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A better understanding of the strains experienced by the Achilles tendon during commonly prescribed exercises and locomotor tasks is needed to improve efficacy of Achilles tendon training and rehabilitation programs. The aim of this study was to estimate in vivo free Achilles tendon strain during selected rehabilitation, locomotor, jumping, and landing tasks. Sixteen trained runners with no symptoms of Achilles tendinopathy participated in this study. Personalized free Achilles tendon moment arm and force-strain curve were obtained from imaging data and used in conjunction with motion capture and surface electromyography to estimate free Achilles tendon strain using electromyogram-informed neuromusculoskeletal modeling. There was a strong correspondence between Achilles tendon force estimates from the present study and experimental data reported in the literature (

The purpose of this study was to assess the similarity of free Achilles tendon shape and 3-D geometry between magnetic resonance imaging (MRI) and freehand 3-D ultrasound (3-DUS) imaging methods. Fourteen elite/sub-elite middle-distance runners participated in the study. MRI and 3-DUS scans of the Achilles tendon were acquired on two separate imaging sessions, and all 3-D reconstructions were performed using identical methods. Shape similarity of free Achilles tendon reconstructed from MRI and 3-DUS data was assessed using Jaccard index, Hausdorff distance and root mean square error (RMSE). The Jaccard index, Hausdorff distance and RMSE values were 0.76 ± 0.05, 2.70 ± 0.70 and 0.61 ± 0.10 mm, respectively. The level of agreement between MRI and 3-DUS for free Achilles tendon volume, length and average cross-sectional area (CSA) was assessed using Bland-Altman analysis. Compared to MRI, freehand 3-DUS overestimated volume, length and average CSA by 30.6 ± 15.8 mm3 (1.1% ± 0.6%), 0.3 ± 0.7 mm (0.6% ± 1.9%) and 0.3 ± 1.42 mm2 (0.4% ± 2.0%), respectively. The upper and lower limits of agreement between MRI and 3-DUS for volume, length and average CSA were -0.4 to 61.7 mm3 (-0.2% to 2.3%), -1.0 to 1.5 mm (-3.2% to 4.5%) and -2.5 to 3.1 mm2 (-3.5% to 4.3%), respectively. There were no significant differences between imaging methods in CSA along the length of the tendon. In conclusion, MRI and freehand 3-DUS may be considered equivalent methods for estimating shape and 3-D geometry of the free Achilles tendon. These findings, together with the practical benefits of being able to assess 3-D Achilles tendon shape and geometry in a laboratory environment and under isometric loading, make 3-DUS an attractive alternative to MRI for assessing 3-D free Achilles tendon macro-structure in future studies.

This study investigated the association between synthetic ovarian hormone use [i.e., the oral contraceptive (OC) pill] and basal C-reactive protein (CRP), peripheral blood immune cell subsets, and circulating pro- and anti-inflammatory cytokine concentrations in elite female athletes. Elite female athletes (n = 53) selected in Rio Summer Olympic squads participated in this study; 25 were taking an OC (AthletesOC) and 28 were naturally hormonally cycling (AthletesNC). Venous blood samples were collected at rest for the determination of sex hormones, cortisol, CRP, peripheral blood mononuclear memory and naïve CD4+ T-cells, CD8+ T-cells and natural killer cells, as well as pro- and anti-inflammatory cytokine concentrations. C-reactive protein concentrations were elevated (p < 0.001) in AthletesOC (median = 2.02, IQR = 3.15) compared to AthletesNC (median = 0.57, IQR = 1.07). No differences were reported for cortisol, cytokines, or PBMC immune cell subsets, although there was a trend (p = 0.062) for higher IL-6 concentrations in AthletesNC. Female Olympians had substantially higher CRP concentrations, a marker of inflammation and tissue damage, before the Rio Olympic Games if they used an OC. Future research should examine the potential consequences for athlete performance/recovery so that, if necessary, practitioners can implement prevention programs.

