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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.

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.

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.

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

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.

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.

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。

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.

■ The aim of the Expert Approach section is to contribute to the dissemination and standardization of new endoscopic procedures. Authors from three distinct geographic areas combine forces, sharing their experience to form a consensus of opinion. Readers' comments are welcome and will be published in the Mailbox which appears at the end of each Expert Approach article.

Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4–8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

The most important performance requirements of a tyre are safety and comfort of mobility, along with reduced environmental impact. these requirements are best met by deploying a combination of technologies on both a microscopic and a macroscopic level in design and manufacturing. this chapter discusses examples of such technologies. it also discusses natural rubber (NR), the most important raw material used in tyres, including its quality control and the challenges facing its use in the future.

Point defect complexes related to the yellow luminescence (YL; ∼2.2 eV) produced in un-doped GaN by 30 MeV electron irradiation are studied using a photoluminescence method. The YL intensity in 700°C annealed samples is about five times larger than that in un-irradiated materials, indicating that deep level defects are created by electron irradiation and subsequent annealing. The YL is associated with point defect complexes arising from the combination of the irradiation introduced Ga vacancies and the residual donor impurities driven by high temperature annealing. The YL is not annealed out by annealing at 1000°C, showing the thermal stability of artificially introduced defects.

BACKGROUND In Japan, endoscopic mucosal resection (EMR) is accepted as a treatment option for cases of early gastric cancer (EGC) where the probability of lymph node metastasis is low. The results of EMR for EGC at the National Cancer Center Hospital, Tokyo, over a 11 year period are presented. METHODS EMR was applied to patients with early cancers up to 30 mm in diameter that were of a well or moderately histologically differentiated type, and were superficially elevated and/or depressed (types I, IIa, and IIc) but without ulceration or definite signs of submucosal invasion. The resected specimens were carefully examined by serial sections at 2 mm intervals, and if histopathology revealed submucosal invasion and/or vessel involvement or if the resection margin was not clear, surgery was recommended. RESULTS Four hundred and seventy nine cancers in 445 patients were treated by EMR from 1987 to 1998 but submucosal invasion was found on subsequent pathological examination in 74 tumours. Sixty nine percent of intramucosal cancers (278/405) were resected with a clear margin. Of 127 cancers without “complete resection”, 14 underwent an additional operation and nine were treated endoscopically; the remainder had intensive follow up. Local recurrence in the stomach occurred in 17 lesions followed conservatively, in one lesion treated endoscopically, and in five lesions with complete resection. All tumours were diagnosed by follow up endoscopy and subsequently treated by surgery. There were no gastric cancer related deaths during a median follow up period of 38 months (3–120 months). Bleeding and perforation (5%) were two major complications of EMR but there were no treatment related deaths. CONCLUSION In our experience, EMR allows us to perform less invasive treatment without sacrificing the possibility of cure.

This report concerns an autopsy case of rapidly progressive aphasia and motor neuron disease. The patient was a Japanese woman who was 75 years old at the time of death. The family history did not reveal hereditary burden. She developed language disturbances and difficulty in swallowing at age 74. Neurological examination 1 month after the disease onset revealed motor aphasia without dementia and bulbar sign, followed by muscle weakness of the four extremities. Neuroradiological examination revealed progressive atrophy of the anterior part of the left temporal lobe. She died of respiratory difficulty 10 months after the disease onset. Macroscopically, neuropathological examination showed circumscribed atrophy of the left perisylvian region and, histologically, neuronal loss in the cerebral cortex, including the primary motor area, substantia nigra, brain stem motor nuclei, and anterior horns of the spinal cord, in addition to obvious degeneration of the pyramidal tracts and presence of Bunina bodies. Ubiquitin-immunoreactive neuronal inclusions were present in the hippocampal dentate granular cells and frontotemporal cortical layer II neurons. Based on these clinicopathological findings and a review of the literature, we concluded that our case is the first reported case of amyotrophic lateral sclerosis with dementia that clinically showed rapidly progressive aphasia.

