Neuromuscular Markers of High Performance Sport Preparation: Muscle Contractile Mechanics

Assessments of skeletal muscle functional capacity or bilateral muscular asymmetry often necessitate maximal contractile effort, which exacerbates muscle fatigue or injury. Tensiomyography (TMG) has been investigated in laboratory settings, as a means to assess muscle contractile function following fatigue; however observations have not been contextualised by concurrent physiological measures. TMG has more sparingly been applied in the field, with elite athletes. The aim of this thesis was to examine acute alterations and underlying variations in muscle contractile mechanics, through the application of TMG, contextualised with established physiological measures; and to apply TMG within high performance sports programmes. TMG successfully detected fatigue, evident from reduced strength, by displaying impaired muscle displacement, accompanied by elevated resting muscle tension. Greater asymmetry was detected in individuals with asymmetric strength; however, symmetry was masked during more complex tasks. Increased day-to-day variability was detected among highly trained athletes compared to recreationally active individuals. Acute training adaptations were detected, in contractile mechanics, in individual muscles. TMG could be useful in establishing fatigue status of skeletal muscle without exacerbating the functional decrements of the muscle, whilst also providing useful screening information for detecting asymmetry which may not be apparent during functional actions

Reduced Radial Displacement of the Gastrocnemius Medialis Muscle After Electrically Elicited Fatigue

Context: Assessments of skeletal muscle functional capacity often necessitate maximal contractile effort, which exacerbates muscle fatigue or injury. Tensiomyography (TMG) has been investigated as a means to assess muscle contractile function following fatigue; however observations have not been contextualised by concurrent physiological measures. Objective: The aim of the present investigation was to measure peripheral fatigue-induced alterations in mechanical and contractile properties of the plantar flexor muscles through non-invasive TMG concurrently with maximal voluntary contraction (MVC) and passive muscle tension (PMT) in order to validate TMG as a gauge of peripheral fatigue. Design: Pre- and post-test intervention with control. Setting: University laboratory. Participants: Twenty-one healthy male volunteers. Interventions: Subjects plantar flexors were tested for TMG parameters, along with MVC and PMT, before and after either a 5 minute rest period (control) or a 5 minute electrical stimulation intervention (fatigue). Main Outcome Measures: Temporal (contraction velocity) and spatial (radial displacement) contractile parameters of the Gastrocnemius Medialis were recorded through TMG. MVC was measured as an indicator of muscle fatigue and PMT was measured to assess muscle stiffness. Results: Radial displacement demonstrated a fatigue-associated reduction (3.3 ± 1.2 vs. 4.0 ± 1.4 mm vs, p=0.031), while contraction velocity remained unaltered. Additionally, MVC significantly declined by 122.6 ± 104 N (p<0.001) following stimulation (fatigue). PMT was significantly increased following fatigue (139.8 ± 54.3 vs. 111.3 ± 44.6 N, p=0.007).  Conclusion: TMG successfully detected fatigue, evident from reduced MVC, by displaying impaired muscle displacement, accompanied by elevated PMT. TMG could be useful in establishing fatigue status of skeletal muscle without exacerbating the functional decrement of the muscle

Tensiomyography Derived Parameters Reflect Skeletal Muscle Architectural Adaptations Following 6-Weeks of Lower Body Resistance Training

Measurement of muscle specific contractile properties in response to resistance training (RT) can provide practitioners valuable information regarding physiological status of individuals. Field based measurements of such contractile properties within specific muscle groups, could be beneficial when monitoring efficacy of training or rehabilitation interventions. Tensiomyography (TMG) quantifies contractile properties of individual muscles via an electrically stimulated twitch contraction and may serve as a viable option in the aforementioned applications. Thus, aims of this study were; (i) to investigate the potential use of TMG to quantify training adaptations and differences, in response to exercise specific lower limb RT; and (ii) investigate any associations between TMG parameters and accompanying muscle architectural measures. Non-resistance trained male participants (n = 33) were randomly assigned to 1 of 3 single-exercise intervention groups (n = 11 per group); back squat (BS), deadlift (DL), or hip thrust (HT). Participants completed a 6-week linearized training program (2× per week), where the assigned exercise was the sole method of lower body training. Pre- and post-intervention testing of maximal dynamic strength was assessed by one repetition maximum (1RM) of BS, DL, and HT. Radial muscle belly displacement (Dm) and contraction time (Tc) were obtained via TMG from the rectus femoris (RF) and vastus lateralis (VL) pre- and post-intervention, alongside muscle architectural measures (pennation angle and muscle thickness). All three groups displayed significant increases all 1RM strength tests (p < 0.001; pη2 = 0.677–0.753). Strength increases were accompanied by significant overall increases in RF muscle thickness (p < 0.001, pη2 = 0.969), and pennation angle (p = 0.007, pη2 = 0.220). Additionally, an overall reduction in RF Dm (p < 0.001, pη2 = 0.427) was observed. Significant negative relationships were observed between RF Dm and pennation angle (p = 0.003, r = −0.36), and with RF Dm and muscle thickness (p < 0.001, r = −0.50). These findings indicate that TMG is able to detect improved contractile properties, alongside improvements in muscle function within an untrained population. Furthermore, the observed associations between Dm and muscle architecture suggest that TMG contractile property assessments could be used to obtain information on muscle geometry