ISSUE ADDRESSED The aim of this study was to characterise lifestyle and training habits of a large cohort of Australian recreational runners. Understanding the health benefits of recreational running and differentiating between the habits of males and females may allow for the development of gender-specific messaging for promoting recreational running as a form of physical activity. METHODS An online questionnaire was used to collect data from 4720 Australian recreational runners. Data on physical, lifestyle and training characteristics of male and female subgroups were compared using chi-square tests. Multiple logistic regression method was used to assess the effect of running experience on the reported clinically significant weight loss. RESULTS The study cohort was 54.1% female and 45.9% male. Smoking was uncommon among surveyed runners. The most typical weekly running distance in the cohort was 20-40 km, usually distributed by 2-5 running sessions. Significantly more males than females reported running over 40 km per week (29.9% vs 18.9%, P < .001) and running at least six sessions per week (11.5% vs 6.7%, P < .001). The majority (72.9%) of runners had normal BMI, and the cohort reported a lower overweight/obesity rate than the Australian population. The logistic regression model indicated that commencing running may lead to a clinically significant weight loss irrespectively of sex, participation in other sports and injury history. CONCLUSION Recreational running was associated with beneficial health outcomes. Commencement of running is associated with weight loss, and regular running supports healthy weight maintenance. Male and female runners had different running preferences which should be taken into account for physical activity promotion. SO WHAT?: Captured health outcomes associated with running and described sex differences in training patterns may assist in development of physical activity promotion programmes involving recreational running, particularly targeting weight loss and healthy weight maintenance.

The automatic segmentation of Achilles tendon tissues is one of the preliminary steps towards creating a tool for diagnosing, prognosing, or monitoring changes in tendon organization over time. Manual delineation is the current approach of identifying Achilles region-of-interest (ROI), it is a tedious and time-consuming task. In this respect, the current work describes the first steps taken towards creating an automatic approach for Achilles tendon segmentation that utilize the capabilities of Deep Convolutional Neural Networks (CNNs). Firstly, the dataset has been pre-processed and manually segmented to be used as the ground-truth in the training and testing of the proposed automated model. Secondly, the model was trained and validated using three CNN architectures SegNet, ResNet-18 and ResNet-50. Finally, Tversky loss function, 3D augmentation and network ensembling approaches were used to improve the segmentation performance and to tackle challenges such as the limited size of the training dataset and data imbalance. The proposed fully automated segmentation method reached average Dice score of 0.904. In conclusion, this novel study demonstrates that a CNN approach is useful for performing accurate Achilles tendon segmentation in musculoskeletal imaging.

Objective The use of intravenous fluids in out-of-hospital settings has evolved from the practices used by military and emergency response teams. When used in the elite sporting environment, IV fluid use must comply with the World Anti-Doping Code. Uncertainty can arise as clinicians seek to balance the appropriate use of IV fluids in delivering athlete care against the need for World Anti-Doping Code compliance. Design and method This position statement reviews the current literature and incorporates clinical experiences to present best-practice recommendations on the clinical use of Intravenous fluids in the elite sport environment, framing recommendations in the context of the World Anti-Doping Code. Results and conclusion The World Anti-Doping Code restricts the use of Intravenous fluids in athletes under certain conditions. This report takes into account the World Anti-Doping Code and the risks of Intravenous fluid administration to provide guidelines around the judicious use of IV fluids for: 1. Treatment of severe dehydration in an athlete, 2. Management of exertional heat illness in an athlete, 3. Hypovolaemia because of trauma in sport, 4. Administering medications.

As Australia's peak high-performance sport agency, the Australian Institute of Sport (AIS) has developed this position statement to address the implications of recent advances in the field of genetics and the ramifications for the health and well-being of athletes. Genetic testing has proven of value in the practice of clinical medicine. There are, however, currently no scientific grounds for the use of genetic testing for athletic performance improvement, sport selection or talent identification. Athletes and coaches should be discouraged from using direct-to-consumer genetic testing because of its lack of validation and replicability and the lack of involvement of a medical practitioner in the process. The transfer of genetic material or genetic modification of cells for performance enhancement is gene doping and should not be used on athletes. There are, however, valid roles for genetic research and the AIS supports genetic research which aims to enhance understanding of athlete susceptibility to injury or illness. Genetic research is only to be conducted after careful consideration of a range of ethical concerns which include the provision of adequate informed consent. The AIS is committed to providing leadership in delivering an ethical framework that protects the well-being of athletes and the integrity of sport, in the rapidly changing world of genomic science.

