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To evaluate the polarity, energy band diagram, and oxygen (O) distribution of a heavily Mg-doped InN (InN:Mg+) epilayer with a Mg concentration of 1.0±0.5×1020cm-3, the core-level and valence band (VB) photoelectron spectra are investigated by angle-resolved soft and hard X-ray photoelectron spectroscopies. The InN:Mg+ epilayers are grown by radio-frequency plasmaassisted molecular beam epitaxy. In this doping level, the polarity inversion from In-polar to N-polar occurs with the increase in the Mg flow rate under the same growth conditions, and the VB spectrum clearly indicates the direction of polarity of InN:Mg+, which is N-polar. The energy band diagram is considered to exhibit a two-step downward bending structure due to the coexistence of the n+ surface electron accumulation layer and heavily Mg-doped p+ layer formed in the bulk. The O concentration rapidly increases until ∼4 nm with respect to the surface, which is deduced to be one of the reasons of the formation of the anomalous two-step energy band profile. [ABSTRACT FROM AUTHOR]

Objectives: To clarify the effects of follow-on therapy after denosumab (DMAb) discontinuation. Methods: In this retrospective, multicenter study, postmenopausal patients with osteoporosis who were previously treated by oral bisphosphonates (BP) (n = 26) or teriparatide (TPTD) (n = 27) were switched to DMAb (administered 2.6 times), and then discontinued. Patients (73.1 years, T-scores of the lumbar spine [LS] - 2.7 and femoral neck [FN] - 2.2) were switched to either (1) raloxifene (RAL) (n = 13) or BP [(2) weekly or monthly BP (wmBP) (n = 29) or (3) zoledronate (ZOL) (n = 11)], based on each physician's decision (mean interval after final DMAb administration was 7.2 months). Bone mineral density (BMD) at final DMAb administration were set as baseline. Results: Changes in LS BMD at 1.5 years after final DMAb administration were -2.7% in the RAL, 0.7% in the wmBP, and 1.9% in the ZOL (p = .31 between groups), and in FN BMD were -3.8%, -0.8%, and 1.8%, respectively (p = .02 between the RAL and ZOL; p = .048 between the RAL and BP). Clinical vertebral fracture incidence during 1.5 years after final DMAb administration was 23.1% in the RAL, 3.4% in the wmBP, and 0.0% in the ZOL (p = .048 between the RAL and ZOL; p = .015 between the RAL and BP). No significant differences were observed in these parameters between the wmBP and ZOL. Conclusion: These results may contribute to the selection of adequate follow-on therapy after DMAb discontinuation, although further investigations are required. [ABSTRACT FROM AUTHOR]

A fracture that does not unite in nine months is defined as nonunion. Nonunion is common in fragmented fractures and large bone defects where vascularization is impaired. The distal third of the tibia, the scaphoid bone or the talus fractures are furthermore prone to nonunion. Open fractures and spinal fusion cases also need special monitoring for healing. Bone tissue regeneration can be attained by autografts, allografts, xenografts and synthetic materials, however their limited availability and the increased surgical time as well as the donor site morbidity of autograft use, and lower probability of success, increased costs and disease transmission and immunological reaction probability of allografts oblige us to find better solutions and new grafts to overcome the cons. A proper biomaterial for regeneration should be osteoinductive, osteoconductive, biocompatible and mechanically suitable. Cytokine therapy, where growth factors are introduced either exogenously or triggered endogenously, is one of the commonly used method in bone tissue engineering. Transforming growth factor ß (TGFß) superfamily, which can be divided structurally into two groups as bone morphogenetic proteins (BMPs), growth differentiation factors (GDFs) and TGFß, activin, Nodal branch, Mullerian hormone, are known to be produced by osteoblasts and other bone cells and present already in bone matrix abundantly, to take roles in bone homeostasis. BMP family, as the biggest subfamily of TGFß superfamily, is also reported to be the most effective growth factors in bone and development, which makes them one of the most popular cytokines used in bone regeneration. Complications depending on the excess use of growth factors, and pleiotropic functions of BMPs are however the main reasons of why they should be approached with care. In this review, the Smad dependent signaling pathways of TGFß and BMP families and their relations and the applications in preclinical and clinical studies will be briefly summarized. [ABSTRACT FROM AUTHOR]

Objectives: To establish anti-C1q monoclonal antibodies which can measure serum C1q levels discriminating disease severity subsets of rheumatoid arthritis (RA) within 5 years of onset. Methods: In this multi-centre, longitudinal, observational study, 122 RA patients [102 females, baseline age 58.5 years, rheumatoid factor (RF) positivity 78.7%, serum C-reactive protein (CRP) 1.2 mg/dl, and concomitant methotrexate (MTX) 4.9mg/week (29.5%)] within 5 years of onset (disease duration 21.0 months) were enrolled from 1985 to 2000. Patients were not treated by more than 8mg/week of MTX or biologics which may strongly affect the course of joint destruction. Disease severity at 10-15 years of onset was classified according to the number of destructed joints of overall 68 joints on plain radio- graphs (36 patients were mild RA group involving only peripheral joints and 86 were severe RA group involving large axial joints). Baseline serum C1q levels were evaluated by ELISA with newly developed 4 monoclonal anti-C1q antibodies, and compared between two groups as well as conventional RA disease activity markers. Results: There were no significant differences between two groups in baseline conventional RA disease activity markers such as RF, erythrocyte sedimentation rate, CRP, and matrix metalloproteinase-3. However, compared to mild RA group, severe RA group showed higher baseline serum C1q levels (µg/ml) evaluated by anti-C1q monoclonal antibodies of no.33 (104.8 ±22.3 vs. 118.3 ±19.3; p = .0024), no. 40 (102.6±21.9 vs 121.2±22.3; p = .000069), no. 54 (102.1 ±22.5 vs. 119.3±26.9; p = .00052), and no. 76 (105.6±21.8 vs. 122.6±26.4; p = .00043). Receiver operating characteristic curve analysis revealed that in patients with serum C1q levels of ≥110.5 µg/ml (measured by antibody no. 40), 78.9% (75/95) belonged to severe RA group. Conclusion: Measuring serum C1q levels of RA within 5 years of onset by newly developed anti-C1q antibodies may be useful in predicting the prognosis of disease severity evaluated by the extent of joint destruction. [ABSTRACT FROM AUTHOR]