A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease

The host- and bacteria-derived extracellular polysaccharide coating of the lung is a considerable challenge in chronic respiratory disease and is a powerful barrier to effective drug delivery. A low molecular weight 12–15-mer alginate oligosaccharide (OligoG CF-5/20), derived from plant biopolymers, was shown to modulate the polyanionic components of this coating. Molecular modeling and Fourier transform infrared spectroscopy demonstrated binding between OligoG CF-5/20 and respiratory mucins. Ex vivo studies showed binding induced alterations in mucin surface charge and porosity of the three-dimensional mucin networks in cystic fibrosis (CF) sputum. Studies in Humans showed that OligoG CF-5/20 is safe for inhalation in CF patients with effective lung deposition and modifies the viscoelasticity of CF-sputum. OligoG CF-5/20 is the first inhaled polymer therapy, represents a novel mechanism of action and therapeutic approach for the treatment of chronic respiratory disease, and is currently in Phase IIb clinical trials for the treatment of CF

Spirit, mind and body: the archaeology of monastic healing

Archaeology and material culture are used in this chapter to consider how monastic experience responded to illness, ageing and disability. The approach taken is influenced by the material study of religion, which interrogates how bodies and things engage to construct the sensory experience of religion, and by practice-based approaches in archaeology, which examine the active role of space and material culture in shaping religious agency and embodiment. The archaeology of monastic healing focuses on the full spectrum of healing technologies, from managing the body in order to prevent illness, through to the treatment of the sick and preparation of the corpse for burial

The Evolutionary Map of the Universe Pilot Survey

We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers 270 deg2 of an area covered by the Dark Energy Survey, reaching a depth of 25–30 μJy beam−1 rms at a spatial resolution of ∼11–18 arcsec, resulting in a catalogue of ∼220 000 sources, of which ∼180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here

Genome-wide association for major depression through age at onset stratification:Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Background Major depressive disorder (MDD) is a disabling mood disorder and, despite a known heritable component, a large meta-analysis of GWAS revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age-at-onset (AAO) in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by AAO. Method Discovery case-control GWASs were performed where cases were stratified using increasing/decreasing AAO-cutoffs; significant SNPs were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 controls for sub-setting. Polygenic score analysis was used to examine if differences in shared genetic risk exists between earlier and adult onset MDD with commonly co-morbid disorders of schizophrenia, bipolar disorder, Alzheimer’s disease, and coronary artery disease. Results We identify one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, OR=1.16, 95%CI=1.11-1.21, p=5.2x10-11). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset. Conclusions We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder

IMI - Myopia Genetics Report

The knowledge on the genetic background of refractive error and myopia has expanded dramatically in the past few years. This white paper aims to provide a concise summary of current genetic findings and defines the direction where development is needed. We performed an extensive literature search and conducted informal discussions with key stakeholders. Specific topics reviewed included common refractive error, any and high myopia, and myopia related to syndromes. To date, almost 200 genetic loci have been identified for refractive error and myopia, and risk variants mostly carry low risk but are highly prevalent in the general population. Several genes for secondary syndromic myopia overlap with those for common myopia. Polygenic risk scores show overrepresentation of high myopia in the higher deciles of risk. Annotated genes have a wide variety of functions, and all retinal layers appear to be sites of expression. The current genetic findings offer a world of new molecules involved in myopiagenesis. As the missing heritability is still large, further genetic advances are needed. This Committee recommends expanding large-scale, in-depth genetic studies using complementary big data analytics, consideration of gene-environment effects by thorough measurement of environmental exposures, and focus on subgroups with extreme phenotypes and high familial occurrence. Functional characterization of associated variants is simultaneously needed to bridge the knowledge gap between sequence variance and consequence for eye growth

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms