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Background and Objective: Interstitial lung disease (ILD) is characterized by dyspnoea on exertion and exercise-induced hypoxaemia. High-flow nasal cannula (HFNC) therapy reduces the respiratory workload through higher gas flow and oxygen supplementation, which may affect exercise tolerance. This study aimed to examine the effects of oxygen and gas flow rates through HFNC therapy on exercise tolerance in ILD patients., Methods: We conducted three-treatment crossover study. All ILD patients performed the exercises on room air (ROOM AIR setting: flow, 0 L/min; fraction of inspired oxygen [FiO 2 ], 0.21), HFNC (FLOW setting: flow 40 L/min, FiO 2 0.21), and HFNC with oxygen supplementation (FLOW + OXYGEN setting: flow 40 L/min, FiO 2 0.6). The primary endpoint was the endurance time, measured using constant-load cycle ergometry exercise testing at a peak work rate of 80%., Results: Twenty-five participants (10 men, 71.2 ± 6.7 years) were enrolled. The increase in exercise duration between the ROOM AIR and FLOW was 46.3 s (95% CI, -6.1 to 98.7; p = 0.083), and the FLOW and FLOW + OXYGEN was 91.5 s (39.1-143.9; p < 0.001). The percutaneous oxygen saturation (SpO 2 ) at rest was significantly higher with the FLOW + OXYGEN setting than with the ROOM AIR and FLOW settings, and the difference persisted during exercise. At equivalent time points during exercise, the SpO 2 with the FLOW setting was significantly higher than that with the ROOM AIR setting., Conclusion: Oxygen supplementation in HFNC therapy improved exercise tolerance and SpO 2 . We found that gas flow alone did not improve exercise tolerance, but improved SpO 2 during exercise., (© 2024 Asian Pacific Society of Respirology.)

Background: Lung resection is the standard of care for patients with clinical stage I/II non-small cell lung cancer. This surgery reduces both the duration and quality of patients' daily ambulatory activities 1 month after surgery. However, little is known about physical activity after lung resection in patients with lung cancer. To evaluate the recovery process of physical activity with pulmonary rehabilitation in patients after lung resection and examine whether physical activity is affected by age., Methods: In this prospective, observational study, we measured and analysed participants' postoperative physical activity using a uniaxial accelerometer daily from postoperative day 1 to 30., Findings: We analysed 99 patients who underwent thoracic surgery. The number of walking steps significantly increased until day 4 and then reached a plateau thereafter. The duration of exercise at <3 metabolic equivalents significantly increased until day 3, and no significant difference was observed thereafter. Exercise at >3 metabolic equivalents significantly increased until day 4 and reached a plateau thereafter. A significant correlation was observed between age and number of steps after day 4. Compared with video-assisted thoracoscopic surgery, thoracotomy significantly decreased the number of steps from day 3 to 4., Interpretation: We found that the level of physical activity varied by index in patients with non-small cell lung cancer who underwent lung resection. Age and surgical procedure affect different periods with the increase in post-operative walking steps., Competing Interests: Declaration of competing interest Shinichi Arizono reports grants from Hoshi Iryo-Sanki Co. Ltd. and NPO Central Japan Lung Study Group outside the submitted work. All other authors declare that they have no competing interests. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Shinichi Arizono reports a relationship with Hoshi Iryo-Sanki Co. Ltd. and NPO Central Japan Lung Study Group that includes: funding grants., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study aimed to investigate the association between the level of tissue oxygen saturation (StO 2 ) and quadriceps/skeletal muscle dysfunction, measured using the Medical Research Council (MRC) scale and ultrasonography, in critically ill patients. Thirty-four patients hospitalized at the Critical Care Medicine Center of Kindai University Hospital, between January 2022 and March 2023, were enrolled in this study. The StO 2 of the quadriceps muscle was measured via near-infrared spectroscopy. Muscle atrophy was measured by the thickness, cross-sectional area (CSA), and echo intensity of the rectus femoris (RF). These values were evaluated every alternate day until 13 days after admission or until discharge, whichever occurred first. Muscle weakness was assessed using the sum score of the MRC scale (MRC-SS), with the patient sitting at bedside. The mean age of the patients was 67.3 ± 15.3 years, and 20 (59%) were men. Seven patients (21%) were admitted for trauma, and 27 (79%) were admitted for medical emergencies or others. The mean score for the MRC-SS was 51.0 ± 7.9 points. RF thickness and CSA significantly decreased after day 7 (p < 0.05). There were no significant changes in StO 2 levels during hospitalization. However, there were positive correlations between the nadir StO 2 during hospitalization and MRC-SS, and changes in RF thickness and CSA at discharge (r = 0.41, p = 0.03; r = 0.37, p = 0.03; and r = 0.35, p = 0.05, respectively). StO 2 in the quadriceps muscle may be useful for predicting muscle atrophy and dysfunction in patients with critical illnesses., (© 2024. The Author(s).)

Cough is known as a protective reflex to keep the airway free from harmful substances. Although brain activity during cough was previously examined mainly by functional magnetic resonance imaging (fMRI) with model analysis, this method does not capture real brain activity during cough. To obtain accurate measurements of brain activity during cough, we conducted whole-brain scans during different coughing tasks while correcting for head motion using a restraint-free positron emission tomography (PET) system. Twenty-four healthy right-handed males underwent multiple PET scans with [ 15 O]H 2 O. Four tasks were performed during scans: "resting"; "voluntary cough (VC)", which simply repeated spontaneous coughing; "induced cough (IC)", where participants coughed in response to an acid stimulus in the cough-inducing method with tartaric acid (CiTA); and "suppressed cough (SC)", where coughing was suppressed against CiTA. The whole brain analyses of motion-corrected data revealed that VC chiefly activated the cerebellum extending to pons. In contrast, CiTA-related tasks (IC and SC) activated the higher sensory regions of the cerebral cortex and associated brain regions. The present results suggest that brain activity during simple cough is controlled chiefly by infratentorial areas, whereas manipulating cough predominantly requires the higher sensory brain regions to allow top-down control of information from the periphery., (© 2024. The Author(s).)

Objective The treatment background, as well as the frequency and type of complications, in autologous (auto-) and allogeneic (allo-) hematopoietic stem cell transplantation (HSCT) survivors influence the appearance of moderate to vigorous physical activity (MVPA) or sedentary behavior. We therefore assessed differences in the MVPA and sedentary behavior between auto- and allo-HSCT survivors. Methods This prospective observational study included 13 auto- and 36 allo-HSCT survivors (approximately 4 years after HSCT). The MVPA and sedentary behavior were assessed using a triaxial accelerometer. Results There were no significant between-group differences in the MVPA or sedentary behavior (p=0.768 and 0.739, respectively). In allo-HSCT survivors, the MVPA was negatively correlated with the Hospital Anxiety and Depression Scale score (r=-0.358, p=0.032). A stepwise multiple regression analysis showed that age was a significant predictor of sedentary behavior in allo-HSCT survivors (β=0.400, p=0.016). Conclusion We observed no significant between-group differences in the MVPA or sedentary behavior. Our results suggest that it may be unnecessary to change the rehabilitation program according to the donor type in interventions for promoting MVPA and reducing sedentary behavior in long-term HSCT survivors.

