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Purpose Although platelet-rich plasma (PRP) therapy has become an increasingly popular treatment for sports-related injuries, the molecular mechanisms of PRP on tissue healing process remain poorly understood. The aim of the present study was to develop an experimental method quantifying the efficacy of PRP with murine patellar tendon injury model, leading to future elucidation of the mechanisms of PRP on healing processes. Methods Full-thickness defects were created in the central third of the murine patellar tendon. The prepared allogenic PRP gel was applied on the defect of the patellar tendon (PRP group), while the remaining mice served as the untreated control group. Mice were sacrificed at 2, 4, 6, 8, and 10 weeks after the operation, with histological sections obtained in each time point (n = 4 / time point / group). Semi-quantitative histological evaluation was performed in accordance with the Bonar score. The variables included in this scoring system were cell morphology, ground substance, collagen arrangement, and vascularity, with higher grades indicating worse tendon structures. In addition, the ratio of the collagen fibers to the entire tendon tissue (FT ratio) was measured using KS400 software as a quantitative histological evaluation. Results The total Bonar score in the PRP group was significantly lower than in control group. With regard to the variables in the Bonar score, the vascularity score was significantly higher in the PRP group at 2 and 4 weeks, while the collagen arrangement score was significantly lower in the PRP group at 8 weeks. Based on a quantitative evaluation, the recovery speed of the patellar tendon determined by FT ratio was significantly faster in the PRP group than in the control group at 6 and 8 weeks. Conclusions We have developed an experimental method for histological and quantitative evaluation of the effects of PRP on tissue healing using murine patellar tendon injury model. The results of this study suggest that the local application of PRP could enhance the tissue-healing process both directly through action on localized cells and indirectly through the recruitment of reparative cells through the blood flow. Further investigations will be needed to confirm the mechanisms of PRP in tissue-healing processes with the development of this experimental model.

IntroductionThe number of cataract surgeries, the most common ophthalmic surgery, is expected to increase due to ageing populations. Dry eye disease (DED) is a frequent side effect of cataract surgery, contributing to lower postoperative patient satisfaction and suboptimal quality of vision. It is unclear which eye-drops commonly used in these patients should be recommended for postoperative DED treatment. This study aims to compare the efficacy of topical administration of diquafosol sodium 3% vs hyaluronic acid 0.1% eye-drops in patients with DED after cataract surgery.Methods and analysisThe study is designed as a single-blind randomised controlled trial. The participants will be randomly (1:1) allocated to either the diquafosol sodium 3% topical administration group (n=21) or the hyaluronic acid 0.1% topical administration group (n=21). Each group will receive its assigned eye-drop intervention over a 12-week period. The primary outcome will be measured using the total score of the Japanese version of the Ocular Surface Disease Index during the visit 5 weeks postoperatively. Both groups will be followed up after their respective eye-drop application for 12 weeks according to the intervention regimens. Secondary outcome measures including meibomian gland function assessment, tear film break-up time, keratoconjunctival staining score, maximum blink interval and tear secretion volume using Schirmer’s test I will be assessed at 1, 5, 9, 13 and 25 weeks postoperatively.Ethics and disseminationThis study has been approved by the Juntendo Hospital Certified Review Board, Tokyo, Japan (Approved protocol V.7.0 dated 7 May 2021. Approval number: J20-018) and has been registered with the Japan Registry of Clinical Trials. Written informed consent will be collected from every patient prior to study participation. The results of this trial will be presented at local and international meetings and submitted to peer-reviewed journals for publication.Trial registration numberjRCT1031210018.

To assess psychological components after anterior cruciate ligament (ACL) injury, we developed a new patient-reported outcome measure, the Japanese anterior cruciate ligament injury questionnaire 25 (JACL-25), and demonstrated that the JACL-25 is valid, reliable, and sufficiently responsive to evaluate psychological factors that are associated with outcomes in individuals with ACL injuries. The purpose of this study was to identify the optimum cutoff score for the JACL-25 that indicates successful clinical outcomes, combining with the graphical data obtained using the KT-2000. We studied 30 patients who underwent primary ACL reconstruction with a patella tendon or hamstring tendon autograft. On the same day of the JACL-25 evaluation, anterior knee laxity tests were performed using the KT-2000 arthrometer. ACL stiffness was calculated on the graphs of the hysteresis, which can be used to measure side-to-side differences in anterior translation. Akaike’s information criterion (AIC) was used to determine the most appropriate cutoff level for the JACL-25 score for the stiffness reduction ratio and anterior–posterior (AP) translation. The average JACL-25 score was 23.8 (standard deviation (SD) 18.4). The average side-to-side displacement difference in AP translation was 2.4 (SD 4.2) mm. The average stiffness reduction ratio was 24.4% (SD 31.8). The smallest AIC values for the cutoff level for the JACL-25 score, the stiffness reduction ratio, and side-to-side differences of the anterior translation were 9, 27%, and 1.1 mm, respectively. We determined the optimal cutoff score for the JACL-25 that identifies successful clinical outcomes.

