Predictors for Incident Mild Parkinsonian Signs in Older Japanese

Background: Mild parkinsonian signs are important clinical symptoms related to the decline of motor and cognitive functions. We aimed to identify predictors for the incidence of mild parkinsonian signs in older Japanese by conducting an 8-year longitudinal community-based cohort study. Methods: Participants aged 65 years or older, living in Ama-cho, a rural island town in western Japan, underwent a baseline assessment of motor function, cognitive function, depression score, the Pittsburgh Sleep Quality Index (PSQI), the Tanner questionnaire, and cerebral white matter lesions on brain magnetic resonance imaging from 2008 to 2010, and then underwent a follow-up neurological examination from 2016 to 2017. Mild parkinsonian signs were defined according to a modified Unified Parkinson’s Disease Rating Scale score. Results: Of the 316 participants without mild parkinsonian signs at baseline, 94 presented with incident mild parkinsonian signs at follow-up. In addition to an absence of exercise habits, a higher score on the Tanner questionnaire, PSQI, and deep white-matter hyperintensity Fazekas scores were significant independent predictors for incidence of mild parkinsonian signs. Conclusion: We suggest multiple factors related to incidence of mild parkinsonian signs. Vascular lesions and sleep disorders are associated with a pathogenesis of mild parkinsonian signs, the Tanner questionnaire is useful for early detection of subclinical mild parkinsonian signs, and exercise has a possibility of being associated with preventing onset of mild parkinsonian signs

Brain Angiotensin II Type 1 Receptor Blockade Improves Dairy Blood Pressure Variability via Sympathoinhibition in Hypertensive Rats

Abnormal blood pressure (BP) elevation in early morning is known to cause cardiovascular events. Previous studies have suggested that one of the reasons in abnormal dairy BP variability is sympathoexcitation. We have demonstrated that brain angiotensin II type 1 receptor (AT1R) causes sympathoexcitation. The aim of the present study was to investigate whether central AT1R blockade attenuates the excess BP elevation in rest-to-active phase in hypertensive rats or not. Stroke-prone spontaneously hypertensive rats (SHRSP) were treated with intracerebroventricular infusion (ICV) of AT1R receptor blocker (ARB), oral administration of hydralazine (HYD), or ICV of vehicle (VEH). Telemetric averaged mean BP (MBP) was measured at early morning (EM), after morning (AM), and night (NT). At EM, MBP was significantly lower in ARB to a greater extent than in HYD compared to VEH, though MBP at AM was the same in ARB and HYD. At NT, MBP was also significantly lower in ARB than in HYD. These results in MBP were compatible to those in sympathoexcitation and suggest that central AT1R blockade attenuates excess BP elevation in early active phase and continuous BP elevation during rest phase independent of depressor response in hypertensive rats

A Safe, Simple, and Facile Staining Method Using Polysiloxanes for High-Contrast Visualization of Gelator Aggregates by Transmission Electron Microscopy

The staining of TEM samples using Si atoms was investigated using aggregates of loose gels formed by twelve structurally different gelators in several solvents. Thirteen commercially available siloxanes were used as stains. TEM images of non-stained and OsO4-stained samples of molecular aggregates formed by the dodecamethylenediamide of N-methacryloyl-oxyethylaminocarbonyl-L-isoleucine in 1-propanol were poorly defined and low-contrast. However, the image of a methacryloyloxypropyl-terminated polydimethylsiloxane (S1)-stained sample was characterized by very clear bundles of fine fibers. The staining effect was explained by the wrapping of fibers, the stabilizing of the individual fibers, and reinforcing by S1. An S1 concentration of more than 5 mgmL(-1) was found to be necessary for satisfactory contrast. S1 was successfully applied to the observation of aggregates of eleven other gelators. S1 worked universally as an aggregate stain regardless of the gelator or solvent polarity. The staining effect was observed for other siloxanes. This effect was found to depend on the molecular weight of the siloxane (>1,000) rather than the kind of siloxane employed. Energy-dispersive X-ray spectroscopy indicated that the molecules of S1 gather on the surface of the fibers during drying, wrapping them. The results indicate that the present staining method guarantees reproducibility and universality.ArticleBULLETIN OF THE CHEMICAL SOCIETY OF JAPAN.91(7):1176-1185(2018)journal articl