The centre of the Milky Way Galaxy hosts a black hole with a solar mass of about 4 million (Sagittarius A * (Sgr A)) that is very quiescent at present with a luminosity many orders of magnitude below those of active galactic nuclei 1 . Reflection of X-rays from Sgr A * by dense gas in the Galactic Centre region offers a means to study its past flaring activity on timescales of hundreds and thousands of years 2 . The shape of the X-ray continuum and the strong fluorescent iron line observed from giant molecular clouds in the vicinity of Sgr A * are consistent with the reflection scenario 3-5 . If this interpretation is correct, the reflected continuum emission should be polarized 6 . Here we report observations of polarized X-ray emission in the direction of the molecular clouds in the Galactic Centre using the Imaging X-ray Polarimetry Explorer. We measure a polarization degree of 31% ± 11%, and a polarization angle of -48° ± 11°. The polarization angle is consistent with Sgr A * being the primary source of the emission, and the polarization degree implies that some 200 years ago, the X-ray luminosity of Sgr A * was briefly comparable to that of a Seyfert galaxy., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The impact of real-time remote cardiac rehabilitation (CR) on health and disability-related outcomes and its correlation with physical function are unknown. We compared the effectiveness of real-time remote CR with that of hospital-based CR on physical function improvement and physical functions of improvement (Δ) to clarify the relationship between health and disability at baseline., Methods: Patients with cardiovascular diseases (CVDs) were enrolled (n = 38) in this quasi-randomised controlled trial and underwent 4 weeks of hospital-based CR, followed by 12 weeks of remote or hospital-based CR based on quasi-randomised allocation. Patients were assessed at baseline and after 12 weeks of remote or hospital-based CR using the shortened version of the World Health Organization (WHO) Quality of Life scale (WHOQOL-BREF) for subjective satisfaction, WHO Disability Assessment Schedule (WHODAS2.0-J) for objective performance, and cardiopulmonary exercise test for physical function and peak oxygen uptake (peak VO 2 ). The trends in measured variables from baseline to the post-CR stage were analysed., Results: Sixteen patients (mean age, 72.2 ± 10.4 years) completed remote CR, and 15 patients (mean age, 77.3 ± 4.8 years) completed hospital-based CR. The post-CR physical function differed significantly between the groups (Δ peak VO 2 , 2.8 ± 3.0 versus 0.84 ± 1.8 mL·min -1 ·kg -1 ; p < 0.05). The differences in post-CR changes in the WHOQOL-BREF scores between the groups were insignificant. The post-CR changes in the WHODAS2.0-J scores were significantly lower in the remote CR group than in the hospital-based CR group (ΔWHODAS2.0-J score, -8.56 ± 14.2 versus 2.14 ± 7.6; p < 0.01). Forward multiple stepwise regression analysis using overall data showed that the intervention method (β = 0.339, p < 0.05), baseline cognition (β =  - 0.424, p < 0.05), and social interaction level (β = 0.658, p < 0.01; WHODAS2.0-J) were significant independent contributors to Δpeak VO 2 (r 2  = 0.48, F = 8.13, p < 0.01)., Conclusions: Remote CR considerably improved physical function and objective performance in patients with CVDs. Remote CR can be used to effectively treat stable patients who cannot visit hospitals., Trial Registration: This interventional trial was registered at the UMIN-CTR registry (trial title: Development of remote programme for cardiac rehabilitation using wearable electrocardiograph; trial ID: UMIN000041746; trial URL: https://center6.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000046564 ; registration date: 2020/09/09)., (© 2023. The Author(s).)

Objective: To evaluate the factors that influence walking ability in patients hospitalized due to aspiration pneumonia., Methods: This retrospective observational study evaluated patients hospitalized with aspiration pneumonia. The primary endpoint was preservation of walking ability. Univariate and multivariate logistic regression analyses were performed with the preservation of walking ability as the dependent variable., Results: A total of 143 patients were enrolled in this study. The patients were divided into two groups: those whose walking ability decreased after hospitalization ( n  = 61) and those whose walking ability was maintained after hospitalization ( n  = 82). Multivariate logistic regression analyses showed that A-DROP (odds ratio [OR] 3.006; 95% confidence interval [CI] 1.452, 6.541; P  < 0.01), the Geriatric Nutritional Risk Index (OR 0.919; 95% CI 0.875, 0.960; P <  0.001) and days to initial mobilization (OR 1.221; 95% CI 1.036, 1.531; P <  0.05) were the independent early predictors for preservation of walking ability., Conclusion: Nutritional status and early mobilization were important risk factors affecting the maintenance of walking ability in patients hospitalized due to aspiration pneumonia. Thus, a combination of nutrition and early rehabilitation is needed for these patients., Registry of Research Studies Involving Human Subjects: This study was registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN 000046923).

Pulsar wind nebulae are formed when outflows of relativistic electrons and positrons hit the surrounding supernova remnant or interstellar medium at a shock front. The Vela pulsar wind nebula is powered by a young pulsar (B0833-45, aged 11,000 years) 1 and located inside an extended structure called Vela X, which is itself inside the supernova remnant 2 . Previous X-ray observations revealed two prominent arcs that are bisected by a jet and counter jet 3,4 . Radio maps have shown high linear polarization of 60% in the outer regions of the nebula 5 . Here we report an X-ray observation of the inner part of the nebula, where polarization can exceed 60% at the leading edge-approaching the theoretical limit of what can be produced by synchrotron emission. We infer that, in contrast with the case of the supernova remnant, the electrons in the pulsar wind nebula are accelerated with little or no turbulence in a highly uniform magnetic field., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

A black hole x-ray binary (XRB) system forms when gas is stripped from a normal star and accretes onto a black hole, which heats the gas sufficiently to emit x-rays. We report a polarimetric observation of the XRB Cygnus X-1 using the Imaging X-ray Polarimetry Explorer. The electric field position angle aligns with the outflowing jet, indicating that the jet is launched from the inner x-ray-emitting region. The polarization degree is 4.01 ± 0.20% at 2 to 8 kiloelectronvolts, implying that the accretion disk is viewed closer to edge-on than the binary orbit. These observations reveal that hot x-ray-emitting plasma is spatially extended in a plane perpendicular to, not parallel to, the jet axis.

Magnetars are neutron stars with ultrastrong magnetic fields, which can be observed in x-rays. Polarization measurements could provide information on their magnetic fields and surface properties. We observed polarized x-rays from the magnetar 4U 0142+61 using the Imaging X-ray Polarimetry Explorer and found a linear polarization degree of 13.5 ± 0.8% averaged over the 2- to 8-kilo-electron volt band. The polarization changes with energy: The degree is 15.0 ± 1.0% at 2 to 4 kilo-electron volts, drops below the instrumental sensitivity ~4 to 5 kilo-electron volts, and rises to 35.2 ± 7.1% at 5.5 to 8 kilo-electron volts. The polarization angle also changes by 90° at ~4 to 5 kilo-electron volts. These results are consistent with a model in which thermal radiation from the magnetar surface is reprocessed by scattering off charged particles in the magnetosphere.

