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As outcomes of organ transplantation have improved with advances in medicine, managing medical ethics issues has become increasingly more important. Although a basic consensus has been formed on the respect of autonomy in decision-making by prospective donors regarding living kidney transplantation, concrete and practical measures at the clinical site are required to ensure donor autonomy. The aim of the study was to identify elements related to autonomy in the kidney donor decision-making process., Methods: We systematically collected relevant studies from multiple databases in and out of Japan and conducted qualitative and inductive analyses., Results: The identified elements were categorized into 12 subcategories and then regrouped into the following 4 categories based on the similarity of the contents: donor personality and values, inability to fully understand the implications of donation, possibility of direct pressure on donor's decision-making process, and donor's environment and situation., Discussion: The autonomy-related elements were highly diverse, including obvious pressure upon the donor and their values as well as influences from health care professionals. Some elements had room for change, such as the informed consent procedure, while some elements were unchangeable. Other elements were changeable by intervention, but discussion is required about the appropriateness of the intervention itself. Further, a classification of clinical approach was suggested by the development of an analytical framework using 2 axes of "site where the element arises" and "room for change" based on the practical viewpoint of clinical circumstances., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Carbon and nitrogen stable isotope ratios (δ 13 C and δ 15 N) were determined in activated sludge, which was exposed to endogenous conditions for 36 days and contained a wide diversity of organisms across several trophic levels. The aim of this study was to elucidate the fluctuation of δ 13 C and δ 15 N through trophic transfer in the microbial consortia. The sludge was evaluated in view of sludge mass, bacterial community, higher trophic organisms, sludge δ 13 C and δ 15 N, and δ 15 N and δ 18 O of nitrate. The results show that the activated sludge became more enriched with 15 N as degradation proceeded. Eventually, the mixed liquor volatile suspended solid concentrations in the activated sludge decreased from 1610 to 710 mg/L and the δ 15 N of the sludge increased from 8.3‰ to 10.8‰. In contrast, the δ 13 C values of the sludge were stable. Microscope observations confirmed that consumers such as Rotifera, Tardigrada and Annelida (Aelosoma sp.) were present in the activated sludge for the entire operational period. The abundance of those organisms drastically changed during the operational periods, and the diversity in bacterial community also changed, resulting in community succession. Changes in biotic community, reduction in sludge mass, and increase in δ 15 N of the sludge occurred during the sludge degradation processes. This implies that the sludge degradation was partly caused by the trophic conversion of the sludge-derived nitrogen in the food web. The δ 15 N of the sludge can be used as an indicator of the sludge degradation through trophic transfer in wastewater treatment reactors. These findings provide new insights into understanding trophic transfer during microbial community succession and the effects of the feeding process on sludge degradation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and study aims  We report the effectiveness of a newly developed plastic stent for preventing bile leakage after endoscopic ultrasonography (EUS)-guided antegrade stenting. This treatment was performed on a 59-year-old woman with malignant obstructive jaundice caused by peritoneal metastasis. First, we attempted transpapillary drainage using short-type single-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography, but we could not achieve it. We then attempted EUS-guided antegrade stenting through the intrahepatic bile duct from the esophagojejunal anastomosis. We successfully inserted uncovered metallic stents for common bile duct and a newly plastic stent for hepaticojejunostomy from the antegrade approach. There were no adverse events after the treatment.

A rotational sponge (RS) reactor was proposed as an alternative sewage treatment process. Prior to the application of an RS reactor for sewage treatment, this study evaluated reactor performance with regard to organic removal, nitrification, and nitrogen removal and sought to optimize the rotational speed and hydraulic retention time (HRT) of the system. RS reactor obtained highest COD removal, nitrification, and nitrogen removal efficiencies of 91%, 97%, and 65%, respectively. For the optimization, response surface methodology (RSM) was employed and optimum conditions of rotational speed and HRT were 18 rounds per hour and 4.8 h, respectively. COD removal, nitrification, and nitrogen removal efficiencies at the optimum conditions were 85%, 85%, and 65%, respectively. Corresponding removal rates at optimum conditions were 1.6 kg-COD m -3 d -1 , 0.3 kg-NH 4 + -N m -3 d -1 , and 0.12 kg-N m -3 d -1 . Microbial community analysis revealed an abundance of nitrifying and denitrifying bacteria in the reactor, which contributed to nitrification and nitrogen removal., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

P2X 2 receptors are ligand-gated cation channels activated by extracellular ATP that modulate neural transmission in various neuronal systems. Although the function and distribution of P2X 2 receptors in the cochlea portion of the inner ear are well established, their physiological role in the vestibular portion is still not understood. Therefore, we investigated P2X 2 receptor localization in the peripheral vestibular portion, and assessed their physiological function in vivo using P2X 2 receptor knock out (P2X 2 -KO) mice. Histological analysis revealed that P2X 2 receptors were localized on the epithelial surface of supporting and transitional cells of the vestibular end organs. To examine vestibular function in P2X 2 -KO mice, we conducted behavioral tests and tested the vestibulo-ocular reflex (VOR) during sinusoidal rotations. P2X 2 -KO mice exhibited significant motor balance impairment in the balance beam test. VOR gain in P2X 2 -KO mice was significantly reduced, with no decrease in the optokinetic response. In conclusion, we showed that P2X 2 receptors are mainly localized in the supporting cells of the vestibular inner ear, and the loss of P2X 2 receptors causes mild vestibular dysfunction. Taken together, our findings suggest that the P2X 2 receptor plays a modulatory role in vestibular function., (Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.)

We investigated fibroblast growth factor 12 (FGF12) as a transcript enriched in the inner ear by searching published cDNA library databases. FGF12 is a fibroblast growth factor homologous factor, a subset of the FGF superfamily. To date, its localisation and function in the inner ear have not been determined. Here, we show that FGF12 mRNA is localised in spiral ganglion neurons (SGNs) and the vestibular ganglion. We also show that FGF12 protein is localised in SGNs, the vestibular ganglion, and nerve fibres extending beneath hair cells. Moreover, we investigated FGF12 function in auditory and vestibular systems using Fgf12-knockout (FGF12-KO) mice generated with CRISPR/Cas9 technology. Our results show that the inner ear morphology of FGF12-KO mice is not significantly different compared with wild-type mice. However, FGF12-KO mice exhibited an increased hearing threshold, as measured by the auditory brainstem response, as well as deficits in rotarod and balance beam performance tests. These results suggest that FGF12 is necessary for normal auditory and equilibrium function.

Membrane fouling in membrane bioreactors (MBR) remains a major issue and knowledge of microbes associated with biofilm formation might facilitate the control of this phenomenon, Thus, an anoxic/oxic membrane bioreactor (A/O-MBR) was operated under an extremely low organic loading rate (0.002 kg-COD·m -3 ·day -1 ) to induce membrane fouling and the major biofilm-forming bacteria were identified. After operation under extremely low organic loading condition, the reactor showed accumulation of total nitrogen and phosphorus along with biofilm development on the membrane surface. Thus, membrane fouling induced by microbial cell lysis was considered to have occurred. Although no major changes were observed in the microbial community structure of the activated sludge in the MBR before and after membrane fouling, uncultured bacteria were specifically increased in the biofilm. Therefore, bacteria belonging to candidate phyla including TM6, OD1 and Gammaproteobacteria could be important biofilm-forming bacteria.

The aim of this study was to propose a new pathophysiological hypothesis for involuntary eye oscillation in infantile nystagmus (IN): patients with IN exhibit impaired gaze fixation, horizontal smooth pursuit and optokinetic nystagmus (OKN) and use saccadic eye movements for these underlying impairments. In order to induce saccades, they make enough angle between gaze and target by precedent exponential slow eye movements. IN consists of the alternate appearance of the saccade and the slow eye movements. Unlike most previous theories, IN is therefore considered a necessary strategy allowing for better vision and not an obstacle to clear vision. In five patients with IN, eye movements were analyzed during the smooth pursuit test, saccadic eye movement test, OKN test and vestibulo-ocular reflex (VOR) test. Their gaze fixation, horizontal smooth pursuit, OKN and the last half of the slow phase of VOR were impaired. The lines obtained by connection of the end eye positions of fast phase of nystagmus coincided with the trajectories of targets. The findings indicate that patients followed the target by the fast but not the slow phase of nystagmus, which supports our hypothesis. By setting the direction of slow phase of nystagmus opposite to the direction of the OKN stimulation, enough angle can be effectively made between the gaze and target for the induction of saccade. This is the mechanism of reversed OKN response. In darkness and when eyes are closed, IN weakens because there is no visual target and neither the saccade for catching up the target or slow phase for induction of the saccade is needed.

The study of inner ear specific transcripts has revealed novel information about hereditary hearing loss and a mechanism of normal hearing. In this study, by analyzing a published cDNA library, we focused on Epiphycan (Epyc), a member of the small leucine-rich repeat proteoglycan family, whose transcript is enriched in the inner ear. Epyc mRNA was expressed abundantly and specifically in adult mice cochleae and was localized in supporting cells within the organ of Corti of both neonatal and adult mice. To examine the function of Epyc, we generated Epyc knockout (KO) mice using the CRISPR/Cas9 system. Epyc KO mice cochleae exhibited normal morphology. However, measurement of the auditory brain-stem response in Epyc KO mice revealed an elevated hearing threshold above 16 kHz frequency. This study suggests that Epyc is necessary for normal auditory function., (Copyright © 2017 Elsevier Inc. All rights reserved.)

When participants undergo eccentric rotation (ER), i.e., they are rotated while displaced from the axis of rotation, they undergo both rotational stimulation and linear acceleration, which induces both the angular vestibulo-ocular reflex (aVOR) and linear VOR (lVOR). During ER, the lVOR induced by tangential linear acceleration enhances the eye movement induced by aVOR. In this study, we attempted to measure aVOR and lVOR separately, while participants underwent ER while facing the ground in a dark room. We analyzed three-dimensional eye movements using a video-oculography system. The participants sat on the ER chair either directly above the center of rotation, or with their head out, head in, right ear out, or left ear out against the center of rotation. Under these conditions, the rotational axis of the eye was perpendicular to the ground for rotational stimulation (aVOR), and the axis was parallel to the ground for linear stimulation (lVOR). Thus, measured eye movements could be separated into these two components. At 0.1 and 0.3 Hz rotation, we observed aVOR but not lVOR. However, when the stimulation frequency was above 0.5 Hz, we observed both aVOR and lVOR. These data indicate that lVOR is activated when the stimulation frequency is above 0.5 Hz. We conclude that it is possible to separately analyze aVOR and lVOR, and to simultaneously assess the function of aVOR and lVOR by analyzing eye movements induced when participants undergo ER above 0.5 Hz while facing the ground.

Background: Brain imaging studies using magnetic resonance imaging (MRI) sometimes reveal incidental findings (IFs) that might be relevant to some of the health issues in research participants. Although professional communities have discussed how to manage these IFs, there is no global consensus on the concrete handling procedures including how to inform participants of IFs., Methods: First, this study reviewed previous studies for the number of IFs discovered in brain imaging studies using MEDLINE. Second, a multi-institutional study determined the number of IF discoveries and evaluated the method of informing participants at multiple institutions, which participated in a national brain science project in Japan., Results: Both the review and multi-institutional study showed that IFs with a high urgency level were discovered in 0-2.0% of participants, including healthy volunteers, and that the rate of IF discovery in general was higher in studies conducted in elderly population. Moreover, multi-institutional study suggested the criteria used to judge whether or not to inform participants of IFs may differ by institution., Conclusions: Our results suggest that in order to ensure informing the participants of high urgency IFs, physicians who are capable of interpreting brain images clinically should review all brain images, and the establishment of a support system is required for brain imaging studies at nonmedical institutions. Since the method of informing participants of IFs might affect their understanding and acceptance of IFs, which are related to managing risks of false "clean bill of health" or psychological impacts of informing IFs, further research focusing on communication of IFs is needed.

Ménière's disease is associated with hydrops of the inner ear endolymphatic space, and histopathologically, the cochlea and vestibule are usually involved. We used gadolinium-enhanced magnetic resonance imaging and measured cervical and ocular vestibular evoked myogenic potentials and the gain in the utricular induced linear vestibulo-ocular reflex to test the hypothesis that vestibular hydrops in Ménière's disease patients is associated with otolith organ dysfunction. We evaluated 21 patients diagnosed with unilateral definitive Ménière's disease using gadolinium magnetic resonance imaging to detect endolymphatic hydrops in the cochlea and vestibule. Cervical and ocular vestibular evoked myogenic potentials and the gain in utricular induced linear vestibulo-ocular reflex during eccentric rotation were measured to assess otolith organ function. For eccentric rotation, patients were rotated while displaced from the axis of rotation, while linear acceleration stimulated the utricle and induced the vestibulo-ocular reflex. Magnetic resonance imaging revealed vestibular hydrops in 14 of 20 patients (70%). Among the 14 patients, ten (71%) had abnormal cervical and three (21%) had abnormal ocular vestibular evoked myogenic potentials. Four patients (4/21, 19%) had abnormal linear vestibulo-ocular reflexes, three of whom also had abnormal ocular vestibular evoked myogenic potentials. Overall, 16 of 17 patients had normal linear vestibulo-ocular reflexes and normal ocular vestibular evoked myogenic potentials. Vestibular endolymphatic hydrops in Ménière's disease patients caused otolith organ dysfunction, mainly in the saccule. The number of Ménière's disease patients with abnormal ocular vestibular evoked myogenic potentials was low (19%), and they also had abnormal utricular induced linear vestibulo-ocular reflexes.

Cisplatin is a chemotherapeutic agent commonly used for the treatment of solid tumors, and its side-effects include vestibulotoxicity. Previous studies have reported cisplatin-induced vestibulotoxicity in various animal models, but no study has investigated in vivo mouse vestibular dysfunction after cisplatin. The aim of this study was to investigate cisplatin-induced vestibulotoxicity in C57BL/6J mice. Vestibular function was assessed by recording the vestibulo-ocular reflex (VOR). This was done during sinusoidal rotations in the horizontal plane at three frequencies (0.5, 1.0 and 2.5Hz). A high-resolution, high-frequency digital infra-red camera was used with eye-tracking algorithms. Cisplatin at 16mg/kg, but not 8mg/kg, decreased the VOR gain at 2.5Hz compared with the vehicle control. Following 16mg/kg cisplatin treatment, the animals showed no change in the optokinetic nystagmus response, suggesting that no major changes in visual or oculomotor functions had occurred. This mouse model may be useful for studying cisplatin-induced vestibulotoxicity and its treatment., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Cadmium (Cd) is a highly toxic and non-essential element for plants, whereas phytochelatins and glutathione are low-molecular-weight sulfur compounds that function as chelators and play important roles in detoxification. Cadmium exposure is known to induce the expression of sulfur-assimilating enzymes and sulfate uptake by roots. However, the molecular mechanism underlying Cd-induced changes remains largely unknown. Accordingly, we analyzed the effects of Cd treatment on the uptake and translocation of sulfate and accumulation of thiols in Arabidopsis thaliana Both wild type (WT) and null mutant (sel1-10 and sel1-18) plants of the sulfate transporter SULTR1;2 exhibited growth inhibition when treated with CdCl 2 However, the mutant plants exhibited a lower growth rate and lower Cd accumulation. Cadmium treatment also upregulated the transcription of SULTR1;2 and sulfate uptake activity in WT plants, but not in mutant plants. In addition, the sulfate, phytochelatin and total sulfur contents were preferentially accumulated in the shoots of both WT and mutant plants treated with CdCl 2 , and sulfur K-edge XANES spectra suggested that sulfate was the main compound responsible for the increased sulfur content in the shoots of CdCl 2 -treated plants. Our results demonstrate that Cd-induced sulfate uptake depends on SULTR1;2 activity, and that CdCl 2 treatment greatly shifts the distribution of sulfate to shoots, increases the sulfate concentration of xylem sap and upregulates the expression of SULTRs involved in root-to-shoot sulfate transport. Therefore, we conclude that root-to-shoot sulfate transport is stimulated by Cd and suggest that the uptake and translocation of sulfate in CdCl 2 -treated plants are enhanced by demand-driven regulatory networks., (© The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

When a participant is rotated while displaced from the axis of rotation (eccentric rotation, ER), both rotational stimulation and linear acceleration are applied to the participant. As linear acceleration stimulates the otolith, the vestibulo-ocular reflex (VOR) caused by the otolith (linear VOR; lVOR) would be induced during ER. Ten participants were rotated sinusoidally at a maximum angular velocity of 50°/s and at frequencies of 0.1, 0.3, 0.5, and 0.7Hz. The radius of rotation during ER was 90cm. The participants sat on a chair at three different positions: on the axis (center rotation, CR), at 90cm backward from the axis (nose-in ER, NI-ER) and at 90cm forward from the axis (nose-out ER, NO-ER). Their eye movements during rotation were recorded and analyzed three-dimensionally. The VOR gain during NI-ER was lower at 0.5 and 0.7Hz, and that during NO-ER was higher at 0.3, 0.5, and 0.7Hz than during CR. These results indicate that lVOR actually worked at 0.5 and 0.7Hz during ER and that the enhancement and decline of the VOR gain relative to the VOR gain during CR was seen in humans. Thus, we suggest that otolith function can be assessed via rotational testing of NI-ER and NO-ER., (Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.)

Background: Rosmarinic acid (RA) is a natural substance that may be useful for treating diabetes mellitus. The present study investigated the effects of RA on glucose homeostasis and insulin regulation in rats with streptozocin (STZ)-induced type 1 diabetes or high-fat diet (HFD)-induced type 2 diabetes., Methods: Glucose homeostasis was determined using oral glucose tolerance tests and postprandial glucose tests, and insulin activity was evaluated using insulin tolerance tests and the homeostatic model assessment for insulin resistance. Additionally, the protein expression levels of PEPCK and GLUT4 were determined using Western blot analysis., Results: RA administration exerted a marked hypoglycemic effect on STZ-induced diabetic rats and enhanced glucose utilization and insulin sensitivity in HFD-fed diabetic rats. These effects of RA were dose-dependent. Meanwhile, RA administration reversed the STZ- and HFD-induced increase in PEPCK expression in the liver and the STZ- and HFD-induced decrease in GLUT4 expression in skeletal muscle., Conclusion: RA reduces hyperglycemia and ameliorates insulin sensitivity by decreasing PEPCK expression and increasing GLUT4 expression.

In 2014, the Japanese government amended the laws concerning regenerative medicine. This reform aimed to contribute to the appropriate promotion of regenerative medicine and new drug discovery for intractable diseases using stem cells. It also helped restrict stem cell tourism, that is, provision of stem cell therapy of unclear efficacy and safety to tourists from abroad, and its relaxed regulations may even lead to the resolution of the drug lag problem. Stem cell medicine is positioned as a part of a national growth strategy that requires cooperation among the industry, government, healthcare field, and academia. It can be characterized as a "mesoscopic strategy," in that it aims to achieve high-level technological developments that would allow results from human-induced pluripotent stem cell and traditional stem cell research to contribute to regenerative medicine and drug development for intractable diseases, while attempting to strike a balance with commercialization and improved access of citizens to cutting-edge medical care.

Background: The mouse is the most commonly used animal model in biomedical research because of recent advances in molecular genetic techniques. Studies related to eye movement in mice are common in fields such as ophthalmology relating to vision, neuro-otology relating to the vestibulo-ocular reflex (VOR), neurology relating to the cerebellum's role in movement, and psychology relating to attention. Recording eye movements in mice, however, is technically difficult., Methods: We developed a new algorithm for analyzing the three-dimensional (3D) rotation vector of eye movement in mice using high-speed video-oculography (VOG). The algorithm made it possible to analyze the gain and phase of VOR using the eye's angular velocity around the axis of eye rotation., Results: When mice were rotated at 0.5 Hz and 2.5 Hz around the earth's vertical axis with their heads in a 30° nose-down position, the vertical components of their left eye movements were in phase with the horizontal components. The VOR gain was 0.42 at 0.5 Hz and 0.74 at 2.5 Hz, and the phase lead of the eye movement against the turntable was 16.1° at 0.5 Hz and 4.88° at 2.5 Hz., Conclusions: To the best of our knowledge, this is the first report of this algorithm being used to calculate a 3D rotation vector of eye movement in mice using high-speed VOG. We developed a technique for analyzing the 3D rotation vector of eye movements in mice with a high-speed infrared CCD camera. We concluded that the technique is suitable for analyzing eye movements in mice. We also include a C++ source code that can calculate the 3D rotation vectors of the eye position from two-dimensional coordinates of the pupil and the iris freckle in the image to this article.

Manuka honey is known as one of the premium honeys because of its unique property: a potent antibacterial activity. Leptosperin, methyl syringate 4-O-β-d-gentiobioside, has been specifically identified in manuka honey. Because leptosperin is relatively stable under warmer conditions, measuring leptosperin levels may be applied to authenticate manuka honey. In this study, an immunochromatographic separation and quantification of leptosperin techniques have been developed. The concentration of leptosperin measured by immunochromatography was significantly correlated with the concentration measured by high-performance liquid chromatography (HPLC) or enzyme-linked immunosorbent assay (ELISA). Because the immunochromatographic method is rapid and reliable, it could be applied to on-site quality control or inspection of honey samples by a beekeeper, a manufacturer, an inspector, a retailer, or a consumer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Conclusion This study investigated a novel instrument to diagnose benign paroxysmal positional vertigo (BPPV). Objective To develop a new scoring system of an interview for the diagnosis of BPPV. Methods The answers to questions on dizziness and/or vertigo (D/V) (571 patients) were analyzed and the questions for which the answers differed significantly between the patients with and without BPPV were selected. Results This study established an intensive questionnaire with a scoring system. It consists of the following questions: (1) Is rotary vertigo a characteristic of your D/V? (2) Is your D/V triggered when you roll your head over in a supine position? (3) Does your D/V disappear within 5 min? (4) Have you previously experienced hearing loss in one ear, or have you experienced hearing loss, tinnitus, or ear fullness with this D/V? One point each was given to an answer of 'yes' to questions (1) and (2). Two points were given to an answer of 'yes' to question (3). One point was subtracted upon an answer of 'yes' to question (4). When the total score was greater than two points, the patient was diagnosed with BPPV. The sensitivity of the diagnosis of BPPV by this scoring system was 81% and the specificity was 69%.

Transient receptor potential vanilloid (TRPV) 4 is a nonselective cation channel expressed in sensory neurons such as those in the dorsal root and trigeminal ganglia, kidney, and inner ear. TRPV4 is activated by mechanical stress, heat, low osmotic pressure, low pH, and phorbol derivatives such as 4α-phorbol 12,13-didecanoate (4α-PDD). We investigated the expression of TRPV4 in rat vestibular ganglion (VG) neurons. The TRPV4 gene was successfully amplified from VG neuron mRNA using reverse-transcription polymerase chain reaction. Furthermore, immunoblotting showed positive expression of TRPV4 protein in VG neurons. Immunohistochemistry indicated that TRPV4 was localized predominantly on the plasma membrane of VG neurons. Calcium (Ca2+) imaging of VG neurons showed that 4α-PDD and/or hypotonic stimuli caused an increase in intracellular Ca2+ concentration ([Ca2+]i) that was almost completely inhibited by ruthenium red, a selective antagonist of TRPV channels. Interestingly, a [Ca2+]i increase was evoked by both hypotonic stimuli and 4α-PDD in approximately 38% of VG neurons. These data indicate that TRPV4 is functionally expressed in VG neurons as an ion channel and that TRPV4 likely participates in VG neurons for vestibular neurotransmission as an osmoreceptor and/or mechanoreceptor., (© 2016 S. Karger AG, Basel.)

Agmatine, an endogenous ligand of imidazoline receptors, is reported to exhibit anti-hyperglycaemic and many other effects. It has been established that the imidazoline I3 receptor is involved in insulin secretion. The current study characterizes the role of the imidazoline I3 receptor in the protection of pancreatic islets. The activity effect of agmatine against on streptozotocin (STZ)-induced (5 mmol/L) rat β cell apoptosis was examined by using ApoTox-Glo triplex assay, live/dead cell double staining assay, flow cytometric analysis, and western blot. Imidazoline I3 receptors antagonist KU14R and the phospholipase C inhibitor named U73122 were treated in β cells to investigate the potential signalling pathways. The serum glucose and recovery of insulin secretion were measured in STZ-treated rats after continuously injected agmatine. The apoptosis in rat β cells was reduced by agmatine in a dose-dependent manner, cell viability was improved after treatment with agmatine and these effects were suppressed after the blockade of KU14R and U73122. Western blot analysis confirmed that agmatine could decrease caspase-3 expression and increase the p-BAD levels. In STZ-treated rats, injection of agmatine for 4 weeks may significantly lower the serum glucose and recovery of insulin secretion. This improvement of pancreatic islets induced by agmatine was deleted by KU14R in vivo. Agmatine can activate the imidazoline I3 receptor linked with the phospholipase C pathway to induce cell protection against apoptosis induced by a low dose of STZ. This finding provides new insight into the prevention of early stage pancreatic islet damage., (© 2015 Wiley Publishing Asia Pty Ltd.)

Conclusion: Contrast-enhanced magnetic resonance imaging (MRI) reveals variations in the endolymphatic morphology of the cystic lateral semicircular canal (CLSC) that correlate with inner ear function. This report is the first to suggest a relationship between the morphology and function of this common inner ear malformation in clinical cases., Objectives: This study investigated the radiological and functional findings of a common inner ear malformation using computed tomography (CT), gadolinium contrast-enhanced magnetic resonance imaging (MRI), caloric testing, and cervical and ocular vestibular evoked myogenic potential (VEMP) testing., Method: Four ears in three patients who were radiologically diagnosed with a CLSC and a normal cochlea on high-resolution CT and contrast-enhanced MRI were included. Semicircular canal and vestibular functions were analyzed using the caloric test and cervical and ocular VEMP testing., Results: Unilateral and bilateral cystic canals were found in two and one patients, respectively. In the first patient, the malformed vestibule and cystic space were separate on imaging, and perilymph filled the cystic space. The functional test results were normal. In the second patient, endolymph filled both cystic spaces, and the functional responses were poor. In the third patient, endolymph filled the cystic space, and the ear did not respond during functional testing.

Leptosperin, a novel glycoside of methyl syringate, is exclusively present in manuka honey derived from the Leptospermum species Leptospermum scoparium. Quantification of leptosperin might thus be applicable for authentication of honey. The concentration of leptosperin has high linearity with antibacterial activity. We established a monoclonal antibody to leptosperin and characterized the antibody in detail by a competitive enzyme-linked immunosorbent assay (ELISA), comparing the results with those of the high-performance liquid chromatography (HPLC) method for validation. The antigen in manuka honey was confirmed as leptosperin by HPLC fractionation with quantitation by an ELISA. Leptosperin contents of 50 honey samples were analyzed by an established ELISA, which can handle 20 samples (duplicate) on one 96-well plate. Significant coincidence with the chemical quantitation was observed. Immunochemical quantitation of leptosperin would be an economical and facile method for the possible authentication of manuka honey, allowing many honey samples to be processed and analyzed by an ELISA simultaneously.

Purpose: Autonomic dysfunction of the cardiovascular system in anorexia nervosa (AN) was reported not only in the rest position, but also in the standing position in some previous studies, which might contribute to cardiac complications such as lethal arrhythmia. However, there has not been sufficient literature in this issue. Therefore, we performed a head-up tilt test, and compared the changes after tilting in indices of autonomic function between AN patients and healthy subjects by heart rate variability (HRV) and blood pressure variability (BPV)., Methods: The subjects were 21 females with AN and 30 age-matched healthy women. A head-up tilt test was performed following the protocol recommended by the American Heart Association. Blood pressure and heart rate data were collected for 10 min before and after tilting. In the frequency analysis, the powers of low-frequency (LF) and high-frequency (HF) components were calculated by a fast Fourier transformation., Results: Regarding interactions between groups and head-up tilting, the head-up tilting-induced reduction of the HF component of HRV was significantly greater in the AN group. In addition, increases in the LF/HF of HRV and the LF component of BPV after head-up tilting were significantly smaller in the AN group., Conclusions: Regardless of the posture, changes in HF and LF/HF of HRV and LF of BPV in AN patients suggested the presence of autonomic insufficiency.

