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Effects of GSK3beta inhibition on the formation of invadopodium-like microstructures and matrix degradation by U251 cells.

Source and working dilutions of the primary antibodies used for Western blotting, immunofluorescence and immunohistochemical staining and pull-down assay.

Purpose: Glioblastoma represents the malignant brain tumor that is most refractory to treatment and in which the identification of molecular target(s) is urgently required. We investigated the expression, activity, and putative pathologic role of glycogen synthase kinase 3β (GSK3β), an emerging therapeutic target for neurodegenerative diseases, in human glioblastoma.Experimental Design: The active fraction of GSK3β that is phosphorylated at the tyrosine 216 residue (pGSK3βY216) was identified in glioblastoma cell lines. GSK3β activity for phosphorylating its substrate was detected in these cells by nonradioisotopic in vitro kinase assay.Results: Higher expression levels of GSK3β and pGSK3βY216 were frequently detected in glioblastomas compared with nonneoplastic brain tissues. Inhibition of GSK3β activity by escalating doses of a small-molecule inhibitor (AR-A014418) or inhibition of its expression by RNA interference induced the apoptosis and attenuated the survival and proliferation of glioblastoma cells in vitro. Inhibition of GSK3β was associated with increased expression of p53 and p21 in glioblastoma cells with wild-type p53 and with decreased Rb phosphorylation and expression of cyclin-dependent kinase 6 in all glioblastoma cell lines. Administration of AR-A014418 at a low dose significantly sensitized glioblastoma cells to temozolomide and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea, chemotherapeutic agents used in the clinical setting, as well as to ionizing radiation.Conclusion: These results indicate that GSK3β exerts a pathologic role by promoting the survival and proliferation of glioblastoma cells and by protecting them from apoptosis via the inactivation of p53- and/or Rb-mediated pathways. Consequently, we propose that GSK3β provides a potential therapeutic target in glioblastoma.

Supplementary Data from Potential Therapeutic Effect of Glycogen Synthase Kinase 3β Inhibition against Human Glioblastoma

Carbon fiber reinforced plastics (CFRP) with the matrix of thermoplastic resin called as carbon fiber reinforced thermoplastics (CFRTPs) has been widely used in the industrial fields. Recently, a thermoplastic epoxy resin (TP-EP resin) has been developed as the matrix of CFRTP and carbon fiber reinforced TP-EP strands (CF/TP strands) molded by pultrusion method began to be used as tension rods for infrastructure under water absorption. On the other hand, an accelerated testing methodology (ATM) for predicting statistically long-term creep and fatigue strengths of CFRP was established by the authors. This study examines the prediction of statistical life time for these developed CF/TP strands at creep and fatigue tension loadings under the wet condition of water absorption with comparison to similar prediction under a dry condition by using our developed ATM. First, the static, creep, and fatigue tensile strengths of CF/TP strands were measured statistically at various constant temperatures under wet and dry conditions. The statistical long-term creep and fatigue tensile strengths for CF/TP strands under wet and dry conditions are predicted by substituting the measured data into the formulations of these strengths on our developed ATM. Finally, the influences of water absorption on the statistical long-term creep and fatigue strengths of CF/TP strands are cleared. In particular, the degradation of relaxation modulus of matrix TP-EP resin with increasing of elapsed time is accelerated with the water absorption, and the degradation of creep strength of CF/TP strand with increasing of elapsed time is also accelerated with the water absorption in the similar manner of matrix resin. On the other hand, the fatigue strength of CF/TP strand decreases scarcely with water absorption although this fatigue strength depends remarkably on the number of cycles to failure.

The flutter of thin elastic plates (sheets) in a fluid flow is an interesting nonlinear problem, as well as an important engineering problem, because the sheets are used in many industrial applications. A detailed understanding of flutter characteristics and sustaining mechanism of limit cycle oscillation (LCO) is important to suppress the flutter. In this study, a nonlinear analysis on a LCO of rectangular sheets in a three-dimensional uniform fluid flow using the nonlinear beam model and vortex-lattice method is performed. The influence of the vortex element model of the vortex-lattice method on the post-critical behavior is investigated in detail. Moreover, fluid–structure interaction simulations are performed using computational fluid dynamics and computational structural dynamics to examine the flow field and pressure distributions acting on a sheet surface in detail. It is found that flow separation around the side edges of a fluttering sheet can affect the post-critical behavior.

According to the Global Historical Database by the National Centers for Environmental Information, the oldest historical tsunami record in Central America is the earthquake tsunami that occurred in Mexico in 1537; however, this record is doubtful because this tsunami is reported by no authority outside Japan. Here, I examined earthquake and tsunami catalogs and found the source of this suspicious data. Imamura (1925) compiled the first part of the chronological table of major earthquakes in the world from the earthquake catalog of the world by Milne (1912). During this compilation, information on the tsunami caused by the 1531 Spain–Portugal earthquake was not copied. The chronological table was published almost annually until 1962; during this time the table was revised in 1958 by Kawasumi, who was the author in charge at the time. The remarks for the 1531 Spain–Portugal earthquake tsunami should have been added during the revision, but the text “tsunami existence” was erroneously added to the next entry for the 1537 Mexico earthquake. The source of the 1537 tsunami report was this miscopy.

