Correction: Hasegawa et al. Impacts of Interaction of Mental Condition and Quality of Life between Donors and Recipients at Decision-Making of Preemptive and Post-Dialysis Living-Donor Kidney Transplantation. J. Pers. Med. 2021, 11, 414.

The authors wish to make the following corrections to this paper [...].

Analysing effects of financial support for regional suicide prevention programmes on methods of suicide completion in Japan between 2009 and 2018 using governmental statistical data.

OBJECTIVES: To explore the mechanisms of reduction of suicide mortality in Japan (from 25.7 to 16.5 per 100 000 population) between 2009 and 2018, the present study determined the effects of execution amounts of regional suicide prevention programmes (Emergency Fund to Enhance Community-Based Suicide Countermeasure: EFECBSC) on gender-specific trends of suicide mortality by disaggregated methods. DESIGN AND SETTING: Stepwise multiple regression analysis was used to determine the effects of execution amounts of 10 subdivisions of execution amounts of financial support for regional suicide prevention programmes (EFECBSC) on suicide methods and gender disaggregated suicide mortalities in Japan between 2009 and 2018 using the statistical data obtained from national governmental database. RESULTS: The suicide mortalities by the most common/frequent suicide methods, hanging, charcoal burning and jumping were significantly decreased between 2009 and 2018. Male hanging suicide was decreased by prefectural enlightenment, municipal development programmes, but female hanging suicide was decreased by municipal personal consultation programmes. Municipal development and enlightenment programmes decreased male and female charcoal-burning suicide mortalities, respectively. Jumping suicide was decreased by prefectural telephone consultation programmes but was unexpectedly increased by municipal personal consultation and enlightenment programmes. CONCLUSIONS: This study revealed the contribution of ECEFBSC on reduction of suicide mortalities, especially hanging, charcoal-burning and jumping suicides, via enhancement of regional suicide prevention programmes in Japan; however, notably, the 'means substitution' from parts of hanging and charcoal burning to jumping is probably generated by EFECBSC. Therefore, these findings provide important aspects for planning evidence-based and cost-effective regional suicide prevention programmes.

Longitudinal Improvement of Neurocognition after Electroconvulsive Therapy in Bipolar Depression.

Electroconvulsive therapy (ECT) is applied to treatment-resistant mood disorders. Its therapeutic effect on neurocognition remains unclear. We report the case of a 55-year-old man with treatment-resistant bipolar depression who underwent ECT series. We longitudinally monitored his neurocognition with the Brief Assessment of Cognition in Schizophrenia-Japanese version (BACS-J). The patient's scores on all of the BACS-J domains except working memory recovered after the ECT series. Interestingly, his verbal memory, motor speed, and executive function recovered 1 month after ECT, whereas his verbal fluency and attention scores recovered approx. 1 year after ECT. The BACS can be useful for monitoring ECT's longitudinal effects on individuals' cognitive recovery. Further studies with a large sample size are needed to confirm our present findings.

Impacts of Interaction of Mental Condition and Quality of Life between Donors and Recipients at Decision-Making of Preemptive and Post-Dialysis Living-Donor Kidney Transplantation.

