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The aim of this study was to investigate the association between habitual dietary intake for patients with diabetes and the content of family support for medical nutritional therapy (MNT). Analyzed were 289 Japanese with type 2 diabetes (men, 58.5%; mean age, 62.0 years; mean HbA1c, 53.4 mmol/mol) who completed the Food Frequency Questionnaire and Diabetes Family Behavior Checklist (DFBC). Relationships of mean values for food group intake to DFBC responses regarding MNT were examined using multivariate analysis of covariance. Positive response to "Praise for following diet" was associated with lower sweets intake (none: 60.1 g/day; ≥once monthly: 50.9 g/day, p = 0.038) and higher seasoning intake (none: 21.6 g/day, ≥once monthly: 24.1 g/day, p = 0.046). Energy intake was higher with positive responses to "Eat at the same time that you do" (none: 1636 kcal/day, ≥once monthly: 1818 kcal/day, p = 0.038). "Nags about not following diet" was associated with higher fish (none: 68.7 g/day, ≥once monthly: 78.7 g/day, p = 0.042) and salt intake (none: 8.3 g/day, ≥once monthly: 9.0 g/day, p = 0.014). Eating foods not part of the diabetic diet (none: 218.4 g/day, ≥once monthly: 246.9 g/day, p = 0.014) resulted in a higher vegetable intake. In females, significant differences in relationships in the overall analysis were reversed. Our results clarified relationships between types of family support of patients with type 2 diabetes and their dietary intake and the importance of sex differences for more effective MNT.

The nuclear receptor peroxisome proliferator-activated receptor (PPAR)γ has been implicated in the pathogenesis of various human diseases including fatty liver. Although nuclear translocation of PPARγ plays an important role in PPARγ signaling, details of the translocation mechanisms have not been elucidated. Here we demonstrate that PPARγ2 translocates to the nucleus and activates signal transduction through H 2 O 2 -dependent formation of a PPARγ2 and transportin (Tnpo)1 complex via redox-sensitive disulfide bonds between cysteine (Cys)176 and Cys180 of the former and Cys512 of the latter. Using hepatocyte cultures and mouse models, we show that cytosolic H 2 O 2 /Tnpo1-dependent nuclear translocation enhances the amount of DNA-bound PPARγ and downstream signaling, leading to triglyceride accumulation in hepatocytes and liver. These findings expand our understanding of the mechanism underlying the nuclear translocation of PPARγ, and suggest that the PPARγ and Tnpo1 complex and surrounding redox environment are potential therapeutic targets in the treatment of PPARγ-related diseases., Competing Interests: Declaration of competing interest All authors have declared that no conflict of interest exists., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

New/worsening cognitive and physical impairments following critical care pose significant problems. Multidisciplinary cardiac rehabilitation (CR) can improve physical function after cardiac intensive care (CIC). This observational study aimed to evaluate cognitive function in patients participating in multidisciplinary CR and to identify correlates of impaired cognitive function after CIC. We analyzed 111 consecutive patients admitted to our comprehensive care ward at least 7 days after CIC and assessed factors associated with cognitive function using the Functional Independence Measure (FIM). Patients were stratified into two groups based on the median FIM-Cognitive scores: impaired (n = 56) and preserved cognition (n = 55) groups. Multiple logistic regression analysis identified age [odds ratio (OR) 1.06; 95% confidence interval (CI) 1.00-1.13; p = 0.042], Mini-Nutrition Assessment-Short Form (MNA-SF; OR 0.73; 95% CI 0.56-0.95; p = 0.017), and FIM-Physical scores (OR: 0.94; 95% CI 0.90-0.99; p = 0.012) as significant and independent factors associated with impaired cognition. The median length of hospital stay was 28 (interquartile range: 18, 43) days. The FIM-Cognitive and FIM-Physical scores significantly increased from admission to discharge [32.0 (27.0, 35.0) vs. 34.0 (29.0, 35.0) points; p < 0.001; 67.0 (53.0, 75.0) vs. 85.0 (73.5, 89.0) points; p < 0.001, respectively]. On subgroup analysis within the impaired cognition group, increased FIM-Cognitive scores positively and significantly correlated with increased FIM-Physical scores (ρ = 0.450; p = 0.001). Multiple linear regression analysis identified atrial fibrillation (AF; β = - 0.29; p = 0.016), ln(glycated hemoglobin; HbA1c) (β = 0.29; p = 0.018), and ln(high-sensitivity C-reactive protein; hs-CRP) (β = - 0.26; p = 0.034) as significant and independent factors correlated with increased FIM-Cognitive scores. In conclusion, advanced age, low MNA-SF score, and FIM-Physical score were independent factors associated with impaired cognition in post-CIC patients. Multidisciplinary CR improved both physical and cognitive functions, and AF, HbA1c, and hs-CRP were independent factors correlated with increased FIM-Cognitive score.

Purpose: Currently, knowledge regarding the intra-articular pathology and its relationship to outcomes after joint-preserving surgery in patients with osteonecrosis of the femoral head (ONFH) is lacking. The purposes were to evaluate the intra-articular pathology and its relationship with outcomes of joint-preserving surgery in ONFH., Methods: We reviewed 41 hips with ONFH in 41 patients (27 women; mean age, 34.9 years old) who underwent intertrochanteric curved varus osteotomy. Radiographic evaluations were based on pre-operative imaging studies, including radiographs, computed tomography (CT), and magnetic resonance imaging (MRI). Intra-articular pathology was evaluated by arthroscopic inspection of the femoral head, labrum, and acetabular cartilage during surgery. In addition, we performed radiographic measurements of the hip, including the collapse of the femoral head and minimal joint space width at three  years post-operatively and at final follow-up., Results: Arthroscopy revealed damage to the acetabular cartilage and labrum in 22 (54%) and 13 patients (32%), respectively. However, these lesions could be detected on imaging in only 13 (32%) and ten patients (24%), respectively. The change in joint space width after surgery was significantly higher in patients with cartilage degeneration and labral injury (P = 0.02, P = 0.02). Logistic regression analysis for subsequent progression of osteoarthritis showed an association with degenerative changes of articular cartilage and the labral tear as independent predictors (P = 0.001, P = 0.03)., Conclusions: Our data demonstrate the presence of labral and acetabular cartilage lesions in ONFH patients, while images do not reveal the full extent of the tissue damage. These intra-articular pathologies can be associated with the outcomes after joint-preserving surgery.

The surgical efficacy for supratentorial intracerebral hemorrhage (ICH) remains unknown. We compared the advantages of the widely practiced endoscopic hematoma removal under local anesthesia with that of craniotomy under general anesthesia for ICH. We also focused on our novel operative concept of intentional hematoma leaving technique to avoid further damage to the brain. We retrospectively analyzed 134 consecutive patients (66 endoscopies and 68 craniotomies) who were surgically treated for supratentorial ICH. The characteristics of the 134 patients were as follows: The median (interquartile range) age was 73 (61-82) years. The median Glasgow Coma Scale scores at admission, on day 7, and the median modified Rankin Scale (mRS) score at 6 months were 10 (7-13), 13 (10-14), and 4 (3-5) respectively. The statistical comparison revealed there were no differences in GCS score on day seven between the endoscopy 13 (12-14) and craniotomy group 12 (9-14). No differences were observed in mRS scores at 6 months between the endoscopy 4 (2-5) and craniotomy group 4 (3-5). However, the patients treated with our technique tended to have favorable outcomes. Multivariate analysis revealed the operative time was significantly decreased in the endoscopy group compared to the craniotomy group (p < 0.001).

