Search

Ruminiclostridium josui Fae1A is a modular enzyme consisting of an N-terminal signal peptide, family-1 carbohydrate esterase module (CE1), family-6 carbohydrate-binding module (CBM6), and dockerin module in that order. Recombinant CE1 and CBM6 polypeptides were collectively and separately produced as RjFae1A, RjCE1, and RjCBM6. RjFae1A showed higher feruloyl esterase activity than RjCE1 towards insoluble wheat arabinoxylan, but the latter was more active towards small synthetic substrates than the former. This suggests that CBM6 in RjFae1A plays an important role in releasing ferulic acid from the native substrate. RjCBM6 showed a higher affinity for soluble wheat arabinoxylan than for rye arabinoxylan and beechwood xylan in native affinity polyacrylamide gel electrophoresis. Isothermal titration calorimetry analysis demonstrated that RjCBM6 recognized a xylopyranosyl residue at the nonreducing ends of xylooligosaccharides. Moreover, it showed exceptional affinity for 23-α-l-arabinofuranosyl-xylotriose (A2XX) among the tested branched arabinoxylooligosaccharides. Fluorometric titration analysis demonstrated that xylobiose and A2XX competitively bound to RjCBM6, and both bound to the same site in RjCBM6. RjCBM6's preference for the xylopyranosyl residue at the nonreducing end of xylan chains explains why the positive effect of CBM6 on RjFae1A activity was observed only during short incubation but not after extended incubation.

Background Although anticoagulation effectively prevents stroke in patients with atrial fibrillation (AF), it has been underused in elderly AF patients for many reasons, mainly because of knowledge gaps regarding cardiovascular treatment of these populations with multiple comorbidities and poor prognosis. The objectives of the All Nippon AF In the Elderly (ANAFIE) Registry are to collect real-world information about the clinical status of patients with non-valvular AF (NVAF) aged ≥75 years, current status of anticoagulant therapy, and prognosis with/without anticoagulation to establish a database for this specific patient population that is increasing remarkably worldwide. Methods and design The ANAFIE Registry is an observational, multicenter, prospective study of Japanese patients with NVAF aged ≥75 years that will include 30,000 patients and have the primary endpoint of composite of stroke and systemic embolism over a 2-year follow-up period. In parallel with the main study, seven sub-cohort studies will be conducted with assessments including coagulation-fibrinolysis markers, echocardiography, heart rate, hypertension, cognitive function, frailty, and medication adherence. Subgroup analyses will be performed, and stratified by renal function, HbA1c, and maximum number of drugs used. The study was started in October 2016, with a planned 2-year recruitment period. As of January 31, 2018, 33,213 patients were enrolled; the recruitment was therefore ended 8 months earlier than the original plan. Conclusions The ANAFIE Registry will provide a valuable database for the clinical status, management, and outcomes of mortality, stroke, systemic embolism, and hemorrhagic events with/without anticoagulation in the increasing population of elderly NVAF patients, and will identify risk factors associated with these clinical events.

Ruminiclostridium josui Abf62A-Axe6A is a modular enzyme comprising (in order from the N-terminus): an N-terminal signal peptide, a glycoside hydrolase family 62 (GH62) catalytic module, a family 6 carbohydrate binding module (CBM6), a dockerin module and an additional carbohydrate esterase family 6 catalytic module (CE6). In this study, three Abf62A-Axe6A derivatives were constructed, overexpressed in Escherichia coli, purified, and biochemically characterized: RjAbf62A-Axe6A, containing all four modules but lacking the signal peptide; RjAbf62A-CBM6, containing the GH62 and CBM6 modules; and RjAxe6A, containing only CE6. RjAbf62A-Axe6A was highly active toward arabinoxylan and moderately active toward sugar beet arabinan, and released mainly arabinose. Analysis of the arabinoxylooligosaccharide hydrolysis products revealed that RjAbf62A-Axe6A released α-1,2- and α-1,3-linked arabinofuranose from both singly and doubly substituted xylosyl residues. Furthermore, RjAbf62A-Axe6A exhibited a weak activity toward linear 1,5-α-l arabinan and arabinooligosaccharides, indicating that it is capable of cleaving α-1,5-linkage. Surprisingly, RjAbf62A-Axe6A also demonstrated an endoxylanase activity toward birchwood and beechwood xylans and xylooligosaccharides. Although RjAbf62A-CBM6 exhibited a similar substrate specificity to RjAbf62A-Axe6A, RjAbf62A-CBM6 showed lower activities toward soluble arabinoxylans, birchwood and beechwood xylans and arabinoxylooligosaccharides but not toward insoluble arabinoxylan. RjAbf62A-Axe6A is the first reported GH62 enzyme with α-l-arabinofuranosidase and endoxylanase activities. Although both RjAbf62A-Axe6A and RjAxe6A had acetylxylan esterase activities, RjAbf62A-Axe6 exhibited a higher activity toward insoluble wheat arabinoxylan compared with RjAxe6.

