Therapeutic efficacy of intra-arterial docetaxel and nedaplatin infusion concomitant with radiotherapy for T4 maxillary sinus squamous cell carcinoma.

The aim of this study was to evaluate the efficacy of intra-arterial chemoradiotherapy with docetaxel and nedaplatin for T4 maxillary sinus squamous cell carcinoma (MSSCC). Data were retrospectively analysed for 22 consecutive patients with T4 MSSCC who underwent intra-arterial chemoradiotherapy. Participants received intensity-modulated radiotherapy (70 Gy in 35 fractions) concomitantly with docetaxel (60 mg/m2) and nedaplatin (80 mg/m2) administered every 4 weeks for a total of three sessions. The median follow-up period was 49 months (range 12-91 months). T4a tumours were found in 16 patients (73%) and T4b tumours in six patients (27%). Cervical metastasis was found in nine patients (41%; five N2b, four N2c). The 5-year loco-regional control, disease-free survival, and overall survival rates for patients with T4a disease were 92.3%, 92.3%, and 90.3%, respectively, compared to 83.3% (P = 0.42), 66.7% (P = 0.07), and 83.3% (P = 0.46), respectively, for those with T4b disease. The 5-year loco-regional control, disease-free survival, and overall survival rates for patients with cervical lymph node metastasis were all 87.5% compared to 92.3% (P = 0.86), 84.6% (P = 0.69), and 92.3% (P = 0.93), respectively, for those without cervical metastasis. Intra-arterial chemoradiotherapy with docetaxel and nedaplatin may provide favourable loco-regional control and increased survival in T4 MSSCC.

An experimental setup for creating and imaging 4He2 * excimer cluster tracers in superfluid helium-4 via neutron-3He absorption reaction.

For the purpose of future visualization of the flow field in superfluid helium-4, clusters of the triplet state excimer 4He2 * are generated along the micro-scale recoil tracks of the neutron-absorption reaction n + 3He → 3T + p. This reaction is induced by neutron irradiation of the 3He fraction contained in natural isotopic abundance liquid helium with neutron beams either from the Japan Proton Accelerator Research Complex, Materials and Life Science Experimental Facility (JPARC)/Materials and Life Science Experimental Facility or from the Kyoto University Institute for Integrated Radiation and Nuclear Science. These 4He2 * clusters are expected to be ideal tracers of the normal-fluid component in superfluid helium with several advantageous properties. Evidence of the excimer generation is inferred by detection of laser induced fluorescence emitted from the 4He2 * clusters excited by a purpose-built short pulse gain-switched titanium:sapphire (Ti:sa) laser operating at a wavelength of 905 nm. The setup and performance characteristics of the laser system including the Ti:sa and two continuous wave re-pumping lasers are described. Detection at the fluorescence wavelength of 640 nm is performed by using optical bandpass filtered photomultiplier tubes (PMT). Electrical noise in the PMT acquisition traces could successfully be suppressed by post-processing with a simple algorithm. Despite other laser-related backgrounds, the excimer was clearly identified by its fluorescence decay characteristics. Production of the excimer was found to be proportional to the neutron flux, adjusted via insertion of different collimators into the neutron beam. These observations suggest that the apparatus we constructed does function in the expected manner and, therefore, has the potential for groundbreaking turbulence research with superfluid helium.

CT and MRI characteristics for differentiating mediastinal Müllerian cysts from bronchogenic cysts.