RAD51 forms a complex with BRCA2 and plays a central role in the DNA damage response pathway that is associated with homologous recombination. The structures of RAD51 and its homologues are highly conserved from prokaryotes to higher eukaryotes. Although a large number of BRCA2 mutations have been reported, there are only a few reports on the mutations of RAD51, which have been shown in humans and dogs. However, several mutations of canine RAD51 were identified from mammary gland tumour tissues in a recent study. Some of these mutations seem to have an influence on the homo-oligomerization or interaction with "Partner and localizer of BRCA2" (PALB2). In this study, we cloned the canine PALB2 homologue and investigated the effect on its interaction with the RAD51 mutants to evaluate the alteration in the function of RAD51 mutants. The A209S and T225S mutants of RAD51 show an attenuation of the interaction between RAD51 and PALB2. These results indicate that the canine RAD51 mutations can potentially alter the homologous recombination pathways in response to DNA damage in dogs., (© 2019 John Wiley & Sons Ltd.)

Background and Aims: Psychologic stress can affect the pathogenesis of inflammatory bowel disease (IBD), but the precise contribution of psychologic stress to IBD remains unclear. We investigated the association of psychologic stress with disease activity in patients with IBD, especially in terms of mental state and sleep condition., Methods: This was a multi-center observational study comprising 20 institutions. Data were collected using survey forms for doctors and questionnaires for patients, and the association of psychologic stress with clinical parameters was investigated. Mental state was evaluated using the Center for Epidemiologic Studies Depression (CES-D) scale, and sleep condition was evaluated by querying patients about the severity of insomnia symptoms., Results: A total of 1078 IBD patients were enrolled, including 303 patients with Crohn's disease and 775 patients with ulcerative colitis. Seventy-five percent of IBD patients believed that psychologic stress triggered an exacerbation of their disease (PSTE group) and 25% did not (non-PSTE group). The CES-D scores were significantly higher for patients with clinically active disease than for those in remission in the PSTE group (median (interquartile range) = 7 (4-9.5) vs. 5 (3-7), p < .0001), but not in the non-PSTE group (5 (2-8) vs. 4 (3-7), p = 0.78). Female sex and disease exacerbation by factors other than psychologic stress were independent factors of psychologic stress-triggered disease exacerbation. Also, patients with insomnia had higher disease activity than those without insomnia, especially in the PSTE group., Conclusions: A worsened mental state correlates with disease activity in IBD patients, especially those who believe that their disease is exacerbated by psychologic stress., Competing Interests: The author has declared that no competing interests exist. The authors have no competing interests which can alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Subarachnoid hemorrhage with multiple aneurysms is very challenging because it is difficult to identify the ruptured aneurysm. We could not identify the ruptured aneurysm preoperatively, so we decided to treat all of the aneurysms as a single-stage surgery., Case Description: A 79-year-old woman was diagnosed with subarachnoid hemorrhage with multiple cerebral aneurysms at the right distal anterior cerebral artery, left middle cerebral artery, and right internal carotid artery- posterior communicating artery bifurcation. We could not identify the ruptured aneurysm preoperatively. We fixed her head using the Sugita head holding system (Mizuho Co., Ltd., Tokyo) and performed clipping for each aneurysm with bifrontal craniotomy and bilateral frontotemporal craniotomy as a single-stage operation. The last aneurysm seemed ruptured, and clipping for all the aneurysms was successful. She was discharged with a good postoperative course. The Sugita head holding system allowed turning the head of the patient toward the right and left with single fixation, leading to this single-stage operation., Conclusion: Several methods for identifying a ruptured aneurysm from multiple aneurysms have been reported, but under limited medical resources, this procedure would be one of the treatment strategies., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Surgical Neurology International.)

Contrast-enhanced computed tomography angiography is usually valuable for the evaluation of clipped cerebral aneurysm, but it has side effects of contrast medium. Time-of-flight magnetic resonance angiography (MRA) is a non-invasive and fast method. However, clip-induced artifact limits assessment of the artery in the vicinity of a clip. MRA with ultrashort echo time (TE) reduces metal artifact. We use MAGNETOM Aera 1.5T (SIEMENS, München, Germany) and perform pointwise encoding time reduction with radial acquisition (PETRA)-MRA using ultrashort TE for the assessment of the cerebral aneurysm after clipping. We, herein, presented two representative cases with a clipped aneurysm which could be evaluated by PETRA- MRA. Especially in one of them, the neck remnant was revealed by PETRA-MRA. PETRA-MRA can reduce the time and the invasiveness and may be helpful for the usual follow-up of the clipped aneurysm with the development of MRA technology in the future., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Surgical Neurology International.)

We encountered a case of panniculitis of the lesser omentum in 2018 after a long time since our first case report in 2007. We reviewed previously reported three cases of lesser omental panniculitis including our first case to investigate its clinical characteristics. Total four cases were relatively young with mean age of 30, and had common chief complaint of considerable epigastric pain and tenderness. Blood test showed increase in the white blood cell, C-reactive protein, or erythrocyte sedimentation rate. Computed tomography revealed mass like change in the fat tissue outside of the lesser curvature of the stomach. Histopathological diagnosis was made in one operated patient. Other three patients were treated conservatively, and progressed well. Lesser omental panniculitis is a possible cause of acute abdomen, which shows characteristic images of computed tomography and probably good progress by conservative treatment.

Endoscopic treatment for chronic subdural hematoma (CSDH) has been reported, but endoscopic findings of CSDH have not been thoroughly investigated. This study aimed to elucidate the relationship between endoscopic findings and CSDH recurrence. Furthermore, it examined the association between Nagahori's histopathological staging of CSDH and outer membrane color. Here, we retrospectively analyzed the operative videos of 70 patients with CSDH. The endoscopic findings were investigated, and their correlations with CSDH recurrence, the reduction ratio of the midline shift, and hematoma thickness on day 30 after the operation were analyzed. The outer membrane was white in 21 cases, yellow in 25 cases, and red in 24 cases. CSDH recurred in three (4.2%) patients, all of whom had a white outer membrane (adjusted odds ratio, 18; 95% confidence interval, 1.6-20.6; P = 0.007). The other endoscopic findings were not significantly related to CSDH recurrence, extent of the reduction ratio of the midline shift, or hematoma thickness. The outer membrane colors of white, red, yellow, and white almost corresponded to the histopathological staging from type I to IV in order. Our findings suggest that a white outer membrane is a risk factor for recurrence; these colors may represent the extent of inflammation related to the evolution of CSDH estimated from the histopathological findings.

Background and Objectives: Pediatric obesity is associated with clustered cardiometabolic risk and the future incidence of cardiovascular disease. However, few studies have determined the effect of pediatric obesity in Asia, where obesity is less common than in Western countries. We aimed to clarify whether weight status including underweight and slightly overweight is associated with metabolic risk factors in Japanese adolescents., Methods and Study Design: We performed a cross-sectional analysis of 2241 adolescents aged 13-14 years. Participants were classified as underweight, normal weight, slightly overweight, overweight, or obese according to the International Obesity Task Force. The clustered cardiometabolic risk (Z-CMR) was estimated by summing standardized sex-specific Z scores of mean arterial pressure (MAP), non-high-density lipoprotein cholesterol (non-HDLC), and HbA1c., Results: Linear regression analysis showed that MAP, non-HDL-C, and Z-CMR were higher in the slightly overweight, overweight, and obese groups than in the normal weight group after adjusting for confounders. Compared with the normal weight group, the slightly overweight, overweight, and obese groups had higher prevalence of high BP [odds ratios (ORs): 1.38 (95% CI, 1.03, 1.85); 2.63 (1.77, 3.91); and 2.39 (1.57, 3.64), respectively]. Compared with the normal weight group, underweight boys, but not girls, had a lower prevalence of high Z-CMR [OR=0.20 (0.05, 0.84)]., Conclusions: Adolescents classified as slightly overweight had higher levels of BP, serum lipids, and clustered cardiometabolic risk than those classified as normal weight. This observation showed significant associations between weight status and cardiometabolic risk factors during adolescence even in East Asians.

