Immunoglobulin A Autoreactivity toward Brain Enriched and Apoptosis-Regulating Proteins in Saliva of Athletes after Acute Concussion and Subconcussive Impacts.

The diagnosis and management of concussion is hindered by its diverse clinical presentation and assessment tools reliant on subjectively experienced symptoms. The biomechanical threshold of concussion is also not well understood, and asymptomatic concussion or "subconcussive impacts" of variable magnitudes are common in contact sports. Concerns have risen because athletes returning to activity too soon have an increased risk of prolonged recovery or long-term adverse health consequences. To date, little is understood on a molecular level regarding concussion and subconcussive impacts. Recent research suggests that neuroinflammatory mechanisms may serve an important role subsequent to concussion and possibly to subconcussive impacts. These studies suggest that autoantibodies may be a valuable tool for detection of acute concussion and monitoring for changes caused by cumulative exposure to subconcussive impacts. Hence, we aimed to profile the immunoglobulin (Ig)A autoantibody repertoire in saliva by screening a unique sport-related head trauma biobank. Saliva samples (n = 167) were donated by male and female participants enrolled in either the concussion (24-48 h post-injury) or subconcussion (non-concussed participants having moderate or high cumulative subconcussive impact exposure) cohorts. Study design included discovery and verification phases. Discovery aimed to identify new candidate autoimmune targets of IgA. Verification tested whether concussion and subconcussion cohorts increased IgA reactivity and whether cohorts showed similarities. The results show a significant increase in the prevalence of IgA toward protein fragments representing 5-hydroxytryptamine receptor 1A (HTR1A), serine/arginine repetitive matrix 4 (SRRM4) and FAS (tumor necrosis factor receptor superfamily member 6) after concussion and subconcussion. These results may suggest that concussion and subconcussion induce similar physiological effects, especially in terms of immune response. Our study demonstrates that saliva is a potential biofluid for autoantibody detection in concussion and subconcussion. After rigorous confirmation in much larger independent study sets, a validated salivary autoantibody assay could provide a non-subjective quantitative means of assessing concussive and subconcussive events.

The mechanism and prevention of mitochondrial injury after exercise.

With the development of society, physical activity has come to be an effective means by which people pursue good health to improve the quality of life. However, with the increase of intensity and the passage of time, exercise injury has become a hazard that can no longer be ignored. It is imperative to find effective ways to inhibit or reduce the negative effects of exercise. Mitochondria are important organelles involved in exercise and play an important role in exercise injury and prevention. Studies have found that exercise preconditioning and increased mitochondrial nutrition can effectively decrease mitochondrial damage after exercise. Against this background, some of the newest developments in this important field are reviewed here. The results discussed indicate that exercise preconditioning and supplement mitochondrial nutrition need to be increased to prevent exercise-related injuries.

Bilateral Looser zones or pseudofractures in the anteromedial tibia as a component of medial tibial stress syndrome in athletes.

PURPOSE: Medial tibial stress syndrome (MTSS) represents a common diagnosis in individuals exposed to repetitive high-stress loads affecting the lower limb, e.g., high-performance athletes. However, the diagnostic approach and therapeutic regimens are not well established. METHODS: Nine patients, diagnosed as MTSS, were analyzed by a comprehensive skeletal analysis including laboratory bone turnover parameters, dual-energy X-Ray absorptiometry (DXA), and high-resolution peripheral quantitative computed tomography (HR-pQCT). RESULTS: In 4/9 patients, bilateral pseudofractures were detected in the mid-shaft tibia. These patients had significantly lower levels of 25-hydroxycholecalciferol compared to patients with MTSS but similar levels of bone turnover parameters. Interestingly, the skeletal assessment revealed significantly higher bone mineral density (BMD) Z-scores at the hip (1.3 ± 0.6 vs. - 0.7 ± 0.5, p = 0.013) in patients with pseudofractures and a trend towards higher bone microarchitecture parameters measured by HR-pQCT at the distal tibia. Vitamin D supplementation restored the calcium-homeostasis in all patients. Combined with weight-bearing as tolerated, pseudofractures healed in all patients and return to competition was achieved. CONCLUSION: In conclusion, deficient vitamin D levels may lead to pseudofractures due to localized deterioration of mineralization, representing a pivotal component of MTSS in athletes with increased repetitive mechanical loading of the lower limbs. Moreover, the manifestation of pseudofractures is not a consequence of an altered BMD nor microarchitecture but appears in patients with exercise-induced BMD increase in combination with reduced 25-OH-D levels. The screening of MTSS patients for pseudofractures is crucial for the initiation of an appropriate treatment such as vitamin D supplementation to prevent a prolonged course of healing or recurrence. LEVEL OF EVIDENCE: III.

