OBJECTIVES:To investigate adherence to 2 pain threshold protocols during a 26-week exercise intervention for chronic rotator cuff tendinopathy. The main objective was to evaluate adherence to pain thresholds defined as maintaining a consistent difference in pain levels between groups; secondary objectives included adherence to exercise and physiotherapy sessions. DESIGN:Secondary data on adherence to the intervention in a randomized controlled trial with a 1-year follow-up. SETTING:Outpatient clinic in a secondary care setting. PARTICIPANTS:Eighty-four patients (N=84) diagnosed with chronic rotator cuff tendinopathy who were enrolled in the randomized controlled trial, the Pain during Shoulder Exercise trial. Inclusion required shoulder pain for >3 months and a clinical diagnosis of supraspinatus and/or infraspinatus tendinopathy verified by ultrasound. INTERVENTIONS:Participants were assigned to 1 of 2 protocols: exercising with pain allowed up to 5 on the Numeric Pain Rating Scale (PAllow), or exercising below 3 pain (PAvoid). Both groups followed a standardized physiotherapy program and completed pain and exercise logbooks. MAIN OUTCOME MEASURES:Adherence to assigned pain thresholds, logbook completion (pain and exercise), and physiotherapy attendance. RESULTS:Mean exercise pain was 2.8 (SD ±0.21) in PAllow and 1.6 (SD ±0.19) in PAvoid (p<.001), confirming adherence to protocols. Pain logbook adherence declined from 76% to 68%; exercise logbook from 75% to 61%, with no group difference (p=.847). Seventy-five percent of participants attended ≥6 of 8 physiotherapy sessions; no group difference was observed (p=.726). A drop in logbook adherence after week 20 may relate to the final physiotherapy session occurring that week. CONCLUSIONS:Participants adhered to their assigned pain thresholds. Adherence to exercise and physiotherapy was good across groups, though logbook use declined over time, particularly after supervision ended.

PURPOSE:The primary aim was to evaluate if individual suturing of the gastrocnemius and soleus parts of the ruptured Achilles tendon could reestablish their length 1 week post-surgery compared to previously published results using a standard operative technique. We hypothesised that this new suturing technique would reduce the soleus subtendon length by 50% compared to the standard technique 1 week after surgery (primary endpoint). Secondary aims included soleus and gastrocnemius subtendon lengths at 26 weeks. METHODS:The ambi-directional design included a retrospective part using a standard Kessler repair of the tendon as a single structure (n = 24) and a prospective part using a novel surgery that sutured the soleus and gastrocnemius subtendons separately (n = 23). One and 26 weeks after surgery, both groups underwent 3D MRI to determine the length of the soleus and gastrocnemius subtendons. RESULTS:For the soleus subtendon, the individual suturing technique yielded a smaller side-to-side (injured-uninjured) difference (1.9 ± 14.7 mm) compared to the standard surgery (17.0 ± 11.5 mm, p < 0.0001) at week 1 and week 26 (individual 10.7 ± 14.9 mm, standard 21.5 ± 12.7 mm, p < 0.0001), although there was an increase in the individual suturing from week 1 to week 26, (p < 0.05). The side-to-side difference in gastrocnemius subtendon length was not significantly affected by suturing technique but increased with time for individual suturing from week 1 (-1.5 ± 10.6 mm) to week 26 (9.2 ± 9.4 mm, p < 0.0001), and for standard suturing from week 1 (1.8 ± 11.1 mm) to week 26 (8.4 ± 10.9 mm, p < 0.0001). CONCLUSION:Using an individual suturing approach, soleus and gastrocnemius subtendon lengths were nearly restored to normal values 1 week postoperatively. Subsequent elongation of the soleus subtendon over 6 months was also significantly less with individual suturing than standard surgical repair. LEVEL OF EVIDENCE:Level III.

