Exercise treatment effect modifiers in persistent low back pain: an individual participant data meta-analysis of 3514 participants from 27 randomised controlled trials.

BACKGROUND: Low back pain is one of the leading causes of disability worldwide. Exercise therapy is widely recommended to treat persistent non-specific low back pain. While evidence suggests exercise is, on average, moderately effective, there remains uncertainty about which individuals might benefit the most from exercise. METHODS: In parallel with a Cochrane review update, we requested individual participant data (IPD) from high-quality randomised clinical trials of adults with our two primary outcomes of interest, pain and functional limitations, and calculated global recovery. We compiled a master data set including baseline participant characteristics, exercise and comparison characteristics, and outcomes at short-term, moderate-term and long-term follow-up. We conducted descriptive analyses and one-stage IPD meta-analysis using multilevel mixed-effects regression of the overall treatment effect and prespecified potential treatment effect modifiers. RESULTS: We received IPD for 27 trials (3514 participants). For studies included in this analysis, compared with no treatment/usual care, exercise therapy on average reduced pain (mean effect/100 (95% CI) -10.7 (-14.1 to -7.4)), a result compatible with a clinically important 20% smallest worthwhile effect. Exercise therapy reduced functional limitations with a clinically important 23% improvement (mean effect/100 (95% CI) -10.2 (-13.2 to -7.3)) at short-term follow-up. Not having heavy physical demands at work and medication use for low back pain were potential treatment effect modifiers-these were associated with superior exercise outcomes relative to non-exercise comparisons. Lower body mass index was also associated with better outcomes in exercise compared with no treatment/usual care. This study was limited by inconsistent availability and measurement of participant characteristics. CONCLUSIONS: This study provides potentially useful information to help treat patients and design future studies of exercise interventions that are better matched to specific subgroups. PROTOCOL PUBLICATION: https://doi.org/10.1186/2046-4053-1-64.

Chinese translation and validation of the Sport Concussion Assessment Tool 3 (SCAT3).

OBJECTIVE: The aim of this study was to translate, adapt and validate the Sport Concussion Assessment Tool 3rd edition (SCAT3), a test for assessing athletes for concussion, into the Chinese context. METHODS: Translation and adaptation were performed in several stages, which included forward translation by two independent teams, translation merging, backward translation, reviews by both native Cantonese-speaking and Mandarin-speaking multidisciplinary expert panels (n=49) for semantic and conceptual equivalence and reviews by pitch-side physiotherapists (n=18) as end-users of the SCAT3 and rugby players (n=11) for face validity. The Serial 3 s subtraction test was used as a substitute for the Months Backward Test (MBT) for measures of concentration in the Standardized Assessment of Concussion subscale. English-speaking and Chinese-speaking rugby players (n=52) were recruited to perform these tests to assess the level of difficulty, time for completion and accuracy. Inter-rater and test-retest reliability were assessed in 33 and 38 healthy young individuals, respectively. RESULTS: Despite the longer mean completion time (p<0.05) for the Serial 3 s test, no significant difference was found in the percentage accuracy between MBT and the Serial 3 s test. No significant difference was found in either the percentage accuracy or completion time between English-speaking and Cantonese-speaking rugby players. All subscales in the Chinese SCAT3 had excellent levels of inter-rater reliability for all items (ICC2,1 range: 0.96-0.99) but a low to moderate test-retest reliability (ICC3,2 range: 0.32-0.65). The mean completion time of the Chinese SCAT3 was 10.6±1.1 min. CONCLUSION: Chinese SCAT3 is a valid instrument for pitch-side assessment of concussed Chinese-speaking athletes.

Overexpression of Mechano-Growth Factor Modulates Inflammatory Cytokine Expression and Macrophage Resolution in Skeletal Muscle Injury.