PURPOSE. Acute anterior uveitis (AAU) is a common intraocular inflammatory disease. AAU occurs in 30% to 50% of patients with ankylosing spondylitis (AS), and both conditions are strongly associated with human leukocyte antigen (HLA)-B27, implying a shared etiology. This study aims to apply genomewide association study (GWAS) to characterize the genetic associations of AAU and their relationship to the genetics of AS. METHODS. We undertook the GWAS analyses in 2752 patients with AS with AAU (cases) and 3836 patients with AS without AAU (controls). There were 7,436,415 single-nucleotide polymorphisms (SNPs) available after SNP microarray genotyping, imputation, and quality-control filtering. RESULTS. We identified one locus associated with AAU at genomewide significance: rs9378248 (P = 2.69 × 10−8, odds ratio [OR] = 0.78), lying close to HLA-B. Suggestive association was observed at 11 additional loci, including previously reported AS loci ERAP1 (rs27529, P = 2.19 × 10−7, OR = 1.22) and NOS2 (rs2274894, P = 8.22 × 10−7, OR = 0.83). Multiple novel suggestive associations were also identified, including MERTK (rs10171979, P = 2.56 × 10−6, OR = 1.20), KIFAP3 (rs508063, P = 5.64 × 10−7, OR = 1.20), CLCN7 (rs67412457, P = 1.33 × 10−6, OR = 1.25), ACAA2 (rs9947182, P = 9.70 × 10−7, OR = 1.37), and 5 intergenic loci. The SNP-based heritability is approximately 0.5 for AS alone, and is much higher (approximately 0.7) for AS with AAU. Consistent with the high heritability, a genomewide polygenic risk score shows strong power in identifying individuals at high risk of either AS with AAU or AS alone. CONCLUSIONS. We report here the first GWAS for AAU and identify new susceptibility loci. Our findings confirm the strong overlap in etiopathogenesis of AAU with AS, and also provide new insights into the genetic basis of AAU.

The current pilot study investigates whether oral supplementation of specific collagen peptides improves symptoms and tendon vascularisation in patients with chronic mid-portion Achilles tendinopathy in combination with structured exercise. Participants were given a placebo or specific collagen peptides (TENDOFORTE&reg, ) in combination with a bi-daily calf-strengthening program for 6 months. Group AB received specific collagen peptides for the first 3 months before crossing over to placebo. Group BA received placebo first before crossing over to specific collagen peptides. At baseline (T1), 3 (T2) and 6 (T3) months, Victorian Institute of Sports Assessment&ndash, Achilles (VISA-A) questionnaires and microvascularity measurements through contrast-enhanced ultrasound were obtained in 20 patients. Linear mixed modeling statistics showed that after 3 months, VISA-A increased significantly for group AB with 12.6 (9.7, 15.5), while in group BA VISA-A increased only by 5.3 (2.3, 8.3) points. After crossing over group AB and BA showed subsequently a significant increase in VISA-A of, respectively, 5.9 (2.8, 9.0) and 17.7 (14.6, 20.7). No adverse advents were reported. Microvascularity decreased in both groups to a similar extent and was moderately associated with VISA-A (Rc2:0.68). We conclude that oral supplementation of specific collagen peptides may accelerate the clinical benefits of a well-structured calf-strengthening and return-to-running program in Achilles tendinopathy patients.

