Optimization of Sulfide Annealing Conditions for Ag8SnS6 Thin Films.

Ag8SnS6 (ATS) has been reported to have a band gap of 1.33 eV and is expected to be a suitable material for the light-absorbing layers of compound thin-film solar cells. However, studies on solar cells that use ATS are currently lacking. The objective of this study is to obtain high-quality ATS thin films for the realization of compound thin-film solar cells using vacuum deposition and sulfide annealing. First, glass/SnS/Ag stacked precursors are prepared by vacuum deposition. Subsequently, they are converted to the ATS phase via sulfide annealing, and various process conditions, namely, annealing time, annealing temperature, and number of steps, are studied. By setting the heat treatment temperature at 550 °C and the heat treatment time at 60 min, a high-quality ATS thin film could be obtained. Multi-step heat treatment also produces thin films with nearly no segregation or voids.

Breakfast Skipping and Declines in Cognitive Score Among Community-Dwelling Older Adults: A Longitudinal Study of the HEIJO-KYO Cohort.

Previous studies outlined the correlation of adverse effects of breakfast skipping with cognitive function. However, the majority of these studies have focused on the short-term effects; to date, the long-term effect of breakfast skipping on cognitive function among older adults remains unclear. In this prospective cohort study of 712 older adults (mean age, 70.8 years), breakfast skipping was defined as skipping breakfast one or more times per week, and declines in cognitive score was defined as decreases in Mini-Mental State Examination (MMSE) score of two or more in the observed period. During follow-up (median, 31 months), 135 of 712 participants developed declines in cognitive score. Poisson regression models revealed that the incidence rate for declines in cognitive score was significantly higher in breakfast skipper (n = 29) than breakfast eaters (n = 683) [incidence rate ratio (IRR), 2.10; 95% CI, 1.28-3.44]. Additional propensity score adjustments related to breakfast skipping from baseline parameters (age, gender, smoking and drinking status, BMI, household income, educated level, depressive symptoms, hypertension, diabetes, sleep medication, physical activity, caloric intake, and baseline cognition) produced consistent results (IRR, 2.21; 95% CI, 1.33-3.68). Sensitivity analysis, when the cut-off value of decreases in MMSE score was changed to three points, suggested a significant and stronger association (IRR, 3.03; 95% CI, 1.72-5.35). Regarding daily intakes of food groups, breakfast skippers consumed a significantly lower amount of vegetables, fruits, and fish than breakfast eaters. In conclusion, our findings suggest that breakfast skipping is longitudinally associated with declines in cognitive score among older adults.

Effectiveness of Additional Risk Minimization Measures for Atezolizumab in the European Union.

BACKGROUND: A Guide for Healthcare Professionals (HCP Guide) and patient alert card (PAC) for atezolizumab as additional risk minimization measures for physicians were distributed to raise awareness and help in the detection and management of immune-related adverse drug reactions. OBJECTIVES: The main objective of this study was to assess the receipt, knowledge, and behaviors of physicians regarding the atezolizumab HCP Guide and PAC. METHODS: A multi-country, one-wave, observational, cross-sectional, web-based, self-reported physician survey was conducted to assess the level of knowledge of key messages related to immune-related adverse drug reactions summarized in the atezolizumab HCP Guide and PAC among physicians (oncologists, pulmonologists, and urologists) prescribing atezolizumab in six European countries (Denmark, Germany, Italy, Spain, Sweden, and the UK). Responses regarding the receipt, understanding and use of the materials, and knowledge and behavior related to the HCP Guide and PAC are presented as percentages and continuous scores scaled out of 100 points, with corresponding 95% confidence intervals (CIs). RESULTS: Among 313 physicians (255 oncologists, 30 pulmonologists, and 28 urologists), 77.4% received the HCP Guide and 74.2% the PAC. The HCP Guide was read by 71.3% of the 267 physicians who received the materials, and the mean usage score was 69.5 (95% CI 66.0-72.9), and 57.1% of physicians had scores ≥ 70. The HCP Guide was completely understood by 85.4% of physicians who had read it. Mean knowledge scores were 63.9 (95% CI 62.1-65.7) and 39.4% of physicians had correct knowledge scores ≥ 70. Mean knowledge scores were 66.8 (95% CI 64.9-68.7) for receipt of both the HCP Guide and PAC, 59.4 (95% CI 55.5-63.4) for one of the materials, and 60.8 (95% CI 55.4-66.2) for having received none of the materials. Mean behavior scores were 78.9 (95% CI 76.8-81.0), and 74.8% of physicians had behavior scores ≥ 70. The mean behavior score was 79.0 (95% CI 76.5-81.5) for those who received both the HCP Guide and PAC, 76.9 (95% CI 72.2-81.5) for receipt of one of the materials, and 81.5 (95% CI 75.0-88.0) for those who received none of the materials. CONCLUSIONS: The study assessed the effectiveness of the atezolizumab additional risk minimization educational materials among physicians in six European countries, using process indicators. The educational materials reached over 70% of target physicians, 57.1% of whom reported using them. Knowledge and behavior related to immune-related adverse drug reactions for atezolizumab were no better in those who received the additional risk minimization educational materials. The results support the safe use of atezolizumab by these physician groups and contributed to the European Medicines Agency permitting removal of the HCP Guide.

Results of a Dose-Finding Phase 1b Study of Subcutaneous Atezolizumab in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer.

Intravenous (IV) atezolizumab is approved for non-small cell lung and other cancers. Subcutaneous (SC) atezolizumab coformulated with recombinant human hyaluronidase, a permeation enhancer for SC dispersion and absorption, is being developed to improve treatment options, reduce burden, and increase efficiency for patients and practitioners. IMscin001 (NCT03735121), a 2-part, open-label, global, multicenter, phase 1b/3 study, is evaluating the pharmacokinetics (PK), safety, and efficacy of SC atezolizumab. The part 1 (phase 1b) objective was determination of an SC atezolizumab dose yielding a serum trough concentration (Ctrough ) comparable with IV. Patients enrolled in 3 cohorts received SC atezolizumab 1800 mg (thigh) once (cohort 1), 1200 mg (thigh) every 2 weeks for 3 cycles (cohort 2), or 1800 mg (abdomen) every 3 weeks cycle 1, then cycles 2 and 3 (thigh) every 3 weeks (cohort 3). In subsequent cycles, IV atezolizumab 1200 mg every 3 weeks was administered until loss of clinical benefit. SC atezolizumab 1800 mg every 3 weeks and 1200 mg every 2 weeks provided similar Ctrough and area under the curve values in cycle 1 to the corresponding IV atezolizumab reference, was well tolerated, and exhibited a safety profile consistent with the established IV formulation. Exposure following SC injection in the abdomen was lower (20%, 28%, and 27% for Ctrough , maximum concentration, and area under the concentration-time curve from time 0 to day 21, respectively) than in the thigh. Part 1 SC and IV PK data were analyzed using a population PK modeling approach, followed by simulations. Part 2 (phase 3) will now be initiated to demonstrate that SC atezolizumab PK exposure is not lower than that of IV.

Contrasting open-loop dynamic characteristics of sympathetic and vagal systems during baroreflex-mediated heart rate control in rats.