Most of the light from blazars, active galactic nuclei with jets of magnetized plasma that point nearly along the line of sight, is produced by high-energy particles, up to around 1 TeV. Although the jets are known to be ultimately powered by a supermassive black hole, how the particles are accelerated to such high energies has been an unanswered question. The process must be related to the magnetic field, which can be probed by observations of the polarization of light from the jets. Measurements of the radio to optical polarization-the only range available until now-probe extended regions of the jet containing particles that left the acceleration site days to years earlier 1-3 , and hence do not directly explore the acceleration mechanism, as could X-ray measurements. Here we report the detection of X-ray polarization from the blazar Markarian 501 (Mrk 501). We measure an X-ray linear polarization degree Π X of around 10%, which is a factor of around 2 higher than the value at optical wavelengths, with a polarization angle parallel to the radio jet. This points to a shock front as the source of particle acceleration and also implies that the plasma becomes increasingly turbulent with distance from the shock., (© 2022. The Author(s).)

[Purpose] In this study, we investigated the association between exertional dyspnea and length of the mobilization program in patients with acute decompensated heart failure. [Participants and Methods] We recruited all consecutive patients with heart failure who were hemodynamically stabilized after administration of intravenous medication and were able to walk >10 m before admission. Exertional dyspnea was evaluated using the visual analog scale in all patients after the 10-m walk during each session of the mobilization program. Multiple regression analysis was used to determine the factors associated with length of the mobilization program. [Results] Our study included 52 patients. Multiple regression analysis showed that the length of the mobilization program was significantly associated with the visual analog scale on day 3 and the length before the start of the mobilization program; however, the length of the mobilization program showed no significant association with age and blood urea nitrogen levels. The standardized coefficients for the visual analog scale scores on day 3 and the length before the start of the mobilization program were 0.49 and 0.33, respectively. [Conclusion] Exertional dyspnea is a good predictor of the length of the mobilization program. Our findings highlight the importance of evaluation of exertional dyspnea., (2022©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Introduction: Aspiration pneumonia is a common problem among older adults; it has a high mortality rate and the prevalence is increasing. Reports on the risk factors for mortality in patients with aspiration pneumonia are limited. This study aimed to evaluate the risk factors for 90-day survival in patients with aspiration pneumonia., Methods: This retrospective observational study was conducted at Seirei Mikatahara General Hospital between 1 April 2015 and 31 March 2016. Patients with aspiration pneumonia who had dysphagia or aspiration confirmed by modified water swallow test or VideoEndoscopic examination of swallowing were included. The primary endpoint was 90-day survival. We performed univariate and multivariate logistic regression analyses with survival and non-survival at 90 days as the independent variables., Results: A total of 276 patients were recruited for this study. The A-DROP score (odds ratio [OR] = 2.440; 95% confidence interval [CI], 1.400-4.270; p < 0.01), Geriatric Nutritional Risk Index score (OR = 0.383; 95% CI, 0.178-0.824; p < 0.05) and sex (OR = 0.365; 95% CI, 0.153-0.869; p < 0.05) were independent early predictors of mortality., Conclusion: The results suggest that nutritional status and the severity of pneumonia are important factors that predict life expectancy in patients with aspiration pneumonia., (© 2022 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Background and Objective: The International Primary Airways Group (IPAG) questionnaire is a useful tool for screening for chronic obstructive pulmonary disease. The cut-off score of the IPAG questionnaire is investigated in Japan. However, its validity has not been examined according to sex, which was the aim of this study., Methods: We included 4364 participants aged 40 years or older, all current and ex-smokers and never-smokers, who completed the IPAG questionnaire and underwent spirometry. The IPAG questionnaire consists of eight items and the cut-off score is set to 17. We calculated the odds ratios of airflow limitation for each of the eight questions, by sex. We performed receiver operating characteristic analysis, calculating the area under the curve, sensitivity, and specificity for each sex., Results: For both men (n=2784) and women (n=1580), only three questions were independent risk factors of airflow limitation. The odds ratios for age (≥70 years), wheezing, and smoking history (≥50 pack-years) were 10.61, 3.50, and 2.40, respectively, for men (all p <0.001), and 4.30 ( p <0.001), 2.32 ( p =0.026), and 5.69 ( p =0.014), respectively, for women. For men and women, the areas under the curve were 0.741 and 0.670, respectively. The sensitivity and specificity values, respectively, were as follows: 83.6% and 47.1% for men with a cut-off score of 17; 80.0% and 53.7% for men with a cut-off score of 18; 56.7%, and 65.9% for women with a cut-off score of 17; and 76.7% and 43.9% for women with a cut-off score of 15., Conclusion: Regardless of sex, only three IPAG questions were deemed useful as screening for airflow limitation. The cut-off scores for men and women may be appropriately set at 18 and 15, respectively, in the Japanese population., Competing Interests: Mr. S Arizono reports grants from Hoshi Iryou-Sanki Co. Ltd and NPO Central Japan Lung Study Group, outside the submitted work and grants from Science Research from Japan Society for the Promotion of Science, during the conduct of the study. The other authors have no known conflicts of interest to declare., (© 2022 Machiguchi et al.)

Background: High-flow nasal cannula therapy is used as a noninvasive treatment for people with acute respiratory disease. The aim of this study was to assess the impact of high-flow nasal cannula different flow rates on different characteristics of swallowing in healthy volunteers., Methods: A prospective cohort study where healthy adult volunteers were subject to high-flow nasal cannula at different flow rates (0, 10, 20, 30, 40, and 50 L/min, in random order). The 30-mL water swallow test, repetitive saliva swallowing test, and 0-100 mm visual analog scale assessed aspiration, swallow frequency and effort, respectively., Findings: Thirty subjects (mean age 30 years) were enrolled. Nine subjects (30.0%) choked at 10, 40 and 50 L/min during the 30-mL water swallow test (p < 0.05). Swallowing effort was increased during flow rates ≥20 compared to 10 L/min (p < 0.05). Flow rates ≥20 L/min resulted in lower number of swallows during the repetitive saliva swallowing test compared to 0 and 10 L/min (p < 0.05)., Interpretation: High-flow nasal cannula flow rates above 40 L/min associated with choking (increased risk of aspiration), and was associated with decreased swallowing function in healthy volunteers. It may be important to assess swallowing function in patients with various clinical conditions and treated with high-flow nasal cannula, especially those at risk of aspiration pneumonia., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective The early detection and treatment of chronic obstructive pulmonary disease (COPD) requires comprehensive follow-up over a long period. The aim of this study was to determine the effects of a comprehensive long-term intervention system developed by the COPD Task Force for a rural city in Japan during a 7-year period. Methods This prospective, community-based longitudinal study encompassed 2006-2013 in Matsuura City, Japan. Primary and secondary screenings were performed for the early diagnosis and treatment of COPD. Individuals diagnosed with COPD were managed by the COPD Task Force's comprehensive early intervention system. The outcomes of interest were the rate of continuous follow-up after the diagnosis of COPD, the smoking cessation rate, and changes in the pulmonary function during a 7-year period. Subjects The study included 8,878 residents of 50-89 years of age who resided in Matsuura in 2006. Results In total, 140 participants received definitive diagnoses of COPD in 2006. After 7 years of intervention, 34 patients withdrew; 78 (74%) patients continued with treatment in our intervention system. The rate of smoking cessation was significantly increased in the intervention group (from 30% to 68%; p<0.01) over the 7-year period. The change in forced expiratory volume in 1 second (FEV 1 ) was -23.2 mL/year. Conclusion Our systematic longitudinal intervention system during a 7-year period led to high rates of follow-up and smoking cessation. Furthermore, our system may be able to prevent the decline of FEV 1 in COPD patients. This intervention system may be effective in rural cities with few respiratory physicians.