Background There has been considerable growth in basic knowledge and understanding of how genes are influencing response to exercise training and predisposition to injuries and chronic diseases. On the basis of this knowledge, clinical genetic tests may in the future allow the personalisation and optimisation of physical activity, thus providing an avenue for increased efficiency of exercise prescription for health and disease. Results This review provides an overview of the current status of genetic testing for the purposes of exercise prescription and injury prevention. As such there are a variety of potential uses for genetic testing, including identification of risks associated with participation in sport and understanding individual response to particular types of exercise. However, there are many challenges remaining before genetic testing has evidence-based practical applications; including adoption of international standards for genomics research, as well as resistance against the agendas driven by direct-to-consumer genetic testing companies. Here we propose a way forward to develop an evidence-based approach to support genetic testing for exercise prescription and injury prevention. Conclusion Based on current knowledge, there is no current clinical application for genetic testing in the area of exercise prescription and injury prevention, however the necessary steps are outlined for the development of evidence-based clinical applications involving genetic testing.

Objectives The role of neovascularisation in tendinopathy is still poorly understood, potentially due to technical limitations of conventional power Doppler ultrasound. This study aimed to investigate the association between contrast-enhanced ultrasound (CEUS) microvascular volume (MV), Victorian Institute of Sports Assessment-Achilles (VISA-A) scores and intrinsic Achilles tendon tenderness, as well as two different Power Doppler modes. Design Cross-sectional study. Methods 20 individuals with uni- or bilateral Achilles tendinopathy completed a VISA-A questionnaire, and underwent microvascular volume measurements of the Achilles tendon mid-portion using both conventional, ultrasensitive (SMI™) power Doppler ultrasound and CEUS. Intrinsic tendon tenderness was assessed with sensation detection threshold to extracorporeal shock waves (ESW). Linear Mixed Model analysis was used to determine the association between microvascular volume (MV), VISA-A, and ESW-detection threshold for both symptomatic and asymptomatic Achilles tendons. Results There was a significant association between VISA-A and MV (B = −5.3, 95%CI = [−8.5; −2.0], P = 0.0004), and between MV and symptom duration (B = −1.7, 95%CI = [−3.2; −5.0], P = 0.023). No significant associations were found between power Doppler ultrasound and CEUS-based MV or between CEUS-based MV and ESW-detection threshold. In comparison with conventional power Doppler ultrasound, SMI™ showed on average similar detection capacity for neovessels in the mid-portion of the Achilles tendon, whilst being superior for detecting neovessels within Kager’s fat pad (t = 3.46, 95%CI = [0.27; 1.03], P Conclusions Our results indicate that CEUS-based MV of the Achilles tendon is moderately associated with Achilles tendon symptoms. In accordance, CEUS-detected MV could be a novel target for treatment as it seems to be more sensitive than PDU and is correlated with symptoms.

ObjectiveEstablish the prevalence of illness symptoms, poor sleep quality, poor mental health symptoms, low energy availability and stress-recovery state in an Olympic cohort late in the 3 months prior to the Summer Olympic Games.MethodsOlympic athletes (n=317) from 11 sports were invited to complete questionnaires administered 3 months before the Rio 2016 Olympic Games. These questionnaires included the Depression, Anxiety and Stress Questionnaire, Perceived Stress Scale, Dispositional Resilience Scale, Recovery-Stress Questionnaire (REST-Q-52 item), Low Energy Availability in Females Questionnaire (LEAF-Q), Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index and custom-made questionnaires on probiotic usage and travel. Multiple illness (case) definitions were applied. ORs and attributable fractions in the population were used. Factor analyses were used to explore the relationships between variables.ResultsThe response rate was of 42% (male, n=47, age 25.8±4.1 years; female, n=85, age 24.3±3.9 years). Low energy availability was associated with sustaining an illness in the previous month (upper respiratory, OR=3.8, 95% CI 1.2 to 12). The main factor relating to illness pertained to a combination of anxiety and stress-recovery states (as measured by the REST-Q-52 item). All participants reported at least one episode of illness in the last month (100% prevalence).ConclusionsAll participants reported at least one illness symptom in the previous month. Low energy availability was a leading variable associated with illness in Olympic-class athletes. The estimates duration of symptoms ranged from 2 to 7 days. Factor analyses show the interdependence of various health domains and support multidisciplinary care.