Recently, the Innovative Composite Center of Kanazawa Institute of Technology developed a thermoplastic epoxy resin (TP-EP). Resin-impregnated carbon fiber reinforced TP-EP (CF/TP) strands molded by pultrusion were developed by Komatsu Matere Co., Ltd., for use as tension rods. This study examines the prediction of the statistical life time for these developed CF/TP strands under cyclic tension loading with comparison to our earlier report of similar predictions for carbon fiber reinforced thermoset epoxy resin (CF/TS) strands having a thermoset epoxy resin (TS-EP) as a matrix. First, test methods for static and fatigue strengths at elevated temperatures were developed for CF/TP strands. Second, static and fatigue tensile strengths of CF/TP strands were measured statistically at various constant temperatures under a constant strain rate and frequency. The master curves of statistical fatigue tensile strengths for CF/TP strands were constructed by substituting the measured data into the formulations of these strengths based on the matrix resin viscoelasticity. The fatigue strength characteristics of CF/TP strands were discussed through comparison to those of CF/TS strands with thermosetting epoxy resin as the matrix.

The epidemiology of patients with traumatic brain injury (TBI) has changed dramatically over recent decades as a result of rapid advances in aging societies. We assessed the influence of age on outcomes of patients with TBI and sought to identify prognostic factors for in-hospital mortality of TBI among elderly patients.Using a nationwide database, we analyzed data from 5651 patients with TBI. Univariate analysis was conducted to compare patient demographics, neurologic status on admission, radiologic findings, systemic complication rates, length of hospital stay, in-hospital mortality, and home discharge rates between elderly and nonelderly groups. Multivariable analysis was conducted to determine prognostic factors for in-hospital mortality among elderly patients.Overall in-hospital mortality was significantly higher in elderly patients (12.8% vs. 19.3%; P0.001). In-hospital mortality of elderly patients with mild TBI increased significantly at7 days after admission, whereas that of elderly patients with moderate or severe TBI was significantly higher immediately after admission. Age (odds ratio [OR], 1.62; P = 0.024), male sex (OR, 1.30; P = 0.004), Japan Coma Scale score on admission (OR, 5.95, P0.001), and incidence of acute subdural hematoma (OR, 1.89; P0.001) were associated with in-hospital mortality in elderly patients with TBI.Elderly patients with TBI showed significantly higher in-hospital mortality. Delayed increases in in-hospital mortality were observed among elderly patients with mild TBI. Level of consciousness on admission was the strongest predictor of in-hospital mortality among elderly patients.

Laparoscopic hepatojejunostomy (HJ) with continuous sutures is commonly performed in laparoscopic pancreaticoduodenectomy (LPD). This study aimed to investigate the long-term surgical outcomes of HJ in LPD. We retrospectively evaluated 103 consecutive patients who underwent pancreaticoduodenectomy via laparoscopic HJ with continuous suturing using multifilament (n = 48) or monofilament-absorbable sutures (n = 47). During follow-up, anastomotic stricture of HJ was identified in 8 (7.8%) patients via balloon enteroscopy-assisted cholangiography. The median time from surgery to confirmation of stricture formation was 7.6 months (range 3.6–19.4). The incidence of HJ stricture was significantly higher in patients with a thin bile duct (diameter

Objectives Infected subdural hematoma (ISH) is a rare type of subdural empyema, with fewer than 50 cases reported to date. Its radiological features have not been adequately described, making diagnosis challenging. At our institution, two adults presented with ISH, which exhibited a characteristic shape on preoperative imaging. Patients and methods This study examined ISH cases and chronic subdural hematoma (CSH) cases that underwent surgery at the Ishikawa Prefectural Central Hospital between January 2016 and March 2018. To distinguish ISH from CSH, we focused on three specific radiological features: the biconvex shape of the hematoma, presence of a high-density region at the lower end of the hematoma on plain computed tomography (CT), and presence of a hyper-intense signal within the hematoma on diffusion weighted imaging (DWI). Results We analyzed 30 ISH (current and previously reported) and 102 CSH cases in our study. We found no statistically significant associations between the hematoma type (ISH or CSH) and the presence of a high-density region at the lower end of the hematoma on plain CT (p = 0.13) or the presence of hyperintensity in the hematoma on DWI (p = 1.00). Conversely, a statistically significant association was found between the hematoma type and the biconvex shape of the hematoma (p Conclusion These results suggest that the shape of the hematoma on imaging provides valuable information that can be used to differentiate ISH from CSH and optimize therapeutic approaches.

