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Aims Recent clinical trials indicate that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in heart failure patients, but the underlying mechanisms remain unknown. We explored the direct effects of canagliflozin, an SGLT2 inhibitor with mild SGLT1 inhibitory effects, on myocardial redox signalling in humans. Methods and results Study 1 included 364 patients undergoing cardiac surgery. Right atrial appendage biopsies were harvested to quantify superoxide (O2.−) sources and the expression of inflammation, fibrosis, and myocardial stretch genes. In Study 2, atrial tissue from 51 patients was used ex vivo to study the direct effects of canagliflozin on NADPH oxidase activity and nitric oxide synthase (NOS) uncoupling. Differentiated H9C2 and primary human cardiomyocytes (hCM) were used to further characterize the underlying mechanisms (Study 3). SGLT1 was abundantly expressed in human atrial tissue and hCM, contrary to SGLT2. Myocardial SGLT1 expression was positively associated with O2.− production and pro-fibrotic, pro-inflammatory, and wall stretch gene expression. Canagliflozin reduced NADPH oxidase activity via AMP kinase (AMPK)/Rac1signalling and improved NOS coupling via increased tetrahydrobiopterin bioavailability ex vivo and in vitro. These were attenuated by knocking down SGLT1 in hCM. Canagliflozin had striking ex vivo transcriptomic effects on myocardial redox signalling, suppressing apoptotic and inflammatory pathways in hCM. Conclusions We demonstrate for the first time that canagliflozin suppresses myocardial NADPH oxidase activity and improves NOS coupling via SGLT1/AMPK/Rac1 signalling, leading to global anti-inflammatory and anti-apoptotic effects in the human myocardium. These findings reveal a novel mechanism contributing to the beneficial cardiac effects of canagliflozin., Graphical Abstract Proposed mechanism of canagliflozin-induced improvement of myocardial redox state. Canagliflozin increases intracellular AMP/ATP ratio through inhibition of SGLT1, which can activate AMPK/NOS signalling and increase NO that suppresses pro-inflammatory signalling. AMPK activation also inhibits activation of Rac1 and membrane translocation of Rac1 and p47phox, which decrease NADPH oxidase activity and superoxide (O2.−) production, attenuates inflammatory and apoptotic pathways and increasing the bioavailability of tetrahydrobiopterin (BH4), a key factor for NOS coupling.

Objectives: This study aimed to compare differences in mortality risk factors between admission and follow-up incorporated models. Methods: A retrospective cohort study of 524 patients with confirmed COVID-19 infection admitted to a tertiary medical center in São Paulo, Brazil from 13 March to 30 April 2020. Data were collected on admission, and the third, eighth and fourteenth days of hospitalization. The hazard ratio (HR) was calculated and 28-day in-hospital mortality risk factors were compared between admission and follow-up models using a time-dependent Cox regression model. Results: Of 524 patients, 50.4% needed mechanical ventilation. The 28-day mortality rate was 32.8%. Compared with follow-up, admission models under-estimated the mortality HR for peripheral oxygen saturation 100 bpm (1.19 versus 2.04), respiratory rate >24/min (1.01 versus 1.82) and mechanical ventilation (1.92 versus 12.93). Low oxygen saturation, higher oxygen support and more biomarkers–including lactate dehydrogenase, C-reactive protein, neutrophil-lymphocyte ratio, and urea remained associated with mortality after adjustment for clinical factors at follow-up compared with only urea and oxygen support at admission. Conclusions: The inclusion of follow-up measurements changed mortality hazards of clinical signs and biomarkers. Low oxygen saturation, higher oxygen support, lactate dehydrogenase, C-reactive protein, neutrophil-lymphocyte ratio, and urea could help with prognosis of patients during follow-up.

Tetraploid plants of Antirrhinum majus L. were obtained from the seeds of the F1 variety ‘Maryland True Pink’ by amiprophos-methyl (APM) treatment and subsequent in vitro culture. Seeds were treated with 0, 10 and 20 mgl−1 APM for 1, 3, or 7 d (day) with or without osmopriming. Overall, the seedlings established from the seeds treated with 10 or 20 mgl−1 APM for 3–7 d exhibited malformation with rudimentary roots and swollen hypocotyls that eventually produced adventitious shoots. The highest adventitious shoot formation frequency reached 71.6% in non-primed seeds treated with 10 mgl−1 APM for 7 d; this decreased to 54.4% in osmoprimed seeds that received the same APM treatment. The plantlets from the adventitious shoots were identified as tetraploids at frequencies of 51.4% and 90.4%, respectively. Tetraploid frequency increased with higher concentration and/or longer duration of APM treatment and ranged from 0 to 65.9% in the non-primed seeds and 10.3% to 100% in the osmoprimed seeds. Osmopriming of seeds accelerated the induction of tetraploids by APM treatment at the same concentration and duration by 10.3–39.0%, except in the case of treatment with 20 mgl−1 APM for 3 d treatment. In the osmoprimed seeds treated with 20 mgl−1 APM for 7 d, all the plantlets from the adventitious shoots were revealed to be tetraploids. This study revealed that APM has dual effects, namely the inhibitory effect on the growth of seedlings and the stimulatory effect on the induction of adventitious shoots on the hypocotyl of seedlings. APM induced adventitious shoots on the hypocotyl of seedling by seed treatment and the induced-adventitious shoots were identified to be tetraploids. Osmopriming accelerated the frequency of tetraploid induction.