In muscle regeneration, infiltrating myeloid cells, such as macrophages mediate muscle inflammation by releasing key soluble factors. One such factor, insulin-like growth factor 1 (IGF-1), suppresses inflammatory cytokine expression and mediates macrophage polarization to anti-inflammatory phenotype during muscle injury. Previously the IGF-1Ea isoform was shown to be anti-inflammatory. Another isoform of IGF-1, mechano-growth factor (MGF), is structurally and functionally distinct from IGF-1Ea, but its role in muscle inflammation has not yet been characterized. In this study, we hypothesized that MGF expression in muscle injury modulates muscle inflammation. We first investigated changes of transcription and expression of MGF in response to skeletal muscle injury induced by cardiotoxin (CTX) in vivo. At 1-2 days post-injury, Mgf expression was significantly upregulated and positively correlated with that of inflammatory cytokines. Immunostaining revealed that infiltration of neutrophils and macrophages coincided with Mgf upregulation. Furthermore, infiltrating neutrophils and macrophages expressed Mgf, suggesting their contribution to MGF upregulation in muscle injury. Macrophages seem to be the predominant source of MGF in muscle injury, whereas neutrophil depletion did not affect muscle Mgf expression. Given the association of MGF and macrophages, we then studied whether MGF could affect macrophage infiltration and polarization. To test this, we overexpressed MGF in CTX-injured muscles and evaluated inflammatory marker expression, macrophage populations, and muscle regeneration outcomes. MGF overexpression delayed the resolution of macrophages, particularly the pro-inflammatory phenotype. This coincided with upregulation of inflammatory markers. Annexin V-based flow cytometry revealed that MGF overexpression likely delays macrophage resolution by limiting macrophage apoptosis. Although MGF overexpression did not obviously affect muscle regeneration outcomes, the findings are novel and provide insights on the physiological roles of MGF in muscle regeneration.

Risk factors that predict severe injuries in university rugby sevens players.

OBJECTIVES: To investigate injury incidence and the influence of physical fitness parameters on the risk of severe injuries in players on rugby sevens university teams. DESIGN: Prospective cohort study. METHODS: Rugby players from three universities (N=104; 90M:14F; 20.6±1.9years) were recruited before the beginning of the season. Players underwent pre-season assessments of power, strength, speed, agility, endurance, stability, and flexibility. Throughout the season, rugby-related injury and exposure data were collected. Potential predictor variables were analyzed using Cox proportional regression model to identify risk factors associated with severe injuries (time loss>28days). RESULTS: Thirty-one injuries occurred during the rugby season. The match and training injury incidence rates were 59.3 injuries and 3.3 injuries per 1000 player-hours, respectively. Lower limb injuries were most common and most severe. The ankle joint was the most prevalent site of injury, and ligamentous injury was most common (48.4%). Nine severe injuries were sustained resulting in an average time loss of 51.3±14.6days. Female (hazard ratio [HR]=8.35; 95% confidence intervals [CI]=2.01-34.8), slower (HR=3.51; 95% CI=1.17-10.5), and less agile (HR=2.22; 95% CI=1.26-3.92) players as well as those with hip flexors tightness (HR=1.12; 95% CI=1.00-1.25) were at significantly greater risk for sustaining severe injuries. CONCLUSIONS: Limited studies are available on risk factors associated with amateur rugby players in the Sevens version. The development of gender-specific injury prevention measures that emphasize speed and agility training, and improve hip flexor extensibility may be important to reduce the risk of severe injuries.

Acute Effects of Kinesio Taping on Knee Extensor Peak Torque and Stretch Reflex in Healthy Adults.

Kinesio Tex tape (KT) is used to prevent and treat sports-related injuries and to enhance muscle performance. It has been proposed that the direction of taping may either facilitate or inhibit the muscle by having different effects on cutaneous receptors that modulate excitability of the motor neurons. This study had 2 goals. First, we wished to determine if KT application affects muscle performance and if the method of application facilitates or inhibits muscle performance. This was assessed by measuring isokinetic knee extension peak torque in the knee extensor. Second, we assessed neurological effects of taping on the excitability of the motor neurons by measuring the reflex latency and action potential by electromyography (EMG) in the patellar reflex. The study was a single-blind, placebo-controlled crossover trial with 28 healthy volunteers with no history of knee injuries. Participants received facilitative KT treatment, inhibitory KT treatment, or Hypafix taping of the knee extensor. There were significant differences in the peak torque between 3 treatments (F(2,54) = 4.873, P < 0.01). Post hoc analysis revealed that facilitative KT treatment resulted in higher knee extensor peak torque performance than inhibitory KT treatment (P = 0.036, effect size 0.26). There were, however, no significant differences in the reflex latency (F(2,54) = 2.84, P = 0.067) nor in the EMG values (F(2,54) = 0.18, P = 0.837) in the patellar reflex between the 3 taping applications. The findings suggest that the direction of KT application over the muscle has specific effects on muscle performance. Given the magnitude of effect is small, interpretation of clinical significance should be considered with caution. The underlying mechanism warrants further investigation.

