Effects of dapagliflozin on myoglobin efflux from cardiomyocyte during myocardial ischemia/reperfusion in anesthetized rats.

It has been suggested that sodium-glucose cotransporter 2 (SGLT2) inhibitors have cardioprotective effects during myocardial ischemia/reperfusion (I/R) independent of glucose-lowering action. However, the effects of SGLT2 inhibitors on structural damage to cardiomyocytes in the ischemic region during I/R remain unknown. We applied a microdialysis technique to the heart of anesthetized rats and investigated the effects of an SGLT2 inhibitor, dapagliflozin, on myocardial interstitial myoglobin levels in the ischemic region during coronary occlusion followed by reperfusion. Dapagliflozin was administered systemically (40 µg/body iv) or locally via a dialysis probe (100 µM and 1 mM) 30 min before coronary occlusion. In the vehicle group, coronary occlusion increased the dialysate myoglobin concentration in the ischemic region. Reperfusion further increased the dialysate myoglobin concentration. Intravenous administration of dapagliflozin reduced dialysate myoglobin concentration during ischemia and at 0-15 min after reperfusion, but local administration (100 µM and 1 mM) did not. Therefore, acute systemic administration of dapagliflozin prior to ischemia has cardioprotective effects on structural damage during I/R.

Fabrication and photoelectric conversion of densely packed C60-ethylenediamine adduct microparticle films-modified electrode covered with electrochemically deposited polythiophene thin-films.

Polythiophene-modified densely packed C60-ethylenediamine adduct microparticle films were prepared using a combination of liquid-liquid interfacial precipitation of the adduct microparticles and electrochemical polymerization of 2,2'-bithiophene. The amount of polythiophene was varied as a function of scanning cycles of the applied potential during electrochemical polymerization. Fluorescence-emission properties of these composite films suggested the role of C60-ethylenediamine adduct microparticle film as a photosensitizer in addition to an electron acceptor for polythiophene. Furthermore, cathodic photocurrents were generated via excitation of C60-ethylenediamine adduct microparticle film and polythiophenes using the half-photocell properties of the electrode modified with composite film in the presence of methylviologen.

Photothermal therapeutic ability of copper open-shell nanostructures that are effective in the second biological transparency window based on symmetry breaking-induced plasmonic properties.

In this study, a photothermal therapy agent that works efficiently in the second biological transparency window was developed based on the localized surface plasmon (LSP) resonance of symmetry-broken open-shell nanostructures of low-cost Cu (CuOSNs). The strong LSP resonance and superior photothermal conversion ability in the second biological transparency window were achieved by generating the dipolar bonding mode due to the plasmon hybridization between the nanoshell dipole and the nanohole dipole at the opening edge in CuOSNs derived from the symmetry breaking of a Cu nanoshell. Oxidative dissolution of CuOSNs in water was significantly suppressed by successive coating with the self-assembled monolayer of 16-mercaptohexadecanoic acid and a thin silica layer. Furthermore, the stability in phosphate buffered saline, which models the biological environment, was attained by further coating the nanoparticles with polyethylene glycol. It was demonstrated from in vitro cell tests using HeLa cells that the cytotoxicity of CuOSNs was effectively suppressed by the surface protection. The viability of HeLa cells incubated with CuOSNs was decreased under the irradiation of low intensity 1060 nm laser with increasing number of CuOSNs. These results demonstrate that low-cost symmetry-broken Cu-based nanostructures can act as an excellent photothermal therapy agent in the second biological transparency window.

Effects of disaster-related traumatic events on worry about radiation and COVID-19: A decade after the Fukushima nuclear power plant accident.