Background: The transtrochanteric rotational osteotomy is a common osteotomy for osteonecrosis of the femoral head, although the results of conversion total hip arthroplasty after the osteotomy are controversial. We evaluated how deformities in the proximal femur after the osteotomy affect hip impingement and the contact state of the stem in total hip arthroplasty., Methods: We retrospectively reviewed 35 hips (24 men) that had undergone the transtrochanteric rotational osteotomy for osteonecrosis of the femoral head (TRO-group) and compared them with 31 contralateral, unoperated hips (Primary group). The distance between the anterior and posterior greater trochanter at the cutting point of the femur, defined as the greater trochanter width and the contact area of the femoral implant surface with cortical bone were measured by CT-based three-dimensional templating software. We also calculated the hip range of motion in conversion total hip arthroplasty and analyzed the correlations between the greater trochanter width and the range of motion., Findings: The number of bony-impingement cases was significantly greater, and the range of motion in flexion, internal rotation and external rotation was significantly less in TRO-group. There was a significant negative correlation between the greater trochanter width and range of motion of internal rotation. There were no significant differences between two groups in percentages of femoral-implant contact area., Interpretations: The femoral implant fixation appears to be satisfactorily fixed in all zones in conversion total hip arthroplasty. However, the greater attention should be paid to minimizing bony impingement, especially on the anterior side, in conversion total hip arthroplasty., (Copyright © 2019. Published by Elsevier Ltd.)

This data informs about the characteristics of elderly patients over 75 with subarachnoid hemorrhage whose World Federation of Neurosurgical Societies (WFNS) grade were I to III. We retrospectively collected data from medical records in our hospital regarding physiological symptoms, laboratory data, radiological data on admission, and outcomes at discharge. Our article entitled "Clinical characteristics of aneurysmal subarachnoid hemorrhage in the elderly over 75; would temporal muscle be a potential prognostic factor as an indicator of sarcopenia? [1]" was based on this data. Remarkably, this is the first dataset on temporal muscle thickness/area and other characteristics of elderly patients over 75 with subarachnoid hemorrhage whose WFNS grade were I to III. Temporal muscle thickness and area were large in the elderly patients with SAH whose outcome were favorable., (© 2019 The Author(s).)

Objectives: Age of patients with subarachnoid hemorrhage (SAH) is increasing. It is challenging to decide whether to perform aneurysm treatment and to predict their prognosis. We assumed that elderly patients with SAH who do not suffer from sarcopenia tend to have good outcomes. Temporal muscle thickness (TMT) and area (TMA) are useful indicators of sarcopenia. We investigated the clinical characteristics, including temporal muscle, in SAH patients over 75 years old., Patients and Methods: We retrospectively analyzed 49 SAH patients over 75 years old from 2014 to 2018, who accounted for 37% of the patients in all age group. The correlations between the clinical variables and the modified Rankin Scale (mRS) at discharge were analyzed., Results: Of the all 49 SAH patients over 75 years old, premorbid mRS, WFNS grade, lymphocyte, aneurysm size, TMT, TMA, showed significant correlations with mRS at discharge. Men and the absence of hydrocephalus were correlated with favorable outcomes. Thirteen of the 24 patients over 75 years old whose WFNS grade were I to III but also who underwent aneurysm treatment had favorable outcomes (mRS 0-2), and their standardized TMT divided by height, by weight, and TMA divided by weight were significantly larger than that with poor outcomes., Conclusion: Aneurysm intervention should be considered when patients over 75 years old do not suffer from sarcopenia. Temporal muscle would indicate premorbid mRS and be potentially useful to decide surgical indication and to predict outcome after aneurysm treatment in the elderly., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Intrahepatic cholangiocarcinoma (ICC) is an extremely aggressive carcinoma. Useful predictors for the patients' prognosis after surgery have not been fully established. From the University of Tokyo Hospital pathology archives, we reviewed 107 cases of ICC, 54 cases of perihilar cholangiocarcinoma, and 40 cases of extrahepatic cholangiocarcinoma (ECC); we also investigated the significance of tumor budding in ICC, in comparison with perihilar cholangiocarcinoma and ECC. The tumor-budding frequencies were different by tumor location: 40.2% (43/107) in ICC, 70.4% (38/54) in perihilar cholangiocarcinoma, and 60.0% (24/40) in ECC. Tumor budding in ICC was associated with many pathologic indicators associated with invasion, such as major vascular invasion (P=0.012) and Union for International Cancer Control stage (P=0.007). Univariate and multivariate Cox regression analyses revealed tumor budding as a powerful prognostic factor for both recurrence-free survival (RFS) and overall survival (OS) in ICC by univariate (RFS: hazard ratio [HR]: 2.666; 95% confidence interval [CI]: 1.517-4.683, OS: HR: 4.206; 95% CI: 2.447-7.230) and by multivariate analyses (RFS: HR: 3.038; 95% CI: 1.591-5.973, OS: HR: 4.547, 95% CI: 2.348-8.805). Tumor budding was also a significant prognostic factor of perihilar cholangiocarcinoma, but not of ECC. When ICC was divided into 2 subtypes, type 1 (hilar) and type 2 (peripheral), tumor budding was the strong prognostic factor in type 2 ICC, but not in type 1 ICC, suggesting that some differences in biological behavior exist between type 1 ICC and perihilar cholangiocarcinoma. Tumor budding is prognostically important in ICC, and its pathogenetic role in biliary tract carcinomas might be different by anatomic location.

