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We conducted a meta-analysis to comprehensively evaluate the current data on the overall efficacy of levetiracetam (LEV), a new generation antiepileptic drug, in patients with brain tumors. The efficacy of LEV in patients diagnosed with brain tumors has been evaluated in several studies, however, with inconsistent results. Bibliographic searches of the EMBASE, MEDLINE, ClinicalTrials.gov and Cochrane Central Register of the Controlled Trials databases were performed to identify articles and conference abstracts that investigated the efficacy of LEV in the treatment of brain tumor patients. Fourteen studies were included in this meta-analysis. Among the 14 included studies, two were randomized controlled trials. The subgroup analysis demonstrated that the complete response rate of LEV was 94% during the postoperative period and 84% during the long-term follow-up period. Our results suggest that LEV is a relatively effective drug for the treatment of brain tumor patients and its efficacy is slightly lower during the long-term follow-up period than during the postoperative period. Further randomized controlled trials are warranted., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Previous studies showed the prognostic impact of preoperative levels of neutrophil-to-lymphocyte ratio (NLR), plasma fibrinogen, and serum C-reactive protein (CRP) in surgically treated upper tract urothelial carcinoma; however, few papers have discussed the proper use of these indices., Objective: To investigate whether combinations of these three markers, as a cumulative marker score (CMS), improve the accuracy of prognostic models following radical nephroureterectomy (RNU)., Design, Setting, and Participants: A total of 394 patients from multiple institutions were included. Median follow-up was 30 mo., Intervention: All patients underwent RNU without neoadjuvant chemotherapy., Outcome Measurements and Statistical Analysis: Associated outcomes were assessed using multivariate analysis. The CMS was defined as the number of elevated levels of preoperative NLR, plasma fibrinogen, and serum CRP., Results and Limitations: Multivariate analyses revealed that an increasing CMS was independently associated with high rates of disease recurrence, cancer-specific mortality, and all-cause mortality following RNU. Addition of the CMS to a model that included standard clinicopathologic predictors significantly improved predictive accuracy by 2.7% for disease recurrence, 3.9% for cancer-specific mortality, and 4.0% for all-cause mortality, which were the highest among other prognostic models using each marker alone or combinations of two. The study is limited by its retrospective nature., Conclusions: Although the use of each inflammatory marker alone may be as predictive as clinicopathologic indices for prognosis, combinations like CMS can provide more accurate prognostic models following RNU., Patient Summary: Elevation of blood-based inflammatory markers may be useful for predicting prognosis because of their low cost and accessibility. Among blood-based indices, we examined the efficacy of preoperative neutrophil-to-lymphocyte ratio, plasma fibrinogen, and serum C-reactive protein levels. Although use of each marker alone provides additional prognostic information, the combination of all three markers would be more predictive than any single marker or combinations of two., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Surgery for lumbar spinal degeneration disease is widely performed. While posterior decompression and fusion are popular, anterior lumbar interbody fusion (ALIF) is also used for treatment. Extreme lateral interbody fusion (XLIF) is commonly used for noninvasive ALIF; however, several complications, such as spinal nerve and psoas muscle injury, have been reported. In the current study, we examined the clinical efficacy and complications of oblique lateral interbody fusion (OLIF) for lumbar spinal degeneration disease., Materials and Methods: Thirty-five patients with degenerated spondylolisthesis, discogenic pain, and kyphoscoliosis were examined. All patients underwent OLIF surgery (using a cage and bone graft from the iliac crest) with or without posterior decompression, without real-time electromyography monitoring. Posterior screws were used in all patients. Visual analog scale (VAS) score and Oswestry Disability Index (ODI) were evaluated before and 6 months after surgery. Surgical complications were also evaluated., Results: Pain scores significantly improved after surgery, compared to those before surgery (p<0.05). There was no patient who underwent revision surgery. There was no spinal nerve, major vessel, peritoneal, or urinary injury. Few patients showed symptoms from psoas invasion., Conclusion: OLIF surgery produced good surgical results without any major complication.

Background: Our aim was to evaluate the effect of visceral obesity and impact of severe hydronephrosis on surgical complexity in patients undergoing laparoscopic radical nephroureterectomy (LRNU)., Methods: From January 2000 to December 2013, 169 patients underwent radical nephroureterectomy at our institution. We retrospectively reviewed the medical records of 70 patients who underwent LRNU. We measured total fat area (TFA) and visceral fat area (VFA) at the level of the umbilicus using computed tomography. We defined accumulated visceral fat distribution as a VFA/TFA ratio ≥0.45. Ipsilateral hydronephrosis was graded from 0 to 4 by two uro-radiologists blinded to the clinical outcomes., Results: Among the 70 patients, VFA/TFA ratio was ≥0.45 in 40 patients (57.1%) and 28 (40.0%) had severe hydronephrosis (grade 3 or greater). Patients with a VFA/TFA ratio ≥0.45 had significantly longer pneumoperitoneum and total operation times compared to their counterparts (p = 0.047 and p = 0.002, respectively). Patients with severe hydronephrosis had significantly longer pneumoperitoneum and total operative times compared to their counterparts (p = 0.006 and p = 0.002, respectively). Multivariate logistic regression analysis showed that a high VFA/TFA and severe hydronephrosis were independent predictive factors for prolonged pneumoperitoneum (p = 0.048, HR = 2.90; p = 0.015, HR = 3.82, respectively) and total operative times (p < 0.001, HR = 18.7; p = 0.003, HR = 10.7; respectively). Other pre-clinical factors such as age, gender, BMI, clinical stage, tumor size, location, laterality, degree of perinephric stranding, and surgical procedure did not affect the operation times., Conclusion: The present data indicated that the visceral type of adipose accumulation and presence of severe hydronephrosis could provide preoperative information on the degree of technical difficulty associated with LRNU.

Microinjection is considered the gold standard technique for delivery of nucleic acids (NAs; transgenes or genome editing tools such as CRISPR/Cas9 systems) into embryos, for creating genetically modified organisms. It requires sophisticated equipment as well as well-trained and highly skilled personnel to perform the micro-injection technique. Here, we describe a novel and simple microinjection-independent technique, called Genome-editing via Oviductal Nucleic Acids Delivery (GONAD). Using GONAD, we show that NAs (e.g., eGFP mRNA or Cas9 mRNA/sgRNAs) can be effectively delivered to pre-implantation embryos within the intact mouse oviduct by a simple electroporation method, and result in the desired genetic modification in the embryos. Thus GONAD can bypass many complex steps in transgenic technology such as isolation of zygotes, microinjection of NAs into them, and their subsequent transfer to pseudo-pregnant animals. Furthermore, this method can potentially be used for genome editing in species other than mice.

Tilapia (Oreochromis niloticus) do not survive well at low temperatures. Therefore, improvement of the low-temperature resistance has become an important issue for aquaculture development of tilapia. The objective of this study was to construct a digital gene expression tag profile to identify genes potentially related to low temperature in tilapia. In this study, tilapia was treated at 30°C to lethal temperature 10°C in decrement of 1°CD(-1). Digital gene expression analysis was performed using the Illumina technique to investigate differentially expressed genes in tilapia cultured at different temperatures (30°C, 26°C, 20°C, 16°C, and 10°C). A total of 206,861, 188,082, 185,827, 188,067, and 214,171 distinct tags were obtained by sequencing these five libraries, respectively. Compared with the 30°C library, there were 304, 407, 709, and 772 upregulated genes and 342, 793, 771, and 1466 downregulated genes in 26°C, 20°C, 16°C, and 10°C libraries, respectively. Trend analysis of these differentially expressed genes identified six statistically significant trends. Functional annotation analysis of the differentially expressed genes identified various functions associated with the response to low-temperature stress. When tilapia are subjected to low-temperature stress, expression changes were observed in genes associated with nucleic acid synthesis and metabolism, amino acid metabolism and protein synthesis, lipid and carbohydrate content and types, material transport, apoptosis, and immunity. The differentially expressed genes obtained in this study may provide useful insights to help further understand the effects of low temperature on tilapia., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Colovesical fistula (CVF) resulting from colon diverticulosis is a comparatively rare disease, and neither the diagnosis nor treatment has been established. Our experience with CVF due to sigmoid diverticulitis over a 9-year period was reviewed to clarify the clinical presentation and diagnostic confirmation. Ten patients with CVF were identified in this period, and chief complaints, laboratory findings, presenting symptoms, diagnostic investigations, and subsequent treatments were reviewed. Preoperative urinalysis showing bacteriuria (100%) was the most common presentation, followed by fecaluria (40%), abdominal pain (40%), pneumaturia (30%), hematuria (30%), pain on urination (30%), pollakiuria (10%), and dysuria (10%). The abilities of various preoperative investigations to identify CVF were: computed tomography (CT), 88.9%; magnetic resonance imaging, 40%; cystoscopy, 30%, and gastrografin irrigoscopy, 22.2%. Colonoscopy (0%) was not diagnostic. Bowel resection was performed in nine of ten patients. When inflammation was intense, covering ileostomy was performed, and an omental plasty was placed between the bowel anastomosis and bladder. When CVF is suspected, we recommend CT followed by colonoscopy and cystoscopy as a first-line investigation to rule out malignancy as a cause. Other modalities should only be used if the diagnosis is in doubt or additional information is needed to plan operative management. Primary colic anastomosis appears to be safely performed by applying omental plasty and covering ileostomy.