To search for giant X-ray pulses correlated with the giant radio pulses (GRPs) from the Crab pulsar, we performed a simultaneous observation of the Crab pulsar with the X-ray satellite Hitomi in the 2 - 300 keV band and the Kashima NICT radio observatory in the 1.4 - 1.7 GHz band with a net exposure of about 2 ks on 25 March 2016, just before the loss of the Hitomi mission. The timing performance of the Hitomi instruments was confirmed to meet the timing requirement and about 1,000 and 100 GRPs were simultaneously observed at the main and inter-pulse phases, respectively, and we found no apparent correlation between the giant radio pulses and the X-ray emission in either the main or inter-pulse phases. All variations are within the 2 sigma fluctuations of the X-ray fluxes at the pulse peaks, and the 3 sigma upper limits of variations of main- or inter-pulse GRPs are 22% or 80% of the peak flux in a 0.20 phase width, respectively, in the 2 - 300 keV band. The values become 25% or 110% for main or inter-pulse GRPs, respectively, when the phase width is restricted into the 0.03 phase. Among the upper limits from the Hitomi satellite, those in the 4.5-10 keV and the 70-300 keV are obtained for the first time, and those in other bands are consistent with previous reports. Numerically, the upper limits of main- and inter-pulse GRPs in the 0.20 phase width are about (2.4 and 9.3) ×10 -11 erg cm -2 , respectively. No significant variability in pulse profiles implies that the GRPs originated from a local place within the magnetosphere and the number of photon-emitting particles temporally increases. However, the results do not statistically rule out variations correlated with the GRPs, because the possible X-ray enhancement may appear due to a > 0.02% brightening of the pulse-peak flux under such conditions.

Introduction: Respiratory failure and respiratory tract infections are frequently observed as post-operative pulmonary complications, and significantly contribute to morbidity and mortality. However, the risk factors of post-operative respiratory failure and respiratory tract infections are controversial, and how these factors affect on incidence of complications is still unclear., Objective: To identify risk factors of post-operative respiratory failure and respiratory tract infections, and evaluate its impact on incidences after cardiovascular surgery., Methods: From June 2013 to May 2015, adult patients undergoing cardiovascular surgery in the department of cardiovascular surgery and post-operative rehabilitation of Nagasaki University Hospital (Nagasaki, Japan) were retrospectively investigated., Results: Fifty-two of 416 patients(12.5%)suffered from post-operative respiratory failure and respiratory tract infections. Identified risk stratification indicates the relevant operative factors were more important than pre-operative factors. The operative time (OR 1.696, 95% CI 1.302~2.211), post-operative water balance( OR 1.025, 95% CI 1.004~1.046)and emergency operation( OR 3.607, 95% CI 1.492~8.716)were significant independent risk factors in the development of post-operative respiratory failure and respiratory tract infections., Conclusions: These results indicated that the operative factors are more important as onset of post-operative respiratory failure and respiratory tract infections after cardiovascular surgery.

Background: In cardiothoracic and abdominal surgery, postoperative complications remain major clinical problems. Early mobilization has been widely practiced and is an important component in preventing complications, including orthostatic hypotension (OH) during postoperative management. We investigated cardiovascular response during early mobilization and the incidence of OH after cardiothoracic and abdominal surgery., Methods: In this prospective observational study, we consecutively analyzed data from 495 patients who underwent elective cardiothoracic and abdominal surgery. We examined the incidence of OH, and the independent risk factors associated with OH during early mobilization after major surgery. Multivariate logistic regression was performed using various characteristics of patients to identify OH-related independent factors., Results: OH was observed in 191 (39%) of 495 patients. The incidence of OH in cardiac, thoracic, and abdominal groups was 39 (33%) of 119, 95 (46%) of 208, and 57 (34%) of 168 patients, respectively. Male sex (OR 1.538; p = 0.03) and epidural anesthesia (OR 2.906; p < 0.001) were independently associated with OH on multivariate analysis., Conclusions: These results demonstrate that approximately 40% patients experience OH during early mobilization after cardiothoracic and abdominal surgery. Sex was identified as an independent factor for OH during early mobilization after all three types of surgeries, while epidural anesthesia was only identified after thoracic surgery. Therefore, the frequent occurrence of OH during postoperative early mobilization should be recognized., Trial Registration: University hospital Medical Information Network Center (UMIN-CTR) number UMIN000018632 . (Registered on 1st October, 2008).

This paper describes watershed modeling of catchments surrounding the Fukushima Dai-ichi Nuclear Power Plant to understand radio-cesium redistribution by water flows and sediment transport. We extended our previously developed three-dimensional hydrogeological model of the catchments to calculate the migration of radio-cesium in both sediment-sorbed and dissolved forms. The simulations cover the entirety of 2013, including nine heavy rainfall events, as well as Typhoon Roke in September 2011. Typhoons Man-yi and Wipha were the strongest typhoons in 2013 and had the largest bearing on radio-cesium redistribution. The simulated 137 Cs discharge quantities over the nine events in 2013 are in good agreement with field monitoring observations. Deposition mainly occurs on flood plains and points where the river beds broaden in the lower basins, and within dam reservoirs along the rivers. Differences in 137 Cs discharge ratios between the five basins are explained by differences in the initial fallout distribution within the basins, the presence of dam reservoirs, and the input supply to watercourses. It is possible to use these simulation results to evaluate future radioactive material distributions in order to support remediation planning., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: We established a COPD taskforce for early detection, diagnosis, treatment, and intervention. We implemented a pilot intervention with a prospective and longitudinal design in a regional city. This study evaluates the usefulness of the COPD taskforce and intervention based on COPD case detection rate and per capita medical costs., Method: We distributed a questionnaire to all 8,878 inhabitants aged 50-89 years, resident in Matsuura, Nagasaki Prefecture in 2006. Potentially COPD-positive persons received a pulmonary function test and diagnosis. We implemented ongoing detection, examination, education, and treatment interventions, performed follow-up examinations or respiratory lessons yearly, and supported the health maintenance of each patient. We compared COPD medical costs in Matsuura and in the rest of Nagasaki Prefecture using data from 2004 to 2013 recorded by the association of Nagasaki National Health Insurance Organization, assessing 10-year means and annual change., Results: As of 2014, 256 people have received a definitive diagnosis of COPD; representing 31% of the estimated total number of COPD patients. Of the cases detected, 87.5% were mild or moderate in severity. COPD medical costs per patient in Matsuura were significantly lower than the rest of Nagasaki Prefecture, as was rate of increase in cost over time., Conclusion: The COPD program in Matsuura enabled early detection and treatment of COPD patients and helped to lower the associated burden of medical costs. The success of this program suggests that a similar program could reduce the economic and human costs of COPD morbidity throughout Japan.

Analyses of nuclear emulsion detectors that can detect and identify charged particles or radiation as tracks have typically utilized optical microscope systems because the targets have lengths from several μm to more than 1000 μm. For recent new nuclear emulsion detectors that can detect tracks of submicron length or less, the current readout systems are insufficient due to their poor resolution. In this study, we developed a new system and method using an optical microscope system for rough candidate selection and the hard X-ray microscope system at SPring-8 for high-precision analysis with a resolution of better than 70 nm resolution. Furthermore, we demonstrated the analysis of submicron-length tracks with a matching efficiency of more than 99% and position accuracy of better than 5 μm. This system is now running semi-automatically.