Community residents exposed to nuclear power plant (NPP) accidents have long-term worry about the effects of radiation. After the 2011 Fukushima NPP accident, those who experienced traumatic events during the Great East Japan Earthquake (GEJE) tended to have greater worry about radiation. Along with the prolonged worry about radiation, there may also be cognitive changes caused by the traumatic events. We hypothesized that if there were cognitive changes underlying the prolonged worry about radiation, those who experienced the traumatic events would tend to have greater worry about other issues unrelated to radiation. We examined the effects of the traumatic events during the GEJE on community residents' worry about radiation and COVID-19 a decade after the Fukushima NPP accident. Using the data of a longitudinal questionnaire survey following a random sample of 4900 community residents outside the evacuation zone in Fukushima, this study analyzed 774 responses (15.8%). The traumatic events consisted of (1) injury, (2) injury or death of a family member, and (3) the loss of a house or other property. We developed a mediation model drawing paths from the traumatic events to worry about radiation and COVID-19, including posttraumatic stress symptoms (PTSS) as a mediator, using structural equation modeling. The traumatic events directly affected worry about radiation. Although it did not directly affect worry about COVID-19, it did so indirectly through worry about radiation and PTSS. Traumatic events can increase trauma-related worry independently of PTSS and increase trauma-unrelated worry indirectly through trauma-related worry and PTSS.

Gender Biases Toward People With Difficulty in Balancing Work and Family Due to ADHD: Two Case Vignette Randomized Studies Featuring Japanese Laypersons and Psychiatrists.

Objective The gender gap in labor force participation is likely larger in adults with attention deficit hyperactivity disorder (ADHD) than that in the general population. Thus, we investigated whether gender affected the perception toward persons displaying ADHD symptoms and experiencing difficulty in balancing work and family. Methods Both Japanese laypersons and psychiatrists were recruited for web-based surveys in March and October 2020 via an online survey company, Cross Marketing Inc., and the secretariat of the Japanese Society of Psychiatry and Neurology, respectively. The participants were randomly assigned to read either a male or female case vignette. The vignettes were identical, except for the gender of the patient in the case. The primary and secondary outcomes were the respondents' opinions on the seriousness of the case and the degree to which the case's wish should be maintained, using sliding scales of 0-100. Results We included 560 laypersons and 585 psychiatrists. Neither cohort differed in most outcomes between the groups assigned to the male and female case vignettes. Among laypersons, the average score of seriousness was 58.8 in the female-vignette group and 58.6 in the male-vignette group (mean difference, 0.15; 95% confidence interval, -4.9 to 5.2). Among psychiatrists, the average score of seriousness was 53.9 in the female-vignette group and 53.7 in the male-vignette group (mean difference, 0.18; 95% confidence interval, -3.1 to 3.4). Similarly, between-group differences in the opinions on the degree to which the case's wish should be maintained were 1.2 in laypersons and 0.63 in psychiatrists. We found no significant interaction between the gender of the case and the respondent's gender in any of the outcomes. Conclusion Our results did not support the hypothesis that women were more likely to be pressured to prioritize family over work than men were when there was difficulty balancing work and family due to ADHD symptoms.

Worry about Radiation and Its Risk Factors Five to Ten Years after the Fukushima Nuclear Power Plant Disaster.

Worry about radiation persists long after nuclear power plant accidents. Young age, low socioeconomic status, being married, and disaster-related experiences are known to be associated with greater worry about radiation. This study explored the duration of the effects of these risk factors on worry about radiation after the 2011 Fukushima nuclear power plant accident, using the longitudinal data of randomly sampled non-evacuee community residents who were followed five to ten years after the accident. Questionnaire surveys were conducted five times with 1825 respondents (37.2% of the 4900 initial targets). We examined the interaction of time and risk factors of worry about radiation using a mixed model. Fear or anxiety immediately after the accident had effects on worry about radiation that continued even after 10 years, though it slightly attenuated with time. Family problems stemming from the disaster retained their effects. While direct damage and evacuation experience were significantly associated with worry about radiation in the early phase, their effects diminished and became non-significant during the study period. Being under the age of 65, having low educational attainment, and being married were significantly associated with worry about radiation, although the association with age weakened over time. Individuals who experience intense fear or anxiety post-nuclear power plant accidents or disaster-related family problems may need continuous monitoring for their worry about radiation even 10 years after such accidents.

Transporter-dependent uptake and metabolism of myocardial interstitial serotonin in the rat heart.