One of the quickest means of tsunami evacuation is transfer to higher ground soon after strong and long ground shaking. Ground shaking itself is a good initiator of the evacuation from disastrous tsunami. Longer period seismic waves are considered to be more correlated with the earthquake magnitude. We investigated the possible application of this to tsunami hazard alarm using single-site ground motion observation. Information from the mass media is sometimes unavailable due to power failure soon after a large earthquake. Even when an official alarm is available, multiple information sources of tsunami alert would help people become aware of the coming risk of a tsunami. Thus, a device that indicates risk of a tsunami without requiring other data would be helpful to those who should evacuate. Since the sensitivity of a low-cost MEMS (microelectromechanical systems) accelerometer is sufficient for this purpose, tsunami alarm equipment for home use may be easily realized. Amplitude of long-period (20 s cutoff) displacement was proposed as the threshold for the alarm based on empirical relationships among magnitude, tsunami height, hypocentral distance, and peak ground displacement of seismic waves. Application of this method to recent major earthquakes indicated that such equipment could effectively alert people to the possibility of tsunami.

Rhabdomyosarcoma is the most common soft-tissue sarcoma affecting children and adolescents. It is defined as a malignant neoplasm characterized by morphologic, immunohistochemical, ultrastructural, or molecular genetic evidence of primary skeletal muscle differentiation, usually in the absence of any other pattern of differentiation. Primary intracranial rhabdomyosarcoma (PIRMS) is an extremely rare neoplasm, with only 60 cases reported in the literature, and generally has poor prognosis with an overall survival of only 9.1 months. The DICER1 gene encodes an RNA endoribonuclease that plays a key role in gene expression regulation through the production of small RNAs. Herein, we report two cases of PIRMS with somatic DICER1 mutation showing morphological and immunohistochemical evidence of primary skeletal muscle differentiation; the two cases share common clinical features, including young age, supratentorial tumor, and onset of intratumoral bleeding. Although methylation profiling was not performed, both cases shared clinical and pathological characteristics in common with recently proposed methylation entity “spindle cell sarcoma with rhabdomyosarcoma-like features, DICER1 mutant (SCS-RMSlike-DICER1)’’. Our cases provide further evidence of the link between primary intracranial sarcoma and DICER1 mutation which may form a distinct entity.

The theoretical lateral current of the surface inversion layer in a crystalline silicon (cSi) surface for a p-aSi:H/i-aSi:H/cSi heterojunction (SHJ) solar cell was calculated using computer simulation and was compared with the experimental one to study defects/traps at the aSi:H/cSi interface and/or in the cSi surface and to detect the acceptor concentration (N a) in p-aSi:H. To experimentally extract the lateral surface inversion layer current, a field-effect transistor type test element group device was co-integrated with SHJ cells on the same wafer. From the correlation between the experimental and calculated lateral surface inversion layer current, the density of defects/traps (D it) at the aSi:H/cSi interface and/or in the cSi surface and the value of N a were extracted. The calculated lateral surface inversion layer current stayed unchanged for various minority carrier lifetimes in the substrate, suggesting that this method is not suffered from the variation in the material parameters in the substrate.

Background and purpose To assess the relationship between plaque volume evaluated by multidetector computed tomographic angiography (MDCT) and in-stent restenosis (ISR) after carotid artery stenting (CAS). Materials and methods From a retrospectively maintained database, data were collected for 52 patients with carotid artery stenosis treated with CAS between 2007 and 2012. We defined ISR of ≥ 50% as a peak systolic velocity ≥ 200 cm/s on echo-duplex scan. Carotid plaques were subdivided into four components according to radiodensity in Hounsfield units (HU) as follows: 600 HU. Risk factors that influenced ISR were compared using univariate and multivariate Cox regression analyses. Results During a median follow-up period of 36 months, ISR of ≥ 50% was detected in five patients (9.6%). In the univariate Cox proportional hazard regression analysis, renal insufficiency, coronary artery disease, total plaque volume, and plaque volumes with radiodensities