Interstrand crosslinks (ICLs) of the DNA helix are a deleterious form of DNA damage. ICLs can be repaired by the Fanconi anemia pathway. At the center of the pathway is the FANCD2/FANCI complex, recruitment of which to DNA is a critical step for repair. After recruitment, monoubiquitination of both FANCD2 and FANCI leads to their retention on chromatin, ensuring subsequent repair. However, regulation of recruitment is poorly understood. Here, we report a cluster of phosphosites on FANCD2 whose phosphorylation by CK2 inhibits both FANCD2 recruitment to ICLs and its monoubiquitination in vitro and in vivo. We have found that phosphorylated FANCD2 possesses reduced DNA binding activity, explaining the previous observations. Thus, we describe a regulatory mechanism operating as a molecular switch, where in the absence of DNA damage, the FANCD2/FANCI complex is prevented from loading onto DNA, effectively suppressing the FA pathway., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background:  Although lymphedema is fundamentally abnormal accumulation of excess water in the extracellular space, previous studies have evaluated the efficacy of physiological bypass surgery (lymphaticovenular anastomosis [LVA]) for lymphedema without measuring water volume. This study clarified the water reductive effect of LVA using bioelectrical impedance analysis (BIA)., Methods:  The efficacy of LVA for unilateral lower-limb lymphedema was evaluated using BIA in a retrospective cohort. The water volume of affected and unaffected legs was measured using multifrequency BIA before and after LVA. Preoperative measurements were undertaken after compression therapy for at least 3 months. The follow-up period after LVA was a minimum of 6 months., Results:  Thirty consecutive patients with unilateral lower-limb lymphedema were enrolled. The mean water volume reduction of the affected leg by LVA (ΔLBW) was 0.86 L (standard deviation [SD]: 0.86, median: 0.65) with a mean number of 3.3 anastomoses (SD: 1.7). The mean reduction rate of edema was 45.1% (SD: 36.3). Multiple linear regression analysis revealed water volume difference between the affected and unaffected legs before LVA (excess LBW) as the strongest predictor of ΔLBW ( R 2  = 0.759, p  < 0.01; β = 0.500, p  < 0.01)., Conclusion:  The LVA reduces the volume of accumulated body water in lower-limb lymphedema. As excess LBW most strongly predicted the amount of water volume reduction by LVA, body water volume measurement by BIA before LVA might identify patients with low excess LBW not expected to benefit from LVA, regardless of apparent differences in limb circumference., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Joint-preserving procedures should be considered as much as possible for hip disorders in pediatric and young patients. However, in patients with extensive osteonecrosis (ON) of the femoral head combined with severe collapse and advanced secondary osteoarthritis (OA), the optimal procedure has not been elucidated. This retrospective study aimed to investigate the postoperative outcomes of 11 patients who underwent transtrochanteric rotational osteotomy (TRO) alone or with a combination treatment for various hip disorders in young patients and to evaluate the usefulness of TRO., Methods: Eleven patients (11 hips) with a mean age at operation of 22 years were included. The mean follow-up duration was 9.4 years. Preoperative diagnosis was secondary OA in 6 patients (pigmented villonodular synovitis, 2; after rotational acetabular osteotomy, 1; pyogenic arthritis, 1; femoroacetabular impingement, 1; acetabular dysplasia, 1) and ON in 5 patients (slipped capital femoral epiphysis, 4; femoral neck fracture, 1). Combination treatment was performed in 2 patients with distraction arthroplasty and in 6 patients with intra-articular procedures (mosaicplasty, 1; drilling, 1; microfracture, 4; cam resection, 1). Clinical evaluation was performed by using the Merle d'Aubigne and Postel score (MDPS). Joint congruency and progression of osteoarthritic change in all cases, and progression of collapse in the ON patients were evaluated radiographically., Results: The mean MDPS improved from 10.3 to 14.2 in the OA patients and from 9.4 to 14.8 in the ON patients. The OA grade was maintained or improved in 10 hips (91%). Progressive collapse was prevented in all ON patients, and good remodeling was demonstrated., Conclusion: Even in the highly degenerative cases, TRO enabled repair and prevention of the progression of OA. This procedure might be a useful salvage operation for treating secondary OA and ON of the hip even if the clinical condition is advanced, especially in young patients., (Copyright © 2018 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Multiple studies have shown action to affect perception of motion. The speed intended in the generation of a motion by action affects the apparent speed of the motion. However, it was unclear whether action with no intention of speed affects the apparent speed of a motion. In Experiment 1, we investigated the apparent speed of a motion following a key press action. We manipulated the delay from the action to the consequent motion for shifting the timing of efference copy and found the apparent speed decreasing with increases in the delay. This could be because it is known that speed irrelevant action caused expansion of perceived duration of the consequent stimulus and it might have influenced the result in Experiment 1, we investigated the apparent duration of the action consequent static (Ex. 2-1) and motion (Ex. 2-2) stimulus. We found that the apparent duration was not changed with delay. Moreover, the apparent speed and duration had different characteristics on delay. These results were discussed in terms of the sense of agency., Competing Interests: The authors have declared that no competing interests exist.

Background and study aims  An increasing number of patients have been using anticoagulants including anti-vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs); however, in patients using anticoagulants, limited data are available with regard to the risks of gastrointestinal bleeding and thromboembolic events during the peri-endoscopic period. We aimed to evaluate the peri-endoscopic bleeding and thrombotic risks in patients administered VKAs or DOACs. Patients and methods  Consecutive patients using anticoagulants who underwent endoscopic biopsy, mucosal resection, or submucosal dissection were prospectively enrolled across 11 hospitals. The primary outcome assessed was difference in incidence of post-procedural gastrointestinal bleeding in patients using VKAs and DOACs. Duration of hospitalization and peri-procedural thromboembolic events were also compared. Results  We enrolled 174 patients using VKAs and 37 using DOACs. In total, 16 patients using VKA were excluded from the analysis because of cancellation of endoscopic procedures and contraindications to the use of DOACs; 128 (81 %) patients using VKAs and 17 (46 %) using DOACs received heparin-bridging therapy (HB). The rate of post-procedural gastrointestinal bleeding in DOAC users was similar to that in VKA users (16.2 % vs. 16.4 %, P  = 1.000). Duration of hospitalization was significantly longer in patients using VKAs than in those using DOACs (median 15 vs. 7 days, P  < 0.0001). Myocardial infarction occurred during pre-endoscopic HB in one patient using VKAs. Conclusion  DOAC administration showed similar post-procedural gastrointestinal bleeding risk to VKA administration in patients undergoing endoscopic procedures, but it shortened the hospital stay.

Background: Rotational acetabular osteotomy (RAO) is one of the surgical treatments for acetabular dysplasia, and satisfactory results have been reported. We evaluated the postoperative changes of articular cartilage and whether the pre-operative condition of the articular cartilage influences the clinical results using T2 mapping MRI., Methods: We reviewed 31 hips with early stage osteoarthritis in 31 patients (mean age, 39.6 years), including three men and 28 women who underwent RAO for hip dysplasia. Clinical evaluations including Japanese Orthopedic Association (JOA) score and Japanese Orthopedic Association Hip Disease Evaluation Questionnaire (JHEQ), and radiographical evaluations on X-ray were performed. Longitudinal qualitative assessment of articular cartilage was also performed using 3.0-T MRI with T2 mapping technique preoperatively, 6 months, and at 1 and 2 years postoperatively., Results: There was no case with progression of osteoarthritis. The mean JOA score improved from 70.1 to 93.4 points, the mean postoperative JHEQ score was 68.8 points, and radiographical data also improved postoperatively. We found that the T2 values of the cartilage at both femoral head and acetabulum increased at 6 months on coronal and sagittal views. However, they significantly decreased 1 and 2 years postoperatively. The T2 values of the center to anterolateral region of acetabulum negatively correlated with postoperative JHEQ score, particularly in pain score., Conclusions: This study suggests that biomechanical and anatomical changes could apparently cause decreased T2 values 1-2 years postoperatively compared with those preoperatively. Furthermore, preoperative T2 values of the acetabulum can be prognostic factors for the clinical results of RAO.

The Fanconi Anemia (FA) pathway is important for repairing interstrand crosslinks (ICLs) between the Watson-Crick strands of the DNA double helix. An initial and essential stage in the repair process is the detection of the ICL. Here, we report the identification of UHRF2, a paralogue of UHRF1, as an ICL sensor protein. UHRF2 is recruited to ICLs in the genome within seconds of their appearance. We show that UHRF2 cooperates with UHRF1, to ensure recruitment of FANCD2 to ICLs. A direct protein-protein interaction is formed between UHRF1 and UHRF2, and between either UHRF1 and UHRF2, and FANCD2. Importantly, we demonstrate that the essential monoubiquitination of FANCD2 is stimulated by UHRF1/UHRF2. The stimulation is mediating by a retention of FANCD2 on chromatin, allowing for its monoubiquitination by the FA core complex. Taken together, we uncover a mechanism of ICL sensing by UHRF2, leading to FANCD2 recruitment and retention at ICLs, in turn facilitating activation of FANCD2 by monoubiquitination., Competing Interests: The authors have declared that no competing interests exist.

Object: To examine the clinical outcomes of a project to enhance the awareness of community-based palliative care (awareness-enhancing project), focusing on home death and care rates in communities., Methods: A single-center study on community-based intervention was conducted. The awareness-enhancing project, consisting of three intervention approaches (outreach, palliative care education for community-based medical professionals, and information-sharing tool use), was executed, and changes in the home death rate in the community were examined., Results: The home death rate markedly exceeded the national mean from 2010. In 2012-2013, it was as high as 19.9%, greater than the previous 5.9% (p = 0.001). Through multivariate analysis, the participation of home care physicians and visiting nurses in a palliative care education program, and patients' Palliative Prognostic Index values were identified as factors significantly influencing the home death rate., Conclusion: The three intervention approaches time dependently increased the home death rate as a clinical outcome in the community, although they targeted limited areas. These approaches may aid in increasing the number of individuals who die in their homes.

