Strongly reducing helical phenothiazines as recyclable organophotoredox catalysts.

Recyclable phenothiazine organophotoredox catalysts (PTHS 1-3, E1/2ox* = -2.34 to -2.40 V vs. SCE) have been developed. When the recycling performance was evaluated, PTHS-1 could be recovered at least four times without loss of its catalytic activity. These recyclable organophotoredox catalysts represent a promising tool for sustainable organic synthesis.

Prevalence of and factors influencing Hikikomori in Osaka City, Japan: A population-based cross-sectional study.

OBJECTIVES: Hikikomori is commonly defined as a social condition in which individuals avoid social participation and relationships beyond their family members by confining themselves to a room or their house for 6 months or longer. Hikikomori has been predominantly considered a problem among young people; however, as the population is ageing, hikikomori has also emerged as a social issue among adults. Nevertheless, no comparative studies have examined the differences in the factors associated with hikikomori among teenagers/young adults and middle-aged/older adults. Thus, this phenomenon has not been thoroughly examined, and it remains unclear whether the risk factors vary between teenagers/young adults and middle-aged/older adults. Based on the Japan Cabinet Office's definition of hikikomori, this cross-sectional study evaluated the prevalence and related factors of hikikomori among the working age population (15-64 years), utilising univariate and multivariate analyses. The study also compared differences in the prevalence of and factors related to hikikomori between teenagers/young adults and middle-aged/older adults. METHODS: We distributed self-administered questionnaires to individual participants and their families between 24 December 2020 and 18 January 2021. RESULTS: Data from an anonymised sample of 3,092 individuals (split into two groups of 15-39 and 40-64 years) were subjected to analysis. The results revealed a hikikomori prevalence of 2.3% in the target population; the prevalence rate was 2.12% among individuals aged 15 to 39 years and 2.42% among those aged 40 to 64 years. The analysis demonstrated strong correlations between hikikomori and several factors, including unemployment, truancy, a history of psychiatric consultation or hospitalisation, being male and the absence of ibasho, which is defined as a place where individuals can feel peace, security, acceptance and belonging. The factors associated with hikikomori differed between teenagers/young adults and middle-aged/older adults. CONCLUSION: Our findings, thus, contribute to existing research by providing a comparative analysis of risk factors across different age groups.

Piceatannol Upregulates SIRT1 Expression in Skeletal Muscle Cells and in Human Whole Blood: In Vitro Assay and a Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Comparison Trial.

Piceatannol (PIC), a polyphenol abundant in passion fruit seeds, is reported to promote fat metabolism. This study investigated whether PIC affects sirtuin 1 (SIRT1) expression and metabolic factors in C2C12 skeletal muscle cells. C2C12 myotubes were stimulated with PIC, and alterations in gene expression, protein levels, mitochondrial DNA content, and fatty acid levels were assessed using real-time PCR, Western blotting, and Nile red staining. Furthermore, we examined changes in SIRT1 expression following the consumption of a test food containing 100 mg PIC for 2 weeks among adults with varying age and body mass index ranges. Both PIC and passion fruit seed extract induced SIRT1 expression in C2C12 myotubes to a greater extent than resveratrol. PIC also increased the expression of genes associated with mitochondrial biogenesis and fatty acid utilization, increased mitochondrial DNA content, and suppressed oleic acid-induced fat accumulation. Moreover, participants who consumed PIC exhibited significantly higher SIRT1 mRNA expression in whole blood compared to those in the placebo group. These findings suggest that PIC induces SIRT1 expression both in vitro and in the human body, which may promote mitochondrial biosynthesis and fat metabolism.

Factors associated with difficulty in hospital acceptance during the COVID-19 pandemic period in Osaka Prefecture, Japan: a population-based study.