Genome wide studies indicate that vascular endothelial growth factor A (VEGF) is associated with osteoarthritis (OA), and increased VEGF expression correlates with increased disease severity. VEGF is also a chondrocyte survival factor during development and essential for bone formation, skeletal growth and postnatal homeostasis. This raises questions of how the important embryonic and postnatal functions of VEGF can be reconciled with an apparently destructive role in OA. Addressing these questions, we find that VEGF acts as a survival factor in growth plate chondrocytes during development but only up until a few weeks after birth in mice. It is also required for postnatal differentiation of articular chondrocytes and the timely ossification of bones in joint regions. In surgically induced knee OA in mice, a model of post-traumatic OA in humans, increased expression of VEGF is associated with catabolic processes in chondrocytes and synovial cells. Conditional knock-down of Vegf attenuates induced OA. Intra-articular anti-VEGF antibodies suppress OA progression, reduce levels of phosphorylated VEGFR2 in articular chondrocytes and synovial cells and reduce levels of phosphorylated VEGFR1 in dorsal root ganglia. Finally, oral administration of the VEGFR2 kinase inhibitor Vandetanib attenuates OA progression.

Increased vascular endothelial growth factor (VEGF) levels are associated with osteoarthritis (OA) progression. Indeed, VEGF appears to be involved in OA-specific pathologies including cartilage degeneration, osteophyte formation, subchondral bone cysts and sclerosis, synovitis, and pain. Moreover, a wide range of studies suggest that inhibition of VEGF signaling reduces OA progression. This review highlights both the potential significance of VEGF in OA pathology and pain, as well as potential benefits of inhibition of VEGF and its receptors as an OA treatment. With the emergence of the clinical use of anti-VEGF therapy outside of OA, both as high-dose systemic treatments and low-dose local treatments, these particular therapies are now more widely understood. Currently, there is no established disease-modifying drug available for patients with OA, which warrants continued study of the inhibition of VEGF signaling in OA, as stand-alone or adjuvant therapy. © 2016 American Society for Bone and Mineral Research.

Introduction Intra-articular distal humeral fractures involving both columns require double-plate fixation. In orthogonal plate fixation, screws from the medial plate reach the radial column, while screws from the dorsolateral plate run posterior–anterior, not creating interdigitation. The Synthes LCP-DHP system has an orthogonal plate configuration that enables dorsolateral plating with support, as the radial and ulnar columns are linked via interdigitation of the distal screws. We hypothesized that the transcondylar screw from the posterolateral plate, which interdigitates with screws from the medial plate, enables more rigid stabilization of orthogonal plating in distal humeral AO type C fractures. Methods A previous study reported the biomechanical properties of orthogonal plate fixation using an AO type 13-C2.3 intra-articular fracture model with a 1-cm supracondylar gap using artificial bones (Kudo et al., Injury, 2016). We performed a biomechanical study of the dorsolateral plate with support, and inserted one 2.7-mm locking screw through the support in the lateral-to-medial direction, creating interdigitation of the distal screws. A 0–200 N axial load was applied separately to the radial and ulnar columns. We calculated the stiffness of both columns, and the anterior displacement of the condylar fragment. We compared the biomechanical properties of orthogonal plating with versus without interdigitation. Results There were no significant differences between the two groups in radial or ulnar axial compression. The ulnar column was stiffer than the radial column in both groups. There were no significant differences between groups in the angular displacements of the capitellum or trochlea. The capitellum moved more anteriorly than the trochlea during axial compression in both groups. Discussion The radial and ulnar columns were linked via interdigitation of the distal screws by adding one transcondylar screw from the dorsolateral plate, which did not affect radial column stiffness or capitellar anterior movement under axial compression. In the orthogonal configuration, axial compression induced more anterior displacement of the capitellum than the trochlea, which may induce secondary fragment or screw dislocation on the dorsolateral plate or nonunion at the supracondylar level. Conclusions The transcondylar screw from the dorsolateral plate did not affect axial compression of the radial column or capitellar anterior displacement.

To identify factors associated with quantified rotatory stability (pivot-shift phenomenon) in the anterior cruciate ligament (ACL)-injured knee joint. A consecutive sample of 54 patients who were diagnosed with an ACL injury and admitted to our hospital to undergo ACL reconstruction were enrolled in this study. Antero-lateral rotatory laxity of the knee joint was quantified using a Kinematic Rapid Assessment device (KiRA; Orthokey LTD) under spinal block before initiating reconstruction of the ACL. Univariate and multivariate regressions were performed assuming relationships between patient characteristics (independent variables) and quantified antero-lateral rotatory stability (a dependent variable). It was observed that a low BMI (t = − 1.659, n.s.), greater passive knee extension angle (t = 2.374, P = 0.023), and a narrower lateral femoral condyle width index (t = − 1.712, n.s.) could be candidates associated with the antero-lateral rotatory instability, using univariate analysis. Employing multivariate analysis controlling for these three variables, that the range of passive knee extension was found to be significantly associated with antero-lateral rotatory instability in the ACL-injured knee joint (t = 2.21, P = 0.035). Patients were then divided into two groups (pivot-shift negative versus positive groups) based on the KiRA-documented quantified pivot-shift test. Interestingly, 23.3% of patients were pivot-shift negative, even though their ACL was confirmed as a complete rupture by arthroscopic observations. The degree of passive knee extension was 2.3 ± 4.5 (mean ± SD) in the pivot-shift negative group, while it was 6.8 ± 6.6 in the pivot-shift positive group (n.s.). The lateral femoral condyle width index was 36.6 ± 2.0% in the pivot-shift negative group, and it was significantly wider than in the pivot-shift positive group (33.8 ± 2.6%, P = 0.0046). Finally, we estimated that the risk of positive pivot-shift depends on the degree of knee extension. The logistic regression analysis revealed that genu recurvatum significantly increased the odds ratio for positive pivot-shift (OR = 3.08, P = 0.047, 95% CI = 1.017–9.350). This study revealed that greater antero-lateral rotatory instability in patients with a complete ACL rupture was associated with genu recurvatum and small lateral femoral condyle. These factors should be considered as predictors of a poor outcome from an ACL reconstruction due to a higher load on the ACL graft, and therefore, the attending physicians should modify the treatment strategies accordingly. This study indicates that joint hyperlaxity and bone morphology contribute to the rotational stability of the knee joint, in addition to the ACL and antero-lateral complex (ALC). IV.

Objectives: To examine the factors associated with increase in lumbar spine bone mineral density (LS-BMD) by bisphosphonates (BPs) with active vitamin D analog (aVD). Methods: Two independent postmenopausal osteoporotic patients treated by BPs with aVD for 24 months (Study 1: n = 93, Study 2: n = 99) were retrospectively analyzed. Results: In Study 1, LS-BMD of the patients significantly increased for 24 m (5.4%, p r2: 0.088, p = .02). While average sCa of the patients was 9.2 mg/dL before treatment, it increased time-dependently to 9.6 mg/dL for 24 m by treatment. As each patient had their LS-BMD five times during the study, there were four instances of %LS-BMD in each patient, resulting in 372 instances of %LS-BMD in Study 1. The smallest Akaike’s information criterion value for the most appropriate cut-off levels of sCa for %LS-BMD by treatment every 6 m was 9.3 mg/dL. The %LS-BMD by treatment for 6 m during 24 m period in patients with sCa ≥9.3 mg/dL (1.5%) was significantly higher than that in patients with sCa p = .038). The results of Study 2 were similar to those of Study 1, confirming the phenomena observed. Conclusion: sCa was associated with an increased LS-BMD by BPs with aVD.

Despite objectively good results, up to 70 % of individuals may not return to their pre-injury level of sports activity after anterior cruciate ligament (ACL) reconstruction surgery. Although psychological responses have been shown to affect outcomes after ACL injury, an appropriate means of measuring their effects, in addition to functional status, has not been determined. The purpose of this study was to develop a patient-reported questionnaire for measuring psychological factors associated with outcomes after ACL injury and to evaluate its reliability, validity, and responsiveness. After item analysis based on the results of two pilot studies and a short relevance assessment, 25 questionnaire items were selected for the Japanese Anterior Cruciate Ligament Injury Questionnaire 25 (JACL-25) and assessed for validity, reliability, and responsiveness in subjects with ACL injury. The JACL-25 had no floor or ceiling effects and no confounding factors. A Cronbach’s alpha coefficient of 0.981 and a Guttman split-half coefficient of 0.983 indicated excellent reliability. Large standardized response means (1.30–1.62) and effect sizes (0.96–1.51) from the preoperative to postoperative period indicated good responsiveness. Construct structures were created, and these items were separated into three domains. Strong correlations between the JACL-25 and the International Knee Documentation Committee Subjective Knee Form (r s = −0.86), Lysholm Score (r s = −0.73), and Tegner Activity Scale (r s = −0.65) indicated good concurrent validity of the JACL-25. The present study demonstrated that the JACL-25 was valid, reliable, and responsive enough to evaluate psychological factors associated with outcomes in individuals with ACL injuries. Diagnostic study, Level III.

Mortality in elderly patients after the surgical treatment of hip fractures remains high. Although individual clinical risk factors have been widely studied, there has been limited research on prediction models in this population. The purpose of this study was to develop a prediction model for in-hospital mortality after hip fracture surgery and to evaluate the performance of this model.Using the National Inpatient Sample database from 2012 to 2013, we collected data on 535,475 patients older than 50 years who had hip fracture surgery. Patient characteristics, surgery-specific factors, and Elixhauser comorbidities were used as candidate variables. The patients were randomly divided into training and testing cohorts. The Lasso (least absolute shrinkage and selection operator) method was used to select predictor variables, and points were assigned to each variable based on its coefficient.We identified 8 essential predictors (age, timing of surgery, male sex, congestive heart failure, pulmonary circulation disease, renal failure, weight loss, and fluid and electrolyte disorders) for mortality, with a maximum prediction score of 20. The model's area under the curve was 0.74, and the Hosmer-Lemeshow test P value was 0.59 on the testing set. With the application of cutoff values (scores 0-5, 6-9, and 10-20), the observed in-hospital postoperative mortality was 0.6%, 2.5%, and 7.5%, respectively.We built a simple prediction model with 8 essential clinical factors that predict in-hospital mortality after hip fracture surgery. This model may assist in counseling patients and families and measuring hospital quality of care.Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Purpose Atypical femoral fractures (AFFs) are stress-related fractures that are speculated to associate with long-term treatment with bisphosphonates for osteoporosis. A history of AFF is a high risk factor for the development of a subsequent AFF in the same location of the contralateral femur, suggesting that a patient's individual anatomical factor(s) are related to the fracture site of AFFs. In this study, we investigated the radiographs of fourteen AFFs (four bilateral fractures among ten patients) treated at six hospitals associated with our university between 2005 and 2010. The fracture site and standing femorotibial angle (FTA), which reflects the mechanical axis of the lower limb, were measured on weight-bearing lower limb radiographs. The fracture site and FTA of patients with typical femoral fractures (TFF) were compared to those of patients with AFFs. The correlations were examined using Spearman's rank correlation coefficients. The fracture locations in the femora were almost the same in the patients with bilateral AFFs. There was a positive correlation between the fracture site and the standing FTA in the patients with AFFs (r = 0.82, 95% confidence interval; 0.49 to 0.94), indicating that the larger the standing FTA (varus alignment), the more distal the site of the fracture in the femur. The FTA of the patients with atypical diaphyseal femoral fracture were significantly larger compared to that of those with not only atypical subtrochanteric fractures but also TFFs. In conclusion, the fracture sites of AFFs are associated with the standing lower limb alignment, while those of TFFs are not.