Acute muscle strain injuries belong to the most frequent sports injuries with high recurrence rates. Biopsies obtained from previously strain-injured muscles showed fat intra- and intermuscular, but quantification of fat content in the entire muscle volume following a strain injury has not been performed previously. The aim of the study was to evaluate fat fraction in the injured and the contralateral, uninjured muscle acutely, and 3- and 12-months after a strain injury. DIXON fat fraction was analyzed acutely after the injury, 3- and 12-months post injury in the injured and the contralateral, healthy muscle in 29 individuals with an ultrasound verified strain injury in either the calf or the hamstrings. There was a significant increase in fat content 3 and 12 months post injury in the injured, but not in the contralateral, uninjured muscles. There was a significant negative correlation between the increase in fat fraction and loss of muscle mass, and a significant positive correlation between the enlargement of the aponeurosis and the amount of fat in the injured muscles. Strain injuries lead to a rise in fat fraction in muscles from healthy, sports active individuals. The increased fat fraction appears permanent as fat accumulation in the muscle after the injury was not reversed after 12 months.

OBJECTIVES:Nonpharmacological treatments are recommended for fibromyalgia but are often limited by poor adherence. This study assessed the clinical efficacy of a novel 6-week home-based, low-intensity stretching intervention compared with usual care in patients with fibromyalgia, with the Revised Fibromyalgia Impact Questionnaire (FIQ-R) total score as the primary outcome. DESIGN:Parallel, waitlist-controlled randomized trial. SETTING:Participants were recruited from the general community. PARTICIPANTS:A total of 58 adults with fibromyalgia were enrolled. INTERVENTION:Participants were randomly assigned (1:1), stratified by sex, to 6 weeks of daily low-intensity home-based stretching exercises (6 min/d) or to usual care. MAIN OUTCOME MEASURES:The primary outcome was the change in the FIQ-R total score from baseline to follow-up, analyzed under the intention-to-treat principle. RESULTS:Between October 24, 2024, and May 22, 2025, 89 patients were screened, and 58 were randomly assigned to either the intervention group (n=29) or the control group (n=29). The average self-reported adherence rate to the intervention was 83%. There was a significant group-by-time interaction for FIQ-R total score (F[1,56]=11.30; P<.001; partial η²=0.17), indicating greater improvement in the intervention group. From baseline to follow-up, mean FIQ-R total score decreased by 9.7 points (95% confidence interval [CI], -15.0 to -4.4; P<.001), corresponding to an 18.7% improvement in the intervention group, compared with a nonsignificant change of 0.8 points (-2.7 to 4.2; P=.66) in the control group. CONCLUSIONS:Low-intensity, high-frequency home-based stretching produced significant, clinically meaningful improvements in the FIQ-R total score compared with usual care, suggesting its potential as a feasible, well-tolerated nonpharmacological treatment option. Future research should confirm these findings in longer-term, sex-balanced trials.

Patellar tendinopathy (PT) is a debilitating overuse injury, and one of the current recommended treatments is heavy slow resistance training (HSRT); Recently, low-load resistance training combined with blood flow restriction (LL-BFRT) has been advocated as a clinically relevant rehabilitation tool for PT since it does not involve large joint and tissue stresses and may accelerate recovery. This study aimed to investigate the effect of LL-BFRT compared with HSRT at 3, 6, 12 (primary endpoint), and 52 weeks. Participants with chronic unilateral PT were randomized to a 12-week rehabilitation program based on either LL-BFRT (n = 16) or HSRT (n = 20). The primary outcome was pain (numerical rating scale (NRS) 0-10) during a single-leg decline squat (SLDS). Secondary outcome variables included the Victorian Institute of Sports Assessment-Patella questionnaire (VISA-P), maximal isometric knee extensor strength, patellar tendon morphology assessed by ultrasonography (swelling, vascularization), and magnetic resonance imaging (MRI). Comparable clinically relevant improvements in pain (NRS during SLDS, least squares mean ± SEM) were observed in LL-BFRT (LL-BFRT: 0 weeks 3.9 ± 0.5, 12 weeks 2.2 ± 0.5, 52 weeks 1.8 ± 0.5) and HSRT (0 weeks 4.2 ± 0.4, 12 weeks 2.2 ± 0.4, 52 weeks 1.1 ± 0.5) (p < 0.0001). Likewise, clinically relevant improvements were reported on the VISA-P score. LL-BFRT and HSRT resulted in comparable short-term and long-term clinical improvements in males with chronic PT. These data advocate that LL-BFRT represents an effective rehabilitation tool in the treatment of chronic PT, while preventing high joint and tendon loads. Trial Registration: Clinicaltrials.org (NCT04550013).