In order to examine O2 consumption and CO2 emission in a megacity, continuous observations of atmospheric O2 and CO2 concentrations, along with CO2 flux, have been carried out simultaneously since March 2016 at the Yoyogi (YYG) site located in the middle of Tokyo, Japan. An average O2 : CO2 exchange ratio for net turbulent O2 and CO2 fluxes (ORF) between the urban area and the overlaying atmosphere was obtained based on an aerodynamic method using the observed O2 and CO2 concentrations. The yearly mean ORF was found to be 1.62, falling within the range of the average OR values of liquid and gas fuels, and the annual average daily mean O2 flux at YYG was estimated to be −16.3 µmol m−2 s−1 based on the ORF and CO2 flux. By using the observed ORF and CO2 flux, along with the inventory-based CO2 emission from human respiration, we estimated the average diurnal cycles of CO2 fluxes from gas and liquid fuel consumption separately for each season. Both the estimated and inventory-based CO2 fluxes from gas fuel consumption showed average diurnal cycles with two peaks, one in the morning and another one in the evening; however, the evening peak of the inventory-based gas consumption was much larger than that estimated from the CO2 flux. This can explain the discrepancy between the observed and inventory-based total CO2 fluxes at YYG. Therefore, simultaneous observations of ORF and CO2 flux are useful in validating CO2 emission inventories from statistical data.

We have developed a non-destructive technique to observe Li in an electrode and metallic Li deposition on an anode using muonic x-rays. With high intent negative muon beam at J-PARC, we have attempted operando measurements of Li and metallic Li deposition in LIBs for the first time. Both increase and decrease of Li in a cathode during charging and discharging processes were observed. We also observed significant increase of muonic x-rays of Li with cycles, which may correspond to the degradation of charge capacity with the cycles.

Background Recent clinical trials have demonstrated a role for sodium glucose cotransporter 2 (SGLT2) inhibitors in improving cardiovascular outcomes in heart failure patients, but the underlying mechanisms remain unknown. We investigated the direct effects of canagliflozin, a non-selective SGLT1/SGLT2 inhibitor on myocardial redox signalling in humans. Methods Study 1 included 364 patients undergoing cardiac surgery. Human right atrial appendage biopsies, obtained during surgery, were used to quantify the sources of superoxide (O2.-) and the gene expression of inflammation, fibrosis and myocardial stretch markers. In Study 2, myocardial biopsies from 51 patients were used ex vivo to study the direct effects of canagliflozin on O2.- generation and understand its role in controlling the activity of NADPH-oxidases and uncoupled nitric oxide synthase (NOS). Finally, we used differentiated H9C2 and human primary cardiomyocytes (hCM) to further characterise the key regulatory mechanisms (Study 3). Results SGLT1 was abundantly expressed in the human myocardial biopsies and hCM whilst SGLT2 was barely detectable. SGLT1 expression levels were positively correlated with basal O2.- production and the expression of natriuretic peptides, proinflammatory cytokines and pro-fibrotic markers in human myocardial biopsies from study 1. Incubation of human myocardium with canagliflozin significantly reduced basal and NADPH-oxidase-derived O2.- via AMP kinase (AMPK)-mediated suppression of GTP-activation and consequent reduction of membrane translocation of Rac1, an NADPH-oxidase subunit. This resulted in reduced oxidation and increased bioavailability of tetrahydrobiopterin, the nitric oxide synthase (NOS) co-factor essential for enzymatic coupling, leading to improved NOS coupling. These findings were replicated in hCM, where canagliflozin was shown to regulate AMP/ATP ratio, which could be upstream of AMPK activation. The effects of canagliflozin were significantly attenuated by knocking-down SGLT1 in hCM. Transcriptional profiling of hCM treated with canagliflozin revealed that canagliflozin had striking effects on myocardial redox signalling, causing suppression of apoptotic and inflammatory pathways in the human heart. Conclusions We demonstrate for the first time in humans that canagliflozin suppresses myocardial NADPH-oxidase activity and improves NOS coupling through an SGLT1/AMPK/Rac1-mediated pathway, leading to global anti-inflammatory and anti-apoptotic effects in the human myocardium. These findings provide a mechanistic basis for the beneficial effects of SGLT1/2 inhibitors in patients with heart failure. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): 1. British Heart Foundation (FS/16/15/32047 and PG/13/56/30383 to CA, CH/16/1/32013 to KC, and Centre of Research Excellence award RG/13/1/30181), 2. The Japanese Heart Rhythm Society-European Heart Rhythm Association fellowship grant sponsored by Biotronik.

Introduction: Many reports show that denture adhesives improve the retention and stability of dentures. However, few randomized controlled trials have examined the effects of denture adhesives. Objective: This 10-center randomized controlled trial with parallel groups involving 200 edentulous patients wearing complete dentures aimed to evaluate the effects of short-term use of cream and powder denture adhesives. Methods: Patients were allocated into 2 cream- and powder-type adhesive groups and 1 control group. Intervention groups were treated with the 2 adhesives (1 each), and the control group received saline solution. Adhesive or control was applied to the denture-mucosal surface for 4 d, and data at baseline and after day 4 of intervention (i.e., 8 meals) were obtained. Patient satisfaction was evaluated with a 100-mm visual analog scale. Oral health–related quality of life was measured with the Japanese version of the Oral Health Impact Profile for Edentulous Patients. Perceived chewing ability was evaluated by a questionnaire regarding ease of chewing and swallowing food. Between-group comparisons were performed with Kruskal-Wallis tests with the Mann-Whitney U test adjusted by Bonferroni correction. Within-group comparisons of pre- and postintervention measurements were performed with the Wilcoxon signed-rank test. Intention-to-treat analysis was also performed. Results: Between-group comparisons showed no significant differences for general satisfaction or Oral Health Impact Profile for Edentulous Patients. However, significant differences in satisfaction with various denture functions with cream- and powder-type adhesives were seen in pre- and postintervention comparisons ( P < 0.05). Significant differences were also observed for perceived chewing ability of hard foods ( P < 0.05). Conclusion: These results suggest that although denture adhesives do not invariably improve denture function, they do affect subjective evaluations and possibly chewing of hard foods. Therefore, the effects of denture adhesive use are insufficient to resolve any fundamental dissatisfaction with dentures ( ClinicalTrials.gov NCT01712802 ). Knowledge Transfer Statement: The results of this study suggest that denture adhesives should be applied under certain conditions; however, an appropriate diagnosis is important before application. These practice-based data provide information to establish evidence-based guidelines for applying denture adhesives.

Background Obesity is associated with increased cardiovascular risk; however, the potential role of dysregulations in the adipose tissue (AT) metabolome is unknown. Objectives The aim of this study was to explore the role of dysregulation in the AT metabolome on vascular redox signaling and cardiovascular outcomes. Methods A screen was conducted for metabolites differentially secreted by thoracic AT (ThAT) and subcutaneous AT in obese patients with atherosclerosis (n = 48), and these metabolites were then linked with dysregulated vascular redox signaling in 633 patients undergoing coronary bypass surgery. The underlying mechanisms were explored in human aortic endothelial cells, and their clinical value was tested against hard clinical endpoints. Results Because ThAT volume was associated significantly with arterial oxidative stress, there were significant differences in sphingolipid secretion between ThAT and subcutaneous AT, with C16:0-ceramide and derivatives being the most abundant species released within adipocyte-derived extracellular vesicles. High ThAT sphingolipid secretion was significantly associated with reduced endothelial nitric oxide bioavailability and increased superoxide generated in human vessels. Circulating C16:0-ceramide correlated positively with ThAT ceramides, dysregulated vascular redox signaling, and increased systemic inflammation in 633 patients with atherosclerosis. Exogenous C16:0-ceramide directly increased superoxide via tetrahydrobiopterin-mediated endothelial nitric oxide synthase uncoupling and dysregulated protein phosphatase 2 in human aortic endothelial cells. High plasma C16:0-ceramide and its glycosylated derivative were independently related with increased risk for cardiac mortality (adjusted hazard ratios: 1.394; 95% confidence interval: 1.030 to 1.886; p = 0.031 for C16:0-ceramide and 1.595; 95% confidence interval: 1.042 to 2.442; p = 0.032 for C16:0-glycosylceramide per 1 SD). In a randomized controlled clinical trial, 1-year treatment of obese patients with the glucagon-like peptide-1 analog liraglutide suppressed plasma C16:0-ceramide and C16:0-glycosylceramide changes compared with control subjects. Conclusions These results demonstrate for the first time in humans that AT-derived ceramides are modifiable regulators of vascular redox state in obesity, with a direct impact on cardiac mortality in advanced atherosclerosis. (The Interaction Between Appetite Hormones; NCT02094183 )

Cortical activity during jaw movement has been analyzed using various non-invasive brain imaging methods, but the contribution of orofacial sensory input to voluntary jaw movements remains unclear. In this study, we used functional magnetic resonance imaging (fMRI) to observe brain activities during a simple teeth tapping task in adult dentulous (AD), older dentulous (OD), and older edentulous subjects who wore dentures (OEd) or did not wear dentures (OE) to analyze their functional network connections. (1) To assess the effect of age on natural activation patterns during teeth tapping, a comparison of groups with natural dentition—AD and OD—was undertaken. A general linear model analysis indicated that the major activated site in the AD group was the primary sensory cortex (SI) and motor cortex (MI) (p < 0.05, family wise error corrected). In the OD group, teeth tapping induced brain activity at various foci (p < 0.05, family wise error corrected), including the SI, MI, insula cortex, supplementary motor cortex (SMC)/premotor cortex (PMA), cerebellum, thalamus, and basal ganglia in each group. (2) Group comparisons between the OD and OEd subjects showed decreased activity in the SI, MI, Brodmann’s area 6 (BA6), thalamus (ventral posteromedial nucleus, VPM), basal ganglia, and insular cortex (p ¡ 0.005, uncorrected). This suggested that the decreased S1/M1 activity in the OEd group was related to missing teeth, which led to reduced periodontal afferents. (3) A conjunction analysis in the OD and OEd/OE groups revealed that commonly activated areas were the MI, SI, cerebellum, BA6, thalamus (VPM), and basal ganglia (putamen; p < 0.05, FWE corrected). These areas have been associated with voluntary movements. (4) Psychophysiological interaction analysis (OEd vs OE) showed that subcortical and cortical structures, such as the MI, SI, DLPFC, SMC/PMA, insula cortex, basal ganglia, and cerebellum, likely function as hubs and form an integrated network that participates in the control of teeth tapping. These results suggest that oral sensory inputs are involved in the control of teeth tapping through feedforward control of intended movements, as well as feedback control of ongoing movements.

Objectives To clarify the status of home care massage services provided to patients. This will help in understanding how many patients utilize this service and the circumstances under which treatment is provided. Design A retrospective study. Setting Fifty-four acupuncture, moxibustion, and massage clinics. Participants were patients who had received home care massage for six months or more. We collected a total of 1587 responses from these 54 massage clinics; of these, 1415 responses (mean age = 79.1 ± 11.5 years) were valid (valid response rate 89.2%). Main outcome measures Actual patients and actual care services. Results The most common disorder observed among patients who utilized home care massage services was cerebrovascular disease (at approximately 36%), while the second most common were arthropathy-related disorders (16.3%). Although most patients received massage, approximately 30% received manual therapy (e.g. manual correction) and hot fomentation as part of thermotherapy. Notably, only around 10% of patients received massage alone; the majority received treatment in combination with range of motion and muscle-strengthening exercises. Conclusions This study helped to clarify the actual state of patients receiving home care massage and the details of the massage services provided. This study clearly showed the treatment effectiveness of massage, which can be used by home medical care stakeholders to develop more effective interventions.

Background Sodium glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic drugs that control plasma glucose levels by inhibiting reabsorption of glucose in kidney. Recent clinical trials have suggested a class effect of SGLT2 inhibitors in preventing hospitalization due to heart failure. However, the underlying mechanism has not been fully elucidated. Purpose We investigated the direct effect of the SGLT2 inhibitor, Canagliflozin (Cana), on myocardial redox state in humans. Methods The study included 48 patients undergoing cardiac surgery. Fresh myocardial tissues were incubated ex vivo with or without Cana and then used for superoxide quantification and Western immunoblotting. NADPH-oxidases activity was evaluated with NADPH 100μM stimulation, while nitric oxide synthase (NOS) coupling was assessed by using N(ω)-nitro-L-arginine methyl ester (L-NAME, a NOS inhibitor). A human cardiomyocyte (HCM) cell line was also used for in vitro validation of the effects of Cana on myocardium. Results Ex vivo incubation of myocardium with Cana significantly reduced baseline (A) and NADPH-oxidase-derived O2·− (B) and improved NOS coupling reflected by positive L-NAME delta O2·− values (C). Regulation of NADPH-oxidases activity by Cana was found to result from reduced GTP-activation (D) and consequent membrane translocation (E) of Rac1, a key subunit of NADPH-oxidases. Cana also reduced tetrahydrobiopterin (BH4) oxidation, increasing its bioavailability (F), which is a key mechanism to improve NOS coupling. Incubation with Cana enhanced phosphorylation of AMPK, and the downstream signalling, ACC (not shown). Additional Compound C, which is inhibitor of AMPK, significantly reversed these effects of Cana (A, B, C, D, E, F). These findings were replicated in HCM (not shown). In line with these, Cana increased the ADP/ATP ratio of cytoplasm in HCM, which could provide an upstream mechanism for AMPK activation. Conclusions We demonstrate for the first time in humans, that Cana suppresses myocardial NADPH-oxidases activity and improves NOS coupling through an AMPK-mediated pathway. This could be an underlying mechanism for the cardioprotective effects of SGLT2 inhibitors.

Hollow-structured LiMn2O4 crystals are grown in molten KCl (flux) for the first time via an oxidation reaction of metallic Mn followed by a lithiation reaction. Characterization of the formation process, which is achieved using thermogravimetric differential thermal analysis, X-ray diffraction, and scanning electron microscopy observation, reveals that the hollow structures are formed via a mechanism analogous to the microscale Kirkendall effect, which results from the difference between the solid-state diffusion rates of the core materials and the rate of O2 diffusion through the shell at elevated temperatures occurring during oxidation. Interestingly, the development of well-defined crystal facets is observed on the surfaces of the LiMn2O4 crystals, implying that the crystal growth is driven by supersaturation in the same manner as the flux growth. We also examine two possible approaches to reduce the volume of the inner space in the crystal: crystal growth under O2 flow for enhancement of the O2 diffusion and insertion of a Co and Ni layer between Mn and the substrate to induce the formation of the LiNi1/3Co1/3Mn1/3O2 phase.

We demonstrate a new way to prepare hollow-structured LiCoO2 crystals directly on a Pt substrate for the first time through a combination of semi-additive electrodeposition of a Co core and subsequent flux growth in molten LiNO3. The reaction process was characterized by time-dependent X-ray diffraction and scanning electron microscopy. The vertically oriented crystals having a platelet shape grew densely on the Co dot surface. The crystal growth was driven by supersaturation in the same manner as the flux growth. Significantly slower oxidation of the Co core and rapid lithiation of Co3O4 lead to pore formation, which suggests that slow oxygen diffusion in the Co core is rate limiting. Galvanostatic tests revealed that the LiCoO2 crystal array exhibited typical capacity–voltage profiles with no heavy capacity loss during the first three cycles without any additives.

Tin-phosphate glasses with Sn metal crystals have been considered to be candidates of new anode materials for lithium and sodium ion batteries. A new route (not electro-chemical reaction) for the synthesis of Sn crystals in 72SnO·28P2O5 glass was proposed, in which aluminum nitride AlN powders were used as a reducing agent and reacted with SnO–P2O5 glass powders. Sn particles with sphere shapes were formed in the samples heat-treated for the mixture of glass and AlN powders (72SnO·28P2O5 + 48AlN) in 3%H2/Ar. The mean diameter of Sn particles was ~ 1.3 μm for the sample heat-treated at 550 °C for 3 h, and that was ~ 10 μm for the sample heat-treated at 600 °C. The formation of AlPO4 crystals besides Sn metals was detected in the samples obtained in the present reaction. It was also found that AlPO4 crystals transform into amorphous AlPO4 by a planetary ball milling. It was demonstrated that the samples with Sn particles work as anode materials for Li+ ion batteries, in which the irreversible capacity observed in the first charging process is becoming small.

Aerogels are highly porous solids formed by replacing the liquid in a gel by air, without changing the original structure. The present cellulose aerogels are made by sublimating the water from a colloidal suspension of cellulose nanofibers. The nanofibers form three-dimensional networks, crosslinked by hydrogen bonds bridging the surface hydroxyl groups and also by mechanical entanglements between nanofibers. Although the studies on aerogels from cellulose nanofiber hydrogels by freeze-drying reported so far had produced small samples, improved cooling techniques that produces larger samples were attempted and the obtained cellulose nanofiber aerogels were impregnated with epoxy resin to fabricate composites. The highly porous structure allowed complete impregnation of resin and translucent composites were produced. The modulus of composites was increased in relation to neat epoxy, but due to high brittleness the ultimate strength was decreased. This is likely to be caused by nanofiber agglomerations of uneven pore sizes acting as stress concentrators. The evaluation of the mechanical properties of composites serves as an indirect way to assess the quality of the aerogels produced.