The long-term treatment with anti-resorptive drugs for osteoporotic patients is suggested to be associated with an increase in atypical femoral fractures (AFFs). However, their incidence, patient characteristics, and risk factors have not been fully elucidated especially in Asian countries. This retrospective observational cohort study found fourteen AFFs in ten patients (four bilateral fractures) among 2,238 hip and femoral shaft fractures treated in our associated hospitals between 2005 and 2010; this incidence (0.63%) was similar to Caucasians. Of the ten patients with AFFs, nine (90%) and six (60%) were using bisphosphonates (BPs) and glucocorticoids (GCs), respectively, compared to 14.3 and 8.6% for patients with typical femoral fractures who were using these agents. As comorbid conditions, five patients had collagen disease (CD) and two had diabetes. A fracture location-, age- and gender-matched (1:3) case-control study revealed that administration of BPs, GCs, and suffering from collagen disease (CD) were significant risk factors for developing AFFs [odds ratios 36.0 (95% confidence intervals 3.8-342.2), 13.0 (2.3-74.1) and 9.0 (1.6-50.3), respectively]. Interestingly, all of the patients with atypical subtrochanteric femoral fractures, defined as those within 5 cm of the lesser trochanter, were taking GCs due to CD, and the age of these patients (average of 54.8 years) was significantly younger than those with atypical diaphyseal femoral fractures (average of 77.2 years, p < 0.05). In conclusion, the incidence of AFFs in the Japanese population was similar to that of Caucasians, and taking BPs and GCs and suffering from CD were risk factors for developing AFFs.

Rodent hindlimb unloading (HU) by tail-suspension is a model to investigate disuse-induced bone loss in vivo. Previously, we have shown that osteopontin (OPN, also known as Spp1) is required for unloading-induced bone loss. However, how unloading affects OPN expression in the body is not fully understood. Here, we examined OPN expression in peripheral blood of mice subjected to HU. Real-time RT-PCR analysis indicated that OPN expression is increased in circulating peripheral blood cells. This HU-induced increase in OPN mRNA expression was specific in circulating peripheral blood cells, as OPN was not increased in the blood cells in bone marrow. HU-induced enhancement in OPN expression in peripheral blood cells was associated with an increase in the fraction of monocyte/macrophage lineage cells in the peripheral blood. In contrast, HU decreased the fraction size of B-lymphocytes in the peripheral blood. We further examined if B-lymphogenesis is affected in the mice deficient for osteopontin subjected to HU. In bone marrow, HU decreased the population of the B-lymphocyte lineage cells significantly, whereas it did not alter the population of monocyte/macrophage lineage cells. HU also increased the cells in T-lymphocyte lineage in bone marrow. Interestingly, these changes were observed similarly both in OPN-deficient and wild-type mice. These results indicate for the first time that HU increases OPN expression in circulating cells and suppresses bone marrow B-lymphogenesis.

Elder populations have been increasing in Japan and estimated 24 million people have knee osteoarthritis(OA). Recently, people have diverse sociological background and demand for participating sports has been growing. People may participate sports to prevent some diseases such as locomotive syndrome. According to the recent studies, excessive high impact sports increase the risk of OA, while daily life exercise decrease the risk. Epidemiological approach demonstrated that reduced knee extension muscle strength increases the risk of OA. We reviewed and discussed the recent topics including efficacy of physical therapy for knee OA and how much sports activities could be beneficial after knee surgery.

To identify unknown risk factors associated with fifth metatarsal stress fracture (Jones fracture). A case–controlled study was conducted among male Japanese professional football (soccer) players with (N = 20) and without (N = 40) a history of Jones fracture. Injury history and physical examination data were reviewed, and the two groups were compared. Univariate and multivariate logistic regression controlling for age, leg dominance and body mass index were used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to describe the association between physical examination data and the presence or absence of Jones fractures. From 2000 to 2014, among 162 professional football club players, 22 (13.6%; 21 Asians and one Caucasian) had a history of Jones fracture. Thirteen out of 22 (60%) had a Jones fracture in their non-dominant leg. The mean range of hip internal rotation (HIR) was restricted in players with a history of Jones fracture [25.9° ± 7.5°, mean ± standard deviation (SD)] compared to those without (40.4° ± 11.1°, P

ObjectiveThe fifth metatarsal stress fracture is a common injury among football players. Although several risk factors have been proposed, the association between the playing surface and development of fifth metatarsal stress fractures (MT-5) has not been evaluated. We conducted an epidemiological study using a computer-based survey to investigate the association between the playing surface and development of MT-5.MethodsThis study included 1854 football players, of which 41 experienced MT-5 within the past 24 months. Baseline demographic data and the percentage of time spent playing on artificial turf and clay fields were compared between the non-MT-5 and MT-5 player groups, and the risks for development of MT-5 associated with the playing surfaces were estimated by univariate and multivariate analyses.ResultsThere were significant differences in body mass index, years of play, playing categories and playing time on artificial turf between non-MT-5 and MT-5 groups (p80% of the time increased (3.44: 1.65 to 7.18), and for playing on a clay field 61%–80% of the time, the OR decreased (0.25: 0.11 to 0.59).ConclusionsA higher percentage of playing time on an artificial turf was a risk factor for developing MT-5 in football players. This finding could be beneficial for creating strategies to prevent MT-5.