Background: In many countries, emergency medical systems were responsible for initial treatment of patients with COVID-19. Generally, acceptance by medical institutions may not be sufficient, and it may take much time to determine the medical institution to which to transport the patient. This problem is termed "difficulty in hospital acceptance (DIH)," and it is used as a key performance indicator in the assessment of the EMS in Japan. The purpose of this study was to reveal the factors associated with the DIH during the COVID-19 pandemic using dataset in the ORION (Osaka emergency information Research Intelligent Operation Network system). Methods: This was a retrospective descriptive study with a 3-year study period from January 1, 2019 to December 31, 2021. We included patients who were recorded in the ORION system during the study period. The primary endpoint was defined as DIH. Multivariable logistic regression model was used to assess factors associated with DIH during the COVID-19 pandemic and calculated their adjusted odds ratio (AOR) and associated 95% confidence interval (CI). Results: 1,078,850 patients included in this study. Of them, 41,140 patients (3.8%) experienced DIH and 1,037,710 patients (96.2%) did not experience DIH. The median age was 71 years (IQR: 45-82), and 543,760 patients (50.4%) were male. In this study, SpO2, body temperature, and epidemic period of COVID-19 were associated with difficulty in hospital acceptance. The highest AOR of SpO2 was 80% or less (AOR: 1.636, [95% CI: 1.532-1.748]), followed by 81-85% (AOR: 1.584, [95% CI: 1.459-1.721]). The highest AOR of body temperature was 38.0-38.9°C (AOR: 1.969 [95% CI: 1.897-2.043]), followed by 39°C or higher (AOR: 1.912 [95% CI: 1.829-1.998]). The highest AOR of epidemic period of COVID-19 was the 4th wave (AOR: 2.134, [95% CI: 2.065-2.205]), followed by the 3rd wave (AOR: 1.842, [95% CI: 1.785-1.901]). Conclusion: In this study, we revealed factors associated with the DIH during the COVID-19 pandemic. As various factors are involved in the spread of an unknown infectious disease, it is necessary not only to plan in advance but also to take appropriate measures according to the situation in order to smoothly accept emergency patients.

Blood pressure during long-term cilostazol-based dual antiplatelet therapy after stroke: a post hoc analysis of the CSPS.com trial.

We determined the associations of follow-up blood pressure (BP) after stroke as a time-dependent covariate with the risk of subsequent ischemic stroke, as well as those of BP levels with the difference in the impact of long-term clopidogrel or aspirin monotherapy versus additional cilostazol medication on secondary stroke prevention. In a sub-analysis of a randomized controlled trial (CSPS.com), patients between 8 and 180 days after stroke onset were randomly assigned to receive aspirin or clopidogrel alone, or a combination of cilostazol with aspirin or clopidogrel. The percent changes, differences, and raw values of follow-up BP were examined. The primary efficacy outcome was the first recurrence of ischemic stroke. In a total of 1657 patients (69.5 ± 9.3 years, female 29.1%) with median 1.5-year follow-up, ischemic stroke recurred in 74 patients. The adjusted hazard ratio for ischemic stroke of a 10% systolic BP (SBP) increase from baseline was 1.19 (95% CI 1.03-1.36), that of a 10 mmHg SBP increase was 1.14 (1.03-1.28), and that of SBP as the raw value with the baseline SBP as a fixed (time-independent) covariate was 1.14 (1.00-1.31). Such significant associations were not observed in diastolic BP-derived variables. The estimated adjusted hazard ratio curves for the outcome showed the benefit of dual therapy over a wide SBP range between ≈120 and ≈165 mmHg uniformly. Lower long-term SBP levels after ischemic stroke were associated with a lower risk of subsequent ischemic events. The efficacy of dual antiplatelet therapy including cilostazol for secondary stroke prevention was evident over a wide SBP range.

Effects of Concomitant Traumatic Spinal Cord and Brain Injury on In-Hospital Mortality: A Retrospective Analysis of a Nationwide Trauma Registry in Japan.