Effects of Cold Water Immersion on Muscle Oxygenation During Repeated Bouts of Fatiguing Exercise: A Randomized Controlled Study.

Postexercise cold water immersion has been advocated to athletes as a means of accelerating recovery and improving performance. Given the effects of cold water immersion on blood flow, evaluating in vivo changes in tissue oxygenation during cold water immersion may help further our understanding of this recovery modality. This study aimed to investigate the effects of cold water immersion on muscle oxygenation and performance during repeated bouts of fatiguing exercise in a group of healthy young adults. Twenty healthy subjects performed 2 fatiguing bouts of maximal dynamic knee extension and flexion contractions both concentrically on an isokinetic dynamometer with a 10-min recovery period in between. Subjects were randomly assigned to either a cold water immersion (treatment) or passive recovery (control) group. Changes in muscle oxygenation were monitored continuously using near-infrared spectroscopy. Muscle performance was measured with isokinetic dynamometry during each fatiguing bout. Skin temperature, heart rate, blood pressure, and muscle soreness ratings were also assessed. Repeated measures ANOVA analysis was used to evaluate treatment effects. The treatment group had a significantly lower mean heart rate and lower skin temperature compared to the control group (P < 0.05). Cold water immersion attenuated a reduction in tissue oxygenation in the second fatiguing bout by 4% when compared with control. Muscle soreness was rated lower 1 day post-testing (P < 0.05). However, cold water immersion had no significant effect on muscle performance in subsequent exercise. As the results show that cold water immersion attenuated decreased tissue oxygenation in subsequent exercise performance, the metabolic response to exercise after cold water immersion is worthy of further exploration.

The involvement of transient receptor potential canonical type 1 in skeletal muscle regrowth after unloading-induced atrophy.

KEY POINTS: Decreased mechanical loading results in skeletal muscle atrophy. The transient receptor potential canonical type 1 (TRPC1) protein is implicated in this process. Investigation of the regulation of TRPC1 in vivo has rarely been reported. In the present study, we employ the mouse hindlimb unloading and reloading model to examine the involvement of TRPC1 in the regulation of muscle atrophy and regrowth, respectively. We establish the physiological relevance of the concept that manipulation of TRPC1 could interfere with muscle regrowth processes following an atrophy-inducing event. Specifically, we show that suppressing TRPC1 expression during reloading impairs the recovery of the muscle mass and slow myosin heavy chain profile. Calcineurin appears to be part of the signalling pathway involved in the regulation of TRPC1 expression during muscle regrowth. These results provide new insights concerning the function of TRPC1. Interventions targeting TRPC1 or its downstream or upstream pathways could be useful for promoting muscle regeneration. ABSTRACT: Decreased mechanical loading, such as bed rest, results in skeletal muscle atrophy. The functional consequences of decreased mechanical loading include a loss of muscle mass and decreased muscle strength, particularly in anti-gravity muscles. The purpose of this investigation was to clarify the regulatory role of the transient receptor potential canonical type 1 (TRPC1) protein during muscle atrophy and regrowth. Mice were subjected to 14 days of hindlimb unloading followed by 3, 7, 14 and 28 days of reloading. Weight-bearing mice were used as controls. TRPC1 expression in the soleus muscle decreased significantly and persisted at 7 days of reloading. Small interfering RNA (siRNA)-mediated downregulation of TRPC1 in weight-bearing soleus muscles resulted in a reduced muscle mass and a reduced myofibre cross-sectional area (CSA). Microinjecting siRNA into soleus muscles in vivo after 7 days of reloading provided further evidence for the role of TRPC1 in regulating muscle regrowth. Myofibre CSA, as well as the percentage of slow myosin heavy chain-positive myofibres, was significantly lower in TRPC1-siRNA-expressing muscles than in control muscles after 14 days of reloading. Additionally, inhibition of calcineurin (CaN) activity downregulated TRPC1 expression in both weight-bearing and reloaded muscles, suggesting a possible association between CaN and TRPC1 during skeletal muscle regrowth.

