER: ACTRN12618001983291

Digitally enabled aged care and neurological rehabilitation to enhance outcomes with Activity and MObility UsiNg Technology (AMOUNT) in Australia: A randomised controlled trial

Background: Digitally enabled rehabilitation may lead to better outcomes but has not been tested in large pragmatic trials. We aimed to evaluate a tailored prescription of affordable digital devices in addition to usual care for people with mobility limitations admitted to aged care and neurological rehabilitation. Methods and findings: We conducted a pragmatic, outcome-assessor-blinded, parallel-group randomised trial in 3 Australian hospitals in Sydney and Adelaide recruiting adults 18 to 101 years old with mobility limitations undertaking aged care and neurological inpatient rehabilitation. Both the intervention and control groups received usual multidisciplinary inpatient and post-hospital rehabilitation care as determined by the treating rehabilitation clinicians. In addition to usual care, the intervention group used devices to target mobility and physical activity problems, individually prescribed by a physiotherapist according to an intervention protocol, including virtual reality video games, activity monitors, and handheld computer devices for 6 months in hospital and at home. Co-primary outcomes were mobility (performance-based Short Physical Performance Battery [SPPB]; continuous version; range 0 to 3; higher score indicates better mobility) and upright time as a proxy measure of physical activity (proportion of the day upright measured with activPAL) at 6 months. The dataset was analysed using intention-to-treat principles. The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614000936628). Between 22 September 2014 and 10 November 2016, 300 patients (mean age 74 years, SD 14; 50% female; 54% neurological condition causing activity limitation) were randomly assigned to intervention (n = 149) or control (n = 151) using a secure online database (REDCap) to achieve allocation concealment. Six-month assessments were completed by 258 participants (129 intervention, 129 control). Intervention participants received on average 12 (SD 11) supervised inpatient sessions using 4 (SD 1) different devices and 15 (SD 5) physiotherapy contacts supporting device use after hospital discharge. Changes in mobility scores were higher in the intervention group compared to the control group from baseline (SPPB [continuous, 0–3] mean [SD]: intervention group, 1.5 [0.7]; control group, 1.5 [0.8]) to 6 months (SPPB [continuous, 0–3] mean [SD]: intervention group, 2.3 [0.6]; control group, 2.1 [0.8]; mean between-group difference 0.2 points, 95% CI 0.1 to 0.3; p = 0.006). However, there was no evidence of a difference between groups for upright time at 6 months (mean [SD] proportion of the day spent upright at 6 months: intervention group, 18.2 [9.8]; control group, 18.4 [10.2]; mean between-group difference −0.2, 95% CI −2.7 to 2.3; p = 0.87). Scores were higher in the intervention group compared to the control group across most secondary mobility outcomes, but there was no evidence of a difference between groups for most other secondary outcomes including self-reported balance confidence and quality of life. No adverse events were reported in the intervention group. Thirteen participants died while in the trial (intervention group: 9; control group: 4) due to unrelated causes, and there was no evidence of a difference between groups in fall rates (unadjusted incidence rate ratio 1.19, 95% CI 0.78 to 1.83; p = 0.43). Study limitations include 15%–19% loss to follow-up at 6 months on the co-primary outcomes, as anticipated; the number of secondary outcome measures in our trial, which may increase the risk of a type I error; and potential low statistical power to demonstrate significant between-group differences on important secondary patient-reported outcomes. Conclusions: In this study, we observed improved mobility in people with a wide range of health conditions making use of digitally enabled rehabilitation, whereas time spent upright was not impacted. Trial registration: The trial was prospectively registered with the Australian New Zealand Clinical Trials Register; ACTRN1261400093662

Prescriptive variability of drugs by general practitioners

<div><p>Prescription drug spending is growing faster than any other sector of healthcare. However, very little is known about patterns of prescribing and cost of prescribing between general practices. In this study, we examined variation in prescription rates and prescription costs through time for 55 GP surgeries in Northern Ireland Western Health and Social Care Trust. Temporal changes in variability of prescribing rates and costs were assessed using the Mann–Kendall test. Outlier practices contributing to between practice variation in prescribing rates were identified with the interquartile range outlier detection method. The relationship between rates and cost of prescribing was explored with Spearman's statistics. The differences in variability and mean number of prescribing rates associated with the practice setting and socioeconomic deprivation were tested using t-test and <i>F</i>-test respectively. The largest between-practice difference in prescribing rates was observed for Apr-Jun 2015, with the number of prescriptions ranging from 3.34 to 8.36 per patient. We showed that practices with outlier prescribing rates greatly contributed to between-practice variability. The largest difference in prescribing costs was reported for Apr-Jun 2014, with the prescription cost per patient ranging from £26.4 to £64.5. In addition, the temporal changes in variability of prescribing rates and costs were shown to undergo an upward trend. We demonstrated that practice setting and socio-economic deprivation accounted for some of the between-practice variation in prescribing. Rural practices had higher between practice variability than urban practices at all time points. Practices situated in more deprived areas had higher prescribing rates but lower variability than those located in less deprived areas. Further analysis is recommended to assess if variation in prescribing can be explained by demographic characteristics of patient population and practice features. Identification of other factors contributing to prescribing variability can help us better address potential inappropriateness of prescribing.</p></div

Market-dependent production set

A country’s production possibility frontier or PPF is defined as the boundary of its economy’s production set in the net output space for a given technology and fixed quantities of primary factors of production. In general equilibrium theory, exogenous changes in technology or primary-factor supplies alter equilibrium prices; however, government-policy induced domestic relative commodity price changes do not alter the shape of an economy’s production set. We show that, under international capital mobility, which is empirically significant, the shape of a country’s production set does, in fact, depend on market forces and this shape can be manipulated by government policy

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder