Aims. Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut microbiome in PTOA remains elusive. Methods. A total of 18 eight-week Sprague-Dawley rats were assigned into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). PTOA model was induced by transection of the anterior cruciate ligament (ACLT) and the destabilization of the medial meniscus (DMM). Treadmill-walking (15 m/min, 30 min/d, five days/week for eight weeks) was employed in the PTOA/TW group. The response of cartilage, subchondral bone, serology, and gut microbiome and their correlations were assessed. Results. Eight-week treadmill-walking was effective at maintaining the integrity of cartilage-subchondral bone unit and reducing the elevated systematic inflammation factors and microbiome-derived metabolites. Furthermore, 16S ribosomal ribonucleic acid (rRNA) sequencing showed disease-relevant microbial shifts in PTOA animals, characterized by the decreased abundance of phylum TM7 and the increase of phylum Fusobacteria. At the genus level, the abundance of Lactobacillus, Turicibacter, Adlercreutzia, and Cetobacterium were increased in the PTOA animals, while the increase of Adlercreutzia and Cetobacterium was weakened as a response to exercise. The correlation analysis showed that genus Lactobacillus and Adlercreutzia were correlated to the structural OA phenotypes, while phylum Fusobacteria and genus Cetobacterium may contribute to the effects of exercise on the diminishment of serological inflammatory factors. Conclusion. Exercise is effective at maintaining the integrity of cartilage-subchondral bone unit, and the exercise-induced modification of disease-relevant microbial shifts is potentially involved in the mechanisms of exercise-induced amelioration of PTOA. Cite this article: Bone Joint Res 2022;11(4):214–225

Introduction. Osteoarthritis (OA) causes pain, stiffness, and loss of function due to degenerative changes in joint cartilage and bone. In some forms of OA, exercise can alleviate symptoms by improving joint mobility and stability. However, excessive training after joint injury may have negative consequences for OA development. Sensory nerve fibers in joints release neuropeptides like alpha-calcitonin gene-related peptide (alpha-CGRP), potentially affecting OA progression. This study investigates the role of alpha-CGRP in OA pathogenesis under different exercise regimen in mice. Method. OA was induced in C57Bl/6J WT mice and alpha-CGRP KO mice via surgical destabilization of the medial meniscus (DMM) at 12 weeks of age (N=6). Treadmill exercise began 2 weeks post-surgery and was performed for 30 minutes, 5 days a week, for 2 or 6 weeks at intense (16 m/min, 15° incline) or moderate (10 m/min, 5° incline) levels. Histomorphometric assessment of cartilage degradation (OARSI scoring), serum cytokine analysis, immunohistochemistry, and nanoCT analysis were conducted. Result. OARSI scoring confirmed OA induction 4 weeks post-DMM surgery, with forced exercise exacerbating cartilage degradation regardless of intensity. No significant genotype-dependent differences were observed. Serum analysis revealed elevated cytokine levels associated with OA and inflammation in KO mice compared to WT mice 4 and 8 weeks post-surgery (VEGF-A, MCP-1, CXCL10, RANTES, MIP1-alpha, MIP1-beta, and RANKL). The observed effects were often exacerbated by intense exercise but rarely by DMM surgery. NanoCT analysis demonstrated increased sclerotic bone changes after 6 weeks of forced exercise in KO mice compared to WT mice. Conclusion. Our results suggest an OA promoting effect of exercise in early disease stages of posttraumatic OA. Intense exercise induced inflammatory processes correlated to increased cytokine levels in the serum that might exacerbate OA pathogenesis in later stages. The neuropeptide alpha-CGRP might play a role in protecting against these adverse effects

Introduction. Many literatures regarding more specific tests to diagnose the supraspinatus tendon injuries and the best rehabilitation methods to strengthen the supraspinatus have been published. However, conflicting results have been reported. 2-deoxy-2-[18F] fluoro-D-glucose (FDG) positron emission tomography (PET) has been recently used to assess skeletal muscle activities in various fields. Purpose. To evaluate & compare the metabolic activities of deltoid & rotator cuff muscles after the full-can & empty-can exercises using PET-CT. Materials and Methods. Ten healthy volunteers (age 27–34/mean 29.8 ± 2.7) with no history of shoulder pain and diabetes mellitus participated in this study. After FDG injection, both arms were maintained in the position of empty can and full can for ten minutes respectively. PET-CT was performed at forty minutes after the injection. The maximum standardized uptake value (SUV) was measured in the anterior, middle and posterior deltoid, supraspinatus, subacapularis and infraspinauts on the entire axial images. Results. The middle deltoid and subscapularis showed significantly greater activity during the empty-can exercise than during the full-can exercise (P=.006 and P=.003 respectively). The muscular activity of the supraspinatus also increased during the empty-can exercise than during the full-can exercise, although no statistical difference existed between two exercises. Six cases of eight cases who had increased activity of the subscapularis had increased activity in superior one half of the subscapularis than in lower one half of it, although there is no significant difference between two portions. Conclusion. The Empty-can exercise requires more strength of the middle deltoid, subscapularis and supraspinatus to keep the arm in internal rotation. The increased activity of the middle deltoid and subscapularis muscles after the empty-can exercise can make the empty-can test less specific to the supraspinatus muscle. The empty-can test can induce pain and weakness due to the subscapularis pathology. The full-can test can be used to test the function of the supraspinatus with the least amount of surrounding middle deltoid and subacapularis muslce activity

Objective: The UK BEAM trial was designed to evaluate treatments for back pain in primary care. The objective is to briefly describe the different treatments and to present the frequency with which trial participants attended for manipulation, exercise or both. Design: The UK BEAM trial is a national randomised factorial trial in primary care. Participants were randomised to receive one of GP management, exercise classes, manipulation (in either private or NHS premises) or both exercise classes and manipulation. Participants randomised to manipulation alone could receive up to eight sessions delivered by a chiropractor, an osteopath, or a physiotherapist. Those randomised to exercise alone could attend up to nine sessions led by a physiotherapist in a local community facility. Subsequently, those randomised to manipulation followed by exercise could attend up to 17 sessions. Subjects: Participants were recruited from 150 GP practices in 14 centres distributed across the United Kingdom. The target population was patients between 18 and 65 years who present in general practice with non-specific back pain with or without leg pain. Outcome Measures: The frequency that participants attended for manipulation, exercise, or both. Results: The trial recruited 1334 participants. The current analysis shows the mean number of sessions attended by participants for manipulation alone is 6.6. The mean number of sessions attended for exercise alone is 4.4. In contrast, those participants randomised to manipulation followed by exercise attended 5.2 and 3.4 sessions respectively. Conclusions: Those participants who were randomised to manipulation followed by exercise attended fewer sessions on average than those randomised to manipulation or exercise alone

Introduction. Exercise is recommended as first-line treatment for patients with hip osteoarthritis (OA). Interestingly, content and dose of exercise interventions seem to be important for the effect of exercise interventions, but the optimal content and dose is unknown. This warrants randomized controlled trials providing evidence for the optimal exercise program in Hip OA. The aim of this trial was to investigate whether progressive resistance training (PRT) is superior to neuromuscular exercise (NEMEX) for improving functional performance, hip pain and hip-related quality of life in patients with hip OA. Method. This was a multicenter, cluster-randomized, controlled, parallel-group, assessor-blinded, superiority trial. 160 participants with clinically diagnosed hip OA were recruited from hospitals and physiotherapy clinics and randomly assigned to twelve weeks of PRT or NEMEX. The PRT intervention consisted of 5 high-intensity resistance training exercises targeting muscles at the hip and knee joints. The NEMEX intervention included 10 exercises and emphasized sensorimotor control and functional stability. The primary outcome was change in the 30-second chair stand test (30s-CST). Key secondary outcomes were changes in scores on the pain and hip-related quality of life (QoL) subscales of the Hip Disability and Osteoarthritis Outcome Score (HOOS). Result. The mean changes from baseline to 12-week follow-up in the 30s-CST were 1.5 (95% CI, 0.9 to 2.1) chair stands with PRT and 1.5 (CI, 0.9 to 2.1) chair stands with NEMEX (difference, 0.0 [CI, 0.8 to 0.8] chair stands). For the HOOS pain subscale, mean changes were 8.6 (CI, 5.3 to 11.8) points with PRT and 9.3 (CI, 5.9 to 12.6) points with NEMEX. For the HOOS QoL subscale, mean changes were 8.0 (CI, 4.3 to 11.7) points with PRT and 5.7 (CI, 1.9 to 9.5) points with NEMEX. Conclusion. In patients with hip OA, PRT is not superior to NEMEX for improving functional performance, hip pain, or hip-related QoL

Objectives. Osteoporosis is a metabolic disease resulting in progressive loss of bone mass as measured by bone mineral density (BMD). Physical exercise has a positive effect on increasing or maintaining BMD in postmenopausal women. The contribution of exercise to the regulation of osteogenesis in osteoblasts remains unclear. We therefore investigated the effect of exercise on osteoblasts in ovariectomized mice. Methods. We compared the activity of differentially expressed genes of osteoblasts in ovariectomized mice that undertook exercise (OVX+T) with those that did not (OVX), using microarray and bioinformatics. Results. Many inflammatory pathways were significantly downregulated in the osteoblasts after exercise. Meanwhile, IBSP and SLc13A5 gene expressions were upregulated in the OVX+T group. Furthermore, in in vitro assay, IBSP and SLc13A5 mRNAs were also upregulated during the osteogenic differentiation of MC3T3-E1 and 7F2 cells. Conclusion. These findings suggest that exercise may not only reduce the inflammatory environment in ovariectomized mice, indirectly suppressing the overactivated osteoclasts, but may also directly activate osteogenesis-related genes in osteoblasts. Exercise may thus prevent the bone loss caused by oestrogen deficiency through mediating the imbalance between the bone resorptive activity of osteoclasts and the bone formation activity of osteoblasts. Cite this article: W-B. Hsu, W-H. Hsu, J-S. Hung, W-J. Shen, R. W-W. Hsu. Transcriptome analysis of osteoblasts in an ovariectomized mouse model in response to physical exercise. Bone Joint Res 2018;7:601–608. DOI: 10.1302/2046-3758.711.BJR-2018-0075.R2

There is evidence that preoperative physical fitness impacts surgical outcomes, specifically preceding abdominal, cardiovascular and spine surgery. To our knowledge, there are no papers on self-reported exercise frequency as a predictor of cervical spine surgery outcomes. Our objectives were to quantify self-report of exercise frequency in cervical spine surgery patients, and to elucidate if self-reported exercise prior to surgery confers less pain, improved health state and/or less disability post-surgery. We performed a retrospective review of prospectively collected data from the Canadian Spine Outcomes and Research Network (CSORN) Database from the time of its inception. Inclusion criteria specified all elective cervical surgery patients over 18 years old with degenerative pathology who proceeded to surgery and completed the pre- and post-operative outcomes measures up to 24 months post surgery (n=460). Outcome measures were visual analog scales (VAS) for neck and arm pain, Neck Disability Index (NDI), and EuroQOL score at baseline and 3, 12 and 24 months post-op. Exercise frequency was self-reported as “none” (n=212) versus “some” (n=248). These groups were further categorized into “none due to physical limitations”, “none” (not due to physical limitations), those to exercised “once or less per week” and those that exercised “twice or more per week”. Student's t-tests were used to compare the mean scores of the outcome measures, and analysis of variance for subgroup comparisons, with results considered significant at p < 0 .05. At baseline, 56% of total patients reported exercise prior to surgery, of which 73% reported doing so twice or more per week. Of the 44% reporting no exercise, 74% could not exercise due to physical limitations. Those who reported “some” exercise had more favorable VAS neck and arm pain scores pre-operatively (neck: 5.55 vs 6.11, p < 0 .001) (arm: 5.69 vs 6.04, p=0.011), but no difference at 3 and 24 months post-operatively. Significantly lower NDI scores and higher EuroQOL Index scores were seen in the exercise group compared to the no exercise group pre-operatively (NDI: 39 vs 48, p < 0 .001) (EuroQOL: 0.60 vs 0.50 p < 0 .001) as well as at 3, 12, and 24 months post-op (NDI: 24 vs 31, p=0.007) (EuroQOL: 0.75 vs 0.68, p=0.001). Further subgroup analysis demonstrated that compared to the “no exercise due to physical limitation” group, the “twice or more” exercise group showed favorable NDI and EuroQOL scores up to 24 months post-op (NDI: 24.32 vs 32.33, p=0.001) (EuroQOL: 0.76 vs 0.66, p=0.001), whereas the “once or less times per week” group no longer demonstrated any significant difference at 24 months (NDI: 28.79 vs 32.33, p=1) (EuroQOL: 0.73 vs 0.66, p=0.269). Self-reported exercise prior to cervical spine surgery does not predict improved long-term neck and arm pain at 2 years post-op. However, self-reported exercise does demonstrate less disability and improved health state at baseline and up to 2 years post-op and this relationship is dose dependent

Purpose and background. Nearly 70% of UK physiotherapists experience work-related musculoskeletal disorders (WRMSDs) during their career, with a significant proportion occurring in the back and being attributed to patient handling tasks. Evidence suggests that manual handling training alone is ineffective and interventions among nurses indicate that a tailored approach, including targeted exercise (TE), can reduce WRMSD rates. This study aimed to explore physiotherapists’ perspectives of WRMSDs, patient handling, and the role of TE in reducing WRMSDs among physiotherapists. Methods and Results. Key informant interviews were conducted with 4 physiotherapy operational leads and 1 manual handling trainer from NHS Grampian. Interviews were transcribed and Framework Analysis was utilised to identify key themes, including challenges, barriers, and facilitators. Following this, two online focus groups were conducted with 7 qualified NHS physiotherapists across the UK. Views of manual handling training varied across specialities, with some finding it comprehensive and adaptable, and others finding it less applicable to patients in their speciality or community setting. Physiotherapist views on fitness for work varied, with some highlighting the necessity of TE to ensure workforce health whilst others considered exercise to be a personal matter. Facilitators to implementation identified by participants were having support from management and a strong justification for the exercise content. Varied work schedules and facilities were identified as barriers to implementation of a work-based TE intervention. Conclusion. Varying perspectives on TE interventions and barriers to implementation were identified. This work will inform future research to develop TE interventions in consultation with key stakeholders. Conflicts of Interest. No conflicts of interest. Source of Funding. NHS Endowment Research Grant 22/001

Background. Low back pain (LBP) is a major problem across the globe and is the leading cause worldwide of years lost to disability. Self-management is considered an important component the treatment of people with non-specific LBP. However, it seems that the self-management support for people with non-specific LBP provided by physiotherapists can be improved. Moreover, the way exercise therapists (ET) address self-management in practice is unknown. Purpose. To investigate the ideas, opinions and methods used by physiotherapists and ET with regard to self-management and providing self-management support to patients with non-specific LBP. Methods. This study was a qualitative survey. An online questionnaire with open-ended questions was developed. The survey was conducted among physiotherapists and ET working in the Netherlands. Data was analysed using thematic analysis. Results. Respondents considered self-management support an important topic in physiotherapy and exercise therapy for people with non-specific LBP. In the self-management support provided by the respondents, providing information and advice were frequently mentioned. The topics included in the support given by the respondents covered a broad range of important factors. The topics frequently focused on biomechanical factors. Therapists mainly provided patient education rather than self-management support. Moreover, important self-management skills were generally not addressed sufficiently. The majority of respondents had a need with regard to self-management or providing self-management support. These needs include having more knowledge, skills and tools aimed at facilitating self-management. Conclusion. The way physiotherapists and ET address self-management in people with non-specific LBP is not optimal and should be improved. Conflicts of interest: No conflicts of interest. Sources of funding: No funding obtained. Previous publication: This work was published in a scientific journal: Hutting N, Oswald W, Staal JB, Heerkens YF. Self-management support for people with non-specific low back pain: A qualitative survey among physiotherapists and exercise therapists. Musculoskelet Sci Pract. 2020 Dec; 50:102269. doi: 10.1016/j.msksp.2020.102269. This work was never presented at a conference

Purpose. The importance of interpreting clinical trial results in terms of the benefits a treatment may offer to individuals with chronic pain is becoming more widely recognized. The clinical meaningfulness of group differences can better be described by looking at the percentages of responders in each treatment group, rather than between group mean differences. We have reassessed the outcomes of a clinical trial for chronic low back pain (LBP) from this new perspective. Methods. The randomized clinical trial examined short- (12 weeks) and long-term (52 weeks) efficacy of high-dose, supervised trunk exercise (SET), spinal manipulative therapy (SMT), and a course of home exercise and self-care advice (HEA) for the treatment of LBP ≥ 6 weeks duration. We calculated response to care at 2 levels for 2 variables: numeric back pain scores (NRS) and Roland-Morris Disability (RMD), and at 3 timepoints (Weeks 12, 26 and 52). The 2 levels were calculated as percent improvement from baseline ≥ 30% and ≥75%. Finally, we calculated the relative proportion (± 95% confidence intervals) of the sample (∼100 per treatment group) that achieved each level of improvement. Conclusion. In general, 60%-80% of patients had ≥ 30% improvements in pain @ week 12, while 20%-30% showed ≥75% improvement. At week 52, the percentage of patients with ≥ 30% improvement dropped slightly, while ≥75% improvement increased slightly. For RMD scores, 30%-50% of patients showed ≥75% improvement at week 52. We will present these results and compare them to the previous analysis of between group mean differences

Background. Ankle fractures are extremely common but unfortunately, over 20% fail to obtain good to excellent recovery. For those requiring surgical fixation, usual-care post-surgery has included six-weeks cast immobilisation and non-weightbearing. Disuse atrophy and joint stiffness are detrimental sequelae of this management. While rehabilitation, starting at two-weeks post-surgery is viewed as safe, the literature contains methodological flaws and a lack of focus on early exercise, perpetuating the controversy over the effectiveness of early exercise interventions. Objectives. Our objectives were to determine if following operative fixation for Weber B fracture, the physiotherapy intervention, early motion and directed exercise (EMADE), applied in the clinical setting, were superior to Usual-care at 12-weeks (primary outcome) and 24-weeks. Design and Methods. We undertook a pragmatic-RCT, recruiting 157 surgically fixed Weber B ankle fracture patients, to establish if EMADE was superior to the Usual-care of 6-weeks immobilisation. The EMADE physiotherapy intervention (between week-2 and 4 post-surgery) utilised a removable cast and combined non-weightbearing progressive home exercises with manual therapy, advice and education. The primary outcome measure was the OMAS at 12-weeks. Results. 130 participants returned their 12-weeks post-surgery data, exceeding the 60/group threshold set by the a-priory power calculation. Group OMAS means were; 62.0 and 48.8 (SD 21, 22.5) EMADE, Usual-care respectively, yielding a clinically meaningful mean difference of 13.2 on the OMAS and a statistical difference (95% CI p< 0.001, 5.66 to 20.73). Both clinically meaningful and statistically significant findings were maintained at week-24. There were no intervention related or unexpected adverse events, including instability. Conclusions. This clinic set pragmatic-RCT yielded both clinical and statistical outcomes at week-12 in favour of the EMADE physiotherapy intervention over the Usual-care of 6-weeks immobilisation, in surgically fixed Weber B ankle fracture patients. These positive findings were maintained at week-24 and justify EMADE physiotherapy as a viable treatment option

Introduction and Objective. Chronic tendinopathy is a multifactorial disease and a common problem in both, athletes and the general population. Mechanical overload and in addition old age, adiposity, and metabolic disorders are among the risk factors for chronic tendinopathy but their role in the pathogenesis is not yet unequivocally clarified. Materials and Methods. Achilles tendons of young (10 weeks) and old (100 weeks) female rats bred for high (HCR) and low (LCR) intrinsic aerobic exercise capacity were investigated. Both Achilles tendons of 28 rats were included and groups were young HCR, young LCR, old HCR, and old LCR (n = 7 tendons per group/method). In this rat model, genetically determined aerobic exercise capacity is associated with a certain phenotype as LCR show higher body weight and metabolic dysfunctions in comparison to HCR. Quantitative real-time PCR (qPCR) was used to evaluate alterations in gene expression. For histological analysis, semi-automated image analysis and histological scoring were performed. Results. Age-related downregulation of tenocyte marker genes (Tenomodulin), genes related to matrix modelling and remodeling (Collagen type 1, Collagen type 3, Elastin, Biglycan, Fibronectin, Tenascin C), and Transforming growth factor beta 3 (Tgfb3) were detected in tendons from HCR and LCR. Furthermore, inflammatory marker Cyclooxygenase 2 (Cox2) was downregulated, while Microsomal prostaglandin E synthase 2 (Ptges2) was upregulated in tendons from old HCR and old LCR. No significant alteration was seen in Interleukin 6 (Il6), Interleukin 1 beta (Il1b), and Tumor necrosis factor alpha (Tnfa). Histological analysis revealed that Achilles tendons of old rats had fewer and more elongated tenocyte nuclei compared to young rats, indicating a reduced metabolic activity. Even though higher content of glycosaminoglycans as a sign of degeneration was found in tendons of old HCR and LCR, no further signs of tendinopathy were detectable in histological evaluation. Conclusions. Overall, aging seems to play a prominent role in molecular and structural alterations of Achilles tendon tissue, while low intrinsic exercise capacity did not cause any changes. Even though tendinopathy was not present in any of the groups, some of the shown age-related changes correspond to single characteristics of chronic tendon disease. This study gives an insight into tendon aging and its contribution to molecular and cellular changes in Achilles tendon tissue

Background and Aim of Study. Despite several hundred RCTs of exercise for persistent non-specific low back pain (NSLBP), the treatment targets of exercise are unclear. In a systematic review we observed 30 direct and indirect treatment targets of exercise described across 23 RCTs for persistent NSLBP. Since not all treatment targets and outcomes can be assessed in all RCTs, it is therefore important to prioritise these treatment targets through consensus from key stakeholders. These consensus workshops aimed to agree treatment targets for the use of exercise interventions in randomised controlled trials (RCTs) in persistent NSLBP using nominal group workshop (NGW) methodology. Methods and Results. The first UK workshop included people who had experience of exercise to manage their persistent NSLBP, clinicians who prescribe exercise for persistent NSLBP, and researchers who design exercise interventions tested in RCTs. The second workshop included participants attending an international back and neck pain research workshop. Twelve participants took part in the UK NGW and fifteen took part in the final ranking of the exercise treatment targets. In addition to the original list of 30 treatment targets, a further 26 ideas were generated. After grouping and voting, 18 treatment targets were prioritised. The top five ranked targets of exercise interventions for persistent NSLBP were: pain reduction, improvement in function, reduction of fear of movement, encouragement of normal movement and improvement of mobility. The results of the international NGW will also be presented. Conclusion. Future RCTs of exercise should consider more consistent assessment of these treatment targets. Sources of Funding: This PhD is funded by the Research Institute for Primary Care and Health Sciences, Keele University. Prof NE Foster is a UK National Institute for Health Research Senior Investigator, and was supported by a UK National Institute for Health Research Professorship (NIHR-RP-011-015). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Conflicts of Interest: No conflicts of interest

Introduction. Exercise increases tendon collagen synthesis and cross-link formation. Exercise also increases the expression of TGF-β. 1. TGF-β. 1. may contribute to the upregulation of tendon collagen synthesis during exercise, but this relationship has not been established in vivo. The purpose of this study was to evaluate the effects of TGF-β. 1. receptor inhibition on tendon collagen. Materials and Methods. Male Wistar rats were divided into sedentary (SED, n = 9) or exercised (RUN, n=15) groups. Exercised animals completed four days of treadmill exercise (60 minutes/days). The peritendinous space of one Achilles tendon was injected with LY-364947 (ALK5 inhibitor; INHIB) while the opposite leg was injected with a vehicle (SHAM). Injections were given daily after each exercise bout. ERK and Smad 2/3 phosphorylation was evaluated by Western blotting. Collagen I and III gene expression were evaluated via qRT-PCR. Tendon hydroxyproline and hydroxylyslpyridinoline (HP) cross-linking were assayed via HPLC. A longitudinal section of tendon was stained with H&E for evaluation of cell numbers and fibril organization. Results. Phosphorylation of ERK increased by 2.5-fold in both legs given LY-364947 (p<0.05) but was not influenced by exercise (p>0.05). Smad 3 phosphorylation was reduced (p<0.05) in tendons treated with LY-364947. Neither type I nor type III collagen gene expression was affected by TGF-β. 1. receptor inhibition or exercise (p>0.05). Collagen content was not altered by either exercise or LY-364947 (p>0.05). HP cross-linking was 3-fold lower in the RUN-INHIB when compared to the RUN-SHAM tendon (p<0.05). No effect of inhibitor on HP was noted in the sedentary animals. Cell density was greater (p<0.05) in the Achilles tendon of exercised animals (SED: 7.5 cell/100 μm. 2. , RUN: 10.3 cell/100 μm. 2. ) but was not influenced by TGF-β. 1. receptor inhibition (p>0.05). Fiber structure scores were 45% lower (p<0.07) in SED animals treated with inhibitor but normal in RUN animals given inhibitor. Discussion. The changes in ERK and Smad phosphorylation suggest that LY-364947 was effective at altering TGF-β. 1. signaling. Our data suggest that neither acute exercise nor TGF-β. 1. receptor inhibition altered collagen gene expression. In contrast, TGF-β. 1. appears to be important for regulating Achilles tendon cross-link formation during exercise training and inhibition of TGF-β. 1. impacts fiber structure

Background. Venous thromboembolisms are serious complications of arthroplasty of the lower extremities. Although early ambulation and active leg exercise is recommended, postoperative patients with surgical pain have difficulty in moving their legs. Therefore, we developed a novel leg exercise apparatus (LEX) to facilitate active leg movement even during the early postoperative period (Fig 1). LEX is a portable apparatus that allows patients to actively move their legs while in the supine position. LEX enables dorsiflexion, plantar flexion, combined eversion and inversion of the ankle, and multi-joint movement of the leg. Objectives. To describe how LEX facilitates active movement of the leg and thereby increases venous flow in the lower extremities. Participants and Methods. The venous flow volume of the femoral vein of 8 healthy volunteers; 5 men and 3 women, with a mean age of 22.4 (range, 22–26) years, were measured by duplex ultrasonography. The measurements were repeated at 1, 3, 5, and 10 minutes after the completion of one-minute active ankle exercise with LEX, and during the 10-minute use of an intermittent pneumatic compression (IPC) device. The same measurements were taken from 8 healthy volunteers; 5 men and 3 women, with a mean age of 21.6 (19–26) years, after three types of 1 minute LEX exercise: rapid dorsiflexion-plantar flexion (60 reps/min), slow dorsiflexion-plantar flexion (30 reps/min) and combined motion of the leg (30 reps/min). These measurements were repeated at 1, 10, 20, and 30 minutes after the 1 min-LEX exercise. Statistical methods. All data were analyzed in a two-way repeated measures analysis of variance. Post-hoc analyses were performed using the Bonferroni comparisons test. The probability level accepted for statistical significance was p < 0.05 (SPSS Statistics Version 21). Results. Whereas the flow volume of the femoral vein after the 1 min-LEX exercise increased 2.00-fold over the baseline level, the value at 1 minute after the start of IPC did 1.18-fold (p = 0.033). The flow volume at 10 minutes had increased 1.50-fold; the corresponding values during IPC use were the same as those during rest (Fig 2). The flow volume after the 1 min-LEX exercise had increased for 30 minutes. After 30 minutes of rapid dorsiflexion-plantar flexion, it increased 1.63-fold over the baseline level. While 1 minute after slow flexion, the flow volume increased 1.38-fold and remained on the same level, this value was 1.53-fold at 30 minutes after combined leg motion. The combined leg exercise made the flow volume higher than dorsiflexion-plantar flexion at equal speed (Fig 3). Discussion. Short periods of LEX use improved the venous flow volume of the femoral vein more than continuous use of IPC. The 1-min LEX exercise had improved the femoral venous flow volume for 30 minutes, and combined leg exercise was more effective than a single ankle exercise. These results suggest that LEX exercise can induce the lower-extremity venous flow greater than that achieved using IPC. Clinical Relevance: LEX might be effective for enabling postoperative patients to move their legs and to improve venous flow of the lower extremities