Factors Associated With Energy Expenditure and Energy Balance in Acute Sport-Related Concussion.

CONTEXT: Sport-related concussion (SRC) is characterized by a pathologic neurometabolic cascade that results in an increased intracranial energy demand and a decreased energy supply. Little is known about the whole-body energy-related effects of SRC. OBJECTIVE: To examine factors associated with whole-body resting metabolic rate (RMR), total energy expenditure (TEE), energy consumption (EC), and energy balance (EBal) in student-athletes acutely after SRC and healthy matched control individuals. DESIGN: Case-control study. SETTING: University research laboratory. PATIENTS OR OTHER PARTICIPANTS: Student-athletes diagnosed with SRC (n = 28, 50% female, age = 18.4 ± 1.8 years, body mass index [BMI] = 24.1 ± 4.1 kg/m2) assessed ≤72 hours postinjury and a matched control group (n = 28, 50% female, age = 19.4 ± 2.9 years, BMI = 24.7 ± 4.78 kg/m2). MAIN OUTCOME MEASURE(S): Resting metabolic rate was measured via indirect calorimetry. Participants reported their physical activity and dietary intake for 3 days, which we used to estimate TEE and EC, respectively, and to calculate EBal (EC:TEE ratio). Resting metabolic rate, TEE, and EC were normalized to body mass. Group and group-by-sex comparisons were conducted for RMR·kg-1, TEE·kg-1, EC·kg-1, and EBal using independent t tests with the a priori α = .05. Associations of age, sex, concussion history, BMI, and symptom burden with RMR·kg-1 and EBal were explored with linear regression models. RESULTS: Total energy expenditure·kg-1 was lower (P < .01; mean difference ± SD = -5.31 ± 1.41 kcal·kg-1) and EBal was higher (P < .01; 0.28 ± 0.10) in SRC participants than in control participants. Both sexes with SRC had lower TEE·kg-1 than did the control participants (P values ≤ .04); females with SRC had higher EBal than controls (P = .01), but male groups did not differ. Higher RMR·kg-1 was associated with history of concussion (adjusted R2 = .10, ß = 0.65). Younger age (ß = -0.35), fewer concussions (ß = -0.35), lower BMI (ß = -0.32), greater symptom duration (ß = 1.50), and lower symptom severity (ß = -1.59) were associated with higher EBal (adjusted R2 = .54). CONCLUSIONS: Total energy expenditure·kg-1 and EBal appeared to be affected by acute SRC, despite no differences in RMR·kg-1. Sex, concussion history, BMI, and symptom burden were associated with acute energy-related outcomes.

Improved recovery from skeletal muscle damage is largely unexplained by myofibrillar protein synthesis or inflammatory and regenerative gene expression pathways.

The contribution of myofibrillar protein synthesis (MyoPS) to recovery from skeletal muscle damage in humans is unknown. Recreationally active men and women consumed a daily protein-polyphenol beverage targeted at increasing amino acid availability and reducing inflammation (PPB; n = 9), both known to affect MyoPS, or an isocaloric placebo (PLA; n = 9) during 168 h of recovery from 300 maximal unilateral eccentric contractions (EE). Muscle function was assessed daily. Muscle biopsies were collected for 24, 27, 36, 72, and 168 h for MyoPS measurements using 2H2O and expression of 224 genes using RT-qPCR and pathway analysis. PPB improved recovery of muscle function, which was impaired for 5 days after EE in PLA (interaction P < 0.05). Acute postprandial MyoPS rates were unaffected by nutritional intervention (24-27 h). EE increased overnight (27-36 h) MyoPS versus the control leg (PLA: 33 ± 19%; PPB: 79 ± 25%; leg P < 0.01), and PPB tended to increase this further (interaction P = 0.06). Daily MyoPS rates were greater with PPB between 72 and 168 h after EE, albeit after function had recovered. Inflammatory and regenerative signaling pathways were dramatically upregulated and clustered after EE but were unaffected by nutritional intervention. These results suggest that accelerated recovery from EE is not explained by elevated MyoPS or suppression of inflammation.NEW & NOTEWORTHY The present study investigated the contribution of myofibrillar protein synthesis (MyoPS) and associated gene signaling to recovery from 300 muscle-damaging, eccentric contractions. Measured with 2H2O, MyoPS rates were elevated during recovery and observed alongside expression of inflammatory and regenerative signaling pathways. A nutritional intervention accelerated recovery; however, MyoPS and gene signaling were unchanged compared with placebo. These data indicate that MyoPS and associated signaling do not explain accelerated recovery from muscle damage.