Background & Aims: High intake of fruit and vegetables is recommended for cardiovascular health. However, there have been persistent beliefs that fruits having high concentrations of fructose elevate the level of triglycerides (TG) in blood unlike vegetables. This meta-analysis aims to clarify the relationship between fruit intake and TG or hypertriglyceridemia., Methods: Electronic literature searches were conducted for observational studies that investigated the relationship between fruit intake and hypertriglyceridemia or intervention studies that investigated the effect of increasing fruit intake on TG. Each effect size was pooled with an inverse-variance method., Results: Five cross-sectional studies and only 2 intervention studies were eligible. The pooled odds ratio (OR) (95% confidence interval (CI)) of the 5 cross-sectional studies for the highest vs. the lowest fruit intake category was 0.79 (0.72-0.87). In these studies, the pooled OR for the highest vs. the lowest vegetable intake category was not significant (OR = 0.92; 95% CI, (0.82-1.03)). A linear dose-response association was observed between increases in fruit intake and ORs for hypertriglyceridemia; the OR (95% CI) for an incrementally increased intake of fruit by 1 serving/day was 0.91 (0.84-0.98)., Conclusion: This meta-analysis suggests that high intake of fruit but not vegetables is inversely associated with hypertriglyceridemia. More trials are needed to clarify whether increasing fruit intake would reduce the level of TG and/or incident hypertriglyceridemia., (Copyright © 2018 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: In addition to visceral fat, peripheral ectopic fat accumulation is suggested to play a role in the pathophysiology of metabolic syndrome, which is known to be associated with not only cardiovascular diseases and type 2 diabetes mellitus but also colorectal cancer., Objective: This study aims to clarify whether there is ectopic fat accumulation in human colorectal tissue in association with metabolic syndrome or its components such as abdominal obesity and insulin resistance., Methods: Lipid contents of colorectal tissue were measured in 27 patients with colorectal polyp excised endoscopically. In addition, lipid droplets were immunohistochemically estimated using anti-perilipin antibody in 32 patients with colorectal cancer resected surgically., Results: Increasing tissue triglyceride/phospholipid ratio was associated with increasing body mass index, fasting plasma insulin level and homeostasis model assessment as an index of insulin resistance (HOMA-IR), and also decreasing serum adiponectin level. Lipid droplets were observed in the submucosal region of colorectal tissue. The amount of lipid droplets was associated with increasing body mass index, waist circumference and visceral fat area., Conclusion: This study showed the presence of submucosal fat accumulation in human colorectal tissue and its association with abdominal obesity and insulin resistance.

Background: There is little description of the effect of cup position on the hip range of motion in total hip arthroplasty. The purpose is to evaluate the effect of cup medialization/lateralization with a compensatory increase/decrease in femoral offset on the hip range of motion, and whether the bone morphology of the anterior inferior iliac spine affects hip range of motion in total hip arthroplasty., Methods: Using the CT data of 100 patients (male; 30, female; 70), 3D-dynamic motion analysis was performed in four scenarios with cup medialization/lateralization with the same/decreased global offset. We calculated the range of motion before component impingement and bony impingement in flexion, internal rotation and external rotation using the software. Furthermore, we measured bony morphological features of anterior inferior iliac spine, and we analyzed the correlations among them., Findings: We found that the cup medialization with the same stem offset had negative effects on hip range of motion in flexion and internal rotation due to bony impingement, whereas cup medialization caused external rotation to significantly decrease with the same global offset. On the other hand, cup lateralization with the same global offset had negative effects on flexion and internal rotation, whereas external rotation increased. Furthermore, there were negative correlations among flexion and laterally large and steep anterior inferior iliac spine., Interpretation: Our results demonstrated that the advantage of cup medialization can depend on the individual anatomy such as bony morphology of anterior inferior iliac spine in flexion., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Lactoferrin (Lf) and transferrin (Tf) are iron-binding proteins that can bind various metal ions. This study demonstrates the heme-binding activity of bovine Lf and Tf using biotinylated hemin. When both proteins were coated on separate plate wells, each directly bound biotinylated hemin. On the other hand, when biotinylated hemin was immobilized on an avidin-coated plate, soluble native Lf bound to the immobilized biotinylated hemin whereas native Tf did not, suggesting that a conformational change triggered by coating on the plate allows the binding of denatured Tf with hemin. Incubation of Lf with hemin-agarose resulted in negligible binding of Lf with biotinylated hemin. Lf in bovine milk also bound to immobilized biotinylated hemin. These results demonstrate that bovine Lf has specific heme-binding activity, which is different from Tf, suggesting that either Tf lost heme-binding activity during its evolution or that Lf evolved heme-binding activity from its Tf ancestral gene. Additionally, Lf in bovine milk may bind heme directly, but may also bind heme indirectly by interaction with other milk iron- and/or heme-binding proteins.

Hip dysplasia is a common cause of secondary osteoarthritis. To prevent the early onset of secondary osteoarthritis, rotational acetabular osteotomy has been proposed 1 ., Description: The approach combines the anterior iliofemoral and posterior approaches through a single skin incision. The pubic bone is cut independently, and the ilium and ischium are cut in continuity. The rotation of the acetabulum provides a more horizontal weight-bearing area and, at the same time, returns the superiorly subluxated femoral head to a more normal position., Alternatives: The Ganz periacetabular osteotomy involves the same concept as a rotational acetabular osteotomy with a different surgical approach. The rate of major complications, such as intra-articular osteotomy, nerve palsy, loss of fixation, malreduction, and symptomatic heterotopic ossification, is lower in rotational acetabular osteotomy (0% to 18%) 2 than in periacetabular osteotomy (6% to 37%) 3 . Because of a wide surgical exposure, osteotomy can be performed under direct vision in rotational acetabular osteotomy., Rationale: Rotational acetabular osteotomy for osteoarthritis secondary to hip dysplasia can alter the position of the acetabulum en bloc and cover the femoral head with cartilage. For the unstable hip with dysplasia, the surgical procedure is needed for the prevention of osteoarthritis.

Background and Study Aims:  Endoscopic submucosal dissection (ESD) is useful for en bloc resection of superficial colorectal neoplasms to ensure accurate histologic diagnoses. However, colorectal ESD is associated with a high frequency of adverse events (AEs). We aimed to investigate the effectiveness of prophylactic clip closure (PCC) of mucosal defects for AEs after colorectal ESD., Patients and Methods:  This study included 197 patients with 211 lesions who underwent colorectal ESD between June 2010 and August 2016. Patients who had delayed perforation, delayed bleeding, abdominal pain, or fever were defined as AEs after colorectal ESD. Complete PCC was defined as completely sutured mucosal defect using endoclips following colorectal ESD, whereas incomplete PCC was defined as the mucosal defects that did not enable PCC or were partially sutured. Clinical records were retrospectively reviewed and clinical outcomes evaluated., Results: AEs occurred in 29 lesions (13.7 %), including 12 with delayed bleeding, 12 with fever, 2 with abdominal pain, 2 with fever and abdominal pain, and 1 with delayed bleeding and fever. Delayed perforation was not observed in any patient. The frequency of AEs was significantly lower in the group with complete PCC than in the group with incomplete PCC (7.3 % [9/123] vs. 22.7 % [20/88]; P  < 0.001). Multivariate analysis revealed that AEs after colorectal ESD were significantly associated with tumor size and submucosal fibrosis. Subgroup analysis among the resected specimen size of < 40 mm revealed that there was no significant difference in AEs between the 2 groups (5.6 % [6/107] vs. 17.8 % [8/45]; P  = 0.069). However, the frequency of fever with complete PCC was significantly lower than that with incomplete PCC (2.8 % [3/107] vs. 13.3 % [6/45]; P  = 0.020)., Conclusions: Tumor size and submucosal fibrosis were independent risk factors for AEs after colorectal ESD. PCC may be effective in minimizing AEs after colorectal ESD, especially the frequency of fever.