Pre-emptive kidney transplantation (PEKT) is considered one of the most effective types of kidney replacement therapies to improve the quality of life (QOL) and physical prognosis of patients with end-stage renal disease (ESRD). In Japan, living-donor kidney transplantation is a common therapeutic option for patients undergoing dialyses (PDKT). Moreover, during shared decision-making in kidney replacement therapy, the medical staff of the multidisciplinary kidney team often provide educational consultation programmes according to the QOL and sociopsychological status of the ESRD patient. In Japan, the majority of kidney donations are provided by living family members. However, neither the psychosocial status of donors associated with the decision-making of kidney donations nor the interactions of the psychosocial status between donors and recipients have been clarified in the literature. In response to this gap, the present study determined the QOL, mood and anxiety status of donors and recipients at kidney transplantation decision-making between PEKT and PDKT. Deterioration of the recipient's QOL associated with "role physical" shifted the decision-making to PEKT, whereas deterioration of QOL associated with "role emotional" and "social functioning" of the recipients shifted the decision-making to PDKT. Furthermore, increased tension/anxiety and depressive mood contributed to choosing PDKT, but increased confusion was dominantly observed in PEKT recipients. These direct impact factors for decision-making were secondarily regulated by the trait anxiety of the recipients. Unlike the recipients, the donors' QOL associated with vitality contributed to choosing PDKT, whereas the physical and mental health of the donors shifted the decision-making to PEKT. Interestingly, we also detected the typical features of PEKT donors, who showed higher tolerability against the trait anxiety of reactive tension/anxiety than PDKT donors. These results suggest that choosing between either PEKT or PDKT is likely achieved through the proactive support of family members as candidate donors, rather than the recipients. Furthermore, PDKT is possibly facilitated by an enrichment of the life-work-family balance of the donors. Therefore, multidisciplinary kidney teams should be aware of the familial psychodynamics between patients with ESRD and their family members during the shared decision-making process by continuing the educational consultation programmes for the kidney-replacement-therapy decision-making process.

Analysing the Impacts of Financial Support for Regional Suicide Prevention Programmes on Suicide Mortality Caused by Major Suicide Motives in Japan Using Statistical Government Data.

To improve and plan regional suicide prevention programmes that utilise more cost-effective governmental financial support compared with previous programmes, the present study determined the effects of the amount of financial support provided for regional suicide prevention programmes, such as the Emergency Fund to Enhance Community-Based Suicide Countermeasures (EFECBSC), on the trends of suicide mortalities caused by six major suicide motives between 2009 and 2018, using forward multiple regression analysis. The ranking order of motives for male suicide was health, economy, family, employment, romance and school (in that order), whereas the ranking order for females was health, family, economy, romance, employment and school. Male suicide mortality caused by economy-related motives was significantly/inversely related to prefectural intervention programmes, whereas mortality caused by health-related motives was also significantly/inversely related to prefectural intervention programmes, but significantly/positively related to prefectural personal consultation support programmes. Contrary to males, female suicide mortality caused by health-related motives was significantly/inversely related to the municipal development programmes of leaders/listeners, whereas mortality caused by family- and school-related motives was significantly/positively related to prefectural and municipal telephone consultation support programmes, respectively. Contrary to our expectations, school-aged female suicide mortality caused by school-related motives was significantly/positively related to prefectural personal consultation support, enlightenment and municipal telephone consultation support programmes. These results indicate that Japanese regional suicide prevention programmes probably affect the suppression of male suicide mortality. However, these programmes are possibly ineffective, or at least partially, have an adverse effect, in regard to the suicide mortalities of female and school-aged populations. Therefore, we should work to improve regional suicide prevention programmes, making them more cost-effective and targeted towards female and school-aged populations in the future.

Current Limitations and Candidate Potential of 5-HT7 Receptor Antagonism in Psychiatric Pharmacotherapy.

Several mood-stabilizing atypical antipsychotics and antidepressants weakly block serotonin (5-HT) receptor type-7 (5-HT7R); however, the contributions of 5-HT7R antagonism to clinical efficacy and pathophysiology are yet to be clarified. A novel mood-stabilizing antipsychotic agent, lurasidone exhibits predominant binding affinity to 5-HT7R when compared with other monoamine receptors. To date, we have failed to discover the superior clinical efficacy of lurasidone on schizophrenia, mood, or anxiety disorders when compared with conventional mood-stabilizing atypical antipsychotics; however, numerous preclinical findings have indicated the possible potential of 5-HT7R antagonism against several neuropsychiatric disorders, as well as the generation of novel therapeutic options that could not be expected with conventional atypical antipsychotics. Traditional experimental techniques, electrophysiology, and microdialysis have demonstrated that the effects of 5-HT receptor type-1A (5-HT1AR) and 5-HT7R on neurotransmission are in contrast, but the effect of 5-HT1AR is more predominant than that of 5-HT7R, resulting in an insufficient understanding of the 5-HT7R function in the field of psychopharmacology. Accumulating knowledge regarding the pharmacodynamic profiles of 5-HT7R suggests that 5-HT7R is one of the key players in the establishment and remodeling of neural development and cytoarchitecture during the early developmental stage to the mature brain, and dysfunction or modulation of 5-HT7R is linked to the pathogenesis/pathophysiology of neuropsychiatric and neurodevelopmental disorders. In this review, to explore candidate novel applications for the treatment of several neuropsychiatric disorders, including mood disorders, schizophrenia, and other cognitive disturbance disorders, we discuss perspectives of psychopharmacology regarding the effects of 5-HT7R antagonism on transmission and intracellular signaling systems, based on preclinical findings.