Although heart rate (HR) is governed by the sympathetic and parasympathetic nervous systems, a head-to-head comparison of the open-loop dynamic characteristics of the total arc from a baroreceptor pressure input to the HR response has yet to be performed. We estimated the transfer function from carotid sinus pressure input to the HR response (HCSP→HR) before and after bilateral vagotomy (n = 7) as well as before and after the administration of a ß-blocker propranolol (n = 8) in anesthetized male Wistar-Kyoto rats. The carotid sinus pressure was perturbed according to a Gaussian white noise signal so that the input power spectra were relatively flat between 0.01 and 1 Hz. The gain plot of HCSP→HR was V-shaped. Vagotomy reduced the dynamic gain at 1 Hz (0.0598 ± 0.0065 to 0.0025 ± 0.0004 beats·min-1·mmHg-1, P < 0.001) but not at 0.01 or 0.1 Hz. ß-Blockade reduced the dynamic gain at 0.01 Hz (0.247 ± 0.069 to 0.077 ± 0.017 beats·min-1·mmHg-1, P = 0.020) but not at 0.1 or 1 Hz. We also estimated the efferent limb transfer function from electrical vagal efferent stimulation to the HR response (HVN→HR) under ß-blockade conditions. We associated the model parameters of HVN→HR with the mean HR and the standard deviation of HR so that HVN→HR could be estimated based only on the HR data. We finally estimated the neural arc transfer function from a pressure input to efferent vagal nerve activity by dividing HCSP→HR by HVN→HR. The mathematically determined vagal neural arc showed derivative characteristics with its phase near zero radians at the lowest frequency.

Even weak vasoconstriction from rilmenidine can be unmasked in vivo by opening the baroreflex feedback loop.

AIMS: Rilmenidine and moxonidine are centrally acting antihypertensive agents that are more selective for I1-imidazoline receptors than for α2-adrenergic receptors. Moxonidine previously showed a peripheral vasoconstrictive effect stronger than generally recognized, which counteracted an arterial pressure (AP) lowering effect resulting from central sympathoinhibition. We tested whether rilmenidine also showed a significant vasoconstrictive effect that could attenuate its AP lowering effect. MAIN METHODS: Efferent sympathetic nerve activity (SNA) and AP responses to changes in carotid sinus pressure were compared in nine anesthetized Wistar-Kyoto rats before and after low, medium, and high doses (40, 100, and 250 µg/kg, respectively) of intravenous rilmenidine. KEY FINDINGS: High-dose rilmenidine narrowed the range of the SNA response (from 89.6 ±â€¯2.9% to 50.4 ±â€¯7.9%, P < 0.001) and reduced the lower asymptote of SNA (from 13.5 ±â€¯3.0% to 2.7 ±â€¯1.5%, P < 0.001). High-dose rilmenidine significantly increased the intercept (from 57.1 ±â€¯3.8 to 78.2 ±â€¯2.7 mm Hg, P < 0.001) but reduced the slope (from 0.82 ±â€¯0.08 to 0.51 ±â€¯0.07 mm Hg/%, P < 0.001) of the SNA-AP relationship. The reduction in the operating-point AP induced by high-dose rilmenidine did not significantly differ based on whether the peripheral effect was considered (-19.8 ±â€¯2.2 vs. -26.4 ±â€¯5.3 mm Hg, not significant). SIGNIFICANCE: Rilmenidine increased AP in the absence of SNA, which suggests a peripheral vasoconstrictive effect; however, the vasoconstrictive effect was weak and did not significantly counteract the AP-lowering effect through central sympathoinhibition.

Cooling Effects of Wearer-Controlled Vaporization for Extravehicular Activity.

INTRODUCTION: The extravehicular activity suit currently used by the United States in space includes a liquid cooling and ventilation garment (LCVG) that controls thermal conditions. Previously, we demonstrated that self-perspiration for evaporative cooling (SPEC) garment effectively lowers skin temperature without raising humidity in the garment. However, the cooling effect is delayed until a sufficient dose of water permeates and evaporates. In the present study, we hypothesized that wearer-controlled vaporization improves the cooling effect. METHODS: Six healthy subjects rode a cycle ergometer under loads of 30, 60, 90, and 120 W for durations of 3 min each. Skin temperature and humidity on the back were measured continuously. Subjects wore and tested three garments: 1) a spandex garment without any cooling device (Normal); 2) a simulated LCVG (s-LCVG) or spandex garment knitted with a vinyl tube for flowing and permeating water; and 3) a garment that allowed wearer-controlled vaporization (SPEC-W). RESULTS: The use of s-LCVG reduced skin temperature by 1.57 ± 0.14°C during 12 min of cooling. Wearer-controlled vaporization of the SPEC-W effectively and significantly lowered skin temperature from the start to the end of cycle exercise. This decrease was significantly larger than that achieved using s-LCVG. Humidity in the SPEC-W was significantly lower than that in s-LCVG. DISCUSSION: This preliminary study suggests that SPEC-W is effective in lowering skin temperature without raising humidity in the garment. The authors think it would be useful in improving the design of a cooling system for extravehicular activity.Tanaka K, Nagao D, Okada K, Nakamura K. Cooling effects of wearer-controlled vaporization for extravehicular activity. Aerosp Med Hum Perform. 2017; 88(4):418-422.

Adaptation to microgravity, deconditioning, and countermeasures.

Humans are generally in standing or sitting positions on Earth during the day. The musculoskeletal system supports these positions and also allows motion. Gravity acting in the longitudinal direction of the body generates a hydrostatic pressure difference and induces footward fluid shift. The vestibular system senses the gravity of the body and reflexively controls the organs. During spaceflight or exposure to microgravity, the load on the musculoskeletal system and hydrostatic pressure difference is diminished. Thus, the skeletal muscle, particularly in the lower limbs, is atrophied, and bone minerals are lost via urinary excretion. In addition, the heart is atrophied, and the plasma volume is decreased, which may induce orthostatic intolerance. Vestibular-related control also declines; in particular, the otolith organs are more susceptible to exposure to microgravity than the semicircular canals. Using an advanced resistive exercise device with administration of bisphosphonate is an effective countermeasure against bone deconditioning. However, atrophy of skeletal muscle and the heart has not been completely prevented. Further ingenuity is needed in designing countermeasures for muscular, cardiovascular, and vestibular dysfunctions.

Long-term exposure to microgravity impairs vestibulo-cardiovascular reflex.

The vestibular system is known to have an important role in controlling blood pressure upon posture transition (vestibulo-cardiovascular reflex, VCR). However, under a different gravitational environment, the sensitivity of the vestibular system may be altered. Thus, the VCR may become less sensitive after spaceflight because of orthostatic intolerance potentially induced by long-term exposure to microgravity. To test this hypothesis in humans, we investigated the ability of the VCR to maintain blood pressure upon head-up tilt before and after a 4-6 months stay on the International Space Station. To detect the functional state of the VCR, galvanic vestibular stimulation (GVS) was applied. As GVS transiently interrupts the vestibular-mediated pressor response, impaired VCR is detected when the head-up tilt-induced blood pressure response does not depend on GVS. During the first 20 s of head-up tilt, a transient blood pressure increase (11.9 ± 1.6 mmHg) was observed at pre-spaceflight but not at 1-4 days after return from spaceflight. The magnitude of VCR recovered to the pre-spaceflight levels within 2 months after return. These results indicate that long-term exposure to microgravity induces VCR impairment, which may be involved in a mechanism of spaceflight-induced orthostatic intolerance.

Risk for cardiovascular disease in Japanese patients with rheumatoid arthritis: a large-scale epidemiological study using a healthcare database.

OBJECTIVES: To study risk for cardiovascular disease (CVD) in Japanese patients with rheumatoid arthritis (RA). METHODS: We used a Medical Data Vision database mainly composed of health insurance claim data and diagnosis-procedure combination data from Japan. Patients with RA diagnosed from April 2011 to March 2014 at 71 hospitals were identified with the International Classification of Diseases 10th revision (ICD-10) and history of anti-RA drug prescription. Hospitalizations for CVD including ischemic heart disease, heart failure, and stroke were identified by a combination of diagnosis (ICD-10) and diagnostic procedures. CVD incidence rate ratio (IRR) for RA versus osteoarthritis was calculated. Risk factors were analyzed using univariate and multivariate Cox proportional hazard models with baseline C-reactive protein (CRP) and traditional risk factors as covariates. RESULTS: We identified 8658 patients with RA. The age-sex adjusted IRR for RA versus osteoarthritis was high for total CVD [2.12; 95 % confidence interval (CI) 1.93-2.32], ischemic heart disease (2.16; 95 % CI 1.86-2.50), heart failure (2.34; 95 % CI 2.07-2.65), and stroke (1.68; 95 % CI 1.41-2.00). Risk factor analysis showed a tendency for cardiovascular risk to increase with higher baseline CRP, although the difference was not statistically significant (hazard ratio 1.43; 95 % CI 0.99-2.07). CONCLUSION: Our study indicates an increased risk for CVD and an association between systemic inflammation and CVD in Japanese RA patients.

[Temporal Analysis of Body Sway during Reciprocator Motion Movie Viewing].

OBJECTIVES: We aimed to investigate the effect of stereoscopic viewing and the degree of awareness of motion sickness on posture by measuring body sway during motion movie viewing. METHODS: Nineteen students (12 men and 7 women; age range, 21-24 years) participated in this study. The movie, which showed several balls randomly positioned, was projected on a white wall 2 m in front of the subjects through a two-dimensional (2-D)/three-dimensional (3-D) convertible projector. To measure body sway during movie viewing, the subjects stood statically erect on a Wii balance board, with the toe opening at 18 degrees. The study protocol was as follows: The subjects watched (1) a nonmoving movie for 1 minute as the pretest and then (2) a round-trip sinusoidally moving-in-depth-direction movie for 3 minutes. (3) The initial static movie was shown again for 1 minute. Steps (2) and (3) were treated as one trial, after which two trials (2-D and 3-D movies) were performed in a random sequence. RESULTS: In this study, we found that posture changed according to the motion in the movie and that the longer the viewing time, the higher the synchronization accuracy. These tendencies depended on the level of awareness of motion sickness or the 3-D movie viewed. CONCLUSIONS: The mechanism of postural change in movie viewing was not vection but self-defense to resolve sensory conflict between visual information (spatial swing) and equilibrium sense (motionlessness).

Higher Cognitive Function in Elderly Individuals with Previous Cataract Surgery: Cross-Sectional Association Independent of Visual Acuity in the HEIJO-KYO Cohort.

Cataract surgery improves visual acuity and drastically increases the capacity for light reception to the retina. Although previous studies suggested that both light exposure and visual acuity were associated with cognitive function, the relationships between cataract surgery, visual acuity, and cognitive function have not been evaluated in large populations. In this cross-sectional study, we measured cognitive function using the Mini-Mental State Examination and best-corrected visual acuity in pseudophakic (previous cataract surgery) and phakic (no previous cataract surgery) elderly individuals. Of 945 participants (mean age 71.7 years), 166 (17.6%) had pseudophakia and 317 (33.5%) had impaired cognitive function (score ≤26). The pseudophakic group showed significantly better visual acuity than the phakic group (p = 0.003) and lower age-adjusted odds ratio (ORs) for cognitive impairment (OR 0.66; p = 0.038). Consistently, in multivariate logistic regression models, after adjusting for confounding factors, including visual acuity and socioeconomic status, ORs for cognitive impairment were significantly lower in the pseudophakic group than in the phakic group (OR 0.64; 95% confidence interval 0.43-0.96; p = 0.031). This association remained significant in sensitivity analysis, excluding participants with low cognitive score ≤23 (n = 36). In conclusion, in a general elderly population, prevalence of cognitive impairment was significantly lower in pseudophakic individuals independently of visual acuity. The association was also independent of several major causes of cognitive impairment such as aging, gender, obesity, socioeconomic status, hypertension, diabetes, sleep disturbances, depressive symptoms, and physical inactivity.

Glucagon-Like Peptide-1 Strengthens the Barrier Integrity in Primary Cultures of Rat Brain Endothelial Cells Under Basal and Hyperglycemia Conditions.