Purpose: Current guidelines do not yet provide any recommendations for adjuvant chemotherapy in patients with upper tract urothelial carcinoma managed with radical nephroureterectomy. We evaluated whether an adjuvant chemotherapeutic regimen would affect the clinical outcome in patients with high risk upper tract urothelial carcinoma., Materials and Methods: We identified 873 patients who had undergone radical nephrouretectomy for localized upper tract urothelial carcinoma at 14 Japanese institutions between 1993 and 2011. We assessed whether the type of regimen, such as methotrexate, vinblastine, doxorubicin and cisplatin, and gemcitabine and cisplatin, in an adjuvant setting, could affect the subsequent clinical outcome of patients with upper tract urothelial carcinoma., Results: On multivariate analysis pathological T stage, tumor grade, lymphovascular invasion and lymph node involvement were prognostic factors for recurrence-free survival and cancer specific survival. We defined 229 patients with 3 or more of these factors as the high risk group. In an analysis according to adjuvant regimen, Kaplan-Meier curves showed that the 1 and 2-year recurrence-free survival rates in the methotrexate, vinblastine, doxorubicin and cisplatin treated group were 71.4% and 47.9%, which were significantly higher than in the gemcitabine and cisplatin treated group (48.2% and not reached, p=0.022) or those not treated with adjuvant chemotherapy (53.4% and 39.6%, p=0.039). Similar results were observed in terms of cancer specific survival., Conclusions: Our study showed that pT3-4, tumor grade 3, positive lymphovascular invasion and lymph node involvement were independent risk factors for disease mortality in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. In the high risk group methotrexate, vinblastine, doxorubicin and cisplatin adjuvant chemotherapy contributed to improve subsequent mortality compared to gemcitabine and cisplatin or no adjuvant chemotherapy., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: In a previous study, we described the relationship between operating time and obesity, particularly visceral obesity, in laparoscopic surgery. Operating time in laparoscopic surgery is affected by the experience and technique of the surgeon. Here, we investigated whether a difference in the surgeon's experience affects the operating time for laparoscopic radical nephrectomy in patients with visceral obesity., Methods: From January 2006 to February 2012, 167 laparoscopic radical nephrectomies were performed at our institution. Visceral fat area was measured at the level of the umbilicus using computed tomography. A visceral fat area ≥ 100 cm(2) was used as the definition of visceral obesity. All laparoscopic radical nephrectomies were performed by six surgeons. Two of the six surgeons perform 50 cases or more laparoscopic surgeries every year and they were defined as the expert group. We analyzed the relationships between clinical findings, methods, surgeon experience, body mass index or visceral fat area and operating time., Results: The expert and non-expert surgeons performed 77 and 90 laparoscopic radical nephrectomies, respectively, and the median operating time was 167.0 ± 44.0 and 227.5 ± 60.6 min. Twenty-five patients underwent laparoendoscopic single-site nephrectomy by the expert surgeons. For all surgeons, visceral obesity was a significant factor for prolonged operating time. Multivariate analysis showed that visceral obesity and clinical T stage were independent risk factors for prolonged operating time for the non-expert surgeons [P = 0.004, hazard ratio (HR): 5.15, P = 0.037, HR:10.41]. However, for the expert surgeons, clinical T stage was the only independent risk factor for prolonged operating time (P = 0.039, HR: 4.33)., Conclusion: Visceral obesity was a factor of prolonged operating time in laparoscopic radical nephrectomy. The non-expert surgeons were particularly affected by visceral obesity., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The morphological mechanism of alveolar wall destruction during pulmonary emphysema has not been clarified. The aim of this study was to elucidate this process three-dimensionally. Lung specimens from five patients with pulmonary emphysema were used, and five controls with normal alveolar structure were also examined. Sections 150 μm thick were stained with hematoxylin and eosin, elastica, and silver impregnation, and immunostained with selected antibodies. We examined these sections three-dimensionally using a laser confocal microscope and a light microscope. There were only a few Kohn's pores and no fenestrae in the normal alveoli from the controls. In the lungs of the emphysema patients a small rupture appeared in the extremely thin alveolar wall among the alveolar capillaries. This rupture enlarged to form a circle surrounded by the capillaries, which was called an alveolar fenestra. Two neighboring fenestrae fused by breakdown of the collapsed or cord-like capillary between them to form a large fenestra. The large fenestrae fused repeatedly to become larger, and these were bordered by thick elastic fibers constructing an alveolar framework. Alveolar wall destruction during emphysema could start from small ruptures of the alveolar wall that become fenestrae surrounded by capillaries, which fuse repeatedly to become larger fenestrae rimmed with elastic fibers. The alveolar capillary network could initially prevent enlargement of the fenestrae, and the thick elastic fibers constituting the alveolar framework could secondarily prevent destruction of the alveolar wall structure., (© 2014 Wiley Periodicals, Inc.)

