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An increase in the ratio of cellular excitation to inhibition (E/I ratio) has been proposed to underlie the pathogenesis of neuropsychiatric disorders, such as autism spectrum disorders (ASD), obsessive-compulsive disorder (OCD), and Tourette's syndrome (TS). A proper E/I ratio is achieved via factors expressed in neuron and glia. In astrocytes, the glutamate transporter GLT1 is critical for regulating an E/I ratio. However, the role of GLT1 dysfunction in the pathogenesis of neuropsychiatric disorders remains unknown because mice with a complete deficiency of GLT1 exhibited seizures and premature death. Here, we show that astrocyte-specific GLT1 inducible knockout (GLAST(CreERT2/+)/GLT1(flox/flox), iKO) mice exhibit pathological repetitive behaviors including excessive and injurious levels of self-grooming and tic-like head shakes. Electrophysiological studies reveal that excitatory transmission at corticostriatal synapse is normal in a basal state but is increased after repetitive stimulation. Furthermore, treatment with an N-methyl-D-aspartate (NMDA) receptor antagonist memantine ameliorated the pathological repetitive behaviors in iKO mice. These results suggest that astroglial GLT1 has a critical role in controlling the synaptic efficacy at corticostriatal synapses and its dysfunction causes pathological repetitive behaviors.

Tendinopathy is a common overuse injury with limited preventive options. This study evaluated a novel topical metformin lotion (ML) for its ability to prevent Achilles tendinopathy induced by intensive treadmill running (ITR) in mice. ML at concentrations of 3% and 6% was topically applied daily to the skin overlying the Achilles tendons for four weeks prior to the initiation of ITR. After the four-week topical ML pretreatment period prior to ITR induction, blood samples were collected for ELISA-based analysis of inflammatory markers (HMGB1, IL-1β, and PGE 2 ), and tendons were examined using histological and immunofluorescent methods. ML inhibited the release of HMGB1 from cell nuclei into the tendon matrix, reduced serum levels of HMGB1, IL-1β, and PGE 2 , and exerted anti-degenerative effects by decreasing chondroid metaplasia, lowering the number of rounded cells, and enhancing collagen fiber organization. These beneficial effects of ML appeared to be mediated through increased AMPK activity, reduced TGF-β1 expression, decreased myofibroblast presence, lower collagen III levels, and elevated collagen I production. In conclusion, ML effectively prevents tendinopathy development, primarily by inhibiting HMGB1 and activating AMPK. These findings suggest that ML may serve as a convenient, effective, and non-invasive strategy to prevent tendinopathy in at-risk populations—such as athletes and military personnel—while minimizing systemic side effects.

Purpose The incidence of groin pain in athletes is steadily increasing. Symptomatic pubic overload with groin pain and aseptic osteitis pubis represent well-known and frequently misdiagnosed overuse injuries in athletes. This study investigated the benefits of standardised non-surgical treatment for swift return-to-football. Methods In a prospective double-blinded controlled study, 143 amateur football players with groin pain as well as radiological signs and clinical symptoms of pubic overload were analysed for 1 year. Two randomised study groups participated in an intensive physical rehabilitation programme, either with or without shock wave therapy. The control group did not participate in any standardised rehabilitation programme but only stopped participating in sports activity. Follow-up examinations took place 1, 3 months and 1 year after the beginning of therapy. Endpoints were visual analogue scale (VAS), functional tests, the time of return-to-football, recurrent complaints and changes in the MR image. Results Forty-four football players with groin pain and aseptic osteitis pubis were randomised into two study groups; 26 received shock wave therapy, 18 did not. Clinical examination showed pubic overload as a multi-located disease. Players receiving shock wave therapy showed earlier pain relief in the VAS ( p  < 0.001) and returned to football significantly earlier ( p  = 0.048) than players without this therapy. Forty-two of 44 players of both study groups returned to football within 4 months after the beginning of therapy and had no recurrent groin pain within 1 year after trauma. Fifty-one players of the control group returned to football after 240 days ( p  < 0.001), of whom 26 (51%) experienced recurrent groin pain. Follow-up MRI scans did not show any effect of shock wave therapy. Conclusion Non-surgical therapy is successful in treating pubic overload and osteitis pubis in athletes. Shock wave therapy as a local treatment significantly reduced pain, thus enabling return-to-football within 3 months after trauma. Early and correct diagnosis is essential for successful intensive physiotherapy. Level of evidence I.

