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Key Message: Expression of the TaMDC1 in transgenic tomato plants confer resistance to bacterial and fungal pathogens, as well as an insect pest and thus prove in planta function of the wheat cystatin. Cystatins are the polypeptides with cysteine proteinase inhibitory activities. Plant cystatins or phytocystatins are known to contribute to plant resistance against insect pests. Recently, increasing data proved that some of the phytocystatins also have antifungal activities in vitro. Here, we functionally characterized a wheat multidomain cystatin, TaMDC1, using in planta assays. Expression of TaMDC1 in wheat seedlings is up-regulated in response to methyl jasmonate and salicylic acid, indicating that TaMDC1 is involved in biotic stress responses mediated by these plant hormones. The TaMDC1 cDNA was integrated in tomato genome and expressed under cauliflower mosaic virus 35S promoter. Four transgenic plants that show high level of the transgene expression were selected by RNA gel blot and immunoblot analysis and utilized to assess biotic stress resistance against the bacterial pathogen Pseudomonas syringae, the fungal pathogens Botrytis cinerea and Alternaria alternata, and the insect pest Colorado potato beetle (CPB, Leptinotarsa decemlineata). Detached leaf inoculation assays revealed that the tomato plants expressing TaMDC1 showed high levels of resistance against P. syringae and A. alternata, and elevated tolerance against B. cinerea. Sustenance of L. decemlineata larvae to the transgenic plants demonstrated inhibition of CPB larvae growth. Inhibitory activity of TaMDC1 against selected pathogens was also demonstrated by in vitro assays with total protein extracted from transgenic tomato plants. Taken together, the presented data suggest that TaMDC1 is involved in a broad spectrum biotic stress resistance in planta.

Background: Unresectable pediatric osteosarcoma has poor outcomes with conventional treatments., Results: Twenty-six patients aged 11-20 years (median 16) had inoperable osteosarcoma of the trunk (24 pelvic, 1 mediastinal and 1 paravertebral) without any other lesion at initial examination. There were 22 primary, 1 locally recurrent and 3 metastatic cases. Median CIRT dose was 70.4 Gy RBE (relative biological effectiveness) delivered in 16 fractions. Median follow-up was 32.7 months. Overall survival was 50.0% and 41.7% at 3 and 5 years, respectively. Ten patients survived for more than 5 years (range 5-20.7 years). Local control was 69.9% and 62.9% at 3 and 5 years, respectively and progression-free survival was 34.6% at 3 and 5 years. Only largest tumor diameter correlated with 5-year overall survival and local control. There were 4 grade 3-4 CIRT-related late toxicities, 1 case of bone fracture and no treatment-related mortalities. All patients (except 1) were able to ambulate after CIRT., Conclusions: CIRT was safe and efficacious in the treatment of inoperable pediatric osteosarcoma with improved local control and overall survival compared to conventional treatments., Methods: We retrospectively reviewed the records of pediatric and adolescent patients who received carbon ion radiotherapy (CIRT) for inoperable osteosarcoma between 1996 and 2014., Competing Interests: CONFLICTS OF INTEREST None.

A 52-year-old man who had been taking omeprazole, a proton pump inhibitor (PPI), for 25 years developed iron deficiency anemia. An evaluation of the entire gastrointestinal tract did not reveal any possible causes of gastrointestinal blood loss. The cause of the iron deficiency was considered to be a reduction in gastrointestinal iron absorption in association with the reduced secretion of gastric acid due to PPI use. This case demonstrates that long-term PPI use for as long as 25 years may cause iron deficiency anemia and should be considered in the differential diagnosis of iron deficiency anemia in long-term PPI users.

Background: Many patients with panic disorder meet criteria for at least one other diagnosis, most commonly other anxiety or mood disorders. Cognitive-behavioral therapy is the best empirically supported psychotherapy for panic disorder. There is now evidence indicating that cognitive-behavioral therapy for panic disorder yields positive benefits upon comorbid disorders., Objectives: The present study aimed to examine the predictors of broad dimensions of psychopathology in panic disorder after cognitive-behavioral therapy., Methods: Two hundred patients affected by panic disorder were treated with manualized group cognitive-behavioral therapy. We examined if the baseline personality dimensions of NEO Five Factor Index predicted the subscales of Symptom Checklist-90 Revised at endpoint using multiple regression analysis based on the intention-to-treat principle., Results: Conscientiousness score of NEO Five Factor Index at baseline was a predictor of four Symptom Checklist-90 Revised subscales including obsessive-compulsive ( β = -0.15, P < 0.01), depression ( β = -0.13, P < 0.05), phobic anxiety ( β = -0.15, P < 0.05), and Global Severity Index ( β = -0.13, P < 0.05)., Conclusion: Conscientiousness at baseline may predict several dimensions of psychopathology in patients with panic disorder after cognitive-behavioral therapy. For the purpose of improving a wide range of psychiatric symptoms with patients affected by panic disorder, it may be useful to pay more attention to this personal trait at baseline.

Introduction: We analyzed the frequency spectrum of two neonatal sleep stages, namely active sleep and quiet sleep, and the relationship between these sleep stages and autonomic nervous activity in 74 newborns and 16 adults as a comparison., Method: Active and quiet sleep were differentiated by electroencephalogram (EEG) patterns, eye movements, and respiratory wave patterns; autonomic activity was analyzed using the RR interval of simultaneously recorded electrocardiogram (ECG) signals. Power values (LFa, absolute low frequency; HFa, absolute high frequency), LFa/HFa ratio, and the values of LFn (normalized low frequency) and HFn (normalized high frequency) were obtained. Synchronicity between the power value of HFa and the LFa/HFa ratio during active and quiet sleep was also examined by a new method of chronological demonstration of the power values of HFa and LFa/HFa., Results: We found that LFa, HFa and the LFa/HFa ratio during active sleep were significantly higher than those during quiet sleep in newborns; in adults, on the other hand, the LFa/HFa ratio during rapid eye movement (REM) sleep, considered as active sleep, was significantly higher than that during non-REM sleep, considered as quiet sleep, and HFa values during REM sleep were significantly lower than those during non-REM sleep. LFn during quiet sleep in newborns was significantly lower than that during active sleep. Conversely, HFn during quiet sleep was significantly higher than that during active sleep. Analysis of the four classes of gestational age groups at birth indicated that autonomic nervous activity in a few preterm newborns did not reach the level seen in full-term newborns. Furthermore, the power value of HFa and the LFa/HFa ratio exhibited reverse synchronicity., Conclusion: These results indicate that the autonomic patterns in active and quiet sleep of newborns are different from those in REM and non-REM sleep of adults and may be develop to the autonomic patterns in adults, and that parasympathetic activity is dominant during quiet sleep as compared to active sleep from the results of LFn and HFn in newborns. In addition, in some preterm infants, delayed development of the autonomic nervous system can be determined by classifying the autonomic nervous activity pattern of sleep stages., (Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Ribosome biogenesis is a highly complex process that requires several cofactors, including DExD/H-box RNA helicases (RHs). RHs are a family of ATPases that rearrange the secondary structures of RNA and thus remodel ribonucleoprotein complexes. DExD/H-box RHs are found in most organisms and play critical roles in a variety of RNA-involved cellular events. In human and yeast cells, many DExD/H box RHs participate in multiple steps of ribosome biogenesis and regulate cellular proliferation and stress responses. In plants, several DExD/H-box RHs have been demonstrated to be associated with plant development and abiotic stress tolerance through their functions in modulating pre-rRNA processing. In this review, we summarize the pleiotropic roles of DExD/H-box RHs in rRNA biogenesis and other biological functions. We also describe the overall function of the DExD/H-box RH family in ribosome biogenesis based on data from human and yeast.