The new Japanese x-ray astronomy satellite, ASTRO-H, will carry two identical hard x-ray telescopes (HXTs), which cover the energy range of 5 to 80 keV. The HXT mirrors employ tightly nested, conically approximated thin-foil Wolter-I optics, and the mirror surfaces are coated with Pt/C depth-graded multilayers to enhance the hard x-ray effective area by means of Bragg reflection. The HXT comprises foils 120-450 mm in diameter and 200 mm in length, with a focal length of 12 m. To obtain a large effective area, 213 aluminum foils 0.2 mm in thickness are tightly nested confocally. The requirements for HXT are a total effective area of >300  cm 2 at 30 keV and an angular resolution of <1.7 ' in half-power diameter (HPD). Fabrication of two HXTs has been completed, and the x-ray performance of each HXT was measured at a synchrotron radiation facility, SPring-8 BL20B2 in Japan. Angular resolutions (HPD) of 1.9 ' and 1.8 ' at 30 keV were obtained for the full telescopes of HXT-1 and HXT-2, respectively. The total effective area of the two HXTs at 30 keV is 349  cm 2 .

Animal models of obesity show that lipid deposits can injure the kidneys,and there is evidence for the role of lipids in the development of chronic renal dis-ease (CKD). Statins exhibit a lipid-lowering effect that acts on both total cholesterol and triglyceride (TG) levels and pleiotropic effects including their ability to reduce inflammation and fibrosis. The purpose of the present study was to confirm whether obesity induced by a high-fat diet (HFD, 60% fat) promotes lipid accumulation in the tubulointerstitial and/or glomerular areas in the kidney, and whether treatment of several statins, pravastatin (30 mg/kg, p.o.), rosuvastatin (3 mg/kg, p.o.),pitavastatin (1 mg/kg, p.o.) and atorvastatin (10 mg/kg, p.o.), suppresses obesity-induced lipid accumulation. Using male C57Bl/6J mice, we examined parameters related to energy metabolism, lipid accumulation as well as macrophage infiltration in glomeruli and the tubulointerstitial area, and glomerular injury using nephrin and desmin expression. None of the statins affected body weight, glucose metabolism,serum TG and adiponectin levels, or serum inflammatory cytokine levels. However,all statins improved lipid accumulation in the proximal tubules, improved glomerular hypertrophy, increased nephrin expression and decreased desmin expression, compared to non-treated obese animals. Moreover, the reduction of proximal tubular lipid accumulation was greater with pravastatin and rosuvastatin treatment than with pitavastatin and atorvastatin treatment. We concluded that hydrophilic statins may be more effective for preventing lipid accumulation in renal tubules than lipophilic statins., (© 2013 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Multi-pulse laser-induced damage threshold (LIDT) was experimentally investigated up to ~10(6) pulses for Cu, Ag mirrors. The surface roughness and the hardness dependence on the LIDT were also examined. The LIDT of OFHC-Cu decreased with the pulse number and was 1.0 J/cm(2) at 1.8 × 10(6) pulses. The expected LIDT of cutting Ag at 10(7) pulses was the highest; Ag mirror would be one of the best choices for ITER Thomson scattering system. For the roughness and hardness, material dependences of LIDT are discussed with experimental results.

Generic drugs contain the same active ingredient as an original drug and have their bioequivalence proved by pharmacokinetic tests. However, few studies have been reported on whether these bioequivalence studies infer pharmacodynamic equivalence. In this study, in eight healthy Helicobacter pylori-negative CYP2C19 extensive metabolizers, we compared the acid-suppressive effects of repeated administration of 15 mg of three brands of generic lansoprazole, Taiproton, Tapizol, and Lansoral, with those of the original lansoprazole, Takepron. Median intragastric pH value for 24-h and % pH > 4 for daytime (08:00-20:00 h) and night-time were significantly higher with any lansoprazole formulation, compared with the control (P < 0.05, Wilcoxon signed-rank test). However, during the daytime, % pH > 4 with Tapizol was significantly lower than the original (P < 0.05). Compared with the original, no significantly larger, but no small range of inter-subject variations were observed in these two parameters for each of the three brands of generic lansoprazole (Bartlett test). Pharmacokinetic bioequivalence tests do not necessarily guarantee pharmacodynamic equivalence.

Amyotrophic lateral sclerosis (ALS) involves the progressive degeneration of motor neurons in the spinal cord and the motor cortex. It has been shown that 15-20% of patients with familial ALS (FALS) have defects in the Sod1 gene, which encodes Cu,Zn-superoxide dismutase (SOD). To elucidate the pathological role of mutated Cu,Zn-SOD, we examined the issue of whether mutated Cu,Zn-SOD affects the cell cycle. Mouse neuroblastoma Neuro-2a cells were transfected with human wild-type or mutated (G37R, G93A) Cu,Zn-SOD. Mutated, Cu,Zn-SOD-transfected cells exhibited marked retardation in cell growth and G2/M arrest. They also displayed lower reactivity to phalloidin, indicating that the cytoskeleton was disrupted. Immunoprecipitation, two-dimensional gel electrophoresis, and Western blot analysis indicated that mutated Cu,Zn-SOD associates with actin. Similar results were obtained by in vitro incubation experiments with purified actin and mutated Cu,Zn-SOD (G93A). These results suggest that mutated Cu,Zn-SOD in FALS causes cytoskeletal changes by associating with actin, which subsequently causes G2/M arrest and growth retardation.

The International Focusing Optics Collaboration for microCrab Sensitivity (InFOCmicroS) balloonborne hard x-ray telescope incorporates graded Pt/C multilayers replicated onto segmented Al foils to obtain the significant effective area at energies previously inaccessible to x-ray optics. Reflectivity measurements of individual foils demonstrate our capability to produce a mass quantity of multilayered foils with a rms roughness of 0.5 nm. The effective area of the completed mirror is 78 and 22 cm2 at 20 and 40 keV, respectively. The measured half-power diameter is 2.0 +/- 0.6 are min (90% confidence). The successful completion of this mirror demonstrates its applicability to future x-ray telescopes such as Constellation-X.

A hard-x-ray telescope is successfully produced for balloon observations by making use of depth-graded multilayers, or so-called supermirrors, with platinum-carbon (Pt/C) layer pairs. It consists of four quadrant units assembled in an optical configuration with a diameter of 40 cm and a focal length of 8 m. Each quadrant is made of 510 pieces of coaxially and confocally aligned supermirrors that significantly enhance the sensitivity in an energy range of 20-40 keV. The configuration of the telescope is similar to the x-ray telescope onboard Astro-E, but with a longer focal length. The reflectivity of supermirrors is of the order of 40% in the energy range concerned at a grazing angle of 0.2 deg. The effective area of a fully assembled telescope is 50 cm2 at 30 keV. The angular resolution is 2.37 arc min at half-power diameter 8.0 keV. The field of view is 12.6 arc min in the hard-x-ray region, depending somewhat on x-ray energies. We discuss these characteristics, taking into account the figure errors of reflectors and their optical alignment in the telescope assembly. This hard-x-ray telescope is unanimously afforded in the International Focusing Optics Collaboration for muCrab Sensitivity balloon experiment.