Objective: To investigate the prognostic significance of visceral obesity to predict recurrence after curative surgery for Japanese patients with localized renal cell carcinoma., Methods: The data of 285 patients who underwent curative surgery for localized renal cell carcinoma were retrospectively reviewed. Median follow-up was 36.7 months. The association between visceral obesity and recurrence-free survival rate was evaluated using the Kaplan-Meier method and Cox regression models. Visceral fat area at the level of the umbilicus measured using pre-operative computed tomography was used as an index of visceral obesity., Results: Twenty-nine patients (10.2%) experienced recurrence. Five-year recurrence-free survival rates were 91.3% in high visceral fat area group (≥ 120 cm(2)) and 76.9% in low visceral fat area group (<120 cm(2)) (P = 0.037); however, visceral fat area was not an independent predictor of recurrence-free survival in multivariate analysis. In the patients with clear cell renal cell carcinoma, 28 patients (11.6%) experienced recurrence. Five-year recurrence-free survival rates were 88.7% in high visceral fat area group and 71.0% in low visceral fat area group (P = 0.043), and visceral fat area was an independent predictor of recurrence-free survival (hazard ratio: 1.974, P = 0.042) as well as C-reactive protein, Fuhrman nuclear grade, tumor size and microvascular invasion. In patients with organ confined clear cell renal cell carcinoma in particular, visceral fat area was also a useful and independent predictor of recurrence-free survival (hazard ratio: 2.807, P = 0.038). Body mass index was not useful in either cohort., Conclusions: High visceral fat area was a positive predictive biomarker for better recurrence-free survival after curative surgeries for localized clear cell renal cell carcinomas; however, body mass index was not a predictor., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Hematopoietic pre-B-cell leukemia transcription factor-interacting protein (HPIP) is a corepressor of pre-B-cell leukemia homeobox (PBX) 1 and is known to play a role in hematopoiesis. Recently, HPIP was demonstrated to promote breast cancer cell proliferation and hepatocellular carcinoma growth. Moreover, it has been revealed that homeobox and PBX proteins, the expression of which is regulated by HPIP, play key roles in cancer of various organs, including oral squamous cell carcinoma (OSCC). Nevertheless, there has not been any study regarding the role of HPIP in OSCC. This study investigated the expression of HPIP in normal oral mucosa, epithelial precursor lesion (OEPL), and OSCC, and the functional roles of HPIP in OSCC cells and normal keratinocytes., Materials and Methods: Immunohistochemical analysis of HPIP, Ki-67, and involucrin was performed in OSCC specimens, and the change in involucrin expression following RNA interference treatment against HPIP was examined by quantitative RT-PCR and Western blot analysis in SCC9 and NHEK cells undergoing extracellular calcium-induced differentiation. Matrigel transwell and cell proliferation assays for both cell lines transfected with HPIP siRNA were also conducted., Results: HPIP expression increased in OEPL and OSCC specimens. In vitro analysis revealed that HPIP suppressed differentiation and proliferation of SCC9 cells and transwell migration of NHEK cells, while HPIP promoted invasion of SCC9 and proliferation of NHEK cells. However, HPIP has no significant effect on NHEK cell differentiation., Conclusion: HPIP may play a critical role in oral carcinogenesis and is thus a potential target for anticancer therapy, with particular emphasis on its involvement in differentiation and migration/metastasis., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Lymph node metastasis is a major factor for poor prognosis in oral squamous cell carcinoma (OSCC). However, the molecular mechanisms of lymph node metastasis are unclear. We determined that angiopoietin-like protein 4 (ANGPTL4) mRNA and protein expression were increased in OSCC cells established from the primary site in metastatic cases. In addition, ANGPTL4 expression in biopsy specimens was correlated with the presence of lymph node metastasis. Therefore, our initial findings suggest that OSCC cells expressing ANGPTL4 may possess metastatic ability. Furthermore, cell culture supernatants from OSCC cells that metastasized to the lymph node contain ANGPTL4 and promote invasive ability. These findings suggest that secreted ANGPTL4 may affect the invasive ability of OSCC. Moreover, the rates of positive ANGPTL4 expression at the primary site were significantly higher in the lymph node metastasis group. These results demonstrate that ANGPTL4 contributes to OSCC metastasis by stimulating cell invasion. Therefore, ANGPTL4 is a potential therapeutic target for preventing cancer metastasis., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cerebellar hemorrhage remote from the site of surgery can complicate neurosurgical procedures. However, this complication after lumbar surgery is rare. Furthermore, hemorrhage in both the cerebellum and the temporal lobe after spine surgery is rarer still. Herein we present a case of remote hemorrhage in both the cerebellum and the temporal lobe after lumbar spine surgery. A 79-year-old woman with a Schwannoma at the L4 level presented with low back and bilateral leg pain refractory to conservative management. Surgery was undertaken to remove the Schwannoma and to perform posterior fusion. During the surgery, the dura mater was removed in order to excise the Schwannoma. Reconstruction of the dura mater was performed; postoperatively the patient had a cerebrospinal fluid leak. Five days after surgery, clouding of consciousness started gradually, and hemorrhage in the cerebellum and the temporal lobe was revealed by computed tomography. Emergent evacuation of the hemorrhage was performed and the patient recovered consciousness after the surgery. Leakage of cerebrospinal fluid may have induced this hemorrhage. While rare, intracranial hemorrhage after spine surgery can occur, sometimes requiring emergent intervention.

Background: Acute decompensated heart failure (ADHF) is generally considered to be a problem of fluid volume overload, therefore accurately quantifying the degree of fluid accumulation is of critical importance in assessing whether adequate decongestion has been achieved. The aim of this study was to develop and validate a method to quantify the degree of fluid accumulation in patients with ADHF., Methods and results: Using multi-frequency bioelectrical impedance analysis (BIA), we measured extracellular water (ECW) volume in 130 ADHF patients on admission and at discharge. We also predicted optimal ECW volume using original equations based on data from 60 control subjects without the signs of HF. Measured/predicted (M/P) ratio of ECW in ADHF patients was observed to decrease from 1.26±0.25 to 1.04±0.17 during hospitalization (P<0.001). The amount of ECW volume reduction was significantly correlated with reduction in body weight (r=0.766, P<0.001). On multivariate analysis, higher M/P ratio of ECW at discharge was associated with increased risk of ADHF readmission or cardiac death within 6 months after discharge., Conclusions: Multi-frequency BIA-measured ECW was found to offer valuable information for analyzing the pathophysiology of ADHF, and may be a useful guide in the management of this disease.

Aim: To test the effect of dendritic cells (DCs) transduced with recombinant adenoviruses encoding 4-1BBL combined with cytokine-induced killer cells (CIKs) against prostate cancer., Method: Flow cytometry was used to detect the surface markers of the co-cultured cells, and cytotoxicity against prostate cancer cells in vitro as well as antitumor activities in vivo were observed., Results: Our results showed that Ad-4-1BBL-transduced DCs could increase percentage of CD3(+)CD56(+) cells in CIKs, and CIKs co-cultured with Ad-4-1BBL-transduced DCs could augment the secretion of IL-12 and IFN-γ and decrease TGF-β production. In addition, Ad-4-1BBL-transduced DCs enhanced the cytotoxicity of CIKs against prostate cancer and resulted in inhibition of tumor growth and tumor-bearing animals' survival., Conclusion: These results demonstrate that 4-1BBL-engineered DCs can improve CIKs cytotoxicity against prostate cancer cells.

A two-month-old female Chihuahua was diagnosed as severe pulmonary valvular stenosis (PS). Although balloon valvuloplasty (BV) was successfully performed, restenosis was observed 19 months after the procedure. Euthanasia was chosen due to low output syndrome during the surgical repair attempted when the dog was 5 years old. Postmortem examination revealed markedly thickened pulmonary valve due to the increase of extracellular matrix which might be produced by increased α smooth muscle actin-positive myofibroblasts. The thickening of the valve was associated with restriction of the valve's motion, resulting in restenosis in the present case. This is the first case report documented histopathological and immunohistochemical findings of the restenotic pulmonary valve in dogs with PS after BV.

Early detection of oral squamous cell carcinoma (OSCC) improves its prognosis and aids in selecting the appropriate treatment, which may also have a positive effect on quality of life. Early detection, therefore, is an important issue in the treatment of this disease. The purpose of this study was to investigate expression of cytokeratin 13 (CK13), CK17, Ki-67 and p53 as potential markers of tongue SCC. Five areas in 12 specimens were examined: the upper and lower layers of normal epithelium; those of dysplastic epithelial tissue surrounding the cancerous lesion; and the lesion itself. Strong expression of each of the following mRNAs and proteins was observed; CK13 in upper layers of normal epithelium; Ki-67 and p53 in lower layers of normal epithelium; CK13 and CK17 in upper layer of epithelial dysplasia; and CK17, Ki-67, and p53 in lower layer of epithelial dysplasia and cancerous lesions. These results indicate that the characteristic pattern of expression of CK13 and CK17 differs between normal and dysplastic oral epithelium. Oral epithelial dysplasia adjacent to OSCC has high malignant potential, and is similar to early-stage OSCC. This suggests that evaluation of these markers could be a useful secondary procedure for improving detection of early-stage OSCC.