For cell division, negatively charged chromatin, in which nucleosome fibers (10 nm fibers) are irregularly folded [1-5], must be condensed into chromosomes and segregated. While condensin and other proteins are critical for organizing chromatin into the appropriate chromosome shape [6-17], free divalent cations such as Mg 2+ and Ca 2+ , which condense chromatin or chromosomes in vitro [18-28], have long been considered important, especially for local condensation, because the nucleosome fiber has a net negative charge and is by itself stretched like "beads on a string" by electrostatic repulsion. For further folding, other positively charged factors are required to decrease the charge and repulsion [29]. However, technical limitations to measure intracellular free divalent cations, but not total cations [30], especially Mg 2+ , have prevented us from elucidating their function. Here, we developed a Förster resonance energy transfer (FRET)-based Mg 2+ indicator that monitors free Mg 2+ dynamics throughout the cell cycle. By combining this indicator with Ca 2+ [31] and adenosine triphosphate (ATP) [32] indicators, we demonstrate that the levels of free Mg 2+ , but not Ca 2+ , increase during mitosis. The Mg 2+ increase is coupled with a decrease in ATP, which is normally bound to Mg 2+ in the cell [33]. ATP inhibited Mg 2+ -dependent chromatin condensation in vitro. Chelating Mg 2+ induced mitotic cell arrest and chromosome decondensation, while ATP reduction had the opposite effect. Our results suggest that ATP-bound Mg 2+ is released by ATP hydrolysis and contributes to mitotic chromosome condensation with increased rigidity, suggesting a novel regulatory mechanism for higher-order chromatin organization by the intracellular Mg 2+ -ATP balance., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

To study the genetic diversity of enterovirus G (EV-G) among Japanese pigs, metagenomics sequencing was performed on fecal samples from pigs with or without diarrhea, collected between 2014 and 2016. Fifty-nine EV-G sequences, which were >5,000 nucleotides long, were obtained. By complete VP1 sequence analysis, Japanese EV-G isolates were classified into G1 (17 strains), G2 (four strains), G3 (22 strains), G4 (two strains), G6 (two strains), G9 (six strains), G10 (five strains), and a new genotype (one strain). Remarkably, 16 G1 and one G2 strain identified in diarrheic (23.5%; four strains) or normal (76.5%; 13 strains) fecal samples possessed a papain-like cysteine protease (PL-CP) sequence, which was recently found in the USA and Belgium in the EV-G genome, at the 2C-3A junction site. This paper presents the first report of the high prevalence of viruses carrying PL-CP in the EV-G population. Furthermore, possible inter- and intragenotype recombination events were found among EV-G strains, including G1-PL-CP strains. Our findings may advance the understanding of the molecular epidemiology and genetic evolution of EV-Gs.

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Activation of motor-related regions with illusory kinesthesia had been suspected to contribute toward pain alleviation. We used electroencephalography (EEG) to assess the sensorimotor cortex activation during illusory kinesthesia by vibratory tendon stimulation in patients who were in pain. We investigated the relationship between the sensorimotor cortex and postoperative pain to clarify the analgesia mechanism. Patients who had undergone distal radius fracture surgery were studied. A hand massager provided the vibration stimulus for the illusory kinesthesia on the extensor digitorum muscle at the nonaffected hand's wrist joint on 7 consecutive days starting 1 day after surgery. The main outcomes were pain intensity and EEG activity. EEG activity was recorded during illusory kinesthesia. We also analyzed the high α rhythm (10-12 Hz) event-related desynchronization/event-related synchronization. The pain intensity was reduced. Attenuation of the high α wave was observed in the bilateral sensorimotor cortex (C3ch, C4ch) areas during illusory kinesthesia. A significant negative correlation was also observed in the C3 and the C4 of event-related desynchronization/event-related synchronization% values and the variation of pain amelioration at rest. Activation of the sensorimotor cortex by illusory kinesthesia might have influenced parts of the descending pain-inhibitory system. The postoperative pain in the patients might have been alleviated by the descending pain-inhibitory system.

Background: The prognostic impact of red blood cell distribution width (RDW) on adverse outcomes in patients with heart failure with preserved ejection fraction (HFpEF) is unclear. We investigated the association between RDW values at admission and long-term prognosis in patients with acute decompensated HFpEF., Methods: The present study enrolled 278 consecutive patients with acute decompensated HFpEF, whose RDW levels were measured at admission. We divided enrolled patients into 2 groups according to RDW value and investigated the association between RDW and patients' mortality., Results: A Kaplan-Meier analysis demonstrated that patients with higher RDW levels had significantly higher all-cause and non-cardiac mortality, but not cardiac-based mortality, than did patients with lower RDW levels. A multivariate Cox regression analysis revealed that RDW levels were independently correlated with all-cause and non-cardiac mortality after adjusting for other risk factors, including age, brain natriuretic peptide, hemoglobin, and Charlson comorbidity index score. In a receiver-operating curve analysis, the cut-off value to maximize the prognostic impact of RDW on mortality was 15.2%. The evaluation of RDW and other prognostic factors improved their predictive value for both all-cause and non-cardiac mortality., Conclusions: The current study demonstrated that RDW levels at admission independently predict poor outcomes because of non-cardiac events in patients with acute decompensated HFpEF. Evaluation of RDW could provide useful information for the long-term prognosis of HFpEF., (Copyright © 2017. Published by Elsevier Ltd.)

Aim of this work is to establish evaluation criteria for identifying endolymphatic hydrops in the vestibule and cochlea using a magnetic resonance imaging (MRI) scanner. This is a retrospective diagnostic study. We evaluated 70 ears of 35 unilateral Ménière's disease patients. We performed 3-T MRI 4 h after intravenous gadolinium injection. Otologists manually traced the outline of vestibule, cochlea, and endolymphatic space of the vestibule and cochlea on two-dimensional fluid-attenuated inversion-recovery (2D-FLAIR) images. The traced area was measured, and rates of endolymphatic space to the vestibule and cochlea were calculated. The same otologists judged whether the low signal intensity area of the cochlea was at the edge of the cochlea. For measuring the rate of endolymphatic space to the vestibule, when the cut-off value was 30%, the presence of endolymphatic hydrops was determined with sensitivity of 87.1% and specificity of 94.3%. In contrast, the rate of endolymphatic space to the cochlea produced low accuracy. Therefore, when the presence of endolymphatic hydrops in the cochlea was judged by whether the low signal intensity area in the cochlea was at the edge of cochlea, endolymphatic hydrops could be detected with sensitivity of 91.4% and specificity of 94.3%. We were able to identify endolymphatic hydrops in the vestibule when the rate of endolymphatic space to the vestibule was greater than 30%, and could detect endolymphatic hydrops in the cochlea when a low signal intensity area was located at the edge of the cochlea in 2D-FLAIR images. Level of evidence 4.

GaAs nanopillar arrays were successfully fabricated by metal-assisted chemical etching using Au nanodot arrays. The nanodot arrays were formed on substrates by vacuum deposition through a porous alumina mask with an ordered array of openings. By using an etchant with a high acid concentration and low oxidant concentration at a relatively low temperature, the area surrounding the Au/GaAs interface could be etched selectively. Under the optimum conditions, Au-capped GaAs nanopillar arrays were formed with an ordered periodicity of 100 nm and pillar heights of 50 nm.

Background: Carbon ion radiotherapy has precise dose distribution and high biological effectiveness and is likely a promising therapy for patients with sarcomas. We evaluated the outcomes of carbon ion radiotherapy in patients with unresectable chondrosarcomas., Patients and Methods: A retrospective analysis of 75 tumors in 73 patients treated with carbon ion radiotherapy was performed. There were 26 spinal, 38 pelvic, and 11 other types of tumors. Seventy conventional and five dedifferentiated chondrosarcomas were treated in 69 and four patients, respectively., Results: The median follow-up period was 49.4 (range=6.4-146.4) months. The 5-year local control, overall survival, and disease-free survival rates were 53%, 53%, and 34%, respectively. By multivariate analysis, tumor volume and histological grade were significantly related to overall and disease-free survival. Five patients required surgical intervention because of adverse events in the bones., Conclusion: Carbon ion radiotherapy might be a treatment option for unresectable chondrosarcoma., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Social anxiety disorder (SAD) patients commonly have broad dimensions of psychopathology. This study investigated the relationship between a wide range of psychopathology and attention or cognitions during cognitive behavioral therapy (CBT) for SAD., Methods: We treated 96 SAD patients with group CBT. Using multiple regression analysis, we examined the associations between the changes in broad dimensions of psychopathology and the changes in self-focused attention or maladaptive cognitions in the course of CBT., Results: The reduction in self-focused attention was related to the decreases in somatization, obsessive-compulsive, interpersonal sensitivity, anxiety, phobic anxiety, and global severity index. The reduction in maladaptive cognitions was associated with decreases in interpersonal sensitivity, depression, and global severity index., Conclusions: The present study suggests that changes in self-focused attention and maladaptive cognitions may predict broad dimensions of psychopathology changes in SAD patients over the course of CBT. For the purpose of improving a wide range of psychiatric symptoms with SAD patients in CBT, it may be useful to decrease self-focus attention and maladaptive cognitions., Competing Interests: There is no conflict of interest.

Interpersonal postural coordination (IPC) produced by interpersonal light touch (ILT), whereby time-series variations in the postural sway between two people unintentionally resemble each other, may be a possible social interaction. From a sociopsychological standpoint, close mutual behavioral coordination is recognized as "social glue," which represents the closeness of relationships and contributes to the building of a good rapport. Therefore, we hypothesized that if IPC functions as social glue, then IPC produced by ILT also represents a social relationship. Participants were dyadic pairs with a preexisting social relationship (acquaintance, friend, or best-friend), and we assessed the closeness between the partners. Postural sway in two quiet standing conditions-no touch (NT) and ILT (a mutual light touch with <1 N) condition-was concurrently measured with the side-by-side standing position, and the association of IPC with intradyadic closeness (rapport) was analyzed using hierarchical linear modeling. The results showed that unintentional IPC was higher in both axes of the ILT condition than in NT condition. Additionally, IPC in the mediolateral axis (the partner side) of the ILT condition was positively correlated with intradyadic closeness, whereas that in the anteroposterior axis (the non-partner side) showed a negative association. As expected, IPC represented intradyadic closeness (rapport). Results indicate that, in unintentional IPC produced by ILT, the priority of processing sensory feedback for postural control, which is received from the individual and a partner, is modulated depending on the rapport in interactional coupled feedback loops between the two individuals (i.e., good rapport increases the degree of taking in feedback from a partner). Thus, unintentional IPC produced by ILT functions as social glue, and it provides an understanding of the sociopsychological aspect in the human-to-human postural coordination mechanism.

In eukaryotic cells, highly condensed inactive/silenced chromatin has long been called "heterochromatin." However, recent research suggests that such regions are in fact not fully transcriptionally silent and that there exists only a moderate access barrier to heterochromatin. To further investigate this issue, it is critical to elucidate the physical properties of heterochromatin such as its total density in live cells. Here, using orientation-independent differential interference contrast (OI-DIC) microscopy, which is capable of mapping optical path differences, we investigated the density of the total materials in pericentric foci, a representative heterochromatin model, in live mouse NIH3T3 cells. We demonstrated that the total density of heterochromatin (208 mg/ml) was only 1.53-fold higher than that of the surrounding euchromatic regions (136 mg/ml) while the DNA density of heterochromatin was 5.5- to 7.5-fold higher. We observed similar minor differences in density in typical facultative heterochromatin, the inactive human X chromosomes. This surprisingly small difference may be due to that nonnucleosomal materials (proteins/RNAs) (∼120 mg/ml) are dominant in both chromatin regions. Monte Carlo simulation suggested that nonnucleosomal materials contribute to creating a moderate access barrier to heterochromatin, allowing minimal protein access to functional regions. Our OI-DIC imaging offers new insight into the live cellular environments., (© 2017 Imai et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)

Background: Chronic inflammation of the peritoneum causes peritoneal injury in patients on peritoneal dialysis. Intercellular adhesion molecule-1 and its circulating form, soluble intercellular adhesion molecule-1, play pivotal roles in inflammation. However, their role in peritoneal injury is unclear., Methods: We measured changes in intercellular adhesion molecule-1 expression in the peritoneum of a peritoneal injury model in rats. The associations between soluble intercellular adhesion molecule-1 levels in drained dialysate and the solute transport rate (D/P-Cr and D/D0-glucose) determined by the peritoneal equilibration test, and matrix metalloproteinase-2 levels in drained dialysate were investigated in 94 peritoneal drained dialysate samples., Results: Intercellular adhesion molecule-1 expression was increased in the peritoneum of rats with peritoneal injury. Soluble intercellular adhesion molecule-1 levels in drained dialysate were significantly positively correlated with D/P-Cr (r = .51, p < .01) and inversely correlated with D/D0-glucose (r = -.44, p < .01). They were also significantly positively correlated with matrix metalloproteinase-2 levels in drained dialysate (r = .86, p < .01)., Conclusions: Intercellular adhesion molecule-1expression is increased in the peritoneum of a peritoneal injury model in the rat, and soluble intercellular adhesion molecule-1 levels in drained dialysate are associated with peritoneal injury in patients on peritoneal dialysis. These results suggest that soluble intercellular adhesion molecule-1 could be a novel biomarker of peritoneal injury in patients on peritoneal dialysis.

Background: We assessed the long-term safety and efficacy of tolvaptan in 102 patients with heart failure (HF) and chronic kidney disease (CKD). Median follow-up duration was 1.6 years (1.0-4.4 years).Methods and Results:One patient discontinued tolvaptan because of hypernatremia. There were no changes in renal function or electrolytes during the 1-year follow-up. The cardiac-related death-free or HF-related hospitalization-free survival rate was significantly higher in patients receiving tolvaptan than in propensity score-matched patients who did not receive tolvaptan., Conclusions: In patients with HF and CKD, long-term administration of tolvaptan was well-tolerated, relatively safe and effective, suggesting its utility for long-term management of these conditions.

WP1066 is a well-known inhibitor of the JAK/STAT3 signaling pathway. By a screen of known small molecule inhibitors of various enzymes and protein factors, we identified WP1066 as a ceramide glucosyltransferase inhibitor. Ceramide glucosyltransferase catalyzes the first glycosylation step during glycosphingolipid synthesis. We found that WP1066 inhibited the activity of ceramide glucosyltransferase with an IC 50 of 7.2 μM, and that its action was independent of JAK/STAT3 pathway blockade. Moreover, the modes of inhibition of ceramide glucosyltransferase were uncompetitive with respect to both C 6 -NBD-cermide and UDP-glucose., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The currently favoured method for wheat (Triticum aestivum L.) transformation is inapplicable to many elite cultivars because it requires callus culture and regeneration. Here, we developed a simple, reproducible, in planta wheat transformation method using biolistic DNA delivery without callus culture or regeneration. Shoot apical meristems (SAMs) grown from dry imbibed seeds were exposed under a microscope and subjected to bombardment with different-sized gold particles coated with the GFP gene construct, introducing DNA into the L2 cell layer. Bombarded embryos were grown to mature, stably transformed T 0 plants and integration of the GFP gene into the genome was determined at the fifth leaf. Use of 0.6-µm particles and 1350-psi pressure resulted in dramatically increased maximum ratios of transient GFP expression in SAMs and transgene integration in the fifth leaf. The transgene was integrated into the germ cells of 62% of transformants, and was therefore inherited in the next generation. We successfully transformed the model wheat cultivar 'Fielder', as well as the recalcitrant Japanese elite cultivar 'Haruyokoi'. Our method could potentially be used to generate stable transgenic lines for a wide range of commercial wheat cultivars.

The anorexigenic neuropeptide NEFA/nucleobindin 2 (NUCB2)/nesfatin-1-containing neurons are distributed in the brain regions involved in feeding regulation. In spite of the growing knowledge of its physiological functions through extensive studies, its molecular mechanism of reaction, including its receptor, remains unknown. NUCB2/nesfatin-1 is also involved in various peripheral regulations, including glucose homeostasis. In pancreatic beta-cells, NUCB2/nesfatin-1 is reported to enhance glucose-stimulated insulin secretion (GSIS) but its exact mechanism remains unknown. To clarify this mechanism, we measured the effect of nesfatin-1 on the electrical activity of pancreatic beta-cells. Using mouse primary beta cells, we measured changes in the ATP-sensitive K + (K ATP ) channel current, the voltage-gated K + (Kv) channel current, and insulin secretion upon application of nesfatin-1. Nesfatin-1 inhibited the Kv channel, but K ATP channel activity was unaffected. Nesfatin-1 enhanced insulin secretion to a same level as Kv channel blocker tetraethylammonium (TEA). The effect was not further enhanced when nesfatin-1 and TEA were applied simultaneously. The inhibition binding assay with [ 125 I]nesfatin-1 in Kv2.1 channels, major contributor of Kv current in beta cell, expressing HEK239 cells indicated the binding of nesfatin-1 on Kv2.1 channel. Because Kv channel inhibition enhances insulin secretion under high glucose conditions, our present data suggest a possible mechanism of nesfatin-1 on enhancing GSIS through regulation of ion channels rather than its unidentified receptor., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Trehalose 6-phosphate phosphorylase (TrePP), a member of glycoside hydrolase family 65, catalyzes the reversible phosphorolysis of trehalose 6-phosphate (Tre6P) with inversion of the anomeric configuration to produce β-d-glucose 1-phosphate (β-Glc1P) and d-glucose 6-phosphate (Glc6P). TrePP in Lactococcus lactis ssp. lactis (LlTrePP) is, alongside the phosphotransferase system, involved in the metabolism of trehalose. In this study, recombinant LlTrePP was produced and characterized. It showed its highest reverse phosphorolytic activity at pH 4.8 and 40°C, and was stable in the pH range 5.0-8.0 and at up to 30°C. Kinetic analyses indicated that reverse phosphorolysis of Tre6P proceeded through a sequential bi bi mechanism involving the formation of a ternary complex of the enzyme, β-Glc1P, and Glc6P. Suitable acceptor substrates were Glc6P, and, at a low level, d-mannose 6-phosphate (Man6P). From β-Glc1P and Man6P, a novel sugar phosphate, α-d-Glcp-(1↔1)-α-d-Manp6P, was synthesized with 51% yield.

The eukaryotic genome is organized within cells as chromatin. For proper information output, higher-order chromatin structures can be regulated dynamically. How such structures form and behave in various cellular processes remains unclear. Here, by combining super-resolution imaging (photoactivated localization microscopy [PALM]) and single-nucleosome tracking, we developed a nuclear imaging system to visualize the higher-order structures along with their dynamics in live mammalian cells. We demonstrated that nucleosomes form compact domains with a peak diameter of ∼160 nm and move coherently in live cells. The heterochromatin-rich regions showed more domains and less movement. With cell differentiation, the domains became more apparent, with reduced dynamics. Furthermore, various perturbation experiments indicated that they are organized by a combination of factors, including cohesin and nucleosome-nucleosome interactions. Notably, we observed the domains during mitosis, suggesting that they act as building blocks of chromosomes and may serve as information units throughout the cell cycle., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Panic disorder (PD) is a common disease and presents with broad dimensions of psychopathology. Cognitive behavioral therapy (CBT) is known to improve these broad dimensions of psychopathology in addition to PD symptoms. However, little is known about the predictors of treatment response in comorbid psychiatric symptoms after CBT for PD. Recent studies suggest that anxiety sensitivity (AS) may be a key vulnerability for PD. This study aimed to examine AS as a predictor of broad dimensions of psychopathology after CBT for PD., Materials and Methods: In total, 118 patients with PD were treated with manualized group CBT. We used multiple regression analysis to examine the associations between 3 Anxiety Sensitivity Index (ASI) factors (physical concerns, mental incapacitation concerns, and social concerns) at baseline and the subscales of the Symptom Checklist-90 Revised (SCL-90-R) at endpoint., Results: Low levels of social concerns at baseline predicted low levels on 5 SCL-90-R subscales after CBT: interpersonal sensitivity, depression, hostility, paranoid ideation, and psychosis. High levels of mental incapacitation concerns significantly predicted low levels on 3 SCL-90-R subscales after treatment: interpersonal sensitivity, hostility, and paranoid ideation. Physical concerns at baseline did not predict broad dimensions of psychopathology., Conclusion: This study suggested that the social concerns and mental incapacitation concerns subscales of the ASI at baseline predicted several dimensions of psychopathology after CBT for PD. To improve comorbid psychopathology, it may be useful to direct more attention to these ASI subscales., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

[Purpose] It has also been reported that decreased activity in the reward pathway causes a decrease in brain activity in the descending pain control system in people with high trait anxiety. Activation of this system is dependent on both the reward pathway and motor areas. Recently, studies have also shown that motor areas are activated by illusory kinesthesia. It was aimed to explore whether anxiety trait modulates the influence of illusory kinesthesia on pain threshold. [Subjects and Methods] The pain threshold and trait anxiety at rest before vibratory tendon stimulation (the task) were measured. After the task, the pain threshold, the illusory kinesthesia angle, and the intensity of illusory kinesthesia for patients with and without illusory kinesthesia were measured. A total of 35 healthy right-handed students participated, among whom 22 and 13 were included in the illusion and no-illusion groups, respectively. [Results] There was a significant increase in the pain threshold after task completion in both groups; however, there was no statistically significant difference between the two groups. Correlational analysis revealed that State-Trait Anxiety Inventory-trait score correlated negatively with the pain threshold in the no-illusion group, but there was no correlation in the illusion group. [Conclusion] The pain threshold improved regardless of the size of trait anxiety in the illusion group, but did not improve merely through sensory input by vibratory stimulation in the no-illusion group. Thus, illusory kinesthesia has effect of increasing the pain threshold.

