Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy.

Narcolepsy is a sleep disorder caused by deficiency of orexin signaling. However, the neural mechanisms by which deficient orexin signaling causes the abnormal rapid eye movement (REM) sleep characteristics of narcolepsy, such as cataplexy and frequent transitions to REM states, are not fully understood. Here, we determined the activity dynamics of orexin neurons during sleep that suppress the abnormal REM sleep architecture of narcolepsy. Orexin neurons were highly active during wakefulness, showed intermittent synchronous activity during non-REM (NREM) sleep, were quiescent prior to the transition from NREM to REM sleep, and a small subpopulation of these cells was active during REM sleep. Orexin neurons that lacked orexin peptides were less active during REM sleep and were mostly silent during cataplexy. Optogenetic inhibition of orexin neurons established that the activity dynamics of these cells during NREM sleep regulate NREM-REM sleep transitions. Inhibition of orexin neurons during REM sleep increased subsequent REM sleep in "orexin intact" mice and subsequent cataplexy in mice lacking orexin peptides, indicating that the activity of a subpopulation of orexin neurons during the preceding REM sleep suppresses subsequent REM sleep and cataplexy. Thus, these results identify how deficient orexin signaling during sleep results in the abnormal REM sleep architecture characteristic of narcolepsy.

[Challenges, prevention, and countermeasures for social withdrawal (hikikomori) by age group].

　The term "hikikomori" was recognized by society between 1980 and 2000, when the term "NEET" also appeared and it was regarded as a problem of irresponsible youth. However, accumulation of surveys and research both in Japan and abroad, including those conducted by the Cabinet Office, has revealed that the reasons behind social withdrawal are not only limited to mental illness. There are many people who exhibit withdrawal because they are unable to establish relationships with the community and other people owing to various factors such as social systems, attachment formation, family background, and education. In other words, withdrawal is better described as a "symptom" or "condition" than a disease. Therefore, it is necessary to understand and analyze the diverse backgrounds and needs of individuals with withdrawal and confront them about their state. Currently, many hikikomori people with prolonged withdrawal are now in their 40s and 50s. With their parents' aging, there are cases where people with hikikomori and their families become socially isolated and are unable to make ends meet. It is undeniable that, until now, the society we live in as a whole has little interest in or understanding of hikikomori. In contrast, withdrawal among older adults (tojikomori), which has become a problem in the super-aging society. Tojikomori is defined as "going out less than once a week and not requiring nursing care", which is not equivalent with hikikomori. Owing to the decline in the frequency of going out among the elderly in the recent coronary crisis, the number of pre-frailty in older adults has become a nationwide problem.　Thus, both hikikomori and tojikomori are reversible conditions, and can be alleviated by providing necessary support. This paper summarizes the findings of the symposium "Challenges, Prevention, and Countermeasures for Social Withdrawal (Hikikomori) by Age Group" organized by the Committee on Mental Health and Suicide Prevention of the Japanese Society of Public Health at the 79th Annual Meeting of the Japanese Society of Public Health. This article is a compilation of findings that can benefit public health practitioners and researchers.

The relationships between three-axis accelerometer measures of physical activity and motor symptoms in patients with Parkinson's disease: a single-center pilot study.

