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A π-electron donor incorporating pyran-4-ylidene moiety, 2-(pyran-4-ylidene)-1,3-dithiole (PDT, 1a), and its derivatives (1b–e) have been synthesized. Cyclic voltammetry revealed that the derivatives of 1exhibited two pairs of redox waves. Comparison of the first redox potentials (E1) indicated that the donating ability of PDT (E1= −0.16 V vs. Fc/Fc+, in benzonitrile) is stronger than that of TTF (E1= −0.09 V), but is weaker than the sulfur analog TPDT (E1= −0.19 V). X-ray structure analyses of radical cation salts based on the ethylendithio derivative (1d)2X (X = ClO4, ReO4, and GaCl4) revealed that the donors form two-dimensional conducting sheets, in which the donors adopt the so-called β-type packing with a uniform head-to-tail stacking. Calculation of the overlap integrals of the HOMOs suggest that (1d)2X has a small intrastack overlap compared to the TTF-type conductors because of a head-to-tail stacking of the unsymmetrical π-electron framework. A tight-binding band calculation suggested that all the salts have quasi-one-dimensional Fermi surfaces. They exhibited relatively high conductivity of σrt= 0.79–20 S cm−1on a single crystal and showed weak but metal-like temperature dependence of resistivity.Organic conductors based on the ethylenedithio derivative pyran-4-ylidene moiety, 2-(pyran-4-ylidene)-1,3-dithiole (1d) have been developed. X-ray structure analyses and band calculations of (1d)2X (X = ClO4, ReO4, and GaCl4) revealed that the donors adopt the so-called β-type packing with a head-to-tail stacking with quasi-one-dimensional Fermi surfaces. They exhibited weak but metal-like temperature dependence of resistivity down to low temperatures.

ABSTRACTIntroductionHypertension is highly prevalent in patients with end-stage kidney disease on hemodialysis and is often not well controlled. Blood pressure (BP) levels before and after hemodialysis have a U-shaped relationship with cardiovascular and all-cause mortality. Although antihypertensive drugs are recommended for patients in whom BP cannot be controlled appropriately by non-pharmacological interventions, large-scale randomized controlled clinical trials are lacking.Areas coveredThe authors review the pharmacotherapy used in hypertensive patients on dialysis, primarily focusing on reports published since 2000. An electronic search of MEDLINE was conducted using relevant key search terms, including ‘hypertension’, ‘pharmacotherapy’, ‘dialysis’, ‘kidney disease’, and ‘antihypertensive drug’. Systematic and narrative reviews and original investigations were retrieved in our research.Expert opinionWhen a drug is administered to patients on dialysis, the comorbidities and characteristics of each drug, including its dialyzability, should be considered. Pharmacological lowering of BP in hypertensive patients on hemodialysis is associated with improvements in mortality. β-blockers should be considered first-line agents and calcium channel blockers as second-line therapy. Renin-angiotensin-aldosterone system inhibitors have not shown superiority to other antihypertensive drugs for patients on hemodialysis.

Chronic inflammation is accompanied by recurring cycles of tissue destruction and repair and is associated with an increased risk of cancer1–3. However, how such cycles affect the clonal composition of tissues, particularly in terms of cancer development, remains unknown. Here we show that in patients with ulcerative colitis, the inflamed intestine undergoes widespread remodelling by pervasive clones, many of which are positively selected by acquiring mutations that commonly involve the NFKBIZ, TRAF3IP2, ZC3H12A, PIGRand HNRNPFgenes and are implicated in the downregulation of IL-17 and other pro-inflammatory signals. Mutational profiles vary substantially between colitis-associated cancer and non-dysplastic tissues in ulcerative colitis, which indicates that there are distinct mechanisms of positive selection in both tissues. In particular, mutations in NFKBIZare highly prevalent in the epithelium of patients with ulcerative colitis but rarely found in both sporadic and colitis-associated cancer, indicating that NFKBIZ-mutant cells are selected against during colorectal carcinogenesis. In further support of this negative selection, we found that tumour formation was significantly attenuated in Nfkbiz-mutant mice and cell competition was compromised by disruption of NFKBIZin human colorectal cancer cells. Our results highlight common and discrete mechanisms of clonal selection in inflammatory tissues, which reveal unexpected cancer vulnerabilities that could potentially be exploited for therapeutics in colorectal cancer.