Purpose: To evaluate the correlation between apparent diffusion coefficient ( ADC apparent diffusion coefficient ) values and the Ki-67 labeling index for luminal-type (estrogen receptor-positive) breast cancer not otherwise specified ( NOS not otherwise specified ) diagnosed by means of biopsy., Materials and Methods: The institutional review board approved this retrospective study, and the requirement for informed consent was waived. Between December 2009 and December 2012, 86 patients with 86 lesions with luminal-type invasive breast cancer NOS not otherwise specified underwent magnetic resonance imaging, including dynamic contrast material-enhanced imaging and diffusion-weighted imaging with b values of 0 and 1000 sec/mm(2). Conventional measurement of the minimum and mean ADC apparent diffusion coefficient s by placing regions of interest and histogram analysis of pixel-based ADC apparent diffusion coefficient data of the entire tumor were performed by two observers independently and correlated with the Ki-67 labeling index of surgical specimens., Results: For the interobserver reliability, interclass correlation coefficients for all parameters with the exception of the minimum ADC apparent diffusion coefficient exceeded 0.8, indicating almost perfect agreement. The minimum ADC apparent diffusion coefficient and mean ADC apparent diffusion coefficient and the 25th, 50th, and 75th percentiles of the histograms showed negative correlations with the Ki-67 labeling index (r = -0.49, -0.55, -0.54, -0.53, and -0.48, respectively). Receiver operating characteristic curve analysis for the differential diagnosis between the high-proliferation (Ki-67 ≥ 14; n = 44) and low-proliferation (Ki-67 < 14; n = 42) groups revealed that the most effective threshold for the mean ADC apparent diffusion coefficient was lower than 1097 × 10(-6) mm(2)/sec, with sensitivity and specificity of 82% and 71%, respectively. The area under the receiver operating characteristic curve (AUC) was 0.81 for the mean ADC apparent diffusion coefficient . There were no significant differences in the AUC among the parameters., Conclusion: Considering convenience for routine practice, the authors suggest that the mean ADC apparent diffusion coefficient of the conventional method would be practical to use for estimating the Ki-67 labeling index.

In April 2014, Team Watanabe have completed 249 robot-assisted cardiac surgeries. Wide range of procedures include internal thoracic artery harvesting, totally endoscopic coronary artery bypass grafting(CABG), atrial septal defect closure, mitral valve plasty, cardiac tumor resection. The major benefit of robot-assisted cardiac surgery, which differentiates it from minimally invasive cardiac surgery, is that it only requires a few ports instead of small thoracotomy. Mitral valve plasty for regurgitation is one of the most suitable indication, which represents the advantage of robot-assisted cardiac surgery. The da Vinci surgical system completely changed the modality of cardiac surgeries from median sternotomy to endoscopic approach. Endoscopic surgery is expected not only to provide superior cosmesis but also to reduce complications and improve post-operative quality of life. In addition, we consider that sharing the same surgical view on the screen monitor is another great benefit from the educational point of view for the next-generation.

Study Design: Case series., Purpose: To determine the utility of "PainVision" apparatus for the assessment of low back pain., Overview of Literature: A newly developed device, the PainVision PS-2100 (Nipro, Osaka, Japan), has been used to assess the perception of pain in a quantitative manner. In the current study, we aimed to evaluate the efficacy of PainVision for the assessment of low back pain., Methods: We assessed 89 patients with low back pain. The numeric rating scale (NRS) score, McGill Pain Questionnaire (MPQ) score and the degree of pain calculated by PainVision were measured twice at 4-week intervals in each patient. An electrode was patched on the forearm surface of the patients and the degree of pain was automatically calculated (degree of pain=100×[current producing pain comparable with low back pain-current at perception threshold/current at perception threshold]). Correlations between NRS and MPQ scores and the degree of pain were determined using Spearman's rank correlation test., Results: There was a strong correlation between the NRS and MPQ scores at each time point (rs =0.60, p<0.0001). The degree of pain also showed a moderate correlation with NRS and MPQ scores at each time point (rs =0.40, p<0.03). The change in the degree of pain over 4 weeks showed a moderate correlation with changes in the NRS and MPQ scores (rs =0.40, p<0.01)., Conclusions: PainVision as self-reported questionnaires is a useful tool to assess low back pain.

Background: Although mucinous adenocarcinoma (MAC) is has been recognized as a separate entity in colorectal cancer (CRC), adenocarcinoma with a mucinous component (ACM) remains poorly understood., Methods: The association of MAC and ACM with disease-free survival (DFS) and overall survival (OS) was examined using the Cox proportional hazard model in 425 consecutive stage III CRCs., Results: Compared with conventional adenocarcinoma (CAC), patients with MAC exhibited independently worse DFS (hazard ratio [HR], 2.64; 95% CI, 1.21-5.80; P = 0.014) and OS (HR, 3.56; 95% CI, 1.53-8.30; P = 0.003). Unexpectedly, ACM was significantly associated with worse OS than CAC (P = 0.002), despite having a similar DFS to CAC. Further, ACM patients after recurrence exhibited significantly worse OS than CAC patients (P < 0.001), similar to MAC., Conclusions: Although ACM is similar to CAC with regard to estimated risk of recurrence, the outcome is extremely poor once recurrence occurs and is identical to MAC; one of the most aggressive phenotypes of stage III CRC. Thus, both MAC and ACM are adverse prognostic factors for OS., (© 2014 Wiley Periodicals, Inc.)

Purpose: To evaluate the feasibility of transarterial therapy (transcatheter arterial chemoembolization and transcatheter arterial infusion) for patients with hepatocellular carcinoma and chronic kidney disease (CKD)., Materials and Methods: The study enrolled 35 patients who received transarterial therapy. The patients were classified into a CKD group (n = 10 nondialysis chronic kidney disease [NDCKD] and n = 9 end-stage renal disease [ESRD]) or a non-CKD group (n = 16). The survival rates between the two groups were compared using two different starting points: (a) from initial diagnosis of hepatocellular carcinoma and (b) from enrollment in the study. The tolerance of transarterial therapy in patients with CKD was evaluated by comparing the incidence of major adverse events., Results: The 2-year and 5-year survival rates from initial diagnosis were 83.9% and 53.8% in the CKD group and 70.1% and 40.4% in the non-CKD group (P = .478). The corresponding 3-year survival rate from enrollment in the two groups was 25.6% and 41.2%, respectively (P = .995). The 2-year and 5-year survival rates from initial diagnosis were 70.1% and 40.4% in the non-CKD group, 90.0% and 39.4% in NDCKD patients, and 76.2% and 76.2% in ESRD patients (P = .380). The corresponding 2-year survival rates from enrollment in these groups were 54.9%, 48.0%, and 48.6% (P = .943). Severe contrast-induced nephropathy (n = 3) and late-onset death caused by cholesterol crystal embolism (n = 1) were observed in the NDCKD group., Conclusions: Transcatheter arterial chemoembolization is feasible in patients with CKD by instituting periprocedural hemodialysis with similar 2-year and 5-year survival compared with patients without CKD., (Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Synapses are fundamental components of brain circuits and are disrupted in over 100 neurological and psychiatric diseases. The synapse proteome is physically organized into multiprotein complexes and polygenic mutations converge on postsynaptic complexes in schizophrenia, autism and intellectual disability. Directly characterising human synapses and their multiprotein complexes from post-mortem tissue is essential to understanding disease mechanisms. However, multiprotein complexes have not been directly isolated from human synapses and the feasibility of their isolation from post-mortem tissue is unknown., Results: Here we establish a screening assay and criteria to identify post-mortem brain samples containing well-preserved synapse proteomes, revealing that neocortex samples are best preserved. We also develop a rapid method for the isolation of synapse proteomes from human brain, allowing large numbers of post-mortem samples to be processed in a short time frame. We perform the first purification and proteomic mass spectrometry analysis of MAGUK Associated Signalling Complexes (MASC) from neurosurgical and post-mortem tissue and find genetic evidence for their involvement in over seventy human brain diseases., Conclusions: We have demonstrated that synaptic proteome integrity can be rapidly assessed from human post-mortem brain samples prior to its analysis with sophisticated proteomic methods. We have also shown that proteomics of synapse multiprotein complexes from well preserved post-mortem tissue is possible, obtaining structures highly similar to those isolated from biopsy tissue. Finally we have shown that MASC from human synapses are involved with over seventy brain disorders. These findings should have wide application in understanding the synaptic basis of psychiatric and other mental disorders.