Highlights • We report a rare case of adenoma that developed after sigmoidocolocystoplasty. • There were 11 cases of oncogenesis after bladder augmentation in the literature, including our case. • We recommend routine surveillance cytoscopy and cytology for patients after bladder augmentation, although this remains controversial., Introduction We encountered a rare case of tubular adenoma developing after bladder augmentation. We here report our case as well as summarize reports in the literature on adenomas developing after bladder augmentation. Presentation of case A 23-year-old man came to our hospital for routine surveillance cystoscopy. He was born with a lipomyelomeningocele and neurogenic bladder with low bladder compliance, and hence his bladder was routinely emptied by clean intermittent catheterization. He was also treated with anticholinergic agents. However, because the patient’s neurogenic bladder was unstable, he underwent sigmoidocolocystoplasty when he was 8-years old. After the bladder augmentation, he was examined annually by surveillance cystoscopy. On cystoscopy, a 5-mm pedunculated polyp was found on the front side of the sigmoid colon cap. Therefore, we performed snare polypectomy together with electrocoagulation under cystoscopy. The patient’s final diagnosis was tubular adenoma (mild atypia) with no malignancy, as assessed by histopathology. There has been no evidence of recurrence after the polypectomy on routine surveillance cystoscopy. Discussion To the best of our knowledge, there have been 11 cases of adenoma occurring after bladder augmentation reported in the literature, including our present case. There are several carcinogenic pathways associated with colorectal oncogenesis. Adenomas that are larger than 1.0 cm in diameter with a marked villous component have a high risk of oncogenesis. Conclusion We believe that the early detection of carcinoma or adenoma and their treatment at an early stage is crucial. Therefore, we recommend routine surveillance cystoscopy for patients after bladder augmentation.

Effects of an ITO capping layer on the interface workfuncion of MoO x was studied for an ITO/MoO x /SiO2/Si structure device from the viewpoint of the behavior of In atoms. The workfunction of MoO x at the MoO x /SiO 2 interface, which were extracted by capacitance-voltage (C-V) analysis, was largely different from the bulk MoO x film in its value and post-deposition forming gas annealing (PDFGA) temperature dependency. The interface workfunctoin decreased by 0.13 and 0.35 eV by 200 and 400 °C PDFGA, respectively, while bulk workfunction decreased by only 0.1 eV by 400 °C PDFGA. A secondary ion mass spectroscopy (SIMS) analysis showed that In atoms were penetrated from the ITO layer into the MoO x layer by PDFGA. The concentration of In near the MoO x /SiO 2 interface increased from ∼1019 cm−3 for the as-grown ITO sample to ∼1020 cm−3 for the sample with 400 °C PDFGA. The increase in the In concentration near the MoO x /Japan>SiO 2 interface is a possible cause to decrease the interface workfunction.

A boy with myelomeningocele who had sigmoidocolocystoplasty and ureteric reimplantation when 2-years old and normal annual cystoscopies, developed hematuria and abdominal pain with liver dysfunction 14 years postoperatively. Computed tomography showed a tumor on the left side of the augmented bladder, a large lymph node, and large multiple probable metastases in the liver. Cystoscopy 3 months earlier had been normal, but when repeated showed a tumor originating from the augmented sigmoid colon. Biopsy showed undifferentiated sarcoma. Despite chemotherapy, he died 3 months later. The diagnosis at autopsy was undifferentiated sarcoma originating from the sigmoid colon. We report the first case of undifferentiated sarcoma developing 14 years after sigmoidocolocystoplasty for meningomyelocele, and also review the 55 cases of post-bladder augmentation malignancy in the literature.

A silicone retractor that can be attached to suction pipes was developed in order to enhance the usability [1]. The measurement of the retracting force is desired in order to avoid damage to brain tissue due to an unexpected large force. This paper presents a force-sensing embedded silicone retractor that can be attached to suction pipes. The developed silicone retractor can provide three functions at the same time: suction, retracting, and retracting force measurement. The force-sensing system is based on a visualization mechanism that displays the force as a colored pole motion. The surgeon can then roughly estimate the retracting force. With a fiberscope, the retracting force can be measured with a resolution of 0.05-0.3 N. The retractor is made of silicone and has the advantages of disposability, low cost, and easy sterilization/disinfection. The system was validated through finite element method analysis and experiments. © 2015 IEEE., IEEE/ASME International Conference on Advanced Intelligent Mechatronics, AIM 2015; BEXCOBusan; South Korea; 7 July 2015 through 11 July 2015; Category numberCFP15775-ART; Code 117136

A 12-month-old boy presented with left scrotal swelling. The mass was irregular, soft, fleshy, and nontender. It adhered to the scrotal skin and gradually enlarged. Operative findings revealed a mass fixed to the scrotal fundus and diagnosed as angiomyolipoma. This is apparently the first report of scrotal angiomyolipoma in infancy.