Introduction Previous reports have questioned whether an orthogonal or parallel configuration is superior for distal humeral articular fractures. In previous clinical and biomechanical studies, implant failure of the posterolateral plate has been reported with orthogonal configurations; however, the reason for screw loosening in the posterolateral plate is unclear. The purpose of this study was to evaluate biomechanical properties and to clarify the causes of posterolateral plate loosening using a humeral fracture model under axial compression on the radial or ulnar column separately. And we changed only the plate set up: parallel or orthogonal. Materials and methods We used artificial bone to create an Association for the Study of Internal Fixation type 13-C2.3 intra-articular fracture model with a 1-cm supracondylar gap. We used an anatomically-preshaped distal humerus locking compression plate system (Synthes GmbH, Solothurn, Switzerland). Although this is originally an orthogonal plate system, we designed a mediolateral parallel configuration to use the contralateral medial plate instead of the posterolateral plate in the system. We calculated the stiffness of the radial and ulnar columns and anterior movement of the condylar fragment in the lateral view. Results The parallel configuration was superior to the orthogonal configuration regarding the stiffness of the radial column axial compression. There were significant differences between the two configurations regarding anterior movement of the capitellum during axial loading of the radial column. Discussion The posterolateral plate tended to bend anteriorly under axial compression compared with the medial or lateral plate. We believe that in the orthogonal configuration axial compression induced more anterior displacement of the capitellum than the trochlea, which eventually induced secondary fragment or screw dislocation on the posterolateral plate, or nonunion at the supracondylar level. In the parallel configuration, anterior movement of the capitellum or trochlea was restricted because of the angular stability of the plate and locking screws in the condyle. Conclusions The posterolateral plate tended to bend anteriorly under axial compression of the radial column in the orthogonal configuration, which led to secondary displacement of the posterolateral plate and eventual screw loosening.

Vascular abnormalities in the eye are the leading cause of many forms of inherited and acquired human blindness. Loss-of-function mutations in the Wnt-binding co-receptor LRP5 leads to aberrant ocular vascularization and loss of vision in genetic disorders such as osteoporosis-pseudoglioma syndrome. The canonical Wnt-β-catenin pathway is known to regulate retinal vascular development. However, it is unclear what precise role LPR5 plays in this process. Here, we show that loss of LRP5 function in mice causes retinal hypovascularization during development as well as retinal neovascularization in adulthood with disorganized and leaky vessels. Using a highly specific Flk1-CreBreier line for vascular endothelial cells, together with several genetic models, we demonstrate that loss of endothelium-derived LRP5 recapitulates the retinal vascular defects in Lrp5-/- mice. In addition, restoring LRP5 function only in endothelial cells in Lrp5-/- mice rescues their retinal vascular abnormalities. Furthermore, we show that retinal vascularization is regulated by LRP5 in a dosage dependent manner and does not depend on LRP6. Our study provides the first direct evidence that endothelium-derived LRP5 is both necessary and sufficient to mediate its critical role in the development and maintenance of retinal vasculature.

Background:The fifth metatarsal bone is a common site of stress fractures in soccer athletes. Although several endocrine risk factors for stress fractures have been proposed, the endocrine risks for fifth metatarsal (5-MT) stress fractures have not been evaluated.Methods:To evaluate the endocrine risks of fifth metatarsal stress fractures, we conducted a cumulative case-control study. The present study included 37 athletes, of which 18 had a history of a zone 2 or zone 3 fifth metatarsal stress fracture and 19 controls. We analyzed serum 25-hydroxyvitamin D (25-OHD), serum parathyroid hormone (PTH), as well as biochemical markers of bone turnover by univariate or multivariate analyses.Results:Logistic regression analyses adjusted for multiple confounders revealed that insufficient serum 25-OHD levels less than 30 ng/mL (odds ratio [OR], 23.3), higher serum PTH levels (OR, 1.01), or higher serum bone-specific isoform of alkaline phosphatase levels (OR, 1.10) rather than serum tartrate-resistant acid phosphatase 5b were associated with statistically significantly increased odds of 5-MT stress fractures. A postestimation calculation demonstrated that 25-OHD levels of 10 and 20 ng/mL were associated with 5.1 and 2.9 times greater odds for 5-MT stress fractures, respectively.Conclusion:25-OHD insufficiency was associated with an increased incidence of 5-MT stress fractures. This insight may be useful for intervening to prevent 5-MT stress fractures.Level of Evidence:Level III, case-control study.

