Muscle Fatigue from the Perspective of a Single Crossbridge

The repeated intense stimulation of skeletal muscle rapidly decreases its force- and motion-generating capacity. This type of fatigue can be temporally correlated with the accumulation of metabolic by-products, including phosphate (Pi) and protons (H+). Experiments on skinned single muscle fibers demonstrate that elevated concentrations of these ions can reduce maximal isometric force, unloaded shortening velocity, and peak power, providing strong evidence for a causative role in the fatigue process. This seems to be due, in part, to their direct effect on muscle’s molecular motor, myosin, because in assays using isolated proteins, these ions directly inhibit myosin’s ability to move actin. Indeed, recent work using a single molecule laser trap assay has revealed the specific steps in the crossbridge cycle affected by these ions. In addition to their direct effects, these ions also indirectly affect myosin by decreasing the sensitivity of the myofilaments to calcium, primarily by altering the ability of the muscle regulatory proteins, troponin and tropomyosin, to govern myosin binding to actin. This effect seems to be partially due to fatigue-dependent alterations in the structure and function of specific subunits of troponin. Parallel efforts to understand the molecular basis of muscle contraction are providing new technological approaches that will allow us to gain unprecedented molecular detail of the fatigue process. This will be crucial to fully understand this ubiquitous phenomenon and develop appropriately targeted therapies to attenuate the debilitating effects of fatigue in clinical populations

Symposium on scientific literacy: Introduction

This is the publisher's version, also available electronically from http://www.amjbot.org.Not applicabl

Effects of Elevated H\u3csup\u3e+\u3c/sup\u3e And P\u3csub\u3ei\u3c/sub\u3e on The Contractile Mechanics of Skeletal Muscle Fibres From Young and Old Men: Implications for Muscle Fatigue in Humans

The present study aimed to identify the mechanisms responsible for the loss in muscle power and increased fatigability with ageing by integrating measures of whole‐muscle function with single fibre contractile mechanics. After adjusting for the 22% smaller muscle mass in old (73–89 years, n = 6) compared to young men (20–29 years, n = 6), isometric torque and power output of the knee extensors were, respectively, 38% and 53% lower with age. Fatigability was ∼2.7‐fold greater with age and strongly associated with reductions in the electrically‐evoked contractile properties. To test whether cross‐bridge mechanisms could explain age‐related decrements in knee extensor function, we exposed myofibres (n = 254) from the vastus lateralis to conditions mimicking quiescent muscle and fatiguing levels of acidosis (H+) (pH 6.2) and inorganic phosphate (Pi) (30 mm). The fatigue‐mimicking condition caused marked reductions in force, shortening velocity and power and inhibited the low‐ to high‐force state of the cross‐bridge cycle, confirming findings from non‐human studies that these ions act synergistically to impair cross‐bridge function. Other than severe age‐related atrophy of fast fibres (−55%), contractile function and the depressive effects of the fatigue‐mimicking condition did not differ in fibres from young and old men. The selective loss of fast myosin heavy chain II muscle was strongly associated with the age‐related decrease in isometric torque (r = 0.785) and power (r = 0.861). These data suggest that the age‐related loss in muscle strength and power are primarily determined by the atrophy of fast fibres, but the age‐related increased fatigability cannot be explained by an increased sensitivity of the cross‐bridge to H+ and Pi