Idiopathic osteonecrosis of the femoral head (IONFH) is an ischemic disorder that causes bone necrosis of the femoral head, resulting in hip joint dysfunction. IONFH is a polygenic disease and steroid and alcohol have already known to increase its risk; however, the mechanism of IONFH remains to be elucidated. We performed a genome-wide association study using ~60,000 subjects and found two novel loci on chromosome 20q12 and 12q24. Big data analyses identified LINC01370 as a candidate susceptibility gene in the 20q12 locus. Stratified analysis by IONFH risk factors suggested that the 12q24 locus was associated with IONFH through drinking capacity. Our findings would shed new light on pathophysiology of IONFH.

Background: Environmental factors are suggested to affect the pathogenesis of several diseases, including inflammatory bowel disease (IBD). The seasonality of disease onset and exacerbation in IBD, however, are not well established. We herein aimed to clarify the disease seasonality and to investigate the underlying characteristics in IBD patients exhibiting seasonality of the disease course., Methods: This was a multicenter observational study comprising 20 institutions (Osaka Gut Forum) in Japan. Data were collected from November 2013 to August 2014 using survey forms for physicians and questionnaires for patients. Multivariate analysis was performed to clarify the independent factors affecting disease seasonality., Results: A total of 1055 patients, including 298 patients with Crohn's disease (CD) and 757 patients with ulcerative colitis (UC), were enrolled. The proportion of CD patients with disease onset in the summer was significantly larger than that in the other seasons, while UC patients exhibited no seasonality of disease onset. More than half of the IBD patients (51.1%) experienced seasonal exacerbation of IBD, and winter was the most common season for disease exacerbation in both CD and UC patients. Seasonality of disease onset and exacerbation was observed in young-onset patients (≤40 years old), but not in elderly-onset patients. Age at onset was independently associated with the seasonality of both disease onset and exacerbation., Conclusions: Seasonality of disease onset and exacerbation was observed especially in young-onset IBD patients. Underlying pathophysiologic triggers for disease initiation and exacerbation may be influenced by age at disease onset.

Background: Radiographic detection of calcification in pituitary adenoma is relatively rare, and the clinical characteristics of pituitary adenoma with calcification remain unclear. Herein, the clinical characteristics of pituitary adenoma with radiological calcification were investigated., Methods: A total of 160 patients who underwent surgical resection of pituitary adenomas between February 2004 and December 2016 were reviewed. Eighty-one patients had hormone-secreting pituitary adenomas, and 79 patients had nonfunctioning pituitary adenoma. Among these 160 patients, cases with radiological calcifications on preoperative neuroimaging were included in this study, and clinical characteristics with intraoperative findings were analyzed, retrospectively., Results: Pituitary adenoma with calcification on preoperative neuroimaging was observed in only nine cases (5.6%). The study population consisted of these nine patients with nonfunctioning pituitary adenoma (n = 5), mixed growth hormone and prolactin-secreting pituitary adenomas (n = 3), and a prolactinoma (n = 1). In 89% of cases (n = 8), calcified pituitary adenoma was soft enough for suction despite the presence of a granular gritty texture intraoperatively. Besides, in a single patient (11%), evidence of hard thick capsular calcification was seen surrounding a soft tumor component; however, it did not interfere with adequate removal of the soft part, and tumor resection was possible in all cases without any complications., Conclusions: Pituitary adenoma presenting with calcification is relatively rare, but should be kept in mind to avoid making a wrong preoperative diagnosis. As not all pituitary adenomas with calcification are hard tumors, preoperative radiological calcification should not affect decision-making regarding surgical indications.

Aim: As society ages, there is a vast number of elderly people with locomotive syndrome. In this study, the factors associated with functional limitations in daily living activities evaluated by female hip osteoarthritis (OA) patients were investigated., Methods: This study was a cross-sectional study. The subjects were 353 female patients who were newly diagnosed with hip OA at an orthopedic clinic with no history of hip joint surgery. Outcome indices were functional limitations in two daily living activities obtained from a questionnaire completed by the patients: (i) standing up (standing from a crouched position) and (ii) stair-climbing (climbing and/or descending stairs). The odds ratios (ORs) and 95% confidence intervals (CIs) were computed for explanatory variables using the proportional odds model in logistic regression to evaluate their associations with functional limitations., Results: Functional limitations in standing up were associated with heavy weight (third tertile vs. first tertile: 1.91, 1.11-3.27), participation in sports at school (0.62, 0.40-0.98), parity (vs. nullipara: 1.96, 1.08-3.56), old age and OA stage. Associations with functional limitations in stair-climbing were seen with short height (< 151.0 cm vs. ≥ 156.0 cm: 2.05, 1.02-4.12), bilateral involvement (vs. unilateral: 1.71, 1.01-2.88), old age and OA stage., Conclusion: Old age, OA stage, heavy weight, parity, shorter height and bilateral OA were associated with functional limitations in standing up and/or stair-climbing, whereas participation in sports such as club activities in school maintained standing up., (© 2016 The Authors. International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: We previously reported that near-infrared irradiation nonthermally induces long-lasting vasodilation of the subdermal plexus by causing apoptosis of vascular smooth muscle cells. To clarify the possible application of near-infrared irradiation to prevent skin flap necrosis, we evaluated the length of axial pattern flap survival in rats by near-infrared irradiation. Methods: A bilaterally symmetric island skin flap was elevated under the panniculus carnosus on the rat dorsum. Half of the flap was subjected to near-infrared irradiation just before flap elevation with a device that simulates solar radiation, which has a specialized contact cooling apparatus to avoid thermal effects. The length of flap survival of the near-infrared irradiated side was measured 7 days after flap elevation and compared with the nonirradiated side. Results: The irradiated side showed elongation of flap survival compared with the nonirradiated side (73.3 ± 11.7 mm vs 67.3 ± 14.9 mm, respectively, P = .03). Conclusions: Near-infrared irradiation increases the survival length of axial pattern flaps in rats.

Primary small bowel adenocarcinoma (SBA) is a rare cancer for which effective treatment strategies have not yet been established. The results of previous retrospective studies suggest that chemotherapy contributes to a longer survival time in patients with SBA. However, there are few case reports about the efficacy of molecular targeted agent-containing chemotherapy for SBA. In the present study, the treatment and follow-up data of patients with SBA who received chemotherapy with or without molecular targeted agents were retrospectively analyzed. Each patient was treated in one of ten hospitals participating in the Osaka Gut Forum between April 2006 and March 2014. The following factors were evaluated: Age, sex, Eastern Cooperative Oncology Group performance status (PS), tumor location, tumor differentiation, chemotherapy regimen, resection of primary tumor, tumor biomarker expression, distant metastasis, best response under chemotherapy, time to disease progression, subsequent treatments, survival status and treatment toxicity. A total of 27 patients (17 males and 10 females; mean age, 63.4 years old; range, 36-83 years old) received chemotherapy due to non-curative tumor resection, unresectable tumor or post-operative recurrence. The median overall survival time was 14.8 months (range, 2-58 months). A univariate analysis revealed a PS of 0 (P=0.0228) and treatment with platinum-based chemotherapy (P=0.0048) were significant factors for an improved prognosis. An age-adjusted multivariate analysis also revealed that a platinum-based regimen was a significant positive prognostic factor (P=0.0373). Molecular targeted agents were administered to 8 patients, for whom it was their first- or second-line therapy. Among the 17 patients who received oxaliplatin-based chemotherapy as a first-line chemotherapy, a PS of 0 (P=0.0255) and treatment with bevacizumab (P=0.0121) were significant positive prognostic factors. Toxicities higher than Grade 3 occurred in 8/27 patients with SBA; however, serious side effects due to the molecular targeted agents were not experienced. The results of the present study indicate that chemotherapy containing molecular targeted agents is a well-tolerated and effective treatment option for SBA.