AIM: To evaluate how computed tomography (CT) and magnetic resonance imaging (MRI) characteristics can be used to differentiate immunohistochemically confirmed mediastinal Müllerian cysts (MMCs) from bronchogenic cysts (BCs). MATERIALS AND METHODS: Sixteen patients with histopathologically and immunohistochemically confirmed mediastinal cysts (four with MMCs and 12 with BCs) were included in this study. CT and MRI images were reviewed retrospectively and the location, size, CT attenuation, and MRI signal intensity of the two pathologies were compared. RESULTS: On review of CT images, cysts could be located to the anterior mediastinum in four BCs, middle mediastinum in three MMCs and seven BCs, and posterior mediastinum in one MMC and one BC. Contact with a vertebral body was observed in 4/4 MMCs (100%) and 6/12 BCs (50%). The ratios of minimum-to-maximum diameter (0.57±0.09 versus 0.74±0.11, p<0.01), CT attenuation (7.8±6 versus 44.3±12 HU, p<0.01), and cyst-to-spinal cord signal intensity ratios (SIRs) on T1-weighted images (0.56±0.2 versus 1.31±0.4, p<0.01) were significantly lower for MMCs than BCs. No significant differences in maximum diameter, minimum diameter, and SIRs on T2-weighted images were found between MMCs and BCs. CONCLUSION: In characterising mediastinal cysts in a middle-aged female patient, contact with a vertebral body, flattened configuration, hypodensity on CT, and hypointensity compared to spinal cord on T1-weighted images are features that are specific to MMCs.

Condyloma Acuminata of the Urethra in a Male Renal Transplant Recipient: A Case Report.

BACKGROUND: Condyloma acuminatum (CA) is a common sexually transmitted disease associated with human papilloma virus (HPV). CA occurring in the urethra is rare and has not been reported in male renal transplant recipients. In addition, despite immunosuppressive conditions and increased risk of HPV-related malignant neoplasms in transplant recipients, HPV testing in male transplant recipients has been uncommon. Here we report a case of urethral CA in a male deceased donor renal transplantation recipient and discuss the importance of HPV testing in male transplant recipients. CASE PRESENTATION: A 33-year-old male deceased donor renal transplant recipient presented with miction pain 5 years after the transplantation. He reported repeated urinary tract infections with no sexual contact since the renal transplantation. Multiple papillary tumors in his penile urethra were detected by cystoscopy, and a biopsy sample was pathologically diagnosed with CA. Transurethral tumor resection was performed, and the tumors were completely resected. Additional HPV risk type screening with a urethral smear sample showed the prevalence of low-risk HPV. Although tacrolimus was switched to everolimus and imiquimod cream was administered, the tumors recurred 6 months after the resection, and a second resection was performed. No further recurrence has been observed for 1 year to date. CONCLUSION: As the urethral CA was possibly related to immunosuppressive conditions and a risk for HPV-related malignant neoplasm, the case required careful diagnosis, including HPV risk type. The methodology of sampling for HPV testing in men has not been established. This case suggests the necessity for further discussion about HPV testing in male transplant recipients.

Partial Cystectomy of Paraganglioma of the Urinary Bladder Before Living Kidney Transplantation: Case Report.

BACKGROUND: Paraganglioma (extra-adrenal pheochromocytoma) of the bladder is a very rare disease, accounting for 0.06% of all bladder tumors. Optimal management of bladder paraganglioma before kidney transplantation is unknown. We report a case of partial cystectomy for urinary bladder paraganglioma before living kidney transplantation. CASE PRESENTATION: A 59-year-old man with a 27-year history of hemodialysis was referred to our department for further examination of a bladder tumor detected during pre-transplantation testing. Cystoscopy revealed a submucosal tumor on the right side of the bladder. The patient experienced a hypertensive crisis during transurethral resection of the bladder tumor. Endocrinologic and pathologic examinations confirmed the diagnosis of paraganglioma in the urinary bladder. A partial cystectomy was performed before kidney transplantation. Nine months after partial cystectomy, the patient underwent AB0-incompatible living kidney transplantation from his spouse. No disease recurrence or graft rejection was observed 12 months after the transplantation. CONCLUSIONS: To our knowledge, this is the 1st report on the management of paraganglioma in the urinary bladder before living kidney transplantation. Kidney transplantation after partial cystectomy is an option that may be considered in patients with paraganglioma of the urinary bladder, with careful observations of bladder function and vesicoureteral reflux to the grafts.

