Skeletal muscle troponin as a novel biomarker to enhance assessment of the impact of strength training on fall prevention in the older adults.

BACKGROUND: Loss of muscle mass and strength (i.e., sarcopenia) in the older adults is a strong predictor of falls, with subsequent morbidity and inability to execute activities of daily living. Use of biomarkers may enhance assessment of effects of community-based exercise interventions aimed at improving muscle strength. OBJECTIVE: The aim of this study was to investigate the use of troponin as a newly proposed biomarker of skeletal muscle health when determining the outcomes of strength-training programs designed for community-dwelling adults over the age of 65 years. METHODS: Outcomes of two strength training programs ("Peer Exercise Program Promotes Independence" and "Stay Strong, Stay Healthy") were assessed using physical performance tests designed for senior fitness evaluation, grip strength, and changes in serum levels of skeletal muscle-specific troponin T (sTnT). RESULTS: Improvement in physical performance, including a significant increase in grip strength, was associated with a significant reduction in serum levels of sTnT. DISCUSSION: Findings from these studies suggest that, when "Peer Exercise Program Promotes Independence" and "Stay Strong, Stay Healthy" are implemented for at least 10 weeks, significant gains in strength are achieved. This strength improvement was associated with a reduction in serum levels of troponin, supporting the use of troponin as a novel biomarker of muscle health in the assessment of strength training programs for the older adults. Reduced sTnT after exercise intervention suggests that skeletal muscles become stronger and less susceptible to damage because of the exercise regimens.

Sarcopenia: pharmacology of today and tomorrow.

Sarcopenia remains largely undiagnosed and undertreated because of the lack of a universally accepted definition, effective ways to measure it, and identification of the outcomes that should guide treatment efficacy. An ever-growing number of clinicians and researchers along with funding and regulatory agencies have gradually recognized that sarcopenia is a human condition that requires both prevention and treatment. In this article, we review sarcopenia and its common and less known pharmacological treatments, attempt to define sarcopenia in its broader context, and present some new ideas for potential future treatment for this devastating condition.

Musculoskeletal Biomarkers Response to Exercise in Older Adults.

Exercise is an essential component of any good health style, being particularly important for older adults to counteract the effects of aging, including sarcopenia and osteoporosis, which can result in lower fall probability. Exercise programs for older adults are especially designed for that population. A rigorous evaluation of those programs is necessary to assure most benefit is achieved. Serum biomarkers of proteins intrinsic to musculoskeletal homeostasis could contribute objectively to the assessment of the benefits of exercise. In this work, in addition to the usual physical fitness and balance tests, ELISA assays quantified the serum levels of six proteins and one polysaccharide important for the homeostasis of muscle (troponin T and alpha-actinin), tendon/ligament (tenomodulin), cartilage (cartilage oligomeric matrix protein and hyaluronan) and bone (osteocalcin and sclerostin), before and after 8 weeks of an exercise program tailored to older adults, Stay Strong Stay Healthy, offered at a Community Center and at an Independent Senior Living facility. Statistical significance was determined by non-parametric tests (Wilcoxon Signed Ranks and Mann-Whitney U). Physical fitness and balance improved as expected along with a significant decrease in sclerostin, pointing to less inhibition of bone deposition. However, when considering each type of dwelling separately, older adults always saw a significant decrease of the isoform of troponin T associated with fast-twitch muscles, suggesting that daily levels of physical activity may also have a role in the benefit of older adults from exercise.

Neural control of postural sway: Relationship to strength measures in young and elderly adults.

Age-related changes in postural sway are well-established, and studied from a control perspective using an inverted pendulum model. The purpose of the present work was to expand previous research in this area by investigating relationships between sway-related control parameters and musculoskeletal measures of muscle function and health. Eleven female older adults and eight female young adults completed blood draw, grip, leg extension, and balance tests. Serum levels of skeletal muscle-specific troponin T (sTnT), a biomarker for muscle health, were obtained from blood samples. Maximal grip force and leg extension torque were obtained from dynamometer tests. Center of pressure parameters were derived from force platform records obtained during eyes open and eyes closed balance tests. Sway control parameters were derived from an inverted pendulum model with PID-feedback control. Regression analyses were used to quantify the relationship between model parameters and grip strength, leg strength, and sTnT. Model integral gain (Ki) was observed to significantly predict grip strength in the eyes open condition. In the eyes closed condition, model derivative gain (Kd) was observed to significantly predict sTnT, and both proportional (Kp) and noise (Kn) model gains were observed to significantly predict grip and leg strength measures. Collectively, the relationship between control (Ki, Kd, Kp) and musculoskeletal health (strength, sTnT) parameters suggests a compensation mechanism, which may have served to minimize effects of reduced muscle function on sway amplitude, overshoot, and accuracy. Most associations were observed during eyes closed conditions, suggesting that visual input plays a larger role in regulating balance than the proposed compensation mechanisms. This work highlights the potential use for both strength and sTnT tests as biomarkers for postural control and balance impairment in older adults.