The failure of current treatment options for glioblastoma stems from their inability to control tumor cell proliferation and invasion. Biologically targeted therapies offer great hope and one promising target is glycogen synthase kinase-3β (GSK3β), implicated in various diseases, including cancer. We previously reported that inhibition of GSK3β compromises the survival and proliferation of glioblastoma cells, induces their apoptosis, and sensitizes them to temozolomide and radiation. Here, we explore whether GSK3β also contributes to the highly invasive nature of glioblastoma. The effects of GSK3β inhibition on migration and invasion of glioblastoma cells were examined by wound-healing and Transwell assays, as well as in a mouse model of glioblastoma. We also investigated changes in cellular microarchitectures, cytoskeletal components, and proteins responsible for cell motility and invasion. Inhibition of GSK3β attenuated the migration and invasion of glioblastoma cells in vitro and that of tumor cells in a mouse model of glioblastoma. These effects were associated with suppression of the molecular axis involving focal adhesion kinase, guanine nucleotide exchange factors/Rac1 and c-Jun N-terminal kinase. Changes in cellular phenotypes responsible for cell motility and invasion were also observed, including decreased formation of lamellipodia and invadopodium-like microstructures and alterations in the subcellular localization, and activity of Rac1 and F-actin. These changes coincided with decreased expression of matrix metalloproteinases. Our results confirm the potential of GSK3β as an attractive therapeutic target against glioblastoma invasion, thus highlighting a second role in this tumor type in addition to its involvement in chemo- and radioresistance. Mol Cancer Ther; 14(2); 564–74. ©2014 AACR.

To dissect the role of endoplasmic reticulum (ER) stress and unfolded protein response in brain ischemia, we investigated the relevance of activating transcription factor 6α (ATF6α), a master transcriptional factor in the unfolded protein response, after permanent middle cerebral artery occlusion (MCAO) in mice. Enhanced expression of glucose-regulated protein78, a downstream molecular chaperone of ATF6α, was observed in both neurons and glia in the peri-infarct region of wild-type mice after MCAO. Analysis using wild-type and Atf6α−/− mice revealed a larger infarct volume and increased cell death in the peri-ischemic region of Atf6α−/− mice 5 days after MCAO. These phenotypes in Atf6α−/− mice were associated with reduced levels of astroglial activation/glial scar formation, and a spread of tissue damage into the non-infarct area. Further analysis in mice and cultured astrocytes revealed that signal transducer and activator of transcription 3 (STAT3)-glial fibrillary acidic protein signaling were diminished in Atf6α−/− astrocytes. A chemical chaperone, 4-phenylbutyrate, restored STAT3-glial fibrillary acidic protein signaling, while ER stressors, such as tunicamycin and thapsigargin, almost completely abolished signaling in cultured astrocytes. Furthermore, ER stress-induced deactivation of STAT3 was mediated, at least in part, by the ER stress-responsive tyrosine phosphatase, TC-PTP/PTPN2. These results suggest that ER stress plays critical roles in determining the level of astroglial activation and neuronal survival after brain ischemia. We here suggest a mechanism triggered after brain ischemia in which the enhanced level of endoplasmic reticulum (ER) stress—caused by deletion of the activating transcription factor ATF6α—leads to suppression of the STAT3-GFAP signaling, inhibition of astroglial activation/glial scar formation, and enhanced level of neuronal death in the peri-ischemic area. This is mediated, at least in part, through the ER stress-responsive tyrosine phosphatase, TC-PTP. CNTF, ciliary neurotrophic factor; GFAP, Glial fibrillary acidic protein; IL-6, interleukin 6; LIF, leukemia inhibitory factor; STAT3, signal transducer, and activator of transcription 3.

There are many reports on position-related complications in neurosurgical literature but so far, continuous quantification of the patient's position during the surgery has not been reported. This study aims to explore the utility of a new surgical table system and its software in displaying the patient's body positions during surgery on real-time basis. More than 200 neurosurgical cases were monitored for their positions intra-operatively. The position was digitally recorded and could be seen by all the members in the operating team. It also displayed the three-dimensional relationship between the head and the heart positions. No position-related complications were observed during the study. The system was able to serve as an excellent indicator for monitoring the patient's position. The recordings were analyzed and even used to reproduce or improve the position in the subsequent operations. The novel technique of monitoring the position of the head and the heart of the patients and the operating table planes are considered to be useful during delicate neurosurgical procedures thereby, preventing inadvertent procedural errors. This can be used to quantify various surgical positions in the future and define safety measures accordingly.

Implantation of carmustine-impregnated wafers (Gliadel®) into the tumor resection cavity has demonstrated a survival benefit for patients with malignant glioma. However, some precautions should be taken regarding Gliadel implantation. We report a case of a 63-year-old man with glioblastoma who was implanted with Gliadel after a left temporal lobe tumor had been removed, and who later developed vasospasm of the lenticulostriate artery close to the implanted Gliadel, leading to serious cerebral infarction. Therefore, the implantation of Gliadel in cases where important vessels run close to the resection cavity should be considered with great caution.