Manuka honey, obtained from Leptospermum scoparium flowers in New Zealand, has strong antibacterial properties. In this study, plausible authentication of the manuka honey was inspected by measuring leptosperin, methyl syringate 4-O-β-D-gentiobiose, along with methyl syringate. Despite a gradual decrease in methyl syringate content over 30 days at 50 °C, even at moderate 37 °C, leptosperin remained stable. A considerable correlation between nonperoxide antibacterial activity and leptosperin content was observed in 20 certified manuka honey samples. Leptosperin and methyl syringate in manuka honey and related products were analyzed using HPLC connected with mass spectrometry. One noncertified brand displayed significant variations in the leptosperin and methyl syringate contents between two samples obtained from different regions. Therefore, certification is clearly required to protect consumers from disguised and/or low-quality honey. Because leptosperin is stable during storage and specific to manuka honey, its measurement may be applicable for manuka honey authentication.

The 5-hydroxytryptamine type 3 (5-HT3) receptor is a ligand-gated ion channel and a member of the Cys-loop family of receptors. Previous studies have shown 5-HT3 receptor expression in various neural cells of the central and peripheral nervous systems. Although the function and distribution of the 5-HT3 receptor has been well established, its role in the inner ear is still poorly understood. Moreover, no study has yet determined its localization and function in the peripheral vestibular nervous system. In the present study, we reveal mRNA expression of both 5-HT3A and 5-HT3B receptor subunits in the mouse vestibular ganglion (VG) by RT-PCR and in situ hybridization (ISH). We also show by ISH that 5-HT3 receptor mRNA is only expressed in the VG (superior and inferior division) in the peripheral vestibular nervous system. Moreover, we performed Ca(2+) imaging to determine whether functional 5-HT3 receptors are present in the mouse VG, using a selective 5-HT3 receptor agonist, SR57227A. In wild mice, 32% of VG neurons responded to the agonist, whereas there was no response in 5-HT3A receptor knockout mice. These results indicate that VG cells express functional 5-HT3 receptor channels and might play a modulatory role in the peripheral vestibular nervous system., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: Anorexia nervosa (AN) patients often experience gastrointestinal complications caused by their malnutrition. We hypothesized that intestinal integrity is disturbed in AN. Therefore, the objective of the present study was to investigate serum diamine oxidase (DAO) activity, which is considered to be a clinical indicator of the integrity of the intestinal mucosa, in AN patients., Method: Thirty-six AN female patients including 21 AN restricting type (AN-R) and 15 AN binge-eating/purging type (AN-BP) were compared with twenty healthy women on serum DAO activity using immunoassay., Results: DAO levels in AN-R patients were significantly lower than in AN-BP patients and healthy controls., Discussion: DAO levels were decreased in AN-R patients. This finding suggests the presence of intestinal structural disturbance as one of the physical complications of malnutrition in AN-R patients., (Copyright © 2013 Wiley Periodicals, Inc.)

We have determined that a biological molecule can be physically immobilized on a polymer containing an azobenzene (azopolymer) using irradiating light. We immobilized antibodies and antigens on the surface of an azopolymer coated glass slide (antibody array) to establish "on-chip ELISAs". The assays used the flat-surface of a glass slide and could be applied to both sandwich and competitive ELISAs. The sensitivity and accuracy of the on-chip ELISA were similar to a conventional ELISA using a polystyrene plate. Using the assay system, we proved that representative oxidative-biomarkers could be simultaneously measured from uL of urine. That should realize low-cost study on animal or human, and accelerate development of health-promoting foods. So, this new concept antibody array has promising applications in proteomic studies, and could be used to examine biomarkers to investigate health-promoting food.

Background/aims: We investigated the efficacy of endoscope guided transabdominal ultrasonography (EGTUS) for the evaluating the depth of colorectal cancer invasion., Methodology: The subjects were 52 patients with colon cancer and 30 patients with rectal cancer who underwent transabdominal US and curative surgery. During endoscopy, we applied transabdominal US by filling the area around the tumor with de-gassed water. The accuracy of depth invasion assessment using EGTUS was compared with that using endoscopic, computed tomography (CT), surgical or histological findings., Results: The tumor detection rate was 75.6% (62/82), 88.5% (46/52) for colon cancer and 53.3% (16/30) for rectal cancer. The diagnostic accuracies of EGTUS, endoscopic, CT and surgical findings were 87.1% (54/62), 73.2% (60/82), 66.7% (46/69), 65.9% (54/82), respectively. The diagnostic accuracy of EGTUS was 100% (2/2), 66.7% (4/6), and 90.0% (44/49) for T1, T2 and T3 cancer, respectively., Conclusion: The results suggest that EGTUS is useful for evaluating preoperative T staging of colorectal cancer.

Both TRPV1 and TRPA1 are non-selective cation channels. They are co-expressed, and interact in sensory neurons such as dorsal root ganglia (DRG) and trigeminal ganglia (TG), and are involved in nociception, being activated by nociceptive stimuli. Immunohistological localization of TRPV1 in vestibular ganglion (VG) neurons has been reported. Although TRPA1 is co-expressed with TRPV1 in DRG and TG neurons, it is unclear whether TRPA1 channels are expressed in VG neurons. Moreover, it is unknown whether TRPV1 and TRPA1 channels are functional in VG neurons. We investigated the expression of TRPV1 and TRPA1 in rat VG neurons by RT-PCR, in situ hybridization, immunohistochemistry, and Ca(2+) imaging experiments. Both TRPV1 and TRPA1 RT-PCR products were amplified from the mRNA of rat VG neurons. In situ hybridization experiments showed TRPV1 and TRPA1 mRNA expression in the majority of VG neurons. Immunohistochemistry experiments confirmed TRPV1 protein expression. In Ca(2+) imaging experiments, capsaicin, a TRPV1 agonist, induced a significant increase in intracellular calcium ion concentration ([Ca(2+)]i) in rat primary cultured VG neurons, which was almost completely blocked by capsazepine, a TRPV1-specific antagonist. Cinnamaldehyde, a TRPA1 agonist, also caused an increase in [Ca(2+)]i, which was completely inhibited by HC030031, a TRPA1-specific antagonist. Moreover, in some VG neurons, a [Ca(2+)]i increase was evoked by both capsaicin and cinnamaldehyde in the same neuron. In summary, our histological and physiological studies reveal that TRPV1 and TRPA1 are expressed in VG neurons. It is suggested that TRPV1 and TRPA1 in VG neurons might participate in vestibular function and/or dysfunction such as vertigo., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Conclusion: Endolymphatic hydrops could be a reversible inner ear pathological condition. After sac surgery, hydrops was reduced and symptoms went into remission in some cases, although vertigo suppression was not always a result of the reduced hydrops., Objective: To examine the changes in endolymphatic hydrops detected by gadolinium (Gd) contrast-enhanced magnetic resonance imaging (MRI) before and 6 months after endolymphatic sac surgery in patients with unilateral Ménière's disease., Methods: Fluid-attenuated inversion recovery MRI was obtained 4 h after intravenous administration or 24 h after intratympanic administration of Gd contrast medium. An enlarged negative stain corresponding to the cochlear duct and endolymphatic space of the vestibule was assessed as hydrops., Results: Of seven patients with hydrops confirmed by MRI before surgery, both cochlear and vestibular hydrops became negative in two, cochlear hydrops became negative in one, both hydrops were present, but reduced, in one, and there was no change in three patients. The number of vertigo spells was reduced in all cases at 6-12 months after surgery. As for the three cases of negative hydrops, vertigo was completely suppressed. In two cases in which hearing level improved, hydrops became negative after surgery.