BACKGROUND—The CD44 variant (CD44v) isoforms have been noted as markers for tumour metastasis and prognosis in several adenocarcinomas. AIMS—To investigate whether CD44v, especially the CD44v2 (v2) isoform, may be a useful prognostic factor for patients with oesophageal squamous cell carcinoma, using a recently developed monoclonal antibody against a v2 epitope. PATIENTS—233 patients (211 men and 22 women; mean age 61.9 years), with oesophageal squamous cell carcinomas curatively removed without additional treatment between 1987 and 1996 at the National Cancer Center Hospital, were analysed for CD44v expression. METHODS—The expression of CD44v was evaluated immunohistochemically using monoclonal antibodies against epitopes of the standard and variant protein, in paraffin embedded oesophageal squamous cell carcinoma tissue from 233 patients who had undergone cervical, mediastinal, and abdominal lymphadenectomy (three field dissection) for oesophagectomy. The data were evaluated for any correlation with clinicopathological indices or prognosis. RESULTS—Although total CD44 and CD44v6 (v6) were respectively observed in 99% and 97% of the cancer specimens, the expression of v2 was only 30%. Patients whose tumours were v2 positive had a significantly better prognosis than those whose tumours were v2 negative (p = 0.031). Furthermore, in patients without lymph node metastasis, v2 positivity alone was a significant independent factor of prognosis (relative risk of death associated with v2 negativity, 4.7; p = 0.037) in multivariate analysis. CONCLUSIONS—These results indicate that v2 is a useful marker for clinical prognosis in patients with oesophageal squamous cell carcinoma. Particularly in patients without lymph node metastasis, v2 status may thus have implications for the use of adjuvant chemotherapy and/or radiotherapy in patients with oesophageal cancer at an early stage. Keywords: CD44 variants; oesophageal squamous cell carcinoma; metastasis; prognosis; immunohistochemistry

Many important technologies depend on applications of organic thin films. The properties of surfaces and interfaces of film/substrate structures are of particular importance. It is becoming apparent that the atomic force microscope (AFM) has much to offer, especially when in situ non-destructive characterization is required. The ability of AFM to provide high resolution topographical images is well-developed. Recent studies have shown that force vs. distance (F–d) analysis can map at high spatial resolution mechanical properties of organic films, as well as those of the substrate. The same mode will also provide quantitative information about adhesive interactions. A formalism has been developed, based on a series combination of linearly compliant elements, from which film thickness and elastic moduli can be inferred from the detailed structure of F–d curves. The methodology is illustrated for the native lipid layer on wool fibre and for the multilayer structure of magnetic tapes.

Aim Few epidemiological data are available describing the sudden death of persons in their prime. This study aims to elucidate when and how sudden death occurs among employees. Methods A total of 196775 employees from 10 workplaces in Central Japan were surveyed for non-traumatic sudden death during 1989–1995. Demographic data and information regarding onset were collected by their workplace healthcare professionals. Results We identified 251 male and 13 female cases of sudden death. The annual incidence was 21·9 (for men) and 5·7 (for women) per 100000 population. Sudden death occurred more frequently in April when the new business year starts (risk ratio [95% confidence interval], 1·62 [0·94–2·79]) than in other months, without seasonality. Sudden death peaked on Sundays (risk ratio, 1·90 [1·20–2·99]) and Saturdays (risk ratio, 1·36 [0·83–2·21]) as compared with weekdays, and was likely to occur in the small hours (risk ratio, 1·71 [0·94–3·10] at 00–0300h and 1·47 [0·79–2·72] at 0300–0600h vs at 0900–1200h. Only 17% of employees died at work, which was significantly less than expected ( P

We study spatial behavior of heavily excited excitons localized at a two-dimensional space of a specific stacking fault interface in a layered crystal ${\mathrm{BiI}}_{3}.$ Pump-and-probe absorption and resonant luminescence spectra of the exciton states were measured with an intense nanosecond laser not only at the exciting laser spot but at distant points from the exciting spot by applying space-resolved spectroscopy methods. The blueshift proportional to the exciton density was clearly observed on the probe absorption spectra even at the distant points due to high-density excitons flowing out from the exciting spot. The resonant luminescence also shows the spectral change and anomalous spatial expansion depending on the excitation density. The spatial distributions of the energy shift on the probe absorption and the luminescence intensity were analyzed on the basis of a two-dimensional exciton-flow model with dissipation processes. The analysis suggests the existence of an efficient in-phase motion of the exciton polaritons at high density. The results are discussed in terms of a new phase of the interacting high-density exciton-polariton system.

There have been a few studies of the arterial anatomy of the human carpus and several studies have been made of the arterial arches and recurrent arteries in the carpal region. However, further investigation is required. We describe here the results of a study of the vascular anatomy of arterioles, 60μm in minimum diameter, among the extraosseous vessels in 183 human hands. The study was performed by investigating stereoscopic arteriographs. Six arterial arches and six recurrent arteries were investigated. We compared the frequencies of carpal feeding arteries of Japanese with those of Americans (the Americans being of white, oriental, and black origin), and studied the differences from an anatomical standpoint. It has been reported that in Americans, there are only two recurrent arteries on the palmar side, in the ulnar and radial positions, and that the frequencies cannot be compared with those found in other studies, because of differences in methodology. However, we believe that, irrespective of the differences in methodology in the studies reviewed and in our study, it can be assumed that Japanese have a higher frequency of recurrent arteries than Americans.