Introduction: This study examined the relationships between changes in symptoms and changes in quality of life (QOL) during cognitive-behavioral therapy (CBT) for panic disorder (PD)., Methods: We treated 198 PD patients with group CBT in Japan. Using multiple regression analysis, we examined the associations between changes in QOL and changes in PD symptoms or comorbid psychological symptoms during CBT., Results: Changes in anticipatory anxiety, agoraphobic fear/avoidance, and somatization were significant predictors of changes in some aspects of QOL., Discussion: It might be useful to decrease somatization, anticipatory anxiety, and agoraphobic fear to improve QOL in CBT for PD., (© 2016 John Wiley & Sons Australia, Ltd.)

Objective: Prenatal diagnosis of skeletal dysplasia by means of 3D skeletal CT examination is highly accurate. However, it carries a risk of fetal exposure to radiation. Model-based iterative reconstruction (MBIR) technology can reduce radiation exposure; however, to our knowledge, the lower limit of an optimal dose is currently unknown. The objectives of this study are to establish ultra-low-dose fetal CT as a method for prenatal diagnosis of skeletal dysplasia and to evaluate the appropriate radiation dose for ultra-low-dose fetal CT., Subjects and Methods: Relationships between tube current and image noise in adaptive statistical iterative reconstruction and MBIR were examined using a 32-cm CT dose index (CTDI) phantom. On the basis of the results of this examination and the recommended methods for the MBIR option and the known relationship between noise and tube current for filtered back projection, as represented by the expression SD = (milliamperes) -0.5 , the lower limit of the optimal dose in ultra-low-dose fetal CT with MBIR was set. The diagnostic power of the CT images obtained using the aforementioned scanning conditions was evaluated, and the radiation exposure associated with ultra-low-dose fetal CT was compared with that noted in previous reports., Results: Noise increased in nearly inverse proportion to the square root of the dose in adaptive statistical iterative reconstruction and in inverse proportion to the fourth root of the dose in MBIR. Ultra-low-dose fetal CT was found to have a volume CTDI of 0.5 mGy. Prenatal diagnosis was accurately performed on the basis of ultra-low-dose fetal CT images that were obtained using this protocol. The level of fetal exposure to radiation was 0.7 mSv., Conclusion: The use of ultra-low-dose fetal CT with MBIR led to a substantial reduction in radiation exposure, compared with the CT imaging method currently used at our institution, but it still enabled diagnosis of skeletal dysplasia without reducing diagnostic power.

Chordomas are rare, malignant bone tumors of the skull-base and axial skeleton. Until recently, there was no consensus among experts regarding appropriate clinical management of chordoma, resulting in inconsistent care and suboptimal outcomes for many patients. To address this shortcoming, the European Society of Medical Oncology (ESMO) and the Chordoma Foundation, the global chordoma patient advocacy group, convened a multi-disciplinary group of chordoma specialists to define by consensus evidence-based best practices for the optimal approach to chordoma. In January 2015, the first recommendations of this group were published, covering the management of primary and metastatic chordomas. Additional evidence and further discussion were needed to develop recommendations about the management of local-regional failures. Thus, ESMO and CF convened a second consensus group meeting in November 2015 to address the treatment of locally relapsed chordoma. This meeting involved over 60 specialists from Europe, the United States and Japan with expertise in treatment of patients with chordoma. The consensus achieved during that meeting is the subject of the present publication and complements the recommendations of the first position paper., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Objectives: We investigated the effects of the illusion of motion through tendon vibration on hand function in patients with distal radius fractures., Setting: Kawachi General Hospital, Japan., Subjects: A total of 22 patients with distal radius fractures were divided into either an illusory kinesthesia group ( n = 11) or a control group ( n = 11)., Intervention: We performed the intervention for seven consecutive days after surgery. Evaluations were performed at one day, seven days, one month, and two months postsurgery., Main Measures: Data were collected on pain at rest and pain during movement. The Patient-Rated Wrist Evaluation and Pain Catastrophizing Scale were also used., Results: The illusory kinesthesia group showed significantly better scores on Patient-Rated Wrist Evaluation ( p < 0.01) compared with the control group at seven days, one month, and two months postsurgery. The mean (SD) of the Patient-Rated Wrist Evaluation total score was 97.6 (2.2) at one day postsurgery and 9.1 (5.3) at seven days postsurgery in the illusory kinesthesia group, while the Patient-Rated Wrist Evaluation total score was 96.3 (4.4) at one day postsurgery and 20.1 (17.0) at seven days postsurgery in the control group., Conclusion: Our results indicate that illusory kinesthesia is an effective postsurgery management strategy not only for pain alleviation, but also hand function in patients with distal radius fractures. Furthermore, the significant improvements persisted for up to two months after intervention in the illusory kinesthesia group, but not in the control group. In addition, patients in the kinesthetic illusions group showed increased use of the affected limb in daily living.

The traditional Japanese herbal medicine hangeshashinto (HST) has beneficial effects for the treatment of oral ulcerative mucositis (OUM) in cancer patients. However, the ingredient-based mechanism that underlies its pain-relieving activity remains unknown. In the present study, to clarify the analgesic mechanism of HST on OUM-induced pain, we investigated putative HST ingredients showing antagonistic effects on Na + channels in vitro and in vivo. A screen of 21 major ingredients using automated patch-clamp recordings in channel-expressing cells showed that [6]-gingerol and [6]-shogaol, two components of a Processed Ginger extract, considerably inhibited voltage-activated Na + currents. These two ingredients inhibited the stimulant-induced release of substance P and action potential generation in cultured rat sensory neurons. A submucosal injection of a mixture of [6]-gingerol and [6]-shogaol increased the mechanical withdrawal threshold in healthy rats. In a rat OUM model, OUM-induced mechanical pain was alleviated 30min after the swab application of HST despite the absence of anti-bacterial and anti-inflammatory actions in the OUM area. A swab application of a mixture of [6]-gingerol and [6]-shogaol induced sufficient analgesia of OUM-induced mechanical or spontaneous pain when co-applied with a Ginseng extract containing abundant saponin. The Ginseng extract demonstrated an acceleration of substance permeability into the oral ulcer tissue without an analgesic effect. These findings suggest that Na + channel blockage by gingerol/shogaol plays an essential role in HST-associated analgesia of OUM-induced pain. This pharmacological mechanism provides scientific evidence supporting the use of this herbal medicine in patients suffering from OUM-induced pain., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background and Purpose: The efficacy of carbon ion radiotherapy (CIRT) for bone and soft tissue sarcoma has been reported recently. Although histological assessment after CIRT requires skilled interpretation, little information is presently available. In this study, we report sequential histological findings after treatment with CIRT, and evaluate the association between these findings and clinical response., Material and Methods: Seven patients with unresectable sarcoma underwent needle biopsy 12 times at an average of 14.3 months after CIRT and were included in this study., Results: One patient underwent two biopsies after CIRT for chordoma. Although a few suspected residual chordoma cells were observed at 19 and 30 months after CIRT, the tumor continued to shrink at 75 months. Immunohistochemical analysis of post-CIRT specimens revealed CK AE1/3, EMA, and S100 expression, as in the pre-CIRT specimen. In total, viable tumor cells were found in 9 of 12 specimens; however, only 2 patients showed recurrent masses on radiological examination. The other 5 patients had stable disease., Conclusions: Viable tumor cells after CIRT did not always cause recurrence. This may be due to observation of dying cells or radiation-induced deformed cells. Histological evaluation after CIRT should be done carefully.

Type 2 diabetic Tsumura, Suzuki, obese, diabetes (TSOD) mice gradually gain weight as compared to corresponding Tsumura, Suzuki, non-obesity (TSNO) control mice, and develop insulin resistance. Although development of type 2 diabetes mellitus is associated with dysfunction of adipocytes, little is known about the properties of adipocytes from TSOD mice. Therefore, we attempted to remove intracorporeal factors and elucidate inherent properties of adipocytes of TSOD mice using adipocytes differentiated from mouse embryonic fibroblasts (MEFs) in vitro. Here, we show that MEFs of TSOD have low potency for differentiation into adipocytes. The percentage of Oil red O-stained cells and levels of adipogenic markers in cells differentiated from MEFs of TSOD are lower than those in cells differentiated from MEFs of TSNO. We further show that treatment with an agonist of peroxisome proliferator-activated receptor-γ (PPARγ) (rosiglitazone) at an early stage of differentiation increases the percentage of Oil red O-stained cells in TSOD-MEFs differentiated into adipocytes. Moreover, the lipid droplet size in those adipocytes is larger than that in the adipocytes differentiated from MEFs of TSNO. Although persistent treatment of MEFs of TSOD with rosiglitazone during differentiation increases the percentage of Oil red O-stained cells, the lipid droplet size in adipocytes treated as such does not reach the size of those treated in early stage only. Thus, activation of PPARγ by its agonist at an early stage of differentiation compensates for the low potency toward adipogenic differentiation of, and accelerates formation of enlarged lipid droplets in adipocytes derived from, MEFs of TSOD mice.

Background . A new agent, potassium-competitive acid blocker vonoprazan (VPZ) has potent acid-inhibitory effects and may offer advantages over conventional H. pylori eradication therapies. We aimed to compare the eradication rate between VPZ-based treatment and PPI-based one. Methods . This randomized controlled trial was designed to assign 141 patients with H. pylori- positive gastritis to VPZ group (VPZ 20 mg, amoxicillin 750 mg, and clarithromycin 200 or 400 mg twice daily for 7 days) or PPI group (rabeprazole 20 mg or lansoprazole 30 mg, amoxicillin 750 mg, and clarithromycin 200 or 400 mg twice daily for 7 days). Primary endpoints were eradication rates and adverse events. Results . Seventy of 72 patients in VPZ group and 63 of 69 patients in PPI group completed the treatment after 7 days. The eradication rate was significantly higher in VPZ group than PPI group by intention-to-treat analysis (95.8% versus 69.6%, P = 0.00003, 95% confidence interval [CI] 88.3-99.1% versus 57.3-80.1%) and per-protocol analysis (95.7% versus 71.4%, P = 0.0002, 95% CI 88.0-99.1% versus 58.7-82.1%). The incidence of adverse events was not different between the groups (26.3% in VPZ group versus 37.7% in PPI group, P = 0.15). Conclusion . VPZ-based regimen is more useful than that PPI-based regimen as a first-line H. pylori eradication therapy., Competing Interests: The authors have no conflict of interests to disclose.

Background and Purpose: Carbon-ion radiotherapy (C-ion RT) was effective therapy for inoperable spinal and paraspinal sarcomas. However, a significant adverse event following radiotherapies is vertebral compression fractures (VCFs). In this study, we investigated the incidence of and risk factors for post-C-ion RT VCFs in patients with spinal or paraspinal sarcomas., Material and Methods: Thirty consecutive patients with spinal or paraspinal sarcomas treated with C-ion RT were retrospectively reviewed. Various clinical parameters and the Spinal Instability Neoplastic Score (SINS) were used to evaluate the risk factors for post-C-ion RT VCFs., Results: The overall incidence of VCFs was 23% (median time: 7 months). Patients with VCFs showed a markedly higher SINS score (median value, 9 points) than those without VCF (5 points). The area under the receiver operating characteristic curve for the SINS score was 0.88, and the optimum SINS cut-off score was 8 points. The cumulative incidence of VCFs at 1 year was 9% for patients with a SINS score under 8 points, versus 80% for those with a SINS score of 8 points or higher ( p < 0.0001)., Conclusions: In patients with a SINS score of 8 points or higher, referral to a spine surgeon for stabilization and multidisciplinary discussion is appropriate.

Intramyocardial dissecting hematoma is a rare but potentially fatal complication of myocardial infarction. The decision to adopt a surgical or conservative strategy may depend on the clinical and hemodynamic stability of patients. Regardless, the precise and temporal assessment of the structure of hematoma is imperative. We herein report the first case of a patient with early spontaneous remission of intramyocardial dissecting hematoma successfully managed by a conservative approach with multimodality imaging.

The hairy roots (HR) of Ophiorrhiza pumila produce camptothecin (CPT), a monoterpenoid indole alkaloid used as a precursor in the synthesis of chemotherapeutic drugs. O. pumila HR culture is considered as a promising alternative source of CPT, however, the knowledge about the biosynthetic pathway and regulatory mechanism is still limited. In this study, five genes that encode AP2/ERF transcription factors, namely OpERF1 - OpERF5 , were isolated from HR of O. pumila . Phylogenetic analysis of AP2/ERF protein sequences suggested the close evolutionary relationship of Op ERF1 with stress-responsive ERF factors in Arabidopsis and of Op ERF2 with ERF factors reported to regulate alkaloid production, such as ORCA3 in Catharanthus roseus, NIC2 locus ERF in tobacco, and JRE4 in tomato. We generated the transgenic HR lines of O. pumila , ERF1i and ERF2i, in which the expression of OpERF1 and OpERF2 , respectively, was suppressed using RNA interference technique. The transcriptome and metabolome of these suppressed HR were analyzed for functional characterization of Op ERF1 and Op ERF2. Although significant changes were not observed in the metabolome, including CPT and related compounds, the suppression of OpERF2 resulted in reduced expression of genes in the 2- C -methyl-d-erythritol 4-phosphate and secologanin-strictosidine pathways, which supply a precursor, strictosidine, for CPT biosynthesis. Furthermore, while it was not conclusive for Op ERF1, enrichment analysis of differentially expressed genes in the suppressed HR showed that the gene ontology terms for oxidation-reduction, presumably involved in secondary metabolite pathways, were enriched in the ERF2i downregulated gene set. These results suggest a positive role of Op ERF2 in regulating specialized metabolism in O. pumila .

The vascular endothelial growth factor (VEGF) family has a key role in the formation of blood vessels and lymphatics. Among the members of this family, VEGF-C is one of the most important factors involved in lymphangiogenesis via binding with two receptors (vascular endothelial growth factor receptor-2 and -3: VEGFR-2 and VEGFR-3). Soluble VEGFR-2 (sVEGFR-2) has a role in maintaining the alymphatic state of the cornea associated with binding to VEGF-C, and selectively inhibits lymphangiogenesis but not angiogenesis. In this study, we introduced sVEGFR-2 into lung cancer cells and evaluated the influence on tumor progression and on genes regulating lymphatic formation and metastasis in vivo. A retroviral vector was used to introduce the sVEGFR-2 gene into Lewis lung carcinoma cells (LLC), which were designated as LLC-sVEGFR-2 cells. Proteins secreted into the culture supernatant by these cells were detected by western blotting using specific antibodies. To examine lymphangiogenesis by primary lung cancer in vivo, LLC-sVEGFR-2 cells were subcutaneously injected into C57BL/6 mice. At 14days after injection, immunohistochemistry was performed using an antibody directed against lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), a marker of lymphatics. Expression of mRNA for VEGFR-2, VEGFR-3 and matrix metalloproteinases (MMPs) was also determined by real-time PCR. Furthermore, LLC-sVEGFR-2 cells were directly inoculated into the left lung in C57BL/6 mice and the number of micro-metastases in pulmonary lymph nodes was determined. Introduction of sVEGFR-2 into LLC cells resulted in secretion of sVEGFR-2 protein into the culture supernatant. There were fewer LYVE-1 positive lymphatics after inoculation of LLC-sVEGFR-2 into mice compared with the control group. In addition, VEGFR-2, VEGFR-3, and MMPs gene expression was suppressed in the primary tumors of the LLC-sVEGFR-2 group compared with the control group. Furthermore, there were fewer micro-metastases in the pulmonary lymph nodes of the LLC-sVEGFR-2 group compared with the control group after cells were directly inoculated into the lung. These findings indicate that introduction of sVEGFR-2 suppressed lymphangiogenesis in primary lung cancer and also suppressed lymphogenic metastasis by inhibiting VEGF-C, followed by down-regulation of VEGFR-2, VEGFR-3 and MMPs. Accordingly, sVEGFR-2 might be a promising target for treatment of cancer by regulating lymphangiogenesis and lymphogenic metastasis., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Lipoprotein(a) [Lp(a)], which is genetically determined, has been reported as an independent risk factor for atherosclerotic vascular disease. However, the prognostic value of Lp(a) for secondary vascular events in patients after coronary artery disease has not been fully elucidated. This 3-year observational study included a total of 176 patients with ST-elevated myocardial infarction (STEMI), whose Lp(a) levels were measured within 24 h after primary percutaneous coronary intervention. We divided enrolled patients into two groups according to Lp(a) level and investigated the association between Lp(a) and the incidence of major adverse cardiac and cerebrovascular events (MACCE). A Kaplan-Meier analysis demonstrated that patients with higher Lp(a) levels had a higher incidence of MACCE than those with lower Lp(a) levels (log-rank P = 0.034). A multivariate Cox regression analysis revealed that Lp(a) levels were independently correlated with the occurrence of MACCE after adjusting for other classical risk factors of atherosclerotic vascular diseases (hazard ratio 1.030, 95 % confidence interval: 1.011-1.048, P = 0.002). In receiver-operating curve analysis, the cutoff value to maximize the predictive power of Lp(a) was 19.0 mg/dl (area under the curve = 0.674, sensitivity 69.2 %, specificity 62.0 %). Evaluation of Lp(a) in addition to the established coronary risk factors improved their predictive value for the occurrence of MACCE. In conclusion, Lp(a) levels at admission independently predict secondary vascular events in patients with STEMI. Lp(a) might provide useful information for the development of secondary prevention strategies in patients with myocardial infarction.

The impact of variation in mating system on genetic diversity is a well-debated topic in evolutionary biology. The diploid sexual race of Cyrtomium falcatum (Japanese holly fern) shows mating system variation, i.e., it displays two different types of sexual expression (gametangia formation) in gametophytes: mixed (M) type and separate (S) type. We examined whether there is variation in the selfing rate among populations of this species, and evaluated the relationship between mating system, genetic diversity and effective population size using microsatellites. In this study, we developed eight new microsatellite markers and evaluated genetic diversity and structure of seven populations (four M-type and three S-type). Past effective population sizes (Ne) were inferred using Approximate Bayesian computation (ABC). The values of fixation index (FIS), allelic richness (AR) and gene diversity (h) differed significantly between the M-type (FIS: 0.626, AR: 1.999, h: 0.152) and the S-type (FIS: 0.208, AR: 2.718, h: 0.367) populations (when admixed individuals were removed from two populations). Although evidence of past bottleneck events was detected in all populations by ABC, the current Ne of the M-type populations was about a third of that of the S-type populations. These results suggest that the M-type populations have experienced more frequent bottlenecks, which could be related to their higher colonization ability via gametophytic selfing. Although high population differentiation among populations was detected (FST = 0.581, F'ST = 0.739), there was no clear genetic differentiation between the M- and S-types. Instead, significant isolation by distance was detected among all populations. These results suggest that mating system variation in this species is generated by the selection for single spore colonization during local extinction and recolonization events and there is no genetic structure due to mating system., Competing Interests: The authors have declared that no competing interests exist.

Tolvaptan, a vasopressin type 2 receptor antagonist, has an aquaretic effect without affecting renal function. The effects of long-term tolvaptan administration in heart failure patients with renal dysfunction have not been clarified. Here, we assessed the clinical benefit of tolvaptan during a 6-month follow-up in acute decompensated heart failure (ADHF) patients with severe chronic kidney disease (CKD; estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m(2)). We compared 33 patients with ADHF and severe CKD who were administered tolvaptan in addition to loop diuretics (TLV group), with 36 patients with ADHF and severe CKD who were administered high-dose loop diuretics (≥40 mg) alone (LD group). Alterations in serum creatinine and eGFR levels from the time of hospital discharge to 6-month follow-up were significantly different between the groups, with those in the TLV group being more favorable. Furthermore, Kaplan-Meier analysis revealed that rehospitalization for heart failure (HF) was significantly lower in the TLV group compared with the LD group. In ADHF patients with severe CKD, tolvaptan use for 6 months reduced worsening of renal function and rehospitalization rates for HF when compared with conventional diuretic therapy. In conclusion, tolvaptan could be a safe and effective agent for long-term management of HF and CKD.

Touching a stable object with a fingertip using slight force (<1 N) stabilizes standing posture independent of mechanical support, which is referred to as the effect of light touch (LT). In the neural mechanism of the effect of LT, the specific contribution of the cortical brain activity toward the effect of LT remains undefined, particularly the contribution toward steady-state postural sway. The aim of the present study was to investigate the cortical region responsible for the reduction of postural sway in response to the effect of LT. Active LT was applied with the right fingertip and transcranial direct current stimulation (sham or cathodal) was applied to the left primary sensorimotor cortex or the left posterior parietal cortex in the two groups. The experiments were conducted using a single-blind sham-controlled crossover design. Steady-state postural sway was compared with the factors of transcranial direct current stimulation (sham or cathodal) and time (pre or post). In the results, the effect of LT reduced postural stability in the mediolateral direction after cathodal transcranial direct current stimulation of the left posterior parietal cortex. No effect was observed after stimulation of the left primary sensorimotor cortex. This indicates that the left posterior parietal cortex is partly responsible for the effect of LT when touching a fixed point with the right fingertip during suprapostural tasks, where posture is adjusted according to the precision requirements. Cortical processing of sensory integration for voluntary postural orientation in response to touch occurs in the posterior parietal cortex.