Miniaturized electronic devices comprising anisotropic Nd-Fe-B film magnets have been reported by a lot of researchers [1] [2]. Recently, our group reported isotropic Nd-Fe-B+a-Fe dispersed nano-composite film magnets prepared by a PLD method with laser energy density (LED) > 10 J/cm2 in order to apply the films to a multi-polarly magnetized rotor for a miniaturized cylindrical motor [3]. Although the targets had Nd-rich compositions compared to a stoichiometric one such as Nd2.4Fe14B or Nd2.6Fe14B, the above-mentioned nano-composite structure together with good magnetic properties of Br > 0.9 T, Hc > 300 kA/m, and $(BH)_{\max} >$ 90 kJ/m3, respectively, could be obtained. This contribution reports the influence of structure, surface morphology and magnetic properties on target compositions for the isotropic Nd-Fe-B film magnets prepared at LED > 10 J/cm2. An Nd-Fe-B film was deposited on a Ta substrate by ablating each rotated target with eight compositions of Nd x Fe 14 B (X = 1.8, 2.0. 2.2, 2.4, 2.6. 2.8, 3.2, 3.5) in the vacuum atmosphere of 10−5 Pa. An Nd-YAG pulse laser with LED above 10 J/cm2 was could be obtained by a laser beam with the diameter less than 1 mm. All the as-deposited films thicker than 10 $\mu \mathrm{m}$ were crystallized by a pulse annealing (PA) method in the vacuum atmosphere. The observation of X-ray diffraction patterns indicated that the all as-deposited films had amorphous structure with $\alpha-\text{Fe}$ grains. The result suggests that a usage of the small laser beam of high LED enabled us to precipitate $\alpha-\text{Fe}$ phase even if we used an Nd-Fe-B target with large amount of a Nd element such as Nd3.2Fe14B and Nd3.5Fe14B. Moreover, the number and/or size of droplets with Nd-rich composition drastically increased as X of an Nd x Fe 14 B target became larger than 2.6 and the residual magnetic polarization decreased. On the other hand, the coercivity of films prepared by Nd x Fe 14 B (X=1.8, 2.0, 2.2) targets showed less than 300 kA/m. Resultantly, the X range from 2.4 to 2.6 in a Nd x Fe 14 B target is optimum in order to achieve good magnetic properties in Nd-Fe-B films prepared by using a PLD with LED > 10 J/cm2.

SummaryIntroduction To provide target values for the manufacturers’ survey of the Japanese Society for Laboratory Hematology (JSLH), accurate standard data from healthy volunteers were needed for the five-part differential leukocyte count. To obtain such data, JSLH required an antibody panel that achieved high specificity (particularly for mononuclear cells) using simple gating procedures. We developed a flow cytometric method for determining the differential leukocyte count (JSLH-Diff) and validated it by comparison with the flow cytometric differential leukocyte count of the International Council for Standardization in Haematology (ICSH-Diff) and the manual differential count obtained by microscopy (Manual-Diff). Methods First, the reference laboratory performed an imprecision study of JSLH-Diff and ICSH-Diff, as well as performing comparison among JSLH-Diff, Manual-Diff, and ICSH-Diff. Then two reference laboratories and seven participating laboratories performed imprecision and accuracy studies of JSLH-Diff, Manual-Diff, and ICSH-Diff. Simultaneously, six manufacturers’ laboratories provided their own representative values by using automated hematology analyzers. Results The precision of both JSLH-Diff and ICSH-Diff methods was adequate. Comparison by the reference laboratory showed that all correlation coefficients, slopes and intercepts obtained by the JSLH-Diff, ICSH-Diff, and Manual-Diff methods conformed to the criteria. When the imprecision and accuracy of JSLH-Diff were assessed at seven laboratories, the CV% for lymphocytes, neutrophils, monocytes, eosinophils, and basophils was 0.5~0.9%, 0.3~0.7%, 1.7~2.6%, 3.0~7.9%, and 3.8~10.4%, respectively. More than 99% of CD45 positive leukocytes were identified as normal leukocytes by JSLH-Diff. Conclusions When JSLH-Diff method were validated by comparison with Manual-Diff and ICSH-Diff, JSLH-Diff showed good performance as a reference method.

The PCI Express Adaptive Communication Hub (Peach) is an eight-core communication system on chip with four PCI Express Revision 2.0 ports, each with four lanes. Peach realizes a high-performance, power-aware, highly dependable network that uses PCI Express not only for connecting peripheral devices but also as a communication link between computing nodes. This approach opens up new possibilities for a range of communications.

A number of haptic devices have recently become available on the commercial market, and these devices are becoming common not only in research but in consumer use as well. In this paper, a new parallel mechanism, referred to herein as DELTA-R (meaning DELTA-Redundant, formerly referred to as DELTA-4) is proposed for a new haptic device having high-quality force display capability and operability. DELTA-R allows three-degree-of-freedom (DOF) translational motions. The key features of DELTA-R, as compared with conventional parallel mechanisms, are redundant actuation, a smaller footprint, a larger working area, and improved access to the end effector. The prototype is equipped with a 3-DOF rotation mechanism, the center of motion of which is located on the wrist position of the operator. An evaluation test of the force display was conducted using a prototype of the proposed mechanism. This paper describes the kinematic design, kinematic modeling, kinematic analysis, prototype implementation, and evaluations.

We have developed an animal model of learning and memory impairment associated with activation of microglia in the mouse brain. Injection of lipopolysaccharide into the CA1 region of the mouse hippocampus resulted in an increased production of inflammatory cytokines, such as interleukin-1β. Immunostaining for interleukin-1β revealed an increase in the signal at 6 hr after lipopolysaccharide injection. Immunopositive cells for interleukin-1β were colocalized with those immunopositive for CD11b. When subacute lipopolysaccharide treatment (20 μg/2 μl/injection, bilaterally for 5 consecutive days) was performed, long-term activation of microglia and learning and memory deficits as evaluated using a step-through passive avoidance test were observed in the wild-type mice. Gene expression of the N-methyl-D-aspartate receptor NR1 and NR2A subunits was also decreased by the lipopolysaccharide treatment. In contrast, activation of microglia and the associated behavioral deficits were not observed in mice lacking interleukin-1α and -1β following the subacute lipopolysaccharide treatment, together with little change in the gene expression of NR1 and NR2A subunits. However, the subacute lipopolysaccharide treatment produced almost similar changes in those parameters in the tumor necrosis factor-α knockout mice as in the wild-type animals. The injection of interleukin-1β neutralizing antibody with lipopolysaccharide for 5 consecutive days resulted in the improvement of lipopolysaccharide-induced learning and memory deficits. These findings suggest that the expression of interleukin-1 plays an important role in lipopolysaccharide-induced activation of microglia and the associated functional deficits in learning and memory.