Background: Cerebral sparganosis is a rare zoonotic infestation that often mimics glioma and metastatic tumors., Case Description: A 71-year-old man presented with disturbing dysarthria. Initial neuroimages were suggestive of glioma. However, the histology was suggestive of inflammatory lesion. Follow-up neuroimages and serology were suggestive of sparganosis. He subsequently had craniotomy with ultrasound-guided aspiration of a live worm. Saline-soaked Surgicel was used to provide an acoustic window., Conclusions: Ultrasonography was helpful in the intraoperative localization of the worm and is recommended when intraoperative magnetic resonance is not readily available., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background and study aims  Patients who receive warfarin usually require heparin bridge therapy (HBT) to prevent thromboembolic events during endoscopic submucosal dissection (ESD); however, clinical evidence demonstrating the safety and efficacy of HBT during gastric ESD is limited. Conversely, warfarin can be continuously used as a substitute for HBT to endoscopic procedures which have a low risk of bleeding. This study aimed to clarify the safety and efficacy of continuous low-dose warfarin (LDW) for gastric ESD. Patients and methods  This was a prospective observational study at a single institution. A total of 22 patients who received warfarin between December 2014 and January 2016 were enrolled. The patients were treated with gastric ESD with a low dose of warfarin ( ≤ 4 mg) at approximately 1.6 - 2.6 of the international normalized ratio (INR) levels. Furthermore, we analyzed a total of 23 patients with HBT who underwent gastric ESD between January 2011 and November 2014. Results  The average of warfarin dose and the INR level on the day of gastric ESD in the continuous LDW group were 2.3 mg/day (range 0.5 - 4.0) and 1.87 (range 1.41 - 2.75), respectively. Two of the 22 patients (9.1 %) in the continuous LDW group and 5 of the 23 patients (21.7 %) in the HBT group had postoperative bleeding after gastric ESD. Although the postoperative bleeding rate in the continuous LDW group was lower than that in the HBT group, no significant difference was observed between the 2 groups ( P  = 0.414). Conclusions  Gastric ESD with continuous LDW as a substitute for HBT was feasible and may be acceptable.

Background: Autologous fibrin clots derived from peripheral blood (pb-fibrin clot) and bone marrow (bm-fibrin clot) are thought to be effective for tissue regeneration. However, there is no report detailing the amount of growth factors in pb-/bm-fibrin clot. In this study we evaluated the amount of growth factors in human pb-/bm-fibrin clot, and prove the validity of fibrin clot for clinical use., Methods: Human pb-/bm-fibrin clots were obtained during surgery. In the first experiment, enzyme-linked immunosorbent assay (ELISA) was performed for detecting the amount of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), fibroblast growth factor basic (bFGF), hepatocyte growth factor (HGF), transforming growth factor-beta (TGF-β), platelet derived-growth factors-AB (PDGF-AB), and stromal cell-derived factor-1 (SDF-1). In the second experiment, the efficacy of fibrin clot on the osteogenic differentiation and fibroblast proliferation was evaluated. Pb-/bm-fibrin clots were incubated in human osteoblast derived from mesenchymal stromal cells (MSCs) or human skin fibroblast. Alizarin red staining and real-time PCR (COL1A1, RUNX2) were performed for the detection of osteogenic potential. Cell-growth assay (WST-8) and real-time PCR (COL1A1) were also performed for the detection of the potential of fibroblast proliferation., Results: ELISA analysis revealed that the amount of VEGF, HGF, bFGF, IGF-1, and SDF-1 of bm-fibrin clot group is higher than that of pb-fibrin clot group with statistical differences. Besides, we confirmed that bm-fibrin clot has much potential for the osteogenic differentiation and fibroblast proliferation., Conclusion: The positive outcomes confirm the efficacy of pb-/bm-fibrin clot, and bm-fibrin clot was proved to have much potential for tissue regeneration compared with pb-fibrin clot. The current study showed the potential of a strategy for regenerative medicine using bm-fibrin clot.

Aim: To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for small rectal submucosal tumors (SMTs)., Methods: Between August 2008 and March 2016, 39 patients were treated with endoscopic submucosal resection with a ligation device (ESMR-L) ( n = 21) or ESD ( n = 18) for small rectal SMTs in this study. Twenty-five lesions were confirmed by histological evaluation of endoscopic biopsy prior to the procedure, and 14 lesions were not evaluated by endoscopic biopsy. The results for the ESMR-L group and the ESD group were retrospectively compared, including baseline characteristics and therapeutic outcomes., Results: The rate of en bloc resection was 100% in both groups. Although the rate of complete endoscopic resection was higher in the ESD group than in the ESMR-L group (100% vs 95.2%), there were no significant differences between the two groups ( P = 0.462). In one patient in the ESMR-L group with a previously biopsied tumor, histological complete resection with a vertical margin involvement of carcinoid tumor could not be achieved, whereas there was no incomplete resection in the ESD group. The mean length of the procedure was significantly greater in the ESD group than in the ESMR-L group (14.7 ± 6.4 min vs 5.4 ± 1.7 min, P < 0.05). The mean period of the hospitalization was also significantly longer in the ESD group than in the ESMR-L group (3.7 ± 0.9 d vs 2.8 ± 1.5 d, P < 0.05). Postoperative bleeding was occurred in one patient in the ESMR-L group., Conclusion: Both ESMR-L and ESD were effective for treatment of small rectal SMTs. ESMR-L was simpler to perform than ESD and took less time., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.

Background: Hip dysplasia is a common cause of secondary osteoarthritis (OA). Periacetabular osteotomy or rotational acetabular osteotomy has been used as joint-preserving procedures. However, only a few reports of long-term results with these operations have been reported., Questions/purposes: (1) Would satisfactory clinical and radiographic outcomes be maintained at a mean duration of 20 years after rotational acetabular osteotomy for pre- and early-stage OA; and (2) could we identify risk factors for radiographic progression of OA?, Methods: Between 1987 and 2001, we treated 159 patients (173 hips) with rotational acetabular osteotomies for the diagnosis of pre-OA or early-stage OA according to the technique of Ninomiya and Tagawa. During that period, our general indications for this approach were age younger than 60 years, center-edge angle less than 20°, and improved femoral head coverage and joint congruency on preoperative AP plain radiographs of the hip in abduction; we did not use this approach when joint congruency was not improved or no widening of the joint space was noted on preoperative AP plain radiographs of the hip in abduction. Of those patients, 21 patients with pre-OA (followup rate: 84% [27 hips]) and 110 patients in the early-stage group (followup rate: 82% [118 hips]) were available at a minimum of 15 years for a total patient group of 131 (followup rate: 82% [145 hips]). The mean age at the time of surgery was 22 years in the pre-OA group and 38 years in the early-stage group. The mean followup was 21 years in the pre-OA group and 20 years in the early-stage group. Clinical evaluation was performed with the Merle d'Aubigne and Postel rating scale, and radiographic analyses included measurements of the center-edge angle, acetabular roof angle, and head lateralization index on preoperative and postoperative AP radiographs of the pelvis. Postoperative joint congruency was also evaluated. The cumulative probabilities of radiographic signs of OA progression were estimated with use of the Kaplan-Meier product-limited method and parametric survivorship analysis using the Cox proportional-hazards model was used to determine risk factors for radiographic OA progression., Results: The mean clinical score improved very slightly, from 15 (SD, 0.8) to 18 (SD, 1.1) (95% confidence interval [CI], -2.9 to -2.0; p < 0.001) in the pre-OA group and from 15 (SD, 1.0) to 16 (SD, 2.1) (95% CI, -2.0 to -1.2; p < 0.001) in the early-stage group at followup. Fourteen patients (15 hips) including one pre-OA patient (one hip) and 13 early-stage patients (14 hips) experienced worsening of their Merle d'Aubigne and Postel score, from a mean of 15 (SD, 0.9) to 12 (SD, 1.6) (95% CI, 1.8-3.3; p < 0.001). Eight patients (nine hips) with early-stage OA preoperatively underwent total hip arthroplasty at a mean duration after rotational acetabular osteotomy of 20 (SD, 2.5) years. Radiographic indices were improved after surgery in both groups. Radiographic progression of OA occurred in 24 patients (25 hips). Kaplan-Meier survivorship analysis, with radiographic signs of progression of OA as the endpoint, predicted survival of 96% (95% CI, 89%-100%) at 10 years and 20 years in the pre-OA group. For the early-stage group, we found survivorship of 89% (95% CI, 83%-95%) at 10 years and 78% (95% CI, 69%-87%) at 20 years. We identified two factors associated with poor outcome: fair (rather than excellent and good) postoperative joint congruency (hazard ratio, 12.1; 95% CI, 3.8-39; p < 0.001) and age older than 46 years at the time of surgery (hazard ratio, 4.6; 95% CI, 1.9-11; p < 0.01)., Conclusions: Rotational acetabular osteotomy is an effective surgical procedure for symptomatic dysplastic hips in pre- and early-stage OA, and it prevented radiographic OA progression and maintained hip function at a mean 20 years after surgery., Level of Evidence: Level IV, therapeutic study.