To investigate the roles of the serotonin (5-HT) transporter (SERT) and plasma membrane monoamine transporter (PMAT) in 5-HT uptake and its metabolism in the heart, we monitored myocardial interstitial levels of 5-HT and 5-HIAA, a metabolite of 5-HT by monoamine oxidase (MAO), in anesthetized rats using a microdialysis technique. Fluoxetine (SERT inhibitor), decynium-22 (PMAT inhibitor), or their mixture was locally administered by reverse-microdialysis for 60 min. Subsequently, pargyline (MAO inhibitor) was co-administered. Fluoxetine rapidly increased dialysate 5-HT concentration, while decynium-22 gradually increased it. The mixture induced a larger increase in dialysate 5-HT concentration compared to fluoxetine or decynium-22 alone. Fluoxetine increased dialysate 5-HIAA concentration, and this increase was abolished by pargyline. Decynium-22 and the mixture did not change dialysate 5-HIAA concentration, which were not affected by pargyline. Both SERT and PMAT regulate myocardial interstitial 5-HT levels by its uptake; however, 5-HT uptake via PMAT leads to 5-HT metabolism by MAO.

Driving performance of euthymic outpatients with bipolar disorder undergoing real-world pharmacotherapy.

OBJECTIVE: Medications for the treatment of bipolar disorder (BD) could affect patients' cognitive function. Patients with BD present with neurocognitive impairment even in a remission state. Little research is available on the daily functioning, especially driving performance, of stable outpatients with BD under pharmacological treatment. METHODS: In total, 58 euthymic outpatients with BD undergoing real-world pharmacotherapy and 80 sex- and age-matched healthy controls (HCs) were enrolled. Three driving tasks using a driving simulator-road-tracking, car-following, and harsh-braking-and three cognitive tasks-Continuous Performance Test, Wisconsin Card Sorting Test, and Trail-Making Test-were evaluated. Symptom assessment scales-Young Mania Rating Scale, Structured Interview Guide for the Hamilton Depression Rating Scale, Beck Depression Inventory-II, Social Adaptation Self-evaluation Scale, and Stanford Sleepiness Scale-were also completed. RESULTS: Car-following and road-tracking performance were significantly impaired in patients with BD compared with HCs after adjusting for demographic variables, but these performances generally overlapped. Broad neurocognitive functions were significantly lower in the patients with BD compared to HCs, but car-following performance was significantly negatively correlated with sustained attention only. Although most patients received multiple medications rather than monotherapy, no relationship between prescriptions and driving performance was found. CONCLUSION: Euthymic patients with BD under steady-state pharmacotherapy had impaired driving performance compared with HCs, but the overlapping distributions of driving performance suggested that driving performance is not always deteriorated in patients with BD. Therefore, attentional function may be a useful clinical feature for judging driving aptitude in patients with BD.

The Tohoku Theater Project in Postdisaster Japan: An Exemplar for Addressing Community Mental Health in the Context of Disaster.

The Tohoku Theater Project was completed 2 years after the natural and nuclear disasters in Tohoku, Japan, on March 11, 2011. It employed the dramatic arts to support the healing process, promote resilience, and increase dialogue and understanding about mental health among individuals who were directly affected by the disasters. The four performances fostered important discussions regarding the psychological impact of the Tohoku disasters. Participants (N=143) found the theater performance effective at facilitating discussion, increasing empathy, and enhancing mental health knowledge, coping, and resilience. The performances provided critical information about access to services; many participants reported that they had not known where to seek help for mental health prior to their involvement with the Tohoku Theater Project. Lessons learned may inform community-based strategies that promote mental health and healing in the wake of the COVID-19 pandemic and other public health disasters.

Recent Developments in Community-Based Mental Health Care in Japan: A Narrative Review.