Optimizing Electrical Stimulation for Promoting Satellite Cell Proliferation in Muscle Disuse Atrophy.

OBJECTIVE: The aim of this study was to investigate the optimal electrical stimulation (ES) protocol in attenuating disuse muscle atrophy by influencing satellite cell activity. DESIGN: This study used a pretest-posttest design. Six ES protocols of different duration (3 hrs day or 2 × 3 hrs day) and frequencies (2, 10, or 20 Hz) were applied on the soleus muscle in mice (n = 8 in each group) that were hindlimb-suspended for 14 days. Muscle mass, cross-sectional area and fiber-type composition, and peak tetanic force of the muscles were measured. Immunohistochemical staining was used to evaluate satellite cell content, activation, proliferation, and differentiation. Cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL) assay. RESULTS: ES at 2 Hz for 2 × 3 hrs day achieved the best effect in attenuating the loss of muscle fiber cross-sectional area and force. This stimulation parameter led to a 1.2-fold increase in satellite cell proliferation and was effective in rescuing cells from apoptosis. Besides, satellite cells in the atrophic muscles required different stimulation protocols for different cellular activities such as activation, proliferation, and myogenic differentiation. CONCLUSIONS: This study showed that ES at 2 Hz for 2 × 3 hrs day is the optimal protocol for counteracting muscle disuse atrophy.

Core muscle activity during suspension exercises.

OBJECTIVES: Suspension exercise has been advocated as an effective means to improve core stability among healthy individuals and those with musculoskeletal complaints. However, the activity of core muscles during suspension exercises has not been reported. In this study, we investigated the level of activation of core muscles during suspension exercises within young and healthy adults. DESIGN: The study was conducted in a controlled laboratory setting. METHODS: Surface electromyographic (sEMG) activity of core muscles (rectus abdominis, external oblique, internal oblique/transversus abdominis, and superficial lumbar multifidus) during four suspension workouts (hip abduction in plank, hamstring curl, chest press, and 45° row) was investigated. Muscle activity during a 5-s hold period of the workouts was measured by sEMG and normalized to the individual's maximal voluntary isometric contraction (MVIC). RESULTS: Different levels of muscle activation were observed during the hip abduction in plank, hamstring curl, and chest press. Hip abduction in plank generated the highest activation of most abdominal muscles. The 45° row exercise generated the lowest muscle activation. CONCLUSIONS: Among the four workouts investigated, the hip abduction in plank with suspension was found to have the strongest potential strengthening effect on core muscles. Also, suspension training was found to generate relatively high levels of core muscle activation when compared with that among previous studies of core exercises on stable and unstable support surfaces.

Acute effects of kinesio taping on knee extensor peak torque and electromyographic activity after exhaustive isometric knee extension in healthy young adults.

OBJECTIVE: To evaluate the effect of Kinesio Tex tape and its method of application, Kinesio Taping (KT) on knee extensor performance before and after an exhaustive isometric knee extension exercise. DESIGN: Single-blinded, randomized control trial. SETTING: Centre for Sports Training and Rehabilitation at The Hong Kong Polytechnic University. PARTICIPANTS: Twenty-six healthy volunteers with no history of knee injuries. INTERVENTIONS: Subjects were randomized to either the KT or sham taping group. MAIN OUTCOME MEASURES: The effects of KT on the neuromuscular performance of the knee extensors were measured before and after KT application, and immediately and 5 and 10 minutes after an exhaustive isometric knee extension exercise. RESULTS: Within-group analyses revealed a significant effect of time on the peak torque in isometric knee extension (F2.73,65.44 = 24.5, P < 0.001), but no significant group (F2.73,65.44 = 2.13, P = 0.11) or interaction (F1,24 = 0.59, P = 0.45) effect. A significant time effect (F2.52,60.14 = 3.75, P = 0.02) and a significant time × group interaction (F1,24 = 4.59, P = 0.04) was found for the rate of peak torque development. Post hoc comparisons revealed significantly higher rates in the intervention group (F1,24 = 4.594, P = 0.04) over all 5 tests. No significant effects of time (F4,96 = 0.88, P = 0.48; F2.56,61.35 = 2.75, P = 0.06), group (F4,96 = 0.56, P = 0.69; F2.56,61.35 = 1.16, P = 0.33), or time × group interaction (F1,24 = 2.77, P = 0.11; F1,24 = 0.20, P = 0.66) were found for either the electromechanical delay or electromyographic results, respectively. CONCLUSIONS: The present study suggests that KT shortens the time required to generate peak torque during isometric knee extension, which has important implications for sports performances that require the rapid generation of peak muscular force. CLINICAL RELEVANCE: Kinesio taping is commonly seen in the sports arena. The popularity is presumably due to the general belief in its injury prevention and enhancement of muscle performance. The results of the present findings suggested that KT shortens the time to reach peak torque generation. Aside from this, there is no other significant positive effect on muscle performance. Further investigation on the effects of KT on muscle performance is warranted.

