Objective. To investigate whether cartilage degeneration is prevented or minimized following intraarticular injections of lubricin derived from human synoviocytes in culture, recombinant human PRG4 (rhPRG4), or human synovial fluid (SF) in a rat model of anterior cruciate ligament (ACL) injury.Methods. Unilateral ACL transection (ACLT) was performed in Lewis rats (n ؍ 45). Nine animals were left untreated. The remaining rats were given intraarticular injections (50 l/injection) of either phosphate buffered saline (PBS) (n ؍ 9), human synoviocyte lubricin (200 g/ml; n ؍ 9), rhPRG4 (200 g/ml; n ؍ 9), or human SF lubricin (200 g/ml; n ؍ 9) twice weekly beginning on day 7 after injury. Joints were harvested on day 32 after injury. Histologic analysis was performed using Safranin O-fast green staining, and articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI)-modified Mankin criteria. Histologic specimens were immunoprobed for lubricin and sulfated glycosaminoglycans. A 24-hour urine collection was performed on days 17 and 29 postinjury, and urinary C-terminal telopeptide of type II collagen (CTX-II) levels were measured.Results. Treatment with human synoviocyte lubricin resulted in significantly lower OARSI scores for cartilage degeneration compared with no treatment or PBS treatment (P < 0.05). Increased immunostaining for lubricin in the superficial zone chondrocytes and on the surface of cartilage was observed in lubricin-treated, but not untreated or PBS-treated, joints. On day 17, urinary CTX-II levels in human synoviocyte lubricinand human SF lubricin-treated animals were significantly lower than those in untreated animals (P ؍ 0.005 and P ؍ 0.002, respectively) and in PBS-treated animals (P ؍ 0.002 and P < 0.001, respectively).Conclusion. After treatment with any of the 3 types of lubricin evaluated in this study, a reduction in cartilage damage following ACLT was evident, combined with a reduction in type II collagen degradation. Our findings indicate that intraarticular lubricin injection following an ACL injury may be beneficial in retarding the degeneration of cartilage and the development of posttraumatic OA.
Purpose This study compares the frequency and severity of head impacts sustained by football players on days with and without diagnosed concussion and to identify the sensitivity and specificity of single impact severity measures to diagnosed injury. Methods 1,208 players from eight collegiate and six high school football teams wore instrumented helmets to measure head impacts during all team sessions, of which 95 players were diagnosed with concussion. Eight players sustained two injuries and one three, providing 105 injury cases. Measures of head kinematics (peak linear and rotational acceleration, Gadd Severity Index (GSI), Head Injury Criteria (HIC15), change in head velocity (Δv)) and the number of head impacts sustained by individual players were compared between days with and without diagnosed concussion. Receiver operator characteristic curves were generated to evaluate the sensitivity and specificity of each kinematic measure to diagnosed concussion using only those impacts that directly preceded diagnosis. Results Players sustained a higher frequency of impacts and impacts with more severe kinematic properties on days of diagnosed concussion than on days without diagnosed concussion. Forty-five injury cases were immediately diagnosed following head impact. For these cases, peak linear acceleration and HIC15 were most sensitive to immediately diagnosed concussion (AUC = 0.983). Peak rotational acceleration was less sensitive to diagnosed injury than all other kinematic measures (p = 0.01) which are derived from linear acceleration (peak linear, HIC15, GSI, and Δv). Conclusions Players sustain more impacts and impacts of higher severity on days of diagnosed concussion than on days without diagnosed concussion. Additionally, of historical measures of impact severity, those associated with peak linear acceleration are the best predictors of immediately diagnosed concussion.