Background: Cervical MRI is the standard diagnostic imaging technique for patients with cervical myelopathy. However, the utility of conventional cervical MRI as a predictive biomarker for surgical recovery remains unclear, partly because of the limited information obtained from this anatomically small area. Brain resting-state functional MRI (rs-fMRI) may help identify candidate predictive biomarkers. Two analytical methods that assess local spontaneous brain activity are widely used for rs-fMRI: functional connectivity between two brain regions and amplitude of low-frequency fluctuation (ALFF). In our previous analysis of functional connectivity, we discovered that brain functional connectivity may be a predictive biomarker for neurologic recovery in patients with cervical myelopathy; however, the functional connectivity analysis identified a correlation with only one clinical outcome (the 10-second test). To establish a comprehensive prediction measure, we need to explore other brain biomarkers that can predict recovery of other clinical outcomes in patients with cervical myelopathy.Questions/purposes: We aimed to (1) elucidate preoperative ALFF alterations in patients with cervical myelopathy and how ALFF changes after surgery, with a focus on postoperative normalization and (2) establish a predictive model using preoperative ALFF by investigating the correlation between preoperative ALFF and postoperative clinical recovery in patients with cervical myelopathy.Methods: Between August 2015 and June 2017, we treated 40 patients with cervical myelopathy. Thirty patients met our prespecified inclusion criteria, all were invited to participate, and 28 patients opted to do so (93%; 14 men and 14 women; mean age: 67 years). The 28 patients and 28 age- and sex-matched controls underwent rs-fMRI (twice for patients with cervical myelopathy: before and 6 months after cervical decompression surgery). We analyzed the same study population that was used in our earlier study investigating functional connectivity. Controls had none of the following abnormalities: neck or arm pain, visual or auditory disorders, cognitive disorder, structural brain disorder, a history of brain surgery, mental and neurologic disorders, and medications for the central nervous system. We performed ALFF comparisons between preoperative patients with cervical myelopathy and controls, analyzed postoperative ALFF changes in patients with cervical myelopathy, and performed a correlation analysis between preoperative ALFF and clinical recovery in these patients. Clinical outcomes in the cervical myelopathy group were assessed using the 10-second test, the Japanese Orthopaedic Association upper-extremity motor (JOA-UEM) score, JOA upper-extremity sensory score (JOA-UES), and Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire for upper-extremity function (JOACMEQ-UEF) score before and 6 months after surgery, which is when we believe these scores generally reach a plateau. A total of 93% of those enrolled (26 of 28 patients) were analyzed both preoperatively and postoperatively; the other two were lost to follow-up.Results: The cervical myelopathy group had an increase in ALFF in the bilateral primary sensorimotor cortices (right, cluster size = 850 voxels, t-value = 6.10; left, cluster size = 370 voxels, t-value = 4.84) and left visual cortex (cluster size = 556 voxels, t-value = 4.21) compared with the control group. The cervical myelopathy group had a decrease in ALFF in the bilateral posterior supramarginal gyrus (right, cluster size = 222 voxels, t-value = 5.09; left, cluster size = 436 voxels, t-value = 5.28). After surgery, the bilateral sensorimotor cortices (right, cluster size = 468 voxels, t-value = 6.74; left, cluster size = 167 voxels, t-value = 5.40) and left visual cortex (cluster size = 3748 voxels, t-value = 6.66) showed decreased ALFF compared with preoperative ALFF, indicating postoperative normalization of spontaneous brain activities in these regions. However, the bilateral posterior supramarginal gyrus did not show an increase in ALFF postoperatively, although ALFF in this region decreased preoperatively. Greater levels of ALFF at the left and right frontal pole and left pars opercularis of the inferior frontal gyrus before surgery in the cervical myelopathy group were correlated with larger improvements in the JOACMEQ-UEF score 6 months after surgery (r = 0.784; p < 0.001, r = 0.734; p < 0.001 and r = 0.770, respectively; p < 0.001). The prediction formula, based on preoperative ALFF values in the left frontal pole, was as follows: the predicted postoperative improvement in the JOACMEQ-UEF score = 34.6 × preoperative ALFF value - 7.0 (r = 0.614; p < 0.001).Conclusions: Our findings suggest that preoperative ALFF may be a biomarker for postoperative recovery in that it predicted postoperative JOACMEQ-UEF scores. To establish a comprehensive prediction measure for neurologic recovery in patients with cervical myelopathy, a multicenter study is underway.Level Of Evidence: Level II, diagnostic study. [ABSTRACT FROM AUTHOR]

Objectives: Joint-preserving rheumatoid forefoot surgery improves clinical outcomes, but postoperative range of motion (ROM) of the metatarsophalangeal (MTP) joint remains an issue. The objective of this study was to evaluate the effect of ROM exercise from the early period after lesser toe MTP joint-preserving surgery. Methods: A retrospective, observational study of 22 rheumatoid arthritis patients who underwent modified metatarsal shortening offset osteotomy was completed. Lesser toe scales were administered using the Japanese Society for Surgery of the Foot (JSSF) standard rating system, and the maximum distance of continuous walking was checked to evaluate clinical outcomes. Maximum passive ROM of the lesser toe MTP joints and the extension angle of the 2nd MTP joint at the terminal stance phase during gait were measured and evaluated. Results: Pain scores and ROM-related indices of the JSSF lesser toe scale improved significantly in the exercise group. The extension angle of the 2nd MTP joint at the terminal stance phase during gait was increased, and the maximum distance of continuous walking seemed longer. Conclusion: Passive/active ROM exercise from 2-weeks after surgery can improve a patient's activity and forefoot function through increasing ROM of the MTP joint at the terminal stance phase. [ABSTRACT FROM AUTHOR]

Background: For peripheral nerve defects, autografting is considered the therapeutic gold-standard treatment. However, this procedure leads to donor-site morbidity. While various artificial conduits have been recently developed, treatment outcome has been demonstrated to be poorer than that with autograft. In our previous study using a rat sciatic nerve crush injury model, we demonstrated that the delivery of electrospun nanofiber sheets incorporating methylcobalamin (MeCbl sheet) to the local site of a peripheral nerve injury promoted peripheral nerve regeneration. In this study, we examined the effects of combination therapy using an MeCbl sheet and a polyglycolic acid tube filled with collagen sponge (PGA-c) in a rat model of a 10-mm sciatic nerve defect.Methods: The rats were divided into 4 groups: (1) sham group (n = 10); (2) PGA-c group (n = 9), in which the gap was bridged using a PGA-c; (3) PGA-c/Sheet group (n = 8), in which the gap was bridged using a PGA-c wrapped in an MeCbl sheet; and (4) autograft group (n = 10), in which the gap was bridged using a reversed autograft. Motor and sensory function were evaluated, electrophysiological analysis was performed, and histomorphological findings were analyzed at 12 weeks postoperatively.Results: Compared with the PGA-c group, the PGA-c/Sheet group demonstrated significant improvements in the paw-withdrawal threshold expressed as a ratio relative to the contralateral side (mean difference [MD], -1.51; 95% confidence interval [CI], -2.64 to -0.38), terminal latency (MD, -0.86 ms; 95% CI, -1.56 to -0.16 ms), myelinated axon area (MD, 4.97%; 95% CI, 0.14% to 9.80%), proportion of myelinated axons (MD, 8.453%; 95% CI, 0.001% to 16.905%), and g-ratio (MD, -0.018; 95% CI, -0.035 to -0.001). No significant improvements were observed regarding motor function, electrophysiological findings with the exception of terminal latency, and axon numbers.Conclusions: An MeCbl sheet in combination with a PGA-c significantly accelerated recovery with respect to sensory function, electrophysiology, and histomorphometry.Clinical Relevance: An MeCbl sheet may represent an effective therapeutic strategy for promoting regeneration across a nerve gap bridged with an artificial conduit. [ABSTRACT FROM AUTHOR]