BACKGROUND: Various wearable devices for objectively evaluating motor symptoms of patients with Parkinson's disease (PD) have been developed. Importantly, previous studies have suggested protective effects of physical activity in PD. However, the relationships between conventional clinical ratings for PD and three-axis accelerometer measures of physical activity (e.g., daily physical activity levels [PAL] or metabolic equivalents of task [METs]) are still unclear, particularly for METs. In the current study, we sought to elucidate these relationships on a daily basis, and to clarify optimal predictors for clinical states on a 30-min basis. METHODS: Patients who were hospitalized for adjustment of drugs or deep brain stimulation were enrolled. Using waist-worn three-axis accelerometers, PAL and METs parameter data were obtained and compared with UPDRS-3[On] and symptom diary data. We extracted data from the patients' best and worst days, defined by the best and worst UPDRS-3[On] scores, respectively. Thus, 22 data sets from 11 patients were extracted. We examined the correlations and produced scatter plots to represent the relationships, then investigated which METs parameters and activity patterns were the best predictors for "On" and "dyskinesia". RESULTS: The parameter "mean METs value within the 95-92.5 percentile range on a day (95-92.5 percentile value)" exhibited the strongest correlation with conventional daily clinical ratings (Rho: - 0.799 for UPDRS-3[On], 0.803 for On hours [p < 0.001]). Scatter plots suggested that PAL tended to have higher values in patients with involuntary movement. However, METs parameters focusing on higher METs seemed to alleviate this tendency. We clarified that "time over 2.0 METs" and "time over 1.5 METs" could be predictors for "On" and "dyskinesia" on a 30-min basis, respectively (AUROC: 0.779 and 0.959, 95% CI: 0.733-0.824 and 0.918-1.000). The specificity and sensitivity of the optimal activity pattern for "On" were 0.858 and 0.621. CONCLUSIONS: This study suggested feasible activity patterns and METs parameters for objective evaluation of motor symptoms on a 30-min or daily basis. Three-axis accelerometer measures focusing on higher METs may be appropriate for evaluating physical activity. Further larger-scale studies are necessary to clarify the validity, reliability, and clinical utility of these objective measures.

Development and Practical Test of Quality Indicators for Palliative Care in Patients With Chronic Heart Failure.

BACKGROUND: Palliative care is highly relevant for patients with heart failure (HF), and there is a need for quantitative information on quality of care. Accordingly, this study aimed to develop a set of quality indicators (QIs) for palliative care of HF patients, and to conduct a practical pilot measurement of the proposed QIs in clinical practice.Methods and Results:We used a modified Delphi technique, a consensus method that involves a comprehensive literature review, face-to-face multidisciplinary panel meeting, and anonymous rating in 2 rounds. A 15-member multidisciplinary expert panel individually rated each potential indicator on a scale of 1 (lowest) to 9 (highest) for appropriateness. All indicators receiving a median score ≥7 without significant disagreement were included in the final set of QIs. Through the consensus-building process, 35 QIs were proposed for palliative care in HF patients. Practical measurement in HF patients (n=131) from 3 teaching hospitals revealed that all of the proposed QIs could be obtained retrospectively from medical records, and the following QIs had low performance (<10%): "Intervention by multidisciplinary team", "Opioid therapy for patients with refractory dyspnea", and "Screening for psychological symptoms". CONCLUSIONS: The first set of QIs for palliative care of HF patients was developed and could clarify quantitative information and might improve the quality of care.

An integrated community mental healthcare program to reduce suicidal ideation and improve maternal mental health during the postnatal period: the findings from the Nagano trial.

BACKGROUND: During the perinatal period, suicides are more likely to occur in those with depression and who are not receiving active treatment at the time of death. Suicide is a common outcome in people with suicide ideation. We developed an intervention program taking care of comprehensive perinatal maternal mental healthcare to prevent suicide ideation. We hypothesized that our intervention program could reduce postnatal suicide ideation and improve maternal mental health. METHODS: We performed a controlled trial to examine the usual postnatal care plus a maternal suicide prevention program (the intervention group) compared with usual postnatal care alone, which comprised home visits by public health nurses without mental health screening (the control group) in Nagano city, Japan. In total, 464 women were included; 230 were allocated to the control group and 234 to the intervention group. The intervention had three components: 1) all the women received postnatal mental health screening by public health nurses who completed home visits during the neonatal period, 2) the intervention was administered by a multidisciplinary clinical network, and 3) systematic follow-up sheets were used to better understand bio-psycho-social characteristics of both the mothers and their infants and develop responsive care plans. We measured the participants' mental health at 3-4 months postpartum (T1) and 7-8 months postpartum (T2) using the Japanese version of the Edinburgh Postnatal Depression Scale (EPDS). RESULTS: Suicidal ideation was significantly lower in the intervention group compared with the control group at T1 (p = 0.014); however, this significant between-group difference did not continue to T2 (p = 0.111). We measured the intervention effects on maternal mental health using the total score of the EPDS, which was significantly improved in the intervention group compared with the control group at T1. Here, the significant difference continued to T2 (p = 0.049). CONCLUSIONS: Our results indicate that our program may reduce maternal suicidal ideation at 3-4 months postnatally and improve women's mental health during the postnatal periods of 3-4 to 7-8 months. Postnatal maternal mental healthcare, including services to reduce suicide ideation, should be included as an important component of general postnatal care. TRIAL REGISTRATION: Name of registry: A multidisciplinary intervention program for maternal mental health in perinatal periods. UMIN Clinical Trials Registry number: UMIN000033396 . Registration URL: https://upload.umin.ac.jp/cgibin/ctr/ctr_view_reg.cgi?recptno=R000038076 Registration date: July 15, 2018. Registration timing: retrospective.