Relationships between Expenditure of Regional Governments and Suicide Mortalities Caused by Six Major Motives in Japan.

Suicide mortality in Japan reduced in the period of 2009-2018. A number of studies identified the impact of financial governmental support for social welfare systems on suicide mortality; however, the detailed effects of specific regional policies, designed according to regional cultural, economic, education and welfare situations, on suicide mortality remain to be clarified. Therefore, the present study analyses the associations between the regional governmental expenditure of six major divisions, "public health", "public works", "police", "ambulance/fire services", "welfare" and "education", and suicide mortalities caused by six major suicidal motives, related to "family", "health", "economy", "employment", "romance" and "school", across the 47 prefectures in Japan during the period of 2009-2018, using fixed-effect analysis of hierarchal linear regression with robust standard error. The expenditure of "public works" displayed a positive relationship with suicide mortality of females caused by family-related motives but was not related to other suicide mortalities, whereas the expenditures in "public health", "police", "ambulance/fire services", "welfare" and "education" contributed to a reduction in suicide mortality, at least in some statistical indicators. The expenditures of both "ambulance/fire" and "education" were predominantly effective among the six major divisions of regional governmental expenditure in reducing suicide mortalities. In the education subdivisions, the expenditure of "kindergarten" was related to a reduction in suicide mortalities caused by a wide spectrum of motives. The amount of expenditure of welfare indicated the limited possibility of facilitating a reduction in suicide mortalities caused by only motives associated with economy or employment. However, in the welfare subdivisions, the expenditure of "child welfare" and "social welfare" was effective in reducing suicide mortalities, but the expenditure of "elderly welfare" was unexpectedly related to an increase in suicide mortalities. These results suggest that most Japanese people are struggling to bring up children even in the situation of an increasing elderly population with a decreasing birth rate. Therefore, it is important to enhance the investment welfare policy for the future to improve the childcare environment. Although the issue of an increasing elderly population and a decreasing birth rate in Japan has not yet improved, the obtained results suggest that evidence-based welfare expenditure redistributions of prefectures and municipalities could improve Japanese society and welfare systems.

Analysing regional unemployment rates, GDP per capita and financial support for regional suicide prevention programme on suicide mortality in Japan using governmental statistical data.

OBJECTIVES: To explore the mechanisms of reduced suicide mortality in Japan, which decreased from 25.7 to 16.5 per 100 000 people following the comprehensive suicide prevention programme from 2009 to 2018, the present study determined the relationship between regional suicide mortality, socioeconomic data (GDP per capita, unemployment rates) and financial support for regional suicide prevention programmes. DESIGN AND SETTING: Stepwise multiple regression analysis was used to determine the effects of regional GDP per capita, unemployment rates and implementation amount of financial support for regional suicide prevention programmes (Emergency Fund to Enhance Community-Based Suicide Countermeasures-EFECBSC) on age and gender disaggregated suicide mortalities in Japan between 2009 and 2018. Data on each prefecture's complete unemployment rates, GDP per capita and implementation amount of EFECBSC sub-divisions were derived from an official Japanese governmental database. RESULTS: Both prefectural enlightenment and intervention model programmes were found to lead to a decrease in male suicide mortality, but were less effective in reducing female suicide mortality. Municipal enlightenment and intervention model programmes were also less effective in reducing suicide mortality. Municipal development programmes for listener and leader led to a greater decrease in suicide mortality for both men and women compared with such programmes at the prefectural level. Contrary to our expectations, reduced complete unemployment rate only reduced suicide mortality in the older male population without affecting female suicide mortality. CONCLUSION: The study findings suggest an inverse relationship between financial support and suicide mortality in Japan. Furthermore, independent factors in the reduction of suicide mortality rates provide important information for planning evidence-based and cost-effective regional suicide prevention programmes.