Objectives: To clarify the effect of combining medial capsule interposition with modified scarf osteot- omy for hallux valgus. Methods: A multicenter, retrospective study included 64 cases [59 osteoarthritis patients (excluding rheumatoid arthritis); age 68.8 years, range 40-93 years] of modified scarf osteotomy which were performed from 2013 to 2017 and followed for 26.6 (range, 13-50) months. Patients were treated by either (1) without medial capsule interposition (33 cases) or (2) combined with interposition (31 cases) at each senior surgeon-s discretion. The Japanese Society for Surgery of the Foot (JSSF) hallux metatar-sophalangeal (MTP)-interphalangeal scale was evaluated along with radiographic parameters (hallux valgus angle [HVA], first and second metatarsals intermetatarsal angles, and Hardy grade). Results: All JSSF scale and radiographic parameters were similar at baseline and significantly improved at final follow-up in both groups (pre-operation vs. final follow-up: p<.001). However, compared to without interposition group, interposition group showed significantly higher improvement in the JSSF scale (pre-operation to final follow-up: p value between the two groups at final follow-up) for pain (without interposition: 19.4-34.2, interposition: 18.4-37.1; p=.02), function (without interposition: 20.8-33.6, interposition: 18.3-36.6; p=.005), total score (without interposition: 41.5-81.8, interposition: 38.5-88.5; p<.001), and the MTP joint space (without interposition: 1.4-1.5mm, interposition: 1.6-2.6mm; p<.001) with significant correlation between the total JSSF score (r=.40; p=.001). Conclusion: Combining medial capsule interposition with modified scarf osteotomy significantly improved mid-term clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Subperiosteal hematoma of the iliac bone is reported as a rare disorder that specifically occurs in young patients after obvious trauma. This report presents seven cases of male adolescent athletes with subperiosteal iliac hematoma without blunt trauma that was identified as an incidental radiolucent lesion on the iliac bone mimicking neoplasm. The purpose of this report is to describe clinical features and radiological findings of silent subperiosteal hematoma of the iliac bone. Subjects and methods: We retrospectively reviewed the clinical data and radiological appearance of 7 patients who presented with subperiosteal hematoma of iliac bone. Results: All seven patients had no obvious trauma and no serious symptoms. All patients were middle school or high school male students who regularly participated in vigorous sports activity; five soccer players, one baseball catcher, and one basketball player. The X-ray showed radiolucent lesion on the iliac bone. Lens-shaped mass without involvement of psoas muscle with ghost native cortex sign and overlying periosteal calcification on CT scan was characteristic radiological finding on subperiosteal iliac hematoma. Conclusion: Subperiosteal iliac hematomas can be caused by vigorous sports activity in adolescence. This condition is not always associated with serious symptom. It can be identified as a radiolucent lesion mimicking a neoplasm. [ABSTRACT FROM AUTHOR]

Study Design: An open-label, non-randomized prospective study. Purpose: Teriparatide (TPTD) is known to be an antiosteoporotic agent that may accelerate the healing of fractures. This study was designed to investigate the effect of once-weekly TPTD administration on vertebral stability and bony union after acute osteoporotic vertebral fracture (OVF). Overview of Literature: Once-weekly TPTD administration can lead to early vertebral stability and promote bony union of fractured vertebrae in patients with severe osteoporosis. Methods: Forty-eight subjects with acute OVF were assigned to receive activated vitamin D3 and calcium supplementation or onceweekly subcutaneous injection of TPTD (56.5 μg) in combination with activated vitamin D3 and calcium supplementation for 12 weeks. Vertebral stability was assessed using lateral plain radiography. Vertebral height at the anterior location (VHa) and the difference in VHa {δVHa=VHa (supine position)_VHa (weight-bearing position)} were measured at baseline and 12 weeks after starting treatment. Bony union was defined as the absence of a vertebral cleft or abnormal motion (δVHa >2 mm). Results: Although not significant, δVHa, indicating vertebral stability, tended to be lower in the TPTD group at 12 weeks (p =0.17). As for subjects with severe osteoporosis, δVHa at 12 weeks was significantly lower in the TPTD group than in the control group (mean δVHa: control group, 3.1 mm (n=15); TPTD group, 1.4 mm (n=16); p =0.02). The rate of bony union was significantly higher in the TPTD group than in the control group (control group, 40%; TPTD group, 81%; p =0.03). Conclusions: Once-weekly TPTD administration may facilitate early bony union after acute OVF accompanied by severe osteoporosis. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effectiveness of add-on iguratimod (IGU) in patients with rheumatoid arthritis (RA) who showed an inadequate response to tocilizumab (TCZ), especially patients who were intolerant of an effective dose of methotrexate (MTX). Methods: Thirty-one patients with RA (22 women, age 62.4 years, disease duration 13.8 years, prior TCZ duration 35.7 months, 25 intravenous [8 mg/kg/4 weeks] and 6 subcutaneous [162 mg/2 weeks] TCZ treatments, concomitant MTX 8.5 mg/week [35.5%], and prednisolone (PSL) 4.3 mg/day [25.8%]) who showed an inadequate response to TCZ (disease activity score assessing 28 joints with C-reactive protein [DAS28-CRP] 2.9, clinical disease activity index [CDAI] 15.0, 28 secondary inadequate responders) were treated with additional IGU (final dose 41.7 mg/day) and enrolled in this 24-week, multicenter, retrospective study. Results: Twenty-nine patients (93.5%) continued the treatment for 24 weeks (one dropped out for pneumonia and one for digestive symptoms). The TCZ and the concomitant dose and rate of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (MTX, salazosulfapyridine [SASP], and tacrolimus [TAC]) were not significantly changed during this period. Outcome measures improved significantly, as follows: DAS28-CRP from 2.9 to 1.7 (p < .001); CDAI from 15.0 to 6.0 (p < .001); modified Health Assessment Questionnaire (mHAQ) from 0.8 to 0.6 (p < .05); and rheumatoid factor (RF) from 382.1 to 240.3 IU/mL (p < .001). Using the EULAR criteria, 64.5% achieved a moderate response, and 51.6% achieved ACR 20 at 24 weeks. Conclusion: Adding IGU to inadequate responders to TCZ may be a promising and safe complementary treatment option. [ABSTRACT FROM AUTHOR]

Case: A 76-year-old woman underwent L4–L5 posterior lumbar interbody fusion with pedicle screws for lumbar spondylolisthesis. Intraoperative iatrogenic injuries to the right fourth lumbar artery and inferior vena cava occurred, resulting in arteriovenous fistula with extensive retroperitoneal hemorrhage. Endovascular treatment and intraperitoneal drainage were effective in managing retroperitoneal hemorrhage. She showed no sign of organ failure or deep venous thrombosis during her 2-year follow-up. Conclusions: We recommend embolization both proximally and distally in the case of lumbar artery injury. Intra-abdominal hypertension secondary to a massive retroperitoneal hematoma should also be considered to prevent abdominal compartment syndrome. [ABSTRACT FROM AUTHOR]