Background: With the increasing capacity for remote collection of both data and samples for medical research, a thorough assessment is needed to determine the association of population characteristics and recruitment methodologies with response rates. Objective: The aim of this research was to assess population representativeness in a two-stage study of health and injury in recreational runners, which consisted of an epidemiological arm and genetic analysis. Methods: The cost and success of various classical and internet-based methods were analyzed, and demographic representativeness was assessed for recruitment to the epidemiological survey, reported willingness to participate in the genetic arm of the study, actual participation, sample return, and approval for biobank storage. Results: A total of 4965 valid responses were received, of which 1664 were deemed eligible for genetic analysis. Younger age showed a negative association with initial recruitment rate, expressed willingness to participate in genetic analysis, and actual participation. Additionally, female sex was associated with higher initial recruitment rates, and ethnic origin impacted willingness to participate in the genetic analysis (all P

Background Achilles tendinopathy is the most prevalent tendon disorder in people engaged in running and jumping sports. Aetiology of Achilles tendinopathy is complex and requires comprehensive research of contributing risk factors. There is relatively little research focussing on potential biomedical risk factors for Achilles tendinopathy. The purpose of this systematic review is to identify studies and summarise current knowledge of biomedical risk factors of Achilles tendinopathy in physically active people. Methods Research databases were searched for relevant articles followed by assessment in accordance with PRISMA statement and standards of Cochrane collaboration. Levels of evidence and quality assessment designation were implemented in accordance with OCEBM levels of evidence and Newcastle-Ottawa Quality Assessment Scale, respectively. Results A systematic review of the literature identified 22 suitable articles. All included studies had moderate level of evidence (2b) with the Newcastle-Ottawa score varying between 6 and 9. The majority (17) investigated genetic polymorphisms involved in tendon structure and homeostasis and apoptosis and inflammation pathways. Overweight as a risk factor of Achilles tendinopathy was described in five included studies that investigated non-genetic factors. COL5A1 genetic variants were the most extensively studied, particularly in association with genetic variants in the genes involved in regulation of cell-matrix interaction in tendon and matrix homeostasis. It is important to investigate connections and pathways whose interactions might be disrupted and therefore alter collagen structure and lead to the development of pathology. Polymorphisms in genes involved in apoptosis and inflammation, and Achilles tendinopathy did not show strong association and, however, should be considered for further investigation. Conclusions This systematic review suggests that biomedical risk factors are an important consideration in the future study of propensity to the development of Achilles tendinopathy. The presence of certain medical comorbidities and genetic markers should be considered when contemplating the aetiology of Achilles tendinopathy. Further elucidation of biomedical risk factors will aid in the understanding of tendon pathology and patient risk, thereby informing prevention and management strategies for Achilles tendinopathy. Trial Registration PROSPERO CRD42016036558

The existence of a feedback mechanism regulating the precise amounts of muscle structural proteins, such as actin and the actin-associated protein tropomyosin (Tm), in the sarcomeres of striated muscles is well established. However, the regulation of nonmuscle or cytoskeletal actin and Tms in nonmuscle cell structures has not been elucidated. Unlike the thin filaments of striated muscles, the actin cytoskeleton in nonmuscle cells is intrinsically dynamic. Given the differing requirements for the structural integrity of the actin thin filaments of the sarcomere compared with the requirement for dynamicity of the actin cytoskeleton in nonmuscle cells, we postulated that different regulatory mechanisms govern the expression of sarcomeric versus cytoskeletal Tms, as key regulators of the properties of the actin cytoskeleton. Comprehensive analyses of tissues from transgenic and knock-out mouse lines that overexpress the cytoskeletal Tms, Tm3 and Tm5NM1, and a comparison with sarcomeric Tms provide evidence for this. Moreover, we show that overexpression of a cytoskeletal Tm drives the amount of filamentous actin.