Nutritional Considerations and Strategies to Facilitate Injury Recovery and Rehabilitation.

Nutritional interventions are not commonly a standard of care in rehabilitation interventions. A nutritional approach has the potential to be a low-cost, high-volume strategy that complements the existing standard of care. In this commentary, our aim is to provide an evidence-based, practical guide for athletes with injuries treated surgically or conservatively, along with healing and rehabilitation considerations. Injuries are a normal and expected part of exercise participation. Regardless of severity, an injury typically results in the athlete's short- or long-term removal from participation. Nutritional interventions may augment the recovery process and support optimal healing; therefore, incorporating nutritional strategies is important at each stage of the healing process. Preoperative nutrition and nutritional demands during rehabilitation are key factors to consider. The physiological response to wounds, immobilization, and traumatic brain injuries may be improved by optimizing macronutrient composition, caloric consumption, and nutrient timing and using select dietary supplements. Previous research supports practical nutrition recommendations to reduce surgical complications, minimize deficits after immobilization, and maximize the chance of safe return to play. These recommendations include identifying the individual's caloric requirements to ensure that energy needs are being met. A higher protein intake, with special attention to evenly distributed consumption throughout the day, will help to minimize loss of muscle and strength during immobilization. Dietary-supplement strategies may be useful when navigating the challenges of appropriate caloric intake and timing and a reduced appetite. The rehabilitation process also requires a strong nutritional plan to enhance recovery from injury. Athletic trainers, physical therapists, and other health care professionals should provide basic nutritional recommendations during rehabilitation, discuss the timing of meals with respect to therapy, and refer the patient to a registered dietitian if warranted. Because nutrition plays an essential role in injury recovery and rehabilitation, nutritional interventions should become a component of standard-of-care practice after injury. In this article, we address best practices for implementing nutritional strategies among patients with athletic injuries.

Rehabilitation Nutrition for Injury Recovery of Athletes: The Role of Macronutrient Intake.

An adequate and balanced diet is of utmost importance in recovery and rehabilitation. "Rehabilitation nutrition" for injury recovery of athletes is similar to sports nutrition, except for the differences that concern the prevention of the risk or presence of sarcopenia, malnutrition, or dysphagia. Rehabilitation nutrition also aims, combined with training, to an adequate long-term nutritional status of the athlete and also in physical condition improvement, in terms of endurance and resistance. The aim of this paper is to define the proper nutrition for athletes in order to hasten their return to the sports after surgery or injury. Energy intake should be higher than the energy target in order to fight sarcopenia-that is 25-30 kcal/kg of body weight. Macro- and micro-nutrients play an important role in metabolism, energy production, hemoglobin synthesis, lean mass and bone mass maintenance, immunity, health, and protection against oxidative damage. Nutritional strategies, such as supplementation of suboptimal protein intake with leucine are feasible and effective in offsetting anabolic resistance. Thus, maintaining muscle mass, without gaining fat, becomes challenging for the injured athlete. A dietary strategy should be tailored to the athlete's needs, considering amounts, frequency, type and, most of all, protein quality. During rehabilitation, simultaneous carbohydrates and protein intake can inhibit muscle breakdown and muscle atrophy. The long-term intake of omega-3 fatty acids enhances anabolic sensitivity to amino acids; thus, it may be beneficial to the injured athlete. Adequate intakes of macronutrients can play a major role supporting athletes' anabolism.

Whole-Body Metabolism, Carbohydrate Utilization, and Caloric Energy Balance After Sport Concussion: A Pilot Study.