Purpose: Plain hip radiograph is commonly used for the diagnosis of infantile acetabular dysplasia. Many infants are unable to maintain adequate position during radiography. Besides, the infantile hip is much smaller and has a higher cartilage component in the acetabulum and proximal femur compared with the adult hip. In this study, we developed a digitally reconstructed radiograph synthesized from magnetic resonance imaging (MRI) and investigated errors of hip radiographic measurements in different pelvic positions. Patients and methods: MRI of both hips was performed in 10 patients (mean age 3.9 years). Three-dimensional (3D) bone models were created from MRI data. We tilted 3D pelvic bone models between 10° anteversion and retroversion and through 10° rotation on the affected and contralateral sides using 3D axes. Following this, we created digitally reconstructed radiographs in each pelvic position and calculated the acetabular index (AI), center-edge angle (CEA), migration percentage (MP), and teardrop distance (TDD). Results: AI tended to increase with pelvic retroversion and did not change with pelvic rotation. CEA tended to decrease with pelvic retroversion and rotation on the contralateral side. MP increased with pelvic retroversion and rotation on the contralateral side. TDD did not change significantly with pelvic tilt and rotation. Conclusions: Radiographic measurements of hip in infants were highly influenced by pelvic movement. AI was influenced by pelvic tilt; CEA and MP were influenced by both pelvic tilt and rotation. We need to keep in mind that infantile hip radiographs could have about±5° errors in AI and CEA. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to clarify the mechanisms of rotational restriction in malunited forearm diaphyseal fractures.Methods: We retrospectively analyzed the cases of 18 patients with malunited forearm diaphyseal fractures and rotational restriction. All patients underwent bilateral computed tomography (CT) of the forearm in maximum supination, pronation, and neutral positions. From these images, we created 3-dimensional (3-D) bone surface models. We quantified the 3-D deformities, identified instances of osseous impingement between the radius and the ulna during forearm rotation, calculated the path length of the central band (CB) of the interosseous membrane, and measured forearm range of motion.Results: Sixteen patients had extension deformity of the radius (the RE group) and 2 had flexion deformity (the RF group). In the RE group, extension deformity of the radius and valgus deformity of the ulna had significant negative correlation with pronation range of motion (R = -0.50, p = 0.046) and supination range of motion (R = -0.63, p = 0.027), respectively. Osseous impingement was mainly observed during pronation (15 of 16 patients). The CB path with the largest changes in length originated from the distal CB attachment area of the radius and ran toward the proximal area of the ulna (the transverse CB). The transverse CB significantly increased in length in supination compared with that in pronation (p < 0.001). Therefore, tightness of the transverse CB appeared to cause supination restriction in the RE group. In the RF group, osseous impingement caused supination restriction. The greatest increases in the transverse CB length were observed in pronation in the RF group, which appeared to cause pronation restriction.Conclusions: In the RE group, pronation restriction was associated with osseous impingement that was due to extension deformity of the radius, and supination restriction was associated with CB tightness that was due to valgus deformity of the ulna. In the RF group, our results suggested that pronation restriction was caused by CB tightness and that supination restriction was caused by osseous impingement.Clinical Relevance: Three-dimensional corrective osteotomy for extension deformity of the radius in malunited forearm diaphyseal fractures would improve rotational restriction by relieving osseous impingement during pronation and CB tightness during supination. [ABSTRACT FROM AUTHOR]

Background: Arthrodesis of the first metatarsophalangeal (MTP) joint has been recommended for severe hallux valgus deformity in patients with rheumatoid arthritis (RA). However, with the progress of medical treatment of RA, joint preservation surgery has recently been performed. The aim of this study was to investigate the clinical and radiographic outcomes of modified Scarf osteotomy with medial capsule interposition for RA cases including severe destruction of the first MTP joint and to evaluate risk factors for recurrence.Methods: A retrospective observational study of 76 cases (60 patients) followed for a mean of 35.3 months (range, 24 to 56 months) after a modified Scarf osteotomy was performed. Scores on the Japanese Society for Surgery of the Foot (JSSF) RA foot and ankle scale, the JSSF hallux scale, and a self-administered foot evaluation questionnaire (SAFE-Q) were determined along with preoperative and postoperative radiographic parameters.Results: There was a significant improvement, from preoperatively to final follow-up, in the mean JSSF RA foot and ankle score (from 52.2 to 76.9 points) and the mean JSSF hallux score (from 38.2 to 74.5 points). There was a recurrence (hallux valgus angle [HVA] of >20°) in 12 feet (16%). The preoperative DAS28-CRP score (disease activity score [based on 28 joints in the body]-C-reactive protein score) and intermetatarsal angles between the first and second metatarsals (M1M2A) and between the first and fifth metatarsals (M1M5A) were significantly greater in the recurrence group, as were the HVA, M1M2A, M1M5A, and Hardy grade at 3 months after surgery. There was a significant negative correlation between the preoperative DAS28-CRP score and the JSSF RA foot and ankle score at final follow-up (β = -0.39, p = 0.02) and a significant positive correlation between the preoperative DAS28-CRP score and the HVA at final follow-up (β = 0.44, p = 0.001).Conclusions: The modified Scarf osteotomy with medial capsule interposition for hallux valgus deformity improved clinical and radiographic outcomes in RA cases with severe destruction of the first MTP joint. Increased preoperative M1M2A and M1M5A; incomplete reduction of the sesamoid bone; and the HVA, M1M2A, and M1M5A at 3 months after surgery should be evaluated as they are associated with recurrence of the deformity. The preoperative DAS28-CRP score was associated with the clinical and radiographic outcomes after surgery.Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the differences in three-dimensional carpal kinematics between type 1 and 2 lunates. We studied 15 instances of wrist flexion to extension (nine type 1, six type 2), 13 of radial to ulnar deviation (seven type 1, six type 2), and 12 of dart-throwing motion (six each of type 1 and 2) in 25 normal participants based on imaging with computerized tomography. Mean proximal translation of the distal articular midpoint of the triquetrum relative to type 2 lunates during wrist radioulnar deviation was 2.9mm (standard deviation (SD) 0.7), which was significantly greater than for type 1 lunates, 1.6mm (SD 0.6). The hamate contacted the lunate in ulnar deviation and ulnar flexion of wrists with type 2 lunates but not with type 1. We conclude that the four-corner kinematics of the wrist joint are different between type 1 and 2 lunates. [ABSTRACT FROM AUTHOR]

Xanthogranuloma is a benign disease represented as histiocytosis with lipoid deposition which usually occurs in children, but rarely in adults. We report a case of an adult patient with multiple subcutaneous xanthogranuloma at juxta-articular sites with bone cystic changes, manifesting similar clinical profiles to rheumatoid arthritis. Although very rare, we should consider the possibility of xanthogranulomatosis in the diagnosis of rheumatoid arthritis, especially in atypical cases. [ABSTRACT FROM AUTHOR]

Purpose An epithelioid sarcoma is a rare histological subtype of a soft tissue sarcoma with a high local recurrence rate, which frequently shows lymph node metastasis. However, because of the rarity of this tumor, the impact of nodal metastasis and its appropriate management remain unclear. The present study investigated the clinical outcomes of patients with epithelioid sarcomas, with a focus on lymph node metastasis. Methods We retrospectively evaluated the clinical outcomes of 27 patients with epithelioid sarcomas treated between 1985 and 2015. The log-rank test was used to assess the prognostic variables. Results The overall local recurrence rate was 33%, and the estimated overall 5-year survival rate was 62%. Hand and foot locations were associated with favorable overall survival. During the follow-up period, new nodal metastasis was noted in 14 patients (52%). The incidence of local recurrence was higher in patients with new nodal metastasis than in patients who did not develop nodal metastasis. The development of new nodal metastasis had a tendency to worsen survival; however, this association was not statistically significant. Lymphadenectomy did not affect overall survival. Conclusions Peripheral tumor location is associated with a better prognosis. The development of new nodal metastasis tends to be associated with poor prognosis; however, among patients with nodal metastasis, resection of the metastatic lesions has a low impact on survival. [ABSTRACT FROM AUTHOR]