Development of fast neutron pinhole camera using nuclear emulsion for neutron emission profile measurement in KSTAR.

We have developed a compact fast neutron camera based on a stack of nuclear emulsion plates and a pinhole collimator. The camera was installed at J-port of Korea superconducting tokamak advanced research at National Fusion Research Institute, Republic of Korea. Fast neutron images agreed better with calculated ones based on Monte Carlo neutron simulation using the uniform distribution of Deuterium-Deuterium (DD) neutron source in a torus of 40 cm radius.

Unemployment risk among individuals undergoing medical treatment for chronic diseases.

BACKGROUND: Chronic diseases increase the risk of unemployment even in non-disaster settings; therefore, in post-disaster settings, special attention needs to be paid to the employment status of those suffering from chronic diseases. AIMS: To examine the association between chronic disease and the risk of unemployment in a disaster area. METHODS: This cross-sectional study was conducted in Shichigahama Town, Miyagi, north-eastern Japan, where had been severely inundated by the 2011 tsunami. Logistic regression analyses were used to evaluate the association between undergoing medical treatment for a combination of chronic diseases (stroke, cancer, myocardial infarction and angina) and unemployment risk. Confounders such as psychological distress and levels of daily life activity were considered. RESULTS: Among the 2588 individuals studied, there was a statistically significant association between undergoing medical treatment for chronic disease and the risk of unemployment [odds ratio (OR) = 1.7, 95% confidence interval (CI) 1.02-2.7, P < 0.05]. In participants with a lower degree of psychological distress and better levels of daily life activity (n = 1967), no significant associations were observed (OR = 1.1, 95% CI 0.6-2.1). Conversely, in 536 participants with a higher degree of psychological distress and/or poorer levels of daily life activity, statistically significant associations were found (OR = 2.6, 95% CI 1.01-6.6, P < 0.05). CONCLUSIONS: The association between undergoing medical treatment for chronic disease and unemployment risk was observed only in participants with a higher degree of psychological distress and/or poorer levels of daily life activity.

Successful glycemic control with three times a week degludec injection by medical staff for an elderly hemodialysis patient with type 2 diabetes.

For elderly hemodialysis patients with diabetes, the treatment options are restricted, and insulin therapy plays an important role. However, sometimes it might be difficult for them to inject insulin by themselves because of technical and/or social problems. The recently introduced basal insulin analog degludec has a longer half life than the previous basal insulin analogs such as glargine or detemir. Here we report an elderly hemodialysis patient with type 2 diabetes who was successfully treated with insulin degludec injection by the medical staff at every hemodialysis clinic visit. Throughout this treatment, he did not experience any side effects due to degludec, including hypoglycemia. There are few reports of using degludec for HD patients. In addition, this is the first report showing the validity of a three-times-a-week degludec regimen as a basal supported oral therapy for a hemodialysis patient with diabetes who could not inject insulin by himself. The inferiority of the three-times-a-week degludec regimen compared with the once-a-day glargine regimen in non-hemodialysis patients has already been reported. Based on this, this three-times-a-week degludec regimen should also not be considered as a standard regimen in hemodialysis patients. However, this three-times-a-week degludec regimen may be useful as an alternative for hemodialysis patients who cannot inject insulin once a day by themselves to achieve good and safe glycemic control, improving the prognosis and avoiding problems with hyperglycemia.

Local and systemic responses following intravitreous injection of AAV2-encoded modified Volvox channelrhodopsin-1 in a genetically blind rat model.