Isolated traumatic spinal cord injury (t-SCI) and traumatic brain injury (TBI) represent significant public health concerns, resulting in long-term disabilities and necessitating sophisticated care, particularly when occurring concurrently. The impact of these combined injuries, while crucial in trauma management, on clinical, socioeconomic, and health care outcomes is largely unknown. To address this gap, our secondary retrospective cohort study used data from the Japan Trauma Data Bank, covering patients enrolled over a 13-year period (2006-2018), to elucidate the effects of concurrent t-SCI and TBI on in-hospital mortality. Data on patient demographics, injury characteristics, treatment modalities, and outcomes were analyzed. Multivariate logistic regression analysis was performed to examine prognostic variables associated with in-hospital mortality, including interaction terms between t-SCI severity and TBI presence. This study included 91,983 patients with neurotrauma, with a median age of 62 years (69.7% men). Among the patients, 9,018 (9.8%) died in the hospital. Concomitant t-SCI and TBI occurred in 2,954 (3.2%) patients. t-SCI only occurred in 9,590 (10.4%) patients, whereas TBI only occurred in the majority of these cases (79,439, 86.4%). Multivariate logistic regression analysis revealed age; sex; total number of comorbidities; systolic blood pressure at presentation; Glasgow coma scale score at presentation; and Abbreviated Injury Scale (AIS) scores for head, face, chest, abdomen, cervical-SCI, thoracic-SCI, and lumbar-SCI as significant independent factors for in-hospital mortality. The odds ratio of cervical-SCI × head AIS as an interaction term was 0.85 (95% confidence interval: 0.77-0.95), indicating a negative interaction. In conclusion, we identified 12 factors associated with in-hospital mortality in patients with t-SCI. In addition, the negative interaction between cervical t-SCI and TBI suggests that the presence of t-SCI in patients with TBI may be underestimated. This study highlights the importance of early recognition and comprehensive management of these complex trauma conditions while considering the possibility of concomitant t-SCI in patients with TBI.

A multicenter, single-arm, phase II clinical trial of adrenomedullin in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common form of hereditary cerebral small vessel disease (SVD), currently lacks disease-modifying treatments. Adrenomedullin (AM), a vasoactive peptide with angiogenic, vasodilatory, anti-inflammatory, and anti-oxidative properties, shows potential effects on the neuro-glial-vascular unit. Objective: The AdrenoMedullin for CADASIL (AMCAD) study aims to assess the efficacy and safety of AM in patients with CADASIL. Sample size: Overall, 60 patients will be recruited. Methods: The AMCAD is a multicenter, investigator-initiated, single-arm phase II trial. Patients with a confirmed CADASIL diagnosis, based on NOTCH3 genetic testing, will receive an 8-h AM treatment (15 ng/kg/min) for 14 days following a baseline assessment (from day 1 to day 14). Follow-up evaluations will be performed on days 15, 28, 90, and 180. Study outcomes: The primary endpoint is the cerebral blood flow change rate in the frontal cortex, evaluated using arterial spin labeling magnetic resonance imaging, from baseline to day 28. Summary statistics, 95% confidence intervals, and a one-sample t-test will be used for analysis. Conclusion: The AMCAD study aims to represent the therapeutic potential of AM in patients with CADASIL, addressing an unmet medical need in this challenging condition. Clinical Trial Registration: jRCT 2,051,210,117 (https://jrct.niph.go.jp/en-latest-detail/jRCT2051210117).

Influence of monaural auditory stimulation combined with music on brain activity.

Introduction: Recently, the increasing attention to mental states and psychophysical health has fueled the research into methods that can aid in relaxation and recovery. Traditional methods like meditation and sauna, while effective, have their limitations; thus, the need for more accessible and convenient alternatives. Methods: Our innovative approach combines monaural beats with music, attempting to replicate the relaxing effects of a sauna in the auditory domain. Results: In comparison to normal music and silent condition, the power of the theta active band significantly increased when listening to our modified music. Furthermore, after listening to modified music, there was a significant increase in mismatch negativity (MMN) amplitude in the oddball task. Additionally, participants' subjective responses to a questionnaire indicated significant changes in body relaxation and other metrics after listening to the processed music. Discussion: This state is considered similar to the "totonou" state, which manifests in physical and mental feelings of relaxation, pleasure, and mental clarity in the sauna. Thus, the present research proposes a convenient method for achieving relaxation, opening an avenue for individuals to customize their "totonou" music based on personal preferences.