Background: To externally validate the prognostic impact of preoperative neutrophil-lymphocyte ratio (pre-NLR) in patients with upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU)., Methods: A total of 665 patients from 12 institutions were included. The median follow-up was 28 months. Associations between pre-NLR level and outcome were assessed using multivariate analysis. A pre-NLR level of >3.0 was defined as elevated., Results: Pre-NLR levels were elevated in 184 patients (27.7 %), and pre-NLR elevation was significantly associated with worse pathological features such as tumor grade 3, advanced pT stage, positive lymphovascular invasion (LVI), and lymph node involvement in RNU specimens. The 5-year recurrence-free and cancer-specific survival rates were 57.0 % (p < 0.001) and 60.2 % (p < 0.001), respectively, in patients with elevated pre-NLR, and 69.2 and 77.3 %, respectively, in their counterparts. Multivariate analysis showed that elevated pre-NLR was an independent risk factor for predicting subsequent disease recurrence (p = 0.037; hazard ratio (HR) 1.38) and cancer-specific mortality (p = 0.036;, HR 1.47), although the addition of pre-NLR slightly improved the accuracies of the base model for predicting both disease recurrence and cancer-specific mortality to 79.8 % (p = 0.041) and 83.0 % (p = 0.039), respectively (gain in predictive accuracy: 0.2 and 0.1 %, respectively)., Conclusion: This multi-institutional study revealed that elevated pre-NLR was significantly associated with worse pathological features such as tumor grade 3, advanced pT stage, positive LVI, and lymph node involvement in RNU specimens, and elevated pre-NLR was an independent risk factor of disease recurrence and cancer-specific mortality in UTUC patients treated with RNU.

We conducted this study to identify risk factors that may predict whether Candida spp. are causative agents of suspected catheter-related bloodstream infections (CRBSIs). All patients with laboratory-confirmed CRBSIs at Kyoto University Hospital between 2009 and 2011 were included. We compared the clinical features of candidal CRBSIs (78 cases) and non-candidal CRBSIs (258 cases). According to a multivariate analysis, a solid tumor (odds ratio [OR], 3.11; 95% confidence interval [CI], 1.75-5.53), total parental nutrition (OR, 2.65; 95% CI, 1.39-5.06), and the administration of anti-anaerobic agents (OR, 2.22; 95% CI, 1.03-4.79) were significantly more common among candidal CRBSIs. The (1,3)-β-D-glucan (BDG) test was positive among 94.6% (35/37) of candidal CRBSI patients and 9.4% (10/106) of non-candidal CRBSI cases. The administration of antifungal agents may be considered for patients with these risk factors, especially when the BDG test is positive., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Endoscopic transnasal transsphenoidal surgery is gaining wide acceptance as the first-line treatment of pituitary tumors in adults, as this procedure is minimally invasive and associated with good outcomes. On the other hand, conventional transcranial and sublabial approaches are chosen for infants as their small anatomical structures pose some difficulty. This study reports on the case of a 5-year-old boy who had a Langerhans cell histiocytosis appearing in the sella. The biopsy was performed using the endoscopic transnasal transsphenoidal approach, and the patient has not exhibited any post-operative complications. Although the patient was a fairly young child, the endoscopic transnasal transsphenoidal approach resulted in fewer complications as compared to the transcranial and translabial approaches. Otolaryngologists, therefore, should view this approach more positively. The indication for pediatric skull base diseases can be expected to expand to include endoscopic transnasal surgery.

Purpose: Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated nonselective cation channel, which can be activated by capsaicin and other noxious stimuli. Recently, an association between bone pain and TRPV1 has been reported. However, the influence of osteoporosis on TRPV1 in the sensory system innervating the femur has not been reported., Materials and Methods: TRPV1-immunoreactive (ir) in dorsal root ganglia (DRG) neurons labeled with neurotracer [Fluoro-Gold (FG)] innervating the femurs of Sprague Dawley rats were examined in control, sham, and ovariectomized (OVX) rats. We evaluated osteoporosis in the femurs and compared the proportion of TRPV1-ir DRG neurons innervating femur between the 3 groups of rats., Results: OVX rats showed osteoporotic cancellous bone in the femur. FG labeled neurons were distributed from L1 to L6 DRG, but there was no significant difference in the proportion of labeled neurons between the 3 groups (p>0.05). The proportions of FG labeled TRPV1-ir DRG neurons were 1.7%, 1.7%, and 2.8% of DRG neurons innervating the femur, in control, sham-operated, and OVX rats, respectively. The proportion of TRPV1-ir neurons in DRG innervating the femur in OVX rats was significantly higher than that in control and sham-operated rats (p<0.05)., Conclusion: Under physiological conditions, DRG neurons innervating femurs in rats contain TRPV1. Osteoporosis increases the numbers of TRPV1-ir neurons in DRG innervating osteoporotic femurs in rats. These findings suggest that TRPV1 may have a role in sensory perception of osteoporotic femurs.

Microphthalmia is a severe ocular disorder, and this condition is typically caused by mutations in transcription factors that are involved in eye development. Mice carrying mutations in these transcription factors would be useful tools for defining the mechanisms underlying developmental eye disorders. We discovered a new spontaneous recessive microphthalmos mouse mutant in the Japanese wild-derived inbred strain KOR1/Stm. The homozygous mutant mice were histologically characterized as microphthalmic by the absence of crystallin in the lens, a condition referred to as aphakia. By positional cloning, we identified the nonsense mutation c.444C>A outside the genomic region that encodes the homeodomain of the paired-like homeodomain transcription factor 3 gene (Pitx3) as the mutation responsible for the microphthalmia and aphakia. We examined Pitx3 mRNA expression of mutant mice during embryonic stages using RT-PCR and found that the expression levels are higher than in wild-type mice. Pitx3 over-expression in the lens during developmental stages was also confirmed at the protein level in the microphthalmos mutants via immunohistochemical analyses. Although lens fiber differentiation was not observed in the mutants, strong PITX3 protein signals were observed in the lens vesicles of the mutant lens. Thus, we speculated that abnormal PITX3, which lacks the C-terminus (including the OAR domain) as a result of the nonsense mutation, is expressed in mutant lenses. We showed that the expression of the downstream genes Foxe3, Prox1, and Mip was altered because of the Pitx3 mutation, with large reductions in the lens vesicles in the mutants. Similar profiles were observed by immunohistochemical analysis of these proteins. The expression profiles of crystallins were also altered in the mutants. Therefore, we speculated that the microphthalmos/aphakia in this mutant is caused by the expression of truncated PITX3, resulting in the abnormal expression of downstream targets and lens fiber proteins.

Study Design: Experimental animal study., Purpose: To evaluate pain-related behavior and changes in nuclear factor-kappa B (NF-kB), receptor activator of NF-kB (RANK), and ligand (RANKL) in dorsal root ganglia (DRG) after combined sciatic nerve compression and nucleus pulposus (NP) application in rats., Overview of Literature: The pathological mechanisms underlying pain from lumbar-disc herniation have not been fully elucidated. RANKL are transcriptional regulators of inflammatory cytokines. Our aim was to evaluate pain-related behavior and RANKL expression in DRG after sciatic-nerve compression and application of NP in rats., Methods: MECHANICAL HYPERALGESIA AND RANKL EXPRESSION WERE ASSESSED IN THREE GROUPS OF RATS: NP+sciatic nerve compression (2 seconds), sham-operated, and controls (n=20 each). Mechanical hyperalgesia was measured every other day for 3 weeks using von Frey filaments. RANKL expression in L5 DRGs was examined at five and ten days after surgery using immunohistochemistry., Results: Mechanical hyperalgesia was observed over the 12-day observation period in the NP+nerve compression group, but not in the control and sham-operated animal groups (p<0.05). RANKL immunoreactivity was seen in the nuclei of L5 DRG neurons, and its expression was significantly upregulated in NP+nerve compression rats compared with control and sham-operated rats (p<0.01)., Conclusions: The exposure of sciatic nerves to mechanical compression and NP produces pain-related behavior and up-regulation of RANKL in DRG neurons. RANKL may play an important role in mediating pain after sciatic nerve injury with exposure to NP.

The availability of techniques to create desired genetic mutations has enabled the laboratory mouse as an extensively used model organism in biomedical research including human genetics. A new addition to this existing technical repertoire is the CRISPR/Cas system. Specifically, this system allows editing of the mouse genome much more quickly than the previously used techniques, and, more importantly, multiple mutations can be created in a single experiment. Here we provide protocols for preparation of CRISPR/Cas reagents and microinjection into one-cell mouse embryos to create knockout or knock-in mouse models., (Copyright © 2014 John Wiley & Sons, Inc.)

Study Design: Experimental animal study., Purpose: To evaluate pain-related behavior and changes in glial activity in the spinal dorsal horn after combined sciatic nerve compression and nucleus pulposus (NP) application in rats., Overview of Literature: Mechanical compression and inflammation caused by prostaglandins and cytokines at disc herniation sites induce pain. Structural changes and pain-associated cytokines in the dorsal root ganglia and spinal dorsal horn contribute to prolonged pain. Glial cells in the spinal dorsal horn may also function in pain transmission., Methods: The sciatic nerve was compressed with NP for 2 seconds using forceps in the NP+nerve compression group; the sham-operated group received neither compression nor NP; and the control group received no operation. Mechanical hyperalgesia was measured for 3 weeks using von Frey filaments. Glial activity in the spinal dorsal horn was examined 7 days and 14 days postsurgery using anti-glial fibrillary acidic protein and anti-Ionized calcium binding adaptor molecule-1 antibodies to detect astrocytes and microglia, respectively., Results: Mechanical hyperalgesia was detected throughout the 14-day observation in the NP+nerve compression group, but not in control or sham-operated groups (p<0.05). Both astrocytes and microglia were significantly increased in the spinal dorsal horn of the NP+nerve compression group compared to control and sham groups on days 7 and 14 (p<0.05)., Conclusions: Nerve compression with NP application produces pain-related behavior, and up-regulates astrocytes and microglia in the spinal dorsal horn, suggesting that these glia may be related to pain transmission.

Purpose: To optimize the navigator-gating technique for the acquisition of high-quality three-dimensional spoiled gradient-recalled echo (3D SPGR) images of the liver during free breathing., Materials and Methods: Ten healthy volunteers underwent 3D SPGR magnetic resonance imaging of the liver using a conventional navigator-gated 3D SPGR (cNAV-3D-SPGR) sequence or an enhanced navigator-gated 3D SPGR (eNAV-3D-SPGR) sequence. No exogenous contrast agent was used. A 20-ms wait period was inserted between the 3D SPGR acquisition component and navigator component of the eNAV-3D-SPGR sequence to allow T1 recovery. Visual evaluation and calculation of the signal-to-noise ratio were performed to compare image quality between the imaging techniques., Result: The eNAV-3D-SPGR sequence provided better noise properties than the cNAV-3D-SPGR sequence visually and quantitatively. Navigator gating with an acceptance window of 2mm effectively inhibited respiratory motion artifacts. The widening of the window to 6mm shortened the acquisition time but increased motion artifacts, resulting in degradation of overall image quality. Neither slice tracking nor incorporation of short breath holding successfully compensated for the widening of the window., Conclusion: The eNAV-3D-SPGR sequence with an acceptance window of 2mm provides high-quality 3D SPGR images of the liver., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Opioids improve pain from knee and hip osteoarthritis (OA) and decrease the functional impairment of patients. However, there is a possibility that opioids induce analgesia and suppress the physiological pain of OA in patients, thereby inducing the progression of OA changes in these patients. The purpose of the current study was to investigate the possibility of progressive changes in OA among patients using opioids., Materials and Methods: Two hundred knee or hip OA patients were evaluated in the current prospective, randomized, active-controlled study. Patients were randomized 1:1:1 into three parallel treatment groups: loxoprofen, tramadol/acetaminophen, and transdermal fentanyl groups. Medication was administered for 12 weeks. Pain scores and progressive OA changes on X-ray films were evaluated., Results: Overall, pain relief was obtained by all three groups. Most patients did not show progressive OA changes; however, 3 patients in the transdermal fentanyl group showed progressive OA changes during the 12 weeks of treatment. These 3 patients used significantly higher doses than others in the transdermal fentanyl group. Additionally, the average pain score for these 3 patients was significantly lower than the average pain score for the other patients in the transdermal fentanyl group., Conclusion: Fentanyl may induce progressive changes in knee or hip OA during a relatively short period, compared with oral Non-Steroidal Anti-Inflammatory Drugs or tramadol.

Treatment with a carbon monoxide-releasing molecule (tricarbonyldichlororuthenium(II) dimer, CORM-2) or a classical inducible heme oxygenase (HO-1) inducer (cobalt protoporphyrin IX, CoPP) enhanced the antinociceptive effects of morphine during chronic pain but the role played by these compounds in acute thermal nociception was not evaluated. The effects of CORM-2 and CoPP treatments on the local antinociceptive actions of morphine and their interactions with nitric oxide during acute pain were evaluated by using wild type (WT), neuronal (nNOS-KO) or inducible (iNOS-KO) nitric oxide synthase knockout mice and assessing their thermal nociception to a hot stimulus with the hot plate test. Our results showed that the absence of nNOS or iNOS genes did not alter licking and jumping responses nor the antinociceptive effects produced by morphine indicating that the local thermal inhibitory effects produced by this drug in the absence of inflammation or injury are not mediated by the nitric oxide pathway triggered by nNOS or iNOS enzymes. Moreover, while the systemic administration of CORM-2 or CoPP inhibited licking and jumping latencies in all genotypes, these treatments only enhanced the local inhibition of jumping latencies produced by morphine in WT and nNOS-KO mice which effects were reversed by the peripheral administration of an HO-1 inhibitor. These data indicate that the co-administration of morphine with CORM-2 or CoPP produced remarkable local antinociceptive effects in WT and nNOS-KO mice and reveal that a significant interaction between carbon monoxide and nitric oxide systems occurs on the local antinociceptive effects produced by morphine during acute thermal nociception., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: We investigated the impact of unidirectional barbed suture (UBS) for vesicourethral anastomosis (VUA) during laparoscopic radical prostatectomy., Methods: The polyglyconate UBS V-Loc 180 was used for VUA during laparoscopic radical prostatectomy in 30 consecutive patients who were diagnosed with organ-confined prostate cancer between January and October 2012. The operative and postoperative parameters were then compared with those of 30 consecutive patients who had previously undergone the same procedure but with the monofilament poliglecaprone suture Monocryl. All procedures were performed by the same experienced surgeon., Results: VUA time was significantly shorter in the V-Loc group (13.2 ± 2.3 min) than in the Monocryl group (19.1 ± 3.3 min) (P < 0.001). The V-Loc group required significantly more stitches than the Monocryl group (11.4 ± 1.3 vs 10.6 ± 1.6 stitches; P = 0.031). The percentage of patients who required no more than one pad per day at 3 months postoperatively was significantly higher in the V-Loc group (63.3%) than in the Monocryl group (23.3%) (P = 0.020). No significant differences in other perioperative parameters were observed between the two groups., Conclusion: Using UBS prevents suture slippage and enables tieless anastomosis. VUA using a UBS may relieve surgeon stress because a rapid and secure anastomosis is achievable., (© 2014 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.)

The da Vinci surgical system was developed by Intuitive Surgical Inc. in the United States as an endoscopic surgical device to assist remote control surgeries. In 1998, the Da Vinci system was first used for cardiothoracic procedures. Currently a combination of robot-assisted internal thoracic artery harvest together with coronary artery bypass grafting (CABG) through a mini-incision (ThoraCAB) or totally endoscopic procedures including anastomoses under robotic assistance (TECAB) are being conducted for the treatment of coronary artery diseases. With the recent advances in catheter interventions, hybrid procedures combining catheter intervention with ThoraCAB or TECAB are anticipated in the future.On the other hand, with the decrease in number of coronary artery bypass surgeries, the share of valvular surgeries is expected to increase in the future. Among them, mitral valvuloplasty for mitral regurgitation is anticipated to be conducted mainly by low-invasive procedures, represented by minimally invasive cardiac surgery( MICS) and robot-assisted surgery. Apart from the intrinsic good surgical view, robotic-assisted systems offer additional advantages of the availability of an amplified view and the easy to observe the mitral valve in the physiological position. Thus, robotic surgical surgeries that make complicated procedures easier are expected to accomplish further developments in the future. Furthermore, while the number of surgeries for atrial septal defects has decreased dramatically following the widespread use of Amplatzer septal occluder, robotic surgery may become a good indication for cases in which the Amplatzer device is not indicated. In Japan, clinical trial of the da Vinci robotic system for heart surgeries has been completed. Statutory approval of the da Vinci system for mitral regurgitation and atrial septal defects is anticipated in the next few years.