Mechanical loading drives structural and functional improvements in muscle and tendon, protecting against injury at their interface, at the myotendinous junction (MTJ), and within the tendon matrix. However, the early cellular and molecular events that initiate these adaptations in humans remain poorly understood. To investigate this, we applied single-nucleus RNA sequencing and in situ hybridization to map the acute transcriptional response of the human muscle-tendon unit to a single bout of eccentric resistance exercise, with a focus on extracellular matrix (ECM) regulation. We identified four transcriptionally distinct fibroblast subtypes expressing key ECM components, including COL1A1 and DCN. Three of these subtypes were localized to the tendon and responded to exercise: two were spatially restricted to the collagen fascicles or the MTJ, while the third, enriched in the interfascicular matrix (IFM), exhibited the strongest response. This IFM population, marked by PDGFRA, upregulated PRG4 and VCAN, ECM genes linked to tissue lubrication and resilience. In parallel, exercise induced dynamic ECM regulation in myonuclei, particularly in a distinct subset of type II myonuclei at the MTJ, that expanded in number and robustly upregulated COL22A1, a collagen essential for MTJ integrity. Together, these findings uncover a spatially organized, cell type-specific program of ECM remodeling in response to mechanical load, offering new insight into the early molecular events of human muscle-tendon adaptation.NEW & NOTEWORTHY We provide the first high-resolution, in vivo single-nucleus map of the acute human muscle-tendon response to mechanical loading. Within 4 hours of resistance exercise, spatially distinct tendon fibroblasts and myonuclei activate coordinated extracellular matrix programs. Interfascicular fibroblasts upregulate PRG4 and VCAN in the tendon, while myonuclei at the myotendinous junction induce COL22A1 and LAMA2. These findings reveal a new principle of human mechanobiology, where exercise rapidly engages niche-specific programs to initiate extracellular matrix adaptation.

Injuries to the musculoskeletal system are frequent in elite sports and they are detrimental to athletic performance. This can be due to, for example, (1) overuse disorders of tendon (tendinopathy) that not only lower the training efficiency but also, in many cases, are career-ending for the athlete due to pain; (2) acute muscle strain injury that both causes prolonged absence from competition and results in many re-injuries; or (3) tendon rupture that, apart from a very long rehabilitation period, will also result in many athletes never resuming their original high level of competitive sports. For all three injury examples, several evidence-based prevention programs and treatments are available, and yet the incidence of these injuries remains high and single treatments often provide only partial recovery. In this paper, we highlight the current treatments of these three conditions and focus on the unsolved dilemmas that exist in these sports injuries.

BACKGROUND: This protocol was developed to describe the design of a randomised controlled trial that will examine the clinical efficacy of a 6-week, novel, home-based stretching programme compared with usual care on the effect of symptoms experienced by patients with fibromyalgia. The hypothesis is that the total score of the Fibromyalgia Impact Questionnaire (FIQ-R) and other fibromyalgia symptoms will improve 6 weeks following the stretching intervention compared with usual care. METHODS: Fifty-eight adults under 65 years of age diagnosed with fibromyalgia will be recruited for this study. Participants will be randomised into an intervention group and a control group (waitlist). Randomisation will be stratified by sex. The intervention group will perform 6 weeks of daily stretching exercises for 6 min-a day. The control group will maintain usual care. A mHealth app will support stretching adherence. The primary outcome will be the total score of the Revised Fibromyalgia Impact Questionnaire (FIQ-R). The secondary outcomes include regional and widespread pain sensitivity, range of motion, quality of life (SF-36), mental and physical functioning and adherence. Evaluations will be performed at baseline, following 6 weeks of daily stretches (primary endpoint) and 6 months after the termination of the intervention period (secondary endpoint). DISCUSSION: By investigating the clinical efficacy of a 6-week, novel, home-based stretching programme, we hope to provide applicable and generalisable knowledge about the efficacy of stretching exercises that can potentially help ease the burden of symptoms experienced by patients with fibromyalgia. TRIAL REGISTRATION: NTC, NCT06487741. Registered on 24 June 2024.