Objective: The longevity of a knee prosthesis is influenced by the wear of the tibial insert due to its posture and movement. In this study, we assumed that the strain on the tibial insert is one of the main reasons for its wear and investigated the influence of the knee varus-valgus angles on the mechanical stress of the tibial insert. Methods: Knee prosthesis motion was simulated using a knee motion simulator based on a parallel-link six degrees-of-freedom actuator and the principal strain and pressure distribution of the tibial insert were measured. In particular, the early stance phase obtained from in vivo X-ray images was examined because the knee is applied to the largest load during extension/flexion movement. The knee varus-valgus angles were 0° (neutral alignment), 3°, and 5° malalignment. Results: Under a neutral orientation, the pressure was higher at the middle and posterior condyles. The first and second principal strains were larger at the high and low pressure areas, respectively. Even for a 3° malalignment, the load was concentrated at one condyle and the positive first principal strain increased dramatically at the high pressure area. The negative second principal strain was large at the low pressure area on the other condyle. The maximum equivalent strain was 1.3-2.1 times larger at the high pressure area. For a 5° malalignment, the maximum equivalent strain increased slightly. Conclusion: These strain and pressure measurements can provide the mechanical stress of the tibial insert in detail for determining the longevity of an artificial knee joint. [ABSTRACT FROM AUTHOR]

Background: Recent morphological analyses of vertebrae in patients with scoliosis have revealed three-dimensional (3D) deformities in the vertebral bodies. However, it remains controversial whether these deformities are secondary changes caused by asymmetrical vertebral loading or primary changes caused by aberrant asymmetrical vertebral growth. Furthermore, the difference in vertebral morphology between scoliosis with different pathogeneses remains unclear. This study was aimed to investigate the difference in the coronal asymmetry of vertebral bodies between neuromuscular scoliosis (NS) in Duchenne muscular dystrophy (DMD) and idiopathic scoliosis (IS) using in vivo 3D analysis.Methods: Twelve male skeletally immature patients with NS in DMD and 13 female skeletally immature patients with IS who underwent corrective fusion at our institution were included retrospectively. 3D bone models of the apical and adjacent upper and lower vertebrae in the major curve in the NS patients and in the main and compensatory curves in the IS patients were constructed using an image processing workstation. The heights of the concave and convex sides of the vertebral bodies were measured at the anterior, middle, and posterior and the concave-to-convex vertebral height ratios (VHR) were calculated.Results: The mean VHRs (anterior/middle/posterior) for the main curve for IS (0.897 ± 0.072/0.832 ± 0.086/0.883 ± 0.059) were significantly smaller than those for NS (0.970 ± 0.048/0.934 ± 0.081/0.958 ± 0.043) in all three parts (p < 0.001). Those of the compensatory curve in IS (0.968 ± 0.045/0.942 ± 0.067/0.967 ± 0.046) did not differ significantly from the NS values in any part.Conclusions: When compared to the wedging of the vertebral bodies around apical vertebrae in the major curve in NS, which was caused by asymmetric loading, the wedge deformities in both the main and compensatory curves in IS were more severe than would be expected. Our results indicated that morphometric characteristics of vertebral bodies differed according to the pathogenesis of scoliosis and that the pathology of the wedging of vertebral bodies in IS could not be a result only of asymmetric loading to the vertebral bodies. [ABSTRACT FROM AUTHOR]

Objectives: Advances in drug therapy for rheumatoid arthritis (RA) have been encouraging us to preserve the metatarsopharangeal (MTP) joint in correction of forefoot deformities, and original metatarsal shortening offset osteotomy was recommended as one of the conventional surgical options for forefoot deformities in RA cases. The objective of this study was to evaluate short-to mid-term outcomes of modified metatarsal shortening offset osteotomy. Methods: A retrospective observational study was completed for 80 RA cases (mean follow-up period: 3.2 years) who underwent modified metatarsal shortening offset osteotomy. Both lesser toe scales and RA foot ankle scales were administered using the Japanese Society for Surgery of the Foot (JSSF) standard rating system, and a postoperative self-administered foot evaluation questionnaire (SAFE-Q) at final follow-up was also checked to evaluate clinical outcomes. Results: This procedure significantly improved clinical scores of both the JSSF [lesser toes and RA foot and ankle] scales. Of 80 feet, 24 (30%) showed recurrence of MTP joint subluxation/dislocation. Furthermore, the feet in the recurrence group showed significant varus hindfoot. On the other hand, valgus foot in the recurrence group more frequently included midfoot bony ankyloses. All of the affected feet showed the limitation of MTP joints (<70°) after surgery. Conclusions: Modified metatarsal shortening offset osteotomy was recommended for RA forefoot disorders as one of the joint preservation surgeries in short- to mid-term follow-up. However, some modifications to avoid limitation of ROM in the MTP joint are required. It must be borne in mind that varus hindfoot and/or bony ankyloses in the mid-hindfoot can cause recurrence of dorsal dislocation/subluxation of the lesser toe MTP joint. [ABSTRACT FROM AUTHOR]

Objectives: To clarify the difference of patient-based outcome between joint-preserving arthroplasty and resection-replacement arthroplasty in forefoot surgery for patients with rheumatoid arthritis (RA). Methods: A total of 63 feet of 49 RA patients who underwent forefoot surgery were asked to answer pre-operative and post-operative self-administered foot evaluation questionnaire (SAFE-Q). Patients were treated with either (1) metatarsal head resection-replacement arthroplasty (28 feet, post-operative mean age 63.8 years, follow-up 4.2 years, DAS28-CRP 2.2) or (2) metatarsophalangeal joint-preserving arthroplasty (35 feet, post-operative mean age 63.1 years, follow-up 3.6 years, DAS28-CRP 2.1) at each surgeon's discretion. Results: Mean pre-operative and post-operative subscale scores of SAFE-Q of group (1) and (2) were as follows. Pain and pain-related [(1) pre-op 36.8 to post-op 75.0 vs. (2) pre-op 42.2 to post-op 82.6], physical functioning and daily-living [(1) 43.2-68.8 vs. (2) 52.778.1], social functioning [(1) 44.3-72.0 vs. (2) 52.5-81.9], general health and well-being [(1) 48.4-68.4 vs. (2) 45.5-84.4], and shoe-related [(1) 30.1-50.3 vs. (2) 30.6-64.4]. Both general health and well-being subscale scores (p<0.05) and shoe-related subscale scores (p<0.05) were significantly more improved in group (2) compared with group (1). Conclusions: Joint-preserving arthroplasty resulted in better patient-based outcomes than resectionreplacement arthroplasty. [ABSTRACT FROM AUTHOR]