BACKGROUND: Sport concussion (SC) causes an energy crisis in the brain by increasing energy demand, decreasing energy supply, and altering metabolic resources. Whole-body resting metabolic rate (RMR) is elevated after more severe brain injuries, but RMR changes are unknown after SC. The purpose of this study was to longitudinally examine energy-related changes in collegiate athletes after SC. HYPOTHESIS: RMR and energy consumption will increase acutely after SC and will return to control levels with recovery. STUDY DESIGN: Case-control study. LEVEL OF EVIDENCE: Level 4. METHODS: A total of 20 collegiate athletes with SC (mean age, 19.3 ± 1.08 years; mean height, 1.77 ± 0.11 m; mean weight, 79.6 ± 23.37 kg; 55% female) were compared with 20 matched controls (mean age, 20.8 ± 2.17 years; mean height, 1.77 ± 0.10 m; mean weight, 81.9 ± 23.45 kg; 55% female). RMR, percentage carbohydrate use (%CHO), and energy balance (EBal; ratio between caloric consumption and expenditure) were assessed 3 times: T1, ≤72 hours after SC; T2, 7 days after T1; and TF, after symptom resolution. A 2 × 2 × 3 (group × sex × time) multivariate analysis of variance assessed RMR, %CHO, and EBal. Changes in RMR, %CHO, and EBal (T1 to TF) were correlated with days to symptom-free and days to return to play in the concussed group. RESULTS: Women reported being symptom-free (median, 6 days; range, 3-10 days) sooner than men (median, 11 days; range, 7-16 days). RMR and %CHO did not differ across time between groups or for group × sex interaction. SC participants had higher EBal than controls at T1 (P = 0.016) and T2 (P = 0.010). In men with SC, increasing %CHO over time correlated with days to symptom-free (r = 0.735 and P = 0.038, respectively) and days to return to play (r = 0.829 and P = 0.021, respectively). CONCLUSION: Participants with SC were in energy surplus acutely after injury. Although women recovered more quickly than men, men had carbohydrate metabolism changes that correlated with recovery time. CLINICAL RELEVANCE: This pilot study shows that male and female student-athletes may have differing physiologic responses to SC and that there may be a role for dietary intervention to improve clinical outcomes after SC.

The relationship between skin ultrasound images and muscle damage using skin blotting in wheelchair basketball athletes.

STUDY DESIGN: Secondary analysis of a cross-sectional observation study. OBJECTIVES: To determine the relationship between skin ultrasound images and muscle damage in wheelchair basketball athletes, using skin blotting examinations of the ischial regions. SETTING: Community, Japan. METHODS: Fourteen elite wheelchair basketball athletes were recruited. We obtained data regarding participants' characteristics. We undertook ultrasonographic images and quantitative skin blotting of the ischial region before and after training, and after rest. RESULTS: We identified Category II and III pressure injuries in 2 of the 12 participants. Structural features were classified into four categories based on ultrasonographic features, namely, normal skin structure, unclear superficial and deep fascia, cloudy fat layer, and fat infiltration and low-echoic lesion/anechoic lesions. The muscle-type creatinine kinase (CK-M) level (median [interquartile range: IQR], 2.98 [2.80-3.47]) in the fat infiltration and low-echoic lesion/anechoic lesion group was significantly higher (1.43 [1.41-1.49]) than in a nonfat infiltration and low-echoic lesion/anechoic lesion group after training (p = 0.03). The interleukin-6 (IL-6) level (median [IQR], 23.5 [16.15-58.97]) in the fat infiltration and low-echoic lesion/anechoic lesion group was significantly higher (1.94 [1.74-4.44]) than in the nonfat infiltration and low-echoic lesion/anechoic lesion group after rest (mean difference = -25.4, 95% CI -61.1 to 10.7, p = 0.03). CONCLUSIONS: The combination of ultrasonographic images and skin blotting using CK-M and IL-6, could detect early deep tissue damage in wheelchair athletes. These techniques could be potentially useful in the treatment and prevention of pressure injuries. SPONSORSHIP: This study was supported in part by YAMAHA Motor Foundation for Sports.

Differential Expression of Circulating Inflammatory Proteins Following Sport-Related Traumatic Brain Injury.