The myotendinous junction (MTJ) is a weak link in the musculoskeletal system. Here, we isolated the tips of single myofibres from healthy (non-injured) human hamstring muscles for confocal microscopy (n=6) and undertook RNAscope in situ hybridisation (n=6) to gain insight into the profiles of cells and myonuclei in this region, in a fibre type manner. A marked presence of mononuclear cells was observed coating the myofibre tips (confirmed by serial block face scanning electron microscopy and cryosection immunofluorescence), with higher numbers for type I (median 29; range 16-63) than type II (16; 9-23) myofibres (P<0.05). The number of these cells expressing COL22A1 was comparable between fibre types. Myonuclear number and density gradually increased from the myofibre proper towards the tip for both fibre types (P<0.05). COL22A1 was expressed by similar proportions of myonuclei in type I (median 26%; range 13-56) and type II (19%; 3-67) myofibre tips. 70% of the COL22A1-positive nuclei in the MTJ region were myonuclei, and the remaining 30% were MTJ cells. This insight refines our fundamental understanding of the human MTJ at the cell and structural levels.

Menstrual dysfunction (MD) in female athletes might be indicative of the syndrome of relative energy deficiency in sports (REDs), associated with, e.g., impaired bone health, an increased risk of injury, and decreased performance. In the present study, we investigated differences in objective indicators of REDs, bone mineral density (BMD), and blood-based biomarkers in female elite athletes with self-reported MD or eumenorrhoea (CON) from mixed sport disciplines. Athletes reporting < 9 menstrual bleedings within the last year were recruited in the MD group, whereas eumenorrheic athletes with no symptoms of eating disorders were recruited for CON. Of the 24 athletes included, 19 completed the examinations (9 MD; 10 CON, mean age ± SD: 24.8 ± 5.5 years). Dual-energy x-ray absorptiometry (DXA) was used to assess body composition and BMD. Fasted rested blood sampling was performed to assess blood-based biomarkers of bone and endocrine status. Two MD athletes were excluded from the analysis due to suspected polycystic ovary syndrome. Results showed that MD was associated with lower BMD Z-scores across several sites compared to CON (between-group differences ± SE); whole-body Z-score: -1.4 ± 0.5, p=0.03; lumbar spine Z-score: -1.4 ± 0.6, p=0.03; proximal femur: -1.6 ± 0.6, p=0.02). However, no between-group differences in biomarkers of bone turnover were observed. MD was associated with lower plasma concentrations of luteinizing hormone (p=0.02), prolactin (p < 0.001), and free T 3 (p=0.01). In conclusion, the present data indicate impairment in bone health and endocrine homeostasis in female elite athletes with current MD and underline the importance of MD as a potential indicator of REDs in female elite athletes. Furthermore, these findings call for regular screening of symptoms for early identification of athletes at risk in all sport disciplines and more education of athletes, coaches, and medical staff regarding this issue.

People with fibromyalgia face physical and cognitive impairments and are often intolerant to physical activity, making adherence to physical therapy a significant challenge. This prospective pre-post feasibility study aimed to explore the feasibility and acceptability of a six-week home-based stretching intervention for people with fibromyalgia. People aged 18–55 years diagnosed with fibromyalgia were eligible for participation. Participants were offered a home-based stretching intervention with weekly follow-up via a mHealth app. Semi-structured online focus group interviews were conducted to gain insight into the participants’ experience and acceptance of the intervention. Quantitative assessments included the Revised Fibromyalgia Impact Questionnaire, the SF-36, pressure pain thresholds, range of motion, and self-reported adherence. 12 females were recruited over 43 days. One participant withdrew from the study due to illness. The adherence rate was high. Four major themes emerged from the interviews: (1) Factors motivating participation, (2) The advantages of exercising at home, (3) Influence of weekly communication and (4) Potential areas for improvement. Qualitative findings suggest that the intervention was well tolerated and easily implemented in daily life. There were clinically relevant improvements in health-related quality of life, physical health, and mental health scores. A six-week home-based stretching program, supervised via an mHealth application, proved feasible and acceptable for individuals with FM and showed promising clinical outcomes. Based on insights from this feasibility study, an RCT is planned to evaluate whether the program of home-based stretching exercises provides greater benefits than usual care alone in enhancing quality of life and functional outcomes in patients with FM. Trial registration number: NCT06176053. Date of registration: 12/08/2023.