Purpose: The purpose of this study was to transform brain mapping data into a digitized intra-operative MRI and integrated brain function dataset for predictive glioma surgery considering tumor resection volume, as well as the intra-operative and postoperative complication rates. Methods: Brain function data were transformed into digitized localizations on a normalized brain using a modified electric stimulus probe after brain mapping. This normalized brain image with functional information was then projected onto individual patient’s brain images including predictive brain function data. Results: Log data were successfully acquired using a medical device integrated into intra-operative MR images, and digitized brain function was converted to a normalized brain data format in 13 cases. For the electrical stimulation positions in which patients showed speech arrest (SA), speech impairment (SI), motor and sensory responses during cortical mapping processes in awake craniotomy, the data were tagged, and the testing task and electric current for the stimulus were recorded. There were 13 SA, 7 SI, 8 motor and 4 sensory responses (32 responses) in total. After evaluation of transformation accuracy in 3 subjects, the first transformation from intra- to pre-operative MRI using non-rigid registration was calculated as 2.6 ± 1.5 and 2.1 ± 0.9 mm, examining neighboring sulci on the electro-stimulator position and the cortex surface near each tumor, respectively; the second transformation from pre-operative to normalized brain was 1.7 ± 0.8 and 1.4 ± 0.5 mm, respectively, representing acceptable accuracy. Conclusion: This image integration and transformation method for brain normalization should facilitate practical intra-operative brain mapping. In the future, this method may be helpful for pre-operatively or intra-operatively predicting brain function.

Acute loss of kidney function is a critical internal stressor. Arginine vasopressin (AVP) present in the parvocellular division of the paraventricular nucleus (PVN) plays a key role in the regulation of stress responses. However, hypothalamic AVP dynamics during acute kidney dysfunction remain unclear. In this study, we investigated the effects of bilateral nephrectomy on AVP, using a transgenic rat line that expressed the AVP-enhanced green fluorescent protein (eGFP). The eGFP fluorescent intensities in the PVN were dramatically increased after bilateral nephrectomy. The mRNA levels of eGFP, AVP, and corticotrophin-releasing hormonein the PVN were dramatically increased after bilateral nephrectomy. Bilateral nephrectomy also increased the levels of Fos-like immunoreactive cells in brainstem neurons. These results indicate that bilateral nephrectomy upregulates the AVP-eGFP synthesis. Further studies are needed to identify the neural and/or humoral factors that activate AVP synthesis and regulate neuronal circuits during acute kidney dysfunction.

Background: Carnitine deficiency is common in patients on hemodialysis. However, the efficacy of L-carnitine supplementation for improving lean body mass (LBM) and physical function has not yet been evaluated. Methods: In this multicenter, prospective, parallel, randomized, controlled trial, 91 patients on hemodialysis who developed carnitine deficiency were randomly assigned to receive injections of 1,000 mg L-carnitine 3 times per week after each hemodialysis session (L-carnitine group) or no injections (control group) with monitoring for 12 months. Results: The data for 84 of the 91 patients were available for analysis (L-carnitine group, n?=?42; control group, n?=?42). Dry weight and body mass index did not significantly change in the l-carnitine group, but significantly decreased in the control group. Arm muscle area (AMA) did not change significantly in the L-carnitine group but decreased significantly in the control group; the difference in mean AMA between the groups was 6.22% (95% confidence interval [CI] 1.90–10.5; P?=?0.037). Hand grip strength did not change significantly in the L-carnitine group, but decreased significantly in the control group. The difference in change in hand grip strength between the groups was 4.27% (95% CI 0.42–8.12; P?=?0.030). Furthermore, LBM did not change significantly in the l-carnitine group but decreased significantly in the control group; the difference in mean LBM between the groups was 2.92 % (95% CI 1.28–4.61; P?=?0.0007). Conclusions: l-carnitine supplementation is useful in patients who develop carnitine deficiency on hemodialysis because it maintains physical function and LBM.

A system to measure travel times of high‐frequency (HF) radio waves was developed based on a digital receiver technique. Travel times of HF transequatorial propagation (HF‐TEP) of signals of Radio Australia from Shepparton (36.2°S, 145.3°E), Australia to Oarai (36.3°N, 140.6°E), Japan, were measured by the system. Directions of arrival of the signals were simultaneously observed by a HF Direction Finder located at Oarai (Oarai Direction Finder: ODF). When the ODF observed signals arriving from great circle direction, constant multiple discrete values of propagation times were observed. After sunset, propagation times longer than those expected from the great circle propagation were observed and the ODF observed corresponding signals from off‐great‐circle directions (off‐great‐circle propagation). The observed maximum azimuth angle deviation (∼50°) was much larger than the angle that would have been obtained when a single side reflection in HF‐TEP was assumed. This result supports the multireflection model of off‐great‐circle propagation of HF‐TEP proposed by Tsunoda et al. (2016a, https://doi.org/10.1002/2015JA021695). The propagation time measurements are useful to determine the propagation paths, when they are used with HF‐TEP observations by a HF Direction Finder system. Ray tracing analysis with the propagation times and arrival angles will contribute to monitoring locations of plasma bubbles as well as understanding their structures and the physics behind them. The technique can also be applied to determine the propagation paths in the normal great circle propagations and other geophysical phenomena, such as midlatitude trough, deep traveling ionospheric disturbance modulation of the ionospheric height due to Perkins instability and sporadic Elayer irregularities. An HF propagation time can be measured with low‐cost devicesTransequatorial propagation of HF radio waves is simultaneously measured by a direction finder and a propagation time measurement systemMeasurements in the arrival angles and travel times of HF off‐great‐circle propagation indicate multiple reflections along the propagation paths