No effect of supplemented heat stress during an acute endurance exercise session in hypoxia on hepcidin regulation.

Hepcidin is a novel factor for iron deficiency in athletes, which is suggested to be regulated by interleukin-6 (IL-6) or erythropoietin (EPO). PURPOSE: The purpose of the present study was to compare endurance exercise-induced hepcidin elevation among "normoxia", "hypoxia" and "combined heat and hypoxia". METHODS: Twelve males (21.5 ± 0.3 years, 168.1 ± 1.2 cm, 63.6 ± 2.0 kg) participated in the present study. They performed 60 min of cycling at 60% of [Formula: see text] in either "heat and hypoxia" (HHYP; FiO2 14.5%, 32 °C), "hypoxia" (HYP; FiO2 14.5%, 23 °C) or "normoxia" (NOR; FiO2 20.9%, 23 °C). After completing the exercise, participants remained in the prescribed conditions for 3 h post-exercise. Blood samples were collected before, immediately and 3 h after exercise. RESULTS: Plasma IL-6 level significantly increased immediately after exercise (P < 0.05), with no significant difference among the trials. A significant elevation in serum EPO was observed 3 h after exercise in hypoxic trials (HHYP and HYP, P < 0.05), with no significant difference between HHYP and HYP. Serum hepcidin level increased 3 h after exercise in all trials (NOR, before 18.3 ± 3.9 and post180 31.2 ± 6.3 ng/mL; HYP, before 13.5 ± 2.5 and post180 23.3 ± 3.6 ng/mL, HHYP; before 15.8 ± 3.3 and post180 31.4 ± 5.3 ng/mL, P < 0.05). However, there was no significant difference among the trials during post-exercise. CONCLUSION: Endurance exercise in "combined heat and hypoxia" did not exacerbate exercise-induced hepcidin elevation compared with the same exercise in "hypoxia" or "normoxia".

Progressive stenosis and radiological findings of vasculitis over the entire internal carotid artery in moyamoya vasculopathy associated with graves' disease: a case report and review of the literature.