Aims. To assess the effect of physical exercise (PE) on the histological and transcriptional characteristics of proteoglycan-induced arthritis (PGIA) in BALB/c mice. Methods. Following PGIA, mice were subjected to treadmill PE for ten weeks. The tarsal joints were used for histological and genetic analysis through microarray technology. The genes differentially expressed by PE in the arthritic mice were obtained from the microarray experiments. Bioinformatic analysis in the DAVID, STRING, and Cytoscape bioinformatic resources allowed the association of these genes in biological processes and signalling pathways. Results. Arthritic mice improved their physical fitness by 42.5% after PE intervention; it induced the differential expression of 2,554 genes. The bioinformatic analysis showed that the downregulated genes (n = 1,371) were significantly associated with cellular processes that mediate the inflammation, including Janus kinase-signal transducer and activator of transcription proteins (JAK-STAT), Notch, and cytokine receptor interaction signalling pathways. Moreover, the protein interaction network showed that the downregulated inflammatory mediators interleukin (IL) 4, IL5, IL2 receptor alpha (IL2rα), IL2 receptor beta (IL2rβ), chemokine ligand (CXCL) 9, and CXCL12 were interacting in several pathways associated with the pathogenesis of arthritis. The upregulated genes (n = 1,183) were associated with processes involved in the remodelling of the extracellular matrix and bone mineralization, as well as with the processes of aerobic metabolism. At the histological level, PE attenuated joint inflammatory infiltrate and cartilage erosion. Conclusion. Physical exercise influences parameters intimately linked to inflammatory arthropathies. Research on the effect of PE on the pathogenesis process of arthritis is still necessary for animal and human models. Cite this article:Bone Joint Res. 2020;9(1):36–48

Background. After surgical correction of thoracic scoliosis, an improvement in the cardio-respiratory adaptation to exercise would be expected because of the correction of the rib cage associated with the spinal deformity. This work intended to evaluate the physiologic responses to incremental exercise in patients undergoing surgical correction of adolescent idiopathic scoliosis (AIS). The hypothesis of this study was that the exercise limitations described in patients with AIS could be related with the physical deconditioning instead of being linked to the severity of the vertebral deformity. Methods. Cross-sectional study of the exercise tolerance in a series of patients with AIS type Lenke 1A, before and 2 years after surgical correction. Twenty patients with AIS and 10 healthy adolescents aged between 12 and 17 years old were evaluated. The average magnitude of the curves was 60.3±12.9 Cobb. Cardio-respiratory function was assessed before surgery and at 2-year follow-up by maximal exercise tolerance test on treadmill following a Bruce standard protocol. Maximal oxygen uptake (VO2), VCO2, expiratory volume (VE), and VE/VO2 ratio were registered. Results. Before surgery, AIS patients showed lower values than healthy controls in all cardio-respiratory parameters. The most important restrictions were the VO2max in ml/kg/min. (30.3±5.4 vs 49.9±7.5), VE (43.2±10.3 vs 82.3±10.7) and VE/CO2 ratio (25.0±3.9 vs 29.6±4.2). Contrary to expectations, two years after surgery most of these parameters decreased but differences with preoperative data were no statistically significant. Besides the great correction of the deformity (coronal plane, 71.5%; axial rotation, 49.3%), the cardio-respiratory tolerance to the exercise was not modified by surgery. Conclusions. Patients with moderate-severe AIS showed a limited tolerance to maximal exercise that does not change 2 years after surgery. This findings suggests that the reduced cardio-pulmonary function during exercise is not strictly associated to the spinal deformity, since great corrections of the spinal curves does not improve functional ventilatory parameters. In addition, the results point out a severe exercise deconditioning in AIS patients. Level of evidence. Level IV