•Cho/NAA in high-grade gliomas is greater than in tumefactive demyelinating lesions.•There is a positive correlation between Cho/NAA and the methionine-PET TNR.•MRS may be a useful alternative to methionine-PET.

During cancer chemotherapy, drugs such as 5-HT3receptor antagonists have typically been used to control vomiting and anorexia. We examined the effects of oxytocin (OXT), which has been linked to appetite, on cisplatin-induced anorexia in rats. Fos-like immunoreactivity (Fos-LI) expressed in the supraoptic nucleus (SON), the paraventricular nucleus (PVN), the area postrema and the nucleus of the solitary tract (NTS) after intraperitoneal (ip) administration of cisplatin. We also examined the fluorescence intensity of OXT-mRFP1 after ip administration of cisplatin in OXT-mRFP1 transgenic rats. The mRFP1 fluorescence intensity was significantly increased in the SON, the PVN, and the NTS after administration of cisplatin. The cisplatin-induced anorexia was abolished by OXT receptor antagonist (OXTR-A) pretreatment. In the OXT-LI cells, cisplatin-induced Fos expression in the SON and the PVN was also suppressed by OXTR-A pretreatment. These results suggested that central OXT may be involved in cisplatin-induced anorexia in rats.

Orexin-A and -B, and ghrelin are potent orexigenic peptides. The effects of ACT462206, a novel dual orexin receptor antagonist (DORA), on ghrelin-induced feeding were examined in adult male Wistar rats. Hyperphagia induced by the intracerebroventricular (icv) administration of ghrelin was significantly suppressed for at least 2 h by pretreatment with icv administration of DORA. A marked increase was observed in the number of neurons showing Fos immunoreactivity in the paraventricular nucleus, arcuate nucleus and lateral hypothalamic area (LHA), 90 min after icv administration of ghrelin. Pretreatment with DORA significantly decreased the number of Fos-immunoreactive (IR) neurons; however, Fos immunoreactivity remained significantly increased. Double-immunostaining for Fos and orexin-A showed that many orexin-A-IR neurons in the LHA coexisted with Fos immunoreactivity after icv administration of ghrelin, but their number was reduced significantly by DORA pretreatment. These results suggest that centrally administered ghrelin may activate the orexinergic and non-orexinergic pathways responsible for the regulation of feeding.

Ionospheric disturbance was observed in ionograms at Kazan, Russia $$(55.85^\circ \hbox {N}, 48.81^\circ \hbox {E})$$ (55.85∘N,48.81∘E) , associated with the M8.8 Chile earthquake in 2010 $$(35.91^\circ \hbox {S}, 72.73^\circ \hbox {W})$$ (35.91∘S,72.73∘W) . The disturbance was caused by infrasound waves that were launched by seismic Rayleigh waves propagating over 15,000 km along Earth’s surface from the epicenter. This distance was extremely large compared with the detection limit of similar ionospheric disturbances that were previously studied at lower latitudes over Japan. The observations suggest that the sensitivity of ionograms to coseismic atmospheric disturbances in the infrasound range differs at different locations on the globe. A notable difference in the geophysical condition between the Russian and Japanese ionosonde sites is the magnetic inclination (dip angle), which affects the ionosphere–atmosphere dynamical coupling and radio propagation of vertical incidence ionosonde sounding. Numerical simulations of atmospheric–ionospheric perturbation were conducted, and ionograms were synthesized from the disturbed electron density profiles for different magnetic dip angles. The results showed that ionosonde sounding at Kazan was sensitive to the atmospheric disturbances induced by seismic Rayleigh waves compared with that at Japanese sites by a factor of $$\sim$$ ∼ 3.

The Fc receptors (FcR) have pivotal roles in the pathogenesis of the autoimmune glomerulonephritis. We therefore investigated the effects of a Syk inhibitor on the progression of lupus nephritis and SH3 domain binding protein 2 and p38MAP kinase signalings in mice. NZB/W F1 mice, a model of lupus nephritis, received a Syk inhibitor R406. Western blotting and immunohistochemistry revealed that R406 treatment significantly delayed the appearance of proteinuria, histologically improved their glomerulosclerosis and inhibited the increased the expression of MCP-1 and TGF-β1 mRNAs and the nephrin and podocin proteins in the kidney. The treatment suppressed the phosphorylation of 3BP2 in white blood cells from the spleen and significantly inhibited the phosphorylation of p38MAPK in the kidney but did not affect expression of neonatal Fc receptor. These findings indicate the important roles and mechanisms of Fcγ receptors I and III in the development of autoimmune glomerulonephritis and suggest the possible application of Syk inhibitors as novel medicines for the glomerulonephritis.

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Proinflammatory cytokines play critical roles in the pathogenesis of joint diseases. Using a mass spectrometry–based cloning approach, we identified Semaphorin 4D (Sema4D) as an inflammatory cytokine that directly promoted cartilage destruction. Sema4d-deficient mice showed less cartilage destruction than wild-type mice in a model of rheumatoid arthritis. Sema4D induced a proinflammatory response in mouse articular chondrocytes characterized by the induction of proteolytic enzymes that degrade cartilage, such as matrix metalloproteinases (MMPs) and aggrecanases. The activation of Mmp13and Mmp3expression in articular chondrocytes by Sema4D did not depend on RhoA, a GTPase that mediates Sema4D-induced cytoskeletal rearrangements. Instead, it required NF-κB signaling and Ras-MEK-Erk1/2 signaling downstream of the receptors Plexin-B2 and c-Met and depended on the transcription factors IκBζ and C/EBPδ. Genetic and pharmacological blockade of these Sema4D signaling pathways inhibited MMP induction in chondrocytes and cartilage destruction in femoral head organ culture. Our results reveal a mechanism by which Sema4D signaling promotes cartilage destruction.

Introduction Four-dimensional computed tomography angiography (4D CTA) is now becoming an often used diagnostic imaging modality for the assessment of patients with intracranial tumors. The purpose of this study was to demonstrate the utility of 4D CTA for preoperative screening in patients with intracranial tumors as well as to examine the correlation between perfusion data and grading of gliomas.Methods We performed preoperative screening using 320-row detector CT scanner in 186 patients with intracranial tumors, and 115 patients were finally included in the study. Time-resolved subtracted maximum intensity projection images and volume-rendered images were reconstructed to evaluate vascular structures, tumor staining and incidental lesions. We also evaluated the perfusion functional map for gliomas to find correlations between their vascularity and tumor grading.Results We evaluated gliomas in 70 patients, meningiomas in 29, and other tumors in 16. Patients with gliomas of a pathologically higher grade showed high cerebral blood volume (p?

To reveal the temporal change of the equatorial ionization anomaly (EIA) asymmetry, a multipoint satellite-ground beacon experiment was conducted along the meridional plane of the Thailand–Indonesia sector. The observation includes one station near the magnetic equator and four stations at off-equator latitudes. This is the first EIA asymmetry study with high spatial resolution using GNU Radio Beacon Receiver (GRBR) observations in Southeast Asia. GRBR-total electron contents (TECs) from 97 polar-orbit satellite passes in March 2012 were analyzed in this study. Successive passes captured rapid evolution of EIA asymmetry, especially during geomagnetic disturbances. The penetrating electric fields that occur during geomagnetic disturbed days are not the cause of the asymmetry. Instead, high background TEC associated with an intense electric field empowers the neutral wind to produce severe asymmetry of the EIA. Such rapid evolution of EIA asymmetry was not seen during nighttime, when meridional wind mainly controlled the asymmetric structures. Additional data are necessary to identify the source of the variations, i.e., atmospheric waves. Precisely capturing the locations of the crests and the evolution of the asymmetry enhances understanding of the temporal change of EIA asymmetry at the local scale and leads to a future local modeling for TEC prediction in Southeast Asia.

Nuclear IκB‐ζ, a target of TGF‐β signaling in T cells, controls immune homeostasis and IFN‐γ production. The transcriptional regulator IκB‐ζ is important for the control of apoptosis in keratinocytes. Thus, IκB‐ζ‐deficient mice develop autoimmune diseases, such as Sjögren's syndrome. However, T cells also play a pivotal role in Sjögren's syndrome. To study the role of IκB‐ζ in T cells, we generated T cell‐specific, IκB‐ζ‐deficient mice. We observed increased numbers of peripheral effector/memory CD4+cells and IFN‐γ‐producing CD4+cells in 3‐week‐old mice. We found that IκB‐ζ can be up‐regulated by TGF‐β1 in naϊve CD4+T cells and that it negatively regulates IFN‐γ expression. In addition, we generated Treg‐specific, IκB‐ζ deficient mice and found that IκB‐ζ is dispensable for the plasticity and stability of Tregs. However, Tregsfrom T cell‐specific, IκB‐ζ‐deficient mice have reduced immunoregulatory function. Thus, our data reveal a previously unappreciated role for IκB‐ζ in IFN‐γ production in T cells and the immunoregulatory function of Tregs.

We examined the effects of serotonin (5-HT) depletion induced by peripheral injection of 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA) on the expression of feeding-regulating peptides expressions by using in situ hybridization histochemistry in adult male Wistar rats. PCPA pretreatment had no significant effect on basal levels of oxytocin, corticotropin-releasing hormone(CRH), thyrotropin-releasing hormone(TRH), pro-opiomelanocortin(POMC), cocaine and amphetamine-regulated transcript(CART), neuropeptide-Y(NPY), agouti-related protein(AgRP), melanin-concentrating hormone(MCH) or orexinin the hypothalamus. Food deprivation for 48 h caused a significant decrease in CRH, TRH, POMC, and CART, and a significant increase in NPY, AgRPand MCH. After PCPA treatment, POMCand CARTdid not decrease despite food deprivation. NPYwas significantly increased by food deprivation with PCPA, but was attenuated compared to food deprivation without PCPA. These results suggest that the serotonergic system in the hypothalamus may be involved in the gene expression of POMC, CART, and NPYrelated to feeding behavior.

Transforming growth factor-β (TGF-β) receptors (TβRs) are essential components for TGF-β signal transduction in T cells, yet the mechanisms by which the receptors are regulated remain poorly understood. We show here that Poly(ADP-ribose) polymerase-1 (PARP-1) regulates TGF-β receptor I (TβRI) and II (TβRII) expression in CD4+ T cells and subsequently affects Smad2/3-mediated TGF-β signal transduction. Inhibition of PARP-1 led to the upregulation of both TβRI and TβRII, yet the underlying molecular mechanisms were distinct. PARP-1 selectively bound to the promoter of TβRII, whereas the enzymatic activity of PARP-1 was responsible for the inhibition of TβRI expression. Importantly, inhibition of PARP-1 also enhanced expression of TβRs in human CD4+ T cells. Thus, PARP-1 regulates TβR expression and TGF-β signaling in T cells.

Transforming growth factor-β (TGF-β) receptors (TβRs) are essential components for TGF-β signal transduction in T cells, yet the mechanisms by which the receptors are regulated remain poorly understood. We show here that Poly(ADP-ribose) polymerase-1 (PARP-1) regulates TGF-β receptor I (TβRI) and II (TβRII) expression in CD4+T cells and subsequently affects Smad2/3-mediated TGF-β signal transduction. Inhibition of PARP-1 led to the upregulation of both TβRI and TβRII, yet the underlying molecular mechanisms were distinct. PARP-1 selectively bound to the promoter of TβRII, whereas the enzymatic activity of PARP-1 was responsible for the inhibition of TβRI expression. Importantly, inhibition of PARP-1 also enhanced expression of TβRs in human CD4+T cells. Thus, PARP-1 regulates TβR expression and TGF-β signaling in T cells.

Objective Encapsulating peritoneal sclerosis (EPS) is a devastating fibrotic complication in patients treated with peritoneal dialysis (PD). Transforming growth factor β1 (TGF-β1) is a pivotal factor in the induction of EPS.Methods To develop pyrrole-imidazole (PI) polyamide, a novel gene silencer, targeted to the TGF-β1 promoter (Polyamide) for EPS, we examined the effects of Polyamide on messenger RNA (mRNA) expression of TGF-β 1, vascular endothelial growth factor (VEGF), and extracellular matrix (ECM) in mesothelial cells in vitro, and on the thickness of injured peritoneum evaluated by histology and high- resolution regional elasticity mapping in rats in vivo.Results Polyamide significantly lowered mRNA expression of TGF-β 1 and ECM in vitro.Polyamide labeled with fluorescein isothiocyanate was taken up into the injured peritoneum and was strongly localized in the nuclei of most cells. Polyamide 1 mg was injected intraperitoneally 1 or 3 times in rats receiving a daily intraperitoneal injection of chlorhexidine gluconate and ethanol (CHX) for 14 days. Polyamide significantly suppressed peritoneal thickening and the abundance of TGF-β 1 and fibronectin mRNA, but did not affect expression of VEGF mRNA in the injured peritoneum. Elasticity distribution mapping showed that average elasticity was significantly lower in Polyamide-treated rats than in rats treated solely with CHX.Conclusions Polyamide suppressed the stiffness, ECM formation, and thickening of the injured peritoneum that occurs during EPS pathogenesis. These data suggest that PI polyamide targeted to the TGF-β 1 promoter will be a specific and feasible therapeutic strategy for patients with EPS.