Co-doped ZnO films with a Co concentration of 8–20 at.% were fabricated using the low-energy process of gas flow sputtering. X-ray diffraction, X-ray photoelectron spectroscopy, and optical absorption measurements revealed that the Co ions replace Zn ions in the ZnO matrix and that the Co ions have an oxidation state of 2+. The magnetic properties of the film depend on the Co concentration. The plots of magnetization and inverse susceptibility vs. temperature indicate that the film with a high Co concentration (20 at.%) contains a ferromagnetic component, while that with a low Co concentration (8 at.%) contains an antiferromagnetic component. The film with an intermediate Co concentration (10 at.%) contains a ferromagnetic component with a low Curie temperature. Hysteresis was not found in magnetization curves for all the samples, including the sample at 5 K. The films exhibited a high resistivity of 4 × 107–2 × 108 Ω cm at room temperature, and carrier-mediated magnetism is not likely to be applicable for the mechanisms of the magnetism in the films.

Background and Objective: Stroke patients with severe leg paralysis are often bedridden in the acute and subacute phase, which increases the risk of disuse muscle atrophy in the chronic phase. The evidence to date indicates that oxidative stress plays an important role in the mechanism of disuse muscle atrophy. Therefore, the aim of this study was to determine if long-term radical scavenger treatment with edaravone following an acute stroke prevents the progression of disuse muscle atrophy and improves leg locomotor function in the chronic phase. Methods: This randomized controlled pilot study was conducted at 19 acute stroke and rehabilitation centers across Japan. Forty-seven ischemic stroke patients with at least leg motor weakness admitted within 24 hours of onset were randomly assigned to receive continuous intravenous infusions of edaravone 30 mg twice daily for 3 days (short-term group) or 10–14 days (long-term group). The primary endpoints of the study included the degree of leg disuse muscle atrophy, as measured by the percentage change from baseline in femoral muscle circumference 15 cm above the knee, and the improvement in leg locomotor function, as assessed by the maximum walking speed over 10 m, 3 months after the onset of stroke. Results: Three-month follow-up was completed by a total of 41 patients (21 in the short-term group and 20 in the long-term group). On admission, there was no significant difference in the severity of stroke or the grade of leg paresis between the two treatment groups. The grade of disuse muscle atrophy and incidence of gait impairment 3 weeks after stroke onset were also similar between the short- and long-term groups. However, disuse muscle atrophy of the paretic and non-paretic legs was significantly less severe in the long-term versus the short-term treatment group (3.6±5.9% and 1.5±6.0% vs 8.3±5.2% and 5.7±6.4%; p

In order to improve the magnetic properties of PLD-made Pr-Fe-B thick-film magnets deposited on Si substrates, an adoption of a glass buffer layer was carried out. The glass layer could be fabricated under the deposition rate of approximately 70 μm/h on a Si substrate using a Nd-YAG pulse laser in the vacuum atmosphere. The use of the layer enabled us to reduce the Pr content without a mechanical destruction and enhance (BH)max value by approximately 20 kJ/m3 compared with the average value of non-buffer layered Pr-Fe-B films with almost the same thickness. It is also considered that the layer is also effective to apply a micro magnetization to the films deposited on Si ones., AIP Advances, 8(5), 056231; 2018

PLD (Pulsed Laser Deposition) method with high laser energy density (LED) above 10 J/cm2 followed by a flash annealing enabled us to obtain isotropic nano-composite thick-film magnets with (BH)max 80 kJ/m3 on polycrystalline Ta substrates. We also have demonstrated that a dispersed structure composed of α-Fe together with Nd2Fe14B phases with the average grain diameter of approximately 20 nm could be formed on the Ta substrates. In this study, we tried to enhance the (BH)max value by controlling the microstructure due to the usage of different metal based substrates with each high melting point such as Ti, Nb, and W. Although it was difficult to vary the microstructure and to improve the magnetic properties of the films deposited on the substrates, we confirmed that isotropic thick-film magnets with (BH)max 80 kJ/m3 based on the nano-dispersed α-Fe and Nd2Fe14B phases could be obtained on various metal substrates with totally different polycrystalline structure. On the other hand, the use of a glass substrate lead to the deterioration of magnetic properties of a film prepared using the same preparation process., AIP Advances, 8(5), 056223; 2018

A 9-year-old domestic shorthaired cat with clinical signs of neurological disease was determined to have primary T-cell lymphoma of the central nervous system (CNS) on necropsy examination. Microscopically, neoplastic lymphocytes were distributed in the CNS parenchyma bilaterally around the cerebral ventricles, third ventricle, mesencephalic aqueduct, fourth ventricle and central canal of the spinal cord. The neoplastic infiltration was associated with complete loss of ependymal cells and marked astrocytosis. A large, solitary neoplastic lesion was present in the parenchyma around the central canal of the spinal cord at the level of the 13th thoracic vertebra. Immunohistochemically, the majority of neoplastic cells expressed CD3 and many also labelled for proliferating cell nuclear antigen (PCNA) and Ki-67. This is, to our knowledge, the first report of periventricular spread of primary CNS T-cell lymphoma in animals.

A crack in a plate of a functionally graded piezoelectric material is studied under thermal shock loading conditions. The crack faces are supposed to be completely insulated. All material properties are assumed to be exponentially dependent on the distance from the crack line parallel to the boundaries of the plate. By using both the Laplace transform and Fourier transform, the thermal and electromechanical problems are reduced to a singular integral equation and a system of singular integral equations that are solved numerically. The stress and electric displacement intensity factors vs. time for various material constants and geometric parameters are calculated.