X-ray characterization measurements of the x-ray telescope (XRT) onboard the Astro-E satellite were carried out at the Institute of Space and Astronautical Science (Japan) x-ray beam facility by means of a raster scan with a narrow x-ray pencil beam. The on-axis half-power diameter (HPD) was evaluated to be 1.8?-2.2?, irrespective of the x-ray energy. The on-axis effective areas of the XRTs for x-ray imaging spectrometers (XISs) were approximately 440, 320, 240, and 170 cm(2) at energies of 1.49, 4.51, 8.04, and 9.44 keV, respectively. Those of the x-ray spectrometer (XRS) were larger by 5-10%. The replication method introduced for reflector production significantly improved the imaging capability of the Advanced Satellite for Cosmology and Astrophyics (ASCA) XRT, whose HPD is ~3.6?. The increase in the effective area by a factor of 1.5-2.5, depending upon the x-ray energy, compared with that of the ASCA, was brought about by mechanical scale up and longer focal lengths. The off-axis HPDs were almost the same as those obtained on the optical axis. The field of view is defined as the off-axis angle at which the effective area becomes half of the on-axis value. The diameter of the field of view was ~19? at 1.49 keV, decreasing with increasing x-ray energy, and became ~13? at 9.44 keV. The intensity of stray light and the distribution of this kind of light on the focal plane were measured at the large off-axis angles 30? and 60?. In the entire XIS field of view (25.4 mm x 25.4 mm), the intensity of the stray light caused by a pointlike x-ray source became at most 1% of the same pointlike source that was on the optical axis.

Sialic acids play important roles in various biological functions. In the brain, evidence suggests that sialylation of glycoproteins and glycolipids affects neural plasticity. While the 18 sialyltransferase isoenzymes (STs) identified to date synthesize individual sialyl-oligosaccharide structures, they each exhibit activity toward more than one substrate and can overlap in their specificity. Therefore, the distribution of STs is a secondary factor in the study of specific sialylation. Here, seven STs; ST3Gal I-IV, ST8Sia IV, ST6Gal I and ST6GalNAc II, the expressions of which were identified in the adult hippocampus by RT-PCR, showed diverse localization patterns in the hippocampus on in situ hybridization, suggesting that the individual cells expressed relevant STS: Furthermore, to assay activity-related changes in ST expression, we used amygdaloid-kindling among models of neural plasticity. Differential expression of the STs participating in the kindling, notably, up-regulation of ST3Gal IV and ST6GalNAc II mRNAs, and down-regulation of ST3Gal I and ST8Sia IV mRNAs, were observed in the hippocampus following kindled seizures. These results indicate that ST expressions are regulated by physiological activity and may play a role in neural plasticity.

Amygdaloid kindling is a model of human temporal lobe epilepsy, in which excitability in limbic structures is permanently enhanced by repeated stimulations. We report here dendritic aberrations occurring in mice following kindled-seizures. Adult mice received a biphasic square wave pulse [495+/-25.5 (S.E.M.) microA 60 Hz, 200 micros duration, for 2 s] unilaterally in the basolateral amygdaloid complex once a day and mice with electrophysiologically and behaviorally verified seizures were used in the experiments. The hippocampus and amygdaloid complex contralateral to the lesions were observed by immunofluorescence histochemistry with a somatodendritic marker, microtubule-associated protein 2 (MAP2), showing that kindled-seizures caused hypertrophy of proximal dendrites in the granule cells of the dentate gyrus and in neurons of the amygdalohippocampal area. To further characterize the morphological changes of the dendrites, electron micrographic analysis was performed on the contralateral side. (1) In the granular layer of the dentate gyrus and the amygdalohippocampal area, kindled-seizures generated an increase in the number of dendrites containing polymerized microtubules and width of dendritic profiles showing the increase was in the range 0.2-3.0 and 0.2-1.4 microm, respectively. (2) In the granular layer, bundles between dendrites separated by the puncta adhaerentia increased. (3) In the granular layer, the seizure-induced dendritic aberration was more severe in the rostral than the caudal region. These results suggested that growth of dendrites with enriched-stable microtubules is part of the structural plasticity in response to seizure activity in specific areas of the adult brain.

X-ray telescopes (XRT's) of nested thin foil mirrors are developed for Astro-E, the fifth Japanese x-ray astronomy satellite. Although the launch was not successful, the design concept, fabrication, and alignment procedure are summarized. The main purpose of the Astro-E XRT is to collect hard x rays up to 10 keV with high efficiency and to provide medium spatial resolution in limited weight and volume. Compared with the previous mission, Advanced Satellite for Cosmology and Astrophysics (ASCA), a slightly longer focal length of 4.5-4.75 m and a larger diameter of 40 cm yields an effective area of 1750 cm2 at 8 keV with five telescopes. The image quality is also improved to 2-arc min half-power diameter by introduction of a replication process. Platinum is used instead of gold for the reflectors of one of the five telescopes to enhance the high-energy response. The fabrication and alignment procedure is also summarized. Several methods for improvement are suggested for the reflight Astro-E II mission and for other future missions. Preflight calibration results will be described in a forthcoming second paper, and a detailed study of images will be presented in a third paper.

This study was conducted to investigate an effect of heat stress at 44 degrees C for 30 min on intracellular Ca2+ signaling system and on heat shock protein (HSP)-70 expression. 5-HT-induced Ca2+ mobilization was reduced 1, 3 and 6 hrs after heat stress, and recovered to the control level 12 and 24 hrs after heat stress. One hr after heat stress, Ca2+ rise was significantly decreased when the cells were stimulated by any concentration of 5-HT. Thrombin-induced Ca2+ increase was also markedly reduced 1 hr after heat stress. HSP-70 level was increased 6 and 9 hr after heat stress. In HSP synthesis inhibitor quercetin-treated cells, HSP-70 expression was not enhanced after heat stress, and Ca2+ rise in response to 5-HT did not return to the control level. However, the Ca2+ rise induced by 5-HT was not restored to the control level after stress in Ac-Asp-Glu-Val-Asp-H (DEVD)-exposed cells while DEVD had little effect on heat stress-induced synthesis of HSP-70. Dexamethasone did not alter the change in HSP-70 expression or Ca2+ response after heat stress. These results indicate that heat stress attenuated 5-HT-induced Ca2+ mobilization and that HSP-70 expression played an important role in recovery from Ca2+ impairment, possibly via protease activity in C6 cells.

In this study, the authors have demonstrated the effect of lithium, a typical mood stabilizer, on thrombin-evoked Ca2+ mobilization in C6 cells to elucidate the action mechanisms of the drug. Thrombin-induced Ca2 mobilization was reduced 24 hr after 1 or 10 mM lithium chloride (LiCl) pretreatment. The Ca2+ rise was reduced in a time-dependent manner, and the significant inhibition was observed 9 hr pretreatment with 10 mM LiCl. On the other hand, pretreatment of the cells with 10 mM LiCl for 24 hr did not alter the amount of Galphaq/11 significantly. Pretreatment with 10 mM LiCl for 24 hr failed to reduce the 5-HT-induced Ca2+ mobilization or to affect the desensitization of the 5-HT signal. Finally, thrombin-elicited Ca2+ rise was markedly inhibited in the presence of 0.05 U/ml plasmin, however, the Ca2+ rise was not further attenuated in the presence of plasmin in C6 cells pretreated with LiCl for 24 hr. These results indicate that pretreatment with LiCl attenuated thrombin-evoked intracellular Ca2+ mobilization in plasmin sensitive manner in C6 rat glioma cells. Thus, it is important to investigate the effect of lithium on thrombin-induced cellular responses to clarify the action mechanism of lithium in relation to some abnormality in thrombin-evoked Ca2+ rise observed in bipolar disorders.