Platelets, but not erythrocytes, significantly affect cytokine release and scaffold contraction in a provisional scaffold model.

Platelets and erythrocytes are major components of wound provisional scaffolding. In this study, we hypothesized that the concentration of platelets and erythrocytes would significantly affect fibroblast-mediated contraction of three-dimensional scaffolds or the release of cytokines from the scaffold. To test this hypothesis, human anterior cruciate ligament fibroblasts were cultured in one of four scaffolds: a collagen matrix, a collagen-fibrin matrix containing the same concentration of platelets as whole blood, a collagen-fibrin matrix containing a high platelet concentration, and a collagen-fibrin matrix containing a high platelet concentration and red blood cells. Cytokine release from the four groups of gels and gel contraction were measured over a 10-day period. The results of these assays supported greater cytokine release, fibroblast proliferation, and gel contraction in scaffolds with higher platelet concentration. In contrast, the addition of erythrocytes did not significantly stimulate or suppress scaffold contraction or growth factor release from the provisional scaffolds. We concluded that while platelet concentration can significantly impact cytokine release and scaffold retraction in a provisional scaffold, the inclusion of erythrocytes does not have a significant effect on these same behaviors. Therefore, while platelets may be an important regulator of repair processes after injury, it is less likely that erythrocytes have a similar function.

Functional Redundancy in bird community decreases with riparian forest width reduction.

Riparian ecosystems are suffering anthropogenic threats that reduce biodiversity and undermine ecosystem services. However, there is a great deal of uncertainty about the way species composition of assemblages is related to ecosystem function, especially in a landscape fragmentation context.Here, we assess the impact of habitat loss and disturbance on Functional Diversity (FD) components Functional Redundancy (FRed), Functional Evenness (FEve), and Functional Richness (FRic) of riparian forest bird assemblages to evaluate (a) how FD components respond to riparian forest width reduction and vegetation disturbance; (b) the existence of thresholds within these relationships; (c) which of the main birds diet guild (frugivores, insectivores, and omnivores) respond to such thresholds. We predict that FD components will be affected negatively and nonlinearly by riparian changes. However, guilds could have different responses due to differences of species sensitivity to fragmentation and disturbance. We expect to find thresholds in FD responses, because fragmentation and disturbance drive loss of specific FD components.Our results show that FRed and FEve were linearly affected by width and disturbance of riparian habitats, respectively. FRed was significantly lower in riparian forests assemblages below 400 m wide, and FEve was significantly higher above 60% disturbance. These responses of FD were also followed to the decline in insectivores and frugivores richness in riparian forests most affected by these changes.Consequently, our study suggests communities do not tolerate reduction in riparian forest width or disturbance intensification without negative impact on FD, and this becomes more critical for riparian area <400-m wide or with more than 60% disturbance. This minimum riparian width required to maintain FRed is greater than the minimum width required for riparian forests by Brazilian law. Thus, it is important to consider mechanisms to expand riparian habitats and reduce the disturbance intensity in riparian forests so that riparian bird community FD may be effectively conserved.

A multimodal assessment of balance in elderly and young adults.

Falling is a significant health issue among elderly adults. Given the multifactorial nature of falls, effective balance and fall risk assessment must take into account factors from multiple sources. Here we investigate the relationship between fall risk and a diverse set of biochemical and biomechanical variables including: skeletal muscle-specific troponin T (sTnT), maximal strength measures derived from isometric grip and leg extension tasks, and postural sway captured from a force platform during a quiet stance task. These measures were performed in eight young and eleven elderly adults, along with estimates of fall risk derived from the Tinetti Balance Assessment. We observed age-related effects in all measurements, including a trend toward increased sTnT levels, increased postural sway, reduced upper and lower extremity strength, and reduced balance scores. We observed a negative correlation between balance scores and sTnT levels, suggesting its use as a biomarker for fall risk. We observed a significant positive correlation between balance scores and strength measures, adding support to the notion that muscle strength plays a significant role in postural control. We observed a significant negative correlation between balance scores and postural sway, suggesting that fall risk is associated with more loosely controlled center of mass regulation.

Development of a program model to evaluate the potential for reuse of single-use medical devices: results of a pilot test study.