Objective The aim of this study was to examine the relationship between prenatal exposure to atomic bomb (A-bomb) radiation and the development of schizophrenia in adulthood. Method We investigated the lifetime prevalence of schizophrenia among people prenatally exposed to the 1945 Nagasaki A-bomb, using the schizophrenia register and the A-bomb survivors' database. Results Among 1867 prenatally exposed individuals, 18 subjects (0.96%) had developed schizophrenia later in life. The prevalence was significantly higher in people exposed in the second trimester of pregnancy than in those exposed in the third trimester. The closer they had been to the hypocentre, the higher was the prevalence, but no statistically significant linear relationship was seen. Conclusion This investigation could not clarify the nature of exposure to A-bomb radiation as a risk factor for schizophrenia in the prenatal period.

We encountered an instructive case of repetitive reversible severe neurological deficit due to ischemia of the internal capsule after mild head injury. A 1-year-old boy fell and hit his head on the floor without losing consciousness. Intermittent episodes of left hemiparesis lasting from 30 s to 30 min developed 4 h later. Magnetic resonance (MR) imaging revealed acute infarction in the left internal capsule and corona radiata on diffusion-weighted imaging, and no microbleeding on susceptibility-weighted imaging. MR angiography of the intracranial and cervical vessels showed no obstruction of the large cerebral arteries. Motor impairment began to improve the next day with conservative therapy. Neurological deficit gradually resolved over the course of 1 month. This tiny lesion of the internal capsule and corona radiata may have represented a small infarction caused by mechanical vasospasm of the perforating vessels branching from the middle cerebral artery after minor injury. Even mild head injuries may cause infarction of the internal capsule, although minor head injuries are common accidents in childhood and usually do not result in severe complications.

Hazardous chemical, radiological, and nuclear materials threaten public health in scenarios of accidental or intentional release which can lead to external ontamination of people. Without intervention, the contamination could cause severe adverse health effects, through systemic absorption by the contaminated casualties as well as spread of contamination to other people, medical equipment, and facilities. Timely decontamination can prevent or interrupt absorption into the body and minimize opportunities for spread of the contamination, thereby mitigating the health impact of the incident. Although the specific physicochemical characteristics of the hazardous material(s) will determine the nature of an incident and its risks, some decontamination and medical challenges and recommended response strategies are common among chemical and radioactive material incidents. Furthermore, the identity of the hazardous material released may not be known early in an incident. Therefore, it may be beneficial to compare the evidence and harmonize approaches between chemical and radioactive contamination incidents. Experts from the Global Health Security Initiative’s Chemical and Radiological/Nuclear Working Groups present here a succinct summary of guiding principles for planning and response based on current best practices, as well as research needs, to address the challenges of managing contaminated casualties in a chemical or radiological/nuclear incident.

In this article, we study the friction and wear durability of perfluoropolyether (PFPE) with different functional groups and molecular weights (MW) for a range of disk rotational speeds (500–7200 rpm or 1.2–17.33 m/s). A 4 mm diameter silicon nitride ball under a normal load of 4 g was employed as slider against PFPE lubricated diamond like carbon (DLC) film on magnetic hard disk. The coefficient of friction increases with increasing speeds, to certain extent, but it decreases for the higher speeds. At very high speeds, the fluctuations in the coefficient of friction of low MW PFPEs were larger than those of high MW PFPEs. The optical microscope image of the ball after sliding showed that evaporation might have occurred more easily in low MW than in high MW when sliding speed was increased due to the frictional heat generated at the interface. The wear lives of Z-lube (carboxyl group at both ends) and Z-dol are significantly higher than AS1 (alkoxy silano group at both ends) at low speed (1.2 m/s). In comparison to low MW PFPEs, high MW PFPEs show better wear durability at higher rotational speeds.

Laparoscopic colectomy for malignant disease technically is feasible but not widely accepted because there are no large-series studies or data on long-term outcomes. A retrospective, multicenter study investigating a large series of patients was conducted in Japan to evaluate preliminary long-term results of laparoscopic surgery for colorectal cancer. The study group comprised 2,036 patients who underwent laparoscopic colorectal resection April 1993 to August 2002 in 12 participating surgical units (Japanese Laparoscopic Surgery Study Group). Of the 1,495 patients with colon cancer, 781 (59%) had International Union Against Cancer (UICC) stage I, 248 (19%) had stage II, and 284 (22%) had stage III disease. Cancer recurred for 61 (4.1%) of 1,367 curatively treated patients (median follow-up period, 32 months; range, 6–125 months). The 5-year survival rate was 96.7% for stage I, 94.8% for stage II, and 79.6% for stage III disease. Of the 541 patients with rectal cancer, 220 (56%) had stage I, 62 had (16%) stage II, and 108 (28%) had stage III disease. Cancer recurred for 30 (5.6%) of 476 curatively treated patients (median follow-up period, 25 months; range 6–102 months). The 5-year survival rate was 95.2% for stage I, 85.2% for stage II, and 80.8% for stage III disease. The findings indicate that laparoscopic surgery for colorectal cancer yields an oncological outcome as good as that reported for conventional open surgery in the Japanese Registry for all disease stages.

Objectives To determine how diagnosis of malaria may be improved by combining the use of rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria with clinical diagnosis by the presence or history of fever compared with clinical diagnosis alone in emergency situations with flood-affected displaced populations in Mozambique. Study design A cross-sectional study conducted at the emergency outpatient clinic in a village in the Chokwe district of Gaza Province, 3 weeks after Cyclone Eline hit Mozambique in February 2000. Methods A hundred and thirty children aged less than 15 years with clinical malaria were selected for examination by RDT and fluorescent microscopy using acridine orange as a reference test. The diagnosis of clinical malaria was made by a history of fever in the last three days or axillary temperature above 37.0°C at the time of attending the emergency outpatient clinic. Two positive predictive values were calculated; RDTs combined with clinical diagnosis and clinical diagnosis alone. Results Positive predictive values of RDTs combined with clinical diagnosis by the presence of fever or history of fever were 87.6% (92/105) (95% confidence interval (CI) 80.8–92.8) compared with 74.6% (97/130) (95% CI 66.2–81.8) for clinical diagnosis alone. Five patients were diagnosed false negative. Conclusion RDTs combined with clinical diagnosis has sufficient positive predictive value to be used in emergency situations, while RDTs could result in increasing failure to treat when they are used for decisions of treatment compared with clinical diagnosis alone.