Tardive extrapyramidal symptoms (EPS) induced by neuroleptic treatment, and particularly EPS which persist after withdrawal of the drugs, are clinically serious problems. We describe a patient with four types of tardive and persistent EPS such as dystonia, dyskinesia, choreatic movement and myoclonus, induced by haloperidol. These EPS were remarkably inhibited by 3 mg/day risperidone. This is the first published case demonstrating simultaneous development of these four types of tardive EPS induced by a neuroleptic and then reduced by low-dose risperidone treatment. ( Int J Psych Clin Pract 2000; 4: 241 - 243).

The practical use of a grazing x-ray telescope is demonstrated for hard-x-ray imaging as hard as 40 keV by means of a depth-graded d-spacing multilayer, a so-called supermirror. Platinum-carbon multilayers of 26 layer pairs in three blocks with a different periodic length d of 3-5 nm were designed to enhance the reflectivity in the energy range from 24 to 36 keV at a grazing angle of 0.3 deg. The multilayers were deposited on thin-replica-foil mirrors by a magnetron dc sputtering system. The reflectivity was measured to be 25%-30% in this energy range; 20 mirror shells thus deposited were assembled into the tightly nested grazing-incidence telescope. The focused hard-x-ray image was observed with a newly developed position-sensitive CdZnTe solid-state detector. The angular resolution of this telescope was found to be 2.4 arc min in the half-power diameter.

Grazing-incidence specular reflectance and near-specular scattering were measured at Al-K(alpha) (1.486-keV, 8.34-?) radiation on uncoated dielectric substrates whose surface topography had been measured with a scanning probe microscope and a mechanical profiler. Grazing-incidence specular reflectance was also measured on selected substrates at the Cu-K(alpha) (8.047-keV, 1.54-?) wavelength. Substrates included superpolished and conventionally polished fused silica; SiO(2) wafers; superpolished and precision-ground Zerodur; conventionally polished, float-polished, and precision-ground BK-7 glass; and superpolished and precision-ground silicon carbide. Roughnesses derived from x-ray specular reflectance and scattering measurements were in good agreement with topographic roughness values measured with a scanning probe microscope (atomic force microscope) and a mechanical profiler that included similar ranges of surface spatial wavelengths. The specular reflectance was also found to be sensitive to the density of polished surface layers and subsurface damage down to the penetration depth of the x rays. Density gradients and subsurface damage were found in the superpolished fused-silica and precision-ground Zerodur samples. These results suggest that one can nondestructively evaluate subsurface damage in transparent materials using grazing-incidence x-ray specular reflectance in the 1.5-8-keV range.

The optical performance of platinum-carbon multilayers deposited onto different substrates has been examined. Specular reflectivity and non-specular diffuse scattering were measured to study the replication of substrate roughness into the multilayer structure. Surface topography was measured before and after deposition using a scanning probe microscope and a mechanical profiler.

Multilayer supermirrors stacked with three sets of Pt/C combinations have been fabricated on a flat float-glass and conical replica foil mirror using a magnetron DC sputtering system, and applied to X-ray optical systems in the hard X-ray region. The design of the supermirror is optimized to obtain the highest integrated reflectivity in the energy band and at the grazing angle concerned. X-ray reflectivities of 30% in the 25-35 keV band at an incidence angle of 0.3 degrees were obtained.

To investigate the mechanisms by which lipopolysaccharide (LPS) affects Ca2+ signaling systems, we studied the effects of LPS on the serotonin (5-HT)- or thrombin-induced intracellular Ca2+ ([Ca2+]i) increase in rat C6 glioma cells. Pretreatment of the cells with 1 microg/ml LPS for 24 hr significantly inhibited [Ca2+]i increase induced by 10 microM 5-HT- or 0.5 U/ml thrombin. Its inhibitory effects were both dose- and time-dependent. Treatment with 1 mM dibutyryl cGMP (dbcGMP) for 30 min also significantly inhibited the 5-HT- and thrombin-induced [Ca2+]i increase to approximately 60-70% of control. However, simultaneous pretreatment with LPS and dbcGMP did not show any synergistic inhibition. The simultaneous pretreatment with LPS and the potent cGMP-dependent protein kinase (PKG) inhibitors H-8 and KT5823 for 24 hr significantly antagonized the inhibitory effect of LPS. Pretreatment of the cells with 1 microg/ml LPS for 24 hr significantly enhanced cGMP accumulation, while dexamethasone and NMMA (NOS inhibitors) significantly attenuated the LPS-induced enhancement in cGMP accumulation. In addition, pretreatment of the cells with 100 nM dexamethasone for 24 hr significantly suppressed LPS-induced inducible nitric oxide synthase (iNOS; type II NOS, NOS-II) protein expression. These results indicate that LPS may inhibit both 5-HT- and thrombin-induced [Ca2+]i increase via iNOS expression and PKG activation pathway in rat C6 glioma cells.

In this paper, we show the importance of intracellular calcium (Ca2+) signaling systems in the pathophysiology of mood disorders based on our recent work. Patients with affective disorders appear to have an enhanced intracellular Ca2+ rise in response to serotonin. We have observed effects of antidepressant drugs on intracellular Ca2+ signaling in rat cultured neuronal cells and glioma cells, and found that acute application of several classes of antidepressant drugs inhibited intracellular Ca2+ signaling and Ca2+-related signaling. It is important to investigate the role of intracellular Ca2+ signaling system for an understanding of the pathophysiology of affective disorders.

The objective of the present study was to evaluate the efficacy of mianserin and trazodone as antidepressants with serotonin 2 antagonist properties on negative symptoms and tardive dyskinesia in elderly patients with chronic schizophrenia. In this double-blind, placebo-controlled study the dose of each drug was increased gradually, from 20 mg/day mianserin to 60 mg/day, and from 50 mg/day trazodone to 200 mg/day. Symptoms were assessed using the Brief Psychiatric Rating Scale, the Scale for Assessment of Negative Symptoms and the Abnormal Involuntary Movement Scale every week for 5 weeks. A total of 38 patients (23 men and 15 women) completed the trial. Mianserin (n = 13) and trazodone (n = 12) did not alter the Brief Psychiatric Rating Scale positive symptom factor over the 5 weeks. In the mianserin group, the Scale for Assessment of Negative Symptoms total score decreased significantly after 5 weeks. Scores of 'affective flattening and blunting' and 'alogia' scores on the Scale for assessment of Negative Symptoms decreased significantly in both treatment groups. In the trazodone group, the decrease in the Abnormal Involuntary Movement Scale total score was statistically significant at weeks 2 and 3. Results indicate that serotonergic antidepressants, when used in conjunction with neuroleptics, are safe and effective for treating negative symptoms in elderly patients with chronic schizophrenia. Results also indicated a possible beneficial effect of trazodone in treating tardive dyskinesia.