A size-free rolling of bars developed by Kawasaki Steel allows a more flexible operation. New concepts of 4-roll stands offer good size accuracy on a wide range of diameters and flexible production schedules at reduced costs.

Macroscopic and efficient spreading of excitons from an exciting laser spot to the outside area along a quasi two-dimensional space of a planar-defect in BiI3 is presented by space and time-resolved photoluminescence, and the degenerate Four-Wave-Mixing (DFWM) signals by use of spatially separated two laser-beams. The photoluminescence shows wide spreading due to polariton-like transfer of excitons at low density and wider that at higher density. The fast transfer of excitons at high density was detected as a coherent exciton-flow by the DFWM measurements.

High temperature (>125°C) resistant long-wavelength semiconductor lasers are attractive as light sources in a variety of harsh environments. Here, we report extremely high temperature continuous-wave (CW) operation of QD lasers on GaAs substrate emitted at 1300-nm-range by enhancing gain and increasing the quantized-energy separation of the QD active layers. A suppression of the In out-diffusion during MBE from self-assembled InAs QDs significantly reduced inhomogeneous broadening with high QD sheet density maintained. QD-FP laser exhibited record high CW-lasing temperature for long-wavelength laser of 220°C and QD-DFB laser also exhibited high CW-lasing temperature of 150°C by employing high gain QD active media.

Presented are the detailed characteristics of a laser‐plasma x‐ray source that is successfully used for producing x‐ray images of biological specimens in water by contact microscopy. The conversion efficiencies of laser energy to soft x rays are measured for various target materials using a 0.53 μm, 500 ps laser pulse. Yttrium target showed the highest conversion efficiency of around 2.5%/sr to the ‘‘water window’’ region x rays at 3×1012 W/cm2. Angular distributions of x rays and ions are studied to find the best angular position of specimen for reducing the target debris. The effective x‐ray spectrum contributing to making an image of a specimen in water is discussed. It is shown that an extremely small laser could be employed in high‐resolution contact microscopy.

An electro-mechanical Q-switched (EMQ) CO/sub 2/ laser is Q-switched by a mechanical beam chopper in combination with a pulsed discharge current. Such a system can produce pulses with high peak powers (>10 kW) and high repetition rates (>1 kpps). In order to analyze the output characteristics, the peak power and the duration of the output pulses have been measured experimentally in detail over a wide range of Q-switching times up to 250 ns. For a low-pressure ( >

A system for extracting image outlines at the television rate was developed. The system incorporates fourteen DSPs operating in parallel. The extraction is performed by applying a (3/spl times/2) mask which is the connection of a (2/spl times/1) smoothing mask and a (2/spl times/2) differentiating mask. The processing time of 32.7 ms/frame for an image with 512/spl times/512 pixels/spl times/8 bits is attainable. >

The grooved-mirror-type Fabry-Perot (GFP) oscillator was used for coherent power-combining of multiple elements in the millimeter- and submillimeter-wave region. The admittance of the Gunn diode in oscillation was measured experimentally in the millimeter-wave region to design the GFP oscillator. The gain characteristics of the diode were found at the frequencies from 42 to 48 GHz from the measured results. With this Gunn diode in the GFP resonator, oscillation was observed. The experimental results indicated that for impedance matching between the diode and the resonant cavity, the groove height must be adjusted. >

Multielement oscillators with a quasi-optical resonator are reported. The resonator consists of a Fabry-Perot cavity with a grooved mirror (grating) and a concave mirror. It is possible to mount solid-state devices (Gunn diode, GaAs MESFET, etc.) in the grooved mirror. The oscillator has the capability for power-combining of solid-state sources in the millimeter- and submillimeter-wave regions. >

The authors describe the development trends and results of millimeter-wave systems in Japan in such fields as communication, radar, and measurement systems. The applications included are the W-40G waveguide transmission communication system, an automobile traffic control system using the 60-GHz band, a collision avoidance radar system for an automobile, a plasma electron density measuring system, and satellite communication. The authors describe the development of devices such as high-power FET amplifiers, traveling wave tube amplifiers (TWTAs), IMPATT amplifiers, low-noise amplifiers, and monolithic microwave integrated circuit (MMIC) devices used in constructing the millimeter-wave systems. >

In order to reduce undesirable emissions from PCBs, it is important to clarify the mechanism of emissions which occur from bends in transmission lines. We have proposed a method of visualizing Poynting and wave-number vectors that reveals the direction electromagnetic wave propagate. This ability contributes to a better understanding of the propagation mechanism that cannot be recognized from near-EM-field and far-field patterns. In this report, we visualized emissions from a bend of transmission line by using the proposed method. It is found that electromagnetic energy increases around the outside of the bend, then while most of the energy propagates along the transmission line, some of the energy goes outside the line. On the other hand, we found that the wave front of the electric field proceed straight outside without turning around the bend.