Power line communication modem for appliances control/monitoring network was developed. In order to realize robust communication by reducing influence from noise and channel distortion, the power line communication modem employs dispersed-tone technology and utilizes high frequency band for data transmission. Dispersed-tone technology gives the modem compatibility with radio communication as well as immunity from noise and channel distortion of power line. Performance of communication was measured. And compatibility with radio communication was also assessed. The results showed that the power line communication modem proposed in this paper was well qualified as a communication device for the purpose, and was compatible with radio communication.

A numerical investigation of the temperature variation in urban and suburban areas due to the presence of buildings was carried out using a one-dimensional canopy model combined with a meso-scale meteorological model. Since temperature increases in an urban area are caused by sensible heat from building surfaces besides anthropogenic heat and reduction of wind speed due to buildings' drag, we estimated each cause separately to determine the contribution by each to the temperature variation. The simulation was performed for Kanda, an urban area, and for Nerima, a suburban area of Tokyo. Comparisons were made with actual temperatures before the estimation. The comparison indicated that the measured temperatures in the Kanda and Nerima areas were nearly reproduced by the model. The sensitivity analysis indicated that, in a comparison with the temperature in no building environment, the contribution of (i) sensible heat flux from building surfaces to temperature rise was 49% in Kanda and 20% in Nerima, wind reduction due to drag was 41% in Kanda and 59% in Nerima, and (iii) the effect of the interaction between (I) and (II) was +10% in Kanda and +20% in Nerima.

The molecular and crystal structure of the α form of poly(tetramethylene adipate) (PTMA) was analyzed using synchrotron X-ray fiber diffraction data. The crystals belong to the monoclinic system of space group P 2 1 / n . The unit cell constants are a =0.6776(6), b =0.7904(6), c (fiber axis)=1.442(1) nm and β =135.6(1)°. The final crystal structure was obtained by the linked-atom least-squares refinement, which gave an R -factor of 0.130 for 103 observed spots and 64 unobserved reflections. The molecular structure deviates slightly from the fully extended conformation in the ester part. The torsional angle CH 2 –CH 2 –O–C( O) was found to be 155°. The C O groups of the corner and center chains in a unit cell are closely located along the c -axis and are related by the crystallographic 2 1 -axes along the b -axis at z =1/4 and z =3/4. The total dipole moment arising from the C O groups is oriented in one direction at z =1/4, and in the opposite direction at z =3/4. Owing to the close arrangement of the C O groups between neighboring chains along the fiber axis, the c -projected cell dimensions and the setting angle of the polymer chain are different from those of the orthorhombic form of polyethylene and the β form of PTMA.

自動搾乳システム導入後3年経過した農場において、バルク乳と各個体の牛乳中体細胞数が増加した。この牛群の全搾乳牛の76%(19/25頭)の個体、全検査分房の43%(41/96分房)の分房から黄色ブドウ球菌(以下SA)が検出された。11頭では複数分房にSA感染が認められた。本農場の自動搾乳システムでは搾乳機1台の連続稼動であり、一般的なSA防除対策(感染牛の隔離、最後に別搾り、感染分房乳のみの廃棄)は困難であった。そのため本農場でのSA防除対策としては、淘汰、盲乳、泌乳期治療、早期乾乳による一斉乾乳期治療を組み合わせて実施しするように指導した。自動搾乳システムは、伝染性乳房炎が発生した場合、防除対策が取り難く、その対応が困難となることがわかった。そのため、自動搾乳システム導入農場では、SAの侵入及び蔓延防止のため、定期的、或いは体細胞数増加時に細菌培養検査を実施し、早期に感染牛の排除を実施すべきであると考えられた。

Summary. In humans, protein C inhibitor (PCI) is expressed in various tissues and present in many body fluids including plasma and seminal fluid. In rodents, PCI is expressed in reproductive organs only and is absent in plasma. In this study, we characterized the tissue expression and physiological role of PCI in novel human PCI gene transgenic (TG) mice. Northern blot and immunohistochemical analyses demonstrated that human PCI is expressed in liver hepatocytes, renal epithelial cells as well as heart, brain and reproductive organs of the TG mice. This PCI tissue distribution is similar to that found in humans. PCI in plasma of TG mice showed the same immunological and functional properties as human plasma PCI. Next, we evaluated the effect of PCI on coagulation, inflammation and tissue damage in lipopolysaccharide-treated TG mice. The results suggested that PCI efficiently inhibits not only the anticoagulant and anti-inflammatory activities of exogenously injected human activated protein C (APC) but also that of endogenously produced APC in mice with endotoxemia. These findings suggest that PCI exerts a procoagulant and proinflammatory effect by inhibiting APC. We believe our results also show how useful these TG mice may be for assessing the therapeutic effect of human APC in vivo and for evaluating the role of PCI in human physiological and pathological conditions.

To investigate the relationship between aseptic meningitis and anti-U1RNP antibody in patients diagnosed with CTD.Fourteen patients with aseptic meningitis were selected from among patients with CTDs who had visited our hospital. We analyzed their medical records to clarify the clinical and immunological features of aseptic meningitis.A total of 14 patients with aseptic meningitis were subsequently diagnosed as having either SLE (seven cases), MCTD (four), UCTD (one), overlap syndrome (one), or Sjögren's syndrome (one). Eight of the 14 patients had received NSAIDs, such as sulindac, naproxen, or loxoprofen, before the onset of aseptic meningitis. CRP levels were increased (mean +/- SD: 7.1 +/- 7.1 mg/dL) and CRP levels (10.4 +/- 7.7) in the drug-induced group were significantly increased (p0.01). The anti-U1RNP antibody was found in 13 of the 14 patients. There were no significant differences in cerebrospinal fluid findings between the drug-induced group and the non-drug-induced group.SLE or MCTD patients with aseptic meningitis tend to have anti-U1RNP antibody.

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