Efficacy of power training to improve physical function in individuals diagnosed with frailty and chronic disease: A meta-analysis

Muscle power training with emphasis on high-velocity of concentric movement improves physical functionality in healthy older adults, and, maybe superior to traditional exercise programs. Power training may also be advantageous for patients with acute and chronic illnesses, as well as frail individuals. To determine the efficacy of power training compared with traditional resistance training on physical function outcomes in individuals diagnosed with frailty, acute illness or chronic disease. PubMed (MEDLINE), CINAHL, PEDro, Web of Science, and Google Scholar. (1) at least one study group receives muscle power training of randomized controlled trial (RCT) (2) study participants diagnosed as prefrail, frail or have an ongoing acute or chronic disease, condition or illness; (3) study participants over the age of 18; (4) publication in English language; (5) included physical function as the primary or secondary outcome measures. Two independent reviewers assessed articles for inclusion and graded the methodological quality using Cochrane Risk-of- Bias tool for RCTs. Fourteen RCTs met the inclusion criteria. In seven studies, muscle power training was more effective at improving physical function compared to control activities with a mean fixed effect size (ES) of 0.41 (p = 0.006; 95% CI 0.12 to 0.71). Power training and conventional resistance training had similar effectiveness in eight studies with a mean fixed ES of 0.10 (p = 0.061; 95% CI –0.01 to 0.40). Muscle power training is just as efficacious for improving physical function in individuals diagnosed with frailty and chronic disease when compared to traditional resistance training. The advantages of power training with reduced work per session may support power training as a preferential exercise modality for clinical populations. The findings should be interpreted with caution since generalizability is questioned due to the heterogeneity of patient populations enrolled and participants were relatively mobile at baseline

Timing and Amount of Physical Therapy Treatment are Associated with Length of Stay in the Cardiothoracic ICU

Significant variability exists in physical therapy early mobilization practice. The frequency of physical therapy or early mobilization of patients in the cardiothoracic intensive care unit and its effect on length of stay has not been investigated. The goal of our research was to examine variables that influence physical therapy evaluation and treatment in the intensive care unit using a retrospective chart review. Patients (n = 2568) were categorized and compared based on the most common diagnoses or surgical procedures. Multivariate semi-logarithmic regression analyses were used to determine correlations. Differences among patient subgroups for all independent variables other than age and for length of stay were found. The regression model determined that time to first physical therapy evaluation, Charlson Comorbidity Index score, mean days of physical therapy treatment and mechanical ventilation were associated with increased hospital length of stay. Time to first physical therapy evaluation in the intensive care unit and the hospital, and mean days of physical therapy treatment associated with hospital length of stay. Further prospective study is required to determine whether shortening time to physical therapy evaluation and treatment in a cardiothoracic intensive care unit could influence length of stay

Myonuclear Domain Flexibility Challenges Rigid Assumptions on Satellite Cell Contribution to Skeletal Muscle Fiber Hypertrophy

Satellite cell-mediated myonuclear accretion is thought to be required for skeletal muscle fiber hypertrophy, and even drive hypertrophy by preceding growth. Recent studies in humans and rodents provide evidence that challenge this axiom. Specifically, Type 2 muscle fibers reliably demonstrate a substantial capacity to hypertrophy in the absence of myonuclear accretion, challenging the notion of a tightly regulated myonuclear domain (i.e., area that each myonucleus transcriptionally governs). In fact, a “myonuclear domain ceiling”, or upper limit of transcriptional output per nucleus to support hypertrophy, has yet to be identified. Satellite cells respond to muscle damage, and also play an important role in extracellular matrix remodeling during loading-induced hypertrophy. We postulate that robust satellite cell activation and proliferation in response to mechanical loading is largely for these purposes. Future work will aim to elucidate the mechanisms by which Type 2 fibers can hypertrophy without additional myonuclei, the extent to which Type 1 fibers can grow without myonuclear accretion, and whether a true myonuclear domain ceiling exists

BOOSTing Patient Mobility and Function on a General Medical Unit by Enhancing Interprofessional Care