Background Platelet-rich plasma (PRP) therapy has become an increasingly popular treatment for orthopaedics and sports-related injuries, and various clinically available PRP preparation methods exist. However, the differences in PRP quality among numerous preparation methods remain unclear. Specifically, the benefit of including leukocytes in the PRP product remains controversial, and few studies have been conducted to evaluate the effects of the interaction between platelets and leukocytes on the growth factor concentrations. The aim of the present study was to compare the biological characteristics of PRPs focusing on the leukocyte concentration and composition. Methods Leucocyte rich (LR)-PRP, leucocyte poor (LP)-PRP, and pure-PRP were prepared from the peripheral blood of 6 healthy male volunteers (mean age: 31.3 years). The concentrations of platelets, leukocytes, erythrocytes, growth factors (transforming growth factor-beta 1: TGF-β1; fibroblast growth factor-basic: FGF-b; platelet-derived growth factor-BB: PDGF-BB; vascular endothelial growth factor: VEGF) and matrix metalloproteinase-9 (MMP-9) from each of the PRP samples were measured. Considering the interaction between platelets and leukocytes, correlations between platelets/leukocytes and growth factors/MMP-9 were analyzed using partial correlation coefficients. Results The platelet concentration did not differ among the three PRP preparation methods. Conversely, the leukocyte concentration was dramatically different: 14.9 ± 4.5 (10 3 /μl) in LR-PRP, 2.4 ± 1.3 (10 3 /μl) in LP-PRP, 0.2 ± 0.2 (10 3 /μl) in pure-PRP. The platelet concentration positively correlated with all growth factors. On the other hand, the leukocyte concentration positively correlated with PDGF-BB and the VEGF concentration, while it negatively correlated with FGF-b. Regarding catabolic factors, the MMP-9 concentration strongly correlated with the leukocyte concentration, while there was no correlation between the platelet and MMP-9 concentrations. Conclusions These findings demonstrate that leukocytes strongly influence the quality of PRPs. Therefore, modifying the PRP preparation method according to the pathology is essential to achieve better clinical results with PRP therapy.

The sympathetic nervous system suppresses bone mass by mechanisms that remain incompletely elucidated. Using cell-based and murine genetics approaches, we show that this activity of the sympathetic nervous system requires osteopontin (OPN), a cytokine and one of the major members of the noncollagenous extracellular matrix proteins of bone. In this work, we found that the stimulation of the sympathetic tone by isoproterenol increased the level of OPN expression in the plasma and bone and that mice lacking OPN (OPN-KO) suppressed the isoproterenol-induced bone loss by preventing reduced osteoblastic and enhanced osteoclastic activities. In addition, we found that OPN is necessary for changes in the expression of genes related to bone resorption and bone formation that are induced by activation of the sympathetic tone. At the cellular level, we showed that intracellular OPN modulated the capacity of the β2-adrenergic receptor to generate cAMP with a corresponding modulation of cAMP-response element binding (CREB) phosphorylation and associated transcriptional events inside the cell. Our results indicate that OPN plays a critical role in sympathetic tone regulation of bone mass and that this OPN regulation is taking place through modulation of the β2-adrenergic receptor/cAMP signaling system.

Parathyroid hormone/parathyroid hormone-related protein receptor (PPR) signaling is known to be involved in tooth development. In bone, extracellular matrix protein osteopontin (OPN) is a negative regulator of PPR signaling in bone formation. However, the role of OPN in modulation of PPR action in tooth development is not understood. Therefore, we examined the tooth in double mutant mice. Constitutively active PPR was expressed specifically in the odontoblasts and osteoblasts (caPPR-tg) in the presence or absence of OPN. Radiographic analysis indicated that the length of the third molar (M3) and the incisor was decreased in the caPPR-tg mice compared to wild type, and such reduction in molar and incisor length was further enhanced in the absence of OPN (caPPR-tg OPN-KO). With respect to histology of incisors, caPPR-tg induced high cellularity and irregularity in odontoblastic shape and this was enhanced by the absence of OPN. These morphological observations suggest that OPN modulates PPR signaling that are involved in tooth formation.

Per-1 is one of the clock genes and is known to regulate various biological events including bone mass determination. Parathyroid hormone is anabolic to bone while the mechanism of its action is not fully understood. Here, we examined the role of PTH on Per-1 gene expression under osteoblast specific PTH signaling. Constitutively active PTH receptor (caPPR) expressed specifically in osteoblasts in transgenic mice activates Per-1 gene expression in bone. This is specific as expression of other clock gene Bmal-1 is not affected by caPPR over-expression. Per-1 is also expressed in osteoblastic cell line. Interestingly, Per-1 expression is required for PTH signaling-induced CRE dependent transcription. This is forming a positive feed back loop in the anabolic action of PTH signaling and Per-1 in bone. These data indicate that PTH singling in osteoblasts activates Per-1 gene expression in vivo in association with its anabolic action in bone at least in part through the regulation of transcriptional events.