Mood stabilizers and/or antipsychotics for bipolar disorder in the maintenance phase: a systematic review and network meta-analysis of randomized controlled trials

© 2020, The Author(s). We searched Embase, PubMed, and CENTRAL from inception until 22 May 2020 to investigate which antipsychotics and/or mood stabilizers are better for patients with bipolar disorder in the maintenance phase. We performed two categorical network meta-analyses. The first included monotherapy studies and studies in which the two drugs used were specified (i.e., aripiprazole, aripiprazole once monthly, aripiprazole+lamotrigine, aripiprazole+valproate, asenapine, carbamazepine, lamotrigine, lamotrigine+valproate, lithium, lithium+oxcarbazepine, lithium+valproate, olanzapine, paliperidone, quetiapine, risperidone long-acting injection, valproate, and placebo). The second included studies on second-generation antipsychotic combination therapies (SGAs) (i.e., aripiprazole, lurasidone, olanzapine, quetiapine, and ziprasidone) with lithium or valproate (LIT/VAL) compared with placebo with LIT/VAL. Outcomes were recurrence/relapse rate of any mood episode (RR-any, primary), depressive episode (RR-dep) and manic/hypomanic/mixed episode (RR-mania), discontinuation, mortality, and individual adverse events. Risk ratios and 95% credible interval were calculated. Forty-one randomized controlled trials were identified (n = 9821; mean study duration, 70.5 ± 36.6 weeks; percent female, 54.1%; mean age, 40.7 years). All active treatments other than carbamazepine, lamotrigine+valproate (no data) and paliperidone outperformed the placebo for RR-any. Aripiprazole+valproate, lamotrigine, lamotrigine+valproate, lithium, olanzapine, and quetiapine outperformed placebo for RR-dep. All active treatments, other than aripiprazole+valproate, carbamazepine, lamotrigine, and lamotrigine+valproate, outperformed placebo for RR-mania. Asenapine, lithium, olanzapine, quetiapine, and valproate outperformed placebo for all-cause discontinuation. All SGAs+LIT/VALs other than olanzapine+LIT/VAL outperformed placebo+LIT/VAL for RR-any. Lurasidone+LIT/VAL and quetiapine+LIT/VAL outperformed placebo+LIT/VAL for RR-dep. Aripiprazole+LIT/VAL and quetiapine+LIT/VAL outperformed placebo+LIT/VAL for RR-mania. Lurasidone+LIT/VAL and quetiapine+LIT/VAL outperformed placebo+LIT/VAL for all-cause discontinuation. Treatment efficacy, tolerability, and safety profiles differed among treatments

Pharmacological treatment for bipolar mania: a systematic review and network meta-analysis of double-blind randomized controlled trials

A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological interventions for adults with acute bipolar mania. We searched PubMed, the Cochrane Library, and Embase databases for eligible studies published before March 14, 2021. Randomized controlled trials (RCTs) of oral medication monotherapy lasting ≥10 days in adults with mania were included, and studies that allowed the use of antipsychotics as a rescue medication during a trial were excluded. The primary outcomes were response to treatment (efficacy) and all-cause discontinuation (acceptability). The secondary outcomes were the improvement of mania symptoms and discontinuation due to inefficacy. Of the 79 eligible RCTs, 72 double-blind RCTs of 23 drugs and a placebo were included in the meta-analysis (mean study duration = 3.96 ± 2.39 weeks, n = 16442, mean age = 39.55 years, with 50.93% males). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed response to treatment (N = 56, n = 14503); aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation; however, topiramate had higher all-cause discontinuation (N = 70, n = 16324). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed the improvement of mania symptoms (N = 61, n = 15466), and aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy (N = 50, n = 14284). In conclusions, these antipsychotics, carbamazepine, lithium, tamoxifen, and valproate were effective for acute mania. However, only aripiprazole, olanzapine, quetiapine, and risperidone had better acceptability than the placebo

Duration of Electrically Induced Atrial Fibrillation Is Augmented by High Voltage of Stimulus with Higher Blood Pressure in Hypertensive Rats