BACKGROUND: Moyamoya vasculopathy (MMV) associated with Graves' disease (GD) is a rare condition resulting in ischemic stroke accompanied by thyrotoxicity. Radiological findings of vasculitis have been reported in the walls of distal internal carotid arteries (ICAs) in these patients; however, no reports have described in detail the processes of progression of the lesions in the proximal ICA. Moreover, treatments to prevent recurrence of ischemic stroke and progression of MMV have not yet been sufficiently elucidated. CASE PRESENTATION: We report a progressive case of MMV associated with GD and review the literature to clarify relationships among recurrence, progression, thyrotoxicity and treatment. Our patient developed cerebral infarction during thyrotoxicity with no obvious stenosis of ICAs. Five months later, transient ischemic attacks recurred with thyrotoxicity. Antiplatelet therapy and intravenous methylprednisolone stopped the attacks. Stenosis of the left ICA from the proximal to distal portion and champagne bottle neck sign (CBN) were found. She declined any surgery. Afterward, gradual progression with mild thyrotoxicity was observed. Eventually, we found smooth, circumferential, concentric wall thickening with diffuse gadolinium enhancement of the left ICA from the proximal to the distal portion on T1-weighted imaging, suggesting vasculitis radiologically. The clinical and radiological similarities to Takayasu arteritis encouraged us to provide treatment as for vasculitis of medium-to-large vessels. In a euthyroid state and after administration of prednisolone and methotrexate, improved flow in the cerebrovascular arteries on magnetic resonance angiography was observed. Based on our review of the literature, all cases with recurrence or progression were treated with anti-thyroid medication (ATM) alone and accompanied by thyrotoxicity. CBN was observed in all previous cases for which images of the proximal ICA were available. CONCLUSIONS: We report the details of progressive stenosis from a very early stage and radiological findings of vasculitis over the entire ICA in MMV associated with GD. Cerebral infarction can occur with no obvious stenosis of the ICA. We treated the patient as per vasculitis of a medium-to-large vessel. Management of GD by ATM alone seems risky in terms of recurrence. Adequate management of GD and possible vasculitis may be important for preventing recurrence and progression.

Integrated mental health care in a multidisciplinary maternal and child health service in the community: the findings from the Suzaka trial.

BACKGROUND: Perinatal mental health problems such as mood disorders are common. We propose a new multidisciplinary health service intervention program providing continuous support to women and their children from the start of pregnancy till after childbirth. The aim of this study was to examine the effects of the program with respect to making women's mental health better in the postpartum period and improving the state of care for women and their children in the perinatal period. METHODS: We performed a controlled study to investigate the effectiveness of the program in Suzaka City, Japan. The women's mental health status was assessed using the Edinburgh Postnatal Depression Scale (EPDS) 3 months postpartum. Of 349 women, 210 were allocated to the intervention group and 139 to the control group. From April 2014 to March 2015, the number of the pregnant women who were followed-up by the multidisciplinary meeting in the intervention and control groups were 60 and 4, respectively. In the same period, the number of the pregnant women who were identified as requiring intensive care were 21 and 2, respectively. RESULTS: The total EPDS score, which was the primary outcome of the present study, differed significantly between the intervention and control groups (Mean [SD] = 2.74 (2.89) and 4.58 [2.62], respectively; p < 0.001). The number of the women receiving counseling from a public health nurse (5.3% in intervention group, 0.7% in control group, p = 0.02), attending maternal seminars (attendant ratio: 46% whereas 16%, p = 0.01), and receiving home visits by public health nurses (home visit ratio: 93.8% whereas 82.6%, p < 0.001) was significantly higher in the intervention group compared to the control group. CONCLUSIONS: The present study indicates that continuum support provided by integrated mental health care through a multidisciplinary maternal and child health service in the community can make women's mental health better in the postpartum period and help women and their children receive more health services from public health nurses. TRIAL REGISTRATION: Name of registry: Research for the effectiveness of a multi-professional health service intervention program of continuum supports for mother and child which starts for pregnancy periods to enhance maternal mental health. UMIN Clinical Trials Registry number: UMIN000032424 . Registration date: April 29th, 2018. Registration timing: retrospective.

Anti-ganglioside complex antibody profiles in a recurrent complicated case of GQ1b-seronegative miller fisher syndrome and Bickerstaff brainstem encephalitis: a case report.