Objective: Gadolinium (Gd) contrast-enhanced MRI has recently been introduced to clinical practice to detect endolymphatic hydrops. However, since the image depends on the hardware, pulse sequence or the way of Gd administration, the protocol and the evaluating criteria for hydrops on MRI have not yet been standardized. In this study, we assessed the usefulness of the hydrops detection by MRI following the intratympanic or intravenous Gd administration methods, and compared these findings with the electrocochleography and glycerol test., Methods: MRI was taken in 27 patients with Meniere's disease or delayed endolymphatic hydrops. All patients had frequent episodes of vertigo attacks which were clinically considered as of unilateral ear origin. Two types of Gd administration were used; injection into the tympanic cavity in 17 patients or intravenous injection in 10 patients. Axial 2D-FLAIR images were obtained with a 3.0T MRI unit, 24 and 4 h after intratympanic or intravenous administration, respectively. The endolymphatic space was detected as a low signal intensity area, while the surrounding perilymphatic space showed high intensity with Gd contrast. Those cases in which low signal areas corresponding to the cochlear duct could be clearly noticed, were classified as cochlear hydrops. When the greater part of the vestibule was occupied by a low signal area in more than half of the images, it was classified as vestibular hydrops., Results: Endolymphatic hydrops was detected in 88% (15/17 cases) by the intratympanic Gd administration method, and 90% (9/10) by the intravenous method. In the contralateral ears, 20% (2/10) showed hydrops, detected by the intravenous method. ECochG and the glycerol test were difficult when the hearing of the patient was severely impaired. Positive results of EcochG and the glycerol test were obtained only in 15 and 6 cases, respectively. However, as far as the waves could be obtained, ECochG showed a high detection rate of 88% (15/17) in the affected ear. In those cases in which both MRI and EcochG could be obtained, including both ears, the results were matched in 78% (21/27ears)., Conclusion: For the qualitative detection of hydrops, intratympanic and intravenous Gd administration methods were equivalent. Inner ear Gd contrast-enhanced MRI had higher efficacy in the detection of hydrops than the conventional tests.

Conclusion: Because nystagmus induced by ampullopetal inhibition of the posterior semicircular canal (PSCC) rotates around the axis perpendicular to the plane of the anterior semicircular canal (ASCC) of the other side, when free-floating debris is initially located at the distal portion of the PSCC, a patient showing positional nystagmus appears to have the ASCC type of benign paroxysmal positional nystagmus. We name this 'pseudo-anterior canalolithiasis'., Objective: We report on pseudo-anterior canalolithiasis originating in the PSCC and discuss the differential findings between pseudo-anterior and true anterior canalolithiasis by means of three-dimensional (3D) analysis of the positional nystagmus., Methods: We performed 3D analysis of the positional nystagmus in a patient with true anterior canalolithiasis and in another patient with pseudo-anterior canalolithiasis., Results: In the patient with true anterior canalolithiasis, the direction of positional nystagmus during reverse Epley maneuver was constant and its axis was perpendicular to the plane of the right ASCC three-dimensionally. In contrast, in the patient with pseudo-anterior canalolithiasis, the first positional nystagmus of which the axis was perpendicular to the plane of the left ASCC became a second positional nystagmus of which the axis was perpendicular to the plane of the right PSCC during the reverse Epley maneuver.

Conclusions: Because the basic strategies to stop walking are stored as motor programs, visual stimulation may have little influence on body deviation during gait termination and its time course. Walking velocity, however, demonstrated dynamic flexible changes, which may subserve the stable process of gait termination under variable circumstantial changes such as optic flow., Objective: The aim of this study was to examine the effect of repeated optic flow on body deviation and walking velocity during gait termination, which may be more complicated than continuous standing or walking., Methods: Twenty-three healthy subjects were instructed to start walking upon an acoustic cue and to stop walking when the scenery changed in a virtual reality environment. Subjects underwent eight control trials without optic flow and three sets of optic flow conditions including four trials each of optic horizontal and rotational movement randomly., Results: Repeated optic flow caused no significant change of body deviation or the time course of the gait termination process in comparison with that in the control. The walking velocity at the start of the termination process showed short-term flexibility that denoted a gradual increase over the trial for within-set and long-term flexibility that denoted a gradual decrease for between-set.

Gomishi is the dried fruit of Schisandra chinensis Baillon (Fructus Schisandrae chinensis, FSC) and has been used in Japanese Kampo medicine to treat inflammatory and liver diseases. However, it is unclear which constituent of FSC is primarily responsible for its pharmacological effects. FSC was extracted with methanol, fractionated by hydrophobicity, and further purified. We measured the effects of each fraction or constituent thereof on the induction of the inflammatory mediator nitric oxide (NO), which was induced by interleukin 1β in primary cultured rat hepatocytes. The hydrophobic fraction markedly suppressed NO induction and reduced the expression of inducible nitric oxide syntheses (iNOS) in interleukin 1β-treated hepatocytes. Gomisin N and γ-schizandrin, two major constituents of the hydrophobic fraction, significantly reduced NO production and the levels of the iNOS protein, mRNA, and antisense transcript. Gomisin N and γ-schizandrin also decreased the transcription of interleukin 1β and inflammatory chemokines. The overexpression of the p65 subunit of nuclear factor κB or CCAAT/enhancer-binding protein β increased the promoter activity of the iNOS gene in the firefly luciferase assay, whereas gomisin N decreased the promoter activity. The anti-inflammatory activity of FSC and its constituents were analysed, and we demonstrated that gomisin N and γ-schizandrin are involved in the hepatoprotective effect of the FSC extract, which has therapeutic potential for liver disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Extract of Lentinula edodes mycelia (LEM) is currently utilized as an oral biological response modifier (BRM) medicine for cancer patients. However, its effectiveness for breast cancer patients with postoperative adjuvant hormone therapy has not yet been scientifically verified. In this study, we investigated the influence of LEM on the quality of life (QOL) and immune response in breast cancer patients undergoing postoperative adjuvant hormone therapy. Twenty patients were studied in total. They received only hormone therapy in the first 4 weeks followed by hormone therapy and LEM during the next 8 weeks. Laboratory tests, QOL score and peripheral blood cytokine production levels were evaluated during the study period. No changes in QOL or cytokines were noted after the first 4 weeks. In contrast, during the following combined therapy period, improvements were noted in QOL and cytokine levels. Although a future large-scale investigation is necessary to confirm these results, these data suggest that the concomitant use of LEM with postoperative adjuvant hormone therapy improves the QOL and immune function of patients.

To understand the rate-limiting process of oral drug absorption, not only total bioavailability (F) but also intestinal (F(a) · F(g)) and hepatic (F(h)) availability after oral administration should be evaluated. Usually, F(a) · F(g) of drug is calculated from pharmacokinetic parameters after intravenous and oral administration. This approach is influenced markedly by the estimated value of F(h), which varies with the hepatic blood flow used in the calculations. In this study, portal vein-cannulated rats were used to calculate the F(a) · F(g) of drugs from a single oral dosing experiment without data from intravenous injection. Portal vein-cannulated rats were prepared by a new operative method that enables stable portal vein blood flow. This surgery had no effects on hepatic blood flow and metabolic activity. Our method for calculating F(a) · F(g) was validated by determining both portal and systemic plasma concentration profiles of various drugs possessing different pharmacokinetic properties after oral administration to the portal vein-cannulated rats. Simulation of portal and systemic plasma concentrations by physiologically based pharmacokinetic modeling indicated that the balance of the absorption rate constant (k(a)) and elimination rate constant (k(e)) resulted in different patterns in portal and systemic plasma concentration-time profiles. This study is expected to provide a new experimental animal model that enables identification of the factors that limit oral bioavailability and to provide pharmacokinetic information on the oral absorption process of drugs during drug discovery.