Single-use medical devices (SUDs, or disposables) have become a major expense in hospital budgets. The need for cost reduction and the availability of sterilization technologies other than the autoclave have prompted hospitals worldwide to begin reusing disposables, in many cases without proper assessment of the true costs (time, personnel, etc) and ease/difficulty of implementation of an institutional reuse program. Our group has developed a rigorous program model to evaluate SUDs for reuse. The program comprises 3 sequential protocols: (1) device audit, (2) laboratory evaluation, and (3) clinical evaluation. Use of this model can produce scientific and financial data sufficient for any institution interested in reuse to reach an initial decision about its feasibility. In addition to the testing outcomes, regulatory requirements, the position of manufacturers and third-party reprocessors, and legal and ethical concerns must be considered. A successful reuse program must include ongoing evaluations to ensure that the safety levels and cost savings established during the initial audit and evaluation phases continue. Herein, we give the rationale and details of our program model and discuss results of our pilot application of the "ideal" protocol in a real-world context.

Outcomes of Stay Strong, Stay Healthy in community settings.

UNLABELLED: Loss of muscle strength, flexibility, and balance are strong predictors of falls in the elderly. OBJECTIVES: The goal of this research was to investigate the effectiveness of a 10-week, strength-based exercise program delivered by Extension professionals. METHODS: Matched pair t tests were used to compare differences in five measures of fitness collected from 808 participants (mean age = 65.4 years) at the start and finish of the exercise program. RESULTS: Following programming, participants significantly improved strength, flexibility, and balance. DISCUSSION: Results indicate that an evidence-based program can be translated into a community Extension program that is able to improve the fitness level of seniors.

Collagen density significantly affects the functional properties of an engineered provisional scaffold.

The formation of a provisional scaffold is essential in wound healing. However, for tissues inside of joints, this process is impeded by the synovial fluid environment and wound healing is significantly impaired as a result. Therefore, development of substitute provisional scaffolds which are effective in the intra-articular environment is of great interest. Collagen-platelet hydrogels have recently been found useful as substitute provisional scaffolding materials. In this study, our hypothesis was that increasing the collagen density in the hydrogel would result in physiologic changes that would be likely to affect their function as provisional scaffold substitutes. The primary functional outcome measures were modulus of the hydrogel, platelet activation, fibroblast proliferation, and scaffold retraction. Increased collagen density resulted in collagen-platelet hydrogels with a higher storage modulus. Platelet activation was not found to be dependent on the collagen density within the range tested. Increasing the collagen density had a suppressive effect on both fibroblast proliferation and scaffold retraction. These studies suggest that the collagen density may be able to significantly influence the function of collagen-platelet hydrogels used as substitute provisional scaffolds.

Effect of altered mechanical load conditions on the structure and function of cultured tendon fascicles.

We have developed an in vitro model system to investigate the relationships between mechanical unloading and tendon matrix remodeling. Remodeling was characterized by changes in the functional and structural characteristics of rat tail tendon fascicles (RTTF) subjected to no load conditions for 1 week in vitro. We hypothesized that the absence of load will: (I) maintain cross-sectional area (CSA), with decreased elastic modulus and increased stress-relaxation; (II) cause an increase in denatured collagen and a decrease in water and total glycosaminoglycan (GAG) content. Fascicles cultured under a nominal static stress were used as control for culture conditions effects. Unloading resulted in a decrease of approximately 23% in the elastic modulus of cultured fascicles, consistent with previous stress-deprivation studies. Contrary to our hypothesis, a nominal static stress caused an increase in elastic modulus ( approximately 30%) and a significant decrease in stress-relaxation when compared to fresh fascicles at 1% strain. Mechanical changes were associated with changes in the GAG content of the fascicles, but not their CSA, water, or collagen content. Furthermore, we did not find evidence of measurable denatured collagen in the cultured fascicles. Together these results suggest a role for GAG but not collagen or water in the elastic and viscoelastic changes measured in tendon fascicles cultured for 1 week under altered load conditions.

Changes in gene expression of individual matrix metalloproteinases differ in response to mechanical unloading of tendon fascicles in explant culture.

Immobilization of the tendon and ligament has been shown to result in a rapid and significant decrease in material properties. It has been proposed that tissue degradation leading to tendon rupture or pain in humans may also be linked to mechanical unloading following focal tendon injury. Hence, understanding the remodeling mechanism associated with mechanical unloading has relevance for the human conditions of immobilization (e.g., casting), delayed repair of tendon ruptures, and potentially overuse injuries as well. This is the first study to investigate the time course of gene expression changes associated with tissue harvest and mechanical unloading culture in an explant model. Rat tail tendon fascicles were harvested and placed in culture unloaded for up to 48 h and then evaluated using qRT-PCR for changes in two anabolic and four catabolic genes at 12 time points. Our data demonstrates that Type I Collagen, Decorin, Cathepsin K, and MMP2 gene expression are relatively insensitive to unloaded culture conditions. However, changes in both MMP3 and MMP13 gene expression are rapid, dramatic, sustained, and changing during at least the first 48 h of unloaded culture. This data will help to further elucidate the mechanism for the loss of mechanical properties associated with mechanical unloading in tendon.