Acute Whole-Body Vibration does not Facilitate Peak Torque and Stretch Reflex in Healthy Adults.

The acute effect of whole-body vibration (WBV) training may enhance muscular performance via neural potentiation of the stretch reflex. The purpose of this study was to investigate if acute WBV exposure affects the stretch induced knee jerk reflex [onset latency and electromechanical delay (EMD)] and the isokinetic knee extensor peak torque performance. Twenty-two subjects were randomly assigned to the intervention or control group. The intervention group received WBV in a semi-squat position at 30° knee flexion with an amplitude of 0.69 mm, frequency of 45 Hz, and peak acceleration of 27.6 m/s(2) for 3 minutes. The control group underwent the same semii-squatting position statically without exposure of WBV. Two-way mixed repeated measures analysis of variance revealed no significant group effects differences on reflex latency of rectus femoris (RF) and vastus lateralis (VL; p = 0.934 and 0.935, respectively) EMD of RF and VL (p = 0.474 and 0.551, respectively) and peak torque production (p = 0.483) measured before and after the WBV. The results of this study indicate that a single session of WBV exposure has no potentiation effect on the stretch induced reflex and peak torque performance in healthy young adults. Key PointsThere is no acute potentiation of stretch reflex right after whole body vibration.Acute whole body vibration does not improve mus-cle peak torque performance in healthy young adults.

Adaptive responses of TRPC1 and TRPC3 during skeletal muscle atrophy and regrowth.

INTRODUCTION: We assessed the time-dependent changes of transient receptor potential canonical type 1 (TRPC1) and TRPC3 expression and localization associated with muscle atrophy and regrowth in vivo. METHODS: Mice were subjected to hindlimb unloading for 7 or 14 days (7U, 14U) followed by 3, 7, or 14 days of reloading (3R, 7R, 14R). RESULTS: Soleus muscle mass and tetanic force were reduced significantly at 7U and 14U and recovered by 14R. Recovery of muscle fiber cross-sectional area was observed by 28R. TRPC1 mRNA was unaltered during the unloading-reloading period. However, protein expression remained depressed through 14R. Decreased localization of TRPC1 to the sarcolemma was observed. TRPC3 mRNA and protein expression levels were decreased significantly during the early phase of reloading. CONCLUSIONS: Given the known role of these channels in muscle development, changes observed in TRPC1 and TRPC3 may relate closely to muscle atrophy and remodeling processes.

Pathways of Ca²âº entry and cytoskeletal damage following eccentric contractions in mouse skeletal muscle.