Low mobility during hospitalization remains prevalent despite associated negative consequences. The goal of this quality improvement (QI) project was to increase patient mobility and function by adding a physical therapist (PT) to an existing interprofessional care team. A mobility technician assisted treatment group patients with mobility during hospitalization based on physical therapist recommendations. Change in functional status and highest level of mobility achieved by treatment group patients was measured from admission to discharge. Observed hospital length of stay (LOS), LOS index, and 30-day all cause hospital readmission comparisons between treatment group and a comparison group on the same unit, and between cross-sectional comparison groups one year prior were used for Difference in Difference analysis. Bivariate comparisons between the treatment and a cross-sectional comparison group from one year prior showed a statistically significant change in LOS Index. No other bivariate comparisons were statistically significant. Difference in Difference methods showed no statistically significant change in observed LOS, LOS Index, or 30-day readmission. Patients in the treatment group had statistically significant improvements in functional status and highest level of mobility achieved. Physical function and mobility improved for patients who participated in mobility sessions. Mobility technicians may contribute to improved care quality and patient safety in the hospital

Fusion and Beyond: Satellite Cell Contributions to Loading-Induced Skeletal Muscle Adaptation

Satellite cells support adult skeletal muscle fiber adaptations to loading in numerous ways. The fusion of satellite cells, driven by cell-autonomous and/or extrinsic factors, contributes new myonuclei to muscle fibers, associates with load-induced hypertrophy, and may support focal membrane damage repair and long-term myonuclear transcriptional output. Recent studies have also revealed that satellite cells communicate within their niche to mediate muscle remodeling in response to resistance exercise, regulating the activity of numerous cell types through various mechanisms such as secretory signaling and cell–cell contact. Muscular adaptation to resistance and endurance activity can be initiated and sustained for a period of time in the absence of satellite cells, but satellite cell participation is ultimately required to achieve full adaptive potential, be it growth, function, or proprioceptive coordination. While significant progress has been made in understanding the roles of satellite cells in adult muscle over the last few decades, many conclusions have been extrapolated from regeneration studies. This review highlights our current understanding of satellite cell behavior and contributions to adaptation outside of regeneration in adult muscle, as well as the roles of satellite cells beyond fusion and myonuclear accretion, which are gaining broader recognition

Morphoregulatory Functions of the RNA-Binding Motif Protein 3 in Cell Spreading, Polarity and Migration

RNA-binding proteins are emerging as key regulators of transitions in cell morphology. The RNA-binding motif protein 3 (RBM3) is a cold-inducible RNA-binding protein with broadly relevant roles in cellular protection, and putative functions in cancer and development. Several findings suggest that RBM3 has morphoregulatory functions germane to its roles in these contexts. For example, RBM3 helps maintain the morphological integrity of cell protrusions during cell stress and disease. Moreover, it is highly expressed in migrating neurons of the developing brain and in cancer invadopodia, suggesting roles in migration. We here show that RBM3 regulates cell polarity, spreading and migration. RBM3 was present in spreading initiation centers, filopodia and blebs that formed during cell spreading in cell lines and primary myoblasts. Reducing RBM3 triggered exaggerated spreading, increased RhoA expression, and a loss of polarity that was rescued by Rho kinase inhibition and overexpression of CRMP2. High RBM3 expression enhanced the motility of cells migrating by a mesenchymal mode involving extension of long protrusions, whereas RBM3 knockdown slowed migration, greatly reducing the ability of cells to extend protrusions and impairing multiple processes that require directional migration. These data establish novel functions of RBM3 of potential significance to tissue repair, metastasis and development

Myonuclear Transcription is Responsive to Mechanical Load and DNA Content but Uncoupled from Cell Size During Hypertrophy

Myofibers increase size and DNA content in response to a hypertrophic stimulus, thus providing a physiological model with which to study how these factors affect global transcription. Using 5-ethynyl uridine (EU) to metabolically label nascent RNA, we measured a sevenfold increase in myofiber transcription during early hypertrophy before a change in cell size and DNA content. The typical increase in myofiber DNA content observed at the later stage of hypertrophy was associated with a significant decrease in the percentage of EU-positive myonuclei; however, when DNA content was held constant by preventing myonuclear accretion via satellite cell depletion, both the number of transcriptionally active myonuclei and the amount of RNA generated by each myonucleus increased. During late hypertrophy, transcription did not scale with cell size, as smaller myofibers (\u3c 1000 μm2) demonstrated the highest transcriptional activity. Finally, transcription was primarily responsible for changes in the expression of genes known to regulate myofiber size. These findings show that resident myonuclei possess a significant reserve capacity to up-regulate transcription during hypertrophy and that myofiber transcription is responsive to DNA content but uncoupled from cell size during hypertrophy

The Effects of Temperature and Seasons on Subcutaneous White Adipose Tissue in Humans: Evidence for Thermogenic Gene Induction

