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Introduction: Physeal injuries have been overlooked in epidemiological research in youth sports. Our prospective study investigated the incidence, severity, and burden of physeal injuries in a youth elite football academy. Methods: In total, 551 youth male football players from under-9 to under-19 were included and observed over four consecutive seasons. Injuries involving the physis were diagnosed and recorded according to type, location, and diagnosis. Injury incidence (II), severity (days lost), and injury burden (IB) were calculated per squad per season (25 players/squad). Results: There were 307 physeal injuries: 262 apophyseal (85%), 26 physeal (9%), 2 epiphyseal (1%), and 17 other physeal injuries (5%) with 80% (n=245) causing time-loss. The overall mean incidence of time-loss physeal injuries was 6 injuries/squad-season, leading to a total of 157 days lost/squad-season. The U-16s had the highest burden with 444 days lost per squad-season [median: 20 (95% CI: 12–30) days; II: 10 (95% CI: 7.3.1–13.4)]. Apophyseal injuries of the hip–pelvis resulted in the greatest burden [median: 13 (95% CI: 10–17); II: 2.5 (95% CI: 2.1–3.0)]. Peak apophyseal injury incidence per body parts occurred in U-11 for foot–ankle (II: 2.4; 95% CI: 1.0–4.9), U-14 for knee (II: 4.5; 95% CI: 2.7–7.1), and U-17 for hip–pelvis (II: 6.4; 95% CI: 4.2–9.3). Conclusion: Physeal injuries accounted for a quarter of all-time loss with the largest injury burden in U-16. Most physeal injuries involved the lower limb and affected the apophysis. Physeal and apophyseal injuries incidence, burden, and pattern vary substantially depending on age. Hip–pelvic apophyseal injuries accounted for the largest injury burden.

Purposes: Iliac crest avulsion fracture is an unusual pathology. Final functional outcomes are generally excellent, though recurrent symptoms may delay the return to play. There is a lack of publis...

RATIONALE It has been proposed that the increase in the instances of idiosyncratic adverse drug reactions (IADRs) and black box warnings may be attributed to the occurrence of reactive metabolites. Consequently, a high-throughput screen for reactive metabolites formed from liver microsome extracts with added glutathione (GSH) was developed for use in the early stages of drug discovery. METHODS To enhance sensitivity and specificity, as well as accelerate data processing, a mixture of a stable-isotope probe consisting of natural GSH (light GSH) and stable-isotope-labeled [(15) N,(13) C(2)] GSH (heavy GSH) at a ratio of 1:1 was used. Any metabolite that reacted with the GSH results in the formation of light and heavy GSH conjugates with a 3 Da difference. Employing a precursor-ion scan using negative ion electrospray ionization (ESI) corresponding to the expected fragments, signals with the appropriate ratio in the precursor ion scan are then further examined. RESULTS The new method greatly simplifies data collection by assuming molecules containing GSH will fragment to form specific ions. As such, this approach accelerates data processing (and collection) at the risk of missing compounds that do not fragment as expected. The assay was validated with 33 diverse drugs known to form GSH conjugates, 5 drugs known to not form GSH adducts and over 100 samples containing components of the normal in vitro matrix. In all cases data collected matched the expected result. CONCLUSIONS The observed sensitivity, specificity, and fast data processing make this assay an excellent fit for high-throughput screening of reactive metabolites in the early stages of drug discovery. This method is not intended to eliminate compounds or terminate their development. Instead, it is to bring forward molecules with one less liability and thus a greater probability of ultimate success.

Rapid information on metabolic profiling is required to evaluate the structural liabilities of drug candidates in early drug discovery. In this study, a sensitive and rapid semi-quantitative method was developed to simultaneously monitor the drug candidate and metabolites as well as collect tandem mass (MS/MS) spectra for subsequent metabolite identification. The simultaneous semi-quantitation and identification of metabolites in fresh hepatocytes is achieved using high-performance liquid chromatography (HPLC) coupled with a hybrid quadrupole linear ion trap. The survey experiment consists of monitoring multiple-reaction monitoring (MRM) transitions for the internal standard, the parent, and 48 MRM transitions designed to cover the most common phase I and II biotransformations. An information-dependent acquisition (IDA) method was employed to trigger product ion scans above the MRM signal threshold. Three biotransformations of a lead compound have been identified through enhanced product ion scans and the respective MRM transitions of those metabolites were selected for semi-quantitation. Parent disappearance and formation of the metabolites as a function of incubation time in five different species were monitored by their respective MRM responses. The method provides the necessary sensitivity to detect minor metabolites in a relevant therapeutic concentration range. Enzymatic turnover of the parent and the metabolites in different species are revealed based on the different initial concentrations of the parent. This methodology integrates the parent disappearance, metabolite identification, and the formation of the metabolites along the time course using a single rapid LC/MS/MS analysis. This method can be used as a complementary tool to the conventional method of metabolic profiling. It provides a rapid and sensitive initial profile of the metabolism of potential structural series at the lead selection stage. The method can also be incorporated into the overall metabolite profiling scheme to evaluate the drug candidates in drug discovery.