Muscles that are stretched during contraction (eccentric contractions) show deficits in force production and a variety of structural changes, including loss of antibody staining of cytoskeletal proteins. Extracellular Ca(2+) entry and activation of calpains have been proposed as mechanisms involved in these changes. The present study used isolated mouse extensor digitorum longus (EDL) muscles subjected to 10 eccentric contractions and monitored force production, immunostaining of cytoskeletal proteins, and resting stiffness. Possible pathways for Ca(2+) entry were tested with streptomycin (200 µM), a blocker of stretch-activated channels, and with muscles from mice deficient in the transient receptor potential canonical 1 gene (TRPC1 KO), a candidate gene for stretch-activated channels. At 30 min after the eccentric contractions, the isometric force was decreased to 75 ± 3% of initial control and this force loss was reduced by streptomycin but not in the TRPC1 KO. Desmin, titin, and dystrophin all showed patchy loss of immunostaining 30 min after the eccentric contractions, which was substantially reduced by streptomycin and in the TRPC1 KO muscles. Muscles showed a reduction of resting stiffness following eccentric contractions, and this reduction was eliminated by streptomycin and absent in the TRPC1 KO muscles. Calpain activation was determined by the appearance of a lower molecular weight autolysis product and µ-calpain was activated at 30 min, whereas the muscle-specific calpain-3 was not. To test whether the loss of stiffness was caused by titin cleavage, protein gels were used but no significant titin cleavage was detected. These results suggest that Ca(2+) entry following eccentric contractions is through a stretch-activated channel that is blocked by streptomycin and encoded or modulated by TRPC1.

Electrical stimulation influences satellite cell proliferation and apoptosis in unloading-induced muscle atrophy in mice.

Muscle atrophy caused by disuse is accompanied by adverse physiological and functional consequences. Satellite cells are the primary source of skeletal muscle regeneration. Satellite cell dysfunction, as a result of impaired proliferative potential and/or increased apoptosis, is thought to be one of the causes contributing to the decreased muscle regeneration capacity in atrophy. We have previously shown that electrical stimulation improved satellite cell dysfunction. Here we test whether electrical stimulation can also enhance satellite cell proliferative potential as well as suppress apoptotic cell death in disuse-induced muscle atrophy. Eight-week-old male BALB/c mice were subjected to a 14-day hindlimb unloading procedure. During that period, one limb (HU-ES) received electrical stimulation (frequency: 20 Hz; duration: 3 h, twice daily) while the contralateral limb served as control (HU). Immunohistochemistry and western blotting techniques were used to characterize specific proteins in cell proliferation and apoptosis. The HU-ES soleus muscles showed significant improvement in muscle mass, cross-sectional area, and peak tetanic force relative to the HU limb (p<0.05). The satellite cell proliferative activity as detected within the BrdU+/Pax7+ population was significantly higher (p<0.05). The apoptotic myonuclei (detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) and the apoptotic satellite cells (detected by cleaved Poly [ADP-ribose] polymerase co-labeled with Pax7) were reduced (p<0.05) in the HU-ES limb. Furthermore the apoptosis-inducing factor and cleaved caspase-3 were down-regulated while the anti-apoptotic Bcl-2 protein was up-regulated (p<0.05), in the HU-ES limb. These findings suggest that the electrical stimulation paradigm provides an effective stimulus to rescue the loss of myonuclei and satellite cells in disuse muscle atrophy, thus maintaining a viable satellite cell pool for subsequent muscle regeneration. Optimization of stimulation parameters may enhance the outcome of the intervention.

Expression and association of TRPC1 with TRPC3 during skeletal myogenesis.

INTRODUCTION: TRPC1 and TRPC3 proteins are widely expressed in skeletal muscles in forming calcium-permeable channels. Herein we characterize the expression pattern of TRPC transcripts during skeletal myogenesis in C2C12 myoblasts. METHODS: We used polymerase chain reaction and Western blotting to detect expression levels, immunohistochemistry for subcellular localization, and co-immunoprecipitation techniques to assess interaction. RESULTS: TRPC1 localizes to the cytoplasm and is enriched in the perinuclear region in undifferentiated myoblasts. Expression of TRPC1 increases significantly during myogenesis and resides mainly in differentiated myocytes and myotubes. TRPC3 is absent in undifferentiated myoblasts, is dramatically upregulated in differentiated culture, and is preferentially expressed in myotubes. Physical interaction of TRPC1-TRPC3 was observed, suggesting the possible existence of heteromers. CONCLUSIONS: Expression of TRPC1 and TRPC3 is tightly regulated during myogensis. Evidence of TRPC1-TRPC3 interaction was first demonstrated in a muscle cell line. The functional consequences of this interaction remain to be established.

Aerobic exercise training in addition to conventional physiotherapy for chronic low back pain: a randomized controlled trial.

