No abstract

Chronic, low-level elevation of circulating interleukin (IL)-6 is observed in disease states as well as in many outwardly healthy elderly individuals. Increased plasma IL-6 is also observed after intense, prolonged exercise. In the context of skeletal muscle, IL-6 has variously been reported to regulate carbohydrate and lipid metabolism, increase satellite cell proliferation, or cause muscle wasting. In the present study, we used a rodent local infusion model to deliver modest levels of IL-6, comparable to that present after exercise or with chronic low-level inflammation in the elderly, directly into a single target muscle in vivo. The aim of this study was to examine the direct effects of IL-6 on skeletal muscle in the absence of systemic changes in this cytokine. Data included cellular and molecular markers of cytokine and growth factor signaling (phosphorylation and mRNA content) as well as measurements to detect muscle atrophy. IL-6 infusion resulted in muscle atrophy characterized by a preferential loss of myofibrillar protein (-17%). IL-6 induced a decrease in the phosphorylation of ribosomal S6 kinase (-60%) and STAT5 (-33%), whereas that of STAT3 was increased approximately twofold. The changes seen in the IL-6-infused muscles suggest alterations in the balance of growth factor-related signaling in favor of a more catabolic profile. This suggests that downregulation of growth factor-mediated intracellular signaling may be a mechanism contributing to the development of muscle atrophy induced by elevated IL-6.

The beneficial effects of physical activity (PA) are well documented, yet the mechanisms by which PA prevents disease and improves health outcomes are poorly understood. To identify major gaps in knowledge and potential strategies for catalyzing progress in the field, the NIH convened a workshop in late October 2014 entitled "Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits." Presentations and discussions emphasized the challenges imposed by the integrative and intermittent nature of PA, the tremendous discovery potential of applying "-omics" technologies to understand interorgan crosstalk and biological networking systems during PA, and the need to establish an infrastructure of clinical trial sites with sufficient expertise to incorporate mechanistic outcome measures into adequately sized human PA trials. Identification of the mechanisms that underlie the link between PA and improved health holds extraordinary promise for discovery of novel therapeutic targets and development of personalized exercise medicine.

To examine the relationship between body weight in children and aerobic parameters of exercise, we determined the anaerobic threshold (AT), maximum O2 uptake (VO2max), work efficiency, and response time for O2 uptake (RT-VO2) in 109 healthy children (51 girls and 58 boys, range 6-17 yr old) using a cross-sectional study design. Gas exchange during exercise was measured breath by breath. The protocol consisted of cycle ergometry and a linearly increasing work rate (ramp) to the limit of the subject's tolerance. Both AT and VO2max increased systematically with body weight, whereas work efficiency and RT-VO2 were virtually independent of body size. The ratio of AT to VO2max decreased slightly with age, and its mean value was 60%. AT scaled to body weight to the power of 0.92, not significantly different from the power of 1.01 for VO2max. Thus both the AT and the VO2max increase in a highly ordered manner with increasing size, and as judged by AT/VO2max, the onset of anaerobic metabolism during exercise occurred at a relatively constant proportion of the overall limit of the gas transport system. We conclude that in children cardiorespiratory responses to exercise are regulated at optimized values despite overall change in body size during growth.

Current methods for continuous respiration monitoring such as respiratory inductive or optoelectronic plethysmography are limited to clinical or research settings; most wearable systems reported only measures respiration rate. Here we introduce a wearable sensor capable of simultaneously measuring both respiration rate and volume with high fidelity. Our disposable respiration sensor with a Band-Aid© like formfactor can measure both respiration rate and volume by simply measuring the local strain of the ribcage and abdomen during breathing. We demonstrate that both metrics are highly correlated to measurements from a medical grade continuous spirometer on participants at rest. Additionally, we also show that the system is capable of detecting respiration under various ambulatory conditions. Because these low-powered piezo-resistive sensors can be integrated with wireless Bluetooth units, they can be useful in monitoring patients with chronic respiratory diseases in everyday settings.

No abstract

Exercise leads to increases in circulating levels of peripheral blood mononuclear cells (PBMCs) and to a simultaneous, seemingly paradoxical increase in both pro- and anti-inflammatory mediators. Whether this is paralleled by changes in gene expression within the circulating population of PBMCs is not fully understood. Fifteen healthy men (18-30 yr old) performed 30 min of constant work rate cycle ergometry (approximately 80% peak O2 uptake). Blood samples were obtained preexercise (Pre), end-exercise (End-Ex), and 60 min into recovery (Recovery), and gene expression was measured using microarray analysis (Affymetrix GeneChips). Significant differential gene expression was defined with a posterior probability of differential expression of 0.99 and a Bayesian P value of 0.005. Significant changes were observed from Pre to End-Ex in 311 genes, from End-Ex to Recovery in 552 genes, and from Pre to Recovery in 293 genes. Pre to End-Ex upregulation of PBMC genes related to stress and inflammation [e.g., heat shock protein 70 (3.70-fold) and dual-specificity phosphatase-1 (4.45-fold)] was followed by a return of these genes to baseline by Recovery. The gene for interleukin-1 receptor antagonist (an anti-inflammatory mediator) increased between End-Ex and Recovery (1.52-fold). Chemokine genes associated with inflammatory diseases [macrophage inflammatory protein-1alpha (1.84-fold) and -1beta (2.88-fold), and regulation-on-activation, normal T cell expressed and secreted (1.34-fold)] were upregulated but returned to baseline by Recovery. Exercise also upregulated growth and repair genes such as epiregulin (3.50-fold), platelet-derived growth factor (1.55-fold), and hypoxia-inducible factor-I (2.40-fold). A single bout of heavy exercise substantially alters PBMC gene expression characterized in many cases by a brisk activation and deactivation of genes associated with stress, inflammation, and tissue repair.

The overall purpose of this study was to evaluate the effectiveness of a psychosocial supportive intervention called the "Living with Hope Program" (LWHP) in increasing hope and quality of life for older adult, community-living, terminally ill cancer patients. Using a mixed method concurrent nested experimental design, 60 terminally ill cancer patients over the age of 60 years were randomly assigned to a treatment group and a control group. Baseline hope (Herth Hope Index [HHI]) and quality-of-life scores (McGill Quality of Life Questionnaire [MQOL]) were collected at the first visit in the patients' homes by trained research assistants. Those in the treatment group received the LWHP, which consisted of viewing an international award-winning video on hope and a choice of one of three hope activities to work on over a one-week period. The control group received standard care. Hope and quality-of-life data were collected one week later from both groups. Qualitative data using open-ended hope questions were collected from the treatment group. Patients receiving the LWHP had statistically significant higher hope (U=255, P=0.005) and quality-of-life scores at Visit 2 (U=294.5, P=0.027) than those in the control group. Qualitative data confirmed this finding, with the majority (61.5%) of patients in the treatment group reporting the LWHP increased their hope. This preliminary evaluation of the effectiveness of the LWHP suggests that it may increase hope and quality of life for older terminally ill cancer patients at home.