Although substance P (SP) has been implicated as a mediator of neurogenic inflammation in the small intestine, little information is available regarding the role of SP in the pathogenesis of chronic ulcerative colitis. In this study, our aim was to investigate whether the intraperitoneal administration of a nonpeptide neurokinin-1 (NK-1) antagonist, CP-96345, which antagonizes the binding of SP to its NK-1 receptor, results in the attenuation of colonic inflammation induced in rats by 5% dextran sodium sulfate (DSS) in drinking water for 10 days compared with an inactive enantiomer, CP-96344. Disease activity was assessed daily for 10 days, after which colonic tissue damage was scored and myeloperoxidase activity and colon and urinary 8-isoprostanes were measured. Animals receiving DSS exhibited marked physical signs of colitis by day 5 compared with controls. Chronic administration of the NK-1 antagonist significantly reduced the disease activity index, mucosal myeloperoxidase activity, colonic tissue damage score, and mucosal and urinary levels of 8-isoprostanes compared with inactive enantiomer- or vehicle-injected (saline) animals receiving DSS alone. These data indicate that the administration of an NK-1 antagonist can attenuate colonic inflammation and oxidative stress and suggest a novel therapeutic approach in the treatment of chronic ulcerative colitis.

It has been proposed that the increase in the instances of idiosyncratic adverse drug reactions (IADRs) and black box warnings may be attributed to the occurrence of reactive metabolites. Consequently, a high-throughput screen for reactive metabolites formed from liver microsome extracts with added glutathione (GSH) was developed for use in the early stages of drug discovery.To enhance sensitivity and specificity, as well as accelerate data processing, a mixture of a stable-isotope probe consisting of natural GSH (light GSH) and stable-isotope-labeled [(15) N,(13) C(2)] GSH (heavy GSH) at a ratio of 1:1 was used. Any metabolite that reacted with the GSH results in the formation of light and heavy GSH conjugates with a 3 Da difference. Employing a precursor-ion scan using negative ion electrospray ionization (ESI) corresponding to the expected fragments, signals with the appropriate ratio in the precursor ion scan are then further examined.The new method greatly simplifies data collection by assuming molecules containing GSH will fragment to form specific ions. As such, this approach accelerates data processing (and collection) at the risk of missing compounds that do not fragment as expected. The assay was validated with 33 diverse drugs known to form GSH conjugates, 5 drugs known to not form GSH adducts and over 100 samples containing components of the normal in vitro matrix. In all cases data collected matched the expected result.The observed sensitivity, specificity, and fast data processing make this assay an excellent fit for high-throughput screening of reactive metabolites in the early stages of drug discovery. This method is not intended to eliminate compounds or terminate their development. Instead, it is to bring forward molecules with one less liability and thus a greater probability of ultimate success.

Background Lower limbs muscle flexibility remains a common assessment in sports therapy. Nevertheless no clear consensus exists about the methods for performing reliable measurements. Objective The aim of the present study was to examine the reliability of muscle flexibility measures in adolescent athletes. Design Randomised test-retest study. Setting Sports academy physiotherapy laboratory. Participants Height young athletes (age: 15.1±1.6, body mass: 65.4±26.2 kg, height: 171.7±8.8 cm) training in a national sports centre. Interventions Flexibility of the main lower limb muscles was assessed, using a standardised force of stretching for each muscle and a video analysis software for measuring the angles. Each participant was tested on both sides by three operators and on two separate occasions, 4 days apart. Final measurements were reported in degrees. Main outcome measurements Reliability of flexibility measures was assessed by 1) calculating the between-day difference expressed as Cohen9s d (90% CI), no substantial difference was considered if Cohen9s d Results Force of stretching (in N), mean angle (SD), mean between-day difference and CV were 78.5, 132.2 (10.1), −0.05 (−0.3;0.2) and 8.3% (7.5;9.3) for quadriceps, 68.7, 70 (11.2), −0.7 (−1.7;0.4) and 3.3% (3.0;3.7) for hamstrings, 39.2, 53.5 (9.4), 0.05 (−0.2;0.3) and 7.2% (6.5–8.0) for adductors, 147.2, 16 (6.3), 0.10 (−0.1;0.3) and 5.7% (5.1;6.3) for gastrocnemius, 147.2, 30.6 (8.9), 0.01 (−0.2;0.2) and 4.5% (4.0;5.0) for soleus, 98.1, 22.7 (5.9), 0.01 (−0.2;0.2) and 2.6% (2.3;2.9) for hip flexors, 49.1, 54.7 (14.5), −0.04 (−0.2;0.2) and 9.6% (8.6;10.8) for hip medial rotator and 49.1, 43.5 (14.9), −0.08 (−0.3;0.1) and 18.2% (16.3;20.5) for hip lateral rotator. Conclusion The present method for assessing lower limb muscles flexibility has a moderate-to-good level reliability and may integrate prevention programs.