Objective. Many previous clinical studies have suggested that atrial fibrillation (AF) is closely associated with hypertension. However, the benefits of antihypertensive therapy on AF are still inconsistent, and it is necessary to explore the factors augmenting AF in hypertensive rats. The aim of the present study was to investigate the correlation between arterial pressure or voltage stimulus and to the duration of electrically induced AF in normotensive or hypertensive rats. Methods. AF was reproducibly induced by transesophageal atrial burst pacing in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). We did the burst pacing at high (20 V) or low (5 V) voltage. Results. Duration of AF did not correlate with systolic blood pressure (SBP) and stimulus voltage in WKY. However, only in SHR, duration of AF with high stimulus voltage significantly correlated with SBP and was significantly longer in high than in low voltage stimulus. Discussion and Conclusion. Duration of AF is augmented by high voltage stimulus with higher blood pressure in SHR

A Case of Diffuse Alveolar Hemorrhage Associated with Tegafur Plus Uracil and Warfarin Therapy

A 72-year-old man who received warfarin for myocardial infarction (prothrombin time-international normalized ratio [PT-INR] controlled between 2.2 and 2.5) for 2 years. He developed lung cancer, underwent surgery, and received tegafur plus uracil (UFT) after 1 month. After 2 months, he was admitted for hemoptysis and dyspnea. Chest radiography and computed tomography showed bilateral alveolar infiltration (PT-INR, 8.9). Bronchoalveolar lavage fluid (BALF) disclosed hemorrhagic features in sequential samples. And he was diagnosed with diffuse alveolar hemorrhage (DAH). A known interaction exists between fluoropyrimidines and warfarin. So, they were discontinued, and vitamin K was intravenously administered. One day later, the PT-INR returned to 1.14. The symptoms improved and, alveolar infiltration resolved after 2 weeks. Alveolar hemorrhage may be due to an interaction between UFT and warfarin. When fluoropyrimidines and warfarin are prescribed simultaneously, we recommend that PT-INR should be closely monitored

Walking in the uncanny valley: importance of the attractiveness on the acceptance of a robot as a working partner

The Uncanny valley hypothesis, which tells us that almost-human characteristics in a robot or a device could cause uneasiness in human observers, is an important research theme in the Human Robot Interaction (HRI) field. Yet, that phenomenon is still not well-understood. Many have investigated the external design of humanoid robot faces and bodies but only a few studies have focused on the influence of robot movements on our perception and feelings of the Uncanny valley. Moreover, no research has investigated the possible relation between our uneasiness feeling and whether or not we would accept robots having a job in an office, a hospital or elsewhere. To better understand the Uncanny valley, we explore several factors which might have an influence on our perception of robots, be it related to the subjects, such as culture or attitude toward robots, or related to the robot such as emotions and emotional intensity displayed in its motion. We asked 69 subjects (N = 69) to rate the motions of a humanoid robot (Perceived Humanity, Eeriness, and Attractiveness) and state where they would rather see the robot performing a task. Our results suggest that, among the factors we chose to test, the attitude toward robots is the main influence on the perception of the robot related to the Uncanny valley. Robot occupation acceptability was affected only by Attractiveness, mitigating any Uncanny valley effect. We discuss the implications of these findings for the Uncanny valley and the acceptability of a robotic worker in our society

IVC diameter in patients undergoing HD

Background : IVC diameter on expiration (IVCdexp) is measured by echocardiography routinely. It is used to estimate volume status and designated as a definitive marker for determining dry weight (DW) in patients undergoing hemodialysis (HD). Methods : A cross-sectional study. Outpatients (n = 107), and inpatients (n = 35) undergoing HD were enrolled. IVCdexp was measured on non-dialysis days in outpatients and dialysis days before and after the dialysis session in inpatients. In outpatients, the relationship of IVCdexp with echocardiography findings and clinical characteristics was analyzed. IVCdexp was compared with the other DW markers as a predictive factor for intradialytic hypotension. In inpatients, IVCdexp was analyzed by dividing inpatients with or without fluid in extravascular space. Results : IVCdexp ranged from 5.4 to 16.9 mm in outpatients who had optimal DW. IVCdexp could reflect on volume status, but not predictive for intradialytic hypotension and not suggestive of fluid in extravascular space. Conclusions : IVCdexp was a rough marker to estimate volume status and only useful in suggesting apparent hypervolemia or hypovolemia. We should know that the IVCdexp value is affected by a lot of factors and not a definitive marker for estimating practical DW