BACKGROUND: Since the 1950s, mental health care in Japan has been hospital-centered. A set of legislative initiatives were undertaken in 1995, emphasizing the importance of community-based mental health care. However, despite these attempts to develop a community-based mental health care system, the rate of inpatient-based treatment has remained high and the shift from hospital-centered care to community-based has still not fully materialized. AIM: This study aims to conduct a review of the available literature on the development of community-based mental health care in Japan between 2010 and 2020. METHODS: We conducted a standardized literature search in the electronic database Igaku Chuo Zasshi, aiming to identify original studies published between 2010 and 2020 that explored community mental health care in Japan. The included studies' outcomes were categorized as performance surveys, service user reports, service provider reports, and educational activities. A descriptive-analytical method was implemented in the current review. RESULTS: A total of 25 studies were examined. Six studies reported surveys assessing the performance of community-based mental health care on the assertive community treatment (ACT), compulsory treatment, home-visit nursing care, physical complications, and a welfare medicine collaboration on a remote islands. Four studies investigated the perspectives of service users or their families on home-visit nursing care, social participation, community program, and legislative revision. Ten studies focused on social withdrawal, service providers perspectives on local population needs, supporting skills, care programs, and the professional growth of psychiatric social workers. Five studies focused on educational approaches for future healthcare professionals and efforts to improve mental health literacy among adolescents. CONCLUSION: This paper provided the first comprehensive review of Japan's community-based mental health care. Between 2010 and 2020, community mental health care in Japan evolved in many directions, with the understanding that various needs should be met. Home-visit nursing care and ACT can be considered as the most thoroughly investigated and better developed. Research that adopt rigorous methodologies such as randomized controlled trials is required if the goal is to achieve solid conclusions.

Carrier-mediated serotonin efflux induced by pharmacological anoxia in the rat heart in vivo.

Serotonin (5-HT) accumulates in the heart during myocardial ischaemia and induces deleterious effects on the cardiomyocytes. We aimed to investigate whether carrier-mediated 5-HT efflux contributed to the increase in interstitial 5-HT level during ischaemia. Using microdialysis technique applied to the heart of anaesthetised Wistar rats, myocardial interstitial concentration of 5-HT was measured by electro-chemical detection coupled with high-performance liquid chromatography (HPLC-ECD) while simultaneously various pharmacological agents, which create a similar condition to ischaemia, were locally administered by reverse-microdialysis. Sodium cyanide-induced chemical anoxia increased dialysate 5-HT concentration. A similar increase in dialysate 5-HT concentration was induced by ouabain, an inhibitor of sodium-potassium ATPase and reserpine, an inhibitor of vesicular monoamine transporter. Fluoxetine, a selective serotonin reuptake inhibitor raised the baseline level of 5-HT, and neither sodium cyanide nor the combination of ouabain and reserpine induced further increase in 5-HT in the presence of fluoxetine. The results indicate that reverse transport of 5-HT via SERT, which is caused by an impaired ion gradient, contributes to the rise in interstitial level of 5-HT during ischaemia suggesting carrier-mediated 5-HT efflux occurs in the heart in vivo.

Resilience building for mood disorders: Theoretical introduction and the achievements of the Re-Work program in Japan.

Mood disorders are common, tend to recur, cause sickness absence, and lead to economic loss. Since past experiences of mood disorder episodes often increase future vulnerability, it is imperative to assist those mood disorder patients who want to resume working to build resilience to prevent relapse. Paralleling efforts in the West, a resilience-building program utilizing the principles of the Illness Management and Recovery program was first developed in Japan in 1997. The purpose of this survey is to introduce the concept and theory behind the Re-Work program and to review studies that report on program assessment, content, effects and associated factors, and prognosis of participants. A literature search performed with PubMed and Igaku chuou zasshi (Ichushi) identified 30 relevant studies. One of these reported on a tool developed to assess readiness for returning to work. Concerning program content, a group therapy setting and cognitive behavioral therapy were found to be effective. Physical exercise and relaxation techniques may be useful as secondary program components. Several studies report on program effects, but there may be factors that limit these effects. The prognosis for relapse prevention after the resumption of work may be better for Re-Work program participants than for a control group. Further research in this area is needed to confirm program effectiveness and related factors.

Distrust in government and its relationship with mental health after the Fukushima nuclear power plant accident.