On 11 March 2011, Japan experienced a major disaster brought about by a 9.0-magnitude earthquake and a massive tsunami that followed. This disaster caused extensive damage to the Fukushima Daiichi nuclear power plant with the release of a large amount of radiation, leading to a crisis level 7 on the International Atomic Energy Agency scale. In this report, we discuss the obligations of physicians to provide care during the initial weeks after the disaster. We appeal to the obligation of general beneficence and argue that physicians should go to disaster zones only if there is no significant risk, cost or burden associated with doing so. We conclude that physicians were not obligated to go to Fukushima given the high risk of radiation exposure and physical and psychological harm. However, we must acknowledge that there were serious epistemic difficulties in accurately assessing the risks or benefits of travelling to Fukushima at the time. The discussion that follows is highly pertinent to all countries that rely on nuclear energy.

Objectives: The aim of the present study was to elucidate the time course and frequency patterns of transient low-tone air-bone gaps (ABGs) after canal plugging for intractable BPPV., Methods: We investigated eight patients with intractable BPPV who underwent canal plugging. Four were cases with posterior type (pBPPV) and the other four were those with horizontal type (hBPPV). Pure-tone audiometries (PTAs) were performed before and 7 days, 1 month and 6 months after surgery. ABGs (+) were defined as the three-tone-average ≥20dB formulated by (a+b+c)/3, where a, b, and c are ABGs at 0.25, 0.5, and 1kHz, respectively., Results: The ratio of the number of patients with ABGs (+) at the post-operative 7th day and 1st month was 100.0% (8/8). The ratio at the post-operative 6th month was 0.0% (0/8). There were no significant differences in the time course or frequency patterns of the ABGs between pBPPV and hBPPV., Conclusions: We clearly demonstrated eight cases with intractable BPPV showing transient low-tone ABGs during convalescence immediately after canal plugging. During that period, patients also complained of motion-evoked dizziness. All these findings suggest that, during such a convalescence period, the plugged area might not be fixed yet and could still induce the dizziness and low-tone ABGs, as enlarged vestibular aqueduct syndrome and superior semicircular canal deficiency syndrome exhibit low-tone ABGs due to the third mobile inner ear window. More than one month after surgery, both the ABGs and dizziness could disappear according to fixation of the plugged area., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

In the present study, to elucidate the role of vestibular ganglion (VG) after the unilateral labyrinthine damage, we examined quantitative changes in mRNA expression of beta-adrenergic receptors (bARs) and AMP-activated protein kinase alpha catalytic subunits (aAMPKs) in VG after unilateral labyrinthectomy (UL) in rats. Using the real-time PCR method, beta2 AR mRNA expression in bilateral VG and AMPK alpha2 mRNA expression in the ipsilateral VG were significantly up-regulated with the maximum increase at the postoperative 7 day and 1 day, respectively. The up-regulation of beta2 AR in bilateral VG was long-lasting until 28 days after UL and that of AMPK alpha2 in the ipsilateral VG was just transient within 7 days after UL. These mRNA changes were supported by immunohistochemical data. According to previous reports, both of bARs and aAMPKs could regulate mitochondrial uncoupling protein (UCP) mRNA expression in several kinds of tissues and therefore might have thermogenic neurotransmission and antioxidant neuroprotective roles in neuronal tissues. UL requires not only long-lasting response of VG for central vestibular neuro-plasticity around 2-4 weeks but rapid response of VG against apoptosis of peripheral vestibular epithelia-neuronal synapses. The present findings suggest that beta2 AR in bilateral VG and AMPK alpha2 in the ipsilateral VG might play important signaling roles after the unilateral labyrinthine damage., (Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Fibroblast growth factor (FGF) 23, a circulating 26-kDa peptide produced by osteogenic cells, is a novel phosphaturic factor. In our previous study, binge-eating/purging type anorexia nervosa (AN-BP) patients had elevated plasma intact FGF23 (iFGF23) levels, while restricting type (AN-R) patients had plasma iFGF23 levels similar to healthy controls. Although bulimia nervosa (BN) patients as well as some patients with AN-BP regularly engage in binge eating, there have been no studies regarding plasma iFGF23 levels in BN patients. Therefore, this study was performed to determine plasma iFGF23 concentrations in BN patients and healthy controls. The study population consisted of 13 female BN patients and 11 healthy female controls. Blood samples were collected from all subjects after overnight fasting. Plasma iFGF23 was measured using an ELISA kit in a cross-sectional manner. The two-tailed Mann-Whitney U-test was used to assess differences between BN patients and healthy controls. In addition, BN patients were divided into two groups based on questionnaire-reported binge eating frequency immediately prior to participation in this study: high frequency of binge eating (once a week or more; HF group; n = 8) and low frequency of binge eating (less than once a week; LF group; n = 5). Two-tailed Mann-Whitney U-test with Bonferroni's correction was performed after the Kruskal-Wallis test to assess differences between HF group, LF group, and healthy controls. Median (quartiles) plasma iFGF23 levels were greater in BN patients (35.5 [14.8-65.0] pg/ml) than in controls (3.8 [not detected-5.3] pg/ml; p = 0.002). In addition, median (quartiles) plasma iFGF23 levels were greater in the HF group (62.3 [44.4-73.4] pg/ml) than in controls (p < 0.001) and in the LF group (12.9 [not detected-30.3] pg/ml; p = 0.011), while there were no differences between the LF group and controls (p = 0.441). This is the first study to show that BN patients have elevated plasma iFGF23 levels. Moreover, this study showed that BN patients with a high frequency of binge eating have elevated plasma iFGF23 levels, while iFGF23 levels are similar to healthy controls in those with a low frequency of binge eating. Plasma iFGF23 level may be a suitable indicator of binge eating in BN patients.

A-52-year-old man presented to our hospital with nephrotic syndrome caused by membranous nephropathy. Early gastric adenocarcinoma confined to the submucosa, and well-differentiated adenocarcinoma in a sigmoid adenoma were detected by screening endoscopy. Two years after complete endoscopic resection of these tumors, the estimated 24-h urinary protein excretion decreased, and serum total protein and albumin returned to their normal levels although he had no immunosuppressive therapy. Thus, this case was considered to be a case of secondary membranous nephropathy to cancer, although whether the pathogenesis was due to circulating or in situ immune complexes is unknown. The suspected antigen component of this immune complex can include carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). In our patient, however, serum CEA and CA19-9 were within normal values during the clinical course, and detected cancers were early stage and very small. Recently, the existence of anti-mucin 1 (MUC1) antibodies before carcinogenesis and their usefulness for early detection of cancer were reported. We tried to stain tumors and glomeruli for MUC1 but, although we had positive findings in both tumors but not in glomeruli, the role of MUC1 in the pathogenesis of membranous nephropathy is unknown. To the best of our knowledge, paraneoplastic nephrosis caused by double early cancers expressing MUC1 in the gastrointestinal tract has not been previously reported.