Overtraining syndrome (OTS) and related conditions cause decreased training performance and fatigue through an imbalance among training volume, nutrition, and recovery time. No definitive biochemical markers of OTS currently exist. To compare muscular, hormonal, and inflammatory parameters among OTS-affected athletes, healthy athletes, and sedentary controls. Cross-sectional study. Laboratory. Fifty-one men aged 18 to 50 years (14 OTS-affected athletes [OTS group], 25 healthy athletes [ATL group], and 12 healthy sedentary participants [NCS group]), with a body mass index of 20 to 30.0 kg/m (sedentary) or 20 to 33.0 kg/m (athletes), recruited through social media. All 39 athletes performed both endurance and resistance sports. We measured total testosterone, estradiol, insulin-like growth factor 1, thyroid-stimulating hormone, free thyronine, total and fractioned catecholamines and metanephrines, lactate, ferritin, creatinine, creatine kinase, erythrocyte sedimentation rate, C-reactive protein, lipid profile, hemogram, and testosterone : estradiol, testosterone : cortisol, neutrophil : lymphocyte, platelet: lymphocyte, and catecholamine : metanephrine ratios. Each parameter was statistically analyzed through 3-group comparisons, and whenever < .05, pairwise comparisons were performed (OTS × ATL, OTS × NCS, and ATL × NCS). Neutrophils and testosterone were lower in the OTS group than in the ATL group but similar between the OTS and NCS groups. Creatine kinase, lactate, estradiol, total catecholamines, and dopamine were higher in the OTS group than in the ATL and NCS groups, whereas the testosterone : estradiol ratio was lower, even after adjusting for all variables. Lymphocytes were lower in the ATL group than in the OTS and NCS groups. The ATL and OTS groups trained with the same intensity, frequency, and types of exercise. At least in males, OTS was typified by increased estradiol, decreased testosterone, overreaction of muscle tissue to physical exertion, and immune system changes, with deconditioning effects of the adaptive changes observed in healthy athletes.

Myofascial pain syndrome (MPS) is described as the sensory, motor, and autonomic symptoms caused by myofascial trigger points (TrPs). Knowing the potential causes of TrPs is important to prevent their development and recurrence, but also to inactivate and eliminate existing TrPs. There is general agreement that muscle overuse or direct trauma to the muscle can lead to the development of TrPs. Muscle overload is hypothesized to be the result of sustained or repetitive low-level muscle contractions, eccentric muscle contractions, and maximal or submaximal concentric muscle contractions. TrPs may develop during occupational, recreational, or sports activities when muscle use exceeds muscle capacity and normal recovery is disturbed.

Although the risk of osteoarthritis development after acute knee injury has been widely studied, the long-term consequences of knee overuse injury are not well understood.   To identify the relationship between gait-related risk factors associated with osteoarthritis and the development of iliotibial band syndrome (ITBS) in members of a single University Army Reserve Officers' Training Corps unit.   Prospective cohort study.   Biomechanics laboratory.   Sixty-eight cadets undergoing standardized physical fitness training.   Three-dimensional lower extremity kinematics (240 Hz) and kinetics (960 Hz) were collected for 3 bilateral trials during shod running at 4.0 m/s ± 10%. Injury tracking was conducted for 7 months of training.   Biomechanical variables, including varus thrust and knee-adduction moment, were compared between the injured and control groups.   Twenty-six cadets with no history of overuse injury served as the control group, whereas 6 cadets (7 limbs) who developed ITBS that required them to modify their training program or seek medical care (or both) served as the injured group. Maximum varus velocity was higher ( P = .006) and occurred sooner during stance ( P = .04) in the injured group than in the control group, indicating greater varus thrust. Maximum knee-varus angle and maximum knee-adduction moment were higher ( P = .02 and P = .002, respectively) and vertical stiffness was lower ( P = .03) in the injured group.   Measures of dynamic varus stability appeared to be altered in individuals who developed ITBS. Biomechanical knee variables previously identified as increasing the risk for knee osteoarthritis were also associated with the development of ITBS in healthy adults.

The aim of this investigation was to study female workers active in the labour market for differences between those with trapezius myalgia (MYA) and without (CON) during repetitive pegboard (PEG) and stress (STR) tasks regarding (1) relative muscle load, (2) trapezius muscle blood flow, (3) metabolite accumulation, (4) oxygenation, and (5) pain development. Among 812 female employees (age 30–60 years) at 7 companies with high prevalence of neck/shoulder complaints, clinical examination identified 43 MYA and 19 CON. At rest, during PEG, and STR the trapezius muscle was measured using (1) EMG and MMG, (2) microdialysis, and (3) NIRS. Further, subjective pain ratings were scored (VAS). EMGrms in %MVE (Maximal Voluntary EMG-activity), was significantly higher among MYA than CON during PEG (11.74 ± 9.09 vs. 7.42 ± 5.56%MVE) and STR (5.47 ± 5.00 vs. 3.28 ± 1.94%MVE). MANOVA showed a group and time effect regarding data from the microdialysis: for MYA versus CON group differences demonstrated lower muscle blood flow and higher lactate and pyruvate concentrations. Potassium and glucose only showed time effects. NIRS showed similar initial decreases in oxygenation with PEG in both groups, but only in CON a significant increase back to baseline during PEG. VAS score at rest was highest among MYA and increased during PEG, but not for CON. The results showed significant differences between CON and MYA regarding muscle metabolism at rest and with PEG and STR. Higher relative muscle load during PEG and STR, insufficient muscle blood flow and oxygenation may account for the higher lactate, pyruvate and pain responses among MYA versus CON.