BACKGROUND: Distrust in authorities has negative effects on mental health. AIMS: In this study, we aimed to explore whether the impact of distrust in government on mental health became stronger in the area heavily affected by the 2011 Fukushima nuclear power plant accident. METHODS: We examined the effects of distrust in the national government on depressive symptoms three years after the accident among community residents in Fukushima prefecture using those in the Kanto area (the area surrounding Tokyo) as a control. A questionnaire survey was administered to a random sample of 1000 residents in Fukushima prefecture and 1650 residents in the Kanto area. Distrust in the national government was assessed using a four-point single-item scale. Depressive symptoms were measured using the Patient Health Questionnaire-9. The associations of residential area (i.e. living in Fukushima prefecture or in the Kanto area) and distrust in the national government with depressive symptoms were examined, controlling for socio-demographic characteristics and disaster-related experiences using multivariate linear regression analyses. We used the interaction term of residential area and distrust in the government to explore the difference in the association between the respondents in Fukushima prefecture and those in the Kanto area. RESULTS: Valid responses were obtained from 976 (36.8%) residents. Distrust in the government was associated with depressive symptoms and the association was stronger in Fukushima prefecture than in the Kanto area. CONCLUSION: The deleterious effects of distrust in the government on mental health may become more serious after a nuclear power plant accident and require careful attention during support activities in an affected area.

Impact of Peripheral α7-Nicotinic Acetylcholine Receptors on Cardioprotective Effects of Donepezil in Chronic Heart Failure Rats.

PURPOSE: Pharmacological modulation of parasympathetic activity with donepezil, an acetylcholinesterase inhibitor, improves the long-term survival of rats with chronic heart failure (CHF) after myocardial infarction (MI). However, its mechanism is not well understood. The α7-nicotinic acetylcholine receptor (α7-nAChR) reportedly plays an important role in the cholinergic anti-inflammatory pathway. The purpose of this study was to examine whether blockade of α7-nAChR, either centrally or peripherally, affects cardioprotection by donepezil during CHF. METHODS: One-week post-MI, the surviving rats were implanted with an electrocardiogram or blood pressure transmitter to monitor hemodynamics continuously. Seven days after implantation, the MI rats (n = 74) were administered donepezil in drinking water or were untreated (UT). Donepezil-treated MI rats were randomly assigned to the following four groups: peripheral infusion of saline (SPDT) or an α7-nAChR antagonist methyllycaconitine (α7PDT), and brain infusion of saline (SBDT) or the α7-nAChR antagonist (α7BDT). RESULTS: After the 4-week treatment, the role of α7-nAChR was evaluated using hemodynamic parameters, neurohumoral states, and histological and morphological assessment. Between the peripheral infusion groups, α7PDT (vs. SPDT) showed significantly increased heart weight and cardiac fibrosis, deteriorated hemodynamics, increased plasma neurohumoral and cytokine levels, and significantly decreased microvessel density (as assessed by anti-von Willebrand factor-positive cells). In contrast, between the brain infusion groups, α7BDT (vs. SBDT) showed no changes in either cardiac remodeling or hemodynamics. CONCLUSION: Peripheral blockade of α7-nAChR significantly attenuated the cardioprotective effects of donepezil in CHF rats, whereas central blockade did not. This suggests that peripheral activation of α7-nAChR plays an important role in cholinergic pharmacotherapy for CHF.

Contribution of afferent pathway to vagal nerve stimulation-induced myocardial interstitial acetylcholine release in rats.