Background: Songbirds are a preeminent animal model for understanding the neural basis underlying the development and evolution of a complex learned behavior, bird song. However, only a few quantitative methods exist to analyze these species-specific sequential behaviors in multiple species using the same calculation method., New Method: We report a method of analysis that focuses on calculating the frequency of characteristic syllable transitions in songs. This method comprises two steps: The first step involves forming correlation matrices of syllable similarity scores, named syllable similarity matrices (SSMs); these are obtained by calculating the round-robin comparison of all the syllables in two songs, while maintaining the sequential order of syllables in the songs. In the second step, each occurrence rate of three patterns of binarized "2 rows×2 columns" cells in the SSMs is calculated to extract information on the characteristic syllable transitions., Results: The SSM analysis method allowed obtaining species-specific features of song patterns and intraspecies individual variability simultaneously. Furthermore, it enabled quantitative tracking of the developmental trajectory of the syllable sequence patterns., Comparison With Existing Method: This method enables us to extract the species-specific song patterns and dissect the regulation of song syntax development without human-biased procedures for syllable identification. This method can be adapted to study the acoustic communication systems in several animal species, such as insects and mammals., Conclusions: This present method provides a comprehensive qualitative approach for understanding the regulation of species specificity and its development in vocal learning., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To investigate the short-term effects of the life goal concept on subjective well-being and treatment engagement, and to determine the sample size required for a larger trial., Design: A quasi-randomized controlled trial that was not blinded., Setting: A subacute rehabilitation ward., Subjects: A total of 66 patients were randomized to a goal-setting intervention group with the life goal concept (Life Goal), a standard rehabilitation group with no goal-setting intervention (Control 1), or a goal-setting intervention group without the life goal concept (Control 2)., Interventions: The goal-setting intervention in the Life Goal and Control 2 was Goal Attainment Scaling. The Life Goal patients were assessed in terms of their life goals, and the hierarchy of goals was explained. The intervention duration was four weeks., Main Measures: Patients were assessed pre- and post-intervention. The outcome measures were the Hospital Anxiety and Depression Scale, 12-item General Health Questionnaire, Pittsburgh Rehabilitation Participation Scale, and Functional Independence Measure., Results: Of the 296 potential participants, 66 were enrolled; Life Goal (n = 22), Control 1 (n = 22) and Control 2 (n = 22). Anxiety was significantly lower in the Life Goal (4.1 ±3.0) than in Control 1 (6.7 ±3.4), but treatment engagement was significantly higher in the Life Goal (5.3 ±0.4) compared with both the Control 1 (4.8 ±0.6) and Control 2 (4.9 ±0.5)., Conclusions: The life goal concept had a short-term effect on treatment engagement. A sample of 31 patients per group would be required for a fully powered clinical trial., (© The Author(s) 2015.)

Introduction: A pathological nystagmus is an objective sign that a patient feels vertigo. However, there have been few opportunities to observe and record pathological nystagmus during a paroxysmal vertigo attack. Furthermore, it can be difficult to obtain cooperation in pediatric patients. We present two cases of paroxysmal vertigo in children in whom we successfully recorded and analyzed their pathological nystagmus during a vertigo attack., Methods: Of a total sample of 4349 patients seen at our hospital for dizziness in the last decade, a retrospective analysis revealed that 68 were children (<15 years old; 1.6%). Of these 68 children, we successfully identified pathological nystagmus during paroxysmal vertigo in only two (2.9%)., Results: Case 1 was a 4-year-old girl. She felt vertigo the strongest when her left ear was down in the supine position. We observed and recorded her nystagmus during a vertigo attack with her mother's permission. Her positional nystagmus in the supine position was horizontal persistent apogeotropic nystagmus. Rightward nystagmus in the left-ear-down supine position was stronger than leftward nystagmus in the right-ear-down supine position. Therefore, the diagnosis was right lateral canal type of benign paroxysmal positional vertigo, of which the pathophysiology was cupulolithiasis. The other patient was an 11-year-old boy. He had a family history of migraines. His vertigo attacks occurred after onset of a severe migraine and lasted between 2 and 48 h. During an attack that we observed, he showed nystagmus, which was direction-fixed right torsional and rightward in darkness. His mother had noticed that his eyes moved abnormally and that his left eye did not shift to the left side when he looked leftward. He was old enough to clearly express his own symptoms. Other neurological examinations were normal. The diagnosis was vestibular migraine., Conclusions: We analyzed a pathological nystagmus during paroxysmal vertigo in two children. We conclude that children can be diagnosed with a combination of careful history taking and accurate examinations of a pathological nystagmus., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

TAD1 (Triticum aestivum defensin 1) is induced during cold acclimation in winter wheat and encodes a plant defensin with antimicrobial activity. In this study, we demonstrated that recombinant TAD1 protein inhibits hyphal growth of the snow mold fungus, Typhula ishikariensis in vitro. Transgenic wheat plants overexpressing TAD1 were created and tested for resistance against T. ishikariensis. Leaf inoculation assays revealed that overexpression of TAD1 confers resistance against the snow mold. In addition, the TAD1-overexpressors showed resistance against Fusarium graminearum, which causes Fusarium head blight, a devastating disease in wheat and barley. These results indicate that TAD1 is a candidate gene to improve resistance against multiple fungal diseases in cereal crops., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: Recent studies have demonstrated that mouthwash made with the traditional Japanese medicine hangeshashinto exhibits anti-inflammatory action and alleviates oral mucositis scores, including pain complaints, in patients undergoing chemoradiotherapy. However, no study has demonstrated the mechanism underlying how hangeshashinto provides pain relief in oral ulcers., Design: The analgesic effects on pain-related behaviors following the topical application of hangeshashinto were evaluated in an oral ulcer rat model treated with acetic acid using recently developed methods. Indomethacin, the representative anti-inflammatory agent, was intraperitoneally administered. The tissue permeability of the oral mucosa was histologically evaluated after applying the fluorescent substance FluoroGold., Results: The topical application of hangeshashinto in ulcerative oral mucosa suppressed mechanical pain hypersensitivity over 60 min, without any effects on healthy mucosa. The same drug application also inhibited oral ulcer-induced spontaneous pain. Indomethacin administration failed to block the mechanical pain hypersensitivity, though it did largely block spontaneous pain. Topical anesthesia with lidocaine showed hyposensitivity to mechanical stimulation in healthy mucosa. In the ulcer regions in which the oral epithelial barrier was destroyed, deep parenchyma was stained with FluoroGold, in contrast to healthy oral mucosa, in which staining was limiting to the superficial site., Conclusions: Hangeshashinto leads to long-lasting analgesic effects, specifically in the ulcer region by destroying the epithelial barrier. Hangeshashinto alleviates oral ulcer-induced pain in inflammation-dependent and/or independent manner., (Copyright © 2016. Published by Elsevier Ltd.)