Gamma music: a new acoustic stimulus for gamma-frequency auditory steady-state response.

A frequency range exceeding approximately 30 Hz, denoted as the gamma frequency range, is associated with various cognitive functions, consciousness, sensory integration, short-term memory, working memory, encoding and maintenance of episodic memory, and retrieval processes. In this study, we proposed a new form of gamma stimulation, called gamma music, combining 40 Hz auditory stimuli and music. This gamma music consists of drums, bass, and keyboard sounds, each containing a 40 Hz frequency oscillation. Since 40 Hz stimuli are known to induce an auditory steady-state response (ASSR), we used the 40 Hz power and phase locking index (PLI) as indices of neural activity during sound stimulation. We also recorded subjective ratings of each sound through a questionnaire using a visual analog scale. The gamma music, gamma drums, gamma bass, and gamma keyboard sounds showed significantly higher values in 40 Hz power and PLI compared to the control music without a 40 Hz oscillation. Particularly, the gamma keyboard sound showed a potential to induce strong ASSR, showing high values in these indices. In the subjective ratings, the gamma music, especially the gamma keyboard sound, received more relaxed, comfortable, preferred, pleasant, and natural impressions compared to the control music with conventional gamma stimulation. These results indicate that our proposed gamma music has potential as a new method for inducing ASSR. Particularly, the gamma keyboard sound proved to be an effective acoustic source for inducing a strong ASSR while preserving the comfortable and pleasant sensation of listening to music. Our developed gamma music, characterized by its pleasantness to the human ear, offers a significant advantage for the long-term use of gamma stimulation. The utilization of this music could potentially reduce the physical and psychological burden on participants compared to conventional 40 Hz stimuli. This music is not only expected to contribute to fundamental neuroscience research utilizing ASSR but also to facilitate the implementation of gamma music-based interventions aimed at enhancing human cognitive functions in everyday life.

Outcome of emergency patients transported by ambulance during the COVID-19 pandemic in Osaka Prefecture, Japan: a population-based descriptive study.

Background: The novel corona virus (COVID-19) pandemic occurred worldwide. Although an excessive burden was placed on emergency medical institutions treating urgent and severe patients, its impact on patient outcome remains unknown. This study aimed to assess the impact of the COVID-19 pandemic in 2021 on the emergency medical services (EMS) system and patient outcomes in Osaka Prefecture, Japan. Methods: This was a retrospective descriptive study with a study period from January 1, 2019 to December 31, 2021. We included patients who were transported by ambulance and had cleaned data that was recorded in the ORION system. The study endpoints were the number of patients transported by ambulance and the number of deaths among these patients in each month. To assess the impact of the COVID-19 pandemic on the EMS system, the incidence rate ratio (IRR) and 95% confidence interval (CI) were calculated using 2019 as the reference year. Mortalities were evaluated based on deaths in the emergency department and deaths at 21 days after hospitalization. Results: The numbers of patients transported by ambulance were 500,194 in 2019, 443,321 in 2020 (IRR: 0.88, 95% CI: 0.87-0.88), and 448,054 in 2021 (IRR: 0.90, 95% CI: 0.89-0.90). In 2019, the number of patients transported by ambulance and who died in the emergency departments was 4,980, compared to 5,485 in 2020 (IRR: 1.10, 95% CI; 1.06-1.44) and 5,925 in 2021 (IRR: 1.19, 95% CI: 1.15-1.24). In 2019, the number of patients who died within 21 days after hospitalization was 11,931, compared to 11,913 in 2020 (IRR; 1.00, 95% CI; 0.98-1.03) and 13,376 in 2021 (IRR; 1.12, 95% CI; 1.09-1.15). Conclusion: The COVID-19 pandemic decreased the number of ambulance requests and worsened mortality of patients transported by ambulance in Osaka Prefecture during 2021.