Objective/method: Patients with anorexia nervosa (AN) display various physical complications. One such problem is thrombocytopenia. However, no studies have investigated links between AN and thrombopoietin (TPO), which is the primary regulator of megakaryocyte and platelet production produced mainly in the liver, although TPO has been recently reported to play a role in thrombocytopenia in liver diseases. We therefore clarified temporal relationships between platelet counts and TPO level in a woman with AN and severe liver dysfunction in whom platelet count decreased to 53 x 10⁹/L., Results: While international normalized ratio (INR) was low, serum TPO level was relatively low despite low platelet counts. After INR and liver enzymes improved in conjunction with improved nutritional status, a rapid increase in TPO was observed and platelet count began to rise., Discussion: These findings thus suggest that decreased TPO production accompanying liver dysfunction may be related to thrombocytopenia besides myelosuppression in AN with malnutrition., (© 2009 by Wiley Periodicals, Inc.)

Calculations of the hyperpolarizability are typically much more difficult to converge with basis set size than the linear polarizability. In order to understand these convergence issues and hence obtain accurate ab initio values, we compare calculations of the static hyperpolarizability of the gas-phase chloroform molecule (CHCl(3)) using three different kinds of basis sets: Gaussian-type orbitals, numerical basis sets, and real-space grids. Although all of these methods can yield similar results, surprisingly large, diffuse basis sets are needed to achieve convergence to comparable values. These results are interpreted in terms of local polarizability and hyperpolarizability densities. We find that the hyperpolarizability is very sensitive to the molecular structure, and we also assess the significance of vibrational contributions and frequency dispersion.

Lymphoepithelial thymoma was diagnosed in a 14-year-old Samoyed dog with clinical symptoms of myasthenia gravis at 6 months of age. At necropsy, dark red-colored mass with many nodular protuberances was found in the anterior mediastinal area. Histologically, the mass consisted of solid proliferation of neoplastic cells with spindle nuclei and cytoplasm and a few lymphocytes, which is separated by an abundant fibrous and adipose tissue. Immunohistochemically, spindle cells were positive for cytokeratin, and infiltrating lymphocytes were positive for CD3. On the basis of these findings, this tumor was diagnosed as lymphoepithelial thymoma, which is morphologically similar to type A thymoma in humans.

It has been demonstrated that HMG-CoA reductase inhibitors effectively decrease low density lipoprotein and total cholesterol levels, and presently, HMG-CoA reductase inhibitors are most widely used in hyperlipidemia treatment. On the other hand, it has been demonstrated that fibrate agents decrease triglyceride levels more effectively compared to HMG-CoA reductase inhibitors. A cost-effectiveness study comparing fenofibrate, a fibrate agent, and atorvastatin was therefore conducted in hypertriglyceridemia patients. Referring to an analytical method published in the UK, the percentage of patients received fenofibrate and atorvastatin treatments at each dose level was estimated from prescription records at the medical institutions investigated. Changes in the total cholesterol and triglyceride values after the drug administration were investigated examining published reports. Based on the said data, the treatment effectiveness was measured by the percentage of patients who achieved the target lipid levels. The treatment costs were estimated based on the number of patients investigated and reimbursement prices of the drugs. The incremental cost-effectiveness ratio of fenofibrate in decreasing triglyceride levels was dominant over atorvastatin. The incremental cost-effectiveness ratio of atorvastatin in decreasing low density lipoprotein cholesterol levels was JPY 69911. This provides a model for choosing drug treatments that reflects clinical practices at medical institutions by substituting figures for individual cases.

Background: Although hematopoietic stem cell transplantation (HSCT) can potentially cure some hematological malignancies, patients who undergo HSCT experience psychological distress. However, there have been few studies on the short-term influence of HSCT on psychological distress., Methods: The subjects were 71 patients with hematological malignancies who underwent HSCT: 33 with acute leukemia, 19 with chronic leukemia, nine with myelodysplastic syndrome, and 10 with malignant lymphoma. Psychological distress was assessed prior to HSCT and on the seventh day after HSCT using the Profile of Mood States (POMS)., Results: With regard to Anger-Hostility, the interaction of time (pre- and post-HSCT) and group (the four groups) was significant in male patients (p = 0.04), but not in female patients. With regard to the other subscales of POMS, there was no significant main effect or interaction in male or female patients., Conclusion: It may be important to provide psychological support to patients throughout the period of HSCT in consideration of differences in mood changes associated with the underlying disease and patient sex in order to provide efficient psychiatric intervention for both better psychiatric and survival outcomes.

Background: Panic disorder is one of the anxiety disorders, and anxiety is associated with some locomotor activity changes such as "restlessness". However, there have been few studies on locomotor activity in panic disorder using actigraphy, although many studies on other psychiatric disorders have been reported using actigraphy. Therefore, the aim of the present study was to investigate the relationship between panic disorder and locomotor activity pattern using a wrist-worn activity monitor. In addition, an ecological momentary assessment technique was used to record panic attacks in natural settings., Methods: Sixteen patients with panic disorder were asked to wear a watch-type computer as an electronic diary for recording panic attacks for two weeks. In addition, locomotor activity was measured and recorded continuously in an accelerometer equipped in the watch-type computer. Locomotor activity data were analyzed using double cosinor analysis to calculate mesor and the amplitude and acrophase of each of the circadian rhythm and 12-hour harmonic component. Correlations between panic disorder symptoms and locomotor activity were investigated., Results: There were significant positive correlations between the frequency of panic attacks and mesor calculated from double cosinor analysis of locomotor activity (r = 0.55) and between HAM-A scores and mesor calculated from double cosinor analysis of locomotor activity (r = 0.62)., Conclusion: Panic disorder patients with more panic attacks and more anxiety have greater objectively assessed locomotor activity, which may reflect the "restlessness" of anxiety disorders.

Objective: Anorexia nervosa (AN) is considered to have a significant risk for sudden death because of cardiac complications, and abnormalities of the autonomic nervous system might be a cause of cardiac dysfunction. The aim of this study was to investigate autonomic nervous system function in AN patients by analyzing heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS)., Methods: The subjects were 32 AN patients without other psychiatric comorbidities and 37 healthy controls. Beat-to-beat R-R interval and systolic blood pressure recorded in the supine position were analyzed using power spectral analysis and cross-spectrum analysis to quantify the frequency domain properties of HRV, BPV, and BRS. In addition, detrended fluctuation analysis was used to quantify the fractal correlation properties from the scaling exponent alpha1 of HRV., Results: High frequency power and total power of HRV and BRS were significantly higher in AN patients and low frequency power of BPV, low frequency/High frequency ratio of HRV, and the scaling exponent alpha1 of HRV were significantly lower in AN patients, compared with controls., Conclusions: These findings suggest that AN patients have reduced cardiovascular sympathetic nervous responsiveness, increased parasympathetic nervous responsiveness, and increased complexity of the interbeat interval time series compared with healthy controls. Regarding the relationship to prognosis of AN, the study showed conflicting results, and further prospective studies are needed to determine if these results are related to high mortality in AN patients.