OBJECTIVE: To examine the effect of adding aerobic exercise to conventional physiotherapy treatment for patients with chronic low back pain (LBP) in reducing pain and disability. DESIGN: Randomized controlled trial. SETTING: A physiotherapy outpatient setting in Hong Kong. PARTICIPANTS: Patients with chronic LBP (N=46) were recruited and randomly assigned to either a control (n=22) or an intervention (n=24) group. INTERVENTIONS: An 8-week intervention; both groups received conventional physiotherapy with additional individually tailored aerobic exercise prescribed only to the intervention group. MAIN OUTCOME MEASURES: Visual analog pain scale, Aberdeen Low Back Pain Disability Scale, and physical fitness measurements were taken at baseline, 8 weeks, and 12 months from the commencement of the intervention. Multivariate analysis of variance was performed to examine between-group differences. RESULTS: Both groups demonstrated a significant reduction in pain (P<.001) and an improvement in disability (P<.001) at 8 weeks and 12 months; however, no differences were observed between groups. There was no significant difference in LBP relapse at 12 months between the 2 groups (χ(2)=2.30, P=.13). CONCLUSIONS: The addition of aerobic training to conventional physiotherapy treatment did not enhance either short- or long-term improvement of pain and disability in patients with chronic LBP.

Interventions for preventing lower limb soft-tissue running injuries.

BACKGROUND: Overuse soft-tissue injuries occur frequently in runners. Stretching exercises, modification of training schedules, and the use of protective devices such as braces and insoles are often advocated for prevention. This is an update of a review first published in 2001. OBJECTIVES: To assess the effects of interventions for preventing lower limb soft-tissue running injuries. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (March 2011); The Cochrane Library 2010, Issue 4; MEDLINE (1966 to January 2011); EMBASE (1980 to January 2011); and international trial registries (17 January 2011). SELECTION CRITERIA: Randomised or quasi-randomised trials evaluating interventions to prevent lower limb soft-tissue running injuries. DATA COLLECTION AND ANALYSIS: Two authors independently assessed risk of bias (relating to sequence generation, allocation concealment, blinding, incomplete outcome data) and extracted data. Data were adjusted for clustering if necessary and pooled using the fixed-effect model when appropriate. MAIN RESULTS: We included 25 trials (30,252 participants). Participants were military recruits (19 trials), runners from the general population (three trials), soccer referees (one trial), and prisoners (two trials). The interventions tested in the included trials fell into four main preventive strategies: exercises, modification of training schedules, use of orthoses, and footwear and socks. All 25 included trials were judged as 'unclear' or 'high' risk of bias for at least one of the four domains listed above.We found no evidence that stretching reduces lower limb soft-tissue injuries (6 trials; 5130 participants; risk ratio [RR] 0.85, 95% confidence interval [95% CI] 0.65 to 1.12). As with all non-significant results, this is compatible with either a reduction or an increase in soft-tissue injuries. We found no evidence to support a training regimen of conditioning exercises to improve strength, flexibility and coordination (one trial; 1020 participants; RR 1.20, 95% CI 0.77 to 1.87).We found no evidence that a longer, more gradual increase in training reduces injuries in novice runners (one trial; 486 participants; RR 1.02, 95% CI 0.72 to 1.45). There was some evidence from a poor quality trial that additional training resulted in a significant increase in the number of naval recruits with shin splints (one trial; 1670 participants; RR 2.02, 95% CI 1.11 to 3.70). There was limited evidence that injuries were less frequent in prisoners when running duration (one trial; 69 participants; RR 0.41, 95% CI 0.21 to 0.79) or frequency (one trial; 58 participants; RR 0.19, 95% CI 0.06 to 0.66) were reduced.Patellofemoral braces appear to be effective for preventing anterior knee pain (two trials; 227 participants; RR 0.41, 95% CI 0.24 to 0.67).Custom-made biomechanical insoles may be more effective than no insoles for reducing shin splints (medial tibial stress syndrome) in military recruits (one trial; 146 participants; RR 0.24, 95% CI 0.08 to 0.69).We found no evidence in military recruits that wearing running shoes based on foot shape, rather than standard running shoes, significantly reduced rate of running injuries (2 trials; 5795 participants; Rate Ratio 1.03, 95% CI 0.93 to 1.14). AUTHORS' CONCLUSIONS: Overall, the evidence base for the effectiveness of interventions to reduce soft-tissue injury after intensive running is very weak, with few trials at low risk of bias. More well-designed and reported RCTs are needed that test interventions in recreational and competitive runners.