Patients with glioma frequently present with neuropsychological deficits preoperatively and/or postoperatively, and these deficits may remain after the chronic phase. However, little is known about postoperative recovery course of right hemispheric function. We therefore studied the characteristics and causes of persistent cognitive dysfunction in right cerebral hemispheric glioma. Eighteen patients who underwent awake surgery participated in this study. All patients who received preoperative neuropsychological examinations were assigned to two groups according to their test results: preoperative deficit and normal. They were reassessed 1 week and 3 months after surgery. The rates of remaining deficits in the deficit group at chronic phase were higher than those of the normal group for all functions. Despite preoperative normal function, the remaining rate for visuospatial cognitive deficits was the highest among all functions. The voxel-based lesion-symptom mapping analysis for visuospatial cognition revealed that a part of the medial superior and middle frontal gyri were resected with high probability in patients with low visuospatial cognitive accuracy. Our study indicates that in patients with preoperative neuropsychological deficits, these deficits tend to remain until the chronic phase. Visuospatial dysfunction frequently persists until the chronic phase, which might reflect damage to the superior longitudinal fasciclus I and II.

Background/purpose We report the current status of patients who underwent augmentation cystoplasty (AC) at least 20 years previously. Methods Surgical history, incidence of urinary tract infection (UTI) and bladder stones, vesicoureteral reflux (VUR), urine cytology, renal function, a colon cancer tumor marker (carcinoembryonic antigen: CEA), and patient outcomes were assessed. Results Forty patients who underwent AC (mean age: 34.4 years; mean follow-up time: 24.3 years) were analyzed. Mean age at AC was 11 years. Incidence of bladder stones was 30%. There were no incidences of carcinoma after AC, and CEA levels were not increased. Ureteral reimplantation (URI) was performed in 21 patients. URI performed at the same time as AC was successful in 14 cases (93%) and unsuccessful in 1 (7%) because of persistent VUR. UTI developed after AC in only 1 patient (2.5%) with persistent VUR. This patient required unilateral nephrectomy 18 years after the AC because of repeated UTIs. Thirty-four patients (85%) were employed, and 4 (10%) were married. Two of the 19 female patients (11%) had experienced pregnancy and delivery. Five patients (13%) had mental disorders. Conclusion Ultra long-term follow-up suggests that AC is a safe procedure with manageable sequelae, although some mental health issues remain. Type of study Case series with no comparison group. Level of evidence Level IV.

A 58-year-old man presented with slowly progressive chemosis, exophthalmos, and blepharedema of the left eye. Digital subtraction angiography revealed multiple dural arteriovenous fistulas(dAVFs)involving the bilateral tentorium, superior sagittal sinus, and right frontal convexity. In addition, occlusion of the left cavernous sinus and left sigmoid sinus were observed, which could lead to venous hypertension and might be associated with the occurrence of multiple dAVFs. Along with the congestion of the left ophthalmic vein, increased intracranial pressure due to the left tentorial dAVF with cortical venous reflux could have caused the left eye symptoms; therefore, the tentorial lesion was treated first. Although the proximal occlusion of the vein of Labbe, drainer of the left tentorial dAVF, was achieved after embolization using n-butyl cyanoacrylate via the external carotid artery, an arteriovenous shunt between the middle cerebral artery and the distal site of the vein of Labbe was newly visualized after embolization. The newly visualized lesion was treated with further surgical intervention. A pial AVF arising from several peripheral branches of the left middle cerebral artery with drainage into the distal site of the vein of Labbe was confirmed during the surgery, and interruption of the vein of Labbe was performed. The left eye symptoms of the patient significantly improved after the surgery, and postoperative angiogram revealed no residual shunt. Thus, the patient was treated using a combined approach of endovascular and direct surgeries, after which he recovered uneventfully.

Objective: To study the coping pattern of a mother of a child with multiple congenital anomalies (MCAs) based on interview data. Methods: The mother of a child born at Tohoku University Hospital, Japan, who was diagnosed with MCAs at 3 days of age and subsequently underwent surgery at 7 months, was asked to be interviewed. She answered semi structured interviews at the hospital when the child was two years old and again when the child was five years old. Psychological assessment with the State-Trait Anxiety Inventory (STAI) and the Self-rating Depression Scale (SDS) was conducted before each interview. Results: Psychological assessment showed that the mother had high levels of anxiety and depression when the child was two and when the child was five years old. The interview data showed that when the mother first learned that her baby had MCAs, her initial reaction was (1) shock. She then felt (2) Absent-minded. (3) Responsibility to take care of her child. (4) Depression, (5) Defense against acceptance of child’s disease as it is. The mother had this sequence of thoughts and emotions between the times of diagnosis of MCAs up through the time of surgery. In the first stage of coping, the mother showed defense against learning as much as possible about her child’s disease and MCAs. In the second stage of coping, the mother reported (when the child was five years old) that she felt that she had some control over her child’s situation. The mother started to accept her child’s disease as she as possible and learned what would be happened to her child. Conclusion: The mother of the child with MCAs was in a severe psychological condition over at least five years since diagnosis. In order to alleviate the psychological stress on mothers of a child with MCAs or other congenital disease, it is useful to educate the mother so that she can understand her child’s disease. However, it is difficult for parents without medical knowledge to understand a complicated disease such as MCAs. Providers need more training to educate parents with MCAs.