Vagal nerve stimulation (VNS) has been explored as a potential therapy for chronic heart failure. The contribution of the afferent pathway to myocardial interstitial acetylcholine (ACh) release during VNS has yet to be clarified. In seven anesthetized Wistar-Kyoto rats, we implanted microdialysis probes in the left ventricular free wall and measured the myocardial interstitial ACh release during right VNS with the following combinations of stimulation frequency (F in Hz) and voltage readout (V in volts): F0V0 (no stimulation), F5V3, F20V3, F5V10, and F20V10. F5V3 did not affect the ACh level. F20V3, F5V10, and F20V10 increased the ACh level to 2.83 ± 0.47 (P < 0.01), 4.31 ± 1.09 (P < 0.001), and 4.33 ± 0.82 (P < 0.001) nM, respectively, compared with F0V0 (1.76 ± 0.22 nM). After right vagal afferent transection (rVAX), F20V3 and F20V10 increased the ACh level to 2.90 ± 0.53 (P < 0.001) and 3.48 ± 0.63 (P < 0.001) nM, respectively, compared with F0V0 (1.61 ± 0.19 nM), but F5V10 did not (2.11 ± 0.24 nM). The ratio of the ACh levels after rVAX relative to before was significantly <100% in F5V10 (59.4 ± 8.7%) but not in F20V3 (102.0 ± 8.7%). These results suggest that high-frequency and low-voltage stimulation (F20V3) evoked the ACh release mainly via direct activation of the vagal efferent pathway. By contrast, low-frequency and high-voltage stimulation (F5V10) evoked the ACh release in a manner dependent on the vagal afferent pathway.

Long-lasting effects of distrust in government and science on mental health eight years after the Fukushima nuclear power plant disaster.

We aimed to explore the effects of erosion of trust in authorities on the long-term mental health of community residents after the 2011 Fukushima nuclear power plant accident in Japan. We investigated the effects of distrust in authorities on mental health in a cohort study following non-evacuee community residents after the 2011 Fukushima nuclear power plant accident. A baseline questionnaire survey was administered five years after the accident for a random sample of 4900 residents outside the evacuation zone in Fukushima. Distrust in the national government and in science were assessed using a four-point single-item scale. Psychological distress was measured using the K6. Posttraumatic stress symptoms were measured using an abbreviated version of the Posttraumatic Stress Disorder Checklist-Specific version. Longitudinal associations of distrust in the government and science at baseline and psychological distress and posttraumatic stress symptoms eight years after the accident were examined, controlling for the baseline level of distress or symptoms using multivariate logistic regression analyses. Valid responses were obtained from 927 (18.9%) residents. Distrust in the government at baseline was significantly associated with posttraumatic stress symptoms at follow-up, albeit controlling for baseline symptoms. While distrust in the government was also associated with psychological distress at follow-up, the association became non-significant after controlling for baseline distress. Distrust in science at baseline was not associated with posttraumatic stress symptoms or psychological distress at follow-up. Distrust in government after a nuclear power plant accident may have adverse effects on mental health in the long-term.

Open-shell singlet diradicaloid difluoreno[4,3-b:3',4'-d]furan and its radical cation and dianion.

Difluoreno[4,3-b:3',4'-d]furan (DFFu) was prepared via a short, scalable, multi-step synthesis, and characterized by crystallography, spectroscopic measurements, and theoretical calculations. Even though the results revealed an open-shell singlet diradical character, DFFu is stable under ambient conditions. The radical cationic and dianionic species of DFFu were also synthesized and characterized.

Threshold and saturation pressures of baroreflex-mediated myocardial interstitial acetylcholine release in rats.

Cardiac microdialysis allows the assessment of cardiac efferent vagal nerve activity from myocardial interstitial acetylcholine (ACh) levels with minimal influence on the neural control of the heart; however, a total picture of the baroreflex-mediated myocardial interstitial ACh release including the threshold and saturation pressures has yet to be quantified. In eight anesthetized Wistar-Kyoto rats, we implanted microdialysis probes in the left ventricular free wall and measured the myocardial interstitial ACh release simultaneously with efferent sympathetic nerve activity (SNA) during a carotid sinus baroreceptor pressure input between 60 and 180 mm Hg. The baroreflex-mediated ACh release approximated a positive sigmoid curve, and its threshold and saturation pressures were not significantly different from those of an inverse sigmoid curve associated with the baroreflex-mediated SNA response (threshold: 94.3 ± 8.6 vs. 99.3 ± 6.0 mm Hg; saturation: 150.0 ± 10.3 vs. 158.8 ± 5.8 mm Hg). The sympathetic and vagal systems have certain levels of activities across most of the normal pressure range.