Metabolic flexibility in skeletal muscle is essential for maintaining healthy glucose and lipid metabolism, and its dysfunction is closely linked to metabolic diseases. Exercise enhances metabolic flexibility, making it an important tool for discovering mechanisms that promote metabolic health. Here we show that pantothenate kinase 4 (PanK4) is a new conserved exercise target with high abundance in muscle. Muscle-specific deletion of PanK4 impairs fatty acid oxidation which is related to higher intramuscular acetyl-CoA and malonyl-CoA levels. Elevated acetyl-CoA levels persist regardless of feeding state and are associated with whole-body glucose intolerance, reduced insulin-stimulated glucose uptake in glycolytic muscle, and impaired glucose uptake during exercise. Conversely, increasing PanK4 levels in glycolytic muscle lowers acetyl-CoA and enhances glucose uptake. Our findings highlight PanK4 as an important regulator of acetyl-CoA levels, playing a key role in both muscle lipid and glucose metabolism.

To assess the level of agreement among experts on the heel raise exercise parameters that influence midportion and insertional Achilles tendinopathy (AT) rehabilitation outcomes.An international expert panel in AT rehabilitation was invited to complete a three-round Delphi survey. In the first two rounds, experts were asked to review a pregenerated list of exercise parameters (based on the heel raise exercise) and rate their perceived influence on rehabilitation outcome, using a 5-point Likert scale. For each parameter, consensus criteria for major influence on rehabilitation were (a) median≥4, (b) ≥75% of scoring 4 or 5 and (c) IQR≤1. The third round aimed to rank the exercise parameters according to importance (from most to least important) during rehabilitation.17 experts participated in the entire Delphi process. A total of 16 exercise parameters were assessed, of which 4 (intensity of contraction, total time under tension, number of repetitions and sets, type of contraction) reached consensus as having a major influence on rehabilitation for midportion AT and 3 reached consensus for insertional AT (range of ankle dorsiflexion during the exercise, intensity of contraction, number of repetitions and sets). The rankings of parameters that reached consensus showed that contraction intensity was perceived as the most important variable for midportion AT rehabilitation, while range of ankle dorsiflexion was deemed the most important variable for insertional AT rehabilitation.This study identified key exercise parameters for mid-portion and insertional AT rehabilitation based on expert opinion. This information should assist practitioners in optimising their approach to deliver more effective, patient-specific exercises for AT rehabilitation.

Time under tension (TUT) is an important variable in resistance training (RT). A stretch sensor (Bandcizer) attached to an elastic band during RT can quantify TUT reliably. Objective To explore adherence to prescribed TUT for elastic band RT with the Bandcizer during supervised and unsupervised RT at different time points. Methods 22 men and women (66.2 ±2.1 years) performed one supervised and two unsupervised sessions weekly of elastic band RT for the upper and lower extremities with the Bandcizer during a 25-week period. Prescribed TUT was 4 s/repetition. Bandcizer data were extracted from week: 1, 8, and median 24. The effects of time point and supervision on adherence (%) to TUT and number of repetitions were analyzed by Two-way ANOVA. Results During supervised sessions, adherence to prescribed TUT was 79 ±4%, 60 ±4%, and 53 ±5% in week: 1, 8, and median 24, respectively (p < 0.001). There was no difference in adherence between supervised and unsupervised sessions at any time points. Adherence to the prescribed number of repetitions in each training session was close to 100%. Conclusion Adherence to prescribed TUT was low during both supervised and unsupervised, home-based elastic band RT and decreased over time despite weekly supervision. Our results highlight the need to focus on TUT when planning and implementing elastic band resistance training in retirement age individuals.