Sport-related traumatic brain injury (TBI) elicits a multifaceted inflammatory response leading to brain injury and morbidity. This response could be a predictive tool for the progression of TBI and to stratify the injury of which mild TBI is most prevalent. Therefore, we examined the differential expression of serum inflammatory markers overtime and identified novel markers in repetitively concussed athletes. Neuropsychological assessment by Wechsler Adult Intelligence Scale (WAIS) and Immediate Post Concussion Assessment and Cognitive Test (ImPACT) was performed on rugby players and serum was taken from healthy, concussed and repetitively concussed athletes. Serum was also obtained <1 week and >1 week after trauma and analyzed for 92 inflammatory protein markers. Fibroblast growth factor 21 (FGF21) and interleukin-7 (IL-7) differentiated repetitively concussed athletes. Macrophage chemotactic protein-1 (MCP-1), tumor necrosis factor superfamily member 14 (TNFSF14) were significantly reduced >1 week and chemokine (C-X3-C motif) ligand 1 (CX3CL1) upregulated <1 week after injury. FGF21 and MCP-1 negatively correlated with symptoms and their severity. We have identified dynamic changes in the inflammatory response overtime and in different classes of concussion correlating with disease progression. This data supports the use of inflammatory biomarkers as predictors of symptom development due to secondary complications of sport-related mTBI.

Tau Positron Emission Tomographic Findings in a Former US Football Player With Pathologically Confirmed Chronic Traumatic Encephalopathy.

Importance: Biomarkers for chronic traumatic encephalopathy (CTE) are currently lacking. The radiotracer fluorine F 18-labeled (18F)-flortaucipir (FTP) detects tau pathology in Alzheimer disease, and positron emission tomography (PET) with FTP shows elevated binding in individuals at risk for CTE. No study, however, has assessed the correlation between in vivo FTP PET and postmortem tau in CTE. Objective: To assess the regional association between in vivo FTP binding and postmortem tau pathology in a patient with pathologically confirmed CTE. Design, Setting, and Participants: A white male former National Football League player with 17 years of US football exposure was clinically diagnosed with traumatic encephalopathy syndrome at a neurology tertiary referral center. 18F-Fludeoxyglucose, carbon 11-labeled Pittsburgh compound B, and FTP PET were performed 52 months prior to death, and magnetic resonance imaging, 50 months prior to death. Brain images were assessed qualitatively for abnormalities blinded to autopsy data. Autopsy was performed using a neurodegenerative research protocol. The FTP standardized uptake value ratios (inferior cerebellar gray reference region) and W-score (age-adjusted z-score) maps were compared with phosphorylated tau immunohistochemical analysis with monoclonal antibody CP13. Main Outcomes and Measures: Qualitative and quantitative comparisons between antemortem FTP PET and tau pathology at autopsy. Results: Flortaucipir uptake was distributed in a patchy, frontotemporal-predominant pattern that overlapped with regions showing neurodegeneration on magnetic resonance imaging and hypometabolism on 18F-fludeoxyglucose PET. Pathological assessment revealed stage 4 CTE; limbic argyrophilic grain disease; stage 2 limbic-predominant, age-related transactive response DNA-binding protein 43 encephalopathy; and Braak neurofibrillary tangle stage 3. 18F-Flortaucipir W-maps matched areas of high postmortem tau burden in left fusiform and inferior temporal gyri and juxtacortical frontal white matter. High FTP W-scores with low tau burden were found in the basal ganglia, thalamus, motor cortex, and calcarine cortex. No regions with low FTP W-scores corresponded to areas with high pathological tau burden. A modest correlation, which did not reach statistical significance (ρ = 0.35, P = .17), was found between FTP standardized uptake value ratio and tau area fraction at the regional level. Conclusions and Relevance: In this patient, FTP PET findings during life showed a modest correspondence with postmortem pathology in CTE. These findings suggest that FTP may have limited utility as a tau biomarker in CTE.

Effectiveness of whey protein supplements on the serum levels of amino acid, creatinine kinase and myoglobin of athletes: a systematic review and meta-analysis.