Nemaline myopathy (NM), the most common non-dystrophic congenital myopathy, is a variably severe neuromuscular disorder for which no effective treatment is available. Although a number of genes have been identified in which mutations can cause NM, the pathogenetic mechanisms leading to the phenotypes are poorly understood. To address this question, we examined gene expression patterns in an NM mouse model carrying the human Met9Arg mutation of alpha-tropomyosin slow (Tpm3). We assessed five different skeletal muscles from affected mice, which are representative of muscles with differing fiber-type compositions, different physiological specializations and variable degrees of pathology. Although these same muscles in non-affected mice showed marked variation in patterns of gene expression, with diaphragm being the most dissimilar, the presence of the mutant protein in nemaline muscles resulted in a more similar pattern of gene expression among the muscles. This result suggests a common process or mechanism operating in nemaline muscles independent of the variable degrees of pathology. Transcriptional and protein expression data indicate the presence of a repair process and possibly delayed maturation in nemaline muscles. Markers indicative of satellite cell number, activated satellite cells and immature fibers including M-Cadherin, MyoD, desmin, Pax7 and Myf6 were elevated by western-blot analysis or immunohistochemistry. Evidence suggesting elevated focal repair was observed in nemaline muscle in electron micrographs. This analysis reveals that NM is characterized by a novel repair feature operating in multiple different muscles.

The organisation of structural proteins in muscle into highly ordered sarcomeres occurs during development, regeneration and focal repair of skeletal muscle fibers. The involvement of cytoskeletal proteins in this process has been documented, with nonmuscle γ-actin found to play a role in sarcomere assembly during muscle differentiation and also shown to be up-regulated in dystrophic muscles which undergo regeneration and repair [Lloyd et al.,2004; Hanft et al.,2006]. Here, we show that a cytoskeletal tropomyosin (Tm), Tm4, defines actin filaments in two novel compartments in muscle fibers: a Z-line associated cytoskeleton (Z-LAC), similar to a structure we have reported previously [Kee et al.,2004], and longitudinal filaments that are orientated parallel to the sarcomeric apparatus, present during myofiber growth and repair/regeneration. Tm4 is upregulated in paradigms of muscle repair including induced regeneration and focal repair and in muscle diseases with repair/regeneration features, muscular dystrophy and nemaline myopathy. Longitudinal Tm4-defined filaments also are present in diseased muscle. Transition of the Tm4-defined filaments from a longitudinal to a Z-LAC orientation is observed during the course of muscle regeneration. This Tm4-defined cytoskeleton is a marker of growth and repair/regeneration in response to injury, disease state and stress in skeletal muscle. Cell Motil. Cytoskeleton 2008. © 2007 Wiley-Liss, Inc.

Tks5 is a scaffold protein and Src substrate involved in cell migration and matrix degradation through its essential role in invadosome formation and function. We have previously described that Tks5 is fundamental for zebrafish neural crest cell migration in vivo. In the present study, we sought to investigate the function of Tks5 in mammalian development by analyzing mice mutant for sh3pxd2a, the gene encoding Tks5. Homozygous disruption of the sh3pxd2a gene by gene-trapping in mouse resulted in neonatal death and the presence of a complete cleft of the secondary palate. Interestingly, embryonic fibroblasts from homozygous gene-trap sh3pxd2a mice lacked only the highest molecular weight band of the characteristic Tks5 triplet observed in protein extracts, leaving the lower molecular weight bands unaffected. This finding, together with the existence of two human Expressed Sequence Tags lacking the first 5 exons of SH3PXD2A, made us hypothesize about the presence of a second alternative transcription start site located in intron V. We performed 5'RACE on mouse fibroblasts and isolated a new transcript of the sh3pxd2a gene encoding a novel Tks5 isoform, that we named Tks5β. This novel isoform diverges from the long form of Tks5 in that it lacks the PX-domain, which confers affinity for phosphatidylinositol-3,4-bisphosphate. Instead, Tks5β has a short unique amino terminal sequence encoded by the newly discovered exon 6β; this exon includes a start codon located 29 bp from the 5'-end of exon 6. Tks5β mRNA is expressed in MEFs and all mouse adult tissues analyzed. Tks5β is a substrate for the Src tyrosine kinase and its expression is regulated through the proteasome degradation pathway. Together, these findings indicate the essentiality of the larger Tks5 isoform for correct mammalian development and the transcriptional complexity of the sh3pxd2a gene.