A reactive-plasma deposition (RPD) process damage is evaluated for an indium-tin-oxide (ITO)/SiO2/Si structure in terms of the recombination properties at the interface. To calculate the surface recombination velocity (SRV), the defect density at the SiO2/Si interface (Dit), the effective total charge (Qtot) which is the sum of the charges in the SiO2 and the trapped charge at the SiO2/Si interface, and the workfunction of ITO at the ITO/SiO2 interface (ϕITO), are extracted by capacitance-voltage (C-V) analysis as a function of a postdeposition annealing (PDA) temperature. The Dit and Qtot significantly increase by the RPD process to 1.4×1012 cm-2eV-1 and 1.5×1012/q cm-2, respectively, and decrease by the PDA at 200 °C in N2 ambient to 1.4×1011 cm-2eV-1 and 1.1×1011/q cm-2, respectively. The ϕITO also varies from 4.80 eV to 4.35 eV by the PDA. The correlation is examined between the SRV values calculated based on the extended SRH model using the extracted Dit, Qtot, and ϕITO values [SRV(CV)], and the SRV ones obtained from the minority carrier lifetime measurements [SRV(LT)]. It is found that multiple sets of capture cross-sections were required for SRV(CV) values to coincide with SRV(LT) ones. The effect of variation in the Qtot and ϕITO on the band bending is almost canceled out in the present PDA condition. It is thus considered that the increase in Dit is the main cause to decrease the minority carrier lifetime.

We report a rare case of a hemodialysis patient with a calcified amorphous tumor (CAT) on both sides of the atrioventricular valve annulus. A 70-year-old female who had received hemodialysis for 23 years because of chronic glomerulonephritis presented to our hospital with acute heart failure. Echocardiography indicated the presence of mobile cardiac masses on the mitral valve and tricuspid valve annulus. We suspected the presence of a cardiac tumor or vegetation. The patient received 3 g/day sulbactam-ampicillin and 60 mg/day gentamicin. Surgery was performed on the 14th day after hospital admission. The patient underwent mitral valve replacement, tricuspid annuloplasty, and tumor resection. Based on the pathological findings, the cardiac tumor was diagnosed as a CAT.

An intraluminal thrombus in the carotid artery is relatively rare. A high frequency of perioperative symptomatic stroke has been reported in patients undergoing carotid endarterectomy, and no standard therapy has yet been developed.A 69-year-old woman, with no history of trauma, presented with ischemic stroke and mild right hemiparesis. Computed tomography and MRI showed an infarction in the left parietal region. A carotid Doppler study showed carotid stenosis on the left side. Further investigation with digital subtraction angiography confirmed significant carotid artery stenosis with an intraluminal thrombus in the left internal carotid artery. She was treated with initial intravenous anticoagulant therapy followed by carotid endarterectomy with thrombus removal 14 days after admission(subacute phase). There was no postoperative complication and she had uneventful course over 3 years of follow-up.Initial adjuvant anticoagulant therapy for symptomatic intraluminal thrombus followed by carotid revascularization is an effective surgical strategy. A meticulous surgical procedure is required to perform a carotid endarterectomy in patients with an intraluminal thrombus.

Background In photodynamic diagnosis using 5-aminolevulinic acid (5-ALA), discrimination between the tumor and normal tissue is very important for a precise resection. However, it is difficult to distinguish between infiltrating tumor and normal regions in the boundary area. In this study, fluorescent intensity and bright spot analyses using a confocal microscope is proposed for the precise discrimination between infiltrating tumor and normal regions. Methods From the 5-ALA-resected brain tumor tissue, the red fluorescent and marginal regions were sliced for observation under a confocal microscope. Hematoxylin and eosin (H&E) staining were performed on serial slices of the same tissue. According to the pathological inspection of the H&E slides, the tumor and infiltrating and normal regions on confocal microscopy images were investigated. From the fluorescent intensity of the image pixels, a histogram of pixel number with the same fluorescent intensity was obtained. The fluorescent bright spot sizes and total number were compared between the marginal and normal regions. Results The fluorescence intensity distribution and average intensity in the tumor were different from those in the normal region. The probability of a difference from the dark enhanced the difference between the tumor and the normal region. The bright spot size and number in the infiltrating tumor were different from those in the normal region. Conclusions Fluorescence intensity analysis is useful to distinguish a tumor region, and a bright spot analysis is useful to distinguish between infiltrating tumor and normal regions. These methods will be important for the precise resection or photodynamic therapy of brain tumors. © 2016 Elsevier B.V., Embargo Period 12 months