This paper describes the neural network (NN) application for the prediction of the total electron content (TEC) over Chumphon, an equatorial latitude station in Thailand. The studied period is based on the available data during the low-solar-activity period from 2005 to 2009. The single hidden layer feed-forward network with a back propagation algorithm is applied in this work. The input space of the NN includes the day number, hour number and sunspot number. An analysis was made by comparing the TEC from the neural network prediction (NN TEC), the TEC from an observation (GPS TEC) and the TEC from the IRI-2007 model (IRI-2007 TEC). To obtain the optimum NN for the TEC prediction, the root-mean-square error (RMSE) is taken into account. In order to measure the effectiveness of the NN, the normalized RMSE of the NN TEC computed from the difference between the NN TEC and the GPS TEC is investigated. The RMSE, and normalized RMSE, comparisons for both the NN model and the IRI-2007 model are described. Even with the constraint of a limited amount of available data, the results show that the proposed NN can predict the GPS TEC quite well over the equatorial latitude station.

Psychiatric Knowledge and Skills Required of Occupational Physicians: Priorities in the Japanese Setting: Akizumi Tsutsumi, et al. Occupational Health Training Center, University of Occupational Health and Environmental Health, Japan— To prioritize the educational content in psychiatry teaching materials for occupational physicians. A preparatory investigation was performed that included interviews with 13 psychiatrists who were well acquainted with occupational health and practices. Brainstorming among the psychiatrists and 12 occupational physicians was used to develop a list of educational content related to psychiatric issues that should be required for occupational physicians. Using a questionnaire survey constructed based on the preparatory investigations, 135 specialists with extensive experience in occupational medicine were asked to prioritize the selected items. A total of 67 specialists responded to the questionnaire. The following were recommended as high educational priorities for occupational physicians to master: awareness and diagnosis of mood disorders, being able to appropriately deal with depressed workers, screening for depression, understanding cases that should be referred for special treatment, appropriate action for a suicidal person, understanding symptoms that require cooperation in an emergency with a specialist, acquisition of the attitude and skills used in active listening and awareness of diseases such as alcohol dependence, adjustment disorders and schizophrenia. What has been presented here is a consensus view of specialists in this ield. The items included were those obtained from sitting in on the discussions of psychiatrists and occupational physicians. They represent indicators for the development of teaching materials.

A strong earthquake with a magnitude of 9.0 occurred at 1446:23 JST on March 11, 2011, in Japan. Ionospheric disturbances were detected at 1500 JST at four ionosonde stations. An irregular distortion of echo trace was observed at Kokubunji, which is the nearest station to the epicenter and is 440 km from it. Multiple-cusp-type trace indicating extra stratification was observed at Wakkanai and Yamagawa, which are 870 and 1410 km away from the epicenter. A small wavy fluctuation was observed at Okinawa 1910 km away from the epicenter. The real height analysis of the ionograms showed a vertical structure with a scale size of 20~30 km.

Background This study aimed to explore the relationship between recombinant human erythropoietin (EPO) responsiveness, insulin resistance, and malnutrition-inflammation-atherosclerosis (MIA) syndrome in hemodialysis patients.Methods This was an observational cohort study in hemodialysis patients. Adipokines, inflammatory cytokines, and required EPO dosage were measured in diabetes (DM; n=58) and non-diabetes (non-DM; n=58) groups over 48 weeks. Furthermore, the EPO responsiveness index (required EPO dosage divided by hemoglobin) was evaluated with or without MIA syndrome in both groups.Results The DM group had significantly higher plasma leptin, interleukin-6 (IL-6), and high sensitivity C-reactive protein (hs-CRP) levels but lower plasma high molecular weight (HMW) adiponectin levels compared to the non-DM group. Although hemoglobin levels were not significantly different, required EPO dosage was significantly higher in the DM group than in the non-DM group, particularly in the presence of MIA syndrome. The DM group with MIA syndrome had significantly higher plasma leptin, IL-6, and hs-CRP levels but lower plasma HMW adiponectin levels compared to the non-DM group with MIA syndrome. There was also a significant association between EPO dosage and homeostasis model assessment for insulin resistance (HOMA-IR), hs-CRP, IL-6, tumor necrosis factor a, leptin, and HMW adiponectin levels in DM patients with MIA syndrome.Conclusion Diabetic hemodialysis patients with MIA syndrome have a lower response to EPO and a higher resistance to insulin. This fact may explain the poor outcome of these patients and demonstrate the importance of diagnosis and therapeutic management.