Amantadine Improves Delayed Neuropsychiatric Sequelae of Carbon Monoxide Poisoning: A Case Report.

Carbon monoxide (CO) poisoning causes severe brain damage, including delayed neuropsychiatric sequelae (DNS), which occur after a lucid interval following recovery from the insult of acute CO poisoning. We describe a 39-year-old male who developed DNS, including gait disturbance, trunk ataxia, and fecal/urine incontinence, after remission of acute CO poisoning. Furthermore, he showed confusion, with disorientation in terms of time and space. All symptoms, including cognitive impairment, were dramatically improved by amantadine monotherapy. The present case illustrates the possibility of amantadine treatment for cognitive impairment as well as Parkinsonism induced by CO poisoning.

Amantadine Combines Astroglial System Xc- Activation with Glutamate/NMDA Receptor Inhibition.

A glutamate/NMDA receptor (NMDA-R) antagonist, amantadine (AMA) exhibits a broad spectrum of clinically important properties, including antiviral, antiparkinsonian, neuroprotective, neuro-reparative and cognitive-enhancing effects. However, both clinical and pre-clinical studies have demonstrated that noncompetitive NMDA-R antagonists induce severe schizophrenia-like cognitive deficits. Therefore, this study aims to clarify the clinical discrepancy between AMA and noncompetitive NMDA-R antagonists by comparing the effects of AMA with those of a noncompetitive NMDA-R antagonist, MK801, on rat tripartite glutamatergic synaptic transmission using microdialysis and primary cultured astrocytes. Microdialysis study demonstrated that the stimulatory effects of AMA on L-glutamate release differed from those of MK801 in the globus pallidus, entorhinal cortex and entopeduncular nucleus. The stimulatory effect of AMA on L-glutamate release was modulated by activation of cystine/glutamate antiporter (Sxc). Primary cultured astrocytes study demonstrated that AMA also enhanced glutathione synthesis via Sxc activation. Furthermore, carbon-monoxide induced damage of the astroglial glutathione synthesis system was repaired by AMA but not MK801. Additionally, glutamate/AMPA receptor (AMPA-R) antagonist, perampanel enhanced the protective effects of AMA. The findings of microdialysis and cultured astrocyte studies suggest that a combination of Sxc activation with inhibitions of ionotropic glutamate receptors contributes to neuroprotective, neuro-reparative and cognitive-enhancing activities that can mitigate several neuropsychiatric disorders.

Cystine/Glutamate Antiporter and Aripiprazole Compensate NMDA Antagonist-Induced Dysfunction of Thalamocortical L-Glutamatergic Transmission.