Purpose: To determine whether renal injury induced by ischemia-reperfusion (I/R) could be further improved by mesenchymal stem cells (MSCs) modified with survivin., Materials and Methods: Lentiviral vectors were used to introduce the survivin gene into MSCs and the MSCs modified with survivin were transplanted into established mice models of renal I/R injury. Seven days later, serum creatinine (Scr) and blood urea nitrogen (BUN) were measured and the survival of MSCs was determined. Hematoxylin and eosin staining was used to assess renal pathological change. The expressions of hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF) in kidney tissue were detected by western blot., Results: Mice transplanted with survivin-modified MSCs demonstrated good renal function recovery with Scr and BUN decline close to normal levels and improvement of renal I/R injury repair. Additionally, the survival of transplanted MSCs modified with survivin was enhanced and the expression of HGF and bFGF in kidney tissue was increased., Conclusion: Our results demonstrated that MSCs engineered to over-express survivin could enhance their therapeutic effect on renal I/R injury in mice, probably via the improved survival ability of MSCs and increased production of protective cytokines in ischemic tissue.

Background: Polymyositis (PM) and dermatomyositis (DM) are idiopathic inflammatory myopathies. Genetic variability in human leukocyte antigen (HLA) genes plays an important role in the pathogenesis of PM and DM. However, few studies on the subject in Chinese populations have been reported thus far., Methods: We studied the influence of HLA polymorphisms on DM and PM susceptibility by analyzing HLA-DRB1, HLA-DQA1, and HLA-DQB1 alleles in 71 adult DM patients, 20 adult PM patients, and 113 controls in a Han Chinese population., Results: A positive association was found between HLA-DQA1*0104 and DM (p = 0.01; corrected p (pcorr) NS; odds ratio (OR) = 2.58; 95% confidence interval (CI): 1.18-5.64), while an inverse correlation was noted between HLA-DQB1*0303 and myositis patients with interstitial lung inflammation (p = 0.01; pcorr NS; OR = 0.25; 95% CI: 0.07-0.73). A positive relationship was also observed between HLA-DRB1*07 and DM (p = 0.01; pcorr NS; OR = 2.26; 95% CI: 1.12-4.59), while HLA-DRB1*03 seems to be protective against DM (p = 0.01; pcorr NS; OR = 0.26; 95% CI: 0.06-0.81). The lung complication was closely associated with HLA-DRB1*04 (p = 0.01; pcorr NS; OR = 2.82; 95% CI: 1.15-6.76) and HLA-DRB1*12 (p = 0.02; pcorr NS; OR = 2.52; 95% CI: 1.02-6.07). The frequency of HLA-DRB1*07 was significantly higher among myositis patients with dysphagia than among controls (p = 0.01; pcorr NS; OR = 4.78; 95% CI: 1.03-24.42). The putative haplotype DRB1*07-DQA1*01-DQB1*02 was positively correlated with DM (p = 0.03; pcorr NS; OR = 2.90; 95% CI: 1.02-8.93) and the lung complication (p = 0.02; pcorr NS; OR = 3.45; 95% CI: 1.04-11.58)., Conclusions: Our results demonstrate that HLA alleles may be involved in susceptibility to adult DM and PM in the Han Chinese population.

We experienced a rare case of delayed tracheal rupture after thyroidectomy for papillary thyroid cancer, and the infection causing sternomyelitis. A 69-year-old man presented subcutaneous emphysema after 6 days of total thyroidectomy with bilateral cervical and mediastinal dissection for lymph node metastases by adverse T sternotomy. He underwent tracheostomy on 10th postoperative day (POD), debridement of sternum on 14th POD, and implantation of skin-muscle flap using pectolaris major on 43th POD. The flap showed good adaptation and no infectious complications recurred, so that he could consequently receive closing procedure of tracheostomy on 94th POD.

Study Design: Prospective study., Purpose: To examine the long-term effects of interspinous ligament injections of local anesthetics and steroids for the treatment of Baastrup's diseases., Overview of Literature: Baastrup's disease is associated with axial low back pains. Baastrup's disease has been more recently described as the "kissing spinous processes" disease. Several authors have reported methods for the diagnosis and treatment of the disease. However, there has been only one report of patients receiving interspinous ligament injections of agents for the treatment of Baastrup's disease., Methods: Seventeen patients showed severe low back pains between spinous processes at L3-L4 or L4-L5. X-ray imaging, computed tomography, and magnetic resonance imaging revealed kissing spinous processes, consolidation of spinous process, or inflammation of an interspinous ligament. Pain reliefs after lidocaine and dexamethasone administration into interspinous ligament as therapy for low back pains were being examined and followed up., Results: Low back pain scores significantly improved immediately after injection of the agents into interspinous ligaments. At final follow-up (1.4 year), low back pain scores significantly improved as compared with before the treatment., Conclusions: Findings from the current study indicate that lidocaine and dexamethasone administration into interspinous ligament in patients diagnosed with Baastrup's disease is effective for managing the pain associated with this disease.

The junctional epithelium (JE) is an epithelial component that is directly attached to the tooth surface and has a protective function against periodontal diseases. In this study, we determined the origin of the JE using a bioengineered tooth technique. We transplanted the bioengineered tooth germ into the alveolar bone with an epithelial component that expressed green fluorescence protein. The reduced enamel epithelium from the bioengineered tooth fused with the oral epithelium, and the JE was apparently formed around the bioengineered tooth 50 days after transplantation. Importantly, the JE exhibited green fluorescence for at least 140 days after transplantation, suggesting that the JE was not replaced by oral epithelium. Therefore, our results demonstrated that the origin of the JE was the odontogenic epithelium, and odontogenic epithelium-derived JE was maintained for a relatively long period.

Introduction: The aim of this study was to investigate if neoadjuvant hormone therapy (NHT) is associated with surgical outcomes of laparoscopic radical prostatectomy., Methods: A total of 286 patients with organ-confined prostate cancer and a preoperative prostate volume that could be estimated by transrectal ultrasound underwent laparoscopic radical prostatectomy between 2006 and 2011 at our institution. We examined whether NHT was associated with pneumoperitoneum time (PT) or estimated blood loss during laparoscopic radical prostatectomy., Results: NHT was performed in 80 patients; the mean duration of NHT was 5.2 ± 0.2 months. Multivariate analysis demonstrated that history of NHT and no NHT were not independent predictors of prolonged PT or higher estimated blood loss. Next, we evaluated 57 patients whose estimated preoperative baseline prostate volume was over 50 mL. Multivariate analysis demonstrated that no history of NHT (P = 0.011) was an independent predictor of prolonged PT. PT was significantly shorter in the NHT group (164.5 ± 39.0 min, n = 26) than in the non-NHT group (184.0 ± 36.7 min, n = 31) (P = 0.048). In the NHT group, mean prostate volume was reduced from 63.7 ± 16.0 mL to 42.1 ± 18.6 mL (33.9% reduction) by NHT., Conclusion: NHT shortened the PT of the patients whose preoperative baseline prostate volume was over 50 mL. This suggests NHT downsized prostate volume, resulting in greater working space and shorter PT., (© 2014 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.)