Amino acid metabolism plays important roles in innate immune cells, including macrophages. Recently, we reported that a lysosomal adaptor protein, Lamtor1, which serves as the scaffold for amino acid–activated mechanistic target of rapamycin complex 1 (mTORC1), is critical for the polarization of M2 macrophages. However, little is known about how Lamtor1 affects the inflammatory responses that are triggered by the stimuli for TLRs. In this article, we show that Lamtor1 controls innate immune responses by regulating the phosphorylation and nuclear translocation of transcription factor EB (TFEB), which has been known as the master regulator for lysosome and autophagosome biogenesis. Furthermore, we show that nuclear translocation of TFEB occurs in alveolar macrophages of myeloid-specific Lamtor1 conditional knockout mice and that these mice are hypersensitive to intratracheal administration of LPS and bleomycin. Our observation clarified that the amino acid–sensing pathway consisting of Lamtor1, mTORC1, and TFEB is involved in the regulation of innate immune responses.

Polarization of macrophages into pro-inflammatory or anti-inflammatory states has distinct metabolic requirements, with mechanistic target of rapamycin (mTOR) kinase signaling playing a critical role. However, it remains unclear how mTOR regulates metabolic status to promote polarization of these cells. Here we show that an mTOR–Semaphorin 6D (Sema6D)–Peroxisome proliferator receptor γ (PPARγ) axis plays critical roles in macrophage polarization. Inhibition of mTOR or loss of Sema6D blocked anti-inflammatory macrophage polarization, concomitant with severe impairments in PPARγ expression, uptake of fatty acids, and lipid metabolic reprogramming. Macrophage expression of the receptor Plexin-A4 is responsible for Sema6D-mediated anti-inflammatory polarization. We found that a tyrosine kinase, c-Abl, which associates with the cytoplasmic region of Sema6D, is required for PPARγ expression. Furthermore, Sema6D is important for generation of intestinal resident CX3CR1hi macrophages and prevents development of colitis. Collectively, these findings highlight crucial roles for Sema6D reverse signaling in macrophage polarization, coupling immunity, and metabolism via PPARγ. Semaphorins play well-known roles in axon guidance. Kumanogoh and colleagues demonstrate that Semaphorin 6D cell-intrinsically activates anti-inflammatory macrophage polarization.

Lamtor1 is a lysosome-anchored protein that was first reported in 2009. In this review, we describe the discovery and intracellular functions of Lamtor1, as well as physiological roles of Lamtor1 in immune cells, namely, macrophages, CD4+ helper T-cells, and regulatory T-cells. To date, the following three strains of immune cell-specific conditional Lamtor1-knockout mice have been generated: myeloid-specific (LysM-Cre, Lamtor1flox), T-cell-specific (CD4-Cre, Lamtor1flox), and regulatory T-cell-specific (Foxp3-IRES-Cre, Lamtor1flox) knockout mice. The phenotypes observed in Lamtor1-knockouT-cells are partly mediated by decreased mTORC1 activity; however, lipid metabolism, including cholesterol biosynthesis and signaling via 25-hydroxycholesterol, is also involved. Therefore, Lamtor1 dynamically controls cellular function via mTORC1 activation and lipid signaling.

The time series of the H-wave amplitude in soleus muscle (SOL) shows fractal (long-range) correlation, which is attributed to input from supraspinal centers. However, whether such long-range power-law correlated input also contributes to the synergistic muscles remains unclear. The purpose of this study was therefore to examine the correlation in the fractal components of H-wave amplitude fluctuations between the synergistic muscles used for plantar flexion, i.e., the medial head of the gastrocnemius muscle (MG) and SOL. In eight young male participants, consecutive H-reflexes were recorded almost simultaneously from the MG and SOL at a stimulation frequency of 0.5 Hz for 30 min. We performed detrending moving-average cross-correlation analysis (DMCA) for each of the H- and M-wave amplitude time series between MG and SOL to assess the existence of a common noise input contributing to these long-range correlations. The cross-correlation coefficient ρDMCA (-1 to 1) was calculated to quantify the strength of the correlation between two different time series. The results indicated a significant long-range power-law correlation between H-wave amplitudes in MG and SOL (ρDMCA: 0.50 (0.22) and 0.22 (0.17), mean (standard deviation) for the original and randomly shuffled surrogate data, respectively, P 0.05). This was not the case for M-wave amplitudes (ρDMCA: 0.29 (0.23) and 0.20 (0.15), P 0.05). We conclude that there is a common noise input governing these synergistic muscles, possibly due to supraspinal origin, causing long-range power-law correlations in monosynaptic reflexes.

Mechanistic target of rapamycin complex (mTORC)1 integrates intracellular sufficiency of nutrients and regulates various cellular functions. Previous studies using mice with conditional knockout of mTORC1 component proteins (i.e., mTOR, Raptor, and Rheb) gave conflicting results on the roles of mTORC1 in CD4+ T cells. Lamtor1 is the protein that is required for amino acid sensing and activation of mTORC1; however, the roles of Lamtor1 in T cells have not been investigated. In this article, we show that Lamtor1-deficient CD4+ T cells exhibited marked reductions in proliferation, IL-2 production, mTORC1 activity, and expression of purine- and lipid-synthesis genes. Polarization of Th17 cells, but not Th1 and Th2 cells, diminished following the loss of Lamtor1. Accordingly, CD4-Cre–driven Lamtor1-knockout mice exhibited reduced numbers of CD4+ and CD8+ T cells at rest, and they were completely resistant to experimental autoimmune encephalomyelitis. In contrast, genetic ablation of Lamtor1 in Foxp3+ T cells resulted in severe autoimmunity and premature death. Lamtor1-deficient regulatory T cells survived ex vivo as long as wild-type regulatory T cells; however, they exhibited a marked loss of suppressive function and expression of signature molecules, such as CTLA-4. These results indicate that Lamtor1 plays essential roles in CD4+ T cells. Our data suggest that Lamtor1 should be considered a novel therapeutic target in immune systems.