Context: Although brown adipose tissue (BAT) activity is increased by a cold environment, little is known of the response of human white adipose tissue (WAT) to the cold. Design: We examined both abdominal and thigh subcutaneous (SC) WAT from 71 subjects who were biopsied in the summer or winter, and adipose expression was assessed after an acute cold stimulus applied to the thigh of physically active young subjects. Results: In winter, UCP1 and PGC1 α mRNA were increased 4 to 10-fold (p\u3c0.05) and 1.5 to 2-fold, respectively, along with beige adipose markers, and UCP1 protein was 3-fold higher in the winter. The seasonal increase in abdominal SC WAT UCP1 mRNA was considerably diminished in subjects with a BMI \u3e 30 kg/m2, suggesting that dysfunctional WAT in obesity inhibits adipose thermogenesis. After applying an acute cold stimulus to the thigh of subjects for 30 min, PGC1α and UCP1 mRNA was stimulated 2.7-fold (p \u3c 0.05) and 1.9-fold (p = 0.07), respectively. Acute cold also induced a 2 to 3-fold increase in PGC1α and UCP1 mRNA in human adipocytes in vitro, which was inhibited by macrophage-conditioned medium and by the addition of TNFα. Conclusion: Human SC WAT increases thermogenic genes seasonally and acutely in response to a cold stimulus and this response is inhibited by obesity and inflammation. (J Clin Endocrinol Metab 99: E2772–E2779, 2014

Macrophages Expressing Uncoupling Protein 1 Increase in Adipose Tissue in Response to Cold in Humans

Acute cold induces beige adipocyte protein marker expression in human subcutaneous white adipose tissue (SC WAT) from both the cold treated and contralateral leg, and the immune system regulates SC WAT beiging in mice. Cold treatment significantly increased the gene expression of the macrophage markers CD68 and 86 in SC WAT. Therefore, we comprehensively investigated the involvement of macrophages in SC WAT beiging in lean and obese humans by immunohistochemistry. Cold treatment significantly increased CD163/CD68 macrophages in SC WAT from the cold treated and contralateral legs of lean and obese subjects, and had similar effects on CD206/CD68 macrophages, whereas the effects on CD86/CD68 macrophages were inconsistent between lean and obese. However, linear regression analysis did not find significant relationships between the change in macrophage numbers and the change in UCP1 protein abundance. A high percentage of CD163 macrophages in SC WAT expressed UCP1, and these UCP1 expressing CD163 macrophages were significantly increased by cold treatment in SC WAT of lean subjects. In conclusion, our results suggest that CD163 macrophages are involved in some aspect of the tissue remodeling that occurs during SC WAT beiging in humans after cold treatment, but they are likely not direct mediators of the beiging process

Differential Requirement for Satellite Cells During Overload-Induced Muscle Hypertrophy in Growing Versus Mature Mice

Background: Pax7+ satellite cells are required for skeletal muscle fiber growth during post-natal development in mice. Satellite cell-mediated myonuclear accretion also appears to persist into early adulthood. Given the important role of satellite cells during muscle development, we hypothesized that the necessity of satellite cells for adaptation to an imposed hypertrophic stimulus depends on maturational age. Methods: Pax7CreER-R26RDTA mice were treated for 5 days with vehicle (satellite cell-replete, SC+) or tamoxifen (satellite cell-depleted, SC-) at 2 months (young) and 4 months (mature) of age. Following a 2-week washout, mice were subjected to sham surgery or 10 day synergist ablation overload of the plantaris (n = 6–9 per group). The surgical approach minimized regeneration, de novo fiber formation, and fiber splitting while promoting muscle fiber growth. Satellite cell density (Pax7+ cells/fiber), embryonic myosin heavy chain expression (eMyHC), and muscle fiber cross sectional area (CSA) were evaluated via immunohistochemistry. Myonuclei (myonuclei/100 mm) were counted on isolated single muscle fibers. Results: Tamoxifen treatment depleted satellite cells by ≥90% and prevented myonuclear accretion with overload in young and mature mice (p \u3c 0.05). Satellite cells did not recover in SC- mice after overload. Average muscle fiber CSA increased ~20% in young SC+ (p = 0.07), mature SC+ (p \u3c 0.05), and mature SC- mice (p \u3c 0.05). In contrast, muscle fiber hypertrophy was prevented in young SC- mice. Muscle fiber number increased only in mature mice after overload (p \u3c 0.05), and eMyHC expression was variable, specifically in mature SC+ mice. Conclusions: Reliance on satellite cells for overload-induced hypertrophy is dependent on maturational age, and global responses to overload differ in young versus mature mice