Human γδ T-cell lymphoma is a rare clinicopathologic entity with aggressive course and poor prognosis. The etiology and pathogenesis of γδ T-cell lymphoma is unknown. We show here that mice with deficiency in inhibitory helix-loop-helix protein Id3 (Id3−/−) developed γδ T-cell lymphoma that resembled human γδ T-cell lymphoma. The Id3−/−mice with lymphoma showed splenomegaly, hepatomegaly, and lymphadenopathy with involvement of bone marrow, thymus, kidney, and lungs between 6 and 15 months of age. Phenotypic analysis revealed that lymphomatous cells were cluster of differentiation (CD)3+, γδ T-cell receptor (TCR)+, and αβ TCR−, and expressed CD8+CD4−, CD4+CD8−, or a mixture of the two. Id3−/−γδ T-cell lymphoma used predominantly Vγ1.1, some Vγ3, yet no Vγ2 TCR, and some showed increased levels of the oncogene c-Myc. Strikingly, adoptive transfer of the γδ T-cell lymphoma into syngeneic Rag1−/−mice resulted in aggressive γδ T-cell lymphoma, identical to the Id3−/−donor. Thus, our data demonstrate that Id3 regulates the development of γδ T-cell lymphoma in mice, raising a possibility of Id3 gene mutation in human γδ T-cell lymphoma. Our model will provide a tool for studying the molecular mechanisms and development of human γδ T-cell lymphoma.

Human γδ T-cell lymphoma is a rare clinicopathologic entity with aggressive course and poor prognosis. The etiology and pathogenesis of γδ T-cell lymphoma is unknown. We show here that mice with deficiency in inhibitory helix-loop-helix protein Id3 (Id3−/−) developed γδ T-cell lymphoma that resembled human γδ T-cell lymphoma. The Id3−/− mice with lymphoma showed splenomegaly, hepatomegaly, and lymphadenopathy with involvement of bone marrow, thymus, kidney, and lungs between 6 and 15 months of age. Phenotypic analysis revealed that lymphomatous cells were cluster of differentiation (CD)3+, γδ T-cell receptor (TCR)+, and αβ TCR−, and expressed CD8+CD4−, CD4+CD8−, or a mixture of the two. Id3−/− γδ T-cell lymphoma used predominantly Vγ1.1, some Vγ3, yet no Vγ2 TCR, and some showed increased levels of the oncogene c-Myc. Strikingly, adoptive transfer of the γδ T-cell lymphoma into syngeneic Rag1−/− mice resulted in aggressive γδ T-cell lymphoma, identical to the Id3−/− donor. Thus, our data demonstrate that Id3 regulates the development of γδ T-cell lymphoma in mice, raising a possibility of Id3 gene mutation in human γδ T-cell lymphoma. Our model will provide a tool for studying the molecular mechanisms and development of human γδ T-cell lymphoma.

The physical habitat characteristics associated with spatial distribution patterns of the freshwater mussel Pronodularia japanensis, which is used for oviposition by the Tokyo bitterling Tanakia tanago, were investigated in a small stream within a Tokyo bitterling protected area. The distribution of the mussels was found to be in an under-dispersed, non-random spatial pattern. Mussel occurrence correlated negatively with sediment softness, and positively with flow velocity, while mussel abundance was associated negatively with sediment softness and positively with sediment type (particle size). Furthermore, mussels were scarce in riverbed areas with a lack of sediment. These correlations suggest that the population dynamics of mussels and Tokyo bitterling may be influenced by changes in stream sediment conditions. To conserve the symbiosis between Tokyo bitterlings and mussels, a suitable benthic environment is required. [ABSTRACT FROM AUTHOR]

Aims:Benidipine, an L-/T-type calcium channel blocker, dilates renal efferent and afferent arterioles and reduces glomerular pressure; therefore, it may exert renoprotective effects. We conducted an open-labeled randomized trial to compare the effects of benidipine with cilnidipine in hypertensive patients with chronic kidney disease (CKD).Methods:The patients who were already being treated with angiotensin receptor blockers (ARBs) received one of the following treatment regimens: benidipine at a dose of 2 mg/day that was increased up to a dose of 8 mg/day (benidipine group; n 118) or cilnidipine at a dose of 5 mg/day that was increased up to a dose of 20 mg/day (cilnidipine group; n 115).Results:After 12 months of treatment, we observed a significant and comparable reduction in the systolic and diastolic blood pressure in both groups. The urinary protein:creatinine ratio was significantly decreased in both groups after 3 months of treatment and thereafter; however, the difference between both groups was not significant after 12 months of treatment. Benidipine exerted an antiproteinuric effect to a greater extent than cilnidipine in patients with diabetes.Conclusion:The addition of benidipine as well as cilnidipine reduces urinary protein excretion in hypertensive patients with CKD who are already being administered ARBs.