A novel gene (axh43B) from Ruminiclostridium josui encoding a cellulosomal enzyme consisting of a catalytic module of subfamily GH43_10, a family-6 carbohydrate-binding module, and a dockerin module, was expressed using Escherichia coli. RjAxh43B released only arabinose from arabinoxylan and 23,33-di-α-l-arabinofuranosyl xylotriose, but not 32-α-l-arabinofuranosyl xylobiose or 23-α-l-arabinofuranosyl xylotriose, strongly suggesting that RjAxh43B is an arabinoxylan α-l-1,3-arabinofuranohydrolase capable of cleaving α-1,3-linked arabinose residues of doubly arabinosylated xylan. When Axh43B was mixed with the recombinant scaffolding protein RjCipA of R. josui at a molar ratio of 6:1, the activity of the RjAxh43B-RjCipA complex (6:1) toward insoluble wheat arabinoxylan was similar to that of RjAxh43B alone, suggesting that RjAxh43B does not show a proximity effect, which is defined as an activity enhancement effect caused by the presence of plural catalytic subunits adjoining each other. When RjAxh43A was mixed with xylanase RjXyn10C, they acted synergistically toward insoluble wheat arabinoxylan and rice straw powder in the absence of RjCipA. Furthermore, the RjAxh43B-RjXyn10C-RjCipA (3:3:3) complex had higher activity toward insoluble wheat arabinoxylan than a mixture of RjAxh43B and RjXyn10C without RjCipA, suggesting that incorporation of a xylanase and an α-l-arabinofuranosidase into a cellulosome is beneficial for more efficiently degrading arabinoxylan.

Dual-functional fluorinated silsesquioxane nanoparticles (SQ-NPs) containing thiol groups have been developed as efficient hybrid materials for UV-induced nanoimprinting via thiol-ene chemistry. The hydrolytic co-condensation of thiol-containing and fluorinated triethoxysilanes was carried out under suitable conditions to afford dual-functional fluorinated SQ-NPs with tunable thiol contents in high yields. The subsequent thiol-ene reactions of the thiol groups of the SQ-NPs with (perfluoroalkyl)ethylenes resulted in dual-fluorinated SQ-NPs with relatively narrow size distribution (average particle diameter less than 4 nm), good solubility, as well as reasonable hydrophobicity and oleophobicity. UV-cured hybrid films obtained from the dual-functional SQ-NPs and a diacrylate crosslinker in the presence of a photoinitiator exhibited excellent properties, including transparency, thermal property, hydrophobicity, and miscibility with other ingredients. UV-induced nanoimprinting of these components produced high-resolution patterns with features of around 100 nm in size, suggesting that the dual-functional fluorinated-thiolated SQ-NPs developed in this study could represent promising candidates for nanoimprint lithography.

A majority of menstruating women experience some degree of regular recurrences of diverse symptoms-commonly known as premenstrual syndrome (PMS)-during the days before menstruation. Given the multifactorial etiology of PMS, no single treatment is universally recognized as effective, and many women turn to alternative modalities, including aromatherapy. The present study investigated therapeutic effects on premenstrual symptoms using fragrance from yuzu, a Japanese citrus fruit (Citrus junos Sieb. ex Tanaka), and aromatherapy, from the perspective of autonomic nervous system function.Seventeen women in their 20s with subjective premenstrual symptoms.A single-blind randomized crossover study.This study was performed at a laboratory in a university in Osaka, Japan. Subjects were examined on two separate occasions in the luteal phase.Using two aromatic stimulation sources (yuzu and lavender used as the control), this experiment measured heart rate variability (HRV) reflecting autonomic nerve activity and the Profile of Mood States (POMS) as a psychologic index before and after aromatic stimulation.A scant 10-min inhalation of the yuzu scent significantly decreased heart rate and increased high-frequency power of HRV, reflecting parasympathetic nerve activity, in the luteal phase. Additionally, POMS tests demonstrated that inhalation of the yuzu essential oil significantly decreased three negative subscales: tension-anxiety, anger-hostility, and fatigue-common premenstrual symptoms, together with a total mood disturbance as a global measure of affective state, as long as 35 min after the aroma stimulation. These premenstrual psychoneurophysiologic effects of yuzu fragrance did not differ from those of the effects of lavender.The present study indicated that short-term inhalation of yuzu fragrance could alleviate premenstrual emotional symptoms, which, at least in part, is attributable to the improvement of parasympathetic nervous system activity. This study further implies that yuzu fragrance aromatherapy might serve as an anti-PMS modality, given its comparable psychoneurophysiologic effects to those of lavender, a representative relaxing scent.