Objective: To compare the influences of tocilizumab (TCZ) and TNF inhibitors (TNFi) on the angiogenesis in synovial tissues of rheumatoid arthritis (RA). Methods: Synovial tissues were obtained during joint operations from 13 RA patients treated with TCZ for at least 4 months with or without previous use of TNFi, from 13 RA patients with TNFi alone and from 10 RA patients with only conventional synthetic DMARDs (csDMARDs). Synovial tissues were evaluated by hematoxylin and eosin stain as well as by immunohistological staining with anti-CD31 in which the microvessel densities (MVD) were quantitated. Synovial histopathology was scored for various components. Results: The most remarkable change in the synovium with TCZ was reduced angiogenesis as well as degeneration of lining layers irrespective of the previous use of TNFi. Thus, MVD in patients treated with TCZ with or without previous TNFi were significantly decreased compared with those in patients with TNFi alone or with csDMARDs. Moreover, MVD was significantly correlated with lining layer proliferation, but not with synovial stromal proliferation or inflammatory changes. Conclusions: These results demonstrated that inhibition of angiogenesis is a unique action of TCZ. Moreover, the data also suggest that lining layers proliferation might be closely associated with angiogenesis. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the incidence and risk factors for cervical lesions in patients with rheumatic arthritis (RA) under the current pharmacologic treatment paradigm. Methods: Of patients with RA onset after 2000, 151 who introduced biologic agents (BAs) because of high disease activity and underwent cervical radiography more than 5 years after onset were included. Incidence of those with cervical lesions and predictors of cervical lesions were analyzed. Mean disease duration was 8.5 years. The radiographic definitions of cervical lesions were as follows: atlantoaxial subluxation (AAS), atlantodental interval43 mm; vertical subluxation (VS), Ranawat value513 mm; and subaxial subluxation (SS), and listhesis42 mm. Results: Radiographic evaluation indicated AAS in 43 cases (28%), VS in 10 (7%), and SS in 6 (4%). The incidence of those with any cervical lesion was 32% (48/151). Univariate analysis showed that disease duration, time from onset to BA use, and onset before 2005 were significant predictors of cervical lesions, while multivariate regression analysis showed that disease duration and Steinbrocker stage were predictors. Conclusion: The incidence of cervical lesions in patients with RA onset after 2000 was still high (32%). In addition, disease duration and Steinbrocker stage were predictors of cervical lesions. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs) are a promising cell source for the repair of skeletal disorders. Recently, neural crest cells (NCCs) were reported to be effective for inducing mesenchymal progenitors, which have potential to differentiate into osteochondral lineages. Our aim was to investigate the feasibility of MSC-like cells originated from iPSCs via NCCs for osteochondral repair. Initially, MSC-like cells derived from iPSC-NCCs (iNCCs) were generated and characterized in vitro. These iNCC-derived MSC-like cells (iNCMSCs) exhibited a homogenous population and potential for osteochondral differentiation. No upregulation of pluripotent markers was detected during culture. Second, we implanted iNCMSC-derived tissue-engineered constructs into rat osteochondral defects without any preinduction for specific differentiation lineages. The implanted cells remained alive at the implanted site, whereas they failed to repair the defects, with only scarce development of osteochondral tissue in vivo. With regard to tumorigenesis, the implanted cells gradually disappeared and no malignant cells were detected throughout the 2-month follow-up. While this study did not show that iNCMSCs have efficacy for repair of osteochondral defects when implanted under undifferentiated conditions, iNCMSCs exhibited good chondrogenic potential in vitro under appropriate conditions. With further optimization, iNCMSCs may be a new source for tissue engineering of cartilage. [ABSTRACT FROM AUTHOR]

Background: The prognosis of synovial sarcoma (SS), an aggressive soft tissue sarcoma, remains poor. We previously reported that c-MET or platelet-derived growth factor receptor α (PDGFRα) signalling pathway is related to SS progression based upon the findings of phospho-receptor tyrosine kinase (RTK) arrays. TAS-115 is a novel c-MET/ vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitor that has been shown to inhibit multiple RTKs. Here we aimed to investigate the therapeutic potential of TAS-115 against SS.Methods: We first evaluated which signalling pathway was relevant to the viability of three human SS cell lines: Yamato-SS, SYO-1 and HS-SY-II. Next, we assessed the anticancer activity and mechanism of action of TAS-115 in these SS cell lines. Finally, we compared the ability of TAS-115 to inhibit c-MET and PDGFRα phosphorylation with that of pazopanib.Results: We classified the SS cell lines as c-MET-dependent or PDGFRα-dependent based upon the differences in the signalling pathway relevant for growth and/or survival. We also found that c-MET and PDGFRα were the primary activators of both phosphatidylinositol 3-kinase/AKT and mitogen-activated protein kinase pathways in c-MET-dependent and PDGFRα-dependent SS cells, respectively. TAS-115 treatment blocked the phosphorylation of PDGFRα as well as that of c-MET and their downstream effectors, leading to marked growth inhibition in both types of SS cell lines in in vitro and in vivo studies. Furthermore, PDGFRα phosphorylation, on at least four representative autophosphorylation sites, was impeded by TAS-115 equivalently to pazopanib.Conclusions: These experimental results have demonstrated the significance of c-MET and PDGFRα signalling for growth and/or survival of SS tumours. TAS-115 monotherapy may benefit SS patients whose tumours are dependent upon either c-MET or PDGFRα signalling by functioning as a multiple tyrosine kinase inhibitor to suppress c-MET as well as PDGFRα pathways. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether preoperative pain intensity in callosities of the lesser toe metatarsopharangeal (MTP) joint was associated with the grade of fore-mid-hindfoot deformities, because rheumatoid arthritis (RA) foot deformity includes the whole part of foot, and curiously differences between cases in the pain intensity of MTP joint callosities are often observed. Methods: We evaluated 24 feet that had undergone forefoot surgery [August, 2014 - December, 2015] for painful lesser toe MTP joint deformity (callosities) in RA cases. A preoperative self-administered foot evaluation questionnaire (SAFE-Q) and pressure distribution information for foot function were also investigated. X-rays of the whole lower extremities and foot at weight-bearing were used to check fore-mid-hindfoot deformities. Results: Group M (mild) [n = 9] included patients with the pain visual analog scale (VAS) less than 40 mm, while group S (severe) [n=15] included patients whose VAS was over 40 mm. Group M showed stronger hindfoot valgus and pronated (abducted) deformity, and group M showed higher pressure on the first MTP joint compared with group S. Conclusions: These observations reconfirm that hindfoot valgus deformity and/or pronated (abducted) foot deformity affects the forefoot loading distribution, subsequently the pain of callosities in lesser toe MTP joints could be decreased. [ABSTRACT FROM AUTHOR]