Background:We aimed to assess the effect of long-term pioglitazone treatment on erythropoietin responsiveness and insulin resistance in type 2 diabetic patients on hemodialysis.Methods:We conducted a prospective, open-label, parallel-group, controlled study of 63 type 2 diabetic hemodialysis patients who were randomly assigned to two groups: pioglitazone group (P-group; 15 – 30 mg/day pioglitazone plus conventional oral hypoglycemic agents) and control group (C-group; conventional oral hypoglycemic agents alone). We determined the efficacy of pioglitazone by monitoring anemia, glycemic control, insulin resistance, and levels of inflammatory cytokines and high-molecular-weight (HMW) adiponectin for 96 weeks.Results:Pioglitazone effectively reduced erythropoietin dose and maintained the target hemoglobin levels by improving insulin resistance up to the end of the study. In the P-group, hemoglobin A1c, glycated albumin, and triglycerides significantly decreased compared with the C-group. There was a significant reduction in homeostasis model assessment for insulin resistance and the level of high-sensitivity C-reactive protein, and a significant increase in HMW adiponectin level in the P-group; these changes were significantly different compared with values for the C-group. No serious adverse effects such as hypoglycemia, liver impairment, or heart failure were observed in any of the patients.Conclusion:Pioglitazone treatment resulted in better glycemic control, improved lipid levels, an increase in insulin sensitivity and adiponectin levels, and a decrease in inflammatory markers, thus improving the risk factors of cardiovascular disease. Erythropoietin responsiveness improved with a reduction in erythropoietin dose and may be associated with the improvement in insulin resistance due to long-term pioglitazone treatment.

Objective:Mitiglinide, a rapid- and short-acting insulinotropic sulfonylurea receptor ligand, exhibits hypoglycemic action unlike other sulfonylureas. The efficacy of the combination of mitiglinide and α-glucosidase inhibitors for diabetic patients on hemodialysis (HD) has not been prospectively evaluated; therefore, we evaluated the efficacy and safety of mitiglinide in these patients.Research design and methods:We performed an open-label randomized study with 36 type 2 diabetics with poor glycemic control on HD and receiving daily doses of voglibose (0.9 mg). The patients were randomly assigned to two groups: a combination-therapy group (mitiglinide group), mitiglinide initial dose 7.5 – 15 mg titrated to 30 mg daily and constant daily dose 0.9 mg of voglibose, and a monotherapy group (control group), constant daily dose 0.9 mg of voglibose alone. The efficacy of the treatment was determined by monitoring plasma glucose, hemoglobin A1c (HbA1c), and glycated albumin (GA) levels and using homeostasis model assessment of insulin resistance (HOMA-IR). Safety and tolerance were determined by monitoring clinical and laboratory parameters.Results:The final dose of mitiglinide was 22.9 ± 8.9 (mean ± s.d.) mg (0.41 mg/kg) daily. Mitiglinide reduced fasting plasma glucose and GA levels after 4 weeks and HbA1clevels after 8 weeks. Triglyceride levels and HOMA-IR values also decreased significantly after mitiglinide treatment. No significant changes in blood pressure levels or serious adverse effects such as hypoglycemia or liver impairment were observed.Conclusions:This study suggests a combination therapy of mitiglinide and voglibose may have potential for the treatment of diabetics on HD. Due to the small sample size used, further studies should be performed, particularly to assess the safety of mitiglinide treatment.

We examined whether the chemogenetic activation of endogenous arginine vasopressin (AVP) affects central nesfatin-1/NucB2 neurons, using a transgenic rat line that was previously generated. Saline (1 mL/kg) or clozapine-N-oxide (CNO, 1 mg/mL/kg), an agonist for hM3Dq, was subcutaneously administered in adult male AVP-hM3Dq-mCherry transgenic rats (300–370 g). Food and water intake were significantly suppressed after subcutaneous (s.c.) injection of CNO, with aberrant circadian rhythmicity. The percentages of Fos expression in nesfatin-1/NucB2-immunoreactive neurons were significantly increased in the hypothalamus and brainstem at 120 min after s.c. injection of CNO. Suppressed food intake that was induced by chemogenetic activation of endogenous AVP was ablated after intracerebroventricularly administered nesfatin-1/NucB2-neutralizing antibody in comparison with vehicle, without any alteration of water intake nor circadian rhythmicity. These results suggest that chemogenetic activation of endogenous AVP affects, at least in part, central nesfatin-1/NucB2 neurons and may exert anorexigenic effects in the transgenic rats.

A new technique was developed to estimate the ionospheric total electron content (TEC) from Global Navigation Satellite System (GNSS) satellite signals. The vertically distributed electron density was parameterized by two thin-shell layers (double-shell approach). The spatiotemporal variation of TEC (strictly speaking, partial electron content) associated with each shell was approximated by the functional fitting of spherical surface harmonics. The major improvements over the conventional single-shell approach were as follows: (1) the precise estimation of TEC was achieved; (2) the estimated TEC was less dependent on the choice of shell heights; and (3) the equatorial anomaly was captured more correctly. Furthermore, higher and lower shells exhibited a different pattern of local time vs latitude variation, providing information on the ionosphere–thermosphere dynamics.