Background: The purpose of this study was to evaluate the clinical results following intra-articular knee injection of Stromal Vascular Fraction (SVF cell therapy). Methods: This study involved 13 consecutive patients who had received SVF cell therapy at our clinic before November 2015 and completed the 6-month post-treatment follow-up period. For each treatment, approximately 200 mL or more of subcutaneous adipose tissue was harvested using tumescent liposuction technique and manual aspiration of tissue from the lower abdomen using a suction cannula under local anesthesia in the operating room. The adipose tissue harvested was processed using the Celution Centrifuge IV in the cell processing room of our clinic. These cells were injected into the articular cavity of both knees directly. Outcome was assessed on the basis of patient questionnaires using VAS for pain, the Japanese Knee Osteoarthritis Measure (JKOM), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results: The 13 patients (26 knee joints), consisting of 2 men and 11 women, had a mean age of 74.5 ± 5.4 years. Eleven patients (9 women, 2 men) presented Grade IV knee OA according to the KL classification. The remaining two patients, both women, had Grade III. Pre-operative scores of JKOM, WOMAC, VAS, and BS-POP (for patients) were 55.9 ± 21.0, 49.6 ± 20.4, 72.7 ± 18.2, and 18.5 ± 2.0. No serious adverse events were reported. One month after injection of SVF, all the scores of JKOM, WOMAC, and VAS were significantly improved over baseline (P

ObjectivesInappropriate activation of neutrophils plays a pathological role in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The aim of this study was to investigate the functions of semaphorin 4D (SEMA4D) in regulation of neutrophil activation, and its involvement in AAV pathogenesis.MethodsSerum levels of soluble SEMA4D were evaluated by ELISA. Blood cell-surface expression of membrane SEMA4D was evaluated by flow cytometry. To determine the functional interactions between neutrophil membrane SEMA4D and endothelial plexin B2, wild-type and SEMA4D−/− mice neutrophils were cultured with an endothelial cell line (MS1) stained with SYTOX green, and subjected to neutrophil extracellular trap (NET) formation assays. The efficacy of treating human neutrophils with recombinant plexin B2 was assessed by measuring the kinetic oxidative burst and NET formation assays.ResultsSerum levels of soluble SEMA4D were elevated in patients with AAV and correlated with disease activity scores. Cell-surface expression of SEMA4D was downregulated in neutrophils from patients with AAV, a consequence of proteolytic cleavage of membrane SEMA4D. Soluble SEMA4D exerted pro-inflammatory effects on endothelial cells. Membranous SEMA4D on neutrophils bound to plexin B2 on endothelial cells, and this interaction decreased NET formation. Recombinant plexin B2 suppressed neutrophil Rac1 activation through SEMA4D’s intracellular domain, and inhibited pathogen-induced or ANCA-induced oxidative burst and NET formation.ConclusionsNeutrophil surface SEMA4D functions as a negative regulator of neutrophil activation. Proteolytic cleavage of SEMA4D as observed in patients with AAV may amplify neutrophil-mediated inflammatory responses. SEMA4D is a promising biomarker and potential therapeutic target for AAV.

Three cellulosomal subunits of Ruminiclostridium josui, the full-length scaffolding protein CipA (RjCipA), a cellulase Cel5B (RjCel5B) and a xylanase Xyn10C (RjXyn10C), were successfully produced by Escherichia coli recombinant clones. RjCel5B and RjXyn10C were characterized as an endoglucanase and an endoxylanase, respectively. RjCipA, RjCel5B and Xyn10C adsorbed to microcrystalline cellulose (Funacel) and rice straw powder. Interaction between RjCel5B and RjCipA, and RjXyn10C and RjCipA were confirmed by qualitative assays. When a fixed amount of RjCel5B was mixed with different amounts of RjCipA, i.e., at the molar ratio of 6:1 or 6:6, the 6:6 complex showed 6.6-fold higher activity toward Funacel and 11.5-fold higher activity toward rice straw powder than RjCel5B, whereas the 6:1 complex showed only 2.8- and 3.9-folds higher activities toward Funacel and rice straw powder, respectively, than RjCel5B. These results suggest that the family-3 carbohydrate binding module (CBM3) of RjCipA in the RjCel5B-RjCipA complex plays an important role for hydrolysis of cellulose and the substrate-targeting effect of the CBM is more significant than the proximity effect caused by the presence of plural catalytic subunits adjoining each other. In contrast, the 6:1 complex of RjXyn10C and RjCipA showed 45% and 28% of the activities of RjXyn10C toward insoluble wheat arabinoxylan and rice straw powder, respectively. These results suggest that both a negative proximity effect and substrate-isolating effect, but not substrate-targeting effect, are caused by the CBM3 with inappropriate polysaccharide specificity. Substrate-targeting, proximity and substrate-isolating effects are discussed.