Skeletal muscle NADPH oxidase is increased and triggers stretch-induced damage in the mdx mouse.

Recent studies have shown that oxidative stress contributes to the pathogenesis of muscle damage in dystrophic (mdx) mice. In this study we have investigated the role of NADPH oxidase as a source of the oxidative stress in these mice. The NADPH oxidase subunits gp91(phox), p67(phox) and rac 1 were increased 2-3 fold in tibilais anterior muscles from mdx mice compared to wild type. Importantly, this increase occurred in 19 day old mice, before the onset of muscle necrosis and inflammation, suggesting that NADPH oxidase is an important source of oxidative stress in mdx muscle. In muscles from 9 week old mdx mice, gp91(phox) and p67(phox) were increased 3-4 fold and NADPH oxidase superoxide production was 2 times greater than wild type. In single fibers from mdx muscle NADPH oxidase subunits were all located on or near the sarcolemma, except for p67(phox),which was expressed in the cytosol. Pharmacological inhibition of NADPH oxidase significantly reduced the intracellular Ca(2+) rise following stretched contractions in mdx single fibers, and also attenuated the loss of muscle force. These results suggest that NADPH oxidase is a major source of reactive oxygen species in dystrophic muscle and its enhanced activity has a stimulatory effect on stretch-induced Ca(2+) entry, a key mechanism for muscle damage and functional impairment.

The effects of low frequency electrical stimulation on satellite cell activity in rat skeletal muscle during hindlimb suspension.

BACKGROUND: The ability of skeletal muscle to grow and regenerate is dependent on resident stem cells called satellite cells. It has been shown that chronic hindlimb unloading downregulates the satellite cell activity. This study investigated the role of low-frequency electrical stimulation on satellite cell activity during a 28 d hindlimb suspension in rats. RESULTS: Mechanical unloading resulted in a 44% reduction in the myofiber cross-sectional area as well as a 29% and 34% reduction in the number of myonuclei and myonuclear domains, respectively, in the soleus muscles (P < 0.001 vs the weight-bearing control). The number of quiescent (M-cadherin(+)), proliferating (BrdU(+) and myoD(+)), and differentiated (myogenin(+)) satellite cells was also reduced by 48-57% compared to the weight-bearing animals (P < 0.01 for all). Daily application of electrical stimulation (2 × 3 h at a 20 Hz frequency) partially attenuated the reduction of the fiber cross-sectional area, satellite cell activity, and myonuclear domain (P < 0.05 for all). Extensor digitorum longus muscles were not significantly altered by hindlimb unloading. CONCLUSION: This study shows that electrical stimulation partially attenuated the decrease in muscle size and satellite cells during hindlimb unloading. The causal relationship between satellite cell activation and electrical stimulation remain to be established.

IGF-IEc expression, regulation and biological function in different tissues.

Insulin-like growth factor I (IGF-I) is an important growth factor for embryonic development, postnatal growth, tissue repair and maintenance of homeostasis. IGF-I functions and regulations are complex and tissue-specific. IGF-I mediates growth hormone signaling to target tissues during growth, but many IGF-I variants have been discovered, resulting in complex models to describe IGF-I function and regulation. Mechano-growth factor (MGF) is an alternative splicing variant of IGF-I and serves as a local tissue repair factor that responds to changes in physiological conditions or environmental stimuli. MGF expression is significantly increased in muscle, bone and tendon following damage resulting from mechanical stimuli and in the brain and heart following ischemia. MGF has been shown to activate satellite cells in muscle resulting in hypertrophy or regeneration, and functions as a neuroprotectant in brain ischemia. Both expression and processing of this IGF-I variant are tissue specific, but the functional mechanism is poorly understood. MGF and its short derivative have been examined as a potential therapy for muscular dystrophy and cerebral hypoxia-ischemia using experimental animals. Although the unique mode of action of MGF has been identified, the details remain elusive. Here we review the expression and regulation of MGF and the function of this IGF-I isoform in tissue protection.