Objectives: Tocilizumab (TCZ) shows good retention in patients with rheumatoid arthritis (RA), but no previous reports demonstrated hopeful treatment options against inadequate response to TCZ. Tacrolimus (TAC) has proved to show efficacy against inadequate response to tumor necrosis factor alpha inhibitors, yet its add-on effects on TCZ remain unknown. Methods: Twenty patients with RA (17 women, age 58.6 years, disease duration 12.1 years, prior TCZ duration 2.6 years, 18 intravenous [8 mg/kg/month] and 2 subcutaneous [324 mg/month] TCZ treatments, methotrexate 6.1 mg/week [70.0%]) who showed an inadequate response to TCZ (clinical disease activity index [CDAI]≤5.8, 18 secondary non-responders) were additionally treated with TAC (1.1 mg/day), and enrolled in this 24-week, prospective study. Results: Seventeen patients (85.0%) continued the treatment for 24 weeks. Statistically significant decreases in outcome measures were as follows: disease activity score based on 28 joints with C-reactive protein (DAS28-CRP) from 3.3 at baseline to 2.1 at week 24 (p50.001), CDAI from 17.7 to 7.6 (p50.001), and serum matrix metalloproteinase-3 levels from 232.8 to 66.2 ng/ml (p50.001). About 15 patients (75%) achieved low disease activity or remission (DAS28-CRP ≥ 2.7 or CDAI ≥ 10) at week 24. Conclusions: Adding low-dose TAC to inadequate responders to TCZ may be a promising complementary treatment option. [ABSTRACT FROM AUTHOR]

Control of rheumatoid arthritis (RA) disease activity is an important factor related to the development of hallux valgus (HV) deformity. Furthermore, if valgus hindfoot remains and/or appears after HV surgery, the affected foot is at risk of recurrence of HV deformity. We experienced a case suggesting the possibility that hindfoot valgus deformity appeared after HV surgery because of poor control of RA disease activity, and the HV deformity recurred in the very early period after surgery. [ABSTRACT FROM AUTHOR]

Background: Bone and soft tissue sarcomas (BSTS) are rare malignant tumors. Recently, the combination of gemcitabine and docetaxel (GD) was shown to have activity as second-line setting in BSTS. However, the efficacy as first-line and adjuvant settings and precise profiles of adverse events in Japanese patients are not known yet. In the present study, the feasibility and efficacy of GD in patients with BSTS were investigated. Methods: Patients with BSTS treated with GD in our institutions were retrospectively analyzed. Information regarding clinical features, adverse events, and outcome was collected and statistically studied. Factors related to survival were analyzed using log-rank test and Cox proportional hazard regression method. Results: A total of 134 patients were analyzed. GD was carried out as adjuvant setting in 9, first-line in 23, second-line in 56, and third-or-greater line in 46 patients. The response rate (RR) for all patients was 9.7%. RR for the patients treated as adjuvant or first-line setting was 18.8%, whereas that as second-or-greater line was 6.9%. The median progression-free survival (PFS) and overall survival (OS) of all patients were 4.8 (95% CI 3.5-6.1) and 16.4 (95% CI 9.8-22.9) months, respectively. Survival tended to be better in the patients treated as first-line than in those treated as second-or-greater line. Multivariate analysis demonstrated that history of prior chemotherapy (p = 0.046) and response to GD (p = 0.009) was significantly associated with PFS and OS, respectively. The leucopenia and neutropenia were the most frequent adverse events, and grade 3 or 4 leucopenia and neutropenia were observed in 69.4 and 72.4% of the patients. Grade 2 or 3 pneumonitis was observed in one (0.7%) and four (3.0%) patients, respectively. All the patients with pneumonitis had experienced prior chemotherapy and/or radiotherapy. Conclusions: GD used as both first- and second/later line is effective chemotherapy for a proportion of patients with advanced BSTS. Higher response rate and better outcome was achieved in chemotherapy-naïve patients. This regimen is associated with high incidence of severe hematological toxicity, as well as the risk of severe pneumonitis, especially in pre-treated patients. GD is promising for further analysis by phase III study for the patients with BSTS. [ABSTRACT FROM AUTHOR]

The enhancement in electrical conductivity and optical transparency induced by a phase transition from amorphous to polycrystalline in lightly silicon-doped indium oxide (InSiO) thin films is studied. The phase transition caused by simple thermal annealing transforms the InSiO thin films from semiconductors to conductors. Silicon atoms form SiO4 tetrahedra in InSiO, which enhances the overlap of In 5s orbitals as a result of the distortion of InO6 octahedral networks. Desorption of weakly bonded oxygen releases electrons from deep subgap states and enhances the electrical conductivity and optical transparency of the films. Optical absorption and X-ray photoelectron spectroscopy measurements reveal that the phase transition causes a Fermi energy shift of ∼0.2 eV. [ABSTRACT FROM AUTHOR]

Background: Vertebral bodies in patients with adolescent idiopathic scoliosis (AIS) usually have frontal wedge deformities. However, the plasticity of the deformed vertebrae in skeletally immature patients is unknown. The purpose of our study was to clarify the plasticity of vertebral deformities in skeletally immature patients with AIS by using in vivo three-dimensional (3D) analysis. Methods: Ten female patients with AIS (mean age, 12.2 years; three patients, Lenke type 1; five patients, type 2; two patients, type 5) who underwent posterior fusion and whose Risser grade was ⩽3 at surgery were included. Using computed tomography images (0.625-mm slice thickness) obtained 1 week and 1 year postoperatively, a total of seventy-three 3D bone models of vertebrae was made. The 3D bone models were made between the upper and lower end vertebrae within the main thoracic curve for patients with Lenke types 1 and 2 scoliosis, whereas they were made within the thoracolumbar/lumbar curve in patients with Lenke type 5 scoliosis. The height of the concave and convex sides in the anterior, middle and posterior parts of the vertebral bodies was measured using the original digital viewer, and the vertebral height ratio (VHR: concave/convex) was calculated. VHRs at 1 week and 1 year postoperatively were compared using the Wilcoxson signed-rank test. Differences were considered statistically significant at p < 0.05. Results: VHR of the end vertebrae (n = 20) did not change postoperatively for any parts of the vertebral bodies. VHR of the vertebrae in the apical region (n = 28) also remained unchanged postoperatively. In contrast, VHR of the other vertebrae (n = 25) increased significantly in the anterior part postoperatively (from 0.938 to 0.961, p = 0.006). Conclusions: The wedge deformity of vertebral bodies showed a reshaping potential towards a symmetrical configuration in the region other than end and apex, although no plasticity of the vertebrae was observed in the apical region even in skeletally immature patients with AIS. [ABSTRACT FROM AUTHOR]

Background: Alternative medicine is noted for its clinical effect and minimal invasiveness in the treatment of neuropathic pain. Go-sha-jinki-Gan, a traditional Japanese herbal medicine, has been used for meralgia and numbness in elderly patients. However, the exact mechanism of GJG is unclear. This study aimed to investigate the molecular mechanism of the analgesic effect of GJG in a chronic constriction injury model. Results: GJG significantly reduced allodynia and hyperalgesia from the early phase (von Frey test, p<0.0001; cold-plate test, p<0.0001; hot-plate test p=0.011; two-way repeated measures ANOVA). Immunohistochemistry and Western blot analysis revealed that GJG decreased the expression of Iba1 and tumor necrosis factor-a in the spinal cord. Double staining immunohistochemistry showed that most of the tumor necrosis factor-α was co-expressed in Iba1-positive cells at day 3 post-operation. GJG decreased the phosphorylation of p38 in the ipsilateral dorsal horn. Moreover, intrathecal injection of tumor necrosis factor-α opposed the anti-allodynic effect of GJG in the cold-plate test. Conclusions: Our data suggest that GJG ameliorates allodynia in chronic constriction injury model mice via suppression of tumor necrosis factor-α expression derived from activated microglia. GJG is a promising drug for the treatment of neuropathic pain induced by neuro-inflammation. [ABSTRACT FROM AUTHOR]

Hallux valgus (HV) deformity is associated with hindfoot valgus deformity. We experienced a case that suggests the possibility that valgus correction for varus hindfoot with bony ankylosis of the subtalar joint by total ankle arthroplasty may have caused a forefoot HV deformity, despite adequate valgus correction. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 46-year-old woman and a 21-year-old woman with suspected pulmonary hypertension. Topics include Dynamic chest radiography (DCR) performed together with conventional chest radiography in each patient; showing large triangular perfusion defects suggesting central pulmonary thromboembolism in the left and right lung fields; and demonstration of the difference between chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.