BACKGROUND: Guillain-Barré syndrome (GBS), Miller Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis (BBE) are a group of autoimmune neurological disorders (GBS spectrum disorder) that rarely recur. Recently, anti-ganglioside complex antibodies (GSC-Abs) were identified in patients with GBS spectrum disorder. However, there has been no case report describing GSC-Abs profiles in a recurrent case showing different phenotypes. CASE PRESENTATION: We report the case of a 33-year-old male patient with GQ1b-seronegative BBE-GBS after two prior episodes of MFS-GBS. Our patient showed ophthalmoplegia, ataxia, areflexia and a weakness of the extremities (MFS and GBS symptoms) in all episodes. In the episode reported here, our patient showed disturbed consciousness and an extensor response to cutaneous plantar stimulation was observed (BBE symptoms), with severe disability and requirement for artificial respiration management. GSC-Abs detected in previous episodes were also detected in the subsequent episodes, while new GSC-Abs emerged in each episode. Interestingly, whereas antibodies to GA1/GQ1b and GA1/GT1a, which are commonly identified in patients with GBS, MFS or BBE, appeared in all episodes, antibodies to GD1a/GD1b and GD1b/GT1b, which are predominantly associated with severe disability and the requirement for artificial respiration management in GBS, emerged for the first time in this episode. CONCLUSION: This study reports novel phenomena about the GSC-Abs profiles and its relationship with clinical features in a case with recurrent GBS spectrum disorder, showing different phenotypes in different episodes. Further studies are required to reveal the significance of the GSC-Abs profiles in recurrent GBS spectrum disorder.

Feasibility and efficacy of shared decision making for first-admission schizophrenia: a randomized clinical trial.

BACKGROUND: The feasibility of shared decision making (SDM) for patients with schizophrenia remains controversial due to the assumed inability of patients to cooperate in treatment decision making. This study evaluated the feasibility and efficacy of SDM in patients upon first admission for schizophrenia. METHODS: This was a randomized, parallel-group, two-arm, open-label, single-center study conducted in an acute psychiatric ward of Numazu Chuo Hospital, Japan. Patients with the diagnosis of schizophrenia upon their first admission were randomized into a SDM intervention group or a usual treatment group in a 1:1 ratio. The primary outcome was patient satisfaction at discharge. The secondary outcomes were attitudes toward medication at discharge and treatment continuation at 6 months after discharge. RESULTS: Twenty-four patients were randomly assigned. The trial was prematurely terminated due to slow enrollment. At discharge, the mean score on satisfaction was 23.7 in the SDM group and 22.1 in the usual care group (unadjusted mean difference: 1.6; 95% CI: -5.2 to 2.0). Group differences were not observed in attitude toward medication and treatment continuation. There was no statistically significant difference between the groups for the mean Global Assessment of Functioning score at discharge or length of stay as safety endpoint. CONCLUSIONS: No statistical differences were found between the SDM group and usual care group in the efficacy outcomes and safety endpoints. Large trials are needed to confirm the efficacy of the SDM program upon first admission for schizophrenia. TRIAL REGISTRATION: The study has been registered with ClinicalTrials.gov as NCT01869660 (registered 27 May, 2013).

The Radical S-Adenosyl-L-methionine Enzyme QhpD Catalyzes Sequential Formation of Intra-protein Sulfur-to-Methylene Carbon Thioether Bonds.

The bacterial enzyme designated QhpD belongs to the radical S-adenosyl-L-methionine (SAM) superfamily of enzymes and participates in the post-translational processing of quinohemoprotein amine dehydrogenase. QhpD is essential for the formation of intra-protein thioether bonds within the small subunit (maturated QhpC) of quinohemoprotein amine dehydrogenase. We overproduced QhpD from Paracoccus denitrificans as a stable complex with its substrate QhpC, carrying the 28-residue leader peptide that is essential for the complex formation. Absorption and electron paramagnetic resonance spectra together with the analyses of iron and sulfur contents suggested the presence of multiple (likely three) [4Fe-4S] clusters in the purified and reconstituted QhpD. In the presence of a reducing agent (sodium dithionite), QhpD catalyzed the multiple-turnover reaction of reductive cleavage of SAM into methionine and 5'-deoxyadenosine and also the single-turnover reaction of intra-protein sulfur-to-methylene carbon thioether bond formation in QhpC bound to QhpD, producing a multiknotted structure of the polypeptide chain. Homology modeling and mutagenic analysis revealed several conserved residues indispensable for both in vivo and in vitro activities of QhpD. Our findings uncover another challenging reaction catalyzed by a radical SAM enzyme acting on a ribosomally translated protein substrate.