Two Y-shaped molecules combining two dissimilar (hydrophilic and hydrophobic) units with a reactive triethoxysilane moiety were synthesized by Michael addition reaction of (aminopropyl)triethoxysilane with 2-hydroxyethyl acrylate (HEA), followed by the addition of 2,2,2-trifluoroethyl acrylate (TFEA) or 1 H ,1 H ,5 H -octafluoropentyl acrylate (OFPA). Hydrolytic condensations of the Y-shaped triethoxysilane precursors proceeded as homogeneous systems in acetone in presence of the acidic catalyst to afford amphiphilic silsesquioxane nanoparticles (SQ-NPs) having hydroxyl and fluoroalkyl groups (HEA/TFEA-SQ and HEA/OFPA-SQ). Scanning force microscope (SFM), X-ray diffraction (XRD), and size-exclusion chromatography (SEC) measurements indicated the formation of nanoparticles (average particle diameter is about 2.0 nm) with reasonable molecular weights and low dispersities ( M n = 5100-5400, M w / M n = 1.22–1.36) without aggregation. Characteristic assembled structures and surface properties of the amphiphilic SQ-NPs in different solvents were also evaluated. Flexible self-standing films were obtained from the amphiphilic SQ-NPs without any additional compounds, which are due to intermolecular hydrogen bondings.

Background β-Blockers are used to control heart rate (HR) in patients with atrial fibrillation (AF). However, the appropriate dosage and efficacy of carvedilol in Japanese AF patients are yet to be clarified. Methods In this multicenter, randomized, double-blind study, Japanese patients with persistent or permanent AF received carvedilol for 6 weeks in the following three dosage-regimen groups: 5-mg fixed-dose (n = 42), 10-mg dose-escalation (n = 42), or 20-mg dose-escalation (n = 43). To evaluate the efficacy of each dosage regimen and the dose–response relationship, changes in 24-h mean HR (mHR) on Holter electrocardiograms from baseline to weeks 2, 4, and 6 were determined as primary endpoints. The effects on circadian changes in HR, the proportion of patients achieving target HR, clinical symptoms, and adverse events were also examined. Results After 2 weeks, carvedilol 5 mg decreased 24-h mHR significantly [6.6 (95% CI: 5.2–8.0) beats/min, p

Exercise-induced changes in executive function affect the control of action in a dynamic environment. This study aimed to examine the effect of sustained high-intensity exercise on executive function. Nine healthy male and female participants (age, 21-28 years) completed an exercise session with 65-min treadmill running at 75% VO2max. Executive function was assessed before and after exercise with the Stroop Color and Word Test that included congruent and incongruent conditions. The reaction time and response accuracy of the test were measured, and the task difficulty was controlled by adjusting the stimulus duration so that each participant could maintain at least 80% response accuracy to exclude the effect of a speed–accuracy trade-off. The levels of plasma norepinephrine and adrenocorticotropic hormone were examined. A significant interaction with the reaction time was found (condition × time, P = 0.024), in which the reaction time significantly increased after exercise only in the incongruent condition (P = 0.019). The response accuracy was not significantly different between before and after exercise in both conditions, which indicated that the response accuracy was controlled as intended. The levels of plasma norepinephrine and adrenocorticotropic hormone were significantly increased after exercise (P < 0.05). These results demonstrated that the reaction time in the incongruent condition increased after sustained high-intensity exercise with a cognitive function test with the response accuracy controlled, indicating a decline in executive function. Increased levels of plasma norepinephrine and adrenocorticotropic hormone may contribute, at least in part, to such decline in executive function.

This is a population pharmacokinetic (PopPK) analysis to predict PK of edoxaban, a direct-acting oral anticoagulant, in nonvalvular atrial fibrillation (NVAF) patients with severe renal impairment (SRI; creatinine clearance [CLcr ]

Background A majority of women from all cultures and socioeconomic levels experience myriad symptoms known as premenstrual syndrome during the days prior to menstruation. The present study investigated commonly reported symptoms in the premenstrual phase among college students. The authors further scrutinized potential factors, including subjective perceptions of health, which may be related to the premenstrual-symptom constellation. Methods We conducted a cross-sectional survey, which included 200 participants (mean age: 19.8 ± 0.1 years old). The subjects completed a rating of their premenstrual experiences relative to 46 symptoms in eight categories of the self-reporting menstrual distress questionnaire (MDQ) to evaluate the prevalence and severity of premenstrual symptoms. The participants also answered a standardized health questionnaire regarding subjective perceptions of health, self-rating stress, lifestyle, and demographic variables. Results Regardless of severity, the 10 symptoms most often occurring among the participants included skin disorders, irritability, fatigue, mood swings, general aches and pains, lowered school or work performance, backache, painful breasts, weight gain, and swelling. Stepwise multiple regression analysis revealed subjective perception of health (β = 0.28; p p = 0.008) as the factors most strongly related to the MDQ total scores. In addition, the 19 women who evaluated themselves as “unhealthy and stressed” had greater prevalence of severe or extremely severe physical (general aches and pains) and psychosocial symptoms (confusion, lowered school or work performance, decreased efficiency, loneliness, anxiety, restlessness, mood swings, and depression), compared to the healthy and non-stressed women. Conclusions The present study indicates the prevalence of premenstrual symptoms, regardless of severity and number, among college students and suggests that negative subjective perceptions of health and stress may be related to the intensity of premenstrual symptomatology.