Carpal tunnel syndrome is the most common entrapment neuropathy, affecting approximately 3 to 6 percent of adults in the general population. Although the cause is not usually determined, it can include trauma, repetitive maneuvers, certain diseases, and pregnancy. Symptoms are related to compression of the median nerve, which results in pain, numbness, and tingling. Physical examination findings, such as hypalgesia, square wrist sign, and a classic or probable pattern on hand symptom diagram, are useful in making the diagnosis. Nerve conduction studies and electromyography can resolve diagnostic uncertainty and can be used to quantify and stratify disease severity. Treatment options are based on disease severity. Six weeks to three months of conservative treatment can be considered in patients with mild disease. Lifestyle modifications, including decreasing repetitive activity and using ergonomic devices, have been traditionally advocated, but have inconsistent evidence to support their effectiveness. Cock-up and neutral wrist splints and oral corticosteroids are considered first-line therapies, with local corticosteroid injections used for refractory symptoms. Nonsteroidal anti-inflammatory drugs, diuretics, and pyridoxine (vitamin B6 ) have been shown to be no more effective than placebo. Most conservative treatments provide short-term symptom relief, with little evidence supporting long-term benefits. Patients with moderate to severe disease should be considered for surgical evaluation. Open and endoscopic surgical approaches have similar five-year outcomes.

Introduction Although previous studies have related occupational exposure and epicondylitis, the evidence is moderate and mostly based on cross-sectional studies. Suspected physical exposures were tested over a 3-year period in a large longitudinal cohort study of workers in the USA. Method In a population-based study including a variety of industries, 1107 newly employed workers were examined; only workers without elbow symptoms at baseline were included. Baseline questionnaires collected information on personal characteristics and self-reported physical work exposures and psychosocial measures for the current or most recent job at 6 months. Epicondylitis (lateral and medial) was the main outcome, assessed at 36 months based on symptoms and physical examination (palpation or provocation test). Logistic models included the most relevant associated variables. Results Of 699 workers tested after 36 months who did not have elbow symptoms at baseline, 48 suffered from medial or lateral epicondylitis (6.9%), with 34 cases of lateral epicondylitis (4.9%), 30 cases of medial epicondylitis (4.3%) and 16 workers who had both. After adjusting for age, lack of social support and obesity, consistent associations were observed between self-reported wrist bending/twisting and forearm twisting/rotating/screwing motion and future cases of medial or lateral epicondylitis (ORs 2.8 (1.2 to 6.2) and 3.6 (1.2 to 11.0) in men and women, respectively). Conclusions Self-reported physical exposures that implicate repetitive and extensive/prolonged wrist bend/twisting and forearm movements were associated with incident cases of lateral and medial epicondylitis in a large longitudinal study, although other studies are needed to better specify the exposures involved.

ObjectivesTo estimate the risk of surgery for subacromial impingement syndrome (SIS) in relation to occupational exposures, lifestyle factors and diabetes mellitus.MethodsWe conducted a case–control study nested in a register-based cohort study of the Danish working population. For each of 3000 first-time cases of surgery for SIS, two age-matched and sex-matched controls were drawn. Cases and controls received a questionnaire on job history and other factors. Job histories were combined with a psychosocial job exposure matrix (JEM) and the updated Shoulder JEM, which provided exposure intensities on measurement scales. Ten-year cumulative exposures to upper arm elevation >90°, repetitive shoulder movements, forceful shoulder exertions and hand–arm vibrations (HAVs) were estimated. We used conditional logistic regression.ResultsThere were 5396 persons (60%) who answered the questionnaire. For occupational mechanical exposures, the adjusted OR (ORadj) ranged from 1.9 (95% CI 1.5 to 2.5 for HAVs) to 2.5 (95% CI 1.9 to 3.5 for force) among men and 1.7 (95% CI 1.2 to 2.5 for HAVs) to 2.0 (95% CI 1.3 to 2.9 for force) among women. No statistically significant associations were found for occupational psychosocial factors. Body mass index (BMI) and pack-years of smoking showed ORadj up to 2.0. Diabetes mellitus showed ORadj of 1.5 (95% CI 1.1 to 2.2) for men and 2.2 (95% CI 1.4 to 3.4) for women.ConclusionsOur findings add to the evidence of an increased risk of surgery for SIS in relation to occupational cumulative mechanical exposures, even when an increased risk in relation to BMI, smoking and diabetes mellitus is taken into account.