Introduction. Tendon cross-sectional area (CSA) and stiffness increase in men during chronic exercise. The increase in tendon CSA and stiffness is not evident in women. In men, exercise increases tendon production of MMPs, IGF-1, and IL-6, which presumably contribute to tendon remodeling during chronic exercise. The purpose of this study was to determine if exercise-induced production of MMPs, IGF-1, and IL-6 are limited in women when compared to men. Materials and Methods. Young men (n=9, 27±1 y) and women (n=8, 26±1 y) performed a single bout of calf press exercise (8 sets of 15 repetitions at 70% of 15-RM). A microdialysis fiber (3000 kDa cut-off) was inserted into the space anterior to the Achilles tendon immediately after exercise and during a control experiment. All proteins were evaluated with ELISA kits. Results. In men IGF-I increased with exercise at 3 (p<0.05) but not 4 hrs. IGF-1 was not elevated at any measured time points in women. IL-6 increased with exercise to a similar extent in men and women at 3 hrs (p<0.05) but values returned to baseline at 4 hrs. MMP-9 increased with exercise at both 2 and 5 hours (p<0.05) in men but not in women. MMP-2 increased with exercise at 2 and 5 hrs to a similar extent in both men and women (p<0.05). In men TIMP-1 increased with exercise at 2 (p<0.05) but not 5 hrs. In women, TIMP-1 levels were elevated post-exercise at both 2 and 5 hrs (p<0.05). Discussion. In men, resistance exercise resulted in a modest and transient increase in tendon production of IGF-1 and IL-6. In women, this is only evident for IL-6. MMP-2 and MMP-9 increased with exercise in men. The exercise-induced increase in MMP-9 was not seen in women. In contrast, MMP-2 increased in women to a comparable magnitude as men. TIMP-1 increased with exercise in men and women but remained elevated out to 5 hrs in women only. The blunted increase in IGF-1 and MMP-9 and a prolonged increase in TIMP-1 may contribute to the lack of tendon adaptations after chronic training in women when compared to men

Study Design: Prospective analysis of a cohort of patients who underwent a Spinal Fitness Exercise Program in a nurse led spinal assessment clinic in a University Hospital. Objective: To determine if psychological status affects the outcome of a spinal fitness exercise program in patients with low back pain. Background: Evidence for the effectiveness of exercise programs in the treatment of chronic mechanical low back pain is well documented. In this study, the effect of psychological status on the outcome of a self-help spinal fitness exercise programme was studied. Methods: Patients who were referred by their primary care physicians to the nurse led spinal assessment clinic and met the inclusion criteria were given a spinal exercise booklet, which describes with the aid of diagrams how to perform a series of lumbar core stability exercises for them to practise at home. Back pain related disability was assessed before and 3 months after the exercise program using the Oswestry Disability Index (ODI). Psychological status was measured using the Distress and Risk Assessment Method (DRAM). This classifies patients into 4 groups based on the combination of scores from the Modified Somatic Perception Questionnaire (MSPQ, 13 questions, scored 0–13) and Modified Zung Questionnaire (23 questions scored 0–69): normal, at risk, distressed somatic and distressed depressive. Results: Forty one patients were enrolled into the study (19 male, 22 female, mean age at treatment 45.8 years, age range 22–78 years). The DRAM scores showed that 9 had no psychological disturbance (normal), 17 were at risk, 4 were distressed somatic and 11 distressed depressive. Even though there was a statistically significant improvement in the mean ODI after the exercise program for all DRAM groups, the improvement in the ODI was not significantly different between the four groups (ANOVA, p = 0.596). Conclusions: Our study suggests that the outcome of a spinal fitness exercise programme is not affected by the psychological status of the patient. We conclude that patients should not be excluded from spinal fitness exercise programs on the basis of psychological status

Introduction: Impaired muscle function due to pain or inactivity may contribute to poor outcome following disc surgery. This study investigated the effects of postoperative exercise on pain, disability and spinal function in patients undergoing microdiscectomy. Methods: Volunteers who gave informed consent (65M/26F) were blindly randomised to Exercise and Control groups. All patients were assessed the week before surgery. Posture and range of motion were measured using the 3-Space Fastrak, and back muscle fatigue was evaluated during the Biering-Sorensen test from changes in median frequency of the electromyographic signal. In 42 patients, intra-operative muscle biopsies were obtained. Four weeks after surgery, patients underwent a second functional assessment, after which the Exercise group began a 4-week exercise programme. Further assessments were performed at 2, 6, 12, 18 and 24 months after surgery. Pain, disability and psychological status were evaluated throughout using appropriate questionnaires. Results: Marked type II fibre atrophy was evident at surgery, and this was reflected in pre-operative measures of median frequency. At 4 weeks, both groups showed significant improvements in pain, disability and psychological status but limited improvements in function. At 2 months, the Exercise group showed further improvements in pain, disability and psychological status, increased ranges of motion, and improved fatigability. Increases in initial median frequency in the fatigue test suggested fibre hypertrophy. Further improvements in the Control group generally achieved significance 6–12 months after surgery. Conclusions: Surgery is effective in improving pain, disability and psychological status. Recovery of muscle function after surgery is naturally slow but can be accelerated by post-operative exercise