Schnurri (Shn)-2 is a transcriptional modulator of bone formation and bone resorption and its deficiency causes low turnover state with higher cancellous bone mass due to the defects in osteoclasts that exceeds the defects in osteoblasts in mice. We addressed whether such low turnover of bone remodeling in Shn2 deficiency may be modulated in the absence of estrogen that induces high turnover state in vivo. Ovariectomy reduced bone mass in wild type compared to sham operated control mice and such reduction in bone mass was also observed in Shn2 deficient mice. However, due to the high levels of basal bone mass in Shn2 deficient mice, the bone mass levels after ovariectomy were still comparable to sham operated wild-type mice. Analysis indicated that estrogen depletion increased bone resorption at similar levels in wild type and Shn2 deficient mice though the basal levels of osteoclast number was slightly lower in Shn2-deficient mice. In contrast, basal levels of bone marrow cell mineralization in cultures were low in Shn2-deficeint mice while estrogen depletion increased the mineralization levels to those that were comparable to sham wild type. This indicates that Shn2-deficient mice maintain bone mass at the levels comparable to wild-type sham mice even after ovariectomy-induced bone loss and this correlates with the high levels of mineralization activity in bone marrow cells after ovariectomy. J. Cell. Physiol. 226: 573–578, 2011. © 2010 Wiley-Liss, Inc.

Multinuclear complexes consisting of metal ions and a bis(terpyridyl) ligand were covalently bound to carbon substrates. The bonding of the complexes is initiated by the bonding of phenylterpyridine (PT) on the substrates using its in-situ-generated diazonium derivative, followed by stepwise coordination of the metal ions and the ligand on it. The bonding of the PT and the formation of the multinuclear complexes were confirmed by XPS, AFM, and CV measurements. The heterogeneous rate constant (k) at the Co complex-substrate interface was evaluated by chronoamperometry (CA). The estimated high k = (2.9-3.6) x 10(3) s(-1)) would be attributed to the C-C bond at the interface without interrupting the conjugation. These multinuclear complexes bound to the carbon substrates can facilitate electron transfer from redox species such as enzymes.

Ultrafast dynamics of vibrational energy transfer in overlayers of D2O and CO on Pt(111) have been investigated by femtosecond time-resolved (TR) IR−visible sum-frequency-generation (SFG) spectrosc...

The mechanism of cycloaddition reaction between ethylene and the Si dimer on Si (100) is discussed from our recent experimental results using high-resolution electron energy loss spectroscopy and valence photoelectron spectroscopy at ~50 K. The weakly adsorbed π-complex state is identified as a precursor for di-σ bond formation and the activation barrier is roughly estimated to be ~0.2 eV. A different reaction route may exist since a di-σ species is also observed at low temperature. Using cycloaddition reaction, unsaturated organic molecules are chemically attached to the dimer on Si (100), and the adsorbed species are relatively stable. Thus, scanning tunneling spectroscopy (STS) measurements of a single adsorbed molecule can be carried out at room temperature. We report the STS results of 2-butyne adsorbed on Si (100).

吸収式冷凍機内の銅イオンの回収技術について検討し，以下に要約する結果を得た．(1) 実機における冷媒およびLiBr溶液中の銅イオンおよび酸化物の濃度および存在形態を調査し，銅イオンの回収技術の基礎データとした．(2) 電解による銅イオン回収法について検討し，カソード電極電位を－1.0～－0.6 V vs. SSEに保持することで効率良く銅イオンを捕捉回収できることを確認した．(3) 2 電極方式の銅イオン電解回収装置を試作した．実機にて適用，評価し，カソード電極に銅イオンが還元析出し，冷媒およびLiBr溶液中の銅イオンを目標レベルである1 mg dm－3以下に維持できることを検証した．(4) 活性金属電極を応用した置換型浄化フィルターを開発した．実験室および実機で冷媒および LiBr 溶液中の銅イオンおよび酸化物を目標レベル以下に維持できることを検証した．

We investigated the adsorption states and the reaction of vinyl bromide (CH2=CHBr) on Si(100)c(4×2), using high-resolution electron energy loss spectroscopy. We found that the chemisorption of this molecule occurs via a precursor state and a vinyl bromide molecule is di-σ bonded to the Si dimer on Si(100)c(4×2) in the chemisorption state. The precursor species are observed in the temperature range from 58 to 90 K. Judging from the vibrational spectra, we conclude that the structure of the precursor state is a three-atom intermediate state (π complex). The activation energy and the preexponential factor of the reaction from the precursor state to the chemisorption state are estimated to be 27.3 kJ/mol (283 meV) and 1.5 × 1013 s-1, respectively. The activation energy decreases with increasing the vinyl bromide coverage owing to the steric repulsion.

Adsorption of trimethylamine (TMA) on Si(100)c(4×2) has been studied using scanning tunneling microscopy (STM), valence photoelectron spectroscopy (PES), and high-resolution electron energy spectroscopy (HREELS) between 80 and 300 K. The TMA molecule is adsorbed nondissociatively only on the down dimer atom and appears as a triangle shaped bright protrusion in the occupied state STM image. The saturation coverage of TMA on Si(100) is estimated to be ∼0.25 ML (ML = one molecule per surface Si atom). The PES and HREELS results suggest that TMA is adsorbed through the N lone pair by forming an Si−N dative bond. The HREELS spectra indicate that the symmetry of adsorbed TMA is Cs and the molecular C3 axis is tilted from the surface normal. The stretching mode of the SiN dative bond is observed at 525 cm-1. Thus the combined STM, PES, and HREELS results indicate that the chemisorption of TMA on Si(100)c(4×2) occurs selectively on the down dimer atom via dative bonding. Hence, the TMA adsorption on Si(100)c(4×2)...