We previously designed a modified channelrhodopsin-1 (mVChR1) protein chimera with a broader action than that of Chlamydomonas channelrhodopsin-2 and reported that its transduction into retinal ganglion cells can restore visual function in genetically blind, dystrophic Royal College of Surgeons (RCS) rats, with photostimuli ranging from 486 to 640 nm. In the current study, we sought to investigate the safety and influence of mVChR1 transgene expression. Adeno-associated virus type 2 encoding mVChR1 was administered by intravitreous injection into dystrophic RCS rats. Reverse-transcription PCR was used to monitor virus and transgene dissemination and the results demonstrated that their expression was restricted specifically within the eye tissues, and not in non-target organs. Moreover, examination of the blood, plasma and serum revealed that no excess immunoreactivity was present, as determined using standard clinical hematological parameters. Serum antibodies targeting the recombinant adeno-associated virus (rAAV) capsid increased after the injection; however, no increase in mVChR1 antibody was detected during the observation period. In addition, retinal histological examination showed no signs of inflammation in rAAV-injected rats. In conclusion, our results demonstrate that mVChR1 can be exogenously expressed without harmful immunological reactions in vivo. These findings will aid in studies of AAV gene transfer to restore vision in late-stage retinitis pigmentosa.

Progress in development of the neutron profile monitor for the large helical device.

The neutron profile monitor stably operated at a high-count-rate for deuterium operations in the Large Helical Device has been developed to enhance the research on the fast-ion confinement. It is composed of a multichannel collimator, scintillation-detectors, and a field programmable gate array circuit. The entire neutron detector system was tested using an accelerator-based neutron generator. This system stably acquires the pulse data without any data loss at high-count-rate conditions up to 8 × 10(5) counts per second.

A study on fast digital discrimination of neutron and gamma-ray for improvement neutron emission profile measurement.

Neutron and γ-ray (n-γ) discrimination with a digital signal processing system has been used to measure the neutron emission profile in magnetic confinement fusion devices. However, a sampling rate must be set low to extend the measurement time because the memory storage is limited. Time jitter decreases a discrimination quality due to a low sampling rate. As described in this paper, a new charge comparison method was developed. Furthermore, automatic n-γ discrimination method was examined using a probabilistic approach. Analysis results were investigated using the figure of merit. Results show that the discrimination quality was improved. Automatic discrimination was applied using the EM algorithm and k-means algorithm.

Progress in development of neutron energy spectrometer for deuterium plasma operation in KSTAR.

Two types of DD neutron energy spectrometer (NES) are under development for deuterium plasma operation in KSTAR to understand behavior of beam ions in the plasma. One is based on the state-of-the-art nuclear emulsion technique. The other is based on a coincidence detection of a recoiled proton and a scattered neutron caused by an elastic scattering of an incident DD neutron, which is called an associated particle coincidence counting-NES. The prototype NES systems were installed at J-port in KSTAR in 2012. During the 2012 and 2013 experimental campaigns, multiple shots-integrated neutron spectra were preliminarily obtained by the nuclear emulsion-based NES system.

Highly sensitive nanoscale spin-torque diode.

Highly sensitive microwave devices that are operational at room temperature are important for high-speed multiplex telecommunications. Quantum devices such as superconducting bolometers possess high performance but work only at low temperature. On the other hand, semiconductor devices, although enabling high-speed operation at room temperature, have poor signal-to-noise ratios. In this regard, the demonstration of a diode based on spin-torque-induced ferromagnetic resonance between nanomagnets represented a promising development, even though the rectification output was too small for applications (1.4 mV mW(-1)). Here we show that by applying d.c. bias currents to nanomagnets while precisely controlling their magnetization-potential profiles, a much greater radiofrequency detection sensitivity of 12,000 mV mW(-1) is achievable at room temperature, exceeding that of semiconductor diode detectors (3,800 mV mW(-1)). Theoretical analysis reveals essential roles for nonlinear ferromagnetic resonance, which enhances the signal-to-noise ratio even at room temperature as the size of the magnets decreases.

Notch signaling pathway regulates proliferation and differentiation of immortalized Müller cells under hypoxic conditions in vitro.