Impact of medication adherence on renal function in comorbid patients with type 2 diabetes and depression: protocol for a cohort study.

BACKGROUND: Prevention, or slowing the progression, of diabetic nephropathy is one of the important goals in diabetes care. Although the impact of depression is a concern in patients with diabetes, it is unknown whether there is an association between adherence to hypoglycemic medication and the decline of renal function in comorbid patients with diabetes and depression. We will conduct a cohort study aimed at examining (1) depression as a predictor of renal function decline, and (2) how adherence to hypoglycemic medication relates to depression and renal function decline in patients with type 2 diabetes. METHODS/DESIGN: In this multicenter cohort study, 550 patients with type 2 diabetes aged 20 years and older will be recruited at 20 outpatient clinics in general medicine and psychiatry. We will measure depression (Patient Health Questionnaire), medication adherence (medication possession ratio, Morisky Medication Adherence Scale, and one-item hypoglycemic medication adherence scale), and renal function (urinary albumin-creatinine ratio and estimated glomerular filtration rate) at baseline and at the 12-month follow-up. The primary endpoint is decline of renal function at 12 months. The secondary endpoints include clinical variables, quality of life, and the attitude of professionals toward depression. We will perform multivariable linear regression analysis to evaluate the effects of medication adherence on the decline of renal function in comorbid patients with type 2 diabetes and depression. DISCUSSION: To our knowledge, this will be the first study to examine how adherence to hypoglycemic medication relates to the decline of renal function in comorbid patients with type 2 diabetes and depression. The results of the study will have implications for practitioners of diabetes care, policy makers, and researchers for the prevention and treatment of diabetic nephropathy. TRIAL REGISTRATION: UMIN000017513 (Registered on May 22, 2015).

Efficacy of shared decision making on treatment satisfaction for patients with first-admission schizophrenia: study protocol for a randomised controlled trial.

BACKGROUND: Shared decision making is a promising model for patient-centred medicine, resulting in better clinical outcomes overall. In the mental health field, interventions that consider the patient-centred perspective--such as patient quality of life, involvement in the treatment, treatment satisfaction, and working alliance--have increased and better clinical outcomes discovered for patients with schizophrenia. However, few studies have examined the efficacy of shared decision making for schizophrenia treatment. The objective of this study is to evaluate the effect of a shared decision making intervention compared to treatment as usual on patient satisfaction at discharge for first-admission patients with schizophrenia. METHODS/DESIGN: This is a randomised, parallel-group, two-arm, open-label, single-centre study currently being conducted in an acute psychiatric ward of Numazu Chuo Hospital, Japan. We are recruiting patients between 16 and 65 years old who are admitted to the ward with a diagnosis of schizophrenia without prior experience of psychiatric admission. Fifty-eight participants are being randomised into a shared decision making intervention group or a treatment as usual control group in a 1:1 ratio. The intervention program was developed based on a shared decision making model and is presented as a weekly course lasting the duration of the patients' acute psychiatric ward stay. The primary outcome measure is patient satisfaction at discharge as assessed by the Client Satisfaction Questionnaire. Due to the study's nature, neither the patient nor staff can be blinded. DISCUSSION: This is the first randomised controlled trial to evaluate the efficacy of shared decision making for patients with early-treatment-stage schizophrenia. The intervention program in this study is innovative in that it includes both of the patient and staff who are involved in the treatment. TRIAL REGISTRATION: The study has been registered with ClinicalTrials.gov as NCT01869660.

Phosphorescent cyclometalated complexes for efficient blue organic light-emitting diodes.