To explore pathophysiology of schizophrenia, this study analyzed the regulation mechanisms that are associated with cystine/glutamate antiporter (Sxc), group-II (II-mGluR), and group-III (III-mGluR) metabotropic glutamate-receptors in thalamo-cortical glutamatergic transmission of MK801-induced model using dual-probe microdialysis. L-glutamate release in medial pre-frontal cortex (mPFC) was increased by systemic- and local mediodorsal thalamic nucleus (MDTN) administrations of MK801, but was unaffected by local administration into mPFC. Perfusion into mPFC of activators of Sxc, II-mGluR, and III-mGluR, and into the MDTN of activators of Sxc, II-mGluR, and GABAA receptor inhibited MK801-evoked L-glutamate release in mPFC. Perfusion of aripiprazole (APZ) into MDTN and mPFC also inhibited systemic MK801-evoked L-glutamate release in mPFC. Inhibition of II-mGluR in mPFC and MDTN blocked inhibitory effects of Sxc-activator and APZ on MK801-evoked L-glutamate release; however, their inhibitory effects were blocked by the inhibition of III-mGluR in mPFC but not in MDTN. These results indicate that reduced activation of the glutamate/NMDA receptor (NMDAR) in MDTN enhanced L-glutamate release in mPFC possibly through GABAergic disinhibition in MDTN. Furthermore, MDTN-mPFC glutamatergic transmission receives inhibitory regulation of Sxc/II-mGluR/III-mGluR functional complex in mPFC and Sxc/II-mGluR complex in MDTN. Established antipsychotic, APZ inhibits MK801-evoked L-glutamate release through the activation of Sxc/mGluRs functional complexes in both MDTN and mPFC.

Identification of pyridinoline, a collagen crosslink, as a novel intrinsic ligand for the receptor for advanced glycation end-products (RAGE).

Advanced glycation end-products (AGEs) elicit inflammatory responses via the receptor for AGEs (RAGE) and participate in the pathogenesis of diabetic complications. An earlier study showed that 3-hydroxypyridinium (3-HP), a common moiety of toxic AGEs such as glyceraldehyde-derived pyridinium (GLAP) and GA-pyridine, is essential for the interaction with RAGE. However, the physiological significance of 3-HP recognition by RAGE remains unclear. We hypothesized that pyridinoline (Pyr), a collagen crosslink containing the 3-HP moiety, could have agonist activity with RAGE. To test this hypothesis, we purified Pyr from bovine achilles tendons and examined its cytotoxicity to rat neuronal PC12 cells. Pyr elicited toxicity to PC12 cells in a concentration-dependent manner, and this effect was attenuated in the presence of either the anti-RAGE antibody or the soluble form of RAGE. Moreover, surface plasmon resonance-based analysis showed specific binding of Pyr to RAGE. These data indicate that Pyr is an intrinsic ligand for RAGE. ABBREVIATIONS: AGEs: advanced glycation end-products; RAGE: receptor for advanced glycation end-products; DAMPs: damage-associated molecular patterns; PRR: pattern recognition receptor; TLR: toll-like receptor; GLAP: glyceraldehyde-derived pyridinium; 3-HP: 3-hydroxypyridinium; Pyr: pyridinoline; HFBA: heptafluorobutyric acid; GST: glutathione S-transferase; SPR: surface plasmon resonance; ECM: extracellular matrix; EMT: epithelial to mesenchymal transition.

Receptor for advanced glycation end products (RAGE)-mediated cytotoxicity of 3-hydroxypyridinium derivatives.

Advanced glycation end products (AGEs) formed from glyceraldehyde (Gcer) and glycolaldehyde (Gcol) are involved in the pathogenesis of diabetic complications, via interactions with a receptor for AGEs (RAGE). In this study, we aimed to elucidate the RAGE-binding structure in Gcer and Gcol-derived AGEs and identify the minimal moiety recognized by RAGE. Among Gcer and Gcol-derived AGEs, GLAP (glyceraldehyde-derived pyridinium) and GA-pyridine elicited toxicity in PC12 neuronal cells. The toxic effects of GLAP and GA-pyridine were suppressed in the presence of anti-RAGE antibody or the soluble form of RAGE protein. Furthermore, the cytotoxicity test using GLAP analog compounds indicated that the 3-hydroxypyridinium (3-HP) structure is sufficient for RAGE-dependent toxicity. Surface plasmon resonance analysis showed that 3-HP derivatives directly interact with RAGE. These results indicate that GLAP and GA-pyridine are RAGE-binding epitopes, and that 3-HP, a common moiety of GLAP and GA-pyridine, is essential for the interaction with RAGE.