Previous studies have indicated that Müller glia in chick and fish retinas can re-enter the cell cycle, express progenitor genes, and regenerate neurons via the Notch signaling pathway in response to retinal damage or growth factors. Here, we investigated the role of Notch signaling and the effect of hypoxia, as a means to induce retinal damage, on the proliferation of an immortalized Müller cell line (rMC-1 cells). Our data showed that rMC-1 cells expressed Müller glia and neural and retinal progenitor markers but did not express neuronal or retinal markers. Hypoxia increased rMC-1 cell proliferation by activating the positive cell-cycle regulators, cyclins A and D1, as well as the neural and retinal progenitor markers, Notch1, Hes1, nestin, Sox2, Msi1, Pax6, and NeuroD1. However, hypoxia did not significantly influence the expression of Müller glial markers GS, CRALBP, and cyclin D3 or the death of the rMC-1 cells. The increase in cell proliferation induced by hypoxia was greatly attenuated by blocking Notch signaling with the inhibitor DAPT, resulting in the reduced expression of positive cell-cycle regulators (cyclins A and D1) and neural and retinal progenitor markers (Notch1, Hes1, Sox2, Pax6, and NeuroD1). Blockade of the Notch signaling pathway by DAPT after hypoxia promoted the differentiation of rMC-1 cells to neurons, as demonstrated by the induction of neural marker (Tuj1), retinal amacrine (Syntaxin1), and retinal ganglion cell (Brn3b) markers, although the expression of the latter marker was low. Taken together, our data indicate that Notch signaling is required for proliferation under hypoxic conditions either by activating the positive cell-cycle regulators or by skewing their de-differentiation towards a neural progenitor lineage. These findings indicate that the Notch signaling pathway regulates hypoxia-induced proliferation and differentiation of Müller glia.

Coupling factor 6-induced activation of ecto-F1F(o) complex induces insulin resistance, mild glucose intolerance and elevated blood pressure in mice.

AIMS/HYPOTHESIS: Despite advances in pharmacological treatments, diabetes with hypertension continues to be a major public health problem with high morbidity and mortality rates. We recently identified a circulating peptide coupling factor 6 (CF6), which binds to the plasma membrane ATP synthase (ecto-F(1)F(o) complex), resulting in intracellular acidosis. We investigated whether overexpression of CF6 contributes to diabetes and hypertension by intracellular acidosis. METHODS: Transgenic mice overexpressing CF6 (also known as ATP5J) were generated, and physiological, biochemical and molecular biology studies were performed. RESULTS: CF6 overexpression elicited a sustained decrease in intracellular pH in tissues (aorta, kidney, skeletal muscle and liver, with the exception of adipose tissue) that express its receptor, the ß-subunit of ecto-F(1)F(o) complex. Consistent with the receptor distribution, phospho-insulin receptor ß, phosphoinositide 3-kinase activity and the phospho-Akt1:total Akt1 ratio were all decreased in the skeletal muscle and the liver in transgenic compared with wild-type mice, resulting in a decrease of plasma membrane-bound GLUT4 and an increase in hepatic glucose production. Under a high-sucrose diet, transgenic mice had insulin resistance and mild glucose intolerance; under a high-salt diet, they had elevated blood pressure with increased renal RAS-related C3 botulinum substrate 1 (RAC1)-GTP, which is an activator of mineralocorticoid receptor. CONCLUSIONS/INTERPRETATION: Through its action on the ß-subunit of ecto-F(1)F(o) complex, which results in intracellular acidosis, CF6 plays a crucial role in the development of insulin resistance and hypertension. This finding might advance our understanding of the mechanisms underlying diabetes and hypertension, possibly also providing a novel therapeutic target against cardiovascular disease.

Molecular characterization of erm(B)- and mef(E)-mediated erythromycin-resistant Streptococcus pneumoniae in China and complete DNA sequence of Tn2010.