BACKGROUND: Consuming whey protein supplements, along with physiotherapy and psychotherapy, have been recognised in sports performance. Whey protein supplements (WPS) is one of the commonly used supplements as ergogenic aids for athletes to enhance their muscle performance and recovery during sport-related injuries. The purpose of this systematic review is to investigate the effectiveness of WPS over the blood biochemistry mainly amino acids, creatinine kinase and myoglobin which influence performance and recovery among athletes. METHOD: A comprehensive literature search was conducted to identify randomised control trials (RCTs) and non-RCTs that investigated the effectiveness of WPS on amino acids, creatinine kinase and myoglobin among athletes. Risk of Bias in Non-Randomised Studies of Interventions tool (ROBINS-I) and Cochrane Risk of Bias Assessment tool were used to rule out the quality of studies. Meta-analysis was performed using a random effect model with STATA version 14.2. The weighted mean difference was used to estimate the effectiveness of WPS against other supplements. RESULTS: A total of 333,257 research articles were identified; of these, 15 records were included to proceed with the analysis. Meta-analysis has shown that WPS has significantly overall increased the level of essential amino acids level by 624.03 nmol/L (CI = 169.27, 1078.8; I2 = 100%; p = 0.00) and branched-chain amino acids level by 458.57 nmol/L (CI = 179.96, 737.18; I2 = 100%; p = 0.00) compared to the control group (without WPS). Moreover, was observed to decrease myoglobin level by 11.74 ng/ml (CI = - 30.24, 6.76; I2 = 79.6%; p = 0.007) and creatine kinase level by 47.05 U/L (CI = - 129.47, 35.37; I2 = 98.4%; p = 0.000) compared to the control group. CONCLUSION: The findings revealed that the clinical evidence supports the effectiveness of WPS as a positive ergogenic aid on athletes' amino acids, creatinine kinase and myoglobin.

Resting CMRO2 fluctuations show persistent network hyper-connectivity following exposure to sub-concussive collisions.

Exposure to head impacts may alter brain connectivity within cortical hubs such as the default-mode network (DMN). However, studies have yet to consider the confounding effects of altered resting cerebral blood flow (CBF0) and cerebrovascular reactivity (CVR) on changes in connectivity following sub-concussive impacts. Here, 23 Canadian collegiate football players were followed during a season using calibrated resting-state MRI and helmet accelerometers to examine the interplay between the neural and vascular factors that determine functional connectivity (FC). Connectivity-based analyses using blood oxygen level dependent (BOLD) and cerebral metabolic rate of oxygen consumption (CMRO2) mapping were used to study the DMN longitudinally. Network-specific decreases in CBF0 were observed one month following the season, while impaired CVR was documented at both mid-season and one month following the season, compared to pre-season baseline. Alterations in CBF0 and BOLD-based CVR throughout the season suggest that neurophysiological markers may show different susceptibility timelines following head impacts. DMN connectivity was increased throughout the season, independent of changes in cerebrovascular physiology, suggesting that alterations in FC following sub-concussive impacts are robust and independent of changes in brain hemodynamics. No significant correlations between impact kinematics and DMN connectivity changes were documented in this study. Altogether, these findings create a strong paradigm for future studies to examine the underlying neural and vascular mechanisms associated with increases in network connectivity following repeated exposure to sub-concussive collisions, in an effort to improve management of head impacts in contact sports.

Sex, but not skin tone affects penetration of red-light (660 nm) through sites susceptible to sports injury in lean live and cadaveric tissues.

Red-light treatment is emerging as a novel therapy for promoting tissue recovery but data on red-light penetration through human tissues are lacking. We aimed to: (1) determine the effect of light irradiance, tissue thickness, skin tone, sex and bone/muscle content on 660 nm light penetration through common sites of sports injuries, and (2) establish if cadaver tissues serve as a useful model for predicting red-light penetration in live tissues. Live and cadaver human tissues were exposed to 660 nm light at locations across the skull, spinal cord and upper and lower limbs. Red-light was produced by a light emitting diode array of various irradiances (15-500 mW/cm2 ) and measured by a light-probe positioned on the tissue surface opposite to the light emitting diodes. 100 mW/cm2 successfully penetrated tissue <50 mm thick; a disproportionate irradiance increase was required to achieve deeper penetration. Penetration was unaffected by skin tone, increased with irradiance and relative bone/muscle composition, and decreased with greater tissue thickness and in males. Live and cadaveric tissue penetration did not differ statistically for tissues <50 mm but cadavers required more red-light to penetrate >50 mm. These results assist clinicians and researchers in determining red-light treatment intensities for penetrating human tissues.

Pituitary dysfunction due to sports-related traumatic brain injury.