We have constructed recombinant human adenoviruses that express wild-type human p53 under the control of either the Ad 2 major late promoter (MLP) or the human cytomegalovirus (CMV) immediate early gene promoter. Each construct replaces the Ad 5 E1a and E1b coding sequences necessary for viral replication with the p53 cDNA and MLP or CMV promoter. These p53/Ad recombinants are able to express p53 protein in a dose-dependent manner in infected human cancer cells. Tumor suppressor activity of the expressed p53 protein was assayed by several methods. [3H]Thymidine incorporation assays showed that the recombinant adenoviruses were capable of inhibiting DNA synthesis in a p53-specific, dose-dependent fashion. Ex vivo treatment of Saos-2 tumor cells, followed by injection of the treated cells into nude mice, led to complete tumor suppression using the MLP/p53 recombinant. Following a single injection of CMV/p53 recombinant adenovirus into the peritumoral space surrounding an in vivo established tumor derived from a human small cell lung carcinoma cell line (NIH-H69), we were able to detect p53 mRNA in the tumors at 2 and 7 days post-injection. Continued treatment of established H69 tumors with MLP/p53 recombinant led to reduced tumor growth and increased survival time compared to control treated animals. These results indicate that recombinant adenoviruses expressing wild-type p53 may be useful vectors for gene therapy of human cancer.
Accumulation of head impacts may contribute to acute and long-term brain trauma. Wearable sensors can measure impact exposure, yet current sensors do not have validated impact detection methods for accurate exposure monitoring. Here we demonstrate a head impact detection method that can be implemented on a wearable sensor for detecting field football head impacts. Our method incorporates a support vector machine classifier that uses biomechanical features from the time domain and frequency domain, as well as model predictions of head-neck motions. The classifier was trained and validated using instrumented mouthguard data from collegiate football games and practices, with ground truth data labels established from video review. We found that low frequency power spectral density and wavelet transform features (10~30 Hz) were the best performing features. From forward feature selection, fewer than ten features optimized classifier performance, achieving 87.2% sensitivity and 93.2% precision in cross-validation on the collegiate dataset (n = 387), and over 90% sensitivity and precision on an independent youth dataset (n = 32). Accurate head impact detection is essential for studying and monitoring head impact exposure on the field, and the approach in the current paper may help to improve impact detection performance on wearable sensors.
Context: The Functional Movement Screen (FMS) is a popular test to evaluate the degree of painful, dysfunctional, and asymmetric movement patterns. Despite great interest in the FMS, test-retest reliability data have not been published.Objective: To assess the test-retest and interrater reliability of the FMS and to compare the scoring by 1 rater during a live session and the same session on video.Design: Cross-sectional study. Setting: Human performance laboratory in the sports medicine center.Patients or Other Participants: A total of 21 female (age ¼ 19.6 6 1.5 years, height ¼ 1.7 6 0.1 m, mass ¼ 64.4 6 5.1 kg) and 18 male (age ¼ 19.7 6 1.0 years, height ¼ 1.9 6 0.1 m, mass ¼ 80.1 6 9.9 kg) National Collegiate Athletic Association Division IA varsity athletes volunteered.Intervention(s): Each athlete was tested and retested 1 week later by the same rater who also scored the athlete's first session from a video recording. Five other raters scored the video from the first session.Main Outcome Measure(s): The Krippendorff a (K a) was used to assess the interrater reliability, whereas intraclass correlation coefficients (ICCs) were used to assess the testretest reliability and reliability of live-versus-video scoring.Results: Good reliability was found for the test-retest (ICC ¼ 0.6), and excellent reliability was found for the live-versus-video sessions (ICC ¼ 0.92). Poor reliability was found for the interrater reliability (K a ¼ .38).Conclusions: The good test-retest and high live-versusvideo session reliability show that the FMS is a usable tool within 1 rater. However, the low interrater K a values suggest that the FMS within the limits of generalization should not be used indiscriminately to detect deficiencies that place the athlete at greater risk for injury. The FMS interrater reliability may be improved with better training for the rater.Key Words: repeatability, preparticipation screening, injuryprevention screening Key PointsWithin the limits of generalizability, the Functional Movement Screen (FMS) had good test-retest reliability but low interrater reliability. Given that FMS scores are not comparable between raters and these differences may influence the score's clinical utility, the FMS should be used cautiously to detect deficiencies that place the athlete at greater risk for injury. Including a population with a wider range of FMS scores may improve the reliability of the scoring system. S creening tools identify the presence or absence of an identified risk factor, which then requires follow up.
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