We have investigated the effects of interleukin (IL)-1 beta and lipopolysaccharide (LPS) on endothelin (ET)-induced intracellular Ca2+ rise in C6 rat glioma cells in order to study the mechanisms of their effects on Ca2+ signaling systems. Pretreatment with IL-1 beta (10(3) U/mL) and LPS (1 microgram/mL) for 24 h significantly inhibited 100 nM ET-1-induced increase in intracellular Ca2+ either in the presence or absence of external Ca2+. Their inhibitory effects were in dosedependent (IL-1 beta; 50-1000 U/mL, LPS; 10-1000 ng/mL) and time-dependent (12-24 h) manners. A tyrosine kinase antagonist genistein (50 microM) but not a protein kinase C inhibitor H7 (30 microM) prevented the inhibition of the ET response by IL-1 beta and LPS. These results suggest that activation of tyrosine kinase may be essential for the inhibition of the ET receptor-mediated Ca2+ signaling systems by IL-1 beta and LPS.

A 22-year-old woman was admitted to our hospital because she showed psychomotor excitement and signs of schizophrenia following psychological stress. Nine days after neuroleptic medication, she could not eat and exhibited high fever, diaphoresis, excessive salivation, and severe extrapyramidal signs with cogwheel rigidity and resting tremor of the upper extremities. The next day, bucco-linguomasticatory dyskinesia, which is quite similar to tardive dyskinesia, appeared. The dyskinesia lasted intermittently for 6 days. The present case shows that buccolingual dyskinesia can occur even after early neuroleptic exposure in certain patients.

To determine whether nitric oxide (NO) is a possible mediator in the inhibitory action of CCK-octapeptide (CCK-OP) on circular muscle contractions of the rat proximal colon, contractile activities of the circular muscle were recorded in the proximal colon of unrestrained conscious rats in the fasting state using a miniature strain gauge force transducer and an implantable telemetry system. Regular and rhythmic phasic contractions were observed during the fasted condition, similar to the myoelectric migrating complex seen in intestinal contractions of the fasting dog. These phasic contractions were almost completely inhibited after intraperitoneal (i.p.) administration of CCK-OP at a dose of 15 microg/kg body weight. N(omega)-nitro-arginine, methyl ester (L-NAME), at doses of 20 and 200 mg/kg i.p. administered prior to i.p. injection of CCK-OP, prevented the inhibitory action on the fasting phasic contractions. The degree of prevention was dose-dependent. 100 mg/kg body weight i.p. injection of L-arginine inhibited the circular muscle contractions. The same dose of D-arginine had no action on contractions of the circular muscle of the proximal colon in the fasted rat. From these data, we conclude that NO is one possible mediator in the inhibitory mechanism of CCK-OP on smooth muscle motor activity of the rat proximal colon in vivo.

Dantrolene has been known to affect intracellular Ca2+ concentration ([Ca2+]i) by inhibiting Ca2+ release from intracellular stores in cultured neurons. We were interested in examining this property of dantrolene in influencing the [Ca2+]i affected by the NMDA receptor ligands, KCl, L-type Ca2+ channel blocker nifedipine, and two other intracellular Ca2(+)-mobilizing agents caffeine and bradykinin. Effect of dantrolene on the spontaneous oscillation of [Ca2+]i was also examined. Dantrolene in microM concentrations dose-dependently inhibited the increase in [Ca2+]i elicited by NMDA and KCl. AP-5, MK-801 (NMDA antagonists), and nifedipine respectively reduced the NMDA and KCl-induced increase in [Ca2+]i. Dantrolene, added to the buffer solution together with the antagonists or nifedipine, caused a further reduction in [Ca2+]i to a degree similar to that seen with dantrolene alone inhibiting the increase in [Ca2+]i caused by NMDA or KCl. At 30 microM, dantrolene partially inhibited caffeine-induced increase in [Ca2+]i whereas it has no effect on the bradykinin-induced change in [Ca2+]i. The spontaneous oscillation of [Ca2+]i in frontal cortical neurons was reduced both in amplitude and in base line concentration in the presence of 10 microM dantrolene. Our results indicate that dantrolene's mobilizing effects on intracellular Ca2+ stores operate independently from the influxed Ca2+ and that a component of the apparent increase in [Ca2+]i elicited by NMDA or KCl represents a dantrolene-sensitive Ca2+ release from intracellular stores. Results also suggest that dantrolene does not affect the IP3-gated release of intracellular Ca2+ and that the spontaneous Ca2+ oscillation is, at least partially, under the control of Ca2+ mobilization from internal stores.

Infectious diseases caused by methicillin-resistant Staphylococcus aureus, MRSA, and Candida albicans are often serious in compromised hosts. We enumerated MRSA and C. albicans on denture surfaces and in saliva samples from 29 adults. Staphylococcus species, MRSA, and methicillin-resistant Staphylococcus epidermidis, MRSE, were detected on 17, 3, and 1 of the 29 denture surfaces, respectively. C. albicans were detected on 22 denture surfaces. All saliva samples from patients whose dentures carried Staphylococcus species and C. albicans were also found to contain both microorganisms. Adherence of isolated 3H labeled cells of MRSA and C. albicans to resin beads and saliva-coated resin beads was examined. Cells of both microorganisms adhered in significantly higher numbers to saliva-coated resin beads than to resin beads. The hydrophobicity of the MRSA isolated from denture surfaces varied from strain to strain; that of C. albicans strains was moderately high. The zeta potentials of MRSA isolates and of C. albicans isolates determined in KCI buffer were significantly low. The potential of the resin beads decreased after treatment with saliva. Two out of 5 MRSA strains were found to be inhibited in growth by oral Streptococcus, Actinomyces, and gram-negative bacterial strains, suggesting that some oral bacterial species play a role in inhibiting the colonization of Staphylococcus species. No isolates of C. albicans were inhibited in their growth by any of the oral bacteria tested. Isolates of MRSA and C. albicans coaggregated with Porphyromonas gingivalis and Fusobacterium nucleatum strains. Using denture cleaners every night for 2 weeks did not reduce numbers of Staphylococcus species or C. albicans organisms in saliva.

The x-ray properties of multinested thin-foil mirror x-ray telescopes (XRT's) on board ASCA, the Advanced Satellite for Cosmology and Astrophysics, were fully evaluated with an x-ray pencil beam.Scanning over the telescope aperture of 35 cm in diameter with an x-ray pencil beam, we found the effective area of a set of XRT's to be 325, 200, and 113 cm(2) at energies of 1.5, 4.5, and 8.0 keV, respectively. We derive the point-spread functions (PSF's) of the XRT's by measuring the image profile at the focal plane with an x-ray CCD. The PSF is found to exhibit a sharp core concentrated within 30 arcsec and a broad wing extended to 3 arcmin in half-power diameter. We also evaluate the contribution of stray light, which is caused by the single reflection of x rays by primary or secondary mirrors and by the backside reflection of the mirrors. To obtain the characteristics of the XRT in the energy region of 0.5-10.0 keV, incorporated with the measurements at discrete energies, we develop a ray-tracing method with the telescope design parameter, the PSF, and optical constants. In particular, we obtain the optical constants around the gold-atom M shell (Au-M) absorption-edge energies by measuring the reflectivity of our mirror sample, with monochromatized x-rays in the energy range of 2.0-3.5 keV from synchrotron radiation. Taking into account the PSF's and optical constants, we find that our ray-tracing program can reproduce all these XRT performances.