AIMS: To characterize the erm(B)- and mef(E)-mediated erythromycin-resistant Streptococcus pneumoniae clinical isolates obtained from ten hospitals located different cities in China. METHODS AND RESULTS: Totally 83 S. pneumoniae were collected, and eighteen representative strains of 66 strains that exhibited erythromycin resistance were used for further characterization by antibiograms, serotyping, PFGE, MLST, DNA sequencing of the macrolide-resistance elements and mapping of the elements on the chromosome. Twelve isolates showed a high-level resistance to erythromycin, and six other isolates showed a low-level resistance to erythromycin. Thirteen isolates harboured a Tn2010 transposon (26·4 kbp) encoding the erm(B), tet(M) and mef(E) genes and were classified into three types by Tn2010 structures. The remaining five isolates harboured a Tn6002 transposon (20·9 kbp) encoding the erm(B) and tet(M) genes and were classified into three types by Tn6002 locations on the chromosome. Three of the Tn6002 elements were located within the Tn5252-like element, implying that these composed a large mobile element. The MLST analyses showed that several clones had been disseminated and that the CC271 strains carrying the Tn2010 element expressing the high-level resistance to erythromycin were predominant in China. Four new MLST strains, which were designated as ST3262, ST3263, ST3397 and ST3398 were also identified. CONCLUSIONS: The erythromycin resistance determinant of S.pneumoniae that had been isolated in China was located in Tn2010 or the Tn6002 element and several clones had been disseminated, and the CC271 strains carrying the Tn2010 element expressing the high-level resistance to erythromycin were predominant in China. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first molecular analysis of erythromycin-resistant Streptococcus pneumoniae clinical isolates in China, and the first report of the complete nucleotide sequence of Tn2010 (26,390 bp).

Immune responses to adeno-associated virus type 2 encoding channelrhodopsin-2 in a genetically blind rat model for gene therapy.

We had previously reported that transduction of the channelrhodopsin-2 (ChR2) gene into retinal ganglion cells restores visual function in genetically blind, dystrophic Royal College of Surgeons (RCS) rats. In this study, we attempted to reveal the safety and influence of exogenous ChR2 gene expression. Adeno-associated virus (AAV) type 2 encoding ChR2 fused to Venus (rAAV-ChR2V) was administered by intra-vitreous injection to dystrophic RCS rats. However, rAAV-ChR2 gene expression was detected in non-target organs (intestine, lung and heart) in some cases. ChR2 function, monitored by recording visually evoked potentials, was stable across the observation period (64 weeks). No change in retinal histology and no inflammatory marker of leucocyte adhesion in the retinal vasculature were observed. Although antibodies to rAAV (0.01-12.21 µg ml(-1)) and ChR2 (0-4.77 µg ml(-1)) were detected, their levels were too low for rejection. T-lymphocyte analysis revealed recognition by T cells and a transient inflammation-like immune reaction only until 1 month after the rAAV-ChR2V injection. In conclusion, ChR2, which originates from Chlamydomonas reinhardtii, can be expressed without immunologically harmful reactions in vivo. These findings will help studies of ChR2 gene transfer to restore vision in progressed retinitis pigmentosa.

Development of neutron spectrometer toward deuterium plasma diagnostics in LHD.

Neutron spectrometer based on coincident counting of associated particles has been developed for deuterium plasma diagnostics on Large Helical Device (LHD) at the National Institute for Fusion Science. Efficient detection of 2.5 MeV neutron with high energy resolution would be achievable by coincident detection of a scattered neutron and a recoiled proton associated with an elastic scattering of incident neutron in a plastic scintillator as a radiator. The calculated neutron spectra from deuterium plasma heated by neutral beam injection indicate that the energy resolution of better than 7% is required for the spectrometer to evaluate energetic deuterium confinement. By using a prototype of the proposed spectrometer, the energy resolution of 6.3% and the detection efficiency of 3.3×10(-7) count/neutron were experimentally demonstrated for 2.5 MeV monoenergetic neutron, respectively.