Although it was considered to be impractical to apply surface acoustic wave (SAW) filters in the super high frequency (SHF) range, a technology recently revealed that use of a thin piezoelectric crystal plate may recreate an impression of the past. This paper describes acoustic wave devices comprising the thin piezoelectric crystal plate, interdigital transducers placed on the plate, and an acoustic mirror bonded on a silicon substrate. First, it is theoretically and experimentally shown how the acoustic energy can be confined in the top surface even though longitudinal leaky SAW (LLSAW) is utilized. Then it is shown how the proposed structure is promising for the SHF range filters in mobile terminals upcoming next generation wireless access technology through comparing with the incredible high performance SAW (I.H.P. SAW) and a high velocity A1 Lamb wave resonator.

Background Catheter ablation (CA) has been reported to reduce risk of stroke in patients with nonvalvular atrial fibrillation (NVAF) in retrospective studies. However, the risks and benefits of CA have not been well elucidated in patients with NVAF and who have suffered a recent ischemic stroke in prospective randomized trials. Thus, the aim of the STABLED clinical trial is to investigate the efficacy and safety of CA with anticoagulant therapy using edoxaban in patients with NVAF and a history of recent ischemic stroke. Methods and design The STABLED trial is a multicenter, prospective, randomized, open-label, standard medication-controlled study in Japan. The target patient number is 250, comprising 125 patients receiving standard medication and 125 receiving CA. For patients allocated to the CA group, ablation is to be performed between 1 to 6 months from the onset of index stroke. The observation period will be 3 years from the day of random allocation of the final patient to any of the groups. The primary outcome measure is the composite of recurrence of ischemic stroke, systemic embolism, all-cause death, and hospitalization for heart failure. Conclusion This study will investigate the effectiveness and safety of CA and basic anticoagulation treatment with edoxaban for patients with NVAF who have suffered a recent ischemic stroke. The aim is to determine the best evidence for an optimal treatment strategy for patients with NVAF and recent stroke. Trial registration: UMIN000031424/ NCT03777631 .

Background This study involved a sensory evaluation of edoxaban orally disintegrating (OD) tablets in patients with nonvalvular atrial fibrillation who had been receiving the existing edoxaban film-coated tablets before the study. Methods Edoxaban OD tablets 30 or 60 mg were prescribed for patients who had been receiving the existing 30- or 60-mg edoxaban film-coated tablets before the study. Each dose group was randomized into groups taking the tablets with or without water. After ingestion of the edoxaban OD tablet, each patient was asked to complete a sensory evaluation questionnaire (12 items). Results In the evaluation of satisfaction with edoxaban OD tablets, 52.8% of the patients perceived “no difference” from the existing edoxaban film-coated tablets and 34.9% indicated that they were more satisfied with the OD tablets, thus demonstrating a relatively high degree of satisfaction. When asked about convenience and reliability in using edoxaban OD tablets, about half of the patients perceived “no difference” from the existing edoxaban film-coated tablets and the remaining half indicated preference for the OD tablets. Responses about taste, flavor, ease of ingestion, and motivation to continue taking edoxaban indicated the overall acceptance of the OD tablets. Recognition of edoxaban OD tablets was rated as “easy” by about half of the patients and “difficult” by the remaining half. Among all patients, 49.5% preferred a change to edoxaban OD tablets. The degree of satisfaction with taste, flavor, and ease of ingestion, as well as overall satisfaction, tended to be greater when the OD tablets were taken with rather than without water, and the percentage of patients who preferred a change was higher in the group taking the OD tablets with water. Conclusions This study indicated that the degree of satisfaction with taste, flavor, ease of ingestion, and convenience, as well as overall satisfaction, in addition to motivation to continue drug intake and sense of confidence were greater for OD tablets than for the existing edoxaban film-coated tablets. Edoxaban OD tablet is a promising formulation for inducing greater patient adherence to medication and therefore ensures better treatment response. Trial registration UMIN-CTR UMIN000028788, registered 23-Aug-2017. Electronic supplementary material The online version of this article (10.1186/s12959-019-0192-x) contains supplementary material, which is available to authorized users.

In disaster areas, operating heavy construction equipment remotely and autonomously is necessary, but conventional remote-controlled heavy equipment has problems such as insufficient operability, limited mobility on slopes and stairs, and low work efficiency because of difficult remote control. As part of the ImPACT-TRC Program, a group of Japanese researchers attempts to solve these problems by developing a construction robot for disaster relief tasks with a new mechanism and new control methods. This chapter presents the overview of construction robot and the details of main elemental technologies making up the robot. Section 5.1 describes the basic configuration of the robot and the teleoperation system. Section 5.2 is a tether powered drone which provides extra visual information. Sections 5.4 and 5.3 are force and tactile feedback for skillful teleoperation. Section 5.5 is visual information feedback which consists of an arbitrary viewpoint visualization system and a visible and LWIR camera system to observe surrounding of the robot in a dark night scene and/or a very foggy scene. These functions can dramatically increase construction equipment’s capacity to deal with large-scale disasters and accidents.

Two manganese peroxidases (MnPs), MnP1 and MnP2, and a laccase, Lac1, were purified from Trametes polyzona KU-RNW027. Both MnPs showed high stability in organic solvents which triggered their activities. Metal ions activated both MnPs at certain concentrations. The two MnPs and Lac1, played important roles in dye degradation and pharmaceutical products deactivation in a redox mediator-free system. They completely degraded Remazol brilliant blue (25 mg/L) in 10–30 min and showed high degradation activities to Remazol navy blue and Remazol brilliant yellow, while Lac1 could remove 75% of Remazol red. These three purified enzymes effectively deactivated tetracycline, doxycycline, amoxicillin, and ciprofloxacin. Optimal reaction conditions were 50 °C and pH 4.5. The two MnPs were activated by organic solvents and metal ions, indicating the efficacy of using T. polyzona KU-RNW027 for bioremediation of aromatic compounds in environments polluted with organic solvents and metal ions with no need for redox mediator supplements.

A 31-year-old Japanese male patient with a history of atrial fibrillation showed elevated serum levels of free thyroxine and triiodothyronine and a normal level of thyrotropin. The same abnormal hormone pattern was also found in his son. These data indicated that the index patient and the son have thyroid hormone resistance syndrome. Exon sequencing using DNA from these two patients revealed that both patients harbored a heterozygous mutation in the THRB gene: G1244C in exon 9, which results in R320P substitution. Therefore, thyroid hormone resistance syndrome caused by THRB mutation (RTHβ) was diagnosed. The mutation of the 320th arginine to proline has not been found to date. In conclusion, herein, we have described the first case of RTHβ that is associated with R320P mutation.

[Purpose] This study aimed 1) to assess whether a prediction model for whole body skeletal muscle mass that is based on a sedentary population is applicable to young male athletes, and 2) to develop a new skeletal muscle mass prediction model for young male athletes. [Subjects and Methods] The skeletal muscle mass of 61 male athletes was measured using magnetic resonance imaging (MRI) and estimated using a previous prediction model (Sanada et al., 2006) with B-mode ultrasonography. The prediction model was not suitable for young male athletes, as a significant difference was observed between the means of the estimated and MRI-measured skeletal muscle mass. Next, the same subjects were randomly assigned to a development or validation group, and a new model specifically relevant to young male athletes was developed based on MRI and ultrasound data obtained from the development group. [Results] A strong correlation was observed between the skeletal muscle mass estimated by the new model and the MRI-measured skeletal muscle mass (r=0.96) in the validation group, without significant difference between their means. No bias was found in the new model using Bland-Altman analysis (r=−0.25). [Conclusion] These results validate the new model and suggest that ultrasonography is a reliable method for measuring skeletal muscle mass in young male athletes.

We present a case of a 53-year-old woman with subchondral insufficiency fracture (SIF) of the femoral head without history of severe osteoporosis or overexertion. Plain radiographs showed acetabular overcoverage with excessive lateralization of the acetabular rim. A diagnosis of SIF was made by typical MRI findings of SIF. The lesion occurred at the antipodes of the extended rim. Increased mechanical stress over the femoral head due to impingement against the excess bone was suspected as a cause of SIF. The distinct femoral head deformity is consistent with this hypothesis. This is the first report of SIF associated with acetabular overcoverage.

Two different expression vectors were constructed to investigate two signal peptides on secretion of Geobacillus thermoleovorans IT-08 α-L-arabinofuranosidase (AbfA) in Saccharomyces cerevisiae . They were designed to direct the secretion of AbfA by the aid of one of the following signal peptides, the αF signal peptide in the plasmid YEpFLAG1-Af and HM-1 signal peptide in the plasmid pYHM1-Af. Although some successful results have been reported in proteins secretion with αF leader sequence, in this research no α-L-arabinofuranosidase activity could be observed in recombinants S. cerevisiae YEpFLAG1-Af. The HM-1 leader sequence, originated from Hansenula mrakii IFO 0895 killer toxin, showed the capability to AbfA secretion.

The real-world status of proton pump inhibitor (PPI) use in patients with atrial fibrillation (AF) receiving antithrombotic treatment is largely unknown. The All Nippon AF In the Elderly (ANAFIE) Registry, a prospective, multicenter, observational study, aimed to determine treatment patterns, risk factors, and outcomes among elderly (aged ≥75 years) Japanese non-valvular AF (NVAF) patients in the real-world clinical setting. The present subanalysis of the ANAFIE Registry determined the PPI prescription status of 32,490 elderly Japanese NVAF patients. Patients were stratified by PPI use (PPI+) or no PPI use (PPI−). Risk scores for stroke (CHADS2, CHA2DS2-VASc) and bleeding (HAS-BLED), anticoagulant use, time in therapeutic range (TTR) for warfarin, and anticoagulant/antiplatelet combination use were evaluated. PPIs were used in 11,981 (36.9%) patients. Compared with the PPI− group, the PPI+ group included a greater proportion of female patients (45.2% vs 41.3%; P 2, CHA2DS2-VASc, and HAS-BLED scores (P Trial registration: UMIN000024006