Backgound: Despite the fact that femoral impingement against the anterior inferior iliac spine (AIIS) is increasingly recognized, there is no description of morphologic features of the AIIS in hip dysplasia and their effect on hip range of motion (ROM) in total hip arthroplasty (THA). The purpose is to evaluate the bone morphology of the AIIS in hip dysplasia and whether its morphology affects hip ROM in THA., Methods: Computed tomography-based simulation software was used to create 3-dimensional bone models and perform virtual simulations. Using the computed tomographic data of 85 patients (male: n = 25, female: n = 60, mean age: 60.9) with hip osteoarthritis due to dysplasia, we measured the straight, vertical, and horizontal distances between the anteroinferior edge of the AIIS and the center of rotation in sagittal and axial views. The anterior and lateral versions of the AIIS were also measured. We calculated the ROM of flexion (Flex), and internal rotation (Int-R) in THA in the software, and analyzed the correlations among them., Results: The AIIS prominence is bigger and extends more anteriorly and laterally in males than in females. Furthermore, the taller the patient, the more the AIIS extends anteriorly and laterally. We found that Flex and Int-R decreased inversely proportional to the size and lateral version of the AIIS., Conclusion: Our results demonstrated that the AIIS bone morphology substantially affects the ROM of Flex and Int-R especially in patients with laterally large AIIS bony anatomy in THA. Furthermore, our result indicates that the morphologic features of AIIS in hip dysplasia may be different between males and females., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: In Japan, the majority of hip osteoarthritis (OA) was caused by acetabular dysplasia, and about 90 % of patients were female. The present study focused on Japanese female patients with hip OA due to acetabular dysplasia, and examined the associated factors with OA staging at diagnosis, in special reference to body weight., Methods: Study subjects were 336 Japanese women who were newly diagnosed with hip OA caused by acetabular dysplasia at 15 hospitals in 2008. The self-administered questionnaire elicited patients' body weight at age 20 and at OA diagnosis. Four ranked OA staging according to radiographic findings of the hip joint (pre-OA, initial stage, advanced stage or terminal stage) was regarded as the outcome index. Proportional odds models in logistic regression were used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs) for severer stage of OA., Results: At diagnosis, 45 % of patients suffered from terminal stage of OA, whereas 13 % and 14 % were categorized into pre-OA and initial stage, respectively. After adjustment for potential confounders, weight gain since age 20 revealed the increased ORs for severer OA stage at diagnosis (OR 2.02; 95 % CI, 1.07-3.80). Other significant characteristics were age (67+ vs. 20-49 years, OR 12.4), lower education (junior high school vs. junior college or higher, OR 4.00), parity (OR 2.19), lower acetabular head index (<60.0 vs. 71.1+, OR 2.36), and longer duration since symptom onset (6.0+ vs. <1.0 year, OR 2.94)., Conclusions: Weight gain since age 20 might be involved in mechanisms of OA development, which is independent of age or severity of acetabular dysplasia.

Background: Acute compartment syndrome is an orthopedic emergency requiring urgent fasciotomy to prevent irreversible damage. In hematological malignancies, acute compartment syndrome caused by severe soft tissue bleeding is extremely rare. We present a patient with chronic-phase chronic myeloid leukemia who had acute compartment syndrome caused by severe soft tissue bleeding in her right forearm., Case Presentation: A 72-year-old Japanese woman was referred to our hospital with swelling and pain of her right forearm without a previous history of trauma. She was diagnosed with chronic-phase chronic myeloid leukemia. Extreme thrombocytosis was present, although no evidence of acquired von Willebrand disorder was found. Compartment syndrome caused by soft tissue bleeding was confirmed. An emergency fasciotomy for decompression was conducted. However, sustained postoperative bleeding occurred and required massive red cell concentrate transfusion. As her platelet count decreased by cytoreductive therapy, complete hemostasis was achieved., Conclusions: Patients with an extremely high platelet count might be at high risk for severe bleeding complications even without acquired von Willebrand disease. For the control of severe bleeding complications in patients with myeloproliferative disorder, the importance of thrombocyte reduction should be recognized.

Human immunoglobulin G (IgG) binding with zinc ions was examined using zinc ions immobilized on chelating Sepharose beads (Zn-beads). Human IgG bound to Zn-beads but not to Sepharose beads (control beads). Mouse, rat, bovine and equine IgGs also bound to Zn-beads, similar to human IgG. The human IgG F(c) fragment showed zinc ion-binding activity whereas the Fab fragment did not. Ethylenediaminetetraacetic acid (EDTA)-treated Zn-beads no longer bound human IgG; however, washing the beads, followed by the addition of zinc ions, restored the binding activity towards human IgG. Zn-beads saturated with human fibrinogen could bind human IgG, and Zn-beads saturated with human IgG could bind fibrinogen. These results suggest that animal IgGs, including human, specifically bind zinc ions, probably through a zinc-binding site in the F(c) fragment and not in the Fab fragment. In addition, IgG and fibrinogen interact with each other and/or bind zinc ions through different mechanisms.

Purpose: The purpose of this study is to investigate whether healing potential of the femoral cartilage differs according to the site of injury in a rabbit, and whether poor potential of the cartilage repair correlates with the injured site which is not in contact with acetabulum. Furthermore, the efficacy of intraarticular injection of hyaluronic acid into the hip for the cartilage with lower healing potential was evaluated., Methods: Male Japanese white rabbits were used in this study. Via the posterolateral approach, the articular capsule was incised and a 4 × 4 mm chondral defect was made at the load-bearing area (group A) or at head-neck junction (group B), and intraarticular injection of hyaluronic acid was performed to the group B model (group C)., Results: In group A, histological evaluation at 8 weeks revealed that the chondral defect was filled with cartilaginous tissue. However, in group B, the chondral defect was not filled with any tissue and subchondral bone was exposed. In group C, the defect was filled with synovial-like tissue, and smooth surface was reacquired macroscopically. According to the ICRS score, significant differences were detected between group A and group B, group A and group C, and group B and group C. There were no differences in the radiographic findings among the 3 groups., Conclusions: The cartilage at head-neck junction of the femoral head had poorer healing potential than that at load-bearing area. Administration of HA could be promising for preventing progression of cartilage degeneration even at head-neck junction.