PURPOSE: After traumatic brain injury was accepted as an important etiologic factor of pituitary dysfunction (PD), awareness of risk of developing PD following sports-related traumatic brain injury (SR-TBI) has also increased. However there are not many studies investigating PD following SR-TBIs yet. We aimed to summarize the data reported so far and to discuss screening algorithms and treatment strategies. METHODS: Recent data on pituitary dysfunction after SR-TBIs is reviewed on basis of diagnosis, clinical perspectives, therapy, screening and possible prevention strategies. RESULTS: Pituitary dysfunction is reported to occur in a range of 15-46.6% following SR-TBIs depending on the study design. Growth hormone is the most commonly reported pituitary hormone deficiency in athletes. Pituitary hormone deficiencies may occur during acute phase after head trauma, may improve with time or new deficiencies may develop during follow-up. Central adrenal insufficiency is the only and most critical impairment that requires urgent detection and replacement during acute phase. Decision on replacement of growth hormone and gonadal deficiencies should be individualized. Moreover these two hormones are abused by many athletes and a therapeutic use exemption from the league's drug policy may be required. CONCLUSIONS: Even mild and forgotten SR-TBIs may cause PD that may have distressing consequences in some cases if remain undiagnosed. More studies are needed to elucidate epidemiology and pathophysiology of PD after SR-TBIs. Also studies to establish screening algorithms for PD as well as strategies for prevention of SR-TBIs are urgently required.

The neurobiological effects of repetitive head impacts in collision sports.

It is now recognized that repetitive head impacts (RHI) in sport have the potential for long-term neurological impairments. In order to identify targets for intervention and/or pharmacological treatment, it is necessary to characterize the neurobiological mechanisms associated with RHI. This review aims to summarize animal and human studies that specifically address Blood Brain Barrier (BBB) dysfunction, abnormal neuro-metabolic and neuro-inflammatory processes as well as Tau aggregation associated with RHI in collision sports. Additionally, we examine the influence of physical activity and genetics on outcomes of RHI, discuss methodological considerations, and provide suggestions for future directions of this burgeoning area of research.

Overuse injuries in sport: a comprehensive overview.

BACKGROUND: The absence of a single, identifiable traumatic cause has been traditionally used as a definition for a causative factor of overuse injury. Excessive loading, insufficient recovery, and underpreparedness can increase injury risk by exposing athletes to relatively large changes in load. The musculoskeletal system, if subjected to excessive stress, can suffer from various types of overuse injuries which may affect the bone, muscles, tendons, and ligaments. METHODS: We performed a search (up to March 2018) in the PubMed and Scopus electronic databases to identify the available scientific articles about the pathophysiology and the incidence of overuse sport injuries. For the purposes of our review, we used several combinations of the following keywords: overuse, injury, tendon, tendinopathy, stress fracture, stress reaction, and juvenile osteochondritis dissecans. RESULTS: Overuse tendinopathy induces in the tendon pain and swelling with associated decreased tolerance to exercise and various types of tendon degeneration. Poor training technique and a variety of risk factors may predispose athletes to stress reactions that may be interpreted as possible precursors of stress fractures. A frequent cause of pain in adolescents is juvenile osteochondritis dissecans (JOCD), which is characterized by delamination and localized necrosis of the subchondral bone, with or without the involvement of articular cartilage. The purpose of this compressive review is to give an overview of overuse injuries in sport by describing the theoretical foundations of these conditions that may predispose to the development of tendinopathy, stress fractures, stress reactions, and juvenile osteochondritis dissecans and the implication that these pathologies may have in their management. CONCLUSIONS: Further research is required to improve our knowledge on tendon and bone healing, enabling specific treatment strategies to be developed for the management of overuse injuries.

Collision activity during training increases total energy expenditure measured via doubly labelled water.