e19323 Background: Although the incidence of VTE is known to be high in cancer patients, many details of the frequency, risk factors, and management of VTE in patients with cancer remain unclear, especially in Asian populations. Methods: The multicenter, prospective, Cancer-VTE Registry study (UMIN000024942) aimed to clarify the actual status of VTE in cancer patients. The study enrolled patients diagnosed with colorectal, lung, stomach, breast, gynecological, or pancreatic cancer in Japan. Patients underwent VTE screening before initiating cancer treatment and were observed for 1 year. Registry objectives included the assessment of VTE prevalence and risk factors for VTE before initiating cancer treatment, real-world treatment of VTE, and frequency of new-onset events during the observation period. DVT screening was waived for those with a normal D-dimer level. Using a multivariate logistic regression model, we examined risk factors for DVT in cancer patients prior to initiating cancer treatment. Results: Of the 9726 patients enrolled, 3661 patients underwent DVT screening and 549 subjects were diagnosed with DVT. The risk factors for DVT among patients who underwent DVT screening (n=3661) are shown in the Table. Conclusions: The risk of DVT before initiating cancer treatment was clarified, and the factors strongly influencing DVT risk included age, sex, VTE history, D-dimer concentration, and hemoglobin concentration. [Table: see text]

Cellulase production in filamentous fungi is repressed by various carbon sources. In our preliminary survey in Aspergillus nidulans, degree of de-repression differed depending on carbon sources in a mutant of creA, encoding the transcriptional repressor for carbon catabolite repression (CCR). To further understand mechanisms of CCR of cellulase production, we compared the effects of creA deletion with deletion of protein kinase A (pkaA) and G (ganB) genes, which constitute a nutrient sensing and signaling pathway. In plate culture with carboxymethyl cellulose and d-glucose, deletion of pkaA and ganB, but not creA, led to significant de-repression of cellulase production. In submerged culture with cellobiose and d-glucose or 2-deoxyglucose, both creA or pkaA single deletion led to partial de-repression of cellulase genes with the highest level by their double deletion, while ganB deletion caused de-repression comparable to that of the creA/pkaA double deletion. With ball-milled cellulose and d-glucose, partial de-repression was detected by deletion of creA but not of pkaA or ganB. The creA/pkaA or creA/ganB double deletion led to earlier expression than the creA deletion. Furthermore, the effect of each deletion with d-xylose or L-arabinose as the repressing carbon source was significantly different from that with d-glucose, d-fructose, and d-mannose. Consequently, this study revealed that PkaA and GanB participate in CreA-independent CCR and that contribution of CreA, PkaA, and GanB in CCR differs depending on the inducers, repressing carbon sources, and culture conditions (plate or submerged). Further study of CreA-independent mechanisms is needed to fully understand CCR in filamentous fungi.

The abnA gene from Ruminiclostridium josui encodes the large modular arabinanolytic enzyme, Abf43A-Abf43B-Abf43C, consisting of an N-terminal signal peptide, a Laminin_G_3 module, a GH43_22 module, a Laminin_G_3 module, a Big_4 module, a GH43_26 module, a GH43_34 module and a dockerin module in order with a calculated molecular weight of 204,108. Three truncated enzymes were recombinantly produced in Escherichia coli and biochemically characterized, RjAbf43A consisting of the first Laminin_G_3 module and GH43_22 module, RjAbf43B consisting of the second Laminin_G_3 module, Big_4 module and GH43_26 module, and RjAbf43C consisting of the GH43_34 module. RjAbf43A showed a strong α-l-arabinofuranosidase activity toward sugar beet arabinan, highly branched arabinan but not linear arabinan, thus it acted in the removal of arabinose side chains from sugar beet arabinan. By contrast, RjAbf43B showed a strong exo-α-1,5-l-arabinofuranosidase activity toward linear arabinan and arabinooligosaccharides whereas RjAbf43C showed low activity toward these substrates. Although RjAbf43B was activated by the presence of some metal ions such as Zn2+, Mg2+ and Ni2+, RjAbf43A was inhibited by these ions. RjAbf43A and RjAbf43B attacked sugar beet arabinan in a synergistic manner. By comparison, RjAbf43A-Abf43B containing both GH43_22 and GH43_26 modules showed lower hydrolytic activity toward sugar beet arabinan but higher activity toward sugar beet fiber than the sum of the individual activities of RjAbf43A and RjAbf43B, suggesting that the coexistence of two distinct GH43 modules in a single polypeptide is important for the efficient hydrolysis of an insoluble and natural polysaccharide but not a soluble substrate.

In ImPACT Tough Robotics Challenge(TRC), field evaluations for several robots with different characteristics have been carried out with several “Tough” tasks aiming to R&D evaluation and social implementation of the robots. In this paper, we describe the development and safety management of the rubble field used in TRC field evaluation, where the safety management is based on international safety standards in order to consider several risk parameters in a systematic way. According to the experiences of the field evaluations, the lessons learned was summarized for further development of the field in future.

The co-occurrence of resistance to thyroid hormone beta (RTHβ) and myotonic dystrophy type 1 (DM1) was observed in a Japanese family. Two mutations, P453A and C36Y, were identified in the thyroid h...