The objective of the present study was to determine the effects of glucagon-like peptide-1 (GLP-1) on barrier functions and to assess the underlying mechanism using an in vitro blood-brain barrier (BBB) model comprised of a primary culture of rat brain capillary endothelial cells (RBECs). GLP-1 increased transendothelial electrical resistance and decreased the permeability of sodium fluorescein in RBECs in a dose- and time-dependent manner. The effects on these barrier functions were significantly reduced in the presence of the GLP-1 receptor antagonist exendin-3 (9-39) and the protein kinase A (PKA) inhibitor H-89. Western blot analysis showed that GLP-1 increased the amount of occludin and claudin-5. GLP-1 analogs are approved for treatment of type 2 diabetes mellitus, and thus, we examined the effects of GLP-1 on hyperglycemia-induced BBB damage. GLP-1 inhibited the increase in production of reactive oxygen species under hyperglycemia conditions and improved the BBB integrity induced by hyperglycemia. As GLP-1 stabilized the integrity of the BBB, probably via cAMP/PKA signaling, the possibility that GLP-1 acts as a BBB-protective drug should be considered.

Tocilizumab in systemic juvenile idiopathic arthritis in a real-world clinical setting: results from 1 year of postmarketing surveillance follow-up of 417 patients in Japan.

OBJECTIVES: To evaluate the safety and effectiveness of tocilizumab (TCZ) in patients with systemic juvenile idiopathic arthritis (sJIA) in real-world clinical settings in Japan. METHODS: Paediatric patients with sJIA initiating TCZ between April 2008 and February 2012 and those previously enrolled in clinical trials who initiated TCZ before April 2008 were enrolled in a Japanese registry surveillance programme. Safety and effectiveness parameters were collected for 52 weeks. RESULTS: Of 417 patients enrolled, mean age was 11.2 years and 48.0% were female. TCZ exposure was 407.0 patient-years (PYs). Baseline corticosteroid use was higher than in clinical trials. Rates of total adverse events (AEs) and serious AEs (SAEs) were 224.3/100 PYs and 54.5/100 PYs, respectively, with SAEs higher than previously reported. The most frequent AEs and SAEs were infections and infestations (69.8/100 PYs and 18.2/100 PYs, respectively). 74 serious infections occurred in 55 patients (18.2/100 PYs); higher than previously reported. 26 macrophage activation syndrome events were reported in 24 patients (6.4/100 PYs). Fever and rash symptoms improved from baseline to week 52 (54.6% to 5.6% and 43.0% to 5.6%, respectively). At 4 weeks, 8 weeks and 52 weeks, 90.5%, 96.2% and 99.0% of patients achieved normal C reactive protein levels (<0.3 mg/dL), respectively. CONCLUSIONS: These first real-world data demonstrated that TCZ was well tolerated, with acceptable safety and effectiveness in patients with sJIA. Higher incidences of SAEs and serious infections may be due to differences, such as corticosteroid use and concomitant diseases, between patient populations enrolled in previously reported clinical trials and this study.

Longterm Safety of Tocilizumab: Results from 3 Years of Followup Postmarketing Surveillance of 5573 Patients with Rheumatoid Arthritis in Japan.

OBJECTIVE: To evaluate the longterm safety of tocilizumab (TCZ) for the treatment of rheumatoid arthritis (RA) in a real-world clinical setting in Japan. METHODS: In this longterm extension of a single-arm, observational postmarketing surveillance study, a total of 5573 patients who initiated intravenous TCZ between April 2008 and July 2009 were observed for 3 years, regardless of its continuation, for incidence of fatal events, serious infections, malignancy, gastrointestinal perforations, and serious cardiac dysfunction. RESULTS: Of the 5573 patients who were enrolled, 4527 patients (81.23%) completed 3 years of followup. There were no increases in the proportions of patients with fatal events, serious infection, malignancy, GI perforation, or serious cardiac dysfunction over 3 years. The all-cause mortality rate during followup was 2.58% (0.95/100 patient-yrs), and the standardized mortality ratio was 1.27 (95% CI, 1.08 to 1.50). Patients who were older with longer disease duration and respiratory comorbidities were more likely to discontinue TCZ treatment following serious infection during the first year. Among patients who completed 3 years of TCZ treatment, serious infection developed at a constant rate during the 3-year treatment period. The proportion of malignancy during followup was 2.24% (0.83/100 patient-yrs), and the standardized incidence ratio was 0.79 (95% CI, 0.66 to 0.95). CONCLUSION: The safety profile of TCZ was consistent over time regarding mortality, serious infections, malignancy, gastrointestinal perforation, and serious cardiac dysfunction. These data confirm the longterm safety of TCZ use in patients with RA in a real-world clinical setting.

Physiological Levels of Melatonin Relate to Cognitive Function and Depressive Symptoms: The HEIJO-KYO Cohort.

CONTEXT: In contrast with randomized controlled trials, observational studies have suggested that physiological levels of melatonin are reduced in patients with dementia or depression, but the relationship has not been evaluated in large populations. OBJECTIVE: The objective was to determine the relationships between physiological levels of melatonin and cognitive function and depressive symptoms. DESIGN AND PARTICIPANTS: A cohort of 1105 community-dwelling elderly individuals was enrolled in this cross-sectional study (mean age, 71.8 ± 7.1 y). MEASURES: Urinary 6-sulfatoxymelatonin excretion (UME) and Mini-Mental State Examination (MMSE; n = 935) and Geriatric Depression Scale (GDS; n = 1097) scores were measured as indices of physiological melatonin levels, cognitive function, and depressive symptoms, respectively. RESULTS: With increases in UME quartiles, the prevalence of cognitive impairment (MMSE score ≤ 26) and depressed mood (GDS score ≥ 6) significantly decreased (P for trend = .003 and .012, respectively). In multivariate logistic regression models, after adjusting for confounders such as age, gender, socioeconomic status, physical activity, and sleep/wake cycles, higher UME levels were significantly associated with lower odds ratios (ORs) for cognitive impairment and depressed mood (ORs: Q1 = 1.00; Q2 = 0.88 and 0.76; Q3 = 0.66 and 0.85; Q4 = 0.67 and 0.53; P for trend = .023 and .033, respectively). In addition, the highest UME group showed a significantly lower OR for depressed mood than the lowest UME group (Q4 vs Q1: OR, 0.53; 95% confidence interval, 0.32-0.89; P = .033). UME levels above the median value were significantly associated with a lower OR for cognitive impairment, even after further adjustment for depressive symptoms (OR = 0.74; 95% confidence interval, 0.55-0.99; P = .043). CONCLUSIONS: Significant associations of higher physiological melatonin levels with lower prevalence of cognitive impairment and depressed mood were revealed in a large general elderly population. The association between physiological melatonin levels and cognitive function was independent of depressive symptoms.

Postprandial decrease in vascular resistance correlated with change in second derivative of finger plethysmogram in young subjects.

BACKGROUND: The second derivative of the finger plethysmogram (SDPTG) comprises five waves termed a to e. The magnitudes of waves b-e are normalized by that of wave a for within- and between-patient comparison. In the present study, affects of meal ingestion for SDPTG in young and elderly subjects are examined. SUBJECTS AND METHODS: Mean arterial pressure and SDPTG before and after meal ingestion in young and elderly subjects were measured. For young subjects, stroke volume and pulse rate were also measured, and the total peripheral resistance (TPR) of the blood vessels was analyzed. Relationship between TPR and the ratio of the peak of SDPTG in young subjects was also analyzed. RESULTS: In young subjects, postprandial d/a was significantly larger and TPR was smaller than before intake and was linearly and significantly correlated with TPR. An increase in the postprandial d/a was also observed in the elderly subjects who were not undergoing hypertension treatment. However, this increase was not observed in elderly subjects who were treated for hypertension. CONCLUSIONS: Change in d/a is considered to be an index of change in TPR. TPR is considered to be decreased by agents for treatment of hypertension, and meal ingestion does not appear to further decrease TPR. These results are considered to be useful for understanding cardiodynamics surrounding meal ingestion.