Objective. To clarify the three-dimensional (3D) morphometric characteristics of the spine in patients with degenerative spondylolisthesis (DS). Methods. 3D morphometric analyses of laminae and facets were performed and compared for a DS group, an age-matched spinal canal stenosis (LCS) group, and a control group of young persons without spinal disease. 3D facet sagittal angles (3D-FSAs), 3D facet axial angle (3D-FAAs), and 3D-FAA tropism at L3 and at L4 were measured by extracting the 3D inferior articular process. The 3D lamina inclination angles (3D-LIAs) of L3 and L4 were also measured by extracting the ventral surface of the laminae. Results. The 3D-FSAs at L4 in the DS group were significantly higher than for the other groups, but the difference in 3D-FSAs at L3 was not statistically significant among the groups. The 3D-FAAs at L4 in the DS group were significantly lower than in the control group. There was no significant difference in other factors. Conclusions. 3D morphometric analysis clarified that DS is significantly correlated with horizontalization (higher 3D-FSA), but is not correlated with sagittalization (lower 3D-FAA) and tropism (3D-FAA tropism) of facet joints or horizontalization of laminae (3D-LIA). There were no morphometric characteristics at the cranial adjacent segment of DS. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is one of the most common joint diseases in elderly people, however, the underlying mechanism of OA pathogenesis is not completely clear. Periostin, the extracellular protein, has been shown by cDNA array analysis to be highly expressed in OA, but its function is not fully understood. The purpose of this study was to examine the expression and function of periostin in human OA. Methods: Human cartilage and synovia samples were used for the analysis of periostin expression and function. The human cartilage samples were obtained from the knees of patients undergoing total knee arthroplasty as OA samples and from the femoral bone head of patients with femoral neck fracture as control samples. Quantitative RT-PCR, ELISA, and immunohistochemistry were used for analysis of periostin expression in cartilage and synovia. Human primary chondrocytes isolated from control cartilage were stimulated by periostin, and the alteration of OA related gene expression was examined using quantitative RT-PCR. Immunocytochemistry of p65 was performed for the analysis of nuclear factor kappa B (NFΚB) activation. Results: The periostin mRNA was significantly higher in OA cartilage than in control cartilage. Immunohistochemical analysis of periostin showed that the main positive signal was localized in chondrocytes and their periphery matrix near the erosive area, with less immunoreactivity in deeper zones. There was positive correlation between Mankin score and periostin immunoreactivity. The periostin expression was also detected in the fibrotic cartilage and tissue of subchondral bone. In cultured human chondrocytes, periostin induced the expression of interleukin (IL)-6, IL-8, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, and nitric oxide synthase-2 (NOS2) in a dose- and time-dependent manner. The activation of NFΚB signaling was recognized by the nuclear translocation of p65. Periostin-induced upregulation of these genes was suppressed by NFΚB inactivation in chondrocytes. Conclusion: Periostin was upregulated in OA cartilage, and it may amplify inflammatory events and accelerate OA pathology. [ABSTRACT FROM AUTHOR]

Schwann cells (SCs) are constituents of the peripheral nervous system. The differentiation of SCs in injured peripheral nerves is critical for regeneration after injury. Methylcobalamin (MeCbl) is a vitamin B12 analog that is necessary for the maintenance of the peripheral nervous system. In this study, we estimated the effect of MeCbl on SCs. We showed that MeCbl downregulated the activity of Erk1/2 and promoted the expression of the myelin basic protein in SCs. In a dorsal root ganglion neuron-SC coculture system, myelination was promoted by MeCbl. In a focal demyelination rat model, MeCbl promoted remyelination and motor and sensory functional regeneration. MeCbl promoted the in vitro differentiation of SCs and in vivo myelination in a rat demyelination model and may be a novel therapy for several types of nervous disorders. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is one of the most common joint diseases in elderly people, however, the underlying mechanism of OA pathogenesis is not completely clear. Periostin, the extracellular protein, has been shown by cDNA array analysis to be highly expressed in OA, but its function is not fully understood. The purpose of this study was to examine the expression and function of periostin in human OA. Methods: Human cartilage and synovia samples were used for the analysis of periostin expression and function. The human cartilage samples were obtained from the knees of patients undergoing total knee arthroplasty as OA samples and from the femoral bone head of patients with femoral neck fracture as control samples. Quantitative RT-PCR, ELISA, and immunohistochemistry were used for analysis of periostin expression in cartilage and synovia. Human primary chondrocytes isolated from control cartilage were stimulated by periostin, and the alteration of OA related gene expression was examined using quantitative RT-PCR. Immunocytochemistry of p65 was performed for the analysis of nuclear factor kappa B (NFκB) activation. Results: The periostin mRNA was significantly higher in OA cartilage than in control cartilage. Immunohistochemical analysis of periostin showed that the main positive signal was localized in chondrocytes and their periphery matrix near the erosive area, with less immunoreactivity in deeper zones. There was positive correlation between Mankin score and periostin immunoreactivity. The periostin expression was also detected in the fibrotic cartilage and tissue of subchondral bone. In cultured human chondrocytes, periostin induced the expression of interleukin (IL)-6, IL-8, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, and nitric oxide synthase-2 (NOS2) in a dose- and time-dependent manner. The activation of NFκB signaling was recognized by the nuclear translocation of p65. Periostin-induced upregulation of these genes was suppressed by NFκB inactivation in chondrocytes. Conclusion: Periostin was upregulated in OA cartilage, and it may amplify inflammatory events and accelerate OA pathology. [ABSTRACT FROM AUTHOR]

Schottky junctions made from platinum and niobium-doped strontium titanate (SrTiO3:Nb) were investigated by hard X-ray photoemission (HXPES) and through a band bending behavior simulation using a phenomenological model, which assumes a decrease in dielectric constant due to an electric field. Thus, we confirmed that the observed HXPES spectra at relatively high temperatures, e.g., >250 K, were well simulated using this phenomenological model. In contrast, it was inferred that the model was not appropriate for junction behavior at lower temperatures, e.g., <150 K. Therefore, a reconstruction of the phenomenological model is necessary to adequately explain the dielectric properties of SrTiO3. [ABSTRACT FROM AUTHOR]