Craniosacral therapy for chronic pain: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES:To systematically assess the evidence of Craniosacral Therapy (CST) for the treatment of chronic pain. METHODS:PubMed, Central, Scopus, PsycInfo and Cinahl were searched up to August 2018. Randomized controlled trials (RCTs) assessing the effects of CST in chronic pain patients were eligible. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for pain intensity and functional disability (primary outcomes) using Hedges' correction for small samples. Secondary outcomes included physical/mental quality of life, global improvement, and safety. Risk of bias was assessed using the Cochrane tool. RESULTS:Ten RCTs of 681 patients with neck and back pain, migraine, headache, fibromyalgia, epicondylitis, and pelvic girdle pain were included. CST showed greater post intervention effects on: pain intensity (SMD = -0.32, 95%CI = [- 0.61,-0.02]) and disability (SMD = -0.58, 95%CI = [- 0.92,-0.24]) compared to treatment as usual; on pain intensity (SMD = -0.63, 95%CI = [- 0.90,-0.37]) and disability (SMD = -0.54, 95%CI = [- 0.81,-0.28]) compared to manual/non-manual sham; and on pain intensity (SMD = -0.53, 95%CI = [- 0.89,-0.16]) and disability (SMD = -0.58, 95%CI = [- 0.95,-0.21]) compared to active manual treatments. At six months, CST showed greater effects on pain intensity (SMD = -0.59, 95%CI = [- 0.99,-0.19]) and disability (SMD = -0.53, 95%CI = [- 0.87,-0.19]) versus sham. Secondary outcomes were all significantly more improved in CST patients than in other groups, except for six-month mental quality of life versus sham. Sensitivity analyses revealed robust effects of CST against most risk of bias domains. Five of the 10 RCTs reported safety data. No serious adverse events occurred. Minor adverse events were equally distributed between the groups. DISCUSSION:In patients with chronic pain, this meta-analysis suggests significant and robust effects of CST on pain and function lasting up to six months. More RCTs strictly following CONSORT are needed to further corroborate the effects and safety of CST on chronic pain. PROTOCOL REGISTRATION AT PROSPERO:CRD42018111975

Spatial Attention Modulates Center-Surround Interactions in Macaque Visual Area V4

SummaryIn natural viewing, a visual stimulus that is the target of attention is generally surrounded by many irrelevant distracters. Stimuli falling in the receptive field surround can influence the neuronal response evoked by a stimulus appearing within the classical receptive field. Such modulation by task-irrelevant distracters may degrade the target-related neuronal signal. We therefore examined whether directing attention to a target stimulus can reduce the influence of task-irrelevant distracters on neuronal response. We find that in area V4 attention to a stimulus within a neuron's receptive field filters out a large fraction of the suppression induced by distracters appearing in the surround. When attention is instead directed to the surround stimulus, suppression is increased, thereby filtering out part of the neuronal response to the irrelevant distracter positioned within the receptive field. These findings demonstrate that attention modulates the neural mechanisms that give rise to center-surround interactions

Prevalence, patterns, and predictors of massage practitioner utilization: Results of a US nationally representative survey

© 2017 Elsevier Ltd Background The use of massage therapy is common, especially in patients with musculoskeletal pain. The purpose of this study was to examine the prevalence, utilization, socio-demographic and health-related predictors of massage practitioner consultations in the US population. Methods Cross-sectional data from the 2012 National Health Interview Survey for adults (n = 34,525). Results Prevalence of massage practitioner utilization were 12.8% (lifetime) and 6.8% (last 12 months). Compared to non-users, those who used massage in the last year were more likely: female, at least high school educated, annual income ≥ US$ 15,000, diagnosed with spinal pain or arthritis, report moderate physical activity level as compared to low level, and consume alcohol as compared to being abstinent. Massage was mainly used for general wellness or disease prevention (56.3%), but also for specific, typically musculoskeletal, health problems (41.9%) for which 85.2% reported massage helped to some or a great deal. Most (59.1%) did not disclose massage use to their health care provider, despite 69.4% reporting massage therapy combined with medical treatment would be helpful. Conclusions Approximately 7% (15.4 million) of US adults used massage therapy in the past year, mainly for general disease prevention, wellness or musculoskeletal pain. The majority of respondents reported positive outcomes of massage on specific health problems and overall well-being. Massage utilization was rarely covered by health insurance. Despite the majority of massage users considered massage therapy combined with medical care helpful, most did not disclose massage therapy use to their health care provider