Purpose: To examine the effects of conservative and surgical treatments for nocturnal leg cramps in patients with lumbar spinal stenosis (LSS). Nocturnal leg cramps is frequently observed in patients with peripheral neuropathy. However, there have been few reports on the relationship between nocturnal leg cramps and LSS, and it remains unknown whether conservative or surgical intervention has an impact on leg cramps in patients with LSS., Materials and Methods: The subjects were 130 LSS patients with low back and leg pain. Conservative treatment such as exercise, medication, and epidural block was used in 66 patients and surgical treatment such as decompression or decompression and fusion was performed in 64 patients. Pain scores and frequency of nocturnal leg cramps were evaluated based on self-reported questionnaires completed before and 3 months after treatment., Results: The severity of low back and leg pain was higher and the incidence of nocturnal leg cramps was significantly higher before treatment in the surgically treated group compared with the conservatively treated group. Pain scores improved in both groups after the intervention. The incidence of nocturnal leg cramps was significantly improved by surgical treatment (p=0.027), but not by conservative treatment (p=0.122)., Conclusion: The findings of this prospective study indicate that the prevalence of nocturnal leg cramps is associated with LSS and severity of symptoms. Pain symptoms were improved by conservative or surgical treatment, but only surgery improved nocturnal leg cramps in patients with LSS. Thus, these results indicate that the prevalence of nocturnal leg cramps is associated with spinal nerve compression by LSS.

New catalyst, prepared through Au nanoparticles anchored on the Ionic Liquid of 3,4,9,10-perylene tetracarboxylic acid-noncovalent functionalized graphene (Au/PDIL-GS), was fabricated using a facile and environment-friendly approach. The information of the morphologies, sizes, dispersion of Au nanoparticles (NPs) and chemical composition for the as-prepared catalysts was verified by systematic characterizations, including transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), Raman spectra, X-ray diffraction (XRD) and X-Ray photoelectron spectroscopy (XPS). As a new catalyst, the resulting Au/PDIL-GS exhibited excellent catalytic activity in the reduction of 4-nitrophenol because of the synergistic effect between the PDIL-GS and Au NPs. The facile and environment-friendly approach provides a green way to effectively synthesize low cost Au-based catalysts for 4-NP reduction and is promising for the development of other useful materials., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Study Design: Animal study., Objective: To investigate pain-related expression of NaV1.7 in dorsal root ganglia (DRG) innervating intervertebral discs., Summary of Background Data: The pathophysiology of discogenic low back pain is not fully understood. Prostaglandins and cytokines produced by degenerated discs can cause pain, but nonsteroidal anti-inflammatory and steroid medications are often ineffective at pain reduction. Tetrodotoxin-sensitive, voltage-gated sodium (NaV) channels are associated with sensory transmission in primary sensory nerves, and the NaV1.7 channel has emerged as an attractive analgesic target. The purpose of this study was to investigate pain-related expression of NaV1.7 in DRG innervating intervertebral discs., Methods: Using a rodent model of disc puncture, we labeled DRG neurons innervating L5-L6 discs with FluoroGold neurotracer (n = 20). Half of the rats (n = 10) underwent intervertebral disc puncture using a 23-gauge needle (puncture group), and the other half underwent non-puncture sham surgery (non-puncture group). Seven and 14 days after surgery, DRGs from the L1 to L6 levels were harvested, sectioned, and immunostained for NaV1.7, and the proportion of NaV1.7-immunoreactive DRG neurons was evaluated., Results: NaV1.7 was expressed in DRG neurons innervating intervertebral discs from L1 to L5. The ratio of NaV1.7-expressing DRG neurons to total FG-labeled neurons was 7.2% and 7.6% at 1 and 2 weeks after surgery, respectively, in the non-puncture group and 16.2% and 16.3% at 1 and 2 weeks, respectively, in the puncture group. The upregulation of NaV1.7 after puncture was significant at both 1 and 2 weeks after surgery (P < 0.01)., Conclusion: We found that disc injury increases NaV1.7 expression in DRG neurons innervating injured discs. NaV1.7 may be a therapeutic target for pain control in patients with lumbar disc degeneration.

Purpose: Bupivacaine is commonly used for the treatment of back pain and the diagnosis of its origin. Nonunion is sometimes observed after spinal fusion surgery; however, whether the nonunion causes pain is controversial. In the current study, we aimed to detect painful nonunion by injecting bupivacaine into the disc space of patients with nonunion after anterior lumbar interbody fusion (ALIF) surgery for discogenic low back pain., Materials and Methods: From 52 patients with low back pain, we selected 42 who showed disc degeneration at only one level (L4-L5 or L5-S1) on magnetic resonance imaging and were diagnosed by pain provocation on discography and pain relief by discoblock (the injection of bupivacaine). They underwent ALIF surgery. If the patients showed low back pain and nonunion 2 years after surgery, we injected bupivacaine into the nonunion disc space. Patients showing pain relief after injection of bupivacaine underwent additional posterior fixation using pedicle screws. These patients were followed up 2 years after the revision surgery., Results: Of the 42 patient subjects, 7 showed nonunion. Four of them did not show low back pain; whereas 3 showed moderate or severe low back pain. These 3 patients showed pain reduction after injection of bupivacaine into their nonunion disc space and underwent additional posterior fixation. They showed bony union and pain relief 2 years after the revision surgery., Conclusion: Injection of bupivacaine into the nonunion disc space after ALIF surgery for discogenic low back pain is useful for diagnosis of the origin of pain.

We study the effect of different gas adsorbates (N2, O2, and CO2) on the field emission (FE) properties of graphene film. Our experimental measurements show that, except for N2, adsorption of O2 and CO2 reduces the FE current of the graphene film. Moreover, the measured FE hysteresis loop is almost quenched after adsorbing O2 or CO2. The ab initio calculations quantify the experimental results by predicting a larger work function and smaller FE current for the graphene system after O2 or CO2 adsorption. In contrast, the change of FE properties in N2 adsorbed graphene is negligible. A "depolarization electric field model" is then proposed to explain the observed FE hysteresis behavior.

Purpose: The pathomechanisms of pain resulting from lumbar disc herniation have not been fully elucidated. Prostaglandins and cytokines generated at the inflammatory site produce associated pain; however, non-steroidal anti-inflammatory drugs and steroids are sometimes ineffective in patients. Tetrodotoxin-sensitive voltage-gated sodium (NaV) channels are related to sensory transmission in primary sensory nerves. The sodium channel NaV1.7 has emerged as an attractive analgesic target. The purpose of this study was to evaluate pain-related behavior and expression of NaV1.7 in dorsal root ganglia (DRG) after combined sciatic nerve compression and nucleus pulposus (NP) application in rats., Methods: Rats were divided into three groups and underwent either sciatic nerve compression with NP for 2 s using forceps (n = 20), sham operation with neither compression nor NP (n = 20), or no operation (controls, n = 20). Mechanical hyperalgesia was measured every second day for three weeks using von Frey filaments. NaV1.7 expression in L5 DRG was examined 7 and 14 days after surgery using immunohistochemistry. The number of neurons immunoreactive for NaV1.7 was compared among the three groups., Results: Mechanical hyperalgesia was found over the 14-day observation in the nerve compression plus NP application group, but not in the sham-operated or control groups (P < 0.05). NaV1.7 expression in L5 DRG was up-regulated in the nerve compression plus NP application group, compared with sham-operated and control rats (P < 0.01)., Conclusions: Our results indicate that nerve compression plus NP application produces pain-related behavior. We conclude that NaV1.7 expression in DRG neurons may play an important role in mediating pain from sciatic nerves after compression injury and exposure to NP.

Extreme lateral interbody fusion (XLIF) has been widely used for minimally invasive anterior lumbar interbody fusion (ALIF), but an approach to L5-S1 is difficult because of the iliac crest. In the current study, we present 2 cases using minimally invasive oblique lateral interbody fusion (OLIF) of L5-S1. The patients showed foraminal stenosis between L5 and S1 and severe low back and leg pain. The patients were placed in a lateral decubitus position and underwent OLIF surgery (using a cage and bone graft from the iliac crest) without posterior decompression. Posterior screws were used in the patients. Pain scores significantly improved after surgery. There was no spinal nerve, major vessel, peritoneal, or urinary injury. OLIF surgery was minimally invasive and produced good surgical results without complications.