We have investigated the electronic states of clean and BF 3 adsorbed Si(100) surfaces at low temperature by means of high resolution Si 2p photoelectron spectroscopy. The peak intensities of upper atom and lower atom of the asymmetric dimer in Si 2p spectra do not change even at 30 K compared with those at higher temperature up to 300 K, indicating that the dimer is asymmetric in the ground state. In order to investigate chemical reactivity of asymmetric dimer on Si(100), a typical Lewis acid molecule BF 3 is adsorbed on Si(100). We have found that BF 3 molecules are dissociated into BF 2 and F on Si(100) and dissociated species (BF 2 and F) are adsorbed predominantly on the up dimer atoms of the asymmetric dimers.

The adsorbed states of 1,1,1-trifluoro-2-propanol (TFIP) molecule on Si(1 0 0) c(4 × 2) have been investigated by high resolution electron energy loss spectroscopy. TFIP is dissociatively adsorbed on Si(1 0 0) as CF 3 CH(O–Si)CH 3 and H–Si at 100 K. These species are stable up to 300 K. At 400 K, CF bonds start to be dissociated. At 800 K, all adsorbed species are decomposed into SiH, SiF, SiF 2 and residual carbon species. At 1050 K, the silicon carbide is formed.

We used the energy-selected-photoelectron photoion coincidence (ESPEPICO) method to study site-specific fragmentation caused by C:1s photoionization of 1,1,1-trifluoro-2-propanol-d1 [CF3CD(OH)CH3, TFIP-d1] on a Si(100) surface. High-resolution electron energy loss spectroscopy showed that TFIP-d1 is dissociatively chemisorbed like (CF3)(CH3)CDO–Si(100), and different chemical shifts at the three carbon sites were observed by photoelectron spectroscopy. The site-specific fragmentation evident in the ESPEPICO spectra of the sub-monolayer at room temperature indicates that the TFIP-d1 there has an O–Si bond oriented in the trans position with respect to the C–CF3 bond. Here we discuss the fragmentation processes in light of the results obtained with the ESPEPICO method and the Auger-electron photoion coincidence method.

The interface bonding between adsorbates (ethylene and benzene) and the Si(1 0 0)c(4×2) surface has been investigated by means of angle-dependent Si 2p high resolution photoelectron spectroscopy at 140 K, and several new quantitative properties have been obtained. Upon ethylene adsorption, a drastic decrease of up dimer and down dimer atom components (95%), and the appearance of a new component has been observed. This new component is assigned to the outer most Si atoms which are bonded to ethylene. The originally asymmetric Si dimer atoms become chemically equivalent upon adsorption. In the case of benzene, the decrease of up dimer and down dimer components is about 49% at the saturation coverage, and the unreacted dimers remain asymmetric. The charge transfer between adsorbed molecules and the Si(1 0 0)(2×1) surface has been estimated from the core-level shift and the nature of interface bonding including surface and second layer Si atoms is discussed.

Adsorbed states of cyclopentene on Si(100)(2×1) have been investigated by means of low energy electron diffraction (LEED), valence and Si 2p photoelectron spectroscopy (PES) using synchrotron radiation, and high-resolution electron energy loss spectroscopy (HREELS). Valence and Si 2p PES results indicate that the dangling bonds of the Si(100)(2×1) dimer and the π-bond of cyclopentene interact with each other, resulting in the formation of Si−C bonds. The valence electronic structure of adsorbed cyclopentene is similar to that of gas-phase cyclopentane. In addition, the HREELS spectra of cyclopentene on Si(100)(2×1) resemble the vibrational spectra of free cyclopentane and the cyclopentene di-σ bonded to Pt(111). Therefore, we conclude that cyclopentene is di-σ bonded to the Si(100)(2×1) surface and the molecular structure is similar to that of cyclopentane (all the carbon atoms are in sp3 state); the possible adsorbed structures are discussed. At saturation, 76% of the dimers are reacted, indicating that ...

Background Fifth metatarsal stress fracture (Jones fracture) is one of the issues of sports-related injuries. Objective Exploration of unknown risk factor for developing Jones fractures. Design Case control study. Setting Retrospective cohort study in male Japanese professional football (soccer) players. Patients (or Participants) Case control study conducted between with (n=20) and without (n=40) the history of Jones fractures. Interventions (or Assessment of Risk Factors) Reviewed the medical check data regarding the joint and muscle tightness at the time they joined the team, and compared them between two groups. Main Outcome Measurements Risk factors to develop developing Jones fracture. Results The mean age sustaining Jones fracture was 20.5 years old (95% CI, 19.1–21.8, range 17–28). The fracture occurred in their non-dominant (standing) legs in 60% (12/20) of players. Among the physical examination data, Hip internal rotation (HIR) was significantly restricted in players with history of Jones fracture (25.9 degrees on average) compared with those without Jones fractures (40.4 degrees, p Conclusions Restriction of HIR was significantly associated with increased risk of Jones fracture in professional football players in Japan.

We have studied the adsorption states of cyclohexene on Si(100)(2×1) by means of photoelectron spectroscopy (PES) and scanning tunneling microscopy (STM). PES results indicate the interaction between π bond of cyclohexene and the dangling bond of the dimer. Two adsorbed state are observed in STM images; one shows a symmetric protrusion, and another one is asymmetric and consists of some small protrusions. The former is assigned to the boat conformation of adsorbed cyclohexene, and the latter is assigned to the twist-boat conformation.