Candesartan improves ischemia-induced impairment of the blood-brain barrier in vitro.

Candesartan has been reported to have a protective effect on cerebral ischemia in vivo and in human ischemic stroke. We studied the direct effects of candesartan on blood-brain barrier (BBB) function with our in vitro monolayer model generated using rat brain capillary endothelial cells (RBECs). The in vitro BBB model was subjected to normoxia or 6-h oxygen glucose deprivation (OGD)/24-h reoxygenation, with or without candesartan. 6-h OGD/24-h reoxygenation decreased transendothelial electrical resistance and increased the endothelial permeability for sodium fluorescein in RBEC monolayers. Candesartan (10 nM) improved RBEC barrier dysfunction induced by 6-h OGD/24-h reoxygenation. Immunostaining and immunoblotting analysis indicated that the effect of candesartan on barrier function under 6-h OGD/24-h reoxygenation was not related to the expression levels of tight junction proteins. However, candesartan affected RBEC morphological changes induced by 6-h OGD/24-h reoxygenation. We analyzed oxidative stress and cell viability using chemical reagents. Candesartan improved cell viability following 6-h OGD/24-h reoxygenation, whereas candesartan had no effect on oxidative stress. These results show that candesartan directly improves cell function and viability of brain capillary endothelial cells under OGD/reoxygenation, suggesting that the protective effects of candesartan on ischemic stroke are related to protection of the BBB.

Compression stocking length effects on arterial blood pressure and heart rate following head-up tilt in healthy volunteers.

BACKGROUND: Change in posture from supine to standing induces a footward fluid shift. This shift might decrease arterial pressure (AP) and induce orthostatic hypotension. To prevent decrease in AP, compression stockings are recommended, but the effects of various lengths have not been compared. OBJECTIVE: The aim was to compare AP and heart rate (HR) by compression stocking length during head-up tilt (HUT). METHODS: The effects of elastic compression stockings of three lengths on AP and HR were examined at the onset of HUT. The stockings were knee-high, compressing the foot and calf; thigh-high, compressing the toe to the thigh; and waist-high, compressing the toe to the waist. RESULTS: AP did not significantly change at the onset of HUT without stockings or with any length of stockings compared with the AP in the supine position. HR was significantly higher at the onset of HUT without stockings and with the knee-high and thigh-high stockings than that during supine position. No significant difference in HR was observed among the three conditions. However, the HR increase was significantly depressed with the waist-high stockings. DISCUSSION: These results suggest that the use of waist-high stockings that afford abdominal compression is needed to affect cardiovascular dynamics at the onset of HUT and may prevent orthostatic hypotension.

RR interval variability during galvanic vestibular stimulation correlates with arterial pressure upon head-up tilt.

RR interval variability (RRIV) in the supine position without and with galvanic vestibular stimulation (GVS (off) and GVS (on), respectively), changes in mean arterial pressure (MAP) at the onset of 60° head-up tilt (HUT) during GVS (off), and their relationship were analyzed in 25 healthy young subjects. MAP decreased by less than 5mmHg or increased upon HUT in 12 subjects (UP), but MAP decreased by more than 5mmHg in 13 subjects (DOWN). Applying sinusoidal GVS of 2mA at a random frequency of 0.2 to 10.0Hz did not change the RR intervals or MAP. However, the high frequency component (HF) of RRIV increased in both UP and DOWN subjects. The increase in DOWN subjects was larger than that in UP subjects. The ratio of the low frequency component to HF (L/H) increased in UP subjects during GVS (on), but did not reach a significant level in DOWN subjects. The changes in the HF were significantly correlated with changes in MAP at the onset of HUT; i.e., the subjects with larger increases in the HF during GVS (on) showed larger decreases in MAP. Thus, GVS or vestibular input during HUT possibly activates the vagal nerves, and the dominance of excitation in sympathetic or vagal nerves during vestibular stimulation is important for controlling MAP at the onset of HUT.