Phosphorescent emitters are extremely important for efficient organic light-emitting diodes (OLEDs), which attract significant attention. Phosphorescent emitters, which have a high phosphorescence quantum yield at room temperature, typically contain a heavy metal such as iridium and have been reported to emit blue, green and red light. In particular, the blue cyclometalated complexes with high efficiency and high stability are being developed. In this review, we focus on blue cyclometalated complexes. Recent progress of computational analysis necessary to design a cyclometalated complex is introduced. The prediction of the radiative transition is indispensable to get an emissive cyclometalated complex. We summarize four methods to control phosphorescence peak of the cyclometalated complex: (i) substituent effect on ligands, (ii) effects of ancillary ligands on heteroleptic complexes, (iii) design of the ligand skeleton, and (iv) selection of the central metal. It is considered that novel ligand skeletons would be important to achieve both a high efficiency and long lifetime in the blue OLEDs. Moreover, the combination of an emitter and a host is important as well as the emitter itself. According to the dependences on the combination of an emitter and a host, the control of exciton density of the triplet is necessary to achieve both a high efficiency and a long lifetime, because the annihilations of the triplet state cause exciton quenching and material deterioration.

How different are offline and online diplomacy? A comparative analysis of public statements and SNS posts by delegates to the United Nations.

Introduction: This article investigates the evolving landscape of diplomacy in the digital age, focusing on diplomats at the United Nations (UN) Headquarters in New York. The central inquiry revolves around how diplomatic actors use digital tools to complement or augment traditional face-to-face diplomacy. Methods: We systematically compare a substantial corpus of X posts (tweets) from UN diplomats with their public statements at the United Nations Security Council (UNSC), employing advanced computational social science techniques. This study applies a range of large-scale text analysis methods, including word embedding, topic modeling, and sentiment analysis, to investigate systematic differences between offline and online communication. Results: Our analysis reveals that, while the essence of diplomacy remains consistent across both domains, there is strategic selectivity in the use of online platforms by diplomats. Online communication emphasizes non-security topics, ceremonial matters, and prominent policy stances, in contrast to the operational issues common in UNSC deliberations. Additionally, online discourse adopts a less confrontational, more public diplomacy-oriented tone, with variations among countries. Discussion: This study offers one of the first systematic comparisons between offline and online diplomatic messages. It illuminates how diplomats navigate the digital realm to complement traditional roles. The findings indicate that some elements of public diplomacy and nation branding, directed toward a wider audience far beyond the council chamber, have become an integral part of multilateral diplomacy unfolding at the UNSC.

Excessive dosing and polypharmacy of antipsychotics caused by pro re nata in agitated patients with schizophrenia.

AIMS: It has been recommended that for patients with schizophrenia, antipsychotics should be prescribed simply, using an optimal dose. However, pro re nata (p.r.n., meaning to use on an as-needed basis) antipsychotics may increase the risk of excessive dosing (defined as mean chlorpromazine-equivalent doses above 1000 mg) and polypharmacy (combination use of different antipsychotics). This study aimed to investigate the increased risk caused by p.r.n. antipsychotics. METHOD: The subjects included 413 patients with schizophrenia from 17 acute psychiatric wards in nine hospitals. Over a 24-h period on a survey day, data on regular medication and the use of p.r.n. were collected. The analysis focused on p.r.n. antipsychotics in agitated patients. We used McNemar's test to evaluate differences in the proportions of patients prescribed antipsychotics with excessive dosing or polypharmacy before (i.e., regular medication only) and after prescribed p.r.n. antipsychotics were added to regular medication (i.e., regular medication plus p.r.n. antipsychotics). RESULTS: Of 413 patients, 312 (75.5%) were prescribed p.r.n. for agitated status. Of those, 281 (90.1%) were prescribed p.r.n. antipsychotics. The total doses were significantly higher and more compounded in case patients prescribed p.r.n. antipsychotics than in those who were not. Seventeen patients (4.1%) were actually administered p.r.n. antipsychotics. Their total medication, including p.r.n. on the current day, represented excessive dosing or polypharmacy of antipsychotics. CONCLUSION: The use of p.r.n. antipsychotics may cause hidden excessive dosing and polypharmacy. Our results indicate the importance of careful monitoring of p.r.n. antipsychotics to agitated patients with schizophrenia.