Decline in mitochondrial function associates with decreased muscle mass and strength in multiple conditions, including sarcopenia and type 2 diabetes. Optimal treatment could include improving mitochondrial function, however, there are limited and equivocal data regarding the molecular cues controlling muscle mitochondrial plasticity. Here we uncover the mitochondrial-mRNA-stabilizing protein SLIRP, in complex with LRPPRC, as a PGC-1α target that regulates mitochondrial structure, respiration, and mitochondrially-encoded-mRNA pools in skeletal muscle. Exercise training effectively counteracted mitochondrial defects induced by loss of LRPPRC/SLIRP, despite sustained low mitochondrially-encoded-mRNA pools, via increased mitoribosome translation capacity. In humans, exercise training robustly increased muscle SLIRP and LRPPRC protein content across exercise modalities and sexes, yet this increase was less prominent in subjects with type 2 diabetes. Our work identifies a mechanism of post-transcriptional mitochondrial regulation in skeletal muscle through mitochondrial mRNA stabilization. It emphasizes exercise as an effective approach to alleviate mitochondrial defects by possibly increasing mitoribosome capacity.

Purpose. To assess children's physical function and subjective knee status 1 and 3 years after anterior cruciate ligament (ACL) reconstruction. It was hypothesised that there was no difference between the operated and normal legs in relation to physical strength and function, that there was <-2 mm side-to-side difference in knee laxity, and that the subjective knee function was better 3 years after ACL reconstruction compared to 1 year after. Methods. Children (<16 years of age) who had an ACL reconstruction had follow-up with physical function tests (four hop tests and strength measurement in a power rig [PR]), anterior knee laxity (measured using a Rolimeter) and patient-reported outcome measures (Pedi-International Knee Documentation Committee [IKDC] and Knee injury and Osteoarthritis Outcome Score [KOOS]-Child) 1 and 3 years postoperatively. Changes from 1- to 3-year follow-up were evaluated with a paired t test. Results. Out of 148 ACL reconstructed children, 60 had all measures. The four hop tests and the PR all yielded a Limb Symmetry Index >90% at both follow-ups. There was a significant improvement from 1- to 3-year follow-up in two-hop tests (6 m on time and crossover hop). Side-to-side knee laxity was >2 mm in four children at 1- and 3-year tests. Pedi-IKDC scores increased, and KOOS-Child improved significantly from 1 to 3 years in two of the five domains: 'Sport' and 'Quality of life', but scores were lower than in a cohort of normal children. Conclusion. The children had good objective physical function 1 and 3 years after ACL reconstruction. However, scores from the KOOS-Child sport-specific function and quality of life domains were lower than in normal children.

BACKGROUND:Stretching exercises have effects on local and widespread pain sensitivity. A dose-response relationship may exist between the analgesic effect and the intensity of stretching, such that a higher intensity of stretching may generate a larger reduction in analgesic response, but this remains to be studied. This study aimed to examine the dose-response relationship between stretching intensity and the analgesic effect. METHODS:A randomized, repeated-measures crossover study was performed to examine the effect of stretching to the first point of pain onset and stretching to the point of a sensation of stretching (discomfort). The primary outcome was regional and distant pressure pain thresholds. RESULTS:Thirty-one participants (n = 24 female) were available for analysis. We observed a 22.2% increase in regional pressure pain thresholds (93.2 kPa, p = 0.001) and a 15.0% increase in distant pressure pain thresholds (50.9 kPa, p = 0.012) following stretching to the point of stretch. We observed a 20.0% increase in regional pressure pain thresholds (90.3 kPa, p = 0.001) and a 15.1% increase in distant pressure pain thresholds (52.1 kPa, p = 0.004) following stretching to the point of pain. CONCLUSIONS:The results showed that local and widespread pain sensitivity decreased following acute stretching, regardless of stretching intensity. No differences in pain sensitivity were found between stretching to the point of stretch or stretching to the first onset of pain. Thus, the results showed no evidence of a dose-response relationship between stretching intensity and the analgesic effect. SIGNIFICANCE:The study showed a significant acute hypoalgesic effect of stretching exercises regardless of stretching intensity. This may have appropriate clinical implications for patients with musculoskeletal and nociplastic pain.