Equimolar mixtures of lithium bis(trifluoromethanesulfonyl)amide (LiTFSA) and tetraglyme (G4: CH3O-(CH2CH2O)4-CH3) yield the solvate (or chelate) ionic liquid [Li(G4)][TFSA], which is a homogeneous transparent solution at room temperature. Solvate ionic liquids (SILs) are currently attracting increasing research interest, especially as new electrolytes for Li-sulfur batteries. Here, we performed neutron total scattering experiments with (6/7)Li isotopic substitution to reveal the Li(+) solvation/local structure in [Li(G4)][TFSA] SILs. The experimental interference function and radial distribution function around Li(+) agree well with predictions from ab initio calculations and MD simulations. The model solvation/local structure was optimized with nonlinear least-squares analysis to yield structural parameters. The refined Li(+) solvation/local structure in the [Li(G4)][TFSA] SIL shows that lithium cations are not coordinated to all five oxygen atoms of the G4 molecule (deficient five-coordination) but only to four of them (actual four-coordination). The solvate cation is thus considerably distorted, which can be ascribed to the limited phase space of the ethylene oxide chain and competition for coordination sites from the TFSA anion.

// Takuya Furuta 1 , Hemragul Sabit 1 , Yu Dong 1 , Katsuyoshi Miyashita 1 , Masashi Kinoshita 1 , Naoyuki Uchiyama 1 , Yasuhiko Hayashi 1 , Yutaka Hayashi 1 , Toshinari Minamoto 2 , Mitsutoshi Nakada 1 1 Department of Neurosurgery, Division of Neuroscience, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan 2 Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan Correspondence to: Mitsutoshi Nakada, email: mnakada@med.kanazawa-u.ac.jp Keywords: glioblastoma, GSK3β, drug repositioning, translational research, clinical study Received: May 11, 2016 Accepted: January 25, 2017 Published: February 09, 2017 ABSTRACT Background: Glycogen synthase kinase (GSK)-3β has emerged as an appealing therapeutic target for glioblastoma (GBM). Here, we investigated the therapeutic effect of the current approved drugs against GBM via inhibition of GSK3β activity both, in experimental setting and in a clinical study for recurrent GBM patients by repositioning existent drugs in combination with temozolomide (TMZ). Materials and Methods: Progression-free and overall survival rates were compared between patients with low or high expression of active GSK3β in the primary tumor. GBM cells and a mouse model were examined for the effects of GSK3β-inhibitory drugs, cimetidine, lithium, olanzapine, and valproate. The safety and efficacy of the cocktail of these drugs (CLOVA cocktail) in combination with TMZ were tested in the mouse model and in a clinical study for recurrent GBM patients. Results: Activation of GSK3β in the tumor inversely correlated with patient survival as an independent prognostic factor. CLOVA cocktail significantly inhibited cell invasion and proliferation. The patients treated with CLOVA cocktail in combination with TMZ showed increased survival compared to the control group treated with TMZ alone. Conclusions: Repositioning of the GSK3β-inhibitory drugs improved the prognosis of refractory GBM patients with active GSK3β in tumors. Combination of CLOVA cocktail and TMZ is a promising approach for recurrent GBM.

OBJECTIVE Although the right prefrontal region is regarded as a silent area, chronic deficits of the executive function, including working memory (WM), could occur after resection of a right prefrontal glioma. This may be overlooked by postoperative standard examinations, and the disabilities could affect the patient's professional life. The right prefrontal region is a part of the frontoparietal network and is subserved by the superior longitudinal fasciculus (SLF); however, the role of the SLF in spatial WM is unclear. This study investigated a persistent spatial WM deficit in patients who underwent right prefrontal glioma resection, and evaluated the relationship between the spatial WM deficit and the SLF. METHODS Spatial WM was examined in 24 patients who underwent prefrontal glioma resection (right, n = 14; left, n = 10) and in 14 healthy volunteers using a spatial 2-back task during the long-term postoperative period. The neural correlates of spatial WM were evaluated using lesion mapping and voxel-based lesion-symptom mapping. In addition, the spatial 2-back task was performed during surgery under direct subcortical electrical stimulation in 2 patients with right prefrontal gliomas. RESULTS Patients with a right prefrontal lesion had a significant chronic spatial WM deficit. Voxel-based lesion-symptom mapping analysis revealed a significant correlation between spatial WM deficit and the region that overlapped the first and second segments of the SLF (SLF I and SLF II). Two patients underwent awake surgery and had difficulties providing the correct responses in the spatial 2-back task with direct subcortical electrical stimulation on the SLF I, which was preserved and confirmed by postoperative diffusion tensor imaging tractography. These patients exhibited no spatial WM deficits during the postoperative immediate and long-term periods. CONCLUSIONS Spatial WM deficits may persist in patients who undergo resection of the tumor located in the right prefrontal brain parenchyma. Injury to the dorsal frontoparietal subcortical white matter pathway, i.e., the SLF I or SLF I and II, could play a causal role in this chronic deficit. A persistent spatial WM deficit, without motor and language deficits, could affect the professional life of the patient. In such cases, awake surgery would be useful to detect the spatial WM network with appropriate task during tumor exploration.