PURPOSE: Collision sports are characterised by frequent high-intensity collisions that induce substantial muscle damage, potentially increasing the energetic cost of recovery. Therefore, this study investigated the energetic cost of collision-based activity for the first time across any sport. METHODS: Using a randomised crossover design, six professional young male rugby league players completed two different 5-day pre-season training microcycles. Players completed either a collision (COLL; 20 competitive one-on-one collisions) or non-collision (nCOLL; matched for kinematic demands, excluding collisions) training session on the first day of each microcycle, exactly 7 days apart. All remaining training sessions were matched and did not involve any collision-based activity. Total energy expenditure was measured using doubly labelled water, the literature gold standard. RESULTS: Collisions resulted in a very likely higher (4.96 ± 0.97 MJ; ES = 0.30 ± 0.07; p = 0.0021) total energy expenditure across the 5-day COLL training microcycle (95.07 ± 16.66 MJ) compared with the nCOLL training microcycle (90.34 ± 16.97 MJ). The COLL training session also resulted in a very likely higher (200 ± 102 AU; ES = 1.43 ± 0.74; p = 0.007) session rating of perceived exertion and a very likely greater (- 14.6 ± 3.3%; ES = - 1.60 ± 0.51; p = 0.002) decrease in wellbeing 24 h later. CONCLUSIONS: A single collision training session considerably increased total energy expenditure. This may explain the large energy expenditures of collision-sport athletes, which appear to exceed kinematic training and match demands. These findings suggest fuelling professional collision-sport athletes appropriately for the "muscle damage caused" alongside the kinematic "work required".

Melatonin therapy for blunt trauma and strenuous exercise: A mechanism involving cytokines, NFκB, Akt, MAFBX and MURF-1.

Muscle injury occurs due to trauma, strenuous exercise or sports activities; most people affected are athletes. Ineffectively treated muscle injury can negatively affect sports careers and quality of life after retirement from sports. Reports have indicated that the current therapeutic management of muscle injury, particularly anti-inflammatory drugs, are not necessarily effective. Therefore, better therapies are required. Accumulating evidence has demonstrated melatonin's potent antioxidant and anti-inflammatory actions against muscle pathology in sarcopenia or atrophy in systemic disease. However, the underlying mechanisms for the protective effect of melatonin in the context of trauma/strenuous exercise are multifactorial and not well described. This paper reviews data on melatonin's impact on muscle injury and findings that points toward the mechanisms through which melatonin achieves muscle protection. The general concept described in this review is that melatonin inhibits NFκB, reduces cytokine expression, increases Akt that downregulates the ratio of MAFBX and MURF-1 in order to limit the extent of muscle injury and promote muscle recovery post-injury. The work discussed in this review supports the notion that melatonin may be considered a possible therapy against trauma/sports related muscle injury. Inclusion of melatonin as a therapy in sports medicine could therefore provide a better treatment option for injured athletes and sports individuals.

Cardiorespiratory and metabolic responses after exercise-induced muscle damage: the influence of lowered glycogen.

BACKGROUND: We examined the effect of early-onset of muscle damage and low muscle glycogen on cardiorespiratory and metabolic responses to low-intensity exercise. METHODS: Twelve men cycled for 10 min at 50% maximal oxygen uptake before, and 12 h after a morning downhill run (five, 8 min bouts at -12% gradient, with 2 min rests) under normal (NORM) and lowered glycogen (LOW) conditions, following a cross-over design with conditions separated by six weeks. Cardiorespiratory responses were recorded, with oxidation measures derived from stoichiometry equations. RESULTS: Muscle damage symptoms post-downhill (0 h) were similar between conditions. Carbon dioxide ventilatory equivalent increased 12 h post-downhill for LOW (P<0.05), but not NORM (P=0.7). A trend towards decreased respiratory exchange ratio (RER) was shown 12 h post-downhill for LOW (1.00±0.07 to 0.89±0.12, P=0.06), but not NORM (0.94±0.11 to 0.94±0.08; P=0.6). Twelve hours after LOW downhill running fat oxidation increased (0.21±0.18 g·min-1 to 0.36±0.27 g·min-1; P<0.05) and carbohydrate oxidation decreased (2.68±0.52 g·min-1 to 1.98±0.75 g·min-1; P<0.05); NORM oxidation rates were unchanged (fat: 0.26±0.18 g·min-1 to 0.33±0.18 g·min-1; P=0.5; carbohydrate: 2.51±0.49 g·min-1 to 2.29±0.47 g·min-1; P=0.3). CONCLUSIONS: Cycling at low-intensity 12 h post-downhill running with lowered muscle glycogen increased fat oxidation, decreased carbohydrate oxidation and elevated carbon dioxide ventilation. Damaging exercise with reduced glycogen availability